Clinical trial NCT04811040
Conditions: HIV-1 Infection
Sponsor: Gilead Sciences
Start date: 2021-04-08; Completion date: 2023-10-26
Enrollment: 32 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to evaluate the safety and tolerability of a combination of the broadly neutralizing antibodies (bNAbs) teropavimab (formerly GS-5423) and zinlirvimab (formerly GS-2872) in combination with the HIV capsid inhibitor lenacapavir (LEN).

Detailed description:

Arms: arm 1: Participants will receive a loading dose of 600 milligrams (mg) LEN orally on Day 1 and Day 2, along with 927 mg LEN as subcutaneous (SC) injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an intravenous (IV) infusion on Day 1. arm 2: Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1. arm 3: Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an IV infusion on Day 1. arm 4: Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1.
Interventions: intervention 1: Oral Lenacapavir intervention 2: Subcutaneous Lenacapavir intervention 3: Teropavimab intervention 4: Zinlirvimab
Intervention descriptions: intervention 1: Tablets administered without regard to food intervention 2: Administered in the abdomen via subcutaneous injections intervention 3: Administered intravenously intervention 4: Administered intravenously

Protocol documents:
SAP_002.pdf: 
( r) GI L E A U 
S T A T I S T I C A L  A N A L Y S I S  P L A N 
St u d y  Titl e: 
A  P h as e l b R a n d o mi z e d,  Bli n d e d,  Pr o of- of- C o n c e pt  St u d y 
t o E v al u at e  t h e S af et y  a n d  Effi c a c y of Br o a dl y  N e utr ali zi n g 
A nti b o di es  ( b N A b s) G S- 5 4 2 3  a n d  G S- 2 8 7 2  i n C o m bi n ati o n 
wit h  C a psi d  I n hi bit or L e n a c a p a vir  ( G S- 6 2 0 7) i n 
Vir ol o gi c all y  S u p pr ess e d  A d ults  wit h  HI V - 1 I nf e cti o n 
N a m e of T e st  D r u g: 
G S- 5 4 2 3  a n d  G S- 2 8 7 2  +  L e n a c a p a vir  ( L E N;  G S- 6 2 0 7) 
St u d y  N u m b e r: 
G S- U S- 5 3 6- 5 8 1 6 
P r ot o c ol  V e r si o n  ( D at e): 
A m e n d m e nt  2  ( 3 0 M ar c h  2 0 2 2) 
A n al ysis  T y p e: 
Fi n al  A n al ysis 
A n al ysis  Pl a n  V e rsi o n: 
V ersi o n  1. 0 
A n al y si s  Pl a n  D at e: 
2 6  F e b  2 0 2 4 
A n al y si s  Pl a n  A ut h o r(s): 
! P P D 
C O N FI D E N TI A L A N D P R O P RI E T A R Y I N F O R M A TI O N 


L e n a c a p a vi r  + G S -5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St a ti sti c al A n al ysis  Pl a n  - Fi n al  A n al ys is 
V ersi o n  1. 0 
T A B L E  O F  C O N T E N T S 
S T A TI S TI C A L A N A L Y S I S  P LA N  ..... 
T A B L E O F C O N T E N T S 
. ................ ....... 1 
LI S T O F I N- TE..-"\ T  T A B L E S . .. 
................. ................. 
. ...... 5 
LI S T  O F  I N- TE X T FI G U R E S  ................... ................. ................. ................. .................................. ................. ....... 6 
LI S T O F A B B R E VI A TI O N S  ................................................................................ ................ ......................................... 7 
P H A Rl v I A CO K IN E TI C  A B B R E VI A TI O N S .............. ... ............... .............. .   
. . .............. ....................... 9 
I.  
I N TR O D U C TI O N 
..... 1 0 
2. 
3. 
1. 1. 
1. 2 . 
1. 3 . 
St u d y  O b j e cti v es..   
.. .............. ................. ................... ............... ................. 
. .... 1 0 
St u d y  D es i g n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   
. . . . . . . . . . . . . . . 
. .... 1 0 
1. 2 .1. 
D esi g n  C o nfi g ur ati o n  a n d P art i cip a nt  P o p ul at i o n....... ............... ................. 
. .... 1 0 
1. 2 . 2.    
Treat m e nt  Gr o u ps  . . . . . ........ ... . . . . . . ...........   
. . . . ........... 
. .... 1 1 
1. 2 . 3.  
K e y  E li gi bilit y Crit e ri a ........................... .................................. ................. 
. .... 1 2 
1. 2. 4 .    
Dur ati o n  of  Tr e at m e nt  .................. 
. .... 1 3 
1. 2. 5.   
S t u d y Pr o c e d ures/ Fr e q u e n c y . ................. ................. ................. ................. ................. ..... 1 3 
1. 2. 5. 1. 
S cr e e n i ng  ..... ........... 
. .... 1 3 
1. 2. 5 . 2. 
R a n d o m iz ati o n . ................. ................. ................. ................. ................. ..... 1 4 
1. 2. 5 . 3. 
S c h e d ul e  of  Ass es s m e ni s ... 
. .... 1 4 
S a m pl e  S i ze  a n d P o w e r   
................. ................. ................. ................. ................. ................. ..... 1 6 
T Y P E O F P L A N N E D  A N A L Y SI S  .... ................ . 
2 . 1. 
I nt eri m A n a l y sis .. ................................. . 
2 . 1. 1.    
Gile a d D at a R e v ie w C o m m itte e A n a lys is 
A n al  sis . 
2. 4 .  
Fi n a l A n a lysis ......   
. ............... . 
. ..................... 1 7 
G E N E R A L C O N SI D E R A TI O N S  F O R  D A T A  A N A L Y S E S 
3. 1. 
A n al ysis S e ts ........................ ................. ................. ................. ................. ................. ................. ..... 1 9 
3 . 1. 1.    
All R a n d o m iz ed  A n a l ysis  S et 
..... 1 9 
3. 1. 2 .  
F ul l A n a lys is S et..  ................. ................. ................. ................. ................. ................. ..... 1 9 
3. 1. 3 .   
Per Pr ot o c o l A n a lys is S et...... ................. ................... ................ ................ 
. .... 1 9 
3. 1. 4. 
S a f ety  A n a lysis  S et.  ............................... .................................. .................................. ..... 2 0 
3. 1. 5.   
P h a n n a c o ki n et i c ( P K)  S u bst u d y  A n a l ysis S et ..   
................ ................ 
. .... 2 0 
3. 1. 6 .   
Ph a n n a c o ki net i c ( P K) A n al ysis  S ets ........ 
. ..................... 2 1 
3. 1. 7. 
I m mu n o g e n i cit y A n al ysis  S ets  ................ 
... .............. .................   
. ... 2 1 
3. 2. 
P a rtic i pa nt Gr o u p i n g .... 
................. .................. 
... ..............   
. ..................... 2 1 
3. 2. 1.  
Gr o u p i ng  f or E nr ol l m en t, Eli g i bilit y, Dis p osit io n,  D e m o gr a p h i cs, 
B as eli n e  C h ar a c teristic s  a n d  S af et y  A n a l ys es 
... .............. ..................   
. ... 2 2 
3. 2. 2.  
Gr o u pi n g  f or E ffi c a c y A n al ys es 
................. ..... 2 2 
3. 2. 3. 
Gr o u pi n g  f or P K  a n d h n m u n o g e ni cit y A n al ys es  
................. 
. .... 2 3 
3. 3.  
Str at a  a n d  C o v ar iates 
................. 
. ................ ..... 2 4 
3. 4.    
E x a mi n a ti on of P art i cip a nt  S u b gr o u ps .... 
................. 
. .... 2 4 
3. 5.    
M u lti pl e C o m p ar is o ns ..   
................. 
... ..............   
. ..................... 2 4 
3 . 6. 
M issin g  D at a  a n d  O utli ers ...................... ................. 
..................   
. ... 2 4 
3. 6. l. 
Missi n g  D at a ........ . . . . . . .... ... .... 
. ..................... 2 4 
3. 6. 2.    
O u tli er s .................................................................................................................................. 2 4 
3. 7.    
D a t a H a n d lin g C o n v e nt io ns  a nd  T r ans f omr n tio ns  .................................................................................. 2 5 
3. 7. 1. 
D at a  Ha n dli n g  C o n v e nti o ns  a nd  Tr a ns f om r nti on s f or N o n- P K  D a t a... 
. ..................... 2 5 
C O N FI D E N TI A L 
P a g e 2 
2 6 F e b 2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
3. 7. 2.  
D at a  H a n d li n g C o n v e nti o ns  a n d  Tr a nsf or m at io ns f or P K D a t a   
...................... ....... 2 5 
3. 8. 
A n a lysis  Vi sit Wi n d o ws  ......................................................... ...................................................... ...... 2 6 
3. 8. 1. 
D efi n itio n  of  K e y  D at e s  a n d  S t u d y D a y  .............. ....................................................... ........ 2 7 
3. 8. 2.  
A n al ys is Vis it  Win d o ws ............... .. 
. ............ .. ......... ....................... ...................... ........ 2 8 
3. 8. 3.  
S el e cti o n of D at a  i n t h e E v e nt  of  M u lti pl e R e c or ds  i n a n  A n al ysis  Visit 
Wi n d o w 
.........................   
.2 9 
4.  
P A R TI C I P AN T  DI S P O SI TI O N 
........ 3 2 
4 . 1. 
4. 2. 
4. 3. 
4 . 4. 
P arti ci p a nt E nr oll m e nt a n d  Dis p os iti o n.. 
.... .......... 
. ....... 3 2 
E xt e nt of St u d y Dr u g  E x p os ur e  a n d  A d m inistr a ti o n 
........ 3 3 
4 . 2.1. 
D ur a tio n of E x p os ur e t o  St u d y  Dr u g ..... ...............   
...................... 
. ...... 3 3 
4. 2. 2.  
St u d y  D r u g A d m i nistr ati o n .... 
. ............................... ........... .. ... 3 3 
Pr ot o c o l D e vi ati o n s ... ... ..... .......  
............... 
. ..................... 
. ...... 3 4 
Ass ess m e n t  of CO Vl D - 1 9 Im p a ct... . 
............................................... 
. ....... 3 4 
4. 4 . 1.  
St u d y  Dr u g  or  St u d y  Dis c o n ti n u ati o n D u e  t o C O Vl D - 1 9 .................... 
. ....... 3 4 
4. 4 . 2.  
Pr ot o c ol  D e v iati o ns  D u e  t o C O Vl D - 1 9  
............... ...................... 
. ...... 3 4 
4. 4 . 3.    
Miss e d a n d  Virt u al  Vi sits D u e  t o C O Vl D - 1 9  .................................................. ........... .. ... 3 4 
4. 4. 4 .  
A d v ers e  E v e nts  D u e  t o C O Vl D -1 9 ....... 
...................... 
. ...... 3 5 
4. 4 . 5.  
O v er a ll A ss essm e nt of C O Vl D - 1 9 P a n d e mi c  Im p a c t  ...... .................... 
. ....... 3 5 
5.  
B A S E LI N E  C H A R A C T E RI S TI C S  ...... . 
....... 3 6 
...... 3 6 
5. 1. 
5. 2. 
5. 3. 
D e m o gr a p h i cs a n d  B as e li n e C h ar a ct eristi cs 
Ot h e r B as e lin e C h ar a ct eristi cs .................................. . 
M e di c a l  Hist or y 
.............. . 
. ...... 3 6 
············· ........ 3 6 
6.    E F FI C A C Y  A N A L Y S E S 
....... 3 7 
6 . 1. 
6. 2. 
6. 3. 
S e c o n d ar y  E ffi c a c y  E n d p o i nts 
........ 3 7 
6. 1. 1.  
D efi n iti o n of th e  S e c o n d ar y  Effi c a c y  E n d p oi n t s 
........ 3 7 
6. 1. 2. 
F D A - de fi ne d  S n a ps h ot  Al g o rit h m 
. ..................... 
. ...... 3 7 
6. 1. 3.  
A n a l y sis  of  Se c o n d a r y  Effi ca c y  E n d p o i nt s 
....................... .......... 3 8 
6. 1. 3 . 1. 
A n a lys is of t he Pr o p orti o n of S u bj e cts  wi t h HI V - 1 R N A 2': 
5 0  c o p ies/m L at  W e e k  2 6  as  d et er m i ne d b y  F D A - d efin e d 
S n a ps h ot  Al g or ith m 
...................... ........ 3 8 
6. 1. 3 . 2.  
A n a lysis of t h e Pr o p orti o n of S u b j ects  wit h  HI V- 1  R N A  < 
5 0  c o pi es/ m L at W e ek  2 6  as  d et e r mi ne d  b y  F D A- d e fi ne d 
S n a p s h ot Al g o rith m 
.................. ........ 3 8 
6. 1. 3. 3.  
A n a lys is o n  C D 4 + C e ll C o u nts  at  W e e k 2 6 . ........................................... ...... 3 8 
Ot h e r  Effi c a c y E n d p oi nts  ... .............................................................. ....................... ...................... ....... 3 9 
6. 2. 1.    
D e fi nitio n  of  Ot h er  Ef fi ca c y  E n d p oi n ts 
..................... 3 9 
6. 2. 2.  
A n a l ysis  of  Ot h er  Effi c a c y  E n d p o i nts... . ............... ........ ....... .............. 
. ....... 3 9 
6. 2. 2. 1. 
A n al ys is  of Pr o p ort i on of P a rti ci p a nt s  with  HI V - 1 R N A  < 
5 0  c o pi e s/m L b y  Mi s si ng  =  F ai lur e  a n d Mi ss i ng  =  E x cl u d e d 
A p pr o a c h es ............................................... ....................... ....................... ....... 3 9 
6. 2. 2. 2. 
A n a lys is  of C D 4  P er c ent a g e,  C D S  C o u n t, a n d C D 4/ C D 8 
R ati o. ......... 
. ............... ........ ...................... ...................... ....... . 4 0 
C h a n g es  fro m Pr o t o c ol-S p e c ifie d  E ffi ca c y  A n a l ys e s 
.  . ... .   . ... . ...................... ....... . 40 
7.   S A F E T Y  A N A L Y S E S . 
. ...... . 41 
7. 1. 1 . 
7. 1. 2. 
7 . 1. 3. 
7. 1. 4. 
7. 1. 5. 
C O N FI D E N TI A L 
A d v e rs e E v e nt  Di cti o n ar y ............. . 
A d v e rs e E v e nt  S e v e rit y 
R el ati o ns hi p  of  A d v e rs e E v e nts t o  St u d y  Dr u g 
S er io u s  A d v er s e  Ev e nts 
Tr e a t m e nt- E mer g e nt  A d v ers e  E v e nt s .... 
7. 1. 5. 1. 
D ef i niti o n of Tr e at m e nt-E m er g e nt  A d v e rs e  E v e nts .. 
P a g e  3 
. ..... . 4 1 
......... . 41 
..... . 41 
....... . 41 
. ...... . 42 
. ..... . 42 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
8. 
9. 
7. 2. 
7. 3. 
7 . 4. 
7. 5. 
7. 6. 
7. 7. 
7. 1. 6 . 
7. 1. 7. 
7. 1. 5 . 2. 
I nc o m p l et e D a tes  ........................... . 
S u m m a ri es of A d v ers e  E v e nts  a n d  D e at h s 
A d d iti on al A n a ly s is  of A d v e rs e E v e nts 
. ..................... ...................... ...... . 4 2 
······················ ······················ ..... . 4 3 
. 4 4 
7. 1 . 7. 1.  
St u d y  Dr u g  R e lat e d I nje ctio n Si t e R e a c tio n s  a n d I nf usi on 
R el at e d  R e a ct io n s... . 
. ...... . 4 4 
7. 1. 7. 2.  
St u d y  Dr u g  R e lat e d I nj e cti o n Si t e I n d ur ati o n a nd  N o d u le s 
. 4 5 
L a b or at or y  E v al u at io n s  ........................................................... .. ......................................................... . 4 5 
7. 2 .1. 
S u m m a ries  of  N u m eri c L a b or a tor y  R es u lts 
................................ ...................... ....... . 4 6 
7. 2 . 2.  
Gr a d e d  L a b or a tor y  V al u es  ............. 
. .............. . .. ...............   
. ..................... ....... . 4 6 
7. 2 . 2.1. 
T r e at m e nt-E m erg e nt L a b or at or y  A b n o r malit ie s ............. 
. ...... . 4 7 
7. 2 . 2. 2.   
Su m m ari es of L a b or at o r y A b n o r ma litie s 
...................... ...... . 4 7 
B o d y  W ei g ht an d Vi t al  Si g ns .................................................. .. .................................................... ..... . 4 8 
Pr ior  a n d C o n c o mit a nt M e d i cat io ns 
...................... ...................... ....... . 4 8 
7 . 4.1. 
N o n st u d y  Dr u g A n tir etr o vir al M e d ic at i o ns. ......   
...................... 
. ...... . 4 8 
7. 4 . 2.  
Pr ior  an d C o n c o m ita nt  N o n -A R V  M e d ic at i o n s .............. ...................... 
. ..... . 4 8 
El e ctr o c ardi o gr a m  R es u lt s......... 
. . . . . . . . . . . . . . . . . . . . . . 
. ..... . 4 9 
O t her  S af et y  M e a s ur e s 
. . . . . .. . . . . .. .. . ..   
. . . . . .. .. . .. .. . .. ... .. 
. ...... . 4 9 
C h a n g es  fro m Pr o to c o l- S pe c ifi ed  S af e t y A n a lys es . . ... ............ 
. ..................... . .......... ...........   . . . 4 9 
P H A R M A C O KI N E TI C  E V A L U A TI O N /A N A L Y SI S  ....... . 
······················ ······················ ...... 5 0 
8. 1. 
8. 2. 
8. 3. 
P h ar m a c o k i n eti c ( P K)  S a m p li n g an d P K C o n c entr ati o n .........   
. ..................... ...................... ....... 5 0 
P h ar m a c o k in et i c P ar a m et er s... ......... ....................................... 
. ........................................... ...... 5 0 
St at istic al A n a ly s is  M et h o ds 
......................... ................................ ...................... ........ 5 1 
8. 3. 1. 
St at isti c al A n al ysis of P K  C o n c e ntr a ti on .............. . .. ......................   
. ..................... ........ 5 1 
8. 3. 1. 1. 
P K  C o n c e n tr ati on  D at a  B a s e d o n L E N  P K  S u bst u d y 
A n al ysis  S e t 
...................... ....... 5 1 
8. 3. 1. 2.  
P K  C o n c e n tr ati on  D at a  B a s e d o n P K  A n a ly s is S e ts.. 
. ..................... ...... 5 2 
8. 3. 2.   
St at isti c al A n al ysis of P K  P ar a m e t er s 
........ .................   
. 5 3 
IM M U N O G E NI CI T Y  A N A L Y SI S  ............................. . 
. .... 5 4 
9. 1. 
9. 2. 
D efi n iti o n s ................ . 
E v a lu at io n ofl m m u n o g e n i cit y D a t a ............... . 
······················ ······················ ....... 5 4 
. .... 5 5 
1 0.  R E F E R E N C E S ... ............. . 
. ....... 5 7 
........ 5 8 
1 1. 
S O F T W A R E  ..... . 
1 2.  S A P  R E VI SI O N  .............. . 
. ...... 5 9 
A P P E N DI C E S  ........................... ................... ..................... . 
. ....... 6 0 
C O N FI D E N TI A L 
P a g e  4 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
T a b l e  1-1. 
T a b l e  3-1. 
T a b l e 3- 2 . 
T a b l e 3- 3 . 
LI S T  O F  I N- T E X T T A B L E S 
E stim at e d  Vir o l o gi c F a ilm e  R at e  a n d  its 9 5 %  Ci s (fr o m t he  Cl o p p e r-P e a rs on  E x a ct 
CI)  B as e d  o n  N u m b er  of  Vir ol o gi c F a il m e  E v e nt  i n E a c h  Gr o u p  or  i n  Tot a l   
.................. 1 6 
P art icip a nts  E x cl u d e d fr om  P er  Pr ot o c o l A n al ys is S e t D u e  t o  Pre m at m e 
Dis c onti n u at i on of S t u dy  D r u g a n d/ o r  Missin g  HI V- 1  R N A  Ass ess m e nt  i n W e e k  2 6 
A n al ys is Wi n d o w 
........... 2 0 
A n al ys is Wi n d o ws  f or HI V- 1  R N A ....................................................................................... 2 8 
A n al ys is Wi n d o ws  f or C D 4 + c e ll c o u nt , C D S +  c ell  c o u nt, C D 4/ C D 8 R at i o, 
C h e mistr y,  H e m at ol o g y,  Uri n al ysis ,  Vit al  Si g ns, a n d  W e i ght 
........ 2 9 
T a b l e  3- 4.  
A n al ys is  Win d o ws  f or E C G ... 
. ............. . 
. ....... 2 9 
T a bl e  8- 1.  
P h a r ma c o k in et i c P ar a m et ers  f or E a c h  A n al y t e ....... 
. ............. . 
. ...... 5 0 
T a b l e  Ap p e n d i x-I. 
E x a m p le s of  S e ar c hi n g  T e r ms f or " C O VI D - 1 9"  a n d  " Virt u al "  Us e d 
t o I de ntif y Miss e d  a n d  Vir t ual  Vi sits  ............................... ................................ .   
. .. 6 8 
T a b l e A p p e n d i x- 2. 
P art i cip a nt  Gr o u pi n g f or E m oll m e nt, Eli g i bilit y, Dis p o s iti on, 
D e m o gr a p h ics,  an d  B as e li ne  C h ar a c t eristics .... 
. ....... 7 1 
T a b l e  Ap p e n d i x- 3. 
P art i cip a nt  Gr o u pi n g f or Effi c a c y  A n a lys es ..................... 
. ...... 7 1 
T a b l e  Ap p e n d i x- 4. 
P art i cip a nt  Gr o u pi n g f or S af et y  A n a lys es 
........ 7 1 
T a b l e  Ap p e n di x- 5. 
P art i cip a nt  Gr o u pi n g f or P K  S u b st ud y  A n a lys es of L E N . 
. .. 7 1 
T a b l e A p p e n d i x- 6. 
P art i cip a nt  Gr o u pi n g f or P K  A n a lys es  of  G S -5 4 2 3  a n d  L E N ................ ....... 7 2 
T a b l e  Ap p e n di x - 7. 
P art i cip a nt  Gr o u pi n g f or P K  A n a lys es of G S -2 8 7 2 . 
. ....... 7 2 
T a b l e  Ap p e n d i x- 8. 
P art i cip a nt  Gr o u pi n g f or I mm u n o g e ni cit y  A n a lys es  of  A nt i- G S - 5 42 3 .. ....... 7 2 
T a b l e A p p e n d i x- 9. 
P art i cip a nt  Gr o u pi n g f or Im m u n o g e n i cit y A n a lys es of A nti - G S -2 8 7 2  ......... 7 3 
T a b l e  Ap p e n di x- I O 
P art i cip a nt  Gr o u pi n g f or I m m u n o g eni ci t y A n a lys es of B o t h A nti -
G S - 5 42 3 a n d  A n ti- G S -2 8 7 2 ........................................................................................... ....... 7 3 
C O N FI D E N TI A L 
P a g e  5 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
LI S T O F I N- T E X T  F I G U R E S 
V ersi o n  1. 0 
F i gur e 1- 1. 
St u d y  S c he m a .......................... .............................................................................................. 1 1 
C O N FI D E N TI A L 
P a g e  6 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
A D A 
A E 
A L T 
A Q L 
A R T 
A R V 
A S T 
B E 
BI F! T A F 
BI C 
B L Q 
B MI 
b N A b s 
C F R 
CI 
C R F 
C S R 
C T C A E 
D M C 
E C G 
E T 
E V G 
F A S 
F D C 
F T C 
Gil e a d 
G D R C 
G L S M 
H b 
I V 
L A 
a nti dr u g  a nti b o d y 
a d v er s e  e v e nt 
LI S T  O F  A B B R E V I A T I O N S 
al a ni n e  a mi n otr a n sf er a s e 
a b o v e  q u a ntit ati o n  li mit 
a ntir etr o vir al t h er a p y 
A ntir etr o vir al 
a s p art at e  a mi n otr a nsf er as e 
bi o e q ui v al e n c e 
bi ct e gr a vir/ e mtri cit a bi n e/  t e n of o vir al af e n a mi d e, Bi k t ar v y® 
bi ct e gr a vir,  B,  G S- 9 8 8 3 
b el o w  t h e li mit of q u a ntit ati o n 
b o d y  m a s s  i n d e x 
Br o a dl y  N e utr ali zi n g  A nti b o di e s 
C o d e of F e d er al  R e g ul ati o n s 
c o nfi d e n c e  i nt er v al 
c a s e  re p ort f or m 
cli ni c al  st u d y r e p ort 
C o m m o n  T o xi cit y  Crit eri a  f or A d v er s e  E v e nt s 
d at a  m o n it ori n g c o m mitt e e 
el e ctr o c ar di o gr a m 
e arl y t er mi n ati o n 
el vit e gr a vir,  E 
F ull  a n al y si s s et 
fi xe d d o s e  c o m bi n ati o n 
e mtri cit a bi n e 
Gil e a d  S ci e n c e s 
Gil e a d  D at a  R e vi e w  C o m mitt e e 
g e o m etri c  l e a st- s q u ar e s m e a n 
h e m o gl o bi n 
i ntr a v e n o u s 
L o n g -a c ti ng 
V ersi o n  1. 0 
I C H 
I nte r n ati o n al C o nf er e n c e o n H ar m o ni z ati o n  ( of T e c h ni c al R e q uir e m e nt s  f o r  Re gistr ati o n of 
P h ar m a c e uti c al s  f or  H u m a n  U s e) 
L L O Q 
M e d D R A 
M S T 
P K 
P O C 
p p 
C O N FI D E N TI A L 
l o w er li mit of q u a ntit ati o n 
M e di c al  Di cti o n ar y  f or R e g ul at or y  A cti viti e s 
M e di c al  S ur v eill a n c e  T e a m 
p h ar m a c o ki n eti c 
pr o of of c o n c e pt 
p er  pr ot o c ol 
P a g e  7 
2 6 F e b 2 0 2 4 


L e n a c a p a vir + G S- 5 4 2 3 + G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
P T 
Ql, Q 3 
S A P 
S C 
S D 
pr ef err e d  t er m 
first q u artil e,  t hir d q u artil e 
st ati sti c al a n al y si s  pl a n 
s u b c ut a n e o u s 
st a n d ar d d e vi ati o n 
SI 
s o c 
T A F 
T E A E 
T F L s 
T F V- D P 
U L O Q 
U L N 
I nt er n ati o n al S yst e m of U nit s  ( S yst e m e I nt er n ati o n al d' U nit e s) 
s yst e m  or g a n  cl ass 
V F 
V R 
W H O 
C O N FI D E N TI A L 
t e n of o vir al af e n a mi d e 
tr e at m e nt- e m er g e nt a d v ers e  e v e nt 
t a bl es, fi g ur es,  a n d  listi n gs 
t e n of o vir di p h o s p h at e 
u p p er  li mit of q u a ntifi c ati o n 
u p p er  li mit of n or m al 
vir ol o gi c  f ail ur e 
v e ntri c ul ar  r at e 
W orl d  H e alt h  Or g a ni z ati o n 
P a g e  8 
V ersi o n  1. 0 
2 6 F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St ati sti c al  A n al y si s  Pl a n  - Fi n al  A n al y si s 
V er si o n  1. 0 
¾ A U C e x p 
A U C;
0 r 
A U C 1., 1 
A U C o. 2 6 w k 
C L 
C 2 6 w k 
C m a x 
C m a x d a yl 
t  ½ 
T m a x 
I m a x d ayl 
Yss 
C O N FI D E N TI A L 
P H A R M A C O K I N E T I C  A B B R E V I A T I O N S 
t e n ni n al eli mi n ati o n r at e c o n st a nt, e sti m at e d b y li n e ar r e gr e s si o n of t h e t e n n i n al 
eli mi n ati o n p h a s e of t h e l o g pl as m a/ s er u m  c o n c e ntr ati o n of dr u g  v er s u s  ti m e c ur v e of t he 
dr u g 
p er c e nt a g e of A U C  e xtr a p ol at e d b et w e e n A U C 1.,1 a n d A U C; 0 r 
ar e a  u n d er  t h e c o n c e ntr ati o n v er s u s  ti m e c ur v e  e xtr a p ol at e d t o i nfi nit e ti m e 
ar e a  u n d er  t h e pl a s m a /s er u m  c o n c e ntr ati o n  v er s u s  ti m e c ur v e  fr o m  ti m e z er o t o t h e la st 
q u a ntifi a bl e  c o n c e ntr ati o n 
ar e a  u n d er  t h e pl a s m a /s er u m  c o n c e ntr ati o n  v er s u s  ti m e c ur v e  fr o m  ti m e z er o t o w e e k 2 6 
cl e ar a n c e 
Pl a s m a /s er u m  c o n c e ntr ati o n of dr u g at W e e k 2 6 
m a xi m u m  o b s er v e d  pl a s m a /s er u m  c o n c e ntr ati o n of dr u g 
m a xi m u m  o b s er v e d  pl a s m a /s er u m  c o n c e ntr ati o n of dr u g  at  D a y  1 
e sti m at e of t h e a p p ar ent t e n ni n al h alf-lif e of t he  dr u g i n pl a s m a /s er u m, c al c ul at ed b y 
di vi di n g  t h e n at ur al l o g of 2  b y  t h e t e n ni n al eli mi n ati o n  r at e c o n st a nt ( 1 1.2) 
ti m e ( o b s er v e d ti m e p oi nt) of l a st o b s er v e d  q u a ntifi a bl e  pl a s m a /s er u m  c o n c e ntr ati o n of 
dr u g 
tim e ( o b s er v e d ti m e p o i nt) of   C m a x 
ti m e ( o b s er v e d ti m e p oi nt ) of C m a x da yl 
v ol u m e of di stri b uti o n  at st e a d y st at e 
P a g e  9 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
1. 
I N T R O D U C T I O N 
V ersi o n  1. 0 
T hi s  st ati sti c al  a n al ysis  pl a n  ( S A P) d e s cri b e s  t h e st ati sti c al  a n al ysis  m et h o d s  a n d  d at a 
pr e s e nt ati o n s  t o b e u s e d i n t a bl e s, fi g ur e s,  a n d  listi n gs ( T F L s) i n t h e cli ni c al  st u d y r e p ort ( C S R) 
f or t h e fi n al a n al y s e s of St u d y  G S- U S- 5 3 6- 5 8 1 6.  T his  S A P  is b a s e d o n t h e st u d y Pr ot o c ol 
A m e n d m e nt  2  d at e d  3 0  M ar c h  2 0 2 2  a n d  t h e el e ctr o ni c  c a s e  r e p ort f or m ( e C R F).  T h e  S A P  will 
b e  fi n ali z e d pri or t o d at a b as e  fi n ali z ati o n.  A n y  c h a n g e s  m a d e  aft er  fi n ali z ati o n of t h e S A P  will 
b e  d o c u m e nt e d  i n t h e C S R. 
1. 1. 
St u d y  O bj e cti v e s 
T h e  pri m ar y  o bj e cti v e of t his st u d y is as  f oll o ws: 
•  T o  e v al u at e  t h e s af et y a n d t ol er a bilit y of a  c o m bi n ati o n of t h e b N A b s  G S- 5 4 2 3  a n d 
G S- 2 8 7 2  i n c o m bi n ati o n  wit h  t h e HI V  c a p si d  i n hi bit or l e n a c a p a vir ( L E N; G S- 6 2 0 7) 
T h e  s e c o n d ar y o bj e cti v e s of t his st u d y ar e  a s  f oll o ws: 
•  T o  e v al u at e  effi c a c y of t h e st u d y r e gi m e n s d et er mi n e d  b y  t h e pr o p orti o n of p arti ci p a nt s 
m ai nt ai ni n g  vir ol o gi c  s u p pr e s si o n ( HI V- 1 R N A <  5 0  c o pi e s /m L) at W e e k 2 6 
•  T o  e v al u at e  t h e p h ar m a c o ki n eti c s  ( P K) of G S- 5 4 2 3,  G S- 2 8 7 2,  a n d  L E N 
•  T o  e v al u at e  i m m u n o g e ni cit y of G S- 5 4 2 3  a n d  G S- 2 8 7 2 
•  T o  e v al u at e  t h e e m er g e n c e of r e si st a n c e t o t h e c o m p o n e nt s of t h e st u d y r e gi m e n s 
1. 2.  
St u d y  D e si g n 
1. 2. 1.  
D e si g n  C o nfi g u r ati o n  a n d  P a rti ci p a nt  P o p ul ati o n 
T his  is a  r a n d o mi z e d, bli n d e d, pr o of of c o n c e pt  ( P O C) P h a s e  1 b  st u d y t o e v al u at e t h e s af et y a n d 
effi c a c y of a  si n gl e  d os e  e a c h of l o n g- a cti n g ( L A) r e gi m e n of L E N , G S- 5 4 2 3,  a n d  G S- 2 8 7 2  i n 
a d ult s  wit h  HI V- 1  i nf e cti o n w h o  ar e  vir ol o gi c all y  s u p pr e s s e d o n  or al  a ntir etr o vir al  t h er a p y 
( A R T). 
A n  o v er vi e w of t h e st u d y d e si g n  is d e s cri b e d  b el o w  a n d  s h o w n i n Fi g ur e  1 - 1. 
C O N FI D E N TI A L 
P a g e  1 0 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  + G S- 5 4 2 3 + G S- 2 8 7 2 
G S -U S - 53 6 -5 8 1 6 
St a tistic al A n al ysis  Pl a n  - Fi n al A n al ysis 
Fi g u r e  1- 1.  
St u d y  S c h e m a 
St u d y W e e k s  0 J D a ys 1 , 2• 
V ers io n 1. 0 
1 
St u d y Dr u g D o si n g 
- - - - - - - - - _ J _ _ - - - - - - - - - - ~ _ J 
1"=  ~ 2 0 
V irol o gi c all y S u p pr ess e d 
P art i ci p a nts  + 
N  =  u p  t o 2 0 
f or O pt i o nal Pil ot  C o h ort 
Tr eat m e nt  Gr o u p 1: L E N 9 2 7 m g S C + G S -5 4 2 3 
3 0 m g/ k g + G S -2 8 7 2 1 0 m g/ k g at D a y I 
L  I 
T r e at m e nt G r o u p 2: L E N 9 2 7 m g S C + G S -5 4 2 3 
3 0 m g/ k g  +  G S- 2 8 7 2 3 0  m g/ k g  at D a y  I 
St u d y Vi s,ts 
S nt d y \ V e e ks 
D a y l t >t y a ,.. w e e 1:,. 
w e el: 1 2 
• Cli ni c a n d l a b or at or y tes t visit 
o L a bor a t or y test vi.sit o ul y 
R es u m e b as eli n e d a il y o r al A R T 
( or c o m pati bl e re gi m e n sel e ct ed  b y i nv est ig at o r) 
Cl i ni c al a n d P K f oll o w- u p 
•  D a y I: L E N d o s e: 6 0 0 m g or a l (t abl ets). a d mi nister ed i n c li nic pri or t o L E N S C 
•    Da y 2: L E N d os e: 6 0 0 m g o r al (t abl e ts), se u: a dmi ni ster ed at b o m e 
lf a p a m c, p a ut d L S C O u u n u es p n or  t o W e e k 2 6 E T . P ost- E T  f oll o w -u p visits \\11 1 be  p erf o n n e d 
A R T =  a ntir etr o vir al  t h er ap y; E T =  e a rl y te n n i n ati o n; L E N =  l e n a c a p a vir; P K =  p h a n n a c o ki n eti c( s); S C = s u b c ut a n e o us . 
P arti ci p a nt s i n t he Pri m a r y C o h ort a n d i n t h e o pti o n al Pil ot  C o h o rt will b e r a n d o mi z e d i n a 
1: 1 r ati o t o o n e of th e f oll o wi n g 2  tr e at m e nt gr o u p s b a s ed  o n  t h e d os e of G S- 2 8 7 2 as i n S e cti o n 
1. 2. 2 . 
1. 2. 2. 
T r e at m e nt  G r o u ps 
T r e at m e nt  G r o u p 1: 
Or al  L E N f or lo a di n g  6 0 0  m g  f oll o w e d b y L E N 9 2 7 m g s ub c u t an e ous ( S C) o n D a y  1;  or al L E N 
f or l o a di n g 6 0 0 m g  o n  D a y 2 
G S - 54 2 3 3 0  m g/ k g , a d mi nist er e d  v i a i ntr av e n o us (I V) i nf usi o n o v er  6 0  mi n ut es  o n D a y 1 ( aft er 
L E N S C i nj e cti o n) 
G S- 2 8 7 2 1 0 m g/ k g,  a d mi nist er e d  v i a I V i nf usi o n o v e r 6 0  mi n ut es  o n D a y  1 ( aft er G S- 5 4 2 3 
i nf usi o n). 
C O N FI D E N TI A L 
P a g e  1 1 
2 6 F e b 2 0 2 4 


L e n a c a p a vi r  + G S - 5 4 2 3 +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ys is 
T r e at m e nt  G r o u p  2: 
V ersi o n  1. 0 
Or al  L E N  f or  l o a di n g 6 0 0  m g  f oll o w e d  b y  L E N  9 2 7  m g  S C  o n  D a y  1;  or al  L E N  f or l o a di n g 
6 0 0  m g  o n  D a y  2 
G S- 5 4 2 3  3 0  m g /k g,  a d mi nist e r e d vi a  I V i nf usi o n o v er  6 0  mi n ut es  o n  D a y  1  ( aft er L E N  S C 
i nj e cti o n) 
G S- 2 8 7 2  3 0  m g/ k g,  a d mi nist er e d  vi a  I V i nf usi o n o v er  6 0  mi n ut es  o n  D a y  1  ( aft er G S- 5 4 2 3 
i nf usi o n). 
T h er e  is n o  str atifi c ati o n f or r a n d o miz ati o n f or t h e Pri m ar y  C o h ort.  F or  t h e o pti o n al  Pil ot  C o h ort, 
r a n d o mi z ati o n will  b e  str atifi e d  b y  t h e a nti b o d y  ( G S- 5 4 2 3 or  G S- 2 8 7 2 ) t o w hi c h  t h e p arti ci p a nt 
is s e nsiti v e. 
All  p arti ci p a nts  will  dis c o nti n u e  t h eir b a c k gr o u n d  or al  a ntir etr o vir al  ( A R V) r e gi m e n 1  d a y  pri or 
t o r e c ei vi n g st u d y dr u gs  o n  D a y 1. 
At  W e e k  2 6,  all  p arti ci p a nts  will  r es u m e t h eir b as eli n e  r e gi m e n of o n c e  d ail y  or al  A R T  ( or 
c o m p ati bl e  r e gi m e n s e l e ct e d b y  t h e i n v esti g at or) a n d  r et ur n t o t h e cli ni c  f or visits  at W e e ks  3 8 
a n d 5 2. 
D et ail s of t h es e t w o a n al ysis  p eri o ds  will  b e 
a d dr ess e d  l ater  i n S e cti o n  3. 
U n bli n d e d  tr e at m e nt assi g n m e nts  will b e pr o vi d e d  t o t h e i n v esti g at ors aft er  all  p arti ci p a nts  ar e 
b a c k  o n  t h eir b as eli n e  A R Vs  ( or c o m p ati bl e  r e gi m e n s el e ct e d b y  t h e i n v esti g at or) at  W e e k  2 6  or 
h a v e  dis c o nti n u e d  t h e st u d y, a n d  t h e W e e k  2 6  a n al ysis  h a s  b e e n  c o m pl et e d. 
1. 2. 3.  
K e y Eli gi bilit y C rit e ri a 
HI V - 1 i nf e ct e d p arti ci p a nts  w h o  m e et  t h e f oll o wi n g crit eri a: 
• 
A g e b et w e e n 1 8 a n d 6 5 y e ar s at s cr e e ni n g 
• 
O n first-li n e A R T  f or 2'. 2  y e ars  pri or  t o s cr e e ni n g.  A  c h a n g e  i n A R T  r e gi m e n 2'. 2 8  d a ys  pri or 
t o s cr e e ni n g f or r e as o ns ot h er  t h a n v ir ol o gi c f ail ur e ( V F) ( e g, t ol er a bility,  si m plifi c ati o n, 
dr u g- dr u g  i nt er a cti o n pr ofil e)  is all o w e d 
•  N o  d o c u m e nt e d  hist ori c al  r esist a n c e t o t h e c u n- e nt  A R T  r e gi m e n 
•  Pl a s m a  HI V- 1  R N A < 5 0 c o pi es/ m L  at  s cr e e ni n g 
C O N FI D E N TI A L 
P a g e 1 2 
2 6  F e b  2 0 2 4 


L e n a c a p a vi r  + G S - 5 4 2 3 +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  -  Fi n al A n al ys is 
V ersi o n 1. 0 
•  D o c u m e nt e d  pl a s m a  HI V- 1  R N  A  <  5 0  c o pi es /m L f or ~  1 8  m o nt hs  pr e c e di n g  t h e s cr e e ni n g 
v isit ( or u n d et e ct a bl e  HI V- 1  R N A  l ev el  a c c or di n g t o t h e l o c al a s s a y  b ei n g  u s e d if t h e li mit of 
d et e cti o n  is 2: 5 0 c o pi e s /m L).  U n c o nfi n n e d  v iro l o gi c el e v ati o ns of 2: 5 0  c o pi es /m L (tr a n si e nt 
d et e ct a bl e  vir e mi a,  or  " bli p ")  pri or  t o s cr e e ni n g ar e  a c c e pt a bl e. 
•  Pr o vir al  p h e n ot y pi c  s e n siti vit y t o b ot h  G S- 5 4 2 3  a n d  G S- 2 8 7 2 at s cr e e ni n g b y  t h e 
P h e n o S e ns e  m o n o cl o n al  a nti b o d y  ( m A b) Ass a y  ( M o n o gr a m Bi os ci e n c es)  f or i n cl usi o n i n t h e 
P 1i m a r y  C o h o rt ; s e nsiti vit y at s cr ee ni n g  b y  t h e P h e n o S e ns e  m A b  A s s a y  ( M o n o gr a m 
Bi os ci e n c es)  t o I  m A b , eit h er  G S -5 4 2 3  or  G S- 2 8 7 2, 
ri ort o e nr oll m e nt  f or 
i n cl u si o n i n t h e o pti o n al  Pil ot  C o h o rt 
- 
I n b ot h c o h o 1 1s, G S- 5 4 2 3  s e n siti vit y is d efi n e d  as  9 0 %  i n hi bit or y c o n c e ntr ati o n  (I C9 0)  2 
~t g /m L ; G S- 2 8 7 2  s e n siti vit y is d efi n e d as I C9 0:::; 2 ~t g /m L 
•  C D 4 +  c o u nt n a dir 2: 3 5 0  c ells / µ L 
•  S cr e e ni n g  C D 4 +  c o u nt 2: 5 0 0  c ells /µ L 
•  A v ail a bilit y of a  f ull y a cti v e  alt e m atj v e  A R T  r e gi m e n, i n t h e o pi ni o n of t h e i n v esti g at or, i n 
t h e e v e nt of dis c o nti n u ati o n of t h e c u 1 T e nt A R T  r e gi m e n wit h  d e v el o p m e nt of r esist a n c e 
•  N o  c o m or bi d  c o n diti o n  r e q uiri n g o n g oi n g  i m m u n o s u p pr e s si o n 
•  N o  e vi d e n c e of c urr e nt  h e p atitis  B  vir us  ( H B V) i nf e cti o n 
•  N o  e vi d e n c e of c urr e nt  h e p atiti s  C  v ir us ( H C V) i nf e cti o n ( pri or i nf e ctj o n cl e ar e d 
s p o nt a n e o u sl y  or  wit h  tr e at m e nt is a c c e pt a bl e) 
•  N o  hi st or y of o p p ort u nisti c  i nf e cti o n or  ill n ess i n di c ati v e of St a g e  3  HI V  dis e as e 
1. 2. 4.  
D u r ati o n of T r e at m e nt 
D ur ati o n of st u d y dr u g  tr e at m e nt is a p pr o xi m at el y  2 6  , v e e ks. 
1. 2. 5. 
1. 2. 5. 1. 
St u d y  P r o c e d u r es/ F r e q u e n c y 
S cr e e ni n g 
D u e  t o t h e e xt e n d e d  l a b or at or y pr o c es s i n g ti m e f or b N A b  s e nsiti vit y t estj n g, s cr e e ni n g 
pr o c e d ur e s  f or t h e Pri m ar y  C o h ort  will b e c o n d u ct e d  i n t w o p art s . F or  t h e o pti o n al  Pil ot  C o h ort, 
p arti ci p a nts  will  b e  s el e ct e d  fr o m t h e pr e vi o usl y  s cr e e n e d/f ail e d p arti ci p a nts i n t h e Pri m ar y 
C o h ort  a n d  will  dir e ctl y  pr o c e e d  t o S cr e e ni n g  P art  2  ( n o n e e d  t o r e p e at S cr e e ni n g  P art  1 ). 
S c r e e ni n g  P a rt 1: Ass ess m e nt of m e di c al  hist or y,  a d v er s e  e v e nt s ( A Es), a n d  c o n c o mit a nt 
m e di c ati o ns  will b e p erf or m e d.  A  bl o o d  s a m pl e t o ass ess  f or b N A b  s e n siti vit y  will  b e  c oll e ct e d 
a n d  a n al y z e d t o s u p p o 1i eli gi bilit y  a n d  e ntr y  i nt o S cr e e ni n g  P ali 2. 
C O N F I D E N TI A L 
P a g e 1 3 
2 6 F e b 2 0 2 4 


L e n a c a p a v ir  + G S - 5 4 2 3 +  G S- 2 8 7 2 
G S- U S- 5 3 6 -5 8 1 6 
St at isti c al A n al ys is Pl a n -  Fi n al A n al ys is 
V ersi o n 1. 0 
S c r e e ni n g  P a rt 2: P arti ci p a nts  wit h  pr o vir al  p h e n ot y pi c  s e n siti vit y t o eit h er or  b ot h  G S- 5 4 2 3 
a n d  G S- 2 8 7 2  will  h a v e  t h e f oll o wi n g ass ess m e nts  p erf o n n e d: c h a n g e s  i n m e di c al  hi.st or y , 
c o m pl et e p h ys i c al e x a mi n ati o n,  vit al  s i g ns, h ei g ht,  w ei g ht,  el e ctr o c ar di o gr a m  ( E C G), a n d  s a m pl e 
c oll e cti o n  f or l a b or at or y a n al ys e s  ( he m at ol o g y , c h e mistr y , c o a g ul ati o n,  t h yr oi d f u n cti o n, 
uri n al y si s , s er u m pr e g n a n c y  t est  [f or w o m e n of c hil d b e ari n g  p ot e nti al] , s er u m f olli cl e-
sti m ul ati n g h o n n o n e  [ F S H],  HI V- 1  R N A,  C D 4 +  c ell  c o u nt,  C D 8 +  c ell  c o u nt,  C D 4 /C D 8  r ati o, 
H B V  a n d  H C V s er ol o gi es,  a n d  e sti m at e d  gl o m er ul ar  filtr atio n r at e  [ e G F R]).  L a b or at or y  s a m pl es 
f or pr o vir al  D N A g e n ot y p e  a n d  b ul k  vir al  o ut gr o\- vt h  p h e n ot y p e  will  b e  c oll e ct e d at s cr e e ni n g f or 
s u b s e q u e nt t e sti n g. 
1. 2. 5. 2.  
R a n d o mi z ati o n 
P arti ci p a nts  i n t h e Pri m ar y  C o h ort  w h o  m e et  all  eli gi bilit y  crit eri a will  b e  r a n d o mi z e d  i n a 1: 1 
r ati o t o Tr e at m e nt  Gr o u p  1  or  Tr e at m e nt  Gr o u p  2.  P atti ci p a nt s i n t h e Pil ot  C o h o 1t  w h o  m e et  all 
eli gi bilit y  crit eti a will b e r a n d o mi z e d i n a  I: 1  r ati o t o Tr e at m e nt  Gr o u p  1  or  Tr e at m e nt  Gr o u p  2. 
P atii ci p a nts  i n b ot h  c o h o 1is  will  r et ur n t o t h e cli ni c  wit hi n  2 8  d a ys  aft er t h e S cr e e ni n g  P ati  2  vi sit 
f or t h e D a y  1 visit. 
T h e r e is n o  str atifi c ati o n f or r a n d o mi z ati o n f or t h e Pri m ar y  C o h ort. 
F or  t h e o pti o n al  Pil ot  C o h ort , r a n d o mi z ati o n will  b e  str atifi e d b y  t h e a nti b o d y  ( G S- 5 4 2 3  or  G S-
2 8 7 2)  t o w hi c h  t h e p arti ci p a nt is s e nsiti v e. 
1. 2. 5. 3.  
S c h e d ul e of Ass ess m e nts 
St u d y  dr u g(s)  will  b e  a d mi nist er e d  i n- cli ni c o n  D a y  1  a n d  s elf- a d mi nist er e d  o n  D a y  2  ( n ot e: 
a d mi ni st er e d  i n- cli ni c o n  D a y  2 if p artj ci p ati n g  i n t h e 
. P arti ci p a nts  will 
r et ur n f or st u d y visits  o n  W e e ks  4,  8,  1 2 , 1 6 , 2 0 , 2 4 , 2 6 , 3 8 , a n d  5 2  f or st u d y  ass es sm e nts . 
Cli ni c al  a n d  l a b or at or y ass ess m e nt s i n cl u di n g h e m at ol o g y,  c h e mistr y,  uri n al y si s,  pr e g n a n c y  t e st 
(f or w o m e n of c hil d b e ari n g  p ot e nti al),  HI V- 1  R N A,  C D 4 +  c ell  c o u nt,  C D 8 +  c ell  c o u nt , 
C D 4 /C D 8  r ati o, vit al  si g ns ,  w ei g ht, f o c u s e d p h y si c al  e x a mi n ati o n,  e G F R,  a n d  a s s e s s m e nt of A Es 
a n d  c o n c o mit a nt  m e di c ati o ns  will  b e  p erf or m e d  at  D a y  1,  W e e ks  4,  1 2 , 2 6 , 3 8 , 5 2 , e arl y 
t e 1 mi n ati o n ( E T), a n d  p o st- E T  f oll o w- u p  visits  (n ot e:  c o m pl et e  p h y si cal  e x a mi n ati o n  will b e 
p erf orr n e d at D a y  1  a n d  E T). 
T h yr oi d  will  b e  ass ess e d  at  s cr e e ni n g,  D a y  1,  W e e ks  4,  1 2,  2 6,  3 8,  a n d 5 2. 
E C G will  b e  p erf or m e d at s cr e e ni n g, D a y 1, W e e ks  2 6 , a n d  5 2. 
HI V- 1  R N A  will  als o b e as s ess e d  at  W e e ks  4,  8,  1 2 , 1 6 , 2 0 , 2 4 , 2 6 , 3 8 , a n d 5 2. 
Pl a s m a  st or a g e  s a m pl e f or vir ol o g y  t e sti n g at all  visits  e x c e pt  s cr e e ni n g a n d  D a y s  2  a n d 8. 
C O N F I D E N TI A L 
P a g e  1 4 
2 6 F e b 2 0 2 4 


L e n a c a p a vi r  + G S -5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St a ti sti c al A n al ysis  Pl a n  - Fi n al  A n al ys is 
V ersi o n  1. 0 
S er n m  s a m pl e s f or i m m un o g e ni cit y  ass ess m e nt ( a nti dr n g a nti b o d y  [ A D A]) will b e c oll e ct e d  at 
D a y  1  ( pr ed o s e) a n d  W e e ks  4, 1 2 , 2 6,  3 8,  a n d  5 2. 
D uri n g t he  st u d y, c o m bi n ati o n  A R T  c o n s isti ng of t h e b as eli n e r e gi m e n  ( or  a  c o m p ati bl e  re g i me n 
s ele ct e d  b y  t he  i n ves tig at or)  will b e  r est art e d i n a n y  p arti ci p a nt  \\1h o  m e et c:i crit eri a f or V F  (HI V - 1 
R N A : 2: 2 0 0  c o p ie s/ m L t h at is c o nfir m e d  u p o n  r e p e at t e sti n g or  h a s  HI V- 1 R N A : 2: 2 0 0  c o pi e s/ m L 
at st u d y d m g  dis c o nti n u ati o n). 
F e - ga m m a r e c e pt or ( F c g R) s m g  e  n u c  e o 
p ol y m or p his ms  ( S NP)  will  b e  e v a l uat e d  u s i ng  s a m pl e s  c oll e ct e d  at t h e D a y  1  vi sit 
a n al ysis). 
C O N FI D E N TI A L 
P a g e 1 5 
2 6  F e b  2 0 2 4 


L e n a c a p a v ir  + G S -5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St a ti sti c al A n al ysis  Pl a n  -  F i n al A n al ys is 
V ersi o n  1. 0 
If p arti ci p a nts  pr o vi d e  c o n s e nt ,  a sa m pl e  will  b e  c oll e ct e d  at 
t h e D a y  1  vi sit  b ut  m a y  b e  c oll e ct e d  at  a n y  ti me  d uri n g  t he  s t u d y or  at  a  s e p ar at e  st u d y  visit, if 
n e c e s sar y. 
St u d y  pr o c e d ur es  t a bl e c a n  b e  f o u n d i n A p p e n di x  1. 
1. 3.  
S a m pl e  Si z e  a n d  P o w e r 
Alt h o u g h t he  s a m p l e si z e i n t hi s st u d y is d et e n ni n e d  b a s e d  o n  pr a cti c al  c o n si d er ati o n s  a n d  p a st 
e x p eri e n c e  w it h si mil ar t y p e s of st u di e s,  a s s u mi n g  t h e 2  tr e at m e nt gr o u ps  h a v e  a  si mil ar 
vir ol o gi c  s u p pr e s si o n r at e,  a t ot al of 2 0  p aiii ci p a nt s i n t h e Pri m ar y  C o h o 1i  will  pr o vi d e  at  l e a st 
3 5 %,  t h e p o w er  t o s h o w t h e l o wer  b o u n d of 9 5 %  CI  f or  W e e k  2 6  vir ol o gi c  r es p o n s e r ate  ( HI V- 1 
R N A < 5 0 c o pi e s /m L  as  d efi n e d b y t h e U nit e d  St at e s  ( U S) F o o d  a n d  Dr u g  A d mi ni str atf o n 
( F D A)- d efi n e d s n aps h ot  al g orit h m { U. S. D e p art m e nt of H e alt h  a n d  H u m a n  S er vi c e s  2 0 1 5 })  is 
gr e at er  t h a n 8 3 %. It w as  a s s u m e d  t h at t h e vir o l o gi c r e s p o n se  r ate  at  W e e k  2 6  w a s  9 5 %  ( b a s e d o n 
Gil e a d  st u di e s  G S- U S- 3 8 0- 1 8 4 4  a n d  G S- U S- 3 8 0- 4 0 3 0) , 1 2 %  w as  a  cli ni c all y  t ol er a bl e m ar gi n 
f or P h as e l b st u di e s,  a n d  a  o n e- si d e d  e x a ct t e st w it h a s i g nifi c a n c e l ev el  0. 0 2 5  w as  us e d.  T h e 
s a m pl e si z e a n d  p o w er  c al c ul ati o ns  w er e  m a d e  us i ng  t h e st atistic al  s oft w ar e  p a c k a g e  P A S S 
( V er si o n  1 4 , N C S S,  L L C ; K a ys vill e,  Ut a h,  U S A). 
T h e  e st i m ate d  9 5 %  CI  f or p o s si bl e  r a n g e of V F  r at e i s pr o vi d e d  i n T a bl e  1- 1.  F or  e x a m p l e, v vit h 
1  V F  e v e nt  o c c urr e n c e  ( 5 % es ti m ate d  V F  r at e), a  s a m p l e si z e of 2 0  p arti ci p a nts  c a n  pr o vi d e 
9 5 %  c o nfi d e n c e  t h at t h e tr u e V F r at e  is u nli k el y  t o b e  hi g h er t h a n 2 4. 9 %. 
T a bl e  1- 1.  
Esti m at e d  Vi r ol o gi c  F ail u r e  R at e  a n d  it s 9 5 % Cl s (f r o m t h e 
Cl o p p e r- P e a rs o n  E x a ct Cl) B as e d  o n  N u m b e r  of Vi r ol o gi c  F ail u r e 
E Y e nt i n E a c h  G r o u p o ri n T ot al 
S a m pl e  Si z e 
2 0 
N u m b e r of V F  E v e nts 
0 
I 
2   
3 
4 
Esti m at e  of  I n ci d e n c e of  V F( % ) 
0. 0 
5. 0 
1 0 0 
1 5 . 0  
2 0. 0 
L o w er B o u n d of 9 5 % CI ( %) 
0. 0 
0. 1 
1. 2  
3. 2 
5. 7 
U p p er  B o u n d of 9 5 %  CI  ( %) 
1 6 . 8 
2 4 . 9  
3 1. 7  
3 7. 9 
4 3 . 7 
V F = vi r olo gi c  f ail ur e. 
S oft w ar e  P A S S ®  V ersi o n  14.  ( NC S S  L L C.,  K a ys vill e,  Ut a h,  U S A) 
A  t ot al of a p pr o x i m at el y 2 0  p arti ci p a nts i n t h e Pri m ar y  C o h ort  will  pr o vi d e  r e a s o n a bl e 
a s s e s s m e nt of s af et y a n d t h e d es cri pti v e  P K  pr ofil e  t hr o u g h o ut t h e st u d y.  A  t ot al of u p  t o 
2 0 p arti ci p a nts i n t h e o pti o n al  Pil ot  C o h ort  is b a s e d o n pr a cti c al  c o nsi d er ati o ns. 
C O N F I D E N TI A L 
P a g e 1 6 
2 6  F e b  2 0 2 4 


L e n a c a p a v ir  + G S - 5 4 2 3 +  G S- 2 8 7 2 
G S- U S- 5 3 6 -5 8 1 6 
St at isti c al A n al ys is Pl a n -  F i n al A n al y s is 
2. 
T Y P E  O F  P L A N N E D  A N A L Y S I S 
2. 1. 
I nt e ri m A n al ysis 
V ersi o n  1. 0 
Pri or  t o t h e fi n al a n al ysis , i nt eri m a n al ys es  h a v e  b e e n  c o m pl et e d.  T h e  r es ults fr o m t h e s e a n al ys es 
m a y  b e  s u b mitt e d t o s ci e ntifi c m e eti n g s  a n d  f or p u bli c ati o n s  a n d  t o r e g ul at or y a g e n ci es  t o s e e k 
g ui d a n c e  f or t h e o v er all  cli ni c al  d e v el o p m e nt  pr o gr a m. 
2. 1. 1. 
Gil e a d.  D at a  R e,•i e w  C o m mitt e e  A n al ysis 
T h e  G D R C  r e vi e w e d t h e pr o gr e s s,  u n bli n d e d  s af et y a n d  effi c a c y  d at a of t his st u d y.  T h e  G D R C 
c o n v e n e d  aft er  all  p arti ci p a nts  e nr oll e d  i n t h e Pri m ar y  C o h ort  h a d  c o m pl et e d t h eir W e e k 1 2 vi sit 
or pr e m at ur el y  di s c o nti n u e d  fr o m t h e st u d y. 
N o  f or m aJ  st o p pi n g r ul e s w as  us e d  b y  t h e G D R C  f or s af et y  o ut c o m e s. R at h er,  a  cli ni c aJ 
a s s e s s m e nt  w as  m a d e  t o d et e n ni n e if t h e n at ur e , fr e q u e n c y, a n d  s e v erit y of A Es  a s s o ci at e d  wit h 
a  st u d y r e gi m e n w arr a nt  t h e e arl y t er mi n ati o n of t h e st u d y i n t h e b e st  i nt er e st of t h e p arti ci p a nts. 
B a s e d  o n  s af et y a n d  pr eli mi n ar y  effi c a c y,  t h e G D R C  d et er mi n e d  t h at t h e o pti o n aJ  Pil ot  C o h ort 
w o ul d  b e  i m pl e m e nt e d. 
2. 2.  
P ri m a r y  A n al ysis 
T h e  u n bli n d e d  pri m ar y  a n al ysis  w a s  c o n d u ct e d  aft er aJl p arti ci p a nts  i n t h e Pri m ar y  C o h ort  h a d 
c o m pl et e d  W e e k 2 6 vi s it or  pr e m at ur el y  di s c o nti n u e d  fr o m t h e st u d y. 
2. 4.  
Fi n al  A n al ysis 
T h e  fi n al  a n al ysis  will  b e  p erf or m e d  aft er  all  p arti ci p a nt s  h a v e  c o m pl et e d  t h e st u d y or 
pr e m at ur el y  di s c o nti n u e d  fr o m t h e st u d y, o ut st a n di n g  d at a  q u eri es  h a v e  b e e n  r e s ol v e d or 
a dj u di c at e d  as  u nr e s o lv a bl e,  a n d t h e d at a  h a v e  b e e n  cl e a n e d  a n d  fi n ali z e d.  T h e  fi n al a n al y si s  will 
i n cl u d e d at a  fr o m  t h e Pri m ar y  C o h ort  a n d t h e Pil ot  C o h ort.  T hi s d o c u m e nt  d es cri b e s t h e a n al ysis 
pl a n  f or t h e Fi n al  A n al ysis. 
C O N F I D E N TI A L 
P a g e  1 7 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
3. 
G E N E R A L  C O N S I D E R A T I O N S  F O R  D A T A  A N A L Y S E S 
A n al y si s  r es ults will  b e  pr e s e nt e d  u si n g  d es cri pti v e  st atisti cs.  F or  c at e g ori c al  v ari a bl es,  t h e 
n u m b er  a n d  p er c e nt a g e of p arti ci p a nts  i n e a c h  c at e g or y  will  b e  pr es e nt e d;  f or c o nti n u o u s 
v ari a bl es,  t h e n u m b er of p arti ci p a nt s  ( n), m e a n,  st a n d ar d d e vi ati o n  ( S D) or st a n d ar d e rr or ( S E), 
m e di a n,  first q u artil e ( Ql), t hir d q u artil e  ( Q 3), mi ni m u m,  a n d  m a xi m u m  will b e pr es e nt e d. 
B y- p arti ci p a nt  listi n gs will  b e  pr e s e nt e d  f or all  p arti ci p a nt s  i n t h e All  R a n d o mi z e d  A n al ysis  S et 
a n d  s ort e d b y  p arti ci p a nt  i d e ntifi c ati o n (I D) n u m b er,  vi sit  d at e,  a n d  ti m e (if a p pli c a bl e).  D at a 
c oll e ct e d  o n  l o g f or m s , s u c h a s  A Es,  will  b e  pr e s e nt e d  i n c hr o n ol o gi c al  or d er  wit hi n  t h e 
p arti ci p a nt.  T h e  tr e at m e nt gr o u p t o w hi c h  p arti ci p a nts  w er e  r a n d o mi z e d will  b e  u s e d  i n t h e 
listi n gs. A g e,  s e x at birt h,  r a c e, a n d  et h ni cit y  will  b e  i n cl u d e d i n t h e listi n gs, as s p a c e p er mits. 
T h er e  ar e  t h e f oll o wi n g 2  s et s of a n al ys es  d efi n e d  f or t hi s st u d y.  D at a  i n cl u d e d i n e a c h a n al ysis 
ar e  d efi n e d  as  f oll o ws: 
L o n g  A cti n g  ( L A) R e gi m e n  P e ri o d  A n al y si s 
L o n g- a cti n g  ( L A) R e gi m e n  P eri o d  A n al ysis  i n cl u d e s effi c a c y  (i e, HI V- 1  R N A  a n d  C D 4  c ell 
c o u nt a n d  p er c e nt a g e)  a n d  s af et y d at a  c oll e ct e d  d uri n g L o n g  A cti n g  R e gi m e n  P e ri o d fr o m 
p arti ci p a nts  r a n d o mi z e d a n d  r e c ei v e d at l e ast o n e  d o s e of t h e c o m pl et e  l o n g a cti n g  st u d y dr u g 
r e gi m e n (i e,  S C  L E N +  G S- 5 4 2 3  a n d  G S- 2 8 7 2)  u p  t o A R T  r e st art ( e g, W e e k  2 6).  All  d at a 
c oll e ct e d  u p t o t h e l ast e x p o s ur e  d at e of L A  r e gi m e n ( d efi n e d i n S e cti o n  3. 8. 1 ) will  b e 
s u m m ari z e d e x c e pt f or d at a  o n  A Es,  d e at h  a n d  c o n c o mit a nt m e di c ati o ns.  F or  A Es,  d e at h  a n d 
c o n c o mit a nt  m e di c ati o ns,  o nl y  d at a  c oll e ct e d  pri or  t o t h e l a st e x p o s ur e  d at e of L A  re gi m e n  will 
b e  i n cl u d e d. F or  p arti ci p a nt s  w h o  di d  n ot  re st art  A R T  o n or b ef o r e l a st st u d y  d at e or h a v e 
mi s si n g  A R V  r e st art d at e , all  d at a  will  b e  i n cl u d e d. 
D at a  i n cl u d e d i n t hi s a n al y si s  will b e u s e d t o ass ess  t h e effi c a c y  a n d  s af et y d at a  c oll e ct e d  d uri n g 
t h e L A re gi m e n p eri o d of t h e st u d y.  R e s u lts  will  b e  s u m m ari z e d b y  tr e at m e nt  gr o u p a n d  o v er all. 
W h ol e  St u d y  P e ri o d  A n al y si s 
W h ol e  St u d y  P eri o d  A n al ysis  i n cl u d e s effi c a c y  (i e,  HI V- 1  R N A  a n d  C D 4  c ell  c o u nt a n d 
p er c e nt a g e)  a n d s af et y d at a c oll e ct e d  d uri n g W h ol e  St u d y  P e ri o d fr o m p arti ci p a nts  r a n d o mi z e d 
a n d  r e c ei v e d at  l e a st o n e  d o s e of st ud y  dr u g  u p t o t h e e n d of t h e st u d y  ( e g,  W e e k  5 2) . F or 
effi c a c y  s u m m ar y, all  HI V- 1 R N A a n d  C D 4  d at a  d uri n g  t h e w h ol e  st u d y will  b e  i n cl u de d. F or 
s af et y s u m m ar y,  all  s af et y d at a  c oll e ct e d  u p  t o t h e l a st e x p os ur e  d at e  ( d efi n e d  i n S e cti o n 3. 8. 1 ) 
fr o m p arti ci p a nts  w h o  pr e m at ur el y  di s c o nti n u e d  st u d y or c o m pl et e d  st u d y will  b e  i n cl u de d. 
D at a  i n cl u d e d i n t hi s a n al y si s  will b e u s e d t o ass ess  t h e effi c a c y  a n d  s af et y d at a  c oll e ct e d  d uri n g 
t h e stu d y.  R es ults  will  b e  s u m m ari z e d b y  tr e at m e nt gr o u p  a n d  o v er all. 
C O N FI D E N TI A L 
P a g e 1 8 
2 6  F e b 2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
3. 1.  
A n al y si s  S ets 
V ersi o n  1. 0 
A n al y si s  s et s  d efi n e  t h e p arti ci p a nts  t o b e  i n cl u d e d i n a n  a n al ysis.  A n al ysis  s ets  a n d  t h eir 
d efi niti o ns  ar e  pr o vi d e d  i n t his s e cti o n.  T h e  a n al ysis  s et will  b e  i d e ntifi e d a n d  i n cl u d e d a s  a 
s u btitl e of e a c h  t a bl e, fi g ur e,  a n d  listi n g. 
F or  e a c h  a n al ysis  s et, t h e n u m b er  a n d  p er c e nt a g e of p arti ci p a nt s  eli gi bl e  f or i n cl u si o n will  b e 
s u m m ari z e d b y tr e at m e nt gr o u p  a n d t ot al. 
A  li sti n g of r e as o ns f or e x cl u si o n  fr o m a n al ysis  s ets  will  b e  pr o vi d e d  b y  p arti ci p a nt. 
3. 1. 1.  
All  R a n d o mi z e d  A n al y si s  S et 
T h e  All  R a n d o mi z e d  A n al ysis  S et  i n cl u d e s all  p arti ci p a nts  w h o  w er e  r a n d o mi z e d i nt o t h e st u d y. 
T hi s  is t h e pri m ar y  a n al ysis  s et f or b y- p arti ci p a nt  listi n gs. 
3. 1. 2.  
F ull  A n al y si s  S et 
T h e  F ull  A n al y si s  S et  ( F A S) i n cl u d es all  r a n d o mi z e d p arti ci p a nts  w h o  h a v e  r e c ei v e d at  l e a st o n e 
d os e of t h e c o m pl et e  l o n g a cti n g  st u d y  dr u g  r e gi m e n (i e, S C L E N + G S- 5 4 2 3  a n d  G S- 2 8 7 2),  a n d 
d o  n ot  h a v e  m aj or  pr ot o c ol  vi ol ati o n  ( d efi n e d as m e eti n g  e x cl u si o n  crit eri o n of h a vi n g  c hr o ni c 
h e p atitis  B  vir u s  ( H B V) i nf e cti o n). T hi s  is t h e pri m ar y  a n al ysis  s et f or effi c a c y  a n al ys es. 
3. 1. 3.  
P e r  P r ot o c ol  A n al y si s  S et 
T h e P e r  P r ot o c ol  ( P P) A n al y si s  S et i n cl u d es all  p arti ci p a nts  i n t h e F A S  e x cl u di n g  p arti ci p a nt s 
m e eti n g  a n y of t h e f oll o wi n g crit eri a: 
•  Di d n ot h a v e  o n-tr e at m e nt  HI V- 1  R N A  i n t h e W e e k  2 6  a n al ysis  wi n d o w,  e x c e pt w h e n 
mi s si n g  is d u e t o di s c o nti n u ati o n of st u d y dr u g  f or l a c k of effi c a c y  as  i n T a bl e 3- 1 . ( N ot e: 
l a c k of effi c a c y  is d efi n e d  as  h a vi n g  t h e c h e c k-b o x  f or L a c k of Effi c a c y  m ar k e d as t h e r e a s o n 
f or pr e m at ur e  st u d y  dr u g  di s c o nti n u ati o n  o n  t h e st u d y dr u g  c o m pl eti o n e C R F  p a g e.) 
•  R e c ei v e d  p arti al  or  mi s s e d  d os es  o n  D a y  1 or D a y 2. 
•  Pri or  r e c ei pt of a n y  a nti - HI V- I  m A bs  (i n cl u di n g i b ali z u m a b ). 
•  H a v e  b e e n tr e at e d wit h  i m m u n o s u p pr e s s a nt t h er a pi e s or  c h e m ot h er a p e uti c  a g e nt s  ( e g , 
c orti c ost er oi ds,  i m m u n o gl o b uli n s, a n d  ot h er  i m m u n e- or c yt o ki n e- b a s e d  t h er a pi e s)  wit hi n 4 
w e e k s of st u d y s cr e e ni n g or h a v e  a n  a nti ci p at e d  n e e d  f or s u c h tr e at m e nt d uri n g  t h e stu d y. 
C O N FI D E N TI A L 
P a g e  1 9 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
T a bl e  3- 1.  
P a rti ci p a nt s  E x cl u d e d  f r o m P e r  P r ot o c ol  A n al y si s  S et D u e t o 
P r e m at u r e  Di s c o nti n u ati o n of St u d y  D r u g  a n d/ o r  Mi s si n g  HI V- 1 
R N A  A s s e s s m e nt i n W e e k 2 6 A n al y si s  Wi n d o w 
HI V- 1  R N A  D at a  o n  T r e at m e nt  A v ail a bl e  i n 
Di s c o nti n u ati o n  f r o m  St u d y  D r u g  p ri o r  t o o r o n  t h e 
W e e k 2 6 A n al y si s  Wi n d o w 
U p p e r  B o u n d of W e e k 2 6 A n al ysis  Wi n d o w 
Y e s 
N o 
D u e  t o L a c k of Effi c a c y 
+ 
+ 
Y es 
D u e  t o Ot h er  R e a s o n s 
+ 
-
N o 
+ 
-
+ = I n cl usi o n of P arti ci p a nts i n W e e k 2 6 P P  a n al ysis  s et;  - = E x cl usi o n of P arti ci p a nts i n W e e k  2 6  P P  a n al ysis  s et. 
O n- Tr e at m e nt  HI V-I  R N A  d at a  i n cl u d e all  HI V-I  R N A  d at a  c oll e ct e d u p t o t h e e arli est  d at e of ( 1 9 6 d a y s  [ 2 8 w e e ks]  aft er t h e 
d os e  d at e of c o m pl et e  l o n g a cti n g  r e gi m e n, d at e  ofr e st arti n g  A R T). 
T h e  d at e of st u d y  dr u g  pr e m at ur e  di s c o nti n u ati o n  i s t h e l a st e x p os ur e  d at e  f or p arti ci p a nt s  w h o 
pr e m at ur el y  di s c o nti n u e d  st u d y dr u g. 
F or  t h e P er  Pr ot o c ol  a n al ysis,  effi c a c y  d at a u p t o t h e  e arli e st  d at e of ( 1 9 6  d a ys  [ 2 8 w e e ks]  aft er 
t h e d o s e  d at e of c o m pl et e  l o n g a cti n g  r e gi m e n, d at e of r e st arti n g A R T)  will  b e  i n cl u d e d. 
T h e  P er  Pr ot o c ol  A n al ysis  S et is t h e s e c o n d ar y a n al ysis  s et f or effi c a c y  a n al ysis. 
3. 1. 4.  
S af et y  A n al y si s  S et 
T h e  S af et y  A n al ysis  S et is t h e pri m ar y  a n al ysis  s et f or s af et y  a n al ys es.  S af et y  a n al ysis  s et s ar e 
d efi n e d  f or t hi s st u d y: 
•  T h e  S af et y  A n al ysis  S et  i n cl u d es all  p arti ci p a nts  w h o  w er e  r a n d o mi z e d a n d  r e c ei v e d at  l e ast 
1  d os e of st u d y  dr u g.  T his  is t h e pri m ar y  a n al ysis  s et f or s af et y a n al ys es  f or w h ol e  st u d y 
p eri o d.  T his  a n al ysis  s et will  als o  b e  u s e d  t o d e s cri b e  b a s eli n e  i nf or m ati o n. 
•  T h e  S af et y  A n al ysis  S et  f or L A R e gi m e n  i n cl u d e s all  r a n d o mi z e d p arti ci p a nts  w h o  h a v e 
r e c ei v e d at l e a st o n e  d o s e of t h e c o m pl et e  l o n g a cti n g  st u d y  dr u g  r e gi m e n (i e, S C L E N + G S-
5 4 2 3  a n d  G S- 2 8 7 2).  T his  is t h e pri m ar y  a n al ysis  s et f or s af et y a n al ys es  f or L A r e gi m e n 
p eri o d  a n al ysis. 
3. 1. 5.  
P h a r m a c o ki n eti c  ( P K) S u b st u d y  A n al y si s  S et 
T h e  L E N  P K  S u b st u d y  A n al ysis  S et  i n cl u d e s all  r a n d o mi z e d  p arti ci p a nt s w h o  ar e  e nr oll e d  i n t h e 
o pti o n al  P K  S u bst u d y,  h a v e  r e c ei v e d at l e a st 1  d o s e of st u d y dr u g,  a n d  h a v e at l e a st 1 
n o n mi s si n g  L E N  c o n c e ntr ati o n  v al u e  r e p ort e d b y  t h e P K  l a b or at or y t est. 
C O N FI D E N TI A L 
P a g e  2 0 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
3. 1. 6.  
P h a n n a c o ki n eti c  ( P K) A n al y si s  S et s 
T h e P K A n al y si s  S ets  i n cl u d e t h e f oll o ws: 
V ersi o n  1. 0 
•  L E N  P K  A n al ysis  S et  i n cl u d es all  r a n d o mi z e d p arti ci p a nts  w h o  h a v e  r e c ei v e d at  l e a st 1  d os e 
of st u d y dr u g,  a n d  h a v e  at  l e ast 1  n o n mi s si n g  L E N  c o n c e ntr ati o n  v al u e  r e p ort e d b y  t h e P K 
l a b or at or y t est. 
•  G S- 5 4 2 3  P K  A n al ysis  S et  i n cl u d e s all  r a n d o mi z e d  p arti ci p a nt s w h o  h a v e  r e c ei v e d at  l e a st 1 
d os e of st u d y dr u g,  a n d  h a v e  at  l e a st 1  n o n mi s si n g  G S- 5 4 2 3  c o n c e ntr ati o n  v al u e  r e p o rt e d b y 
t h e P K  l a b or at or y t est. 
•  G S- 2 8 7 2  P K  A n al ysis  S et  i n cl u d e s all  r a n d o mi z e d  p arti ci p a nt s w h o  h a v e  r e c ei v e d at  l e a st 1 
d os e of st u d y dr u g,  a n d  h a v e  at  l e a st 1  n o n mi s si n g  G S- 2 8 7 2  c o n c e ntr ati o n  v al u e  r e p ort e d b y 
t h e P K  l a b or at or y t est. 
3. 1 .7.  
I m m u n o g e ni cit y A n al y si s  S et s 
T h e  I m m u n o g e ni cit y a n al ysis  s et s  i n cl u d e t h e f oll o ws: 
•  A nti- G S- 5 4 2 3  I m m u n o g e ni cit y A n al ysis  S et  will  i n cl u d e all  r a n d o mi z e d p a rti ci p a nts w h o 
h a v e  r e c ei v e d at l e a st 1  d o s e of st u d y dr u g  a n d  h a v e  h a d at l e a st 1  n o n mi s si n g  v al u e  f or a nti-
G S- 5 4 2 3  e v al u ati o n. 
•  A nti- G S- 2 8 7 2  I m m u n o g e ni cit y A n al y sis  S et  will  i n cl u d e all  r a n d o mi z e d p arti ci p a nts  w h o 
h a v e  r e c ei v e d at  l e a st 1  d os e of st u d y dr u g  a n d  h a v e  h a d at le ast 1  n o n mi s s i n g v al u e  f or a nti -
G S- 5 4 2 3  e v al u ati o n. 
•  A nti- G S- 5 4 2 3  a n d  A nti- G S- 2 8 7 2  I m m u n o g e ni cit y A n al ysis  S et  will  i n cl u d e all  r a n d o mi z e d 
p arti ci p a nt s  w h o  h a v e  r e c ei v e d at  l e a st 1  d os e of st u d y dr u g  a n d  h a v e  h a d  at  l e a st 1 
n o n mi s si n g  v al u e  f or b ot h  a nti - G S- 5 4 2 3  a n d  a nti - G S- 2 8 7 2  e v al u ati o n. 
3. 2.  
P a rti ci p a nt  G r o u pi n g 
F or  a n al y s e s  b a s e d o n t h e All  R a n d o mi z e d  A n al ysi s  S et or t h e  F AS, p arti ci p a nt s  will b e gr o u p e d 
a c c or di n g t o t he  tre at m e nt gr o u p  t o w hi c h  t h ey  w er e  r a n d o miz e d.  F or  all  ot h er  a n al y s es, 
p arti ci p a nts  will  b e  gr o u p e d  a c c or di n g  t o t h e a ct u al  tr e at m e nt r e c ei v e d.  T h e  a c t u al tr e at m e nt 
r e c ei v e d will  diff er  fr o m t h e r a n d o mi z e d tr e at m e nt o nl y  w h e n  t h eir a ct u al tr e at m e nt diff ers  fr o m 
r a n d o mi z e d tr e at m e nt f or t h e e ntir e  tr e at m e nt d ur ati o n.  T e m pl at e s of p arti ci p a nt  gr o u pi n g  c a n b e 
f o u n d i n A p p e n di x  6. 
C O N FI D E N TI A L 
P a g e  2 1 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
3. 2. 1. 
G r o u pi n g  f o r E n r ol b n e nt,  Eli gi bilit y,  Di s p o siti o n,  D e m o g r a p hi c s,  B a s eli n e 
C h a r a ct e ri sti c s  a n d  S af et y  A n al y s e s 
F or  e nr oll m e nt,  eli gi bilit y,  pr ot o c ol  d e v ei ati o n , dis p ositi o n,  d e m o gr a p hi c s , b a s eli n e 
c h ar a ct eristi cs  i n cl u di n g b a s eli n e  A R Vs  a n d  s af et y a n al y s e s,  p arti ci p a nt s  will  b e  gr o u p e d  a s 
f oll o ws f or t a bl e s u m m ar y: 
•  Pri m ar y  C o h ort 
- 
Tr e at m e nt  Gr o u p 1: S C  L E N  +  G S- 5 4 2 3  +  G S- 2 8 7 2  1 0  m g/ k g 
- 
Tr e at m e nt  Gr o u p 2: S C L E N + G S- 5 4 2 3  +  G S- 2 8 7 2 3 0 m g /k g 
- 
T ot al  Pri m ar y  C o h orts:  All  p arti ci p a nt s  fr o m Tr e at m e nt  Gr o u ps  1  a n d  2  (f or all t a bl e s a n d 
fi g ur e  s u m m ar y u nl ess  s p e cifi e d ot h er wi s e) 
•  Pil ot  C o h ort 
- 
Tr e at m e nt  Gr o u p 1: S C L E N + G S- 5 4 2 3  +  G S- 2 8 7 2  1 0 m g /k g 
- 
Tr e at m e nt  Gr o u p 2: S C L E N + G S- 5 4 2 3  +  G S- 2 8 7 2 3 0 m g /k g 
- 
T ot al  Pil ot  C o h orts:  All  p arti ci p a nts  fr o m  Tr e at m e nt  Gr o u ps  1  a n d 2  (f or all  t a bl e s a n d 
fi g ur e  s u m m ar y u nl ess  s p e cifi e d ot h er wi s e) 
•  P o ol e d  C o h ort s 
- 
T ot al  P o ol e d  C o h orts:  All  p arti ci p a nt s  fr o m p o ol e d  Tr e at m e nt  Gr o u p s  1  a n d  2  (f or all 
t a bl e s a n d  fi g ur e s u m m ar y u nl e s s  s p e cifi e d ot h er wi s e) 
3. 2. 2. 
G r o u pi n g  f o r Effi c a c y  A n al y s e s 
F or  effi c a c y  a n al ys es,  p arti ci p a nts  will  b e  gr o u p e d as f oll o w s f or ta bl e  s u m m ar y: 
•  Pri m ar y  C o h ort 
- 
Tr e at m e nt  Gr o u p 1: S C L E N + G S- 5 4 2 3  +  G S- 2 8 7 2  1 0 m g /k g 
-
Tr e at m e nt  Gr o u p 2: S C  L E N  +  G S- 5 4 2 3  +  G S- 2 8 7 2 3 0 m g /k g 
- 
T ot al  Pri m ar y  C o h orts:  All  p arti ci p a nt s  fr o m Tr e at m e nt  Gr o u ps  1  a n d  2  (f or all t a bl e s a n d 
fi g ur e  s u m m ar y u nl ess  s p e cifi e d ot h er wi s e) 
•  Pil ot  C o h ort 
- 
Tr e at m e nt  Gr o u p 1: S C  L E N  +  G S- 5 4 2 3  +  G S- 2 8 7 2  1 0  m g/ k g 
- 
Tr e at m e nt  Gr o u p 2: S C  L E N +  G S- 5 4 2 3  +  G S- 2 8 7 2 3 0 m g /k g 
- 
T ot al  Pil ot  C o h orts:  All  p arti ci p a nts  fr o m Tr e at m e nt  Gr o u ps  1  a n d  2  (f or a ll t a bl e s a n d 
fi g ur e  s u m m ar y u nl ess  s p e cifi e d ot h er wi s e) 
C O N FI D E N TI A L 
P a g e  2 2 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
N o  p o ol e d  a n al y s e s  will  b e  c o n d u ct e d  o n  t h e effi c a c y. 
3. 2. 3.  
G r o u pi n g  f o r P K a n d  I m m u n o g e ni cit y A n al y s e s 
V ersi o n  1. 0 
F or  P K  a n al y si s  of G S- 5 4 2 3  a n d  L E N,  as  w ell  as  i m m u n o g e ni cit y a n al ysis of G S- 5 4 2 3  a n d  G S-
2 8 7 2,  p arti ci p a nt s  will b e gr o u p e d as f oll o w s f or t a bl e s u m m ar y: 
•  
Pri m ar y  C o h ort 
- 
Tr e at m ent Gr o u p 1: S C L E N + G S- 5 4 2 3  +  G S- 2 8 7 2  1 0 m g /k g 
- 
Tr e at m e nt  Gr o u p 2: S C  L E N +  G S- 5 4 2 3  +  G S- 2 8 7 2 3 0 m g /k g 
- 
T ot al  Pri m ar y  C o h orts:  All  p arti ci p a nt s  fr o m Tr e at m e nt  Gr o u p s  1  a n d  2  (f or all t a bl e s a n d 
fi g ur e s u m m ar y u nl e s s  s p e cifi e d ot h er wi s e) 
•  
Pil ot  C o h ort 
- 
Tr e at m e nt  Gr o u p 1: S C  L E N +  G S- 5 4 2 3  +  G S- 2 8 7 2  1 0 m g /k g 
- 
Tr e at m e nt  Gr o u p 2: S C L E N + G S- 5 4 2 3  +  G S- 2 8 7 2 3 0 m g /k g 
- 
T ot al  Pil ot  C o h orts:  All  p arti ci p a nt s  fr o m  Tr e at m e nt  Gr o u p s  1  a n d  2  (f or all  t abl e s  a n d 
fi g ur e s u m m ar y u nl e s s  s p e cifi e d ot h er wi s e) 
•  
P o ol e d  C o h ort s 
- 
Tr e at m e nt  Gr o u p 1: S C L E N + G S- 5 4 2 3  +  G S -2 8 7 2  1 0 m g /k g 
- 
Tr e at m ent Gr o u p 2: S C  L E N  +  G S- 5 4 2 3  +  G S- 2 8 7 2 3 0 m g /k g 
- 
T ot al  P o ol e d  C o h orts:  All  p arti ci p a nt s  fr o m p o ol e d  Tr e a t m e nt Gr o u p s  1  a n d  2  (f or all 
t a bl e s a n d  fi g ur e s u m m ar y u nl e s s  s p e cifi e d ot h e r wis e ) 
F or  P K  a n al y si s  of G S- 2 8 7 2,  p arti ci p a nt s  will b e gr o u p e d  a s  f oll o w s  f or t a ble  s u m m ar y: 
•  
Pri m ar y  C o h ort 
- 
Tr e a t m e nt Gr o u p 1: S C  L E N +  G S- 5 4 2 3  +  G S- 2 8 7 2  1 0 m g /k g 
- 
Tr e at m ent Gr o u p 2: S C L E N + G S- 5 4 2 3  +  G S- 2 8 7 2  3 0 m g / k g 
•  
Pil ot  C o h ort 
- 
Tr e at m e nt  Gr o u p 1: S C  L E N +  G S- 5 4 2 3  +  G S- 2 8 7 2  1 0 m g /k g 
-
Tr e at m e nt  Gr o u p 2: S C  L E N  +  G S- 5 4 2 3  +  G S- 2 8 7 2 3 0 m g / k g 
•  
P o ol e d  C o h ort s 
- 
Tr e at m e nt  Gr o u p 1: S C  L E N +  G S- 5 4 2 3  +  G S -2 8 7 2  1 0 m g /k g 
C O N FI D E N TI A L 
P a g e  2 3 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
- 
Tr e at m e nt  Gr o u p 2: S C L E N + G S- 5 4 2 3  +  G S- 2 8 7 2 3 0 m g /k g 
P K r es ults of G S- 2 8 7 2  will  n ot  b e  s u m m ari z e d a cr o s s  t h e tr e at m e nt gr o u ps. 
3. 3. 
St r at a  a n d  C o v a ri at e s 
T h er e  is n o  str atifi c ati o n f or r a n d o mi z ati o n f or t h e Pri m ar y  C o h ort. 
V ersi o n  1. 0 
R e g ar di n g  t h e o pti o n al  Pil ot  C o h ort,  r a n d o mi z ati o n h a s  b e e n  str atifi e d b y  t h e a nti b o d y  ( G S- 5 4 2 3 
or G S- 2 8 7 2)  t o w hi c h  t h e p arti ci p a nt  is s e nsiti v e,  b ut t h e str at a will  n ot  b e  u s e d  i n t he  a n al ys es 
b e c a u s e of t h e s m all  s a m pl e  si z e of t h e st u d y. 
3. 4.  
E x a mi n ati o n of P a rti ci p a nt  S u b g r o u p s 
T h er e  ar e  n o  pr e s p e cifi e d  p arti ci p a nt  s u b gr o u pi n gs  f or effi c a c y  a n d  s af et y a n al ys es  d u e  t o t h e 
s m all s a m pl e si z e. 
3. 5.  
M ulti pl e  C o m p a ri s o n s 
A dj u st m e nt s  f or m ulti pli cit y  will  n ot  b e  c o n d u ct e d  i n t hi s p h as e  1 b  tri al. 
3. 6. 
3. 6. 1. 
Mi s si n g  D at a  a n d  O utli e r s 
Mi s si n g  D at a 
I n g e n er al,  mi s si n g  d at a  will  n ot b e i m p ut e d u nl e s s  m et h o d s  f or h a n dli n g  mi s si n g  d at a  ar e 
s p e cifi e d.  E x c e pti o ns  ar e  pr e s e nt e d i n t hi s d o c u m e nt. 
T h e  h a n dli n g of mi s si n g or i n c o m pl et e d at es  f or  A E  o n s et  is d es cri b e d  i n S e cti o n  7. 1. 5 . 2 a n d  f or 
pri or  a n d  c o n c o mit a nt  m e di c ati o n s  i n S e cti o n  7. 4. 
Mi s si n g  P K  s a m pli n g  d at e s m a y b e  i m p ut e d b a s e d  o n  ot h er  vi sit  i nf or m ati o n. Mi s si n g  P K 
s a m pli n g ti mes  m a y  b e  i m p ut e d t o n o mi n al  ti m es. Mi s si n g  dr u g  c o n c e ntr ati o n s  will  n ot  b e 
i m p ut e d. 
3. 6. 2. 
O utli e r s 
O utli e rs  will  b e  i d e ntifi e d d uri n g  t he  d at a  m a n a g e m e n t a n d  d at a  a n al ysis  pr o c ess,  b ut  n o 
s e n siti vit y a n al ys es  will  b e  c o n d u ct e d.  All  d at a  will  b e  i n cl u de d  i n t h e d at a  a n al ysis. 
I n di vi d u al st u d y dr u g  c o n c e ntr ati o n  v al u e s  m a y  b e  i d e ntifi e d a s  o utli ers  b y  t h e cli ni c al 
p h ar m a c o ki n eti ci st  a n d  e x cl u d e d  fr o m c o n c e ntr ati o n  s u m m ar y t a bl es  a n d  fi g ur es  a n d  fr o m t h e 
n o n c o m p art m e nt al  P K  a n al ysis.  O utli er  dr u g  c o n c e ntr ati o n s  will  b e  i d e ntifi e d i n t h e 
c o n c e ntr ati o n  listi n g al o n g  wit h  t h e j u stifi c ati o n f or e x cl usi o n. 
C O N FI D E N TI A L 
P a g e  2 4 
2 6  F e b 2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
3. 7. 
3. 7. 1. 
D at a  H a n dli n g  C o n v e nti o n s  a n d  T r a n sf o r m ati o n s 
D at a  H a n dli n g  C o n v e nti o n s  a n d  T r a n sf o r m ati o n s  f o r N o n- P K  D at a 
V ersi o n  1. 0 
O nl y  y e ar of birt h  is  c oll e ct e d i n t hi s st u d y.  T h e  f oll o wi n g c o n v e nti o n s  will  b e  u s e d  f or t h e 
i m p ut ati o n of d at e of birt h  w h e n  it is p arti all y  mi s si n g  or  n ot  c oll e ct e d: 
• 
If y e ar of birt h is c oll e ct e d, " 0 1  J ul y " will b e i m p ut e d as  t h e d a y  a n d  m o nt h of birt h 
• 
If y e ar of birt h is missi n g,  d at e of birt h  will  n ot b e i m p ut e d. 
I n g e n er al,  a g e  c oll e ct e d  at  D a y  1  (i n y e ar s)  will  b e  u s e d  f or a n al ys es  a n d  pr e s e nt e d  i n listi n gs. If 
a g e  at  D a y  1  is n ot  a v ail a bl e  f or a  p arti ci p a nt,  a g e  d eri v e d  b a s e d  o n  d at e of birt h  a n d  t h e D a y  1 
vi sit  d at e  will  b e  u s e d  i nst e a d. If a  r a n d o mi z e d p arti ci p a nt  w as  n ot  d o s e d  wit h  a n y  st u d y dr u g, 
t h e r a n d o mi z ati o n d at e  will b e u s e d  i nst e a d of t h e D a y  1  vi sit  d at e.  F or  s cr e e n f ail ur es,  t h e d at e 
t h e fir st i nf or m e d c o n s e nt  w a s  si g n e d will b e u s e d  f or t h e a g e  d eri v ati o n.  A g e  r e q uir e d f or 
l o n git u di n al a n d t e m p or al c al c ul ati o ns  a n d  a n al y s e s  ( e g,  esti m at es of cr e ati ni n e  cl e ar a n c e)  will 
b e  b a s e d  o n  a g e  d eri v e d  fr o m  d at e of birt h  a n d t h e d at e of t h e m e a s ur e m e nt or e v e nt,  u nl e s s 
ot h er wi s e  s p e cifi e d. 
HI V- 1  R N  A  r es ults of ' N o HI V- 1  R N  A  d et e ct e d'  a n d  " < 2 0  c p /m L HI V - 1 R N  A  D et e ct e d "  will 
b e  i m p ut e d as  1 9  c o pi e s/ m L  f or a n al y si s  p ur p o s e s. 
F or  ot h er  n o n- P K  d at a t h at ar e  c o nti n u o us i n n at ur e  b ut  ar e  l ess t h a n t h e l o w er li mit of 
q u a ntifi c ati o n  ( L L O Q) or a b o v e  t h e u p p er  li mit of q u a ntifi c ati o n  ( U L O Q) will b e i m p ut e d as 
f oll o ws: 
•    A v al u e  t h at is 1  u nit  l ess t h a n t h e L L O Q  will b e u s e d  t o c al c ul at e  d e s cri pti v e  st atisti cs if t h e 
d at u m  is r e p ort e d i n t h e f or m of " < x " ( w h er e xi s c o n si d er e d t h e L L O Q).  F or  e x a m pl e, if t h e 
v al u e s  ar e  r e p ort e d as <  5 0  a n d <  5. 0,  v al u e s of 4 9  a n d  4. 9,  r es p e cti v el y, will  b e  u s e d  t o 
c al c ul at e  s u m m ar y st atisti cs.  A n  e x c e pti o n t o t hi s r ul e is a n y  v al u e  r e p ort e d a s <  1  or <  0. 1, 
et c.  F or  v al u es  r e p ort e d as <  1  or <  0. 1,  a  v al u e of 0. 9  or  0. 0 9,  r es p e cti v el y, will  b e  u s e d t o 
c al c ul at e  s u m m ar y st atisti cs. 
•    A v al u e  t h at is 1  u nit  a b o v e  t he  U L O Q  will  b e  us e d t o c al c ul ate  d e s cri pti v e  st ati sti c s if t h e 
d at u m  is r e p ort e d i n t h e f or m of " > x " ( w h er e x is c o n si d er e d t h e U L O Q).  V al u e s  wit h 
d e ci m al  p oi nts  will  f oll o w t h e s a m e  l o gi c as a b o v e. 
•  T h e  li mit of q u a ntifi c ati o n  will  b e  us e d t o c al c ul at e  d e s cri pti v e  st atisti cs if t h e d at u m  is 
r e p ort e d i n t h e f or m of " : S: x " or " ;: c,: x "  ( w h er e xi s c o n si d er e d t h e li mit of q u a ntifi c ati o n). 
3. 7. 2. 
D at a  H a n dli n g  C o n v e nti o n s  a n d  T r a n sf o r m ati o n s  f o r P K D at a 
N at ur al  l o g arit h mi c tr a n sf or m ati o n will  b e  us e d  f or n o n- B L Q  dr u g  c o n c e ntr ati o ns  a n d  a n al y si s of 
P K p ar a m et ers.  C o n c e ntr ati o n  v al u es  t h at ar e  b e l o w t h e li mit of q u a ntit ati o n  ( B L Q) will b e 
pr e s e nt e d  a s " B L Q " i n t h e c o n c e ntr ati o n  d at a  listi n g. 
C O N FI D E N TI A L 
P a g e 2 5 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
F or  s u m m ar y st atisti cs, B L Q v al u e s  will b e tr e at e d as  z er o  at  pr e d o s e  a n d  p ost d os e  ti m e p oi nts. 
At pr e d os e, if all  c o n c e ntr ati o n  v al u es  ar e  B L Q , t h e n t h e m e a n,  a n d  or d er  st atisti cs  (mi ni m u m , 
Ql, m e di a n,  Q 3,  a n d  m a xi m u m)  will  b e  dis pl a y e d  as  O  a n d  t h e r e st of t h e s u m m ar y st atisti cs  (i e, 
S D a n d C V) will  b e  missi n g. If a n y  pr e d o s e  c o n c e ntr ati o n  v al u es  ar e  n o n- B L Q,  t h e n t h e n u m b er 
of s a m pl es,  or d er  st atisti cs,  a n d  all  s u m m ar y st atisti cs  will  b e  dis pl a y e d. 
At a n y  gi v e n  p o st d o s e  ti m e p oi nt, if m or e  t h a n o n e-t hir d of t h e p arti ci p a nt s  h a v e  a  c o n c e ntr ati o n 
v al u e of B L Q,  t h e n o nl y t h e n u m b er of s a m pl es  a n d  or d er  st atisti cs  will  b e  di s pl a y e d  i n t h e 
s u m m ar y t a bl e; ot h er wis e,  or d er  st ati sti c s  a n d  s u m m ar y st atisti cs  will  b e  di s pl a y e d  i n t h e 
s u m m ar y t a bl e. 
T h e  f oll o wi n g c o n v e nti o n s  will  b e  u s e d  f or t h e pr e s e nt ati o n of or d er  st atisti cs  f or p o st d o s e  ti m e 
p oi nts  i n t h e s u m m ar y t a bl e: 
• 
If at  l e a st 1  p arti ci p a nt  h a s  a  c o n c e ntr ati o n  v al u e of " B L Q " f or t h e ti m e p oi nt , t h e mi ni m u m 
v al u e  will  b e  di s pl a y e d as " B L Q ". 
• 
If m or e  t h a n 2 5 % of t h e p arti ci p a nt s  h a v e  a  c o n c e ntr ati o n  v al u e of " B LQ " f or a  gi v e n ti m e 
p oi nt,  t h e mi ni m u m  a n d Ql v al u e s  will  b e  dis pl a y e d  as  " B L Q ". 
• 
If m or e  t h a n 5 0 % of t h e p arti ci p a nt s  h a v e  a  c o n c e ntr ati o n  v al u e of " B L Q "  f or a  gi v e n ti m e 
p oi nt,  t h e mi ni m u m, Ql , a n d  m e di a n  v al u es  will  b e  di s pl a y e d  a s  " B L Q ". 
• 
If m or e  t h a n 7 5 % of t h e p arti ci p a nt s  h a v e  a  c o n c e ntr ati o n  v al u e of " B L Q " f or a  gi v e n  ti m e 
p oi nt , t h e mi ni m u m, Ql, m e di a n , a n d Q 3 v al u e s  will  b e  di s pl ay e d  a s " BL Q " . 
• 
If all  p arti ci p a nts  h a v e  c o n c e ntr ati o n  v al u es of " B L Q " f or a  gi v e n  ti me  p oi nt,  all  or d er 
st atisti cs  ( mi ni m u m, Ql, m e di a n, Q 3 , a n d  m a xi m u m)  a n d  s u m m ar y st ati sti c s will b e 
dis pl a y e d  as  " B L Q ". 
Si mil arl y,  f or P K  c o n c e ntr ati o n  pl otti n gs, if m or e  t h a n o n e-t hir d of t h e p arti ci p a nt s h a v e  a 
c o n c e ntr ati o n  v al u e s of B L Q,  t h e n t h e m e a n  a n d  st a n d ar d d e vi ati o n  ar e  n ot  di s pl a y e d  at t h at 
ti m e p oi nt; a n d if m or e  t h a n o n e- h alf of t h e p arti ci p a nt s  h a v e  a  c o n c e ntr ati o n  v al u es of B L Q , t he n 
t h e m e di a n  a n d  q u artil es  ar e  n ot  di s pl a y e d at t h at ti m e p oi nt. 
C o n c e ntr ati o n  r el at e d P K  p ar a m et er s  ( e g, C m a x a n d  C 2 6w k) t h at ar e  B L Q  will  b e  e x cl u d e d  b ef or e 
l o g tr a n sf or m ati o n or st atisti c al m o d el  fitti n g a n d  di s pl a y e d  a s  d e s c ri b e d a b o v e. 
3. 8. 
A n al y si s  Vi sit  Wi n d o w s 
N o mi n al  vi sit s  will  b e  u s e d  f or t h e P h ar m a c o ki n eti c  a n d  I m m u n o g e ni cit y s u m m ari es.  D et ails  f or 
a n al ysis  vi sit  wi n d o w s  u s e d  f or effi c a c y  a n d  s af et y a n al ys es  i n t h e fi n al  a n al y si s  c a n  b e  f o u n d 
S e cti o n  3 . 8. 2. 
C O N FI D E N TI A L 
P a g e  2 6 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
3. 8. 1.  
D efi niti o n of K e y  D at e s  a n d  St u d y  D a y 
V ersi o n  1. 0 
St u d y  D a y  1 is d efi n e d as t h e d a y  w h e n  t h e fir st d os e of a n y  st u d y dr u g  w as  t a k e n, as r e c or d e d 
o n t h e St u d y  Dr u g  A d mi ni str ati o n  e C R F  (i e, or al  L E N,  S C  L E N or i nf u si o n dr u gs  [ G S- 5 4 2 3, 
G S- 2 8 7 2]). 
L a st  D o s e  D at e is d efi n e d  as  t h e l at e st d os e  d at e of a n y  st u d y  dr u g as r e c or d e d o n  t h e St u d y 
Dr u g  A d mi ni str ati o n  e C R F  (i e,  or al  L E N,  S C  L E N  or  i nf u si o n dr u g s  ( G S- 5 4 2 3, G S- 2 8 7 2)  f or 
p arti ci p a nts  w h o  pr e m at ur el y  di s c o nti n u e d  st u d y dr u g or c o m pl et e d  st u d y dr u g  a c c or di n g  t o 
St u d y  Dr u g  C o m pl eti o n  e C R F. 
St u d y  D a ys ar e  c al c ul at e d  r el ati v e t o St u d y  D a y  1 of st u d y dr u g  a n d  d eri v e d  a s  f oll o ws: 
•  F or  p ost d os e  st u d y  d a ys:  A s s e s s m e nt  D at e  - Fir st  D o s e D at e + 1 
•  F or  d a y s  pri or t o t h e first d os e:  A s s e s s m e nt  D at e  - Fir st  D os e  D at e 
B a s eli n e  V al u e is d efi n e d  as  t h e l ast v al u e  o bt ai n e d  o n or pri or  t o t h e first d os e of st u d y  dr u g. 
L a st  St u d y  D at e is t h e l at e st cli ni c  vi sit  d at e s,  a n d/ or t h e l a b or at or y vi sit  d at es,  w hi c h e v er  is 
l at est, i n cl u di n g t h e a n y  f oll o w- u p vi sit  d at es,  f or p arti ci p a nts  w h o  pr e m at ur el y  di s c o nti n u e d 
st u d y  or  c o m pl et e d  st u d y a c c or di n g t o t h e St u d y  C o m pl eti o n  e C R F. 
L a st  E x p o s u r e  D at e is d efi n e d as f oll o ws  f or p arti ci p a nts  w h o  pr e m at ur el y  di s c o nti n u e d  st u d y 
or c o m pl et e  st u d y a c c or di n g  t o St u d y  C o m pl eti o n  e C R F  (i. e. p aiti ci p a nt  a ns w er e d " N o " or 
" Y e s " f or " Di d t h e p arti ci p a nt  c o m pl et e  t h e pr ot o c ol- pl a n n e d  d ur ati o n of t h e st u d y "  o n  St u d y 
C o m pl eti o n  f or m): 
•  F or  p arti ci p a nts  w h o  r e c ei v e  a n y  i nj e cti o n or i nf usi o n, l a st e x p o s ur e  d at e  is d efi n e d  as  l a st 
st u d y d at e. 
•  F or  p arti ci p a nts  w h o  d o  n ot  r e c ei v e a n y  i nj e cti o n or  i nf u si o n (i. e. f or t h o s e w h o  o nl y  r e c ei v e 
or al  L E N) , l ast e x p o s ur e  d at e is d efi n e d as t h e e arli e st of t h e l a st d o s e  d at e  pl us  6 0  d a ys  a n d 
t h e l ast st u d y d at e. 
T h e  l a st e x p o s ur e  d at e  is d efi n e d  c o n si d eri n g t h e pr ol o n g e d  e x p o s ur e of L E N,  G S- 5 4 2 3 , a n d 
G S- 2 8 7 2  aft er t h e l a st d os e  d at e of L E N,  G S- 5 4 2 3,  a n d  G S- 2 8 7 2  t hr o u g h t h e e n d of st u d y. 
L a st  E x p o s u r e  D at e of L A R e gi m e n is d efi n e d as f oll o w s f or p arti ci p a nt s  w h o  pr e m at ur el y 
di s c o nti n u e d  st u d y  dr u g  or  c o m pl et e  st u d y dr u g  a c c or di n g  t o St u d y  Dr u g  C o m pl eti o n  e C R F  (i. e. 
p arti ci p a nt  a n s w er e d " N o " or " Y e s " f or " Di d p arti ci p a nt  c o m pl et e  st u d y  dr u g  d osi n g  a s  s p e cifi e d 
p er  pr ot o c ol "  o n  St u d y  Dr u g  C o m pl eti o n  f or m): 
•  t h e e arli e st  d at e of l a st st u d y  d a y or A R T  r e st art d a y  f or p arti ci p a nts  w h o  pr e m at ur el y 
di s c o nti n u e d  st u d y or c o m pl et e  st u d y,  or 
C O N FI D E N TI A L 
P a g e  2 7 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
•  t h e A R T  r e st art d at e  f or p arti ci p a nts  w h o  w er e  still  o n  st u d y. If t h e A R T  r e st art d at e  is 
mi s si n g,  t h e d at a c ut d at e  will b e u s e d  t o i m p ut e t h e l ast e x p o s ur e  d at e  f or p arti ci p a nts  w h o 
ar e  still o n  st u d y at  t h e ti m e of t h e d at a  c ut  d at e. 
T h e  l a st e x p o s ur e  d at e of L A  r e gi m e n is d efi n e d  c o n si d eri n g  t h e pr ol o n g e d  e x p os ur e of L E N, 
G S- 5 4 2 3,  a n d  G S- 2 8 7 2  aft er  t h e l ast d o s e  d at e of L E N,  G S- 5 4 2 3,  a n d G S- 2 8 7 2  t hr o u g h t h e A R T 
r e st art d at e. 
A R T  R e st a rt  D at e is d efi n e d  as  t h e d at e  w h e n  A R T  is r es u m e d. 
3. 8. 2.  
A n al y si s  Vi sit  Wi n d o w s 
A n al y si s  Vi sit  Wi n d o w s  P arti ci p a nt  vi sit s  mi g ht  n ot  o c c ur  o n  pr ot o c ol- s p e cifi e d  d a ys.  T h er ef or e, 
f or t h e p ur p o s e of a n al ysis , o b s er v ati o n s  will b e a s si g n e d t o a n al ysis  wi n d o ws. 
T h e  a n al y si s  wi n d o w s  f or  HI V- 1  R N A,  C D 4 +  c ell  c o u nt,  C D 8 +  c ell  c o u nt , C D 4 %, H e m at ol o g y, 
C h e mistr y,  Li pi d  P a n el,  Uri n al ysis,  Uri n e  C h e mistr y,  Uri n e  Pr e g n a n c y  L a b or at or y  T ests , Vit al 
Si g ns,  W ei g ht  a n d  E C G  ar e  pr o vi d e d  i n T a bl e  3- 2  t o T a b l e  3- 4. 
T a bl e  3- 2.  
A n al y si s  Wi n d o w s  f o r HI V- 1  R N A 
Vi sit I D 
N o mi n al D a y 
L o w e r  Li mit 
U p p e r  Li mit 
D a y  1  ( B as eli n e) 
1 
W e e k 4 
2 8 
2 
4 2 
W e e k 8 
5 6 
4 3 
7 0 
W e e k  1 2 
8 4 
7 1 
9 8 
W e e k  1 6 
1 1 2 
9 9 
1 2 6 
W e e k  2 0 
1 4 0 
1 2 7 
1 5 4 
W e e k  2 4 
1 6 8 
1 5 5 
1 7 5 
W e e k  2 6 
1 8 2 
1 7 6 
2 2 4 
W e e k  3 8 
2 6 6 
2 2 5 
3 1 5 
W e e k 5 2 
3 6 4 
3 1 6 
4 1 3 
C O N FI D E N TI A L 
P a g e 2 8 
2 6  F e b 2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
T a bl e  3- 3.  
A n al y si s  Wi n d o w s  f o r C D 4 +  c ell  c o u nt,  C D 8 +  c ell  c o u nt,  C D 4/ C D 8 
R ati o,  C h e mi st r y,  H e m at ol o g y,  U ri n al y si s,  Vit al  Si g n s,  a n d  W ei g ht 
Vi sit I D 
N o mi n al D a y 
L o w e r  Li mit 
U p p e r  Li mit 
D a y  1  ( B as eli n e) 
1 
W e e k 4 
2 8 
2 
5 6 
W e e k  1 2 
8 4 
5 7 
1 3 3 
W e e k  2 6 
1 8 2 
1 3 4 
2 2 4 
W e e k  3 8 
2 6 6 
2 2 5 
3 1 5 
W e e k 5 2 
3 6 4 
3 1 6 
4 1 3 
T a bl e  3- 4.  
A n al y si s  Wi n d o w s  f o r E C G 
Vi sit I D 
N o mi n al D a y 
L o w e r  Li mit 
U p p e r  Li mit 
D a y  1  ( B as eli n e) 
1 
W e e k  2 6 
1 8 2 
2 
2 7 3 
W e e k 5 2 
3 6 4 
2 7 4 
4 1 3 
F or  P h ar m a c o ki n eti c  a n d  I m m u n o g e ni cit y a n al ys es,  t h e n o mi n al  vi sit  as  r e c or d e d o n  t h e C R F 
will  b e  us e d  w h e n  d at a  ar e  s u m m ari z e d b y visit.  A n y  d at a  r el ati n g t o u n s c h e d ul e d  visits  will  n ot 
b e  a s si g n e d  t o a  p arti c ul ar  vi sit or ti m e p oi nt  a n d  i n g e n er al  will  n ot  b e  i n cl u d e d i n b y- vi sit 
s u m m ari es.  H o w e v er,  t h e f oll o wi n g e x c e pti o ns  will b e m a d e: 
•  A n  u n s c h e d ul e d  vi sit  pri or t o t h e fir st d o si n g of st u d y  dr u g  m a y b e i n cl u d e d i n t h e c al c ul ati o n 
of t h e b a s eli n e  v al u e , if a p pli c a bl e. 
•  F or  p arti ci p a nts  w h o  pr e m at ur el y  dis c o nti n u e  fr o m t h e st u d y, e arl y  t er mi n ati o n ( E T) d at a 
will  b e  assi g n e d t o w h at  w o ul d  h a v e  b e e n t he  n e xt  s c h e d ul e d vi sit  w h er e  t h e r es p e cti v e  d at a 
w er e  s c h e d ul e d t o b e  c oll e ct e d . 
3. 8. 3.  
S el e cti o n of D at a i n t h e E v e nt of M ulti pl e  R e c o r d s i n a n A n al y si s  Vi sit 
Wi n d o w 
D e p e n di n g  o n  t h e st ati sti c al  a n al ysis  m et h o d,  si n gl e  v al u es  m a y  b e  r e q uir e d f or e a c h  a n al ysis 
wi n d o w.  F or  e x a m pl e,  c h a n g e  fr o m b a s eli n e  b y  vi sit  u s u all y  r e q uir e s a  si ng l e v al u e,  w h er e a s  a 
ti m e-t o- e v e nt a n al ysis  w o ul d  n ot  r e q uir e  1  v al u e  p er  a n al y si s  wi n d o w. 
If m ulti pl e  v ali d,  n o n mi s si n g  m e a s ur e m e nt s  e xi st  i n a n a n al ysis  wi n d o w,  r e c or ds  will  b e  c h o s e n 
b a s e d  o n  t h e f oll o wi n g r ul es if a  s i ng l e v al u e  is n e e d e d: 
C O N FI D E N TI A L 
P a g e  2 9 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
•  F or  b as eli n e,  t h e l a st n o n mi s si n g  v al u e  o n or pri or  t o t h e first d os e  d at e of st u d y dr u g  will  b e 
s el e ct e d,  u nl e s s  s p e cifi e d diff er e ntl y. If t h er e ar e  m ulti pl e  r e c or d s wit h  t h e s a m e ti m e or n o 
ti m e r e c or d e d o n  t h e s a m e  d a y,  t h e b a s eli n e  v al u e  will  b e  t h e a v er a g e of t h e m e a s ur e m e nt s 
f or c o nti n u o u s  d at a  ( e x c e pt f or HI V- 1  R N A,  s e e  b el o w),  or  t h e m e a s ur e m e nt  wit h  t h e l o w e st 
s e v erit y ( e g, n or m al  will  b e  s el e ct e d  o v er  a b n or m al  f or s af et y E C G  fi n di n g s) f or c at e g ori c al 
d at a. 
•  F or  p o st b a s eli n e  v al u es: 
- 
T h e  r e c or d cl o s e st t o t h e n o mi n al  d a y  f or t h at vi sit  will b e s el e ct e d wit h  t h e e x c e pti o n of 
C D 4  c ell  c o u nts,  C D 4 %,  a n d  C D 8  c ell  c o u nt i n w hi c h  t h e l at est r e c or d will  b e  s el e ct e d 
a n d  HI V- 1  R N A  l e v el (s e e b el o w). 
-
If t h er e ar e  2  r e c or d s t h at ar e  e q ui di st a nt  fr o m t h e n o mi n al  d a y,  t h e l at er r e c or d will  b e 
s el e ct e d. 
-
If t h er e is m or e  t h a n 1  r e c or d o n  t h e s el e ct e d  d a y,  t h e a v er a g e  will  b e  t a k e n f or 
c o nti n u o u s  d at a  ( e x c e pt f or HI V - 1 R N A,  s e e b el o w)  a n d  t h e w or s e  s e v erit y will  b e  t a k e n 
f or c at e g ori c al  d at a,  u nl e s s  ot h er wi s e  s p e cifi e d. 
•  F or  b a s eli n e  HI V- 1  R N A, t h e l at e st ( c o n si d eri n g  b ot h  d at e  a n d  ti m e) r e c or d( s) o n or pri or t o 
t h e first  d os e  d at e  a n d ti m e of st u d y dr u g  will  b e  s el e ct e d. 
•  F or  p o st b a s eli n e  HI V- 1  R N A, t h e l at e st ( c o n si d eri n g  b ot h  d at e  a n d ti m e) r e c or d( s) i n t h e 
wi n d o w  will  b e  s el e ct e d. 
-
If b ot h " HI V R N A C O B A S  6 8 0 0 "  a n d  " HI V R N A  T A Q M A N  2. 0 "  ar e  a v ail a bl e  wit h  t h e 
s a m e  c oll e cti o n ti m e, t h e r es ults fr o m t h e " HI V  R N A  C O B A S  6 8 0 0 "  will  b e  s el e ct e d f or 
a n al ysis  p ur p os e. 
-
If b ot h " HI V C O B A S  6 8 0 0 "  a n d  " HI V  R N A  R E P E A T  C O B A S "  (i e, t h e HI V- 1  R N A 
r e s ult o bt ai n e d  fr o m  a n  a d diti o n al  ali q u ot of t h e ori gi n al  s a m pl e)  ar e  a v ail a bl e  wit h  t h e 
s a m e  c oll e cti o n ti m e, t h e r es ults fr o m t h e " HI V  R N A  R E P E A T C O B A S " will  b e  s e l e ct e d 
f or a n al y si s  p ur p os es ; ot h er wis e,  ift h er e ar e  m ulti pl e  " HI V C O B A S  6 8 0 0 "  r ec or ds  wit h 
t h e s a m e  c oll e cti o n ti m e, t h e g e o m etri c  m e a n  will  b e  t a k e n f or a n al y si s  p ur p os es. 
-
If b ot h " HI V R N A T A Q M A N  2. 0 "  a n d  " HI V R N A  R e p e at "  ar e  a v ail a bl e  wit h  t h e s a m e 
c oll e cti o n ti m e, t h e r es ults fr o m t h e " HI V  R N A  R e p e at "  will  b e  s el e ct e d f or a n al ysis 
p ur p os es;  ot h er wis e, ift h er e ar e  m ulti pl e  " HI V  R N A  T A Q M A N  2. 0 "  r e c or ds wit h  t h e 
s a m e  c oll e cti o n ti m e, t h e g e o m etri c  m e a n  will  b e  t a k e n f or a n al y si s  p ur p o s e s. 
C O N FI D E N TI A L 
P a g e  3 0 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
If m ulti pl e  v ali d  n o n mi s si n g  c at e g ori c al  o bs er v ati o ns  e xi st  i n a  wi n d o w,  r e c or ds will  b e  c h o s e n 
a s  f oll o ws: 
•  F or  b as eli n e,  t h e l a st a v ail a bl e  r e c or d o n or pri or  t o t h e fir st d os e  d at e of st u d y dr u g  will b e 
s el e ct e d. If t h er e ar e  m ulti pl e  r e c or d s wit h  t h e s a m e ti m e or n o  ti m e r e c or d e d o n  t h e s a m e 
d a y,  t h e v al u e  wit h  t h e l o w e st s e v erit y will  b e  s el e ct e d ( e g,  n or m al  will  b e  s el e ct e d o v er 
a b n or m al  f or s af et y  E C G  fi n di n gs). 
•  F or  p o st b a s eli n e  visits,  t h e m o st  c o n s er v ati v e  v al u e  wit hi n  t h e wi n d o w  will  b e  s el e ct e d  ( e g, 
a b n or m al  will  b e  s el e ct e d o v er  n or m al  f or s af et y  E C G  fi n di n gs). 
C O N FI D E N TI A L 
P a g e 3 1 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
4. 
P A R T I C I P A N T  D I S P O S I T I O N 
4. 1.  
P a rti ci p a nt  E n r ol b n e nt  a n d  Di s p o siti o n 
V ersi o n  1. 0 
A  s u m m ar y of p arti ci p a nt  e nr oll m e nt  will  b e  pr o vi d e d  b y  tr e at m e nt gr o u p  a n d t ot al f or e a c h 
c o u ntr y,  i n v e sti g at or wit hi n  a  c o u ntr y , a n d  o v er all.  F or  e a c h  c ol u m n , t h e d e n o mi n at or  f or t h e 
p er c e nt a g e  c al c ul ati o n  will b e t h e t ot al n u m b er of p arti ci p a nt s  a n al y z e d  f or t h at c ol u m n. 
A  s u m m ar y of p arti ci p a nt  dis p ositi o n  will  b e  pr o vi d e d  b y  tr e at m e nt gr o u p  a n d  t ot al b a s e d  o n  all 
s cr e e n e d p arti ci p a nts.  T his  s u m m ar y will  pr e s e nt  t h e n u m b er of p arti ci p a nt s  s cre e n e d , t h e 
n u m b er of p arti ci p a nt s  w h o  di d  n ot  m e et eli gi bilit y  crite ri a a n d  w er e  n ot  r a n d o mi ze d, t he  n u m b er 
of p arti ci p a nt s  w h o  m et  all  eli gi bilit y  crit eri a  b ut  w er e n ot r a n d o mi z e d wit h  r e as o ns p arti ci p a nts 
n ot  r a n d o mi z e d, t h e n u m b er of p arti ci p a nts  r a n d o mi z e d b ut  n e v er  d o s e d (if a p pli c a bl e ), n u m b er 
of p arti ci p a nt s  i n t h e S af et y  A n al ysis  S et  a n d t h e n u m b er of p arti ci p a nts  i n e a c h of t h e f oll o wi n g 
c at e g ori e s as a p pli c a bl e: 
•  C o m pl et e d  st u d y dr u g 
•  Di d n ot c o m pl et e  st u d y  dr u g  wit h  r e a s o n s f or pr e m at ur e  di s c o nti n u ati o n of st u d y dr u g 
•  C o m pl et e d  st u d y 
•  Di d n ot c o m pl et e  t h e st u d y wit h  r e a s o n s f or pr e m at ur e  di s c o nti n u ati o n of st u d y 
F o r s u m m a r y,  p a rti ci p a nt s  wit h  st u d y  d r u g  p r e m at u r e  di s c o nti n u ati o n are  d efi n e d  as 
p arti ci p a nts  w h o  a ns w er e d " N o " t o " Di d  s u bj e ct c o m pl et e  st u d y dr u g  d o si n g as s p e cifi e d p er 
pr ot o c ol ? "  a n d  h a d  a  di s c o nti n u ati o n  r e a s o n ot h er t h a n " I n v e sti g at or Di s cr eti o n "  ( wit h c o m m e nt 
of " D u e t o Cli ni c al  h ol d ") i n St u d y  Dr u g  C o m pl eti o n  e C R F). 
P a rti ci p a nt s w h o p r e m at u r el y  di s c o nti n u e d  st u d y ar e  d efi n e d  a s  p arti ci p a nt s  w h o  a n s w er e d 
" N o " t o " Di d  t h e s u bj e ct c o m pl et e  t h e pr ot o c ol- pl a n n e d  d ur ati o n of t h e st u dy ? "  i n St u d y 
C o m pl eti o n  e C R F) 
F or  t h e st at us of st u d y dr u g  a n d  st u d y  c o m pl eti o n  a n d  r e a s o n s f or pr e m at ur e  di s c o nti n u ati o n , t h e 
n u m b er  a n d  p er c e nt a g e of p arti ci p a nt s  i n e a c h  c at e g or y  w ill b e  pr o vi d e d.  T h e  d e n o mi n at or  f or 
t h e p er c e nt a g e  c al c ul ati o n  w ill b e t h e t ot al n u m b er of p arti ci p a nt s  i n t h e S a f ety  A n al y si s  S et 
c orr e s p o n di n g t o t h at c ol u m n. I n a d diti o n ,  a fl o w c h art will  b e  pr o vi d e d  t o d e pi ct  t h e dis p ositi o n. 
T h e  f oll o wi n g b y- p arti ci p a nt  li sti n g s will  b e  pr o vi d e d  b y  p arti ci p a nt  I D n u m b er  i n a s ce n di n g 
or d er  t o s u p p ort t he  a b o v e  s u m m a r y t a bles: 
•  R e as o ns  f or pr e m at ur e  st u d y  dr u g  or  st u d y di s c o nti n u ati o n 
C O N FI D E N TI A L 
P a g e  3 2 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
4. 2. 
E xt e nt of St u d y  D r u g  E x p o s u r e  a n d  A d mi ni st r ati o n 
V ersi o n  1. 0 
St u d y  dr u g  a d mi ni str ati o n a n d st u d y dr u g  di s p e n si n g  i nf or m ati o n will  b e  c oll e ct e d i n t h e St u d y 
Dr u g  A d mi ni str ati o n  a n d  St u d y  Dr u g  A c c o u nt a bilit y  e C R Fs.  E xt e nt of e x p os ur e t o st u d y dr u g 
will  b e  e x a mi n e d b y a s s e s si n g  t h e t ot al d ur ati o n of e x p o s ur e t o st u d y dr u g  a n d t h e l e v el of 
a d h er e n c e  r el ati v e t o t h e st u d y dr u g if a p pli c a bl e. 
4. 2. 1. 
D u r ati o n of E x p o s u r e t o St u d y  D r u g 
D ur ati o n of e x p o s ur e  t o st u d y dr u g  will b e s u m m ari z e d.  D u e t o l o n g a cti n g  f e at ur e of st u d y dr u g, 
d ur ati o n of f oll o w- u p t o st u d y  dr u g  will  c o n si d er t h e pr ol o n g e d  e x p o s ur e of L A st u d y  dr u g  (i e, 
S C L E N , G S- 5 4 2 3,  G S- 2 8 7 2)  aft er t h e l a st d o s e  d at e of st u d y  dr u g  t hr o u g h t h e A R T  r e st art d at e 
or t h e e n d of st u d y,  r e s p e cti v el y. 
F or  l o n g a cti n g  r e gi m e n p eri o d  a n al ysis,  l a st e x p os ur e  d at e of L A r e gi me n is d e fi n e d  i n 
S e cti o n  3. 8. 1  f or p arti ci p a nt s  w h o  pr e m at ur el y  di s c o nti n u e d  st u d y dr u g or c o m pl et e d  st u d y dr u g. 
D ur ati o n of st u d y dr u g  e x p o s ur e  will  b e  d efi n e d as (t h e l a st e x p o s ur e  d at e  - t h e fir st d o s e  d at e  + 
1 ),  a n d  d ur ati o n of e x p o s ur e  will b e e x pr e s s e d  i n w e e k s  u si n g  u p t o 1  d e ci m al  pl a c e  ( e g , 4. 5 
w e e ks). 
D ur ati o n of e x p os ur e  will  b e  s u m m ari z e d u si n g  d e s cri pti v e  st ati sti c s  ( n, m e a n , S D,  m e di a n, Ql , 
Q 3,  mi ni m u m , a n d  m a xi m u m)  a n d a s t h e n u m b er  a n d  p er c e nt a g e of p arti ci p a nt s  e x p o s e d  a n d 
r e m ai n e d t hr o u g h t h e f oll o wi n g ti m e p eri o ds:  1  d a y,  2  d a y s ,  4 w e e k s  ( 2 8 d a y s) ,  8 w e e k s  ( 5 6 
d a y s) , 1 6 w e e ks  ( 1 1 2 d a ys), 2 4 w e e ks  ( 1 6 8 d a ys), 2 6 w e e k s  ( 1 8 2 d a y s),  3 0  w e e k s  ( 2 1 0 d a y s), 3 4 
w e e ks  ( 2 3 8 d a ys),  3 8  w e e k s  ( 2 6 6 d a y s),  4 2  w e e k s  ( 2 9 4 d a y s),  5 4  w e e ks  ( 3 7 8 d a y s ), etc. 
S u m m ari e s  will b e pr o vi d e d  b a s e d o n t h e S af et y  A n al ysis  S et  f or L A R e gi m e n  P eri o d  ( u p t o 2 6 
w e e k s)  a n d  f or W h ol e  St u d y  P eri o d  s e p ar at el y ( u p t o 5 4  w e e ks).  N o  i nf er e nti al st ati sti c s will  b e 
pr o vi d e d. 
4. 2. 2. 
St u d y  D r u g  A d mi ni st r ati o n 
St u d y  dr u g  a d mi ni si o n  f or p arti ci p a nt s  i n t h e Pri m ar y  C o h ort  a n d  i n t h e o pti o n al  Pil ot  C o h ort 
will  b e  s u m m ari z e d b y  tr e at m e nt gr o u p s  f or t h e f oll o wi n g it e ms: 
•  N u m b er  a n d  p er c e nt a g e of p arti ci p a nt s  w h o  r e c ei v e d or al  L E N o n D a y  1  a n d D a y  2, 
r esp e cti v el y 
•  N u m b er  a n d  p er c e nt a g e of p arti ci p a nt s  w h o  r e c ei v e d L E N  S C  i nj e cti o n o n D a y  1 
•  N u m b er  a n d  p er ce nta ge  of  p arti ci p a nt s  w h o  r ec ei v e d  I V i nf u si on of G S- 5 4 2 3 o n D a y  1 
•  N u m b er  a n d  p er c e nt a g e of p arti ci p a nt s  w h o  r ec ei v e d  I V i nf u si o n of G S- 2 8 7 2 o n D a y 1. 
C O N FI D E N TI A L 
P a g e 3 3 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
4. 3. 
P r ot o c ol  D e vi ati o n s 
V ersi o n  1. 0 
P arti ci p a nt s  w h o  di d  n ot  m e et  t h e eli gi bilit y  crit eri a f or st u d y e ntr y,  b ut  e nr oll e d  i n t h e st u d y will 
b e  s u m m ari z e d.  T h e  s u m m ar y will  pr e s e nt  t h e n u m b er  a n d  p er c e nt a g e of p arti ci p a nt s  w h o  di d 
n ot  m e et  at l e a st 1  eli gi bilit y  crit eri o n  a n d  t h e n u m b er of p arti ci p a nts  w h o  di d  n ot  m e et  s p e cifi c 
crit eri a b a s e d  o n  t h e S af et y  A n al y si s  S et.  A  b y- p arti ci p a nt  li sti n g will  b e  pr o vi d e d  f or t h o s e 
p arti ci p a nts  w h o  di d  n ot  m e et  at  l e a st 1  eli gi bilit y  (i n cl u si o n or e x cl u si o n)  crit eri o n. 
Pr ot o c ol  d e vi ati o ns  o c c urri n g  aft er p arti ci p a nt s  e nt er e d t he  st u d y ar e  d o c u m e nt e d  d uri n g  r o uti ne 
m o nit ori n g.  T h e  n u m b er  a n d  p er c e nt a g e of p arti ci p a nts  wit h  i m p ort a nt pr ot o c ol  d e vi ati o n s  a n d 
n u m b er of i m p ort a nt pr ot o c ol  d e vi ati o ns b y d e vi ati o n  c at e g or y  ( e g , eli gi bilit y  crit eri a,  i nf or m e d 
c o n s e nt)  will b e s u m m ari z e d b y tr e at m e nt gr o u p  a n d t ot al f or t h e S af et y  A n al ysis  S et.  A  b y-
p arti ci p a nt  li sti n g will  b e  pr o vi d e d  f or t h o s e p arti ci p a nts  wit h  i m p ort a nt pr ot o c ol  d e vi ati o n. 
4. 4. 
A s s e s s m e nt of C O V I D- 1 9  I m p a ct 
T hi s  st u d y w a s  o n g oi n g  d uri n g  t h e n o v el  c or o n a vir u s  ( C O VI D- 1 9) p a n d e mi c  w hi c h  h as  a n 
i m p a ct o n  t h e st u d y  c o n d u ct.  S o m e  p arti ci p a nts  w er e  u n a bl e t o att e n d  o n sit e  vi sit s  d u e t o s h e lt er 
i n pl a c e  g ui d eli n es,  sit e  cl os ur es , or ot h er  r e as o ns. T his  s e cti o n d es cri b es  h o w  s p e ci al  sit u ati o ns 
d u e  t o C O VI D- 1 9  will  b e  h a n dl e d  i n t h e a n al ysis. 
4. 4. 1. 
St u d y  D r u g o r St u d y  Di s c o nti n u ati o n D u e t o C O V I D- 1 9 
A  b y- p arti ci p a nt  listi n g of r e a s o n s f or pr e m at ur e  st u d y dr u g or st u d y  di s c o nti n u ati o n  d u e t o 
C O VI D- 1 9  will b e pr o vi d e d if a p pli c a bl e. 
4. 4. 2.  
P r ot o c ol  D e vi ati o n s D u e t o C O V I D -1 9 
A  b y- p arti ci p a nt  listi n g will  b e  pr o vi d e d  f or p arti ci p a nts  wit h  i m p ort a nt pr ot o c ol  d e vi ati o n s 
r el at e d t o C O VI D- 1 9 if a p pli c a bl e.  A  s e p ar at e  li sti n g will  b e  pr o vi d e d  f or p arti ci p a nts  wit h  n o n-
i m p ort a nt pr ot o c ol  d e vi ati o ns  r el at e d t o C O VI D- 1 9 if a p pli c a bl e. 
4. 4. 3. 
Mi s s e d  a n d  Vi rt u al  Vi sit s  D u e t o C O V I D- 1 9 
A  b y- p arti ci p a nt  listi n g of p arti ci p a nts  wit h  mi s s e d or v irt u al vi sit s  d u e  t o C O VI D- 1 9  will  b e 
pr o vi d e d  b y  p arti ci p a nt  I D n u m b er  i n a s c e n di n g  or d er. 
I nf or m ati o n r e g ar di n g mi s s e d  or  virt u al  vi sit s  d u e t o C O VI D- 1 9  will  b e  c oll e ct e d as fr e e t e xt i n 
t h e C R F  c o m m e nt fi el ds.  T h e  d et er mi n ati o n of mis s e d or virt u al  visits  d u e  t o C O VI D- 1 9  will  b e 
d o n e  u si n g  N at ur al  L a n g u a g e  Pr o c e s si n g  ( N L P) t o s e ar c h t h e C R F  c o m m e nt fi el ds.  A  d et ail e d 
e x pl a n ati o n of t h e al g orit h m  is gi v e n  i n A p p e n di x  4. 
C O N FI D E N TI A L 
P a g e  3 4 
2 6  F e b 2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
4. 4. 4. 
A d v e r s e  E v e nt s  D u e t o C O V I D- 1 9 
V ersi o n  1. 0 
A Es of C O VI D- 1 9  will  b e  i n cl u d e d i n a n al ys es of A Es if a p pli c a bl e,  w hi c h  will  b e  d et er mi n e d 
t hr o u g h C O VI D- 1 9 S M Q  N a r r o w s e ar c h.  A  b y- s u bj e ct  li sti n g of A Es of C O VI D- 1 9  will b e 
pr o vi d e d if a p pli c a bl e. 
4. 4. 5. 
O v e r all  A s s e s s m e nt of C O V I D- 1 9 P a n d e mi c  I m p a ct 
F or  s u bj e cts  aff e ct e d  b y  C O VI D- 1 9  i nf e cti o n a n d /or  p a n d e mi c  w hil e  p arti ci p ati n g  i n t h e st u d y,  a 
li sti n g of t h e f oll o wi n g i n di vi d u al C O VI D- 1 9  r el at e d o ut c o m e  c at e g ori es  will  b e  pr o vi d e d: 
•  D e at h  d u e  t o C O VI D- 1 9 
•  A d v ers e  e v e nt of C O VI D- 1 9, as d et er mi n e d  b y  C O VI D- 1 9  S M Q  n arr o w  s e ar c h 
•  S p e cifi c  a d v er s e  e v e nt  dir e ctl y  a s s o ci at e d  wit h  t h e p at h o g e n  c a u si n g  C O VI D- 1 9, as 
d et er mi n e d  b y  M e di c al  S ur v eill a n c e  T e a m  ( M S T) 
•  H o s pit ali z ati o n  ( u si n g d at a  fr o m  A E  e C R F)  d u e  t o a d v ers e  e v e nt of C O VI D- 1 9  a s  d e fi ne d 
a b o v e 
•  T est e d  p o siti v e  f or C O VI D- 1 9 
•  St u d y  dr u g  di s c o nti n u ati o n  d u e  t o C O VI D- 1 9 
•  St u d y  di s c o nti n u ati o n  d u e t o C O VI D- 1 9 
•  Mi s s e d  visits  d u e  t o C O VI D- 1 9 
•  Mi s s e d  k e y  ass ess m e nts  d u e  t o C O VI D- 1 9 , wit h  K e y  ass es s m e nt s  i n cl u d e t h e ass es s m e nts 
c o ntri b uti n g t o pri m ar y  a n d  k e y  s e c o n d ar y e n d p oi nts,  i n cl u di ng  f oll o ws: 
- 
Mi s si n g  r e p orti n g of a n y  n e w  tr e at m e nt- e m er g e nt A E  t hr o u g h W e e k  2 6  visit,  or  a n y 
u p d at e of e xi sti n g  tr e at m e nt- e m er g e nt A E  d uri n g  t h e s a m e  p eri o d of ti m e, c o ul d b e 
f urt her  e v al u at e d  f or mis s i n g k e y  a s s es s m e nt 
- 
Mi s si n g  HI V- 1  R N A  at  W e e k  2 6  vi s it 
I n a d diti o n,  c o m p o sit e  br o a d  C O VI D- 1 9 i m p a ct  i n di c ator  w ill b e d eri v e d  b a s e d  o n  t h e f oll o wi ng 
i n di vi d u al c at e g ori e s  d e fi ne d  a b o v e:  d e at h , a d v ers e  e v e nt , h o spit ali z ati o n , t este d  p o siti v e,  st u dy 
dr u g  di s c o nti n u ati o n , st u d y  dis c o nti n u ati o n,  mi s s e d  visits,  a n d  mi s s e d  k e y  a s s e ss m e nts. 
C o m p o sit e  s pe cifi c  C O VI D- 1 9  i m p a ct i n di c at or will  b e  d eri v e d  b as e d  o n  d e at h,  s p ecifi c  a d v e rse 
e v e nt,  a n d  t e st e d p ositi v e. 
C O N FI D E N TI A L 
P a g e 3 5 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
5. 
B A S E L I N E  C H A R A C T E R I S T I C S 
5. 1.  
D e m o g r a p hi c s  a n d  B a s eli n e  C h a r a ct e ri sti c s 
V ersi o n  1. 0 
P arti ci p a nt  d e m o gr a p hi c  v ari a bl e s  (i e,  a g e, s e x at birt h,  g e n d er  i d e ntit y, s e x u al ori e nt ati o n,  r a c e, 
a n d  et h ni cit y)  a n d  b a s eli n e  c h ar a ct eri sti c s  ( b o d y w ei g ht  [i n k g],  h ei g ht  [i n c m],  b o d y  m a s s  i n d e x 
[ B MI;  i n k gl m 2]) will b e s u m m ari z e d b y tr e at m e nt gr o u p  a n d  o v er all  u si n g  d e s cri pti v e  st ati sti c s 
f or c o nti n u o u s  v ari a bl es  a n d  u si n g  n u m b er  a n d  p er c e nt a g e of p arti ci p a nt s  f or c at e g ori c al 
v ari a bl es.  T h e  s u m m ar y of d e m o gr a p hi c  d at a will b e pr o vi d e d  f or t h e S af et y  A n al y si s  S et. 
A  b y- p arti ci p a nt  d e m o gr a p hi c  a n d  b a s eli n e  c h ar a ct eri sti c  listi n g, i n cl u di n g t h e i nf or m e d c o n s e nt 
d at e,  will b e pr o vi d e d b y p arti ci p a nt  I D n u m b er  i n a s c e n di n g  or d er. 
5. 2.  
Ot h e r  B a s eli n e  C h a r a ct e ri sti c s 
T h e  f oll o wi n g b a s eli n e  dis e as e  c h ar a ct eri sti c s  will  b e  s u m m ari z e d b y tr e at m e nt gr o u p  a n d 
o v er all  u si n g  d e s cri pti v e  st ati sti c s f or p arti ci p a nt s  i n t h e S af et y  A n al y si s  S et: 
•  
HI V- 1  R N A  c at e g ori e s  ( c o pi e s/m L):  ( a) <  5 0,  ( b) 2 5 0 
•  
C D 4  c ell  c o u nt s  (/ u L) 
•  
C D 4  c ell  c o u nt s  c at e g ori e s  (/ u L):  ( a) <  5 0,  ( b) 2 5 0  t o <  2 0 0,  ( c) 2 2 0 0  t o <  3 5 0,  ( d) 2 3 5 0  t o 
<  5 0 0,  a n d  ( e) 2 5 0 0 
•  
C D 4  p er c e nt a g e  ( %) 
•  
M o d e of i nf e cti o n ( HI V ri s k f a ct or s) 
•  
HI V  dis e as e  st at u s 
• 
e G F R c a  ( m L/ mi n) 
•  
D ur ati o n of b as eli n e  A R V  m e di c ati o n 
A  b y- p arti ci p a nt  li sti n g of ot h er b a s eli n e  c h ar a ct eristi cs  will  b e  pr o vi d e d  b y  p arti ci p a nt I D 
n u m b er  i n a s c e n di n g  or d er. 
5. 3.  
M e di c al  Hi st o r y 
M e di c al  hi st or y  will  b e  c oll e ct e d at s cr e e ni n g.  M e di c al  hi st or y  d at a  will  b e  c o d e d  a n d  list e d. 
C O N FI D E N TI A L 
P a g e  3 6 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
6. 
E F F I C A C Y  A N A L Y S E S 
V ersi o n  1. 0 
S e c o n d ar y  e n d p oi nt s of t his st u d y i n cl u d e effi c a c y  e n d p oi nt s  a s  d e s cri b e d  b el o w.  F or  effi c a c y 
a n al y s e s  ( e x c e pt f or F D A- d efi n e d  s n a p s h ot e n d p oi nt s),  t w o s ets of a n al ys es  will  b e  c o n d u ct e d 
u nl ess  ot h er wis e  s p e cifi e d: L A R e gi m e n  P eri o d  a n al ysis  a n d  W h ol e  St u d y  P eri o d  a n al ysis. 
6. 1. 
6. 1. 1. 
S e c o n d a r y  Effi c a c y  E n d  p oi nt s 
D efi niti o n of t h e S e c o n d a r y  Effi c a c y  E n d p oi nt s 
T h e  s e c o n d ar y effi c a c y  e n d p oi nts of t hi s st u d y  ar e: 
•  Pr o p orti o n of p arti ci p a nt s  wit h  HI V- 1  R N A  2  5 0  c o pi es /m L at W e e ks  2 6  as  d efi n e d  b y  t h e 
F D A- d efi n e d  s n a p s h ot  al g orit h m 
•  Pr o p orti o n of p arti ci p a nt s  wit h  HI V- 1  R N A <  5 0  c o pi e s/ m L at W e e ks  2 6  a s  d efi n e d  b y  t h e 
F D A- d efi n e d  s n a p s h ot  al g orit h m 
•  C h a n g e  fr o m b a s eli n e  i n C D 4 +  c ell  c o u nts at W e e k s  2 6. 
6. 1. 2. 
F D A- d efi n e d  S n a p s h ot  Al g o rit h m 
T h e  a n al y si s  wi n d o w  at  W e e k  2 6 is d efi n e d as fr o m St u d y  D a y  1 7 6  t o St u d y  D a y  2 2 4,  i n cl usi v e. 
All  HI V- 1  R N  A  d at a  c oll e ct e d  o n-tr e at m e nt  (i e, d at a  c oll e ct e d  u p t o t h e e arli e st  d at e of ( 1 9 6 
d a ys  [ 2 8 w e e ks]  aft er t h e d os e  d at e of c o m pl et e  l o n g a cti n g  r e gi m e n, d at e  ofr e st arti n g  A R T)  will 
b e  us e d  i n t h e U S  F D A- d efi n e d  s n a p s h ot al g orit h m  { U.  S.  D e p art m e nt of H e alt h  a n d H u m a n 
S er vi c e s  2 0 1 5 }. Vir ol o gi c  o ut c o m e  will  b e  d efi n e d  as  t h e f oll o wi n g c at e g ori es: 
•  HI V- 1  R N A <  5 0  c o pi es/ m L:  t hi s i n cl u d e s p arti ci p a nt s  w h o  h a v e  t h e l a st a v ail a bl e 
o ntr e at m e nt  HI V- 1  R N A <  5 0  c o pi e s /m L  i n t h e W e e k 2 6 a n al y si s  wi n d o w 
•  HI V- 1  R N A  2  5 0  c o pi es /m L:  t hi s i n cl u d es p arti ci p a nts 
a)  W h o  h a v e  t h e l a st a v ail a bl e  o n-tr e at m e nt  HI V- 1  R N A  2  5 0  c o pi es /m L i n t h e W e e k  2 6 
a n al ysis  wi n d o w,  or 
b) W h o  d o  n ot  h a v e  o n-tr e at m e nt  HI V- 1  R N A  d at a  i n t h e W e e k  2 6  a n al y s is wi n d o w  a n d 
i)  dis c o nti n u e  st u d y dr u g  pri or  t o or i n t h e W e e k  2 6  a n al ysis  wi n d o w  d u e t o l a c k of 
effi c a c y , or 
ii)  dis c o nti n u e  st u d y dr u g  pri or  t o or i n t h e W e e k  2 6  a n al ysis  wi n d o w  d u e t o A E or d e at h 
a n d  h a v e  t h e l a st a v ail a bl e  o n-tr e at m e nt  HI V- 1  R N A  2  5 0  c o pi es /m L, or 
iii)  dis c o nti n u e  st u d y dr u g  pri or  t o or i n t h e W e e k  2 6  a n al ysis  wi n d o w  d u e t o r e a s o n s 
ot h er  t h a n A E,  d e at h , or l a c k of effi c a c y  a n d h a v e  t h e l a st a v ail a bl e  o n-tr e at m e nt 
HI V- 1 R N A  2  5 0  c o pi es /m L. 
C O N FI D E N TI A L 
P a g e  3 7 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
•  N o  Vir ol o gi c  D at a i n t h e W e e k  2 6  Wi n d o w:  t hi s i n cl u d e s p arti ci p a nt s  w h o  d o  n ot  h a v e  o n-
tr e at m e nt HI V- 1  R N A  d at a  i n t h e W e e k  2 6  a n al y si s  wi n d o w  b e c a u s e of t h e f oll o wi n g: 
a)  Di s c o nti n u ati o n of st u d y dr u g  pri or t o or i n t h e W e e k  2 6  a n al ysis  wi n d o w  d u e  t o A E or 
d e at h  a n d  t h e l a st a v ail a bl e  o n-tr e at m e nt  HI V- 1  R N  A  <  5 0  c o pi e s /m L, or 
b) Di s c o nti n u ati o n of st u d y dr u g  pri or t o or i n t h e W e e k  2 6  a n al y sis  wi n d o w  d u e  t o r e a s o n s 
ot h er  t h a n A E,  d e at h,  or  l a c k of effi c a c y  a n d  t h e l a st a v ail a bl e  o n-tr e at m e nt  HI V- 1  R N A 
<  5 0  c o pi e s /m L or, 
c)  Mi s si n g  d at a  d uri n g  t h e wi n d o w  b ut  o n  st u d y dr u g. 
T h e  fl o w c h art of t h e U S  F D A- d e fi n e d s n a p s h ot al g orit h m  is pr o vi d e d  i n A p p e n di x  2. 
T h e  W e e k  2 6  vir ol o gi c  o ut c o m e s  f or t h e U S  F D A- d efi n e d  s n a p s h ot al g orit h m  will b e fl a g g e d i n 
t h e listi n gs. 
N ot e,  f or s wit c h tri al s, t h e U S  F D A- d efi n e d  s n a p s h ot al g orit h m  cl a s sifi e s  p arti ci p a nt s  w h o 
di s c o nti n u e  st u d y  dr u g  d u e t o A E or d e at h  a n d  h a v e  t h e l a st a v ail a bl e  o n-tr e at m e nt  HI V- 1  R N A 
v al u e  2  5 0  c o pi e s /m L i n t h e " HI V- 1 R N A 2  5 0  c o pi e s /m L " c at e g or y.  F or  tr e at m e nt n ai: v e st u d y 
p o p ul ati o n , t h e s e p arti ci p a nt s  will  b e  cl a s sifi e d  i n t h e " N o V ir ol o gi c D at a  i n t h e W e e k  2 6 
Wi n d o w "  c at e g or y. 
6. 1. 3. 
6. 1. 3. 1. 
A n al y si s of S e c o n d a r y  Effi c a c y  E n d p oi nt s 
A n al y si s of t h e Pr o p orti o n of S u bj e ct s  wit h  HI V- 1  R N A  2  5 0  c o pi e s /m L at 
W e e k  2 6  as  d et er mi n e d  b y  F D A- d efi n e d  S n a p s h ot  Al g orit h m 
T h e  a n al y si s of t h e pr o p orti o n of p arti ci p a nt s  wit h  HI V- 1  R N A  2  5 0  c o pi e s /m L at W e e k  2 6  a s 
d et er mi n e d b y t h e U S  F D A- d efi n e d  s n a p s h ot al g orit h m  will  b e  b a s e d o n t he  F A S. 
A  s u p p ort ati v e  a n al y si s  b a s e d o n t h e P P  a n al ysis  s et will  als o b e p erf or m e d . P arti ci p a nt s 
e x cl u d e d  fr o m t h e P P  a n al y si s  s et will  b e  d et er mi n e d  b ef or e  d at a b a s e  l o c k. 
6. 1. 3. 2.  
A n al y si s of t h e Pr o p orti o n of S u bj e ct s  wit h  HI V- 1  R N A  <  5 0  c o pi e s /m L at 
W e e k 2 6  as  d et er mi n e d  b y  F D A- d efi n e d  S n a p sh ot A l g orit h m 
Pr o p orti o n of s u bj e ct s wit h  HI V- 1  R N A <  5 0  c o pi e s /m L at W e e k 2 6 a s  d et er mi n e d  b y  U S F D A -
d efi n e d  s n a p s h ot al g orit h m  will  b e  a n al y z e d  b a s e d o n t h e F A S  a n d t h e P P  a n al y si s  s ets,  s i mil ar 
t o t h e effi c a c y  e n d p oi nt of pr o p orti o n of s u bj e ct s wit h  HI V- 1  R N  A  2 5 0 c o pi e s /m L at  W e e k  2 6 
a s  d et er mi n e d b y F D A- d efi n e d  S n a p s h ot  Al g orit h m. 
6. 1. 3. 3.  
A n al y si s o n C D 4 +  C ell  C o u nt s  at  W e e k  2 6 
T h e  c h a n g e s  fr o m b a s eli n e  i n C D 4 +  c ell  c o u nt  at  W e e k  2 6  will  b e  s u m m ari z e d b y tre at m e nt 
gr o u p  a n d  o v er all  f or F A S  u si n g d e s c ri pti v e st atisti cs.  T h e  c h a n g e fr o m b a s eli n e i n C D 4 +  c ell 
C O N FI D E N TI A L 
P a g e 3 8 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
c o u nt  will  als o  b e  s u m m ari z e d f or ot h er  visits  u p t o W e e k  2 6  f or t h e L A R e gi m e n  P eri o d 
A n al ysis,  a n d  u p t o W e e k  5 2  f or t h e W h ol e  St u d y  P eri o d  A n al ysis. 
T h e  a bs ol ut e  v al u es of C D 4  c ell  c o u nt s  will b e als o  s u m m ari z e d b y  tr e at m e nt gr o u p  a n d  o v er all 
si mil arl y.  T h e  a n al y s e s of C D 4  c ell c o u nts  a n d  t h eir c h a n g es  fr o m b a s eli n e  will  b e  c o n d u ct e d 
u si n g  t h e F A S. 
T h e  m e a n  a n d  9 5 %  CI of c h a n g e fr o m b a s eli n e  i n C D 4 +  c ell  c o u nt  o v er  ti m e b y tr e at m e nt 
gr o u ps  a n d  o v er all  will  b e  pl ott e d  f or t h e F A S. 
C D 4 +  c ell  c o u nts  o v er ti m e i n i n di vi d u al p arti ci p a nts  will  b e  pl ott e d  b y  tr e at m e nt gr o u ps. 
6. 2. 
6. 2. 1. 
Ot h e r  Effi c a c y  E n d  p oi nt s 
D efi niti o n of Ot h e r  Effi c a c y  E n d  p oi nt s 
•  T h e  pr o p orti o n of p arti ci p a nts  wit h  HI V- 1  R N A <  5 0  c o pi es /m L  at  W e e k  2 6 as d efi n e d b y 2 
diff er e nt  mi s si n g  d at a  i m p ut ati o n m et h o d s  s p e cifi e d  i n S e cti o n  6. 2. 2. 1. 
•  T h e  c h a n g e  fr o m b a s eli n e  i n C D 4  p er c e nt a g e  ( % ), C D 8  c o u nt,  a n d  C D 4 /C D 8  R ati o at W e e k 
2 6. 
A n al y si s of Ot h e r  Effi c a c y  E n d p oi nt s 
6. 2. 2. 
6. 2. 2. 1. 
A n al y si s of Pr o p orti o n of P arti ci p a nt s  wit h  HI V- 1  R N A <  5 0  c o pi es /m L b y 
Mi s si n g  =  F ail ur e  a n d  Mi s si n g  =  E x cl u d e d  A p pr o a c h es 
N u m b er  a n d  p er c e nt a g e of p arti ci p a nts  wit h  HI V- 1  R N A <  5 0  c o pi es /m L b y  vi sit  will  b e 
a n al y z e d  u si n g  t h e f oll o wi n g 2  m et h o d s  f or i m p uti n g mi s si n g  HI V - 1 R N A  v al u es. 
• 
Mi s si n g = F ail ur e  ( M = F): 
I n t hi s a p pr o a c h,  mi s si n g  d at a  will  b e  tr e at e d a s  vir ol o gi c  f ail ur e a n d  s u m m ari z e d  i nt o t h e 
" mi s si n g "  c at e g or y  (s e e li st of HI V- R N A  c at e g ori e s  b el o w). 
•  Mi s si n g =  E x cl u d e d  ( M =  E): 
I n t hi s a p pr o a c h,  mi s si n g  d at a  will  b e  e x cl u d e d  i n t h e c o m p ut ati o n of t h e p er c e nt a g e s 
(i e, mi s si n g  d at a  p oi nt s  will  b e  e x cl u d e d  fr o m b ot h  t h e n u m er at or  a n d  d e n o mi n at or  i n t h e 
c o m p ut ati o n).  T h e  d e n o mi n at or  f or p er c e nt a g e s  at  a  vi sit  is t h e n u m b er of p arti ci p a nt s  i n t h e 
F A S  wit h  n o n mi s si n g HI V- 1  R N  A  v al u e  at  t h at visit. 
F or  b ot h  M  =  F  a n d  M  =  E  a n al y s e s, t h e n u m b er  a n d  p er c e nt a g e of p arti ci p a nt s  wit h  HI V- 1  R N  A 
i n t h e f oll o wi n g  c at e g ori es  will b e s u m m ari z e d b y tr e at m e nt gr o u p  a n d  t ot al f or W e e k  2 6  a n d 
ot h er  visits  u p  t o W e e k  2 6  f or t h e L A R e gi m e n  P eri o d  A n al ysis , a n d  u p  t o W e e k  5 2  f or t h e 
W h ol e  St u d y  P eri o d  A n al ysis  b a s e d  o n  t h e F A S: 
C O N FI D E N TI A L 
P a g e  3 9 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
•   < 5 0  c o pi e s /m L 
-  
< 2 0  c o pi e s /m L 
•   < 2 0  c o pi e s/ m L  N ot  D et e ct a bl e 
•   < 2 0  c o pi e s/ m L  D et e ct a bl e 
- 
2 0 t o <  5 0  c o pi e s/ m L 
•  5 0  t o <  2 0 0  c o pi e s /m L 
•  2 0 0 t o <  4 0 0  c o pi e s/ m L 
•  
4 0 0 t o <  1 0 0 0  c o pi e s /m L 
•  
1 0 0 0  c o pi e s /m L 
•  
Mi s si n g  ( o nl y a p pli c a bl e  t o M  =  F  a n al y si s) 
V ersi o n  1. 0 
T h e  pr o p orti o n of p arti ci p a nt s  wit h  HI V- 1  R N A <  5 0  c o pi e s /m L as d efi n e d  b y  t h e 2  diff er e nt 
mi s si n g  d at a  i m p ut ati o n m et h o d s  will  b e  a n al y z e d  u si n g  t h e s a m e st ati sti c al m et h o d  a p pli e d  t o 
t h e s e c o n d ar y effi c a c y  e n d p oi nt. 
F or  t h e M  =  F  a n al ysis,  t h e pr o p orti o n of p arti ci p a nt s  wit h  HI V- 1  R N  A  <  5 0  c o pi e s /m L will  b e 
pl ott e d b y tr e at m e nt gr o u p  f or all  visits u p t o W e e k 2 6 f or t h e L A R e gi m e n  P eri o d  A n al y si s,  a n d 
u p t o W e e k  5 2  f or t h e W h ol e  St u d y  P eri o d  A n al ysis  u si n g  t h e F A S. 
6. 2. 2. 2.  
A n al y si s of C D 4  P er c e nt a g e , C D 8 C o u nt,  a n d  C D 4 /C D 8 R ati o 
T h e  c h a n g e fr o m b as e li ne  i n C D 4  p e r ce nt a g e( %), C D 8  c o u nt, a n d  C D 4 /C D 8  r ati o will  b e  b as e d 
o n t h e F A S  a n d  s u m m ari z e d f or W e e k 2 6  a n d  ot h er  vi sit s  u p  t o W e e k  2 6  f or t h e L A R e gi m e n 
P eri o d  A n al y si s,  a n d u p t o W e e k  5 2  f or t h e W h ol e  St u d y  P eri o d  A n al ysis  u si n g  d e s cri pti v e 
st atisti cs. 
6. 3.  
C h a n g e s  f r o m P r ot o c ol- S p e cifi e d  Effi c a c y  A n al y s e s 
T h e  d efi niti o n of F ull  A n al y si s S et ( F A S) is d efi n e d  diff er e ntl y  fr o m t h e Pr ot o c ol.  E x cl u si o n of 
p arti ci p a nt s  w h o  h a v e  m aj or  pr ot o c o l vi ol ati o n  ( d efi n e d as m e eti n g  e x cl u si o n  c rit eri o n of h a vi n g 
c hr o ni c  h e p atiti s  B  vir us  [ H B V] i nf e cti o n) fr o m t he  F ull  A n al ysis  S et  h as  b e e n  a d d e d  i n t h e 
S A P. 
C O N FI D E N TI A L 
P a g e  4 0 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
7. 
S A F E T Y  A N A L Y S E S 
V ersi o n  1. 0 
T h e  pri m ar y  o bj e cti v e of t his st u d y is t o e v al u at e  t h e s af et y  a n d  t ol er a bilit y of a  c o m bi n ati o n of 
t h e b N A b s  G S- 5 4 2 3  a n d  G S- 2 8 7 2  i n c o m bi n ati o n  wit h  t h e  HI V  c a p si d  i n hi bit or L E N,  a n d  t h e 
pri m ar y  e n d p oi nt of t hi s st u d y is i n ci d e n c e of tr e at m e nt- e m er g e nt S A Es  t hr o u g h W e e k  2 6.  T h e 
s e c o n d e n d p oi nt of t hi s st u d y  i n cl u d es i n ci d e n c e of tr e at m e nt- e m er g e nt A Es  t hr o u g h W e e k  2 6. 
S af et y  d at a  will  b e  s u m m ari z e d f or p arti ci p a nts  i n t h e S af et y  A n al ysis  S et  f or t h e w h ol e  st u d y 
p eri o d  a n al ysis  a n d  f or p arti ci p a nts  i n t h e S af et y  A n al ysis  S et  f or L A  r e gi m e n p er i o d a n al ysis, 
s e p ar at el y,  u nl e s s  ot h er wi s e  s p e cifi e d.  All  c oll e ct e d  d at a  will  b e  i n cl u d e d i n d at a  listi n gs. 
7. 1. 1.  
A d v e r s e  E v e nt  Di cti o n a r y 
Cli ni c al  a n d  l a b or at or y A Es  will  b e  c o d e d  u si n g  t h e c urr e nt  v ersi o n of t h e M e di c al  Di cti o n ar y 
f or R e g ul at or y  A cti viti es  ( Me d D R A).  S y st e m  or g a n  cl ass  ( S O C), hi g h-l e v el  gr o u p  t er m ( H L G T), 
hi g h-l e v el  t er m ( H L T), pr ef e rre d t e r m ( P T), a n d  l o w er-le v e l t er m ( L L T) will b e pr o vi d e d  i n t he 
A E  d at as et. 
7. 1. 2.  
A d v e r s e  E v e nt  S e v e rit y 
A d v ers e  e v e nts  ar e  gr a d e d b y t h e i n ves ti g at or as  Gr a d e  1, 2, 3,  4, or 5  a c c or di n g t o t o xi cit y 
crit eri a s p e cifi e d i n t h e pr ot o c ol.  T h e  s e v erit y gr a d e of e v e nts  f or w hi c h t he  i n v e sti g at or di d  n ot 
r e c or d s e v erit y will b e c at e g ori z e d  a s  " mi s si n g " f or t a b ul ar s u m m ari e s  a n d  d at a  listi n gs.  T h e 
mi s si n g  c at e g or y  will  b e  li st e d l a st i n s u m m ar y pr es e nt ati o n. 
7. 1. 3.  
R el ati o n s hi p of A d v e r s e  E v e nt s t o St u d y  D r u g 
R el a t e d A Es  ar e  t h ose  f or w hi c h  t he  i n vesti g at or  s el e ct e d " R el at e d " o n  t h e A E  e C R F t o t he 
q u e sti o n  of  " R el at e d t o St u d y  Tr e at m e nt. "  R el at e d n ess  t o e ac h st u d y dr u g  is j u stifie d  b y 
i n v e sti g at or a n d  r e c or d e d o n  A E  e C R F , f or e x a m pl e , r el at e d n ess t o Or al  L E N  is w hi c h 
i n v e sti g at or s el e ct e d " R el at e d "  o n  t h e A E  e C R F t o t h e q u e sti o n of " R el at e d t o St u d y  Tr e at m e nt 
Or al  L E N ".  R el at e d n ess  will  al w a ys  d ef a ult t o t h e i n v e sti g at or's  c h oi c e,  n ot  t h at of t he  m e di c al 
m o nit or.  E v e nt s  f or w hi c h  t h e i n v e sti g at or di d  n ot  r e c or d r el ati o n s hi p t o st u d y  dr u g  will b e 
c o n si d er e d  r el at e d t o st u d y dr u g  f or s u m m ar y p ur p os es.  H o w e v er ,  b y- p arti ci p a nt d at a  listi n gs 
will  s h o w t h e r el ati o n s hi p as missi n g. 
7. 1. 4. 
S e ri o u s  A d v e r s e  E v e nt s 
S eri o us  a d v er s e  e v e nt s  ( S A Es) wi ll b e  i d e ntifi e d a n d  c a pt ur e d  as  S A E s if t h e A Es  m et  t h e 
d efi niti o ns of S A Es  t h at w er e  s p e cifi e d i n t h e st u d y pr ot o c o l. S A E s  c a pt ur e d  a n d  st o r e d i n t h e 
cli ni c al  d at a b as e  will  b e  r e c o n cil e d wit h  t h e S A E  d at a b as e  fr o m t h e Gil e a d  Gl o b al  P ati e nt  S af et y 
( G L P S) D e pr ut m e nt  b ef or e  d at a  fi n aliz ati o n . 
C O N FI D E N TI A L 
P a g e 4 1 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
7. 1. 5. 
7. 1. 5. 1. 
T r e at m e nt- E m e r g e nt  A d v e r s e  E v e nt s 
D efi niti o n of Tr e at m e nt- E m er g e nt  A d v er s e  E v e nts 
Tr e at m e nt- e m er g e nt  A Es  ( T E A E s) ar e  d efi n e d as f oll o ws: 
•  A n y  A Es  l e a di n g t o pr e m at ur e  di s c o nti n u ati o n of st u d y dr u g, or 
•  A n y  A Es  wit h  a n  o n s et  d at e o n or aft er t h e st u d y dr u g  st art d at e  a n d 
V ersi o n  1. 0 
- 
(i) pri or t o t h e l a st e x p os ur e  d at e of L A R e gi m e n  P eri o d  f or t h e L A  R e gi m e n  P eri o d 
A n al y si s 
- 
(ii) n o  l at er t h a n t h e l a st e x p o s ur e  d at e  f or t h e W h ol e  St u d y  P eri o d  A n al ysis. 
7. 1. 5. 2.  
I n c o m pl et e D at es 
If t h e o n s et  d at e of t h e A E  is i n c o m pl et e a n d  t h e A E  st o p  d at e  is n ot  pri or  t o t h e first d os e  d at e of 
st u d y  dr u g,  t h e n t h e m o nt h  a n d  y e ar  ( or y e ar  al o n e if m o nt h  is n ot  r e c or d e d) of o n s et  d et er mi n e 
w h et h er  a n  A E  is tr e at m e nt e m er g e nt.  T h e  e v e nt is c o n si d er e d tr e at m e nt  e m er g e nt as  f oll o ws: 
•  P arti ci p a nts  w h o  r e c ei v e a n y  i nj e cti o n or i nf u si o n dr u g:  t h e A E  o n s et  d at e  is t h e s a m e as or 
aft er t h e m o nt h  a n d  y e ar  ( or y e ar) of t h e first d o s e  d at e of st u d y dr u g 
•  P arti ci p a nts  w h o  d o  n ot  r e c ei v e  a n y  i nj e cti o n or i nf usi o n: 
- 
T h e  A E  o n s et is t h e s a m e  as or aft er t h e m o nt h  a n d  y e ar  ( or y e a r) of t h e first d os e  d at e of 
st u d y  dr u g,  a n d 
- 
T h e  A E  o n s et  d at e  is t h e s a m e as or b ef or e  t h e m o nt h  a n d  y e ar  ( or y e ar) of t h e l a st 
e x p o s ur e  d at e 
A n  A E  wit h  c o m pl et el y  mi s si n g  o n s et  a n d  st o p  d at es, or wit h  t h e o n s et  d at e  mi s si n g  a n d  a  s t o p 
d at e  l at er t h a n t he  fir st d os e  d at e of st u d y dr u g,  will b e c o n si d er e d t o b e tr e at m e nt e m er g e nt.  I n 
a d di ti o n, a n  A E  wit h  t h e o n s et  d at e  mi s si n g  a n d  i n c o m pl et e st o p d at e  wit h  t h e s a m e or l at er 
m o nt h  a n d  y e ar  ( or  y e ar  al o n e if m o nt h  is n ot  r e c or d e d) a s  t h e first d o s e  d at e of st u d y dr u g  will 
b e  c o n si d er e d  tr e at m e nt e m er g e nt. 
W h e n  c al c ul ati n g t h e d ur ati o n of e v e nt or ti m e t o o n s et,  t h e f oll o wi n g i m p ut ati o n r ul e will  b e 
us e d: 
Mi s si n g  st art m o nt h /d a y:  J a n I/first d a y of t h e m o nt h  will  b e  u s e d  u nl ess  t hi s is b ef or e  t h e st art 
d at e of st u d y  dr u g ; i n t hi s c a s e  t h e st u d y dr u g  st art d at e  will  b e  us e d; 
Mi s si n g  st o p  m o nt h /d a y:  D e c  3 1/l a st  d a y of t h e m o nt h  w ill b e u s e d,  u nl e s s  t hi s is aft er t h e la st 
st u d y d at e;  i n t hi s c a s e  t h e l ast st u d y d at e  will b e us e d. 
C O N FI D E N TI A L 
P a g e  4 2 
2 6  F e b 2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
7. 1. 6.  
S u m m a ri e s of A d v e r s e  E v e nt s  a n d  D e at h s 
V ersi o n  1. 0 
Tr e at m e nt- e m er g e nt  A Es  will  b e  s u m m ari z e d b a s e d  o n  t h e S af et y  A n al ysis  S et  or  S af et y 
A n al y si s  S et  f or L A  r e gi m e n, a n d  will b e s u m m ari z e d s e p ar at el y f or t h e w h ol e  st u d y p eri o d 
a n al ysis  a n d  L A  r e gi m e n p eri o d  a n al ysis. 
F or  e a c h  p eri o d  a n al y si s,  a  bri ef,  hi g h-l e v el  s u m m ar y of t h e n u m b er  a n d  p er c e nt a g e of 
p arti ci p a nts  w h o  e x p eri e n c e d  at  l e a st 1  T E A E  i n t h e c at e g ori es  d e s cri b e d  b el o w  will b e pr o vi d e d 
b y tr e at m e nt gr o u p  a n d t ot al. All  d e at h s  o bs er v e d i n t h e p eri o d  will  als o  b e  i n cl u d e d i n t hi s 
s u m m ar y.  T h e  n u m b er  a n d  p er c e nt a g e of p arti ci p a nt s  w h o  e x p eri e n c e d  at  l e ast 1  T E A E  will  b e 
pr o vi d e d  a n d  s u m m ari z e d b y  S O C  a n d P T a n d  b y P T o nl y  f or t h e f oll o wi n g A E  c at e g ori es: 
•  T E A E s 
•  T E A E s  wit h  Gr a d e  3  or  hi g h er 
•  T E A E s  wit h  Gr a d e  2  or  hi g h er 
•  T E  tr e at m e nt-r el at e d A Es 
•  T E  tr e at m e nt-r el at e d A Es  wit h  Gr a d e  3 or hi g h er 
•  T E  tr e at m e nt-r el at e d A Es  wit h  Gr a d e  2 or hi g h er 
•  T E  S A E s 
•  T E  tr e at m e nt-r el at e d S A Es 
•  T E A E s  l e a di n g t o d e at h  ( b y S O C  a n d P T o nl y) 
•  T E A E s  l e a di n g t o pr e m at ur e  dis c o nti n u ati o n of st u d y dr u g 
•  T E A E s  l e a di n g t o pr e m at ur e  dis c o nti n u ati o n of st u d y 
M ulti pl e  e v e nt s  will  b e  c o u nt e d  o nl y  o n c e  p er  p arti ci p a nt  i n e a c h  s u m m ar y. F or s u m m ari e s b y 
S O C  a n d  P T,  A Es  will  b e  s u m m ari z e d a n d  list e d fir st i n al p h a b eti c al  or d er of S O C  a n d t h e n b y 
P T i n d e s c e n di n g  or d er of t ot al fr e q u e n c y wit hi n  e a c h  S O C.  F or  s u m m ari z e s b y P T  o nl y,  A E s 
will  b e  s u m m ari z e d a n d  list e d b y P T  i n d e s c e n di n g  or d er of t ot al p o ol e d  c o h orts  fr e q u e n c y.  F or 
s u m m ari e s  b y  s e v erit y gr a d e,  t h e m o st  s e v er e  gr a d e  will  b e  u s e d  f or t h o s e A Es  t h at o c c urr e d 
m or e  t h a n o n c e  i n a n  i n di vi d u al p arti ci p a nt  d uri n g  t h e p eri o d. 
C O N FI D E N TI A L 
P a g e 4 3 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
I n a d diti o n,  d at a  listi n gs will  b e  pr o vi d e d  f or t h e f oll o wi n g: 
•  All  A Es 
•  All  S A E s 
•  All  D e at hs 
•  All  A Es  wit h  s e v erit y of Gr a d e  3  or  hi g h er 
•  All  A Es  l e a di n g t o di s c o nti n u ati o n of st u d y dr u g 
•  All  A Es  l e a di n g t o di s c o nti n u ati o n of st u d y 
F or  e a c h  listi n g, w h et h er  t h e e v e nt  is tr e at m e nt  e m er g e nt will  b e  i n di c at e d. 
A d diti o n al  A n al y si s of A d v e r s e  E v e nt s 
V ersi o n  1. 0 
7. 1. 7. 
7. 1. 7. 1.  
St u d y  Dr u g  R el at e d  I nj e cti o n Sit e  R e a cti o ns  a n d  I nf u si o n R el at e d  R e a cti o ns 
A d diti o n al  a n al ysis of A Es  will  b e  p erf or m e d  f or  i nj e cti o n sit e  r e a cti o n (I S R) a s  d efi n e d b y hi g h 
l e v el t er m ( H L T) of "I nj e cti o n sit e r e a cti o ns ",  a n d  i nf u si o n r el at e d r e a cti o n (I R R) as  d efi n e d  p er 
e C R F  (i e,  A E  wit h  " Y e s " a n s w er t o "I s t his p art of a n  i nf u si o n-r el at e d r e a cti o n ? " i n A E  C R F) , 
r es p e cti v el y.  T h e  f oll o wi n g s u m m ari e s  will  b e  pr o vi d e d  f or  L A  r e gi m e n p eri o d  a n al ysis  o nl y. 
•  N u m b er of p arti ci p a nts  r e c ei v e d a n y  i nj e cti o n or  i nf u si o n 
•  N u m b er  a n d  p er c e nt a g e of p arti ci p a nts  wit h  st u d y dr u g  r el ate d I S Rs or I R R s 
•  N u m b er  a n d  p er c e nt a g e of p arti ci p a nts  wit h  st u d y dr u g  r el at e d I S Rs or I R R s b y  gr a d e 
•  N u m b er  a n d  p er c e nt a g e of p arti ci p a nts  wit h  st u d y dr u g  r el at e d I S Rs or I R Rs b y P T 
T h e  d e n o mi n at or  f or t h e p er c e nt a g e  c al c ul ati o n  will  b e  b a s e d  o n  t h e n u m b er of p arti ci p a nts 
r e c ei v e d at  l e ast o n e  i nje cti o n or i nf usi o n i n S af et y  A n al ysis  S et  . 
D ur ati o n of t he  I S R will  als o b e c al c ul at e d  a n d  s u m m ari z e d.  D ur ati o n of a  gi v e n  I S R e v e nt is 
d efi n e d  as  t h e I S R st o p  d at e  mi n u s  t h e I S R o n s et  d at e  pl u s  1 d a y.  F or  I S Rs wit h  o n g oi n g  st o p 
d at e , st o p d at e  will  b e  i m p ut e d as  l ast st u d y d at e  or  d at a b a s e  fi n ali z ati o n d at e , w hi c h e v er  is t h e 
e arli est.  D ur ati o n of I S R e v e nts  i n d a ys  will  b e  s u m m ari z e d b y P T a n d  o v er a ll us i n g d e s cri pti v e 
st atisti cs.  D ur ati o n of a  g i v e n I R R e v e nt  is d efi n e d as t h e I R R st o p  d at e  mi n u s  t h e I R R o n s et 
d at e  pl us  1  d a y , a n d  d ur ati o n of I R R will  b e  li st e d als o. 
B y- p arti ci p a nt  listi n gs f or I S Rs or I R R s will  b e  pr o vi d e d. 
C O N FI D E N TI A L 
P a g e  4 4 
2 6  F e b 2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
7. 1. 7. 2.  
St u d y  Dr u g  R el at e d  I nj e cti o n Sit e  I n d ur ati o n a n d  N o d ul e s 
V ersi o n  1. 0 
P er c e nt a g e of o n g oi n g  a n d  r e s ol v e d st u d y dr u g  r el at e d "I nj e cti o n  Sit e  I n d ur ati o n " ( o n e of 
pr ef err e d  t er m s of I S R) will  b e  s u m m ari z e d at b ot h  p arti ci p a nt-l e v el  a n d  e v e nt-l e v el. 
F or  t h e p arti ci p a nt-l e v el  s u m m ar y, if a  p arti ci p a nt  h a d  m or e  t h a n o n e  i nj e cti o n sit e  i n d ur ati o n s, 
t h e p arti ci p a nt  will  b e  c o u nt e d  i n t h e " O n g oi n g "  c at e g or y  u nl ess  all  st u d y  dr u g  r el at e d i nj e cti o n 
sit e  i n d ur ati o n e v e nts  h a v e  b e e n  r es ol v e d. 
F or  t h e e v e nt-l e v el  s u m m ar y,  d ur ati o n of t h e r e s ol v e d e v e nts  will  b e  s u m m ari z e d u si n g 
d e s cri pti v e  st atisti cs. 
St u d y  dr u g  r el at e d "I nj e cti o n  Sit e  N o d ul e s "  ( a n ot h er pr ef err e d  t er m ofI S R) will  b e  s u m m ari z e d 
i n t h e s a m e  m a n n er  as  d efi n e d  f or st u d y  dr u g  r el at e d i nj e cti o n sit e  i n d ur ati o n. 
A  b y- p arti ci p a nt  listi n g f or st u d y dr u g  r el at e d i nj e cti o n sit e  i n d ur ati o n a n d  n o d ul e s  a n d  t h e 
c orr e s p o n di n g  d ur ati o n  will  b e  pr o vi d e d. 
7. 2.  
L a b o r at o r y  E v al u ati o n s 
S u m m ari es of l a b or at or y d at a  will  b e  pr o vi d e d  f or t h e w h ol e  st u d y p eri o d  a n d L A r e gi m e n 
p eri o d  a n al ysis,  r es p e cti v el y. L a b or at or y  d at a  c oll e ct e d  d uri n g  t h e st u d y will  b e  a n al y z e d  a n d 
s u m m ari z e d u si n g  b ot h  q u a ntit ati v e  a n d q u alit ati v e  m et h o ds. 
F or  w h ol e  st u d y p eri o d  a n al y si s , s u m m ari e s of l a b or at or y d at a  will  b e  pr o v i d e d f or t he  S af et y 
A n al y si s  S et  a n d  will  i n cl u d e d at a  c oll e ct e d  u p  t o t h e l a st e x p o s ur e  d at e  f or p arti ci p a nts  w h o 
h a v e  p er m a n e ntl y  di s c o nti n u e d  st u d y,  or  all  a v ail a bl e  d at a  at t he  ti m e of  t h e d at a b as e  s n a p s h ot 
f or p arti ci p a nt s  w h o  w er e  o n g oi n g  o n  st u d y  at t he  ti me of a n  i nte ri m a n al ysi s. 
F or  L A  r e gi m e n a n al ysis , s u m m ari e s of l a b or at or y d at a  will b e pr o v i d e d f or t h e S af et y  A n al y sis 
S et  f or L A r e gi m e n a n d  will  i n cl u d e d at a  c oll e ct e d  u p  t o t h e l a st e x p o s ur e  d at e of L A  r e gi m e n 
f or p arti ci p a nt s w h o  h a v e  p e r m a n e ntl y dis c o nti n u e d  st u d y dr u g, or all  a v ail a bl e  d at a  at  t he  ti m e 
of t he  d at a b as e  s n a p s h ot f or p arti ci p a nts  w h o  w er e  o n g oi n g  o n  st u dy  dr u g  at  t he  ti me of a n 
i nt eri m a n al y sis. 
C al ci u m  C o r r e ct e d  f o r Al b u mi n 
C al ci u m  c orr e ct e d  f or  al b u mi n  will  b e  c al c ul a t e d a n d  s u m ma riz e d  f or t h e st u dy . T h e  f oll o w i n g 
f or m ul a will b e u s e d w h e n  b ot h  s er u m c al ci u m  a n d  a l b u mi n r esult s  f or  a  gi v e n  bl o o d  dr a w n  ar e 
a v ail a bl e  a n d  s e r u m al b u mi n  v al u e  is <  4. 0  g/ d L. 
C al ci u m  c orr e ct e d  f or  al b u mi n  ( m g/d L)  =  s er u m  c al ci u m  ( m g/ d L) +  0. 8  x  ( 4. 0 - al b u mi n  ( g/d L)) 
T o x i city  gr a di n g  f or  c al ci u m  will  b e  a p pli e d  b as e d  o n  t h e c orr e cte d  v al u e s. 
C O N FI D E N TI A L 
P a g e 4 5 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
E sti m at e d  Gl o m e r ul a r  Filt r ati o n  R at e 
V ersi o n  1. 0 
T h e  f oll o wi n g f or m ul a e will b e u s e d  t o c al c ul at e  t h e e sti m at e d  gl o m er ul ar  filtr ati o n r at e u si n g 
C o c k cr oft- G a ult  f or m ul a ( e G F R C G): 
e G F R c a ( m L/ mi n) =  [( 1 4 0 - a g e  ( yrs))  x  w ei g ht  ( k g)  x  ( 0. 8 5 if f e m al e)] / ( S Cr ( m g/ d L)  x  7 2), 
w h er e  w ei g ht  is t ot al b o d y  m a s s i n kil o gr a m s  a n d  S Cr is s er u m  cr e ati ni n e. 
T h e  a n al y si s  will b e b a s e d o n v al u es  r e p ort e d i n c o n v e nti o n al  u nits.  W h e n  v al u e s  ar e  b el o w t h e 
L L O Q,  t h e y will  b e  li st e d as s u c h,  a n d t h e cl o s e st i m p ut e d v al u e  will  b e  u s e d  f or t h e p ur p o s e of 
c al c ul ati n g s u m m ar y st ati sti c s as s p e cifi e d i n S e cti o n  3. 7. 
N o  f or m al st ati sti c al t e sti n g is pl a n n e d. 
7. 2. 1.  
S u m m a ri e s of N u m e ri c  L a b o r at o r y  R e s ult s 
D e s cri pti v e  st ati sti c s will b e pr o vi d e d b y tr e at m e nt gr o u p  f or s el e ct e d l a b or at or y t e st as  f oll o ws: 
•  
B a s eli n e  v al u es 
•  
V al u es at e a c h p o st b a s eli n e  vi sit 
•  
C h a n g e  fr o m b a s eli n e at e a c h p o st b a s eli n e  vi sit 
A  b a s eli n e  l a b or at or y v al u e  will b e d efi n e d  as  t h e l a st m e a s ur e m e nt  o bt ai n e d o n or pri or  t o t h e 
d at e of fir st d os e of st u d y dr u g.  C h a n g e  fr o m b a s eli n e t o a  p o st b a s eli n e  vi sit  will b e d efi n e d  a s 
t h e vi sit  v al u e  mi n u s  t h e b a s eli n e  v al u e.  T h e  m e a n,  m e di a n , Ql, Q 3,  mi ni m u m,  a n d  m a xi m u m 
v al u es  will  b e  di s pl a y e d  t o t h e r e p ort e d n u m b er of di git s;  S D  v al u e s  will  b e  di s pl a y e d t o t h e 
r e p ort e d n u m b er of di gits  pl u s 1. 
I n t h e c a s e of m ulti pl e  v al u e s  i n a n  a n al ysis  wi n d o w,  d at a  will  b e  s el e ct e d f or a n al y si s  a s 
d e s cri b e d  i n S e cti o n  3. 8. 3 . 
7. 2. 2. 
G r a d e d  L a b o r at o r y  V al u e s 
T h e  D AI D S  T a bl e  f or Gr a di n g  t h e S e v erit y of A d ult  a n d  P e di atri c  A d v er s e  E v e nt s , V er si o n  2. 1 
d at e d  J ul y  2 0 1 7,  will  b e  u s e d  t o a s si g n  t o xi cit y gr a d e s  ( 0 t o 4) t o l a b or at or y r es ults f or a n al ysis. 
Gr a d e O i n cl u d e s all  v al u e s  t h at d o n ot m e et  t h e crit eri a f or a n  a b n or m alit y of at  l e a st Gr a d e 1. 
F or  l a b or at or y t e st s wit h  crit eri a f or b ot h  i n cr e a s e d a n d  d e cr e a s e d  l e v els, a n al y s e s  f or e a c h 
dir e cti o n  (i e,  i n cr e ase d, d e cre as e d) will  b e  pr e s e nt e d  s e p ar at el y. 
F or  tri gl y c eri d e s, L D L ( 4t h g e n er ati o n) , a n d  c h ol e st er ol , t o xi cit y gr a di n g  s c al e  is f or f a sti n g t e st 
v al u e s,  s o  n o nf a sti n g  li pi d r e s ult s  ( or  li pi d r e s ult s wit h o ut  a  k n o w n  f a sti n g st at u s) will  n ot  b e 
gr a d e d  or  s u m m ari z e d b y  t o xi cit y gr a d es. 
C O N FI D E N TI A L 
P a g e  4 6 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
7. 2. 2. 1.  
Tr e at m e nt- E m er g e nt  L a b or at or y  A b n or m aliti e s 
V ersi o n  1. 0 
F or  w h ol e  st u d y p eri o d  a n al ysis,  tr e at m e nt- e m er g e nt l a b or at or y a b n or m aliti e s  ar e  d efi n e d  as 
v al u es  t h at i n cr e as e at l e a st 1  t o xi cit y gr a d e  fr o m b as eli n e  at  a n y  p o st b a s eli n e  visit,  u p  t o l a st 
e x p o s ur e  d at e  f or p arti ci p a nts  w h o  p er m a n e ntl y  di s c o nti n u e d  st u d y,  or  t h e l a st a v ail a bl e  d at e  i n 
t h e d at a b a s e  s n a p s h ot f or p arti ci p a nts  w h o  w er e  still o n  st u d y at t h e ti m e of a n  i nt eri m a n al ysis. 
F or  L A  r e gi m e n p eri o d  a n al ysis,  tr e at m e nt- e m er g e nt l a b or at or y a b n or m aliti e s  ar e  d efi n e d  as 
v al u e s  t h at i n cr e as e at l ea st  1  t o xi cit y gr a d e  fr o m b a s eli n e  at  a n y  p o st b a s eli n e  visit,  u p  t o l a st 
e x p o s ur e  d at e of L A r e gi m e n f or p arti ci p a nts  w h o  p er m a n e ntl y  di s c o nti n u e d  st u d y  dr u g , or t h e 
l a st a v ail a bl e  d at e  i n t h e d at a b as e  s n a p s h ot f or p arti ci p a nts  w h o  w er e  still  o n  tr e at m e nt at t h e 
ti m e of a n  i nt eri m a n al ysis. 
If t h e r el e v a nt b a s eli n e  l a b or at or y v al u e is mi s si n g,  a n y  a b n or m alit y of at  l e ast  Gr a d e  1  o b s er v e d 
at a n y  p o st b a s eli n e  vi sit  will  b e  c o n si d er e d tr e at m e nt e m er g e nt. 
7. 2. 2. 2.  
S u m m ari es of L a b or at or y  A b n or m aliti e s 
L a b or at or y  d at a  t h at ar e  c at e g ori c al  will  b e  s u m m ari z e d u si n g  t h e n u m b er  a n d  p er c e nt a g e of 
p arti ci p a nts  i n t h e st u d y wit h  t h e gi v e n  r e s p o n s e at  b a s eli n e  a n d  e a c h  s c h e d ul e d p o st b a s eli n e 
visit. 
T h e  f oll o wi n g s u m m ari e s  ( n u m b er a n d  p er c e nt a g e of p arti ci p a nt s)  f or tr e at m e nt- e m er g e nt 
l a b or at or y a b n or m aliti e s  will  b e  pr o vi d e d  b y  l a b t e st a n d tr e at m e nt gr o u p;  p arti ci p a nts  will  b e 
c at e g ori z e d  a c c or di n g t o t h e m o st  s e v er e  p o st b a s eli n e  a b n or m alit y  gr a d e  f or a  gi v e n  l a b t est: 
•  Gr a d e d  l a b or at or y a b n or m aliti e s 
•  Gr a d e  3  or  4  l a b or at or y a b n or m aliti e s 
F or  all  s u m m ari e s  ofl a b or at or y  a b n or m aliti es , t h e d e n o mi n at or  is t h e n u m b er of p arti ci p a nts 
wit h  n o n mi s si n g  p o st b a s eli n e  v al u es. 
A  b y- p arti ci p a nt  listi n g of tr e at m e nt- e m er g e nt l a b or at or y a b n or m aliti es  a n d  tr e at m e nt- e m erg e nt 
Gr a d e  3 or 4  l a b or at or y a b n or m aliti es , r e s p e ctiv el y,  will  b e  pr o v i d e d b y  p arti ci p a nt  I D n u m b er 
a n d  vi sit  i n c hr o n ol o g i c al or d er . T his  listi ng  will  i n cl u de  all  t e st res ult s  t h at w er e  c oll e cte d 
t hr o u g h o ut t h e st u d y f or t he  l a b t e st of i nter e st, wit h  all  a p pli c a bl e  s e v e rity  g r a des  a n d  a b n or m al 
fl a gs  di spl a y e d. 
C O N FI D E N TI A L 
P a g e  4 7 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
7. 3. 
B o d y  W ei g ht  a n d  Vit al  Si g n s 
V ersi o n  1. 0 
D e s cri pti v e  st ati sti c s will b e pr o vi d e d b y tr e at m e nt  gr o u p a n d t ot al f or b o d y  w ei g ht,  B MI  a n d 
vit al  si g ns  as  f oll o ws: 
•  B as eli n e  v al u e 
•  V al u es at e a c h  p ost b as eli n e  vi sit 
•  C h a n g e  fr o m b a s eli n e at e a c h p ost b as eli n e  vi sit 
A  b a s eli n e  v al u e  will  b e  d efi n e d as t h e l a st a v ail a bl e  v al u e  c oll e ct e d  o n or pri or t o t h e fir st d os e 
d at e of st u d y  dr u g.  C h a n g e  fr o m  b as eli n e  t o a  p o st b a s eli n e  vi sit  will  b e  d efi n e d as t h e 
p ost b as eli n e  v al u e  mi n u s  t h e b a s eli n e  v al u e. 
I n t h e c a s e of m ulti pl e  v al u es  i n a n  a n al ysis  wi n d o w,  d at a  will  b e  s el e ct e d f or a n al y si s  a s 
d e s cri b e d  i n S e cti o n  3. 8 . 3. N o  f or m al st ati sti c al t e sti n g is pl a n n e d. 
A  b y- p arti ci p a nt  listi n g of vit al  si g ns  will  b e  pr o vi d e d  b y  p arti ci p a nt  I D n u m b er  a n d  vi sit i n 
c hr o n ol o gi c al  or d er.  B o d y  w ei g ht,  h ei g ht,  a n d  B MI  will b e i n cl u d e d i n t h e vit al  si g n s listi n g, if 
s p a c e  p er mits. If n ot,  t h e y will  b e  pr o vi d e d  s e p ar at el y. 
7. 4. 
P ri o r  a n d  C o n c o mit a nt  M e di c ati o n s 
M e di c ati o n s  c oll e ct e d at s cr e e ni n g  a n d  d uri n g  t h e st u d y will  b e  c o d e d  u si n g  t h e c urr e nt  v er si o n 
of t h e W orl d  H e alt h  Or g a ni z ati o n  ( W H O) Dr u g  di cti o n ar y.  T h e  W H O  pr ef err e d  n a m e  a n d  dr u g 
c o d e  will  b e  att a c h e d t o t h e cli ni c al d at a b as e. 
7. 4. 1. 
N  o n st u d y  D r u g  A nti r et r o vi r al  M e di c ati o n s 
A n y  n o n st u d y  dr u g  A R V  m e di c ati o n s  u s e d  pri or  t o, d uri n g,  or  aft er t h e st u d y (if c oll e ct e d) will 
b e  list e d. N o  i nf er e nti al st atisti cs will  b e  pr o vi d e d. 
A ntir etr o vir al  m e di c ati o n s  at  b a s eli n e  will  b e  s u m m ari z e d b y  A R V  c at e g or y  a n d  dr u g  n a m e. 
A ntir etr o vir al  m e di c ati o n s  at  b a s eli n e  ar e  d efi n e d  as  t h e A R V  m e di c ati o n s  t a k e n o n or u p t o 2 
d a y  pri or  t o first d os e  d at e of st u d y dr u g. 
7. 4. 2. 
P ri o r  a n d  C o n c o mit a nt  N o n- A R V  M e di c ati o n s 
C o n c o mit a nt  n o n- A R V  m e di c ati o ns  ar e  d efi n e d  a s  n o n- A R V  m e di c ati o n s  t a k e n w hil e  a 
p arti ci p a nt  t o o k st u d y  dr u g.  U s e of c o n c o mit a nt  m e di c ati o ns  fr o m  St u d y  D a y 1 u p  t o t h e l a st 
e xp o s ur e  d at e,  will  b e  s u m m ari z e d ( n u m b er a n d  p er c e nt a g e of p arti ci p a nt s)  b y  tr e at m e nt gr o u p 
a n d  t ot al, a n d  b y pr ef e rr e d n a m e.  M ulti pl e  dr u g  us e  ( b y pr ef err e d  n a m e)  will  b e  c o u nt e d  o nl y 
o n c e  p er  p arti ci p a nt.  T h e  s u m m ar y will b e s ort e d al p h a b eti c all y  b y  pr ef err e d  dr u g  n a m e.  F or 
dr u gs  wit h  t h e s a m e fr e q u e n c y,  s orti n g will b e d o n e  al p h a b eti c all y. 
C O N FI D E N TI A L 
P a g e 4 8 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
If t h e st art or st o p d at e of n o n- A R V  m e di c ati o n s  is i n c o m pl et e, t h e m o nt h  a n d  y e ar  ( or y e ar 
al o n e, if m o nt h  is n ot  r e c or d e d) of t h e st art or  st o p  d at e  will b e u s e d  t o d et er mi n e  w h et h er  t h e 
n o n- A R V s  ar e  c o n c o mit a nt or n ot.  T h e  m e di c ati o n  is c o n c o mit a nt if t h e m o nt h  a n d  y e ar of t h e 
st art or st o p  ( or y e ar of t h e st art or st o p, if m o nt h  is n ot  r e c or d e d) of t h e m e di c ati o n  d o es  n ot 
m e et  eit h er of t h e f oll o wi n g crit eri a: 
T h e  m o nt h  a n d  y e ar of st o p of t h e m e di c ati o n  is b ef or e  t h e fir st d os e  d at e of st u d y dr u g 
If t h e st art a n d  st o p  d at e of n o n- A R V  m e di c at io n s  ar e  c o m pl et e,  t h e st art d at e  is n ot  aft er  l ast 
e x p o s ur e  d at e  a n d t h e st o p  d at e  is n ot  b ef or e  first  d os e  d at e, or t h e n o n- A R V  m e di c ati o n s  ar e 
m ar k e d  as  o n g oi n g  a n d  st art d at e  is o n or b ef or e  l ast e x p o s ur e  d at e , t h e n o n- A R V  m e di c ati o n s 
ar e  c o n c o mit a nt. 
S u m m ari es of n o n- A R V  c o n c o mit a nt m e di c ati o n s  will  b e  b a s e d  o n  t h e S af et y  A n al ysis  S et.  N o 
f or m al st ati sti c al t e sti n g is pl a n n e d.  A  b y- p arti ci p a nt  li sti n g f or all  n o n- A R V  c o n c o mit a nt 
m e di c ati o ns  i n cl u di n g pri or  m e di c ati o n  will  b e  li st e d a n d  s ort e d b y  p arti ci p a nt  I D n u m b er  a n d 
a d mi ni str ati o n  d at e  i n c hr o n ol o gi c al  or d er. 
7. 5.  
El e ct r o c a r di o g r a m  R es ults 
T h e  i n v e sti g at or s' a s s e s s m e nt of E C G  r e s ult s ar e  c oll e ct e d. 
A  s hift t a bl e of t h e i n v e sti g at or s' a s s e s s m e nt of E C G  r es ults at e a c h s c h e d ul e d p o st b a s eli n e  vi sit 
c o m p ar e d  wit h  b a s eli n e  v al u e s  will  b e  pr e s e nt e d b y tr e at m e nt gr o u p  u si n g  t h e f oll o wi n g 
c at e g ori es:  n or m al;  a b n or m al , n ot  cli ni c all y si g nifi c a nt;  a b n or m al,  cli ni c all y  si g nifi c a nt; or 
missi n g.  T h e  n u m b er  a n d  p er c e nt a g e of p arti ci p a nts  i n e a c h  cr o s s- cl a s sifi c ati o n  gr o u p of t h e s hift 
t a bl e will  b e  pr es e nt e d.  P arti ci p a nt s  wit h  a  mi s si n g  v al u e  at  b a s eli n e or p ost b as eli n e  will  n ot  b e 
i n cl u d e d i n t h e d e n o mi n at or  f or p er c e nt a g e  c al c ul ati o n.  N o  i nf er e nti al st ati sti c s will  b e  pr o vi d e d. 
A  b y- p arti ci p a nt  listi n g f or E C G  ass e s s m e nt r es ults  will  b e  pr o vi d e d b y p arti ci p a nt  I D n u m b er 
a n d  vi sit s i n c hr o n ol o gi c al  or d e r. 
7. 6.  
Ot h e r  S af et y  M e a s u r e s 
A  d at a  li sti n g will  b e  pr o vi d e d  f or p arti ci p a nts  e x p eri e n ci n g  pr e g n a n c y  d uri n g  t h e st u dy. 
7. 7. 
C h a n g e s  f r o m P r ot o c ol -S p e cifi e d  S af et y  A n al y s e s 
N o  c h a n g e  fr o m pr ot o c o l-s p e cifie d  s af et y a n a l ys es is  pl a n n e d . 
C O N FI D E N TI A L 
P a g e  4 9 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
8. 
P H A R M A C O K I N E T I C  E V A L U A T I O N/ A N A L Y S I S 
8. 1.  
P h a n n a c o ki n eti c  ( P K) S a m pli n g  a n d P K C o n c e nt r ati o n 
V ersi o n  1. 0 
P K c o n c e ntr ati o n  d at a  fr o m  s er u m P K  s a m pl e s of G S- 5 4 2 3  a n d  G S- 2 8 7 2 , as w ell  as  pl a s m a  P K 
s a m pl es of L E N  ( s e e S e cti o n  1. 2 .5. 3 ) will  b e  li st e d a n d  s u m m ari z e d u si n g  t h e P K  a n al ysis  s ets. 
P K c o n c e ntr ati o n  d at a  fr o m  P K  s u b st u d y  p arti ci p a nts  will  b e  a n al y z e d  s e p ar at el y. 
8. 2.  
P h a n n a c o ki n eti c  P a r a m et e r s 
P K p ar a m et er s  will  b e  e sti m at e d  u si n g  P h o e ni x  Wi n N o nli n ®  s oft w ar e u si n g  st a n d ar d 
n o n c o m p art m e nt al  m et h o ds.  T h e  li n e ar u p/l o g  d o w n  r ul e will  b e  u s e d  i n c o nj u n cti o n  wit h  t h e 
a p pr o pri at e  n o n c o m p art m e nt al  m o d el,  wit h  i n p ut v al u e s  f or d os e  l e v el, d o si n g  ti m e, P K 
c o n c e ntr ati o n , a n d  c orr e s p o n di n g  r e al-ti m e v al u es,  b a s e d  o n  dr u g  d o si n g  ti m es  w h e n e v er 
p ossi bl e. 
All  pr e d o s e  s a m pl e ti m e s b ef or e  ti m e- z er o will b e c o n v ert e d t o z er o  f or t h e c al c ul ati o n of P K 
p ar a m et ers. 
F or  ar e a u n d er  t h e c ur v e  ( A U C), s a m pl e s  b el o w  t h e li mit of q u a ntit ati o n  ( B L Q) of t h e 
bi o a n al yti c al  a s s a y s  o c c urri n g  pri or t o t h e a c hi e v e m e nt of t h e fir st q u a ntifi a bl e  c o n c e ntr ati o n  will 
b e  a s si g n e d  a  c o n c e ntr ati o n  v al u e of z er o t o pr e v e nt  o v er e sti m ati o n of t h e i niti al A U C.  S a m pl es 
t h at ar e B L Q at all  ot h er ti m e p oi nts  will  b e  tr e at e d as mi s si n g  d at a  i n Wi n N o nli n.  T h e  n o mi n al 
ti m e p oi nt  f or  a  k e y  e v e nt  ( e g,  uri n e  c oll e cti o n)  or  d o si n g  i nt er v al ( 1:) m a y  b e  u s e d  t o p er mit 
dir e ct  c al c ul ati o n of A U C  o v er  s p e cifi c ti m e i nt er v als. T h e  a p pr o pri at e n ess of t hi s a p pr o a c h  will 
b e  a s s e s s e d b y t h e P K  s ci e nti st o n a  pr ofil e- b y- pr ofil e  b asis. 
P h ar m a c o ki n eti c  p ar a m et er s  s u c h  a s A U Ci nf, A Z a n d 1 1 1 2 ar e  d e p e n d e nt  o n  a n  a c c ur at e  e sti m ati o n 
of t h e t er mi n al eli mi n ati o n  p h a s e of dr u g.  T h e  a p pr o pri at e n ess of c al c ul ati n g t h e s e p ar a m et er s 
will  b e  e v al u ate d  u p o n  i n s p e cti o n of P K  d at a  o n  a  pr ofil e- b y- pr ofil e  b asis  b y t he  P K  s ci e ntist. 
T h e  a n al yt es  a n d  p ar a m et er s  pr e s e nt e d  i n T a bl e  8- 1  will b e u s e d  t o e v al u at e t he  P K  o bj e cti v es of 
t h e st u d y. 
T a bl e  8- 1.  
P h a n n a c o ki n eti c  P a r a m et e r s  f o r E a c h  A n al yt e 
A n al y si s  S et 
A n al yt e  
S a m pl e  M at ri x 
P a r a m et e r s 
L E N  P K  S u bst u d y 
L E N  
Pl a s m a 
A U C o .2 6 w k, A U C 1 as t, C 2 6 w k, C m a x, C m a x d a y l, t 1 1 2, T 1 ast, I m a x, 
A n al ysis  S et 
T m a x da yl, 
L E N  P K  A n al y si s  S et  
L E N  
Pl a s m a 
C 2 6 w k , t 1 1 2, T l ast 
G S -5 4 2 3  P K 
G S -5 4 2 3  
S er u m 
A U C 0. 2 6 w k, A U C 1 as t, A U C ; nf, % A U C c x p, Ci 6 w k,  C m a x , t 1 1 2, 
A n al ysis  S et 
I ma x, T 1 a,t, C L, Vss 
G S -2 8 7 2  P K 
G S -2 8 7 2 
S er u m 
A U C 0 .2 6 w k, A U C 1 ast, A U C; nf, ¾ A U C c x p, Ci 6 w k, C m a x, t 1 1 2, 
A n al ysis  S et 
T 1., 1 , I m a x, C L, Vss 
C O N FI D E N TI A L 
P a g e  5 0 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
8. 3. 
8. 3. 1. 
St ati sti c al  A n al y si s  M et h o d s 
St ati sti c al  A n al y si s of P K  C o n c e nt r ati o n 
V ersi o n  1. 0 
I n di vi d u al p arti ci p a nt  c o n c e ntr ati o n  d at a of L E N,  G S- 5 4 2 3,  a n d  G S- 2 8 7 2  f or p arti ci p a nts  i n t h e 
P K a n al ysis  s et will b e list e d a n d  s u m m ari z e d u si n g  d es cri pti v e  st atisti cs b y tr e at m e nt gr o u p  f or 
t h e pri m ar y  c o h ort,  t h e pil ot  c o h ort,  a n d f or p o ol e d  c o h orts.  I n a d diti o n,  f or  L E N  a n d  G S- 5 4 2 3, 
i n di vi d u al p arti ci p a nt  c o n c e ntr ati o n  d at a  f or p arti ci p a nts  i n t h e P K a n al ysis  s et will  b e 
s u m m ari z e d  f or c o m bi n e d tr e at m e nt gr o u ps  (t ot al) f or t he  pri m ar y  c o h ort, t he  pil ot  c o h ort,  a n d 
f or p o ol e d  c o h orts.  F or  t h e L E N  P K  s u bst u d y,  i n di vi d u al p arti ci p a nt  c o n c e ntr ati o n  d at a f or P K 
s a m pl e ti m e p oi nt s fr o m  D a y  1  t o D a y  8  will  b e  list e d a n d  s u m m ari z e d o v er all  (i. e., o n e 
s u m m ar y).  S u m m ar y  st atisti cs  ( n u m b er s of p arti ci p a nt s,  m e a n,  S D,  c o effi ci e nt of v ari ati o n 
[ % C V], m e di a n , mi ni m u m,  m a xi m u m, Ql, a n d  Q 3)  will  b e  pr e s e nt e d  f or i n di vi d u al p arti ci p a nt 
c o n c e ntr ati o n  d at a  b y  ti m e p oi nt. 
I n di vi d u al c o n c e ntr ati o n  d at a  listi n gs a n d s u m m ari e s  will  i n cl u d e all  p arti ci p a nt s  wit h 
c o n c e ntr ati o n  d at a. If a  p arti ci p a nt  h a d  q u a ntifi a bl e  pr e- d o s e,  B L Q  at e n d of i nf u si o n, or r e c ei v e d 
i n c orre ct  d os e,  t h e r el at e d P K  c o n c e ntr ati o n( s)  will  b e  c at p ur e d  i n t he  t a ble  b ut  will  b e  e x cl u d e d 
fr o m t he  s u m m ar y st atisti cs,  wit h  r e a s o n s f or e x cl u si o n  i de ntifi e d.  T h e  s a m pl e  si z e  f or e a c h ti me 
p oi nt  will  b e  b a s e d  o n  t h e n u m b er of p arti ci p a nt s  wit h  n o n mi s si n g  c o n c e ntr ati o n  d at a  at t h at ti m e 
p oi nt.  F or  s u m m ar y st atisti cs , B L Q  v al u e s  will b e tr e at e d a s  z er o at pr e d o s e  a n d  p o st d o s e ti m e 
p oi nts.  T h e  n u m b er  a n d  p er c e nt a g e of p arti ci p a nts  wit h  c o n c e ntr ati o n  B L Q , a s  w ell  a s  a n 
i n di c at or if m or e  t h a n o n e-t hir d of t h e p arti ci p a nts  ar e  B L Q,  will  b e  pr e s e nt e d  f or e a c h  ti m e 
p oi nt.  T h e  m et h o d  t o h a n dl e  B L Q  v al u es  f or  P K  s u m m ari e s  ar e  d e s cri b e d  i n S e cti o n  3. 7. 2. 
C o n c e ntr ati o n  v al u es  will  b e  pr e s e nt e d as r e c ei v e d fr o m t h e bi o a n al yti c al  l a b a n d  s u m m ar y 
sta ti sti c s will b e pr e s e nt e d  t o t hr ee  si g nifi c a nt di gits . 
P arti ci p a nt s  wit h  vir al  br e a kt hr o u g h  (i. e ., HI V- 1  R N A 2:: 5 0  c o pi es /m L at  W e e k  2 6  vi sit  as 
d efi n e d b y t h e F D A -d efi n e d  s n a p s h ot  al g orit h m)  will  b e  fl a g g e d i n t h e li sti n gs. 
8. 3. 1. 1. 
P K C o n c e ntr ati o n  D at a  B a s e d o n L E N  P K  S u b st u d y A n al ysis  S et 
F or  a n al y s e s  b as e d o n t he  L E N  P K  S u b st u d y  A n al y si s  s et,  P K  c o n c e ntr ati o n  w ill b e  s u m m ari z e d 
o v er all (i. e ., o n e  s u m m ar y). 
T h e  f oll o wi n g t a bl e s will  b e  pr o v i d e d f or L E N  u si n g  t h e L E N  P K  S u b st u d y  A n al y sis  S et: 
•  I n di vi d u al p arti ci p a nt  c o n c e ntr ati o n  d a t a a n d  s u m m ar y sta ti stics 
T h e  f oll o wi n g fi g ur e s  will  b e  pr o v i d e d f or L E N  u si n g  t h e L E N  P K  S u bst u d y  A n al ysi s  S et: 
C O N FI D E N TI A L 
P a g e 5 1 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
• 
M e a n( ± S D)  c o n c e ntr ati o n  d at a  v er s u s  ti m e ( o n li n e ar a n d s e mil o g arit h mi c s c al es). If m or e 
t h a n o n e-t hir d of t h e v al u e s  at a  ti m e p oi nt ar e  B L Q  t h e n t h e m e a n  a n d  S D  will n ot b e 
pr e s e nt e d  at t h at ti m e p oi nt a n d  r e m ai ni n g p oi nts  c o n n e ct e d. If l o w er err or  b ar  ( m e a n- S D) is 
< 0 at a  ti m e p oi nt t h e n it will  n ot  b e  pr e s e nt e d at t h at ti m e p oi nt. 
•  M e di a n  ( Q 1, Q 3)  c o n c e ntr ati o n  d at a  v er s u s  ti m e ( o n  li n e ar a n d  s e mil o g arit h mi c  s c al es). If 
m or e  t h a n o n e- h alf of t h e v al u es  at  a ti m e p oi nt ar e  B L Q  t h e n t h e m e di a n  a n d  q u artil e  v al u e s 
will n ot b e  pr e s e nt e d  at t h at ti m e p oi nt a n d  r e m ai ni n g p oi nts  c o n n e ct e d. If l o w er err or  b ar 
(  Q 1)  is B L Q at a ti m e p oi nt t h e n it will  b e  pr e s e nt e d  a s  L L O Q at t h at ti m e p oi nt. 
8. 3. 1. 2. 
P K C o n c e ntr ati o n  D at a  B a s e d o n P K  A n al ysis  S ets 
F or  a n al y s e s  b a s e d o n P K  A n al ysis  S ets,  P K  c o n c e ntr ati o n  f or all  a n al yt es  will  b e  s u m m ari z e d 
f or t h e pri m ar y  c o h ort,  t h e pil ot  c o h ort,  a n d  f or p o ol e d  c o h orts. 
T h e  f oll o wi n g t a bl e s will  b e  pr o vi d e d  f or e a c h  a n al yt e  ( L E N, G S- 5 4 2 3,  a n d  G S- 2 8 7 2)  u si n g  t h e 
a s s o ci at e d  P K  A n al y si s  S et: 
•  I n di vi d u al p arti ci p a nt  c o n c e ntr ati o n  d at a  a n d  s u m m ar y st atisti cs 
T h e  f oll o wi n g fi g ur es will  b e  pr o vi d e d  f or e a c h a n al yt e  ( L E N, G S- 5 4 2 3,  a n d  G S- 2 8 7 2)  u si n g  t h e 
ass o ci at e  P K  A n al ysis  S et: 
• 
M e a n( ± S D)  c o n c e ntr ati o n  d at a  v er s u s  ti m e ( o n li n e ar a n d s e mil o g arit h mi c s c al es). If m or e 
t h a n o n e-t hir d of t h e v al u e s  at a  ti m e p oi nt ar e  B L Q  t h e n t h e m e a n  a n d  S D  will n ot b e 
pr e s e nt e d  at t h at ti m e p oi nt a n d  r e m ai ni n g p oi nts  c o n n e ct e d. If l o w er err or  b ar  ( m e a n- S D) is 
< 0 at a  ti m e p oi nt t h e n it will  n ot  b e  pr e s e nt e d at t h at ti m e p oi nt. 
•  M e di a n  ( Q 1, Q 3)  c o n c e ntr ati o n  d at a  v er s u s  ti m e ( o n  li n e ar a n d  s e mil o g arit h mi c  s c al es). If 
m or e  t h a n o n e- h alf of t h e v al u es  at  a ti m e p oi nt ar e  B L Q  t h e n t h e m e di a n  a n d  q u artil e  v al u e s 
will n ot b e  pr e s e nt e d  at t h at ti m e p oi nt a n d  r e m ai ni n g p oi nts  c o n n e ct e d. If l o w er err or  b ar 
(  Q 1)  is B L Q at a ti m e p oi nt t h e n it will  b e  pr e s e nt e d  a s  L L O Q at t h at ti m e p oi nt. 
•  I n di vi d u al p arti ci p a nt  c o n c e ntr ati o n  d at a  v ers us  ti m e ( o n  li n e ar a n d  s e mil o g arit h mi c  s c al es). 
V al u es of B L Q will  b e  di s pl a y e d  a s O o n  t h e li n e ar s c al e a n d  mi s si n g  o n  t h e s e mi-l o g arit h mi c 
s c al e. 
I n a d diti o n,  t h e f oll o wi n g listi n gs will b e pr o vi d e d  f or all  a n al yt es: 
•  Pl a s m a  P K  s a m pli n g d et ails  f or  L E N  b y  p arti ci p a nt,  i n cl u di n g pr o c e d ur e s , diff er e n c e s  i n 
s c h e d ul e d  a n d  a ct u al  dr a w  ti m e s, a n d  s a m pl e  a g e. 
•  S er u m  P K  s a m pli n g d et ails  f or G S- 5 4 2 3  a n d  G S- 2 8 7 2 b y p arti ci p a nt,  i n cl u di n g pr o c e d ur e s, 
diff er e n c es  i n s c h e d ul e d a n d  a ct u al  dr a w  ti m e s, a n d  s a m pl e  a g e. 
C O N FI D E N TI A L 
P a g e  5 2 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
8. 3. 2.  
St ati sti c al  A n al y si s of P K P a r a m et e r s 
V ersi o n  1. 0 
I n di vi d u al esti m at es  of p h ar m a c o ki n eti c  p ar a m et ers of L E N,  G S- 5 4 2 3,  a n d  G S- 2 8 7 2  will  b e 
li st e d a n d  s u m m ari z e d u si n g  d e s cri pti v e  st atisti cs  ( e g , s a m pl e  si z e, arit h m eti c  m e a n,  c o effi ci e nt 
of v ari ati o n %,  S D,  9 5 %  CI  f or t h e arit h m eti c  m e a n , g e o m etri c  m e a n,  % C V , m e di a n,  mi ni m u m , 
m a xi m u m, Ql, Q 3,  s a m pl e si z e of n at ur al  l o g-s c al e [ L N], g e o m etri c  m e a n , G e o m etri c 
C o effi ci e nt of V ari ati o n  [ % G V C], 9 5 %  C o nfi d e n c e  I nt er v al f or G e o m etri c  M e a n  [ G CI], m e a n of 
L N,  S D of L N). P K p ar a m et er s  f or L E N,  G S- 5 4 2 3  a n d G S- 2 8 7 2  will  b e  s u m m ari z e d as 
d e s cri b e d  i n S e cti o n  3. 2. 3 . 
P K p ar a m et er s  list e d i n T a b l e  8- 1 will  b e  i n cl u d e d i n t h e f oll o wi n g t a bl es. 
•  I n di vi d u al esti m at es  a n d  s u m m ar y st atisti cs of pl a s m a  L E N  P K  p ar a m et er s  u s i n g t h e L E N 
P K  S u b st u d y  A n al ysis  S et 
•  I n di vi d u al e sti m at e s  a n d  s u m m ar y st atisti cs of pl a s m a  L E N  P K  p ar a m et er s  u si n g  t h e L E N 
P K  A n al ysis  S et 
•  I n di vi d u al e sti m at e s  a n d  s u m m ar y st atisti cs of s er u m  G S- 5 4 2 3  P K  p ar a m et er s  u si n g  t h e G S-
5 4 2 3  P K  A n al y si s  S et 
•  I n di vi d u al e sti m at e s  a n d  s u m m ar y st atisti cs of s er u m  G S- 2 8 7 2  P K  p a r a m ete rs  u si n g  t h e G S-
2 8 7 2  P K  A n al ysis  S et. 
P K p ar a m et er s  c o ul d  b e  u n e sti m at a bl e  d u e t o i ns uffi ci e nt c o n c e ntr ati o n  d at a or m a y b e e sti m ate d 
b ut  m ar k e d  f or e x cl u si o n  d u e  t o r e a s o n s s u c h a s t he  p a rti ci p a nt r ec ei v e d  a n  i n c orrect d os e.  I n 
s u c h c a s e s,  t h e P K  p ar a m e t er s will  b e  i n cl u de d  i n t he  li sti n g ( a s n ot  r e p orte d  [ N R] or t h e es ti m at e 
v al u e s) b ut  will  b e  e x cl u d e d  fr o m t he  s u m m ar y st atisti cs, wit h  r ea s o n s f or e x cl u s i o n i de ntifi e d. 
I n a d diti o n , d et er mi n ati o n of h alf-lif e  a n d  c orr e s p o n di n g  c orr el ati o n  c o effi ci e nt  will  b e  pr o vi d e d 
i n t h e f oll o wi n g  listi n gs: 
•  I n di vi d u al d at a  o n  d et e r mi n ati o n of L E N  pl a s m a  h alf-lif e  a n d  c o rres p o n di n g  c orre l ati o n 
c o effi ei c e nt  u si n g  t h e L E N  P K  A n al y si s  S et 
•  I n di vi d u al d at a  o n  d et er mi n ati o n of G S- 5 4 2 3  s er u m h alf-lif e  a n d  c orr e s p o n di n g  c orr el ati o n 
c o effi ei c e nt  u si n g  t h e G S- 5 4 2 3  P K  A n al y si s  S et 
•  I n di vi d u al d at a  o n  d e t er mi n ati o n of G S- 2 8 7 2  ser u m  h al f -lif e  a n d  c orr e sp o n di n g  c orr el ati o n 
c o effi ei c e nt  u si n g  t he  G S- 2 8 7 2  P K  A n al y si s  S et. 
C O N FI D E N TI A L 
P a g e 5 3 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
9. 
I M M U N O G E N I C I T Y A N A L Y S I S 
I m m u n o g e ni cit y t o G S- 5 4 2 3  a n d  G S- 2 8 7 2  will  b e  e v al u at e d  b a s e d  u p o n  t h e i n ci d e n c e of a nti-
G S- 5 4 2 3  a nti b o d y,  a nti- G S- 2 8 7 2  a nti b o d y, as w ell as b ot h  a nti- G S- 5 4 2 3  a n d  a nti- G S- 2 8 7 2 
a nti b o d y  f or m ati o n,  r es p e cti v el y. 
9. 1.  
D efi niti o n s 
P a rti ci p a nt s  E v al u a bl e  f o r A D A P r e v al e n c e i n cl u d e s all  p arti ci p a nt s  w h o  h a v e  at  l e a st o n e 
r e p ort a bl e A D A  r e s ult at  b a s eli n e or p o st- b a s eli n e. 
P a rti ci p a nt s  E v al u a bl e  f o r A D A  I n ci d e n c e i n cl u d es all  p arti ci p a nt s  w h o  h a v e  at  l e a st o n e 
r e p ort a bl e A D A  r e s ult at  p o st- b a s eli n e. 
A D A P r e v al e n c e r ef er t o t h e pr o p orti o n of p arti ci p a nt s  w h o  h a v e  at l e a st o n e  p o siti v e  A D A 
s a m pl e ( b a s eli n e or p o st- b a s eli n e)  a m o n g  all  p arti ci p a nt s  e v al u a bl e  f or A D A  pr e v al e n c e. 
A D A I n ci d e n c e r ef er t o t h e pr o p orti o n of p arti ci p a nt s  w h o  h a v e  Tr e at m e nt- E m er g e nt  A D A 
a m o n g  all  p arti ci p a nt s  e v al u a bl e  f or A D A  i n ci d e n c e. 
T r e at m e nt- E m e r g e nt  A D A: i n cl u d e s eit h er  Tr e at m e nt- B o o st e d or Tr e at m e nt-I n d u c e d  A D A s , 
wit h  d et ail s  b e e n  pr e s e nt e d  i n t h e f oll o ws: 
- 
T r e at m e nt- B o o st e d  A D A is d efi n e d as p ositi v e  b a s eli n e  A D A  s a m pl e a n d at l e a st o n e 
p o siti v e  p o st- b a s eli n e  A D A  s a m pl e  a n d t h e ( m a x tit er of t h e p o st- b a s eli n e  A D A / tit er of 
b as eli n e  A D A) 2: 4. If b as eli n e  tit er <  1 0  ( 1 0 is t h e mi ni m u m  r e p ort a bl e tit er v al u e), it 
will  b e  c o n si d er e d  b o o st e d if m a x  tit er of t h e p o st- b a s eli n e 2: 1 0.  T h e  pr o p orti o n of 
p arti ci p a nt s  w h o  h a v e  Tr e at m e nt- B o o st e d A D A is c al c ul at e d  b as e d o n t h e t ot al n u m b er 
of p arti ci p a nt s  e v al u a bl e  f or A D A  i n ci d e n c e a s  t h e d e n o mi n at or. 
- 
T r e at m e nt- I n d u c e d A D A is d efi n e d  a s  n e g ati v e  or  mi s si n g  b as eli n e  A D A  s a m pl e a n d  at 
l e a st o n e  p o siti v e  p o st- b a s eli n e  A D A  s a m pl e.  T h e  pr o p orti o n of p arti ci p a nt s  w h o  h a v e 
Tr e at m e nt-I n d u c e d  A D A  is c al c ul at e d  b a s e d  o n  t h e t ot al n u m b er of p arti ci p a nt s  e v al u a bl e 
f or A D A  i n ci d e n c e as  t h e d e n o mi n at or. 
P e r si st e nt A D A is d efi n e d  as  ( a)  Tr e at m e nt-I n d u c e d  A D A  d et e ct e d  at t w o or m or e  s a m pli n g 
ti m e p oi nt s  d uri n g  t h e st u d y,  w h er e  t h e fir st a n d  l a st A D A- p o siti v e  s a m pl e  (irr e s p e cti v e of a n y 
n e g ati v e  s a m pl e s i n b et w e e n)  ar e  s e p ar at e d b y a  p eri o d of 1 6  w e e k s  or  l o n g er; or ( b) Tr e at m e nt-
I n d u c e d A D A  d et e ct e d  at t h e l ast s a m pli n g ti m e p oi nt of t h e st u d y.  T h e  pr o p orti o n of 
p arti ci p a nt s  w h o  h a v e  p er si st e nt  A D A  is b a s e d  o n  t h e t ot al n u m b er of p arti ci p a nt s  e v al u a bl e  f or 
A D A  i n ci d e n c e as  t h e d e n o mi n at or. 
T r a n si e nt A D A is d efi n e d as Tr e at m e nt-I n d u c e d A D A t h at d o e s  n ot  m e et t he  d efi niti o n of 
p er si st e nt  A D A.  T h e  pr o p orti o n of p arti ci p a nt s  w h o  h a v e  tr a n si e nt A D A  is b a s e d  o n  t h e t ot al 
n u m b er of p arti ci p a nt s  e v al u a bl e  f or A D A  i n ci d e n c e as t h e d e n o mi n at or. 
C O N FI D E N TI A L 
P a g e  5 4 
2 6  F e b  2 0 2 4 


L e n a c a p a vi r  + G S - 5 4 2 3 +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ys is 
V ersi o n 1. 0 
P a rti ci p a nt -l e v el A D A st at. us is d efi n e d  as  ( a)  " A D A + " if t h e p arti ci p a nt  h a s  Tr e at m e nt-
E m er g e nt  A D A;  ( b) " A D A- " if t h e p arti ci p a nt  is e v a l u a bl e f or A D A  i n ci d e n c e a n d  d o es  n ot  h a v e 
Tr e at m e nt- E m er g e nt  A D A;  a n d ( c)  mis s i n g if t h e p arti ci p a nt  is n ot  e v al u a bl e  f or A D A  i n ci d e n c e. 
Ti m e  t o A D A o n s et i s d efi n e d as: 
- 
t h e n u m b er of d a ys  aft er fir st d os e  t o t h e d a y  w h e n  t h e first p ositi v e  A D A  r e s ult w a s 
d et e ct e d  f or  p arti ci p a nts  wit h  Tr e at m e nt-I n d u c e d  A D A 
- 
t h e n u m b er of d a ys  aft er fir st d os e  t o t h e d a y  w h e n  t h e first b o ost e d  p ost- b as eli n e  p o siti v e 
A D A  r es ult w a s  d et e ct e d  f or p arti ci p a nts  wit h  Tr e at m e nt- B o o st e d  A D A. 
9. 2.  
E v al u ati o n of I m m w 1 o g e ni cit y  D at a 
B a s e d  o n  t h e r es p e ctiv e  e v al u a bl e  p o p ul ati o n s , t h e f oll o wi n g m e as ur es of i m m u n o g e ni city  will 
b e r e p ort e d  f or ( a)  A D A  pr e v al e n c e , ( b) A D A i n ci d e n c e, a n d  ( c) Tr a n si e nt/ P er si st e nt  A D A. 
T h e  n u m b ers  a n d  p er c e nt a g es of p artj ci p a nts  wit hi n  e a c h  A D A  c at e g or y  d e s cri b e d  a b o v e  will  b e 
s u m m ari z e d  o v er  t h e e ntir e  st u d y  p eri o d. I n a d diti o n,  t h e n u m b er  a n d  p er c e nt a g e of p ositi v e 
A D A  s a m pl es  will  b e  s u m m ari z e d  b y  n o mi n al  visit.  A D A  tit er v al u es  i n p o siti v e  A D A  s a m pl e s 
will  b e  s u m m ari z e d  b y  visit,  in cl u di n g  m e di a n , QI, Q 3,  mi ni m u m  a n d  m a xi m u m  tit er v al u es. 
S u m m ar y  st atisti cs  f or ti m e t o A D A  o n s et i n A D A +  p a.tti ci p a nts  (i. e. p arti ci p a nts  wit h 
Tr e at m e nt- E m er g e nt  A D A)  will  i n cl u d e m e di a n, Ql, Q 3,  mi ni m u m  a n d  m a xi m u m  o n s et  ti m es. 
S u m m ari es  will  b e  pr o vi d e d  f or e a c h tr e at m e nt a m 1 a n d  all  a cti v e  tr e at m e nt gr o u ps  f or t h e 
c o m p o u n d of i nt er e st c o m bi n e d. 
B y - p arti ci p a nt listi n g of A D A  r es ult, tit er, a n d  c orr e s p o n di n g  P K  c o n c e ntr ati o n b y p arti ci p a nt  I D 
n u m b er  a n d  visit , as w ell  as  p a 1ti ci p a nt-l e v el  A D A  st at us , A D A  t y p e ( p er si st e nt or  tr a n si e nt), a n d 
ti m e t o A D A  o ns et  will b e pr o vi d e d  f or all  p arti ci p a nts  i n t h e I m m u n o g e ni cit y A n al ysis  S et.  A 
s e p ar at e  li sti n g will  b e  pr o d u c e d  f or  p arti ci p a nts  wit h  a n y p ositi v e A D A r es ults.  T h e  A D A  tit er 
v a l u es i n A D A +  p arti ci p a nts  will  b e  pl ott e d  o v er  ti m e b y i n di vi d u al p arti ci p a nt  gr o u p e d  b y 
tr e at m e nt.  F or  t h e p ur p o s e of pl otti n g,  s a m pl e s  wit h  n e g ati v e  A D A  r es ult or  u n d et e ct a bl e  tit er 
will  h a v e  t h e tit er v al u e  i m p ut e d t o z er o  a n d  c o n n e ct e d  wit h  t h e a dj a c e nt ti m e p oi nts. 
I n or d er  t o e v al u at e  t h e i m p a ct of A D A  o n  P K,  c o m bi n e d  i n di vi d u al P K  c o n c e ntr ati o n-ti m e 
pr ofil e  pl ots  b y  tr e at m e nt gr o u p  a n d  t ot al will b e pr o d u c e d  wit h  A D A +  p aiti ci p a nt s  hi g hli g ht e d 
i n r e d. If r el e v a nt,  a d diti o n al 
T h e  f oll o wi n g  A D A s u m m ar y t a bl es will  b e  g e n er at e d  f or ( 1) a nti- G S- 5 4 2 3,  ( 2) a nti- G S- 2 8 7 2, 
a n d  ( 3) b ot h  a nti- G S- 5 4 2 3  a n d  a nti- G S- 2 8 7 2: 
•  I m m u n o g e ni cit y r es ults o v er  t h e e ntir e s n 1 d y p eri o d,  i n cl u di n g c al c ul ati o n of A D A 
pr e v al e n c e , i n ci d e n c e, a n d n u m b er s  a n d  p er c e nt a g es of p aiti ci p a nt s  i n e a c h A D A c at e g or y . 
•  N u m b ers  a n d  p er c e nt a g es of p ositi v e  A D A  r es ults b y  vi sit 
•  M e di a n, Ql , Q 3 , mi ni m u m , m a xi m u m of tit er v al u es  i n p o siti v e A D A  s a m pl e s  b y  vi sit 
C O N FI D E N TI A L 
P a g e 5 5 
2 6 F e b 2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
•  Ti m e t o A D A  o n s et  ( m e di a n, Ql, Q 3,  mi ni m u m,  m a xi m u m)  i n A D A +  p arti ci p a nt s 
T h e  f oll o wi n g fi g ur es will  b e  pr o vi d e d  f or e a c h a n al yt e,  a nti- G S- 5 4 2 3  a n d  a nti- G S- 2 8 7 2: 
•  I n di vi d u al c o n c e ntr ati o n  vs.  ti m e pr ofil e s  gr o u p e d  b y  tr e at m e nt, wit h  A D A +  p arti ci p a nt s 
hi g hli g ht e d  i n r e d 
•  I n di vi d u al A D A  tit er v al u es  o v er ti m e gr o u p e d  b y  tr e at m e nt ( A D A + p arti ci p a nt s  o nl y) 
- 
A D A  tit er v al u e s  l e s s t h a n t h e mi ni m u m  r e p ort a bl e tit er v al u e  a n d tit er v al u e s  f or A D A-
n e g ati v e  s a m pl es  will  b e  i m p ut e d t o 0. 
T h e  f oll o wi n g listi n gs will b e pr o vi d e d: 
•  Li sti n g of A D A  r e s ult s, tit er a n d  c orr e s p o n di n g  P K  c o n c e ntr ati o ns  b y  p arti ci p a nt  I D a n d 
vi sit , as  w ell  as  p arti ci p a nt-l e v el  A D A  st at u s,  A D A  t y p e ( p er si st e nt or tr a n si e nt), a n d ti m e t o 
A D A  o n s et  f or all  p arti ci p a nt s  i n t h e i m m u n o g e ni cit y a n al ysis  s et 
•  S a m e  li sti n g a b o v e  i n p arti ci p a nt s  wit h  a n y  p o siti v e  A D A  r es ult. 
I n a d diti o n,  s u m m ar y of i m m u n o g e ni cit y r e s ult s o v er t h e e ntir e  st u d y p eri o d  f or A D A  a g ai n st 
b ot h  G S- 5 4 2 3  a n d  G S- 2 8 7 2  will  b e  i n cl u d e d. 
C O N FI D E N TI A L 
P a g e  5 6 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
1 0. 
R E F E R E N C E S 
V ersi o n  1. 0 
U. S. D e p art m e nt of H e alt h  a n d  H u m a n  S er vi c es , F o o d  a n d  Dr u g  A d mi ni str ati o n  ( F D A), C e nt er 
f or Dr u g  E v al u ati o n  a n d  R e s e ar c h  ( C D E R).  H u m a n  I m m u n o d efi ci e n c y Vir u s-I 
I nf e cti o n:  D e v el o pi n g  A ntir etr o vir al  Dr u g s  f or Tr e at m e nt.  G ui d a n c e  f or I n d ustr y. 
Sil v er  S pri n g, M D. 
N o v e m b er,  2 0 1 5. 
C O N FI D E N TI A L 
P a g e  5 7 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
1 1. 
S O F T W A R E 
V ersi o n  1. 0 
S A S ® S oft w ar e  V er si o n  9. 4.  ( S A S  I n stit ut e I n c., C ar y,  N C,  U S A)  is u s e d  f or all  pr o gr a m mi n g of 
t a bl e s, li sti n g s, a n d  fi g ur es. 
P A S S ®  V er si o n  1 4  ( N C S S,  L L C;  K a ys vill e,  Ut a h,  U S A)  is u s e d  f or s a m pl e  si z e  a n d  p o w er 
c al c ul ati o n. 
P h o e ni x  Wi n N o nli n ®  8. 3  ( P h ar si g ht C or p or ati o n,  Pri n c et o n , N J,  U S A) is u s e d  f or 
p h ar m a c o ki n eti c/ p h ar m a c o d y n a mi c  ( P K/ P D) a n al ys es. 
C O N FI D E N TI A L 
P a g e 5 8 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
1 2. 
S A P  R E V I S I O N 
R e visi o n  D at e 
( D D M M M Y Y Y Y)  
S e cti o n 
C O N FI D E N TI A L 
V ersi o n  1. 0 
S u m m a r y of R e vi si o n 
R e a s o n  f o r R e visi o n 
P a g e  5 9 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St ati sti c al  A n al y si s Pl a n - Fi n al  A n al y si s 
A P P E N D I C E S 
St u d y  Pr o c e d ur e s  T a bl e 
V er si o n  1. 0 
A p p e n d i x 1. 
A p p e nd i x 2. 
A p p e n d i x 3. 
A p p e n d i x 4. 
A p p e n d i x 5. 
A p p e n d i x 6. 
Fl o w ch art of U S F D A -d efi n e d  S n a p s h ot Al g o rit h m  (f or L o n g A c ti n g S wit c h  T ri al) 
A d v e rs e E v e nt s of C O Vl D- 1 9  a n d  S u s p e ct e d C O Vl D - 1 9 I nf e ctio n 
A d v e rs e E v e nt s of C O Vl D -1 9  an d S u s p e ct e d C O Vl D- 1 9 I nf e ctio n 
Pr o gr a m mi n g S p e ci fic ati o n s 
T a b l e  S hell s  f or P art i cip a nt Gr o u p i ng 
C O N FI D E N TI A L 
P a g e 6 0 
2 6 F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
A p p e n di x  1.  
St u d y  P r o c e d u r e s  T a bl e 
St u d y  Pr o c e d ur e 
S cr e e ni n g•  
D a y 1 
D a y 2 
Writt e n  I nf or m e d C o n s e nt 
X 
M e di c al  Hi st or y 
X 
R e vi e w  C o n c o mit a nt 
X    
X    
X 
M e di c ati o n s 
R e vi e w  A E s 
X    
X    
X 
C o m pl et e  P h y si c al 
X 
X 
E x a mi n ati o n 
F o c u s e d  P h ysi c al 
E x a mi n ati o n 
H ei g ht 
X 
W ei g ht 
X    
X 
Vit al  Si g ns c 
X    
X 
Pr o vir al  D N A P h e n ot y p e 
X 
B ul k  Vir al  O ut gr o wt h 
P h e n ot y p e  a n d  Pr o vir al  D N A 
X 
G e n ot y p e 
C h e mi str y 
X    
X 
H e m at ol o g y 
X 
X 
C o a g ul ati o n 
X 
T h yr oi d  F u n cti o n 
X    
X 
C D 4 +,  C D S +  C e ll C o u n t, 
X    
X 
C D 4/C D 8  R ati o 
C O N FI D E N TI A L 
D a y  8 
W k 4 
X    
X 
X    
X 
X 
X 
X 
X 
X 
X 
X 
V ers io n  1. 0 
F oll o w- u p  Visits 
Tr e at m e nt  Visits  Wi n d o w 
Wi n d o w 
( ± 3  D a ys) 
( ± 6  D a y s) 
P o st- E T 
3 0-,  9 0-, 
a n d  1 8 0-
W k 8 
W k 1 2 
W k 1 6 
W k 2 0 
W k 2 4    
W k 2 6 
W k 3 8 
W k 5 2 
E T 
D a y F U" 
X    
X    
X    
X    
X    
X    
X    
X    
X    
X 
X    
X    
X    
X    
X    
X 
X 
X    
X    
X 
X 
X 
X    
X    
X 
X 
X 
X    
X    
X    
X    
X 
X 
X    
X    
X    
X    
X 
X 
X    
X    
X    
X    
X 
X 
X 
X    
X    
X 
X 
X 
X    
X    
X 
X 
X    
X    
X    
X    
X 
P a g e  6 1 
2 6  F e b 2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
St u d y  P r o c e d u r e 
S c r e e ni n g• 
S er u m  Pr e g n a n c y  T e st 
X 
F S H d 
X 
Uri n al y si s 
X 
Uri n e  Pr e g n a n c y  T e st 
H B V  &  H C V  S er ol o g y 
X 
HI V-I  R N A 
X 
HI V- I G e n ot y p e/ P h e n ot y p e • 
HI V  R e ser v oir A s s a y 
e G F R 
X 
E C G 
X 
I mm u n e  Bi o m ar k er 
C oll e c ti o n 
P l asm a S t or a ge  S a m p l es f or 
Vir ol o g y T e s ti n g 
I m m u n o g e ni cit y A s s e s s m e nt 
S e r u m S a m pl e 
P D  Bi o m ar k ers:  P B M C, 
W h ol e  Bl o o d,  S er u m,  Pl a s m a 
S er u m P K s a m pl e s ( G S- 54 2 3 
&  G S- 2 8 7 2) 1 
P l as m a P K S a m p l e f or L E N g 
Si n gl e P K S a m pl e  ( G S-5 4 2 3 
&  G S - 2 87 2 ) 
C O N FI D E N TI A L 
D a y  1 
D a y 2 
D a y  8 
W k 4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
V ers io n  1. 0 
F oll o w- u p  Vi sit s 
T r e at m e nt  Vi sit s  Wi n d o w 
Wi n d o w 
( ± 3  D a y s) 
( ± 6  D a y s) 
P o st- E T 
3 0-,  9 0- , 
a n d 1 8 0 -
W k 8 
W k 1 2 
W k 1 6 
W k 2 0 
W k 2 4 
W k 2 6 
W k 3 8 
W k 5 2 
E T 
D a y
Fl. J b 
X 
X    
X    
X    
X 
X 
X    
X    
X    
X    
X 
X    
X    
X    
X    
X    
X    
X    
X    
X 
X 
X 
X 
X    
X    
X    
X    
X 
X 
X 
X    
X    
X 
X    
X    
X    
X    
X    
X    
X    
X    
X    
X 
X 
X    
X    
X 
X    
X    
X 
X    
X 
X    
X 
X    
X    
X    
X    
X    
X    
X    
X 
P a g e 6 2 
2 6  F e b  2 0 2 4 


L e n a c a p a vi r  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St a tisti c al A n al ysis  Pl a n  - Fi n al  A n al ys is 
St u d y  Pr o c e d ur e 
S cr e e ni n g • 
Si n gl e  Pl as m a  P K  S a m pl e f or 
L E N 
O pti o n al P K S u bst u d y 
S a m p l e 
R a n d o mi z a tio n 
L E N  Or al  A d mi nistr a ti on h 
L E N  S C  A d mi nistr ati o ni 
G S - 5 42 3 I V I nf usi on 
A d mi nistr ati o ni 
G S - 28 7 2 I V I nf usi o n 
A d mi nistr ati o n ; 
-
D a y  1 
D a y 2 
D a y s 
W k 4 
W k 8 
X    
X 
X 
X 
X 
X    
X 
X 
X 
X 
V e rsio n  1. 0 
F oll o w -u p Visits 
Tr e at m e nt Vi sit s ,' Vl n d o w 
W i n d o w 
( ± 3  D a ys) 
(, 1, 6  D a y s) 
P o st -E T 
3 0-,  9 0-, 
a n d 1 8 0 -
W k 1 2 
W k 1 6 
W k 2 0 
W k 2 4 
\ V k 2 6  
\ V k 3 8 
W k 5 2 
E T 
D a y FlJ' > 
X    
X    
X    
X    
X    
X    
X 
a.  
F or  t h e Pt i m ar y C o h ort , s cr e e ni ng  pr o c e d ur es  will b e c o n d u ct e d i n 2  p arts:  P art  2  will  b e  p erf o 1 m e d  o n c e  r es ults of  b N A b  s e nsiti vit y t esti n g fr o m  P art  I  ar e  re vi e w e d a nd 
p arti ci p a nt i s d e e m e d  eli gi bl e  t o pr o c e e d.  F or  t he  o pti o n al  Pil ot  C o h ort,  p arti ci p a nts  will b e s el e ct e d b y  t h e s p o ns or  fr o m t h e pr e vi o usl y s cr e e n e d/f ail e d p arti ci p a nts i n t h e 
Pri m ar y  C o h ort  a n d will  dir e ctl y  pr o c e e d  t o S cr e e ni n g  P art  2  ( n o n e e d  t o r ep e at  S cr e e ni n g  P art 1). 
b. 
R ef er  t o S e cti o n  6. 5.  l f or P ost- E T  3 0- , 9 0- , a n d  1 8 0- D a y f oll o w- u p  vis its. 
•  
C o u n s el p arti ci p a nt  re g ar di n g t he  i m p ort a n c e of c o n ti n ui 1 1 g a  c o m pl et e A R V t h er a p y i n a c c or d a n c e  t o st a n d ar d of c ar e,  a n d  r ef er p ati e nt  t o a n a p pr o pri at e HI V tr e at m e nt 
f a cilit y. 
c.  
Vit al  si g ns  bl o o d  p r essur e,  p ul s e, r es pir ati o n r ate,  a n d t e mp er at u re. O n  D a y I, vit al  sig n s  s h o ul d b e  re c or d e d  pri or  t o st art of st u d y d m g  a d mi nistr ati o n a n d 3 0 mi n ut es 
( ± I O mi n ut es)  aft er  c o m pl eti o n of t h e G S- 2 8 7 2  i nf or,i o n 
d. 
S er u m F S H  t est (r e q uire d f or f e mal e  p arti ci p a n ts < 5 4 y e ars  of  a g e  w h o  h a v e  st o p p e d  m e nstr u ati n g f or 2: 1 2 m o n t hs  b ut d o n ot h a v e  d o c u m e nt ati o n of o v ari a n h o r m o nal 
f ail ur e) 
HI V - I  e n o 
C O N FI D E N TI A L 
P a g e 6 3 
2 6 F e b 2 0 2 4 


L e n a c a p a vi r  + G S- 5 4 2 3 +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St a tisti c al A n al ysis  Pl a n  - Fi n al  A n al ys is 
V e rsio n 1. 0 
1 
O n D a y  I,  p arti c ip 0J 1ts will  r e c ei v e st u d y tr e at m e nt c o nsisti n g of or al  a n d  S C  L E N,  f oll o w e d b y  G S- 5 4 2 3,  t h e n G S- 2 8 7 2,  e a c h a d mi nist er e d as s e p ar at e I V i nf usi o ns.  I nf usi o n 
of G S -2 8 7 2  will  b e gi n  at l e a st 1 5  mi n ut es  f oll o wi n g , a n d u p t o 1 h o ur  aft er , t h e c o m pl eti o n of G S -5 4 2 3  I V i nf usi o n. P arti ci p a nts wi ll r e m ai n i n a  m o nit or e d  cli ni c al  s etti n g  f or 
at le ast 3 0  mi n ut es  aft er  c o m pl eti o n of G S- 2 8 7 2  i nf usi o n, a n d  vit al  sig ns  will b e r e c or d e d 3 0  mi n ut e s( ± I O mi n ut es)  aft er  c o m pl eti o n of G S- 2 8 7 2  i nf usi on  F or  t h e  D a y  l 
visit, al l slll d y dr u gs  ar e  t o b e a d mi nist er e d o n  t h e s a m e  d a y. O n D a y  2,  t h e p arti ci p a nt  will  s elf- a d mi nist er 2  t a bl ets of or al  L E N f or l o a di n g ( 2 x  3 0 0  m g)  at h o m e  at 
a 
· o x:i m at el t h e s a m e ti m e or a l L E N f or l o a di n  w a s  a d minist er e d  o n  D a 
1. 
j . 
C O N FI D E N TI A L 
P a g e 6 4 
2 6 F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
V er si o n  1. 0 
A p p e n di x  2.  
Fl o w c h a rt of U S  F D A- d efi n e d  S n a p s h ot  Al g o rit h m  {f o r  L o n g  A cti n g 
S wit c h  T ri al) 
T h e  f oll o win g  fl o w c h ait f or U S  F D A- d efi n e d  s n a p s h ot al g orit h m i s b a s e d o n t h e U S  F D A 
G ui d a n c e o n H u m a n I mm u n o d efi ci e n c y  Vir ns- 1  I nf e cti o n: D e v el o pi n g  A ntir etr o vir al  Dr n g s  f or 
tr eat m e nt  { U .  S.  D e p a 1i m e nt of H e alt h  a n d H u m a. 1 1 S er vi c e s  2 0 1 5 }. 
Y e s 
I s t h er e at l e a st 1  o n -
tr e at m e nt + HI V- 1 R N A 
c oll e ct e d i n t h e S n a p s h ot 
wi n d o w ? 
I s t h e l a st a v ail a bl e o n -tr e at m e nt + 
HI V-I R N A i n t h e S n a p s h ot 
wi n d o w < 5 0 c o pi e s/ m L ? 
Y e s 
H I V- 1 R N A < 
5 0 c o pi e s /m L 
N o 
Is  st u d y dr u g pr e m at ur el y 
di s c o nti n u e d o n or pri or t o t h e 
u p p er li mit of t h e S n a p s h ot 
wi n d o w ? 
Y e s 
Is  di s c o nti n u ati o n of t h e st u d y 
d m g d u e t o L a ci e of Effi c a c y ? 
N o 
Is  di s c o nti n u ati o n of t h e st u d y 
dr u g d u e t o A E/ D e at h ? 
Y e s 
N o 
I s t h e l a st a v ail a bl e o n -
tr e at m e nt + HI V - 1 R N A < 
5 0 c o pi e s/ m L 
Is  t h e l a st a v ail a bl e o n -
tr e at m e nt• HI V-I R N A < 
5 0 c o pi e s/ m L 
H I V- 1 R N A ~ 
5 0 c o pi e s/m L 
Y e s 
N o Vir ol o gi c  D at a : 
Di s c o nti n u e d S t u d y D r u g 
D u e t o Ot h e r R e a s o n s a n d 
L a s t  H I V- 1 R N A < 5 0 
c o pi e s/m L 
N o 
N o Vir ol o gi c  D at a: 
Di s c o nti n u e d S t u d y 
Dr u g D u e t o A E/ D e at h 
a n d L a st HI V- 1 R N A 
< 5 0 c o pi e s/m L 
N o Vir ol o gi c  D at a: 
Mi s s i n g D at a d u ri n g 
Wi n d o w b ut o n St u d y 
D r u g 
* O n - Tre at m ent HI V- 1 R N A d at a  i n cl u d e all  HI V- 1 R N A d at a  c oll e ct e d  u p t o t h e e arli e st d at e of 
( 1 9 6 d a y s  [2 8  w e e k s]  aft e r t h e d o s e  d at e of c o m pl et e  l o n g a cti n g  r e gi m e n, d at e  ofr e st arti n g 
A R T ). 
C O N FI D E N TI A L 
P a g e  6 5 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
V e r si o n 1. 0 
T h e  d o s e  d at e of c o m pl et e  l o n g a cti n g  r e gi m e n r ef ers t o t h e d at e of d o si n g  wit h  c o m pl et e  l o n g 
a cti n g  dr u gs  ( G S- 5 4 2 3 , G S- 2 8 7 2,  a n d  S C  L E N)  (i e, D a y 1). 
P arti ci p a nt s  wit h  st u d y dr u g  pr e m at ur e  di s c o nti n u ati o n  ar e  d efi n e d  a s  p arti ci p a nts  w h o  w er e 
a n s w er e d " N o " t o " Di d s u bj e ct c o m pl et e  st u d y dr u g  d o si n g as s p e cifi e d p er  pr ot o c ol ? "  a n d h a d  a 
di s c o nti n u ati o n  r e a s o n ot h er t h a n "I n v e sti g at or Di s cr eti o n "  ( wit h c o m m e nt of " D u e t o Cli ni c al 
h ol d ")  i n St u d y  Dr u g  C o m pl eti o n  e C R F). 
T h e  d at e of st u dy  dr u g pr e m at ur e  di s c o nti n u ati o n  i s t he  l a st e x p o s ur e  d at e of L A r e gi m e n  f or 
p arti ci p a nts  w h o  pr e m at ur el y  di s c o nti n u e d  st u d y dr u g. 
C O N FI D E N TI A L 
P a g e  6 6 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
A p p e n di x  3.  
A d v e r s e  E v e nt s of C O V I D- 1 9  a n d  S u s p e ct e d  C O V I D- 1 9  I nf e cti o n 
A n  a d v er s e  e v e nt  r e c or d will  b e  fl a g g e d as a d v er s e  e v e nt s  f or C O VI D- 1 9  a n d  S u s p e ct e d 
C O VI D- 1 9  i nf e cti o n if its  M e d D R A P T is i n cl u d e d i n t h e pr e- s p e cifi e d P T list, w hi c h  i n cl u d e s 
all  P T s  fr o m t h e n arr o w  s e ar c h of t h e f oll o wi n g  C O VI D- 1 9  S M Q s  u n d er  M e d D R A  v 2 6.  l 
pr o vi d e d  b y  Gil e a d  G L P S  ( s e ar c h n a m e:  C O VI D- 1 9 ( S M Q)- N arr o w)  a n d  r e vi e w e d b y  Gil e a d 
m e di c al  m o nit ors. 
S M Q S o u r c e 
A Es  f or C O Vl D- 1 9  a n d  S us p e ct e d  C O Vl D- 1 9  i nf e cti o n 
C O V I D- 1 9  ( S M Q) ( N a r r o w S c o p e) 
C O N FI D E N TI A L 
P a g e  6 7 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
A p p e n di x  4.  
A d v e r s e  E v e nt s of C O V I D- 1 9  a n d  S u s p e ct e d  C O V I D- 1 9  I nf e cti o n 
T his  a p p e n di x  d es cri b es  t h e cli ni c al  tri al sit e  c oll e ctio n of C O VI D- 1 9  d at a  p ert ai ni n g  t o 
mi s s e d /virt u al  vi sit s  a n d  t h e d at a  pr o c e s si n g  al g orit h m  t h at will  b e  u s e d t o d et er mi n e  w hi c h  visits 
ar e  mi s si n g  a n d  w hi c h  vi sit s  ar e  virt u al. 
D at a  C oll e cti o n 
A  C O VI D- 1 9  s u p pl e m e nt t o t h e e C R F  C o m pl eti o n  G ui d eli n es  ( C C G) w as  pr o vi d e d  b y  Cli ni c al 
D at a  M a n a g e m e nt  t o i n str u ct cli ni c al tri al  sit e s wit h  d at a  e ntr y  e x p e ct ati o n s  p e rt ai ni n g t o 
s c e n ari o s r el at e d t o t h e C O VI D- 1 9  p a n d e mi c. If a  vi sit  w a s  mi s s e d , sit es  w er e  i n str u ct e d t o e nt er 
" Vi sit mi s s e d  d u e  t o C O VI D- 1 9 "  a n d if a n  i n- p er s o n vi sit  w a s  c o n d u ct e d  virt u all y,  sit es  w er e 
i n str u ct e d t o e nt er " Virt u al vi sit  d u e t o C O VI D- 1 9 ". 
D et er mi n ati o n of Mi s s e d  a n d  Virt u al  Visits 
N at ur al  L a n g u a g e  Pr o c e s si n g  ( N L P) will b e u s e d  t o s e ar c h t h e C R F  c o m m e nt  fi el ds t o i d e ntify 
i nst a n c es of " C O VI D- 1 9 ",  " Virt u al ", or s y n o n y m s ( s e e T a bl e  A p p e n di x - I). T h e  s e ar c h t er m s 
will  b e  m ai nt ai n e d i n a  gl o b al  l o o k u p t a bl e a n d  c a n b e  m o difi e d  t o t u n e t h e N L P m o d el.  A n y 
c o m m e nt s  wit h  C O VI D- 1 9  s e ar c h t er ms, " Mi s s e d vi sit " or " Virt u al  vi sit "  will  b e  a s si g n e d  as 
f oll o ws: 
1. 
If C O VI D- 1 9  t er m s ar e  i d e ntifi e d t hr o u g h N L P  a n d  t h e vi sit  d at e is mi s s i n g, t h e n r es ult  is 
" Mi s s e d Vi sit " 
1 1. If C O VI D - 1 9  a n d  Virt u al  t er m s ar e  i d e ntifi e d t hr o u g h N L P  f or a  visit,  t h e n r e s ult is " Virt u al 
Visit ".  W h e n  t h er e ar e  m ulti pl e  r e c or ds f or t h e s a m e p arti ci p a nt  a n d t h e s a m e visit, if o n e 
r e c or d c o ul d  b e  c at e g ori z e d  as  " Virt u al  Vi sit ", all  r e c or d s a s s o ci at e d  wit h  t his  p arti ci p a nt  a n d 
t hi s vi sit  will b e c at e g ori z e d  as  " Virt u al  Vi sit " 
iii.  Ot h e r wis e r e s ult is mi s si n g 
T a bl e  A p p e n di x- 1.  
E x a m pl e s of S e a r c hi n g  T e r m s  f o r " C O V I D- 1 9 "  a n d  " Vi rt u al "  U s e d t o 
I d e ntif y  Mi s s e d  a n d  Vi rt u al  Vi sit s 
S e ar c h  T er m s  f or  " C O VI D- 1 9 " 
C O VI D 1 9 
C O R O N A 
C O R O N A  V I R U S 
P A N D E MI C 
O U T B R E A K 
C RI SI S 
L O C K D O W N 
Q U A R A N T IN E 
S H E L T E R 
C O N FI D E N TI A L 
P a g e 6 8 
S e ar c h  T er m s  f or  " Virt u al " 
VI R T U A L 
T E L E M E D 
T E L E H E A L T H 
T E L E P H O N E 
R E M O T E 
T E L E M E DI CI N E 
T E L E C O N S U L T A TI O N 
T E L E P H O NI C A L L Y 
P H O N E 
H O M E VI S I T 
Z O O M 
S K Y P E 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
A p p e n di x  5.  
P r o g r a m mi n g  S p e cifi c ati o n s 
V ersi o n  1. 0 
1)  F or  c at e g ori c al  effi c a c y  r e s p o n s e  ( e g,  P arti ci p a nt s  wit h  HI V- 1  R N A <  5 0  c o pi e s /m L or 
P arti ci p a nt s  wit h  HI V- 1  R N A 2: 5 0  c o pi e s /m L as d et er mi n e d b y U S  F D A- d efi n e d 
s n a p s h ot al g orit h m,  M = F, or M = E  A n al ys es):  t h e pr o p orti o n  diff er e n c e  b et w e e n  t w o 
tr e at m e nt gr o u ps  a n d  its  9 5 %  Cls  ar e  c al c ul at e d  b a s e d  o n  t h e a n  u n c o n diti o n al  e x a ct 
m et h o d  u si n g  2  i n v ert e d I- si d e d t e st s i n S A S  v 9. 3 or a b o v e. 
2)  T h e  f oll o wi n g  S A S  c o d e  will  b e  u s e d t o c o m p ut e  c ell  c o u nts  a n d  c o nfi d e n c e  i nt er v al. 
d at a e x a m pl e; 
i n p ut gr p trt 0 1 a $ 
o ut c o m e $ c o u nt 
d at ali n e s; 
1 
Tr e at- A 
r u n ; 
Tr e at- A 
Tr e at- B 
Tr e at- B 
2- F ail 
1 - s u c c 
2- F ail 
1 - S u c c 
pr o c fr e q d at a = e x a m pl e; 
1 8 9 
4 
8 8 
t a bl e trt 0 1 a * o ut c o m e / ri s k diff( C L =( e x a ct) ) al p h a = 0. 0 5; 
w ei g ht c o u nt; e x a ct RI S K DI F F( M E T H O D = S C O R E ) ; 
o ut p ut o ut = ci e x a ct( k e e p = _ R DI F 1 _ X L _ R DI F 1 
X U _ R DI F 1 
_ R S K 1 1 _ _ R S K 2 1 ) ri s k diff; 
r u n; 
d at a fi n al( k e e p = A 1 B 1 
E sti m at e L o w er C L U p p er C L 
o c h ar c 1) ; 
s et ci e x a ct; 
l a b el E sti m at e = " P er c e nt a g e Diff er e n c e " 
L o w er C L  =  " 9 5%  L o w er C o nfi d e n c e Li mit " 
U p p er C L 
=  " 9 5%  U p p er C o nfi d e n c e Li mit " 
A 1 
= " P er c e nt a g e of s u c c e s s i n Tr e at- A " 
B 1 
= " P er c e nt a g e of S u c c e s s i n Tr e at- B "; 
E sti m at e = 1 0 0 * _ R DI F 1 _; 
L o w er C L =  1 0 0 * X L _ R DI F 1; 
U p p er C L 
= 1 0 0 * X U _ R DI F 1; 
A 1 
=  1 0 0 * _ R S K 1 1 _; 
B 1 
=  1 0 0 * _ R S K 2 1 _; 
o c h ar c 1  = ri g ht( c o m pr e s s( p ut( E sti m at e, 8. 1 )) II '   % (' II c o m pr e s s( p ut( L o w er C L, 8. 1)) II ' % 
t o' II c o m pr e s s( p ut( U p p er C L, 8. 1)) II '   %)'); 
r u n; 
3)  T h e  9 5 %  CI  f or p er c e nt a g e  esti m at e of HI V- 1  R N  A < 5 0  c o pi e s /m L  f or e a c h tr e at m e nt is 
c al c ul at e d  b a s e d  o n  t h e Cl o p p er- P e ar s o n  e x a ct m et h o d. 
4)  F or  fi g ur es, if at  a  vi sit  w h er e  n  (s a m pl e si z e) f or  a n y  tr e at m e nt gr o u p :::; 5,  d at a f or t h at 
tr e at m e nt gr o u p  will  n ot  b e  di s pl a y e d at t h e vi sit  i n fi g ur e  ( e x c e pt t h e K a pl a n- M ei er 
fi g ur e), b ut  all  d at a  will  b e  i n cl u d e d i n t h e c orr e s p o n di n g t a bl e s u m m ar y. 
5)  All  s cr e e n e d p arti ci p a nts  r ef er t o all  p arti ci p a nts  w h o  ar e  s cr e e n e d  (i e, wit h  n o n mi s si n g 
s cr e e ni n g d at e)  a n d  h a v e  a  s cr e e ni n g n u m b er.  F o r s u m m ari e s t h e s a m e p arti ci p a nt is 
c o u nt e d  o nl y  o n c e.  D O B  a n d  ot h er  d e m o gr a p hi c  i nf or m ati o n s u c h as s e x, r a c e,  et h ni cit y , 
c o u ntr y,  a n d  i niti al s will b e u s e d  t o i de n tif y u ni q u e  s cr ee n e d  p arti ci p a nts. 
C O N FI D E N TI A L 
P a g e  6 9 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
V ersi o n  1. 0 
6) S cr e e n  f ail ur e p arti ci p a nt s  ar e t h e p arti ci p a nt s  w h o  w er e  s cr e e n e d a n d a n s w er e d " N o "  f or 
a n y  i n cl u si o n crit eri a or " Y e s " f or a n y  e x cl u si o n  crit eri a r e g ar dl e s s of w hi c h  v er si o n of 
pr ot o c ol t h e p arti ci p a nt w a s c o n s e nt t o, or p arti ci p a nt s w h o h a v e  mi s si n g  a n s w er t o a n y 
i n cl u si o n or e x cl u si o n  crit eri a. 
7) B a s eli n e A R V m e di c ati o n  is d efi n e d  a s: 
U si n g t h e A R V r a w d at a s et,  i n cl u d e all  pri or A R V s ( w h er e A R V. C M S C A T = " Pri or 
A R V "), t a k e n o n or u p t o 2  d a y pri or t o fir st d o s e  d at e  ( or r a n d o mi z ati o n d at e if n ot 
tr e at e d), i. e. E n d d at e of A R V::::  fir st d o s e  d at e  - 2. 
8) F or l a st d o s e  d at e  c al c ul ati o n: 
-
F or p arti ci p a nt s w h o r e c ei v e i nj e cti o n or i nf u si o n, t h e l a st d o s e  d at e  i s d efi n e d  as t h e 
l at e st n o n mi s si n g  e n d  d at e of t h e st u d y dr u g  u s e d. 
-
F or p arti ci p a nt s w h o d o n ot r e c ei v e i nj e cti o n or i nf u si o n, t h e l a st d o s e  d at e i s d efi n e d  a s 
t h e l a st d o s e  d at e of or al L E N. 
-
If t h e d at e of l a st d o s e  i s i n c o m pl et e or mi s si n g  ( e g,  d u e t o l o st t o f oll o w- u p), t he  l atest 
n o n mi s si n g  st u d y dr u g  st art d at e s t he  cli ni c  vi sit  d at e s , a n d t h e l a b or at or y vi sit  d at e s 
e x cl u di n g t h e d at e s of a n y f oll o w- u p vi sit s  will b e u s e d t o i m p ut e t h e l a st d o s e  d at e . 
C O N FI D E N TI A L 
P a g e  7 0 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
A p p e n di x  6.  
T a bl e  S h ell s  f o r P a rti ci p a nt  G r o u pi n g 
V ers io n  1. 0 
T a bl e  A p p e n di x- 2.  
P a rti ci p a nt  G r o u pi n g  f o r E n r ol b n e nt,  Eli gi bilit y , Di s p o siti o n,  D e m o g r a p hi c s,  a n d  B a s eli n e 
C h a r a ct e ri sti c s 
P ri m a r y  C o h o rt 
Pil ot  C o h o rt 
P o ol e d  C o h o rt s 
S C L E N + G S- 5 4 2 3  
S C L E N + G S- 5 4 2 3  
T ot al  
S C  L E N +  G S- 5 4 2 3  
S C L E N + 
T o t al 
T o t al 
+  G S- 2 8 7 2  1 0  
+  G S- 2 8 7 2  3 0 
+  G S- 2 8 7 2  1 0  
G S- 5 4 2 3  + 
m gl k g 
m gl k g 
m g/ k g  
G S- 2 8 7 2 3 0 m g/ k g 
T a bl e  A p p e n di x- 3.  
P a rti ci p a nt  G r o u pi n g  f o r Effi c a c y  A n al y s e s 
P ri m a r y  C o h o rt 
Pil ot  C o h o rt 
S C L E N + G S- 5 4 2 3  +  
S C L E N +  G S- 5 4 2 3  + 
T ot al 
S C  L E N  +  G S- 5 4 2 3  +  
S C  L E N  +  G S- 5 4 2 3  +    
T ot al 
G S- 2 8 7 2  1 0  m gl k g  
G S- 2 8 7 2  3 0  m gl k g 
G S- 2 8 7 2  1 0  m g / k g  
G S- 2 8 7 2  3 0  m g/ k g 
T a bl e  A p p e n di x- 4.  
P a rti ci p a nt  G r o u pi n g  f o r S af et y  A n al y s e s 
P ri m a r y  C o h o rt 
Pil ot  C o h o rt 
P o ol e d  C o h o rt s 
S C L E N + G S- 5 4 2 3  
S C L E N + G S- 5 4 2 3  
T ot al  
S C  L E N + G S- 5 4 2 3  
S C L E N + 
T o t al 
T ot al 
+  G S- 2 8 7 2  1 0  
+  G S- 2 8 7 2  3 0 
+  G S- 2 8 7 2  1 0  
G S -5 4 2 3  + 
m gl k g 
m gl k g 
m g/ k g  
G S- 2 8 7 2 3 0 m g/ k g 
T a bl e  A p p e n di x- 5.  
P a rti ci p a nt  G r o u pi n g  f o r P K S u b st u d y  A n al y s e s of L E N 
P o ol e d  C o h ort  T ot al 
C O N FI D E N TI A L 
P a g e  7 1 
2 6  F e b  2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
T a bl e  A p p e n di x- 6.  
P a rti ci p a nt  G r o u pi n g  f o r P K A n al y s e s of G S- 5 4 2 3  a n d L E N 
P ri m a r y  C o h o rt 
Pil ot  C o h o rt 
S C L E N + 
S C L E N + 
T ot al  
S C L E N + 
S C L E N + 
T ot al 
G S- 5 4 2 3  +  
G S- 5 4 2 3  + 
G S- 5 4 2 3  +  
G S- 5 4 2 3  + 
G S- 2 8 7 2  1 0  
G S- 2 8 7 2  3 0 
G S- 2 8 7 2  1 0  
G S- 2 8 7 2  3 0 
m g/ k g 
m g/ k g 
m g/ k g  
m g/ k g 
T a bl e  A p p e n di x- 7.  
P a rti ci p a nt  G r o u pi n g  f o r P K A n al y s e s of G S- 2 8 7 2 
P ri m a r y  C o h o rt 
Pil ot  C o h o rt 
S C L E N + 
S C L E N + G S- 5 4 2 3  +  
G S- 5 4 2 3  + 
S C  L E N  +  G S- 5 4 2 3  + 
S C L E N + G S- 5 4 2 3  + 
G S- 2 8 7 2  1 0  m g/ k g 
G S- 2 8 7 2  3 0 
G S- 2 8 7 2  1 0  m g/ k g  
G S- 2 8 7 2  3 0  m g/ k g 
m g/ k g 
V ers io n  1. 0 
P o ol e d  C o h o rt s 
S C  L E N + 
S C  L E N + 
T ot al 
G S - 5 42 3  +  
G S- 5 4 2 3  + 
G S- 2 8 7 2  1 0  
G S- 2 8 7 2  3 0 
m g/ k g  
m g / k g 
P o ol e d  C o h o rt s 
S C L E N + G S -5 4 2 3  +  
S C  L E N + G S -5 4 2 3 
G S- 2 8 7 2  1 0  m g/ k g  
+  G S -2 8 7 2  3 0  m g/ k g 
T a bl e  A p p e n di x- 8.  
P a rti ci p a nt  G r o u pi n g  f o r I m m u n o g e ni cit y A n al y s e s of A nti- G S- 5 4 2 3 
P ri m a r y  C o h o rt 
Pil ot  C o h o rt 
P o ol e d  C o h o rt s 
S C L E N + 
S C L E N + 
T ot al  
S C L E N + 
S C L E N + 
T ot al  
S C  L E N + 
S C  L E N + 
T o t al 
G S- 5 4 2 3  +  
G S- 5 4 2 3  + 
G S- 5 4 2 3  +  
G S- 5 4 2 3  + 
G S- 5 4 2 3  +  
G S- 5 4 2 3  + 
G S- 2 8 7 2  1 0  
G S- 2 8 7 2  3 0 
G S- 2 8 7 2  1 0  
G S- 2 8 7 2  3 0 
G S- 2 8 7 2  1 0  
G S- 2 8 7 2  3 0 
m g/ k g 
m g/ k g 
m g/ k g  
m g/ k g 
m g/ k g  
m g/ k g 
C O N FI D E N TI A L 
P a g e  7 2 
2 6  F e b 2 0 2 4 


L e n a c a p a vir  +  G S- 5 4 2 3  +  G S- 2 8 7 2 
G S- U S- 5 3 6- 5 8 1 6 
St atisti c al  A n al y si s  Pl a n  - Fi n al  A n al ysis 
T a bl e  A p p e n di x- 9.  
P a rti ci p a nt  G r o u pi n g  f o r I m m u n o g e ni cit y A n al y s e s of A nti- G S- 2 8 7 2 
P ri m a r y  C o h o rt 
Pil ot  C o h o rt 
S C L E N + 
S C L E N + 
T ot al  
S C L E N + 
S C L E N + 
T ot al  
S C  L E N + 
G S- 5 4 2 3  +  
G S- 5 4 2 3  + 
G S- 5 4 2 3  +  
G S- 5 4 2 3  + 
G S - 5 42 3  + 
G S- 2 8 7 2  1 0  
G S- 2 8 7 2  3 0 
G S- 2 8 7 2  1 0  
G S- 2 8 7 2  3 0 
G S- 2 8 7 2  1 0 
m g/ k g 
m g/ k g 
m g/ k g  
m g/ k g 
m g/ k g 
P o ol e d  C o h o rt s 
S C  L E N + 
G S- 5 4 2 3  + 
G S- 2 8 7 2  3 0 
m g / k g 
T a bl e  A p p e n di x- 1 0.  P a rti ci p a nt  G r o u pi n g  f o r I m m u n o g e ni cit y A n al y s e s of B ot h  A nti- G S- 5 4 2 3  a n d  A nti- G S- 2 8 7 2 
P ri m a r y  C o h o rt 
Pil ot  C o h o rt 
P o ol e d  C o h o rt s 
S C L E N + 
S C L E N + 
T ot al 
S C  L E N  +  
S C  L E N  + 
T ot al 
S C L E N +   
S C L E N + 
G S- 5 4 2 3  +  
G S- 5 4 2 3  + 
G S- 5 4 2 3  +  
G S- 5 4 2 3  + 
G S- 5 4 2 3  +  
G S- 5 4 2 3  + 
G S- 2 8 7 2  1 0  
G S- 2 8 7 2  3 0 
G S- 2 8 7 2  1 0  
G S- 2 8 7 2  3 0 
G S- 2 8 7 2  1 0  
G S- 2 8 7 2  3 0 
m g/ k g 
m g/ k g 
m g/ k g  
m g/ k g 
m g/ k g  
m g/ k g 
C O N FI D E N TI A L 
P a g e  7 3 
V ers io n  1. 0 
T o t al 
T o t al 
2 6  F e b  2 0 2 4 


G S- U S- 5 3 6- 5 8 1 6- Fi n al- S A P v 1 . 0 
E L E C T R O NI C  SI G N A T U R E S 
Si g n e d b y 
M e a ni n g of Si g n at u r e 
lP P D 
I 
Bi o st ati sti c s  e Si g n e d 
l PP D 
I 
Pr o j e ct  T ea m 
L e a d er  e S i g ne d 
S er v er  D at e 
( d d- M M M-
y y y y h h : m m : s s) 
[ P P D 
[ P P D 

Prot_000.pdf: 
CLINICAL STUDY PROTOCOL
Study Title:
A Phase 1b Randomized, Blinded, Proof-of-Concept Study to 
Evaluate the Safety and Efficacy of Broadly Neutralizing 
Antibodies (bNAbs) GS-5423 and GS-2872 in Combination with 
Capsid Inhibitor Lenacapavir (GS-6207) in Virologically 
Suppressed Adults with HIV-1 Infection 
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
136260
Not Applicable
NCT04811040
Indication:
HIV-1 Infection
Protocol ID:
GS-US-536-5816
Contact Information:
The medical monitor name and contact information will be 
provided on the Key Study Team Contact List.
Protocol 
Version/Date:
Original:
30 October 2020 
Amendment 1:
06 April 2021
Amendment 2:
30 March 2022
This study will be conducted under United States Food and Drug Administration investigational 
new drug (IND) regulations (21 Code of Federal Regulations Part 312).
CONFIDENTIALITY STATEMENT
The information contained in this document, particularly unpublished data, is the property or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable 
institutional review board or independent ethics committee. The information is only to be used 
by you in connection with authorized clinical studies of the investigational drug described in 
the protocol. You will not disclose any of the information to others without written 
authorization from Gilead Sciences, Inc., except to the extent necessary to obtain informed 
consent from those persons to whom the drug may be administered.
 


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TABLE OF CONTENTS
TABLE OF CONTENTS................................................................................................................................................2
LIST OF IN-TEXT TABLES .........................................................................................................................................5
LIST OF IN-TEXT FIGURES........................................................................................................................................6
PROTOCOL SYNOPSIS................................................................................................................................................7
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS ....................................................................16
1.
INTRODUCTION................................................................................................................................................20
1.1.
Background..............................................................................................................................................20
1.2.
Information About GS-5423, GS-2872, and Lenacapavir.......................................................................21
1.2.1.
General Information ..............................................................................................................21
1.2.2.
Preclinical Pharmacology and Toxicology............................................................................22
1.2.3.
Clinical Experience for GS-5423 and GS-2872 ....................................................................23
1.2.4.
Clinical Experience for LEN.................................................................................................33
1.3.
Rationale for This Study..........................................................................................................................45
1.4.
Rationale for Dose Selection of GS-5423 and GS-2872.........................................................................46
1.5.
Rationale for Dose Selection of LEN......................................................................................................47
1.6.
Risk/Benefit Assessment for the Study ...................................................................................................48
1.7.
Compliance..............................................................................................................................................49
2.
OBJECTIVES.......................................................................................................................................................50
3.
STUDY DESIGN.................................................................................................................................................51
3.1.
Endpoints.................................................................................................................................................51
3.2.
Study Design ...........................................................................................................................................52
3.3.
Study Treatments.....................................................................................................................................52
3.4.
Duration of Treatment .............................................................................................................................53
3.5.
End of Study............................................................................................................................................53
3.6.
Poststudy Care.........................................................................................................................................53
3.7.
Source Data .............................................................................................................................................53
3.8.
Biomarker Testing...................................................................................................................................54
3.8.1.
Biomarker Samples to Address the Study Objectives...........................................................54
3.8.2.
Biomarker Samples for Optional Future Research................................................................54
3.8.3.
Biomarker Samples for Optional Genomic Research ...........................................................55
3.9.
Optional Pharmacokinetic Substudy .......................................................................................................55
4.
PARTICIPANT POPULATION..........................................................................................................................56
4.1.
Number of Participants and Participant Selection...................................................................................56
4.1.1.
Participant Replacement........................................................................................................56
4.2.
Inclusion Criteria.....................................................................................................................................56
4.3.
Exclusion Criteria....................................................................................................................................58
5.
INVESTIGATIONAL MEDICINAL PRODUCTS.............................................................................................59
5.1.
Randomization, Blinding and Treatment Codes Access .........................................................................59
5.1.1.
Randomization.......................................................................................................................59
5.1.2.
Blinding .................................................................................................................................59
5.1.3.
Planned Interim Unblinding ..................................................................................................59
5.1.4.
Procedures for Breaking Treatment Codes............................................................................60
5.2.
Description and Handling of Lenacapavir, GS-5423, and GS-2872.......................................................60
5.2.1.
Formulation ...........................................................................................................................60
5.2.2.
Packaging and Labeling ........................................................................................................61




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7.7.2.
Management of Other Toxicities...........................................................................................87
7.8.
Safety Assessment Committee ................................................................................................................88
8.
STATISTICAL CONSIDERATIONS.................................................................................................................89
8.1.
Analysis Objectives and Endpoints.........................................................................................................89
8.1.1.
Analysis Objectives...............................................................................................................89
8.1.2.
Primary Endpoint...................................................................................................................89
8.1.3.
Secondary Endpoints.............................................................................................................89
8.1.4.
Other Endpoints of Interest ...................................................................................................90
8.2.
Planned Analyses.....................................................................................................................................90
8.2.1.
Interim Analysis ....................................................................................................................90
8.2.2.
Primary Analysis ...................................................................................................................91
8.2.3.
Final Analysis........................................................................................................................91
8.3.
Analysis Conventions..............................................................................................................................91
8.3.1.
Analysis Sets .........................................................................................................................91
8.3.2.
Data Handling Conventions ..................................................................................................92
8.4.
Demographic and Baseline Characteristics Analysis..............................................................................92
8.5.
Efficacy Analysis.....................................................................................................................................92
8.6.
Safety Analysis........................................................................................................................................93
8.6.1.
Extent of Exposure ................................................................................................................93
8.6.2.
Adverse Events......................................................................................................................93
8.6.3.
Laboratory Evaluations .........................................................................................................93
8.6.4.
Other Safety Evaluations.......................................................................................................94
8.7.
Adjustments for Multiplicity ...................................................................................................................94
8.8.
Pharmacokinetic Analysis .......................................................................................................................94
8.9.
Immunogenicity Analysis........................................................................................................................94
8.10.
Sample Size .............................................................................................................................................95
9.
RESPONSIBILITIES...........................................................................................................................................96
9.1.
Investigator Responsibilities ...................................................................................................................96
9.1.1.
Good Clinical Practice...........................................................................................................96
9.1.2.
Financial Disclosure ..............................................................................................................96
9.1.3.
Institutional Review Board/Independent Ethics Committee Review and 
Approval................................................................................................................................96
9.1.4.
Informed Consent ..................................................................................................................96
9.1.5.
Confidentiality.......................................................................................................................97
9.1.6.
Study Files and Retention of Records ...................................................................................97
9.1.7.
Case Report Forms ................................................................................................................99
9.1.8.
Investigator Inspections.........................................................................................................99
9.1.9.
Protocol Compliance .............................................................................................................99
9.2.
Sponsor Responsibilities .........................................................................................................................99
9.2.1.
Protocol Modifications ..........................................................................................................99
9.2.2.
Study Report and Publications ............................................................................................100
9.3.
Joint Investigator/Sponsor Responsibilities ..........................................................................................100
9.3.1.
Payment Reporting ..............................................................................................................100
9.3.2.
Access to Information for Monitoring.................................................................................100
9.3.3.
Access to Information for Auditing or Inspections .............................................................100
9.3.4.
Study Discontinuation .........................................................................................................100
10.
REFERENCES...................................................................................................................................................101
11.
APPENDICES....................................................................................................................................................102
Appendix 1.
Investigator Signature Page...................................................................................................103


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Appendix 2.
Study Procedures Table.........................................................................................................104
Appendix 3.
Management of Clinical and Laboratory Adverse Events.....................................................108
Appendix 4.
Toxicity Grading Scale for Severity of Adverse Events and Laboratory 
Abnormalities ........................................................................................................................109
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements..................................................................................................110
Appendix 6.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines)............................113
Appendix 7.
Pandemic Risk Assessment and Mitigation Plan ..................................................................115
LIST OF IN-TEXT TABLES
Table 1-1.
Study YCO-0946: Summary of Reported Adverse Events .....................................................24
Table 1-2.
Study YCO-0946: Postinfusion Laboratory Abnormalities of Moderate or Severe 
Grade .......................................................................................................................................26
Table 1-3.
Study YCO-0971: Summary of Reported Adverse Events .....................................................29
Table 1-4.
Study YCO-0971: Postinfusion Laboratory Abnormalities of Moderate or Severe 
Grade (Maximum Severity Per Volunteer)..............................................................................32
Table 1-5.
Study GS-US-200-4538: Solution Formulations and Doses ...................................................34
Table 1-6.
Study GS-US-200-4538: Preliminary Pharmacokinetic Parameters for Subcutaneous 
LEN Injection, 309 mg/mL .....................................................................................................36
Table 1-7.
Study GS-US-200-4538: Summary of Adverse Events in > 2 Participants by 
Preferred Term.........................................................................................................................37
Table 1-8.
Study GS-US-200-4071: LEN Formulations and Doses Evaluated........................................40
Table 1-9.
Study GS-US-200-4071: Preliminary LEN Plasma Pharmacokinetic Parameters 
Following Single-Dose Administration of Oral LEN Solution in Capsule 
(50 mg/mL; n = 8 Per Cohort).................................................................................................42
Table 1-10.
Study GS-US-200-4071: Preliminary LEN Plasma Pharmacokinetic Parameters 
Following Multiple-Dose Oral Administration of 30 mg and 100 mg Solution in 
Capsule (50 mg/mL; n = 8 Per Cohort) ...................................................................................42
Table 1-11.
Study GS-US-200-4071: Preliminary LEN Plasma Pharmacokinetic Parameters 
Following Single-Dose Oral Administration of LEN Tablets, Fasted or Following a 
High- or Low-Fat Meal (n = 8 Per Cohort) .............................................................................44
Table 5-1.
Treatment Table.......................................................................................................................63
Table 5-2.
List of Representative Medications that are Prohibited or To Be Used with Caution 
due to the Potential for Drug-Drug Interaction with LEN.......................................................64
Table 7-1.
The Common Terminology Criteria for Adverse Events (CTCAE) Version 5 
Grading Scale ..........................................................................................................................86
Table 8-1.
Estimated Virologic Failure Rate and its 95% CIs (from the Clopper-Pearson Exact 
CI) Based on Number of Virologic Failure Event in Each Group or in Total.........................95


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LIST OF IN-TEXT FIGURES
Figure 1-1.
Study YCO-0946: Preliminary Concentration-Time Profiles of Serum GS-5423 
(3BNC117-LS) ........................................................................................................................27
Figure 1-2.
Study YCO-0946: Anti-GS-5423 (Anti-3BNC117-LS) Antibody Response Titers...............28
Figure 1-3.
Study YCO-0971: Preliminary Concentration-Time Profiles of Serum GS-2872..................33
Figure 1-4.
Study GS-US-200-4538: Preliminary Mean (SD) LEN Plasma Concentration-Time 
Profiles Following Single-Dose Administration of Subcutaneous LEN Injection, 
309 mg/mL (n = 8 Per Cohort) ................................................................................................35
Figure 1-5.
Study GS-US-200-4072: Mean and 95% CIs Change From Baseline in HIV-1 RNA 
(log10 copies/mL) (Full Analysis Set)......................................................................................39
Figure 1-6.
Study GS-US-200-4071: Preliminary Mean (SD) LEN Plasma Concentration-Time 
Profiles Following Single-Dose Administration of Oral LEN Solution in Capsule 
(50 mg/mL; n = 8 Per Cohort).................................................................................................41
Figure 1-7.
Study GS-US-200-4071: Preliminary Mean (SD) LEN Plasma Concentration-Time 
Profiles Following Single-Dose Oral Administration of LEN Tablets, Fasted (n = 8 
Per Cohort) ..............................................................................................................................43
Figure 1-8.
Study GS-US-200-4071: Preliminary Mean (SD) LEN Plasma Concentration-Time 
Profiles Following Single-Dose Oral Administration of LEN 300-mg Tablets, 
Fasted or with a High-Fat or Low-Fat Meal (n = 8 Per Cohort) .............................................44
Figure 3-1.
Study Schema ..........................................................................................................................52
Figure 6-1.
Virologic Rebound Schema.....................................................................................................76


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 1b Randomized, Blinded, Proof-of-Concept Study to 
Evaluate the Safety and Efficacy of Broadly Neutralizing 
Antibodies (bNAbs) GS-5423 and GS-2872 in Combination with 
Capsid Inhibitor Lenacapavir (GS-6207) in Virologically 
Suppressed Adults with HIV-1 Infection 
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
136260
Not Applicable
NCT04811040
Study Centers Planned:
Approximately 15-25 centers in the United States (US)
Objectives:
The primary objective of this study is as follows:

To evaluate the safety and tolerability of a combination of the 
broadly neutralizing antibodies (bNAbs) GS-5423 and 
GS-2872 (formerly 3BNC117-LS and 10-1074-LS, 
respectively) in combination with the HIV capsid inhibitor 
lenacapavir (LEN; GS-6207) 
The secondary objectives of this study are as follows: 

To evaluate the efficacy of the study regimens determined by 
the proportion of participants maintaining virologic 
suppression (HIV-1 RNA < 50 copies/mL) at Weeks 26

To evaluate the pharmacokinetics (PK) of GS-5423, 
GS-2872, and LEN

To evaluate immunogenicity of GS-5423 and GS-2872

To evaluate the emergence of resistance to the components of 
the study regimens
The exploratory objectives are as follows:

To evaluate changes in HIV reservoir

To evaluate changes in immune biomarkers


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Study Design:
A randomized, blinded, proof-of-concept (POC) study to evaluate 
the safety and efficacy of a single dose each of a long-acting 
regimen of LEN, GS-5423, and GS-2872 in adults with HIV-1 
infection who are virologically suppressed (HIV-1 RNA 
< 50 copies/mL) on oral antiretroviral treatment (ART).
Participants who provide written consent and meet all eligibility 
criteria will be randomized in a 1:1 ratio to one of 2 treatment 
groups based on the dose of GS-2872.
Participants will discontinue their background oral antiretroviral 
(ARV) regimen one day prior to receiving study drugs on Day 1.
At Week 26, all participants will resume their background oral 
ARV baseline regimen (or compatible regimen selected by the 
investigator) and return to the clinic for visits at Weeks 38 
and 52. 
Unblinded treatment assignments will be provided to the 
investigators after all participants are back on their baseline 
ARVs (or compatible regimen selected by the investigator) at 
Week 26 or have discontinued the study, and the Week 26 
analysis has been completed.
Number of 
Participants Planned:
Approximately 20 in the Primary Cohort, up to 20 in the optional 
Pilot Cohort
Target Population:
Adults with HIV-1, no history of virologic failure (VF) or 
antiretroviral drug resistance, a CD4 nadir ≥ 350 cells/µL, on 
first-line ART for at least 2 years with demonstrated virologic 
suppression (HIV-1 RNA < 50 copies/mL) for at least 18 months 
prior to screening who are willing to modify their ARV regimen 
for an investigational strategy.
Duration of 
Treatment:
26 weeks


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Diagnosis and Main 
Eligibility Criteria:
HIV-1 infected participants who meet the following criteria:

Age between 18 and 65 years at screening

On first-line ART for ≥ 2 years prior to screening. A change 
in ART regimen ≥ 28 days prior to screening for reasons 
other than VF (eg, tolerability, simplification, drug-drug 
interaction profile) is allowed

No documented historical resistance to the current ART 
regimen

Plasma HIV-1 RNA < 50 copies/mL at screening

Documented plasma HIV-1 RNA < 50 copies/mL for 
≥ 18 months preceding the screening visit (or undetectable 
HIV-1 RNA level according to the local assay being used if 
the limit of detection is ≥ 50 copies/mL). Unconfirmed 
virologic elevations of ≥ 50 copies/mL (transient detectable 
viremia, or “blip”) prior to screening are acceptable.

Proviral phenotypic sensitivity to both GS-5423 and GS-2872 
at screening by the PhenoSense monoclonal antibody (mAb) 
Assay (Monogram Biosciences) for inclusion in the Primary 
Cohort; sensitivity at screening by the PhenoSense mAb 
Assay (Monogram Biosciences) to 1 mAb, either GS-5423 or 
GS-2872, within 18 months prior to enrollment for inclusion 
in the optional Pilot Cohort
In both cohorts, GS-5423 sensitivity is defined as 90% 
inhibitory concentration (IC90) ≤ 2 µg/mL; GS-2872 
sensitivity is defined as IC90 ≤ 2 µg/mL 

CD4+ count nadir ≥ 350 cells/µL

Screening CD4+ count ≥ 500 cells/µL

Availability of a fully active alternative ART regimen, in the 
opinion of the investigator, in the event of discontinuation of 
the current ART regimen with development of resistance

No comorbid condition requiring ongoing 
immunosuppression

No evidence of current hepatitis B virus (HBV) infection 

No evidence of current hepatitis C virus (HCV) infection 
(prior infection cleared spontaneously or with treatment is 
acceptable)

No history of opportunistic infection or illness indicative of 
Stage 3 HIV disease


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Study Procedures/
Frequency:
Due to the extended laboratory processing time for bNAb 
sensitivity testing, screening procedures for the Primary Cohort 
will be conducted in two parts. For the optional Pilot Cohort, 
participants will be selected from the previously screened/failed 
participants in the Primary Cohort and will directly proceed to 
Screening Part 2 (no need to repeat Screening Part 1).
Screening Part 1: Assessment of medical history, adverse events 
(AEs), and concomitant medications will be performed. A blood 
sample to assess for bNAb sensitivity will be collected and 
analyzed to support eligibility and entry into Screening Part 2. 
Screening Part 2: Participants with proviral phenotypic 
sensitivity to either or both GS-5423 and GS-2872 will have the 
following assessments performed: changes in medical history, 
complete physical examination, vital signs, height, weight, 
electrocardiogram (ECG), and sample collection for laboratory 
analyses (hematology, chemistry, coagulation, thyroid function, 
urinalysis, serum pregnancy test [for women of childbearing 
potential], serum follicle-stimulating hormone [FSH], HIV-1 
RNA, CD4+ cell count, CD8+ cell count, CD4/CD8 ratio, HBV 
and HCV serologies, and estimated glomerular filtration rate 
[eGFR]). Laboratory samples for proviral DNA genotype and 
bulk viral outgrowth phenotype will be collected at screening for 
subsequent testing.
Participants in the Primary Cohort who meet all eligibility criteria 
will be randomized in a 1:1 ratio to Treatment Group 1 or 
Treatment Group 2. Participants in the Pilot Cohort who meet all 
eligibility criteria will be randomized in a 1:1 ratio to Treatment 
Group 1 or Treatment Group 2. Participants in both cohorts will 
return to the clinic within 28 days after the Screening Part 2 visit 
for the Day 1 visit.
There is no stratification for randomization for the Primary 
Cohort.
For the optional Pilot Cohort, randomization will be stratified by 
the antibody (GS-5423 or GS-2872) to which the participant is 
sensitive.
Study drug(s) will be administered in-clinic on Day 1 and 
self-administered on Day 2 (note: administered in-clinic on Day 2 
if participating in the Optional PK Substudy).
Participants will return for study visits on Weeks 4, 8, 12, 16, 20, 
24, 26, 38, and 52 for study assessments.


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A Gilead Data Review Committee (GDRC) analysis of Primary 
Cohort data will be conducted after the approximately 
20 participants planned to be enrolled in the Primary Cohort 
reach Week 12. After GDRC review, the optional Pilot Cohort of 
up to 20 participants may be enrolled and will have the same 
treatments and assessments as the Primary Cohort.
Clinical and laboratory assessments including hematology, 
chemistry, urinalysis, pregnancy test (for women of childbearing 
potential), HIV-1 RNA, CD4+ cell count, CD8+ cell count, 
CD4/CD8 ratio, vital signs, weight, focused physical 
examination, eGFR, and assessment of AEs and concomitant 
medications will be performed at Day 1, Weeks 4, 12, 26, 38, 52, 
early termination (ET), and post-ET follow-up visits (note: 
complete physical examination will be performed at Day 1 and 
ET). 
Thyroid will be assessed at screening, Day 1, Weeks 4, 12, 26, 
38, and 52.
ECG will be performed at screening, Day 1, Weeks 26, and 52.
HIV-1 RNA will also be assessed at Weeks 4, 8, 12, 16, 20, 24, 
26, 38, and 52.
HIV reservoir assays will be assessed at Day 1 (predose) and 
Week 52. 
Immune biomarker will be collected at Day 1 (predose), 
Weeks 4, 26, 38, and 52. 
Plasma storage sample for virology testing at all visits except 
screening and Days 2 and 8.
Serum PK samples for GS-5423 and GS-2872 will be collected at 
the following time points for all participants: 

Day 1: 0 hour (predose, ≤ 30 minutes prior to dosing of oral 
LEN for loading), within 5 minutes after the end of the first 
antibody infusion (GS-5423) and within 5 minutes after the 
end of the second antibody infusion (GS-2872)

Single anytime sample at Weeks 4, 8, 12, 16, 20, 24, 26, 38, 
and 52
Plasma PK samples for LEN will be collected at the following 
times for all participants: 


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
Day 1: 0 hour (predose, ≤ 30 minutes prior to dosing of oral 
LEN for loading), within 5 minutes after the end of the first 
antibody infusion (GS-5423) and within 5 minutes after the 
end of the second antibody infusion (GS-2872)

Single anytime sample at Weeks 4, 8, 12, 16, 20, 24, 26, 38, 
and 52
Optional PK Substudy: If participants provide specific separate 
consent, plasma PK samples for LEN will be collected at the 
following times in a subset of participants (approximately 
n = 14 evaluable; approximately n = 7 from each treatment 
group): 

Day 1: 0 hour (predose, ≤ 30 minutes prior to dosing of oral 
LEN for loading), within 5 minutes after the end of the first 
antibody infusion (GS-5423) and within 5 minutes after the 
end of the second antibody infusion (GS-2872), 4 hours post 
oral LEN dose for loading, and 8 hours post oral LEN dose 
for loading

Day 2: 0 hour (predose, ≤ 30 minutes prior to dosing of oral 
LEN for loading) and single anytime sample between 1 and 
6 hours post oral LEN dose for loading

Day 8: single anytime sample
Serum samples for immunogenicity assessment (antidrug 
antibody [ADA]) will be collected at Day 1 (predose) and 
Weeks 4, 12, 26, 38, and 52.
During the study, combination ART consisting of the baseline 
regimen (or a compatible regimen selected by the investigator) 
will be restarted in any participant who meets criteria for VF 
(HIV-1 RNA ≥ 200 copies/mL that is confirmed upon repeat 
testing or has HIV-1 RNA ≥ 200 copies/mL at study drug 
discontinuation).

Pharmacodynamic biomarkers: Peripheral blood mononuclear 
cell (PBMC), whole blood, serum, and plasma samples will 
be collected at Day 1 (predose) and Weeks 4, 26, 38, and 52 
for exploratory analysis, which may include HIV-1 specific 
T-cell response, immune cell phenotyping, gene expression, 
antibody profiling, and soluble proteins (eg, cytokines, 
chemokines, inflammatory markers, etc.). Fc-gamma receptor 
(FcgR) single nucleotide polymorphisms (SNP) will be 
evaluated using samples collected at the Day 1 visit 
(exploratory analysis).


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
Optional pharmacogenomic testing: If participants provide 
consent, a sample will be collected at the Day 1 visit but may 
be collected at any time during the study or at a separate 
study visit, if necessary.
Product, Dose, and 
Mode of 
Administration:
Study 
Day
Treatment Group 1
Treatment Group 2
Day 1
LEN 600 mg (two 300 mg 
tablets, PO)
LEN 927 mg (two 1.5 mL 
injections, SC)
GS-5423 30 mg/kg (IV infusion)
GS-2872 10 mg/kg (IV infusion)
LEN 600 mg (two 300 mg 
tablets, PO)
LEN 927 mg (two 1.5 mL 
injections, SC)
GS-5423 30 mg/kg (IV infusion)
GS-2872 30 mg/kg (IV infusion)
Day 2
LEN 600 mg (two 300 mg 
tablets, PO)
LEN 600 mg (two 300 mg 
tablets, PO)
Reference Therapy, 
Dose, and Mode of 
Administration:
None
Criteria for Evaluation:
Safety:
Incidence of treatment-emergent AEs and treatment-emergent 
clinical laboratory abnormalities
Immunogenicity:
Proportion of participants positive with anti-GS-5423 or 
anti-GS-2872 antibodies
Efficacy: 

Proportion of participants with HIV-1 RNA < 50 copies/mL 
at Week 26 as defined by the Food and Drug Administration 
(FDA)-defined snapshot algorithm

Proportion of participants with HIV-1 RNA ≥ 50 copies/mL 
at Week 26 as defined by the FDA-defined snapshot 
algorithm

Change from baseline in CD4+ cell counts at Week 26 

Treatment-emergent resistance to study drugs
Pharmacokinetics:
PK parameters for GS-5423, GS-2872, and LEN 
(and metabolites, if applicable), as appropriate: AUC0-t, AUClast, 
t1/2, Cmax, Tmax, Tlast, Ct
Statistical Methods:
Study endpoints will be assessed in the Primary Cohort excluding 
the optional Pilot Cohort. Exploratory analysis may be conducted 
for the optional Pilot Cohort as applicable. 


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Safety:
Treatment-emergent AEs, serious adverse events (SAEs), and 
AEs leading to permanent study drug discontinuation will be 
summarized by treatment group, system organ class (SOC), and 
preferred term using the current version of the Medical 
Dictionary for Regulatory Activities (MedDRA).
Laboratory results and change from baseline values for selected 
laboratory tests will be summarized by treatment group and visit. 
The incidence of treatment-emergent laboratory abnormalities 
will be summarized by treatment group.
Vital signs and ECG data will be summarized by treatment 
group.
Immunogenicity:
The proportion of participants with detectable anti–GS-5423 or 
anti–GS-2872 antibodies at each specified time point will be 
summarized by treatment group.
Efficacy:
The proportion of participants with HIV-1 RNA < 50 copies/mL 
at Week 26 as defined by the FDA-defined snapshot algorithm 
will be summarized by treatment group and overall using the Full 
Analysis Set. The 95% CIs will be constructed using the exact 
method. These efficacy endpoints will be compared between 
treatment groups by Fisher exact test. 
The proportion of participants with HIV-1 RNA ≥ 50 copies/mL 
at Week 26 as defined by the FDA-defined snapshot algorithm 
will also be summarized by treatment group and overall in a 
similar manner. 
The change from baseline in CD4+ cell count at Week 26 will be 
summarized using descriptive statistics by treatment group.
Treatment-emergent resistance to study drugs will be 
summarized by treatment group.
Pharmacokinetics:
Serum or plasma concentrations and PK parameters for GS-5423, 
GS-2872, and LEN (and metabolites, if applicable) will be listed 
and summarized for each analyte using descriptive statistics by 
treatment group or overall, as appropriate.
Sample Size:


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Although the sample size in this study is determined based on 
practical considerations and past experience with similar types of 
studies, assuming the 2 treatment groups have a similar virologic 
suppression rate, a total of 20 participants in the Primary Cohort 
will provide at least 35% power to show the lower bound of 
95% CI for Week 26 virologic response rate (HIV-1 RNA 
< 50 copies/mL as defined by the FDA-defined snapshot 
algorithm) is greater than 83%. It was assumed that the virologic 
response rate at Week 26 was 95% (based on Gilead studies 
GS-US-380-1844 and GS-US-380-4030), 12% was a clinically 
tolerable margin for Phase 1b studies, and a one-sided exact test 
with a significance level 0.025 was used. The sample size and 
power calculations were made using the statistical software 
package PASS (Version 14).
A total of approximately 20 participants in the Primary Cohort 
will provide reasonable assessment of safety and PK. 
A total of up to 20 participants in the optional Pilot Cohort is 
based on practical considerations.
This study will be conducted in accordance with the guidelines of Good Clinical Practice 
including archiving of essential documents.


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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
ADA
antidrug antibodies
AE
adverse event
AIDS
acquired immunodeficiency syndrome
ALT
alanine aminotransferase
ART
antiretroviral therapy
ARV
antiretroviral
AST
aspartate aminotransferase
ATI
analytical treatment interruption
AUCinf
area under the concentration versus time curve extrapolated to infinite time, calculated 
as AUClast + (Clast/z)
AUClast
area under the concentration versus time curve from time zero to the last quantifiable 
concentration
AUC0-t
partial area under the concentration versus time curve from time “0” to time “t”
%AUCexp
percentage of AUC extrapolated between AUClast and AUCinf
BCRP
breast cancer resistance protein
BLQ
below the limit of quantitation
bNAbs
broadly neutralizing antibodies
BUN
blood urea nitrogen
CBC
complete blood count
CD4
cluster determinant 4
CD8
cluster determinant 8
CI
confidence interval
CK
creatine kinase
Clast
last observed quantifiable concentration of the drug
CLcr
creatinine clearance
Cmax
maximum observed concentration of drug
CPK
creatine phosphokinase
CRF
case report form
CRO
contract research organization
CSR
clinical study report
Ct
concentration at a particular time (t)
CTCAE
Common Terminology Criteria for Adverse Events
Ctrough
concentration at the end of the dosing interval
CYP
cytochrome P450 enzyme
DAIDS
Division of AIDS
DNA
deoxyribonucleic acid
ECG
electrocardiogram
EDC
electronic data capture
eCRF
electronic case report form


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eGFR
estimated glomerular filtration rate
ET
early termination
eTMF
electronic trial master file
EU
European Union
EudraCT
European Clinical Trials Database
FcRn
neonatal Fc receptor
FcgR
Fc-gamma receptor
FDA
Food and Drug Administration
FIH
first in human
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GDRC
Gilead Data Review Committee
GGT
gamma-glutamyltransferase 
GLP
Good Laboratory Practice
GLPS
Global Patient Safety (formerly Pharmacovigilance and Epidemiology)
gp
glycoprotein
HBV
hepatitis B virus
HCV
hepatitis C virus
HDPE
high density polyethylene
HIV
human immunodeficiency virus
HIV-1
human immunodeficiency virus type 1
HLGT
high-level group term
HLT
high-level term
IB
investigator’s brochure
IC90
90% inhibitory concentration
ICF
informed consent form
ICH
International Council for Harmonisation (of Technical Requirements for 
Pharmaceuticals for Human Use)
IEC
independent ethics committee
Ig
immunoglobulin
IQ
inhibitory quotient
IRB
institutional review board
IRT
interactive response technology
ISR
injections site reaction
IV
intravenous
LDH
lactate dehydrogenase
LEN
lenacapavir, GS-6207
LLOQ
lower limit of quantitation
LLT
lower-level term
mAbs
monoclonal antibodies


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MedDRA
Medical Dictionary for Regulatory Activities
NaS
LEN injection
NaSP
LEN injection with poloxamer
NOAEL
no observed adverse effect level
paEC95
protein-adjusted 95% effective concentration
PBMC
peripheral blood mononuclear cell
PD
pharmacodynamic(s)
P-gp
P-glycoprotein
PK
pharmacokinetic(s)
PLWH
people living with HIV
POC
proof of concept
PO
by mouth
Q1
first quartile
Q3
third quartile
RNA
ribonucleic acid
SADR
serious adverse drug reaction
SAE
serious adverse event 
SC
subcutaneous
SD
standard deviation
SDR
source data review
SDV
source data verification
SNP
single nucleotide polymorphisms
SOC
system organ class
SOP
standard operating procedure
SSR
special situation report
SUSAR
suspected unexpected serious adverse reaction
TE
treatment experienced
Tlast
time (observed time point) of Clast
Tmax
time (observed time point) of Cmax
TN
treatment naive
TSH
thyroid-stimulating hormone
t1/2
estimate of the terminal elimination half-life of the drug, calculated by dividing the 
natural log of 2 by the terminal elimination rate constant (λz)
T3
triiodothyronine
T4
thyroxine
UGT1A1
uridine diphosphate glucuronosyltransferase 1A1
ULN
upper limit of normal
ULQ
upper limit of quantitation
URI
upper respiratory infection
US
United States


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VF
virologic failure
VR
virologic rebound


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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus type 1 (HIV-1) infection causes a serious life-threatening 
disease and remains one of the leading causes of morbidity and mortality worldwide. In the 
United States (US), there are approximately 1 million people living with HIV (PLWH) infection, 
and globally there are over 38 million {UNAIDS 2021}. Advances in antiretroviral (ARV) 
therapy (ART) for HIV have led to significant improvements in morbidity and mortality by 
suppressing viral replication, preserving immunologic function, and averting disease progression 
to AIDS. However, current therapeutic strategies have been unable to eliminate the virus and 
cure HIV-1 infection.
While current combination ART for the treatment of HIV-1 infection is efficacious and well 
tolerated, these agents need to be taken every day and require near-perfect adherence to 
minimize the emergence of drug-resistant variants. As a result, “treatment fatigue” can occur, 
defined as “decreased desire and motivation to maintain vigilance in adhering to a treatment 
regimen” among patients prescribed chronic or lifelong treatment {Claborn 2015}, which can 
lead to nonadherence and treatment failure. As such, there remains a significant medical need for 
ARVs that can be administered less frequently (ie, long-acting drug products), thereby providing 
an alternative treatment option for HIV-1 infected individuals. 
Monoclonal antibodies (mAbs) with neutralizing activity against HIV-1 envelope glycoproteins 
of increasing potency and breadth have been identified {Burton 2015} and the parenteral 
administration of broadly neutralizing mAbs produce significant reductions in plasma viremia in 
untreated patients and have maintained virologic suppression in virologically suppressed patients 
who have received broadly neutralizing antibodies (bNAbs) prior to undergoing analytic 
treatment interruption {Caskey 2015, Caskey 2017, Mendoza 2018}. Antibodies can be 
long-acting and have the potential to mitigate the challenges or lifelong adherence to daily 
therapy. Antibodies also engage the immune system which may contribute to a beneficial 
HIV-specific immune response {Niessl 2020}, including the clearance of latently infected cells, 
that is not achieved by ARV drugs. As biologics, bNAbs may spare patients from adverse effects 
associated with chronic ARV therapy. HIV-1, however, is a diverse virus whose variants have 
varying levels of sensitivity for any bNAb. Therefore, bNAbs identified to date have incomplete 
breadth when measured for their ability to neutralize a diversity of HIV-1 isolates {Nishimura 
2017}. 3BNC-117 and 10-1074 are two of the most potent bNAbs that have been identified and 
clinically tested {Mouquet 2012, Scheid 2011}. However, viral resistance to bNAbs can occur 
after antibody titer wanes via mutation {Bar-On 2018}. Combination therapy of bNAbs with an 
ARV drug may overcome this limitation and enable a safe long-acting treatment option for 
PLWH.


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1.2.
Information About GS-5423, GS-2872, and Lenacapavir
GS-5423 
GS-5423 (formerly 3BNC117-LS) is a recombinant, fully human anti–HIV-1 antibody of the 
immunoglobulin (Ig) G1κ isotype that targets the CD4 binding site of HIV-1 glycoprotein 
(gp) 120 and shows neutralization activity against > 80% of viral strains. GS-5423 is the same 
molecule as 3BNC117 with the exception of 2 amino acid substitutions of Met to Leu at Fc 
position 428 (M428L), and Asp to Ser at Fc position 434 (N434S), which enhance the antibody’s 
affinity to the neonatal Fc receptor (FcRn) and prolong its half-life in vivo. 
GS-2872
GS-2872 (formerly 10-1074-LS) is a recombinant, fully human monoclonal antibody of the 
IgG1λ isotype that specifically binds to the V3 loop within the HIV external membrane 
glycoprotein, gp120. GS-2872 is the same molecule as the original antibody 10-1074 with the 
exception of the 2 amino acid substitutions in the Fc domain (M248L and N434S), which were 
made to extend the half-life in vivo. 
Lenacapavir
Lenacapavir (LEN; GS-6207) is a novel, first-in-class, selective inhibitor of HIV-1 capsid 
function, which has potent antiviral activity, low human clearance, and physicochemical 
properties well suited for extended-release parenteral or oral formulations.
The investigational regimen combines 2 potent bNAbs, GS-2872 and GS-5423, targeting 
nonoverlapping epitopes on HIV-1 envelope with LEN, a potent first-in-class inhibitor of HIV-1 
capsid function. Each drug has established antiviral activity and safety. Their complementary 
mechanisms of action and compatible long half-lives allow the study regimen to be dosed only 
once every 6 months while maintaining therapeutic drug levels. 
1.2.1.
General Information
GS-5423
The HIV bNAb GS-5423 (3BNC117-LS) and the original antibody from which it is derived, 
3BNC117, have been characterized in nonclinical and clinical studies, including studies in 
combination with the bNAb GS-2872 (in the case of GS-5423) or 10-1074 (in the case of 
3BNC117). For further information, refer to the current investigator’s brochure (IB) for GS-5423 
(formerly 3BNC117-LS).
GS-2872
The HIV bNAb GS-2872 (10-1074-LS) and the original antibody from which it is derived, 
10-1074, have been characterized in nonclinical and clinical studies. For further information, 
refer to the current IB for GS-2872 (formerly 10-1074-LS).


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Lenacapavir
The HIV capsid inhibitor LEN has been previously characterized in nonclinical and clinical 
studies. For further information, refer to the current IB for LEN.
1.2.2.
Preclinical Pharmacology and Toxicology
GS-5423
A Good Laboratory Practice (GLP) 25-day twice weekly intravenous (IV) and subcutaneous 
(SC) toxicity study with a 47-day recovery period in male and female Sprague Dawley rats was 
conducted with 3BNC117, the precursor antibody for GS-5423. Chronic, active inflammation 
with or without hemorrhage was noted at the SC injection sites but reversed after the recovery 
period. Antidrug antibodies (ADA) were detected in some animals in the IV and SC dose groups 
with no dose dependency. No 3BNC117-related adverse toxicological effects were observed in 
main or recovery group animals administered IV or SC doses of up to 60 mg/kg/injections, 
which was considered the no observed adverse effect level (NOAEL) for animals dosed twice 
weekly for 4 weeks with 3BNC117. 
GS-5423 has the same antigen binding characteristics as 3BNC117 as evaluated in a 
GLP-compliant tissue cross-reactivity study with human tissues. No significant staining was 
observed. The physiochemical characteristics and biological efficacy showed that GS-5423 and 
3BNC117 are similar in all characteristics, except for expected differences in pharmacokinetics 
(PK) due to amino acid substitutions in the Fc domain (M248L and N434S). The results of 
toxicology studies for the precursor antibody, 3BNC117 would be expected to predict the safety 
of GS-5423 when administered with similar drug exposures. For further information, refer to the 
current IB for GS-5423 (formerly 3BNC117-LS).
GS-2872
A GLP 25-day twice weekly IV and SC toxicity study with a 45-day recovery period in male and 
female Sprague Dawley rats was conducted with 10-1074, the precursor antibody for GS-2872. 
Additionally, the combination of 10-1074 with 3BNC117 (once weekly IV injections each) were 
assessed for toxicity at a dose level of 60 mg/kg/antibody/injection. The ADAs were detected in 
some animals in the IV and SC dose groups with no dose dependency. No 10-1074-related 
toxicological effects were observed in main or recovery group animals administered IV or 
SC doses of up to 60 mg/kg/injections or in the combination dosing with 10-1074 and 3BNC117. 
The 60 mg/kg/injection dose was considered the NOAEL for animals dosed twice weekly for 
4 weeks with 10-1074 alone or dosed once weekly in combination with 3BNC117.
GS-2872 has the same antigen binding characteristics as 10-1074 as evaluated in a 
GLP-compliant tissue cross-reactivity study with human tissues. No significant staining was 
observed. The results of toxicology studies for the precursor antibody, 10-1074 would be 
expected to predict the safety of GS-2872 when administered with similar drug exposures. For 
further information, refer to the current IB for GS-2872 (formerly 10-1074-LS).


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Lenacapavir 
The potential systemic toxicology of LEN has been characterized through single-dose IV, 
repeat-dose SC, and repeat-dose oral administration of LEN. The GLP SC toxicity 6-month rat 
study and 9-month dog studies are completed. Reversible liver changes were observed after a 
large single-dose IV administration to dogs. Expected granulomatous inflammation has been 
observed at the SC injection sites. A second 9-month SC toxicity study in dog was initiated in 
January 2020. The purpose is to administer higher doses in order to evaluate higher exposure 
margins than in the previous studies. No adverse events (AEs) have been observed in 
embryo-fetal toxicity studies in rat and rabbit, or in a male and female rat fertility study. 
1.2.3.
Clinical Experience for GS-5423 and GS-2872
1.2.3.1.
GS-5423 and GS-2872 
Clinical experience with the parental antibodies 3BNC117 and with 10-1074 alone and in 
combination are presented in the respective IBs. In aggregate, the clinical experience with 
> 160 participants who have received infusions of either bNAb alone or in combination indicates 
that the bNAbs are generally safe and well tolerated, with the majority of AEs being transient 
and Grade 1. Repeat doses of both antibodies in combination have been administered over 4, 6, 
and 16 weeks, and 3BNC117 has been administered over 27 weeks. 
These data present a summary of available data for GS-5423 and GS-2872 from a first-in-human 
(FIH) Phase 1 study of GS-5423 in PLWH and uninfected individuals (Study YCO-0946) and a 
Phase 1 dose escalation, FIH study of GS-2872 alone and in combination with GS-5423 in 
PLWH and uninfected individuals (Study YCO-0971).
1.2.3.2.
Study YCO-0946: First-in-Human Study of GS-5423 (3BNC117-LS) in 
HIV-Infected and Uninfected Individuals
This was a Phase 1, dose escalation, open-label FIH study of the safety and PK of GS-5423 
(3BNC117-LS) administered IV to PLWH suppressed on ART and administered either IV or SC 
in HIV-uninfected participants by Rockefeller University. Participants received a single dose of 
GS-5423 at one of the following dose levels: 3 mg/kg, 10 mg/kg, or 30 mg/kg administered IV, 
or a single SC injection of GS-5423 or placebo at 150 mg or 300 mg.
A total of 43 participants were enrolled (31 HIV-uninfected and 12 HIV-infected individuals on 
suppressive ART) from September 2017 to May 2019; 39 received GS-5423 and 4 received 
placebo. Two manufacturing lots were used for this study. The manufacturing process for lot 2 
was the same as that for lot 1 except for the addition of a supplement to increase sialic acid 
content in order to increase serum half-life. Four participants were lost to follow-up. All enrolled 
PLWH remained on ART during study follow-up, according to protocol. Follow-up was 
completed on 07 April 2020. As GS-5423 was produced for the current protocol using the 
manufacturing process for lot 2 and will be administered 30 mg/kg IV, only the relevant 
preliminary PK data (following a single dose of GS-5423 at 30 mg/kg from lot 2) are presented 
in Table 1-1. Safety data from all cohorts are summarized.


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Safety Results
The occurrence of AEs was assessed at multiple time points following administration of the 
study products. Four participants reported a single reactogenicity event (nausea, headache, 
tenderness, and malaise/fatigue), all were graded as mild (Grade 1). A single local reactogenicity 
event has been reported (Grade 1 tenderness) following SC administration. Serious adverse 
events (SAEs) were reported for 2 participants (cellulitis and transient ischemic attack); neither 
was judged as related to study drug. There were 44 nonreactogenicity AEs reported to date, with 
79.5% of the reported AEs of Grade 1 severity (one of which was an SAE). Six reported AEs 
were of Grade 2 severity, 2 were of Grade 3 severity (hyperalbuminuria and cellulitis, the latter 
reported as an SAE), and 1 was of Grade 4 severity (hypokalemia). The Grade 1 SAEs and 
Grade 3 and 4 AEs were:

SAE Grade 1 transient ischemic attack – Transient ischemic attack was reported in 
1 participant whose workup revealed a vascular anatomic abnormality treated with a stent 
and was judged not related to study drug.

Grade 3 hyperalbuminuria – Baseline urinalysis showed 100 mg/dL albumin prior to study 
drug infusion in a participant with trace proteinuria at screening and was judged not related 
to study drug.

SAE Grade 3 cellulitis – Cellulitis was judged not related to study drug and resolved with 
treatment.

Grade 4 hypokalemia – Serum potassium was 3.0 mEq/L 1 week after SC injection in a 
participant with no symptoms and no concomitant study drugs associated with hypokalemia. 
At Week 2, the participant’s potassium level was 4.0 mEq/L.
One pregnancy was reported at Week 36 in a participant who received study drug or placebo SC. 
The participant reported spontaneous abortion at approximately 10 weeks gestational age. The 
pregnancy and miscarriage event were judged not related to study drug.
Table 1-1.
Study YCO-0946: Summary of Reported Adverse Events
AEs Table
No. 
AEs
No. Mild 
(Grade 1)
No. 
Moderate 
(Grade 2)
No. 
Severe 
(Grade 3)
No. Potentially 
Life-
Threatening 
(Grade 4)
No. of 
Participants 
(N = 39)
% of 
Participants
0-28 Days from Study Drug Dosing
Solicited
Nausea
1
1
—
—
—
1
2.6
Headache
1
1
—
—
—
1
2.6
Tenderness
1
1
—
—
—
1
2.6
Malaise/fatigue
1
1
—
—
—
1
2.6
 I 
 
I 
 


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AEs Table
No. 
AEs
No. Mild 
(Grade 1)
No. 
Moderate 
(Grade 2)
No. 
Severe 
(Grade 3)
No. Potentially 
Life-
Threatening 
(Grade 4)
No. of 
Participants 
(N = 39)
% of 
Participants
Unsolicited
URI
4
4
—
—
—
4
10.3
Dizziness
2
2
—
—
—
2
5.1
Vulvovaginal candidiasis
2
2
—
—
—
1
2.6
Abdominal pain
1
1
—
—
—
1
2.6
Borborygmus
1
1
—
—
—
1
2.6
Cellulitis
1
—
—
1
—
1
2.6
Contact dermatitis
1
1
—
—
—
1
2.6
Elevated creatinine
1
1
—
—
—
1
2.6
Gonorrhea
1
1
—
—
—
1
2.6
Hematoma
1
1
—
—
—
1
2.6
Hyperalbuminuria
1
—
—
1
—
1
2.6
Hyperbilirubinemia
1
—
1
—
—
1
2.6
Hypokalemia
1
—
—
—
1
1
2.6
Muscle twitching
1
1
—
—
—
1
2.6
Ocular pruritis
1
1
—
—
—
1
2.6
Pruritis
1
1
—
—
—
1
2.6
Pruritis at injection site
1
1
—
—
—
1
2.6
Urethral chlamydia
1
1
—
—
—
1
2.6
Worsening hypertension
1
—
1
—
—
1
2.6
Subtotal AEs
28
23
2
2
1
—
—
> 28 Days from Study Drug Dosing
Solicited
—
—
—
—
—
—
—
Unsolicited
URI
5
4
1
—
—
4
10.3
Decreased hemoglobin
2
2
—
—
—
2
5.1
Musculoskeletal pain
2
2
—
—
—
2
5.1
Worsening hypertension
2
1
1
—
—
2
5.1
Anemia
1
1
—
—
—
1
2.6
Chalazion
1
1
—
—
—
1
2.6
Elevated creatinine
1
—
1
—
—
1
2.6


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AEs Table
No. 
AEs
No. Mild 
(Grade 1)
No. 
Moderate 
(Grade 2)
No. 
Severe 
(Grade 3)
No. Potentially 
Life-
Threatening 
(Grade 4)
No. of 
Participants 
(N = 39)
% of 
Participants
Fatigue
1
1
—
—
—
1
2.6
Lipodystrophy
1
1
—
—
—
1
2.6
Miscarriage
1
—
1
—
—
1
2.6
Transient ischemic attack
2
2
—
—
—
1
2.6
Vomiting
1
1
—
—
—
1
2.6
Subtotal AEs
20
16
4
—
—
—
—
Total reported AEs
48
39
6
2
1
25
64.1
AE(s) = adverse event(s); URI = upper respiratory infection
Laboratory abnormalities of moderate or severe grade were uncommon and are summarized in 
Table 1-2. Both HIV-1 viral load and CD4 counts were monitored in ART-treated participants 
and have generally remained stable during follow-up.
Table 1-2.
Study YCO-0946: Postinfusion Laboratory Abnormalities of 
Moderate or Severe Grade
Postinfusion Laboratory 
Results
Number of Participants 
with Moderate Laboratory 
Abnormalities
Number of Participants 
with Severe Laboratory
Abnormalities
Number of Participants 
with Life-Threatening
Abnormalities
Chemistry
Total bilirubin
2
—
—
Direct bilirubin
—
1
—
Creatinine
1
—
—
AST
2
—
—
ALT
2
—
—
Potassium (decreased)
—
—
—
Hematology
Hemoglobin (decreased)
16
—
—
Neutrophils (decreased)
3
1
—
Lymphocytes (decreased)
2
—
—
ALT = alanine aminotransferase; AST = aspartate aminotransferase
In summary, GS-5423 (3BNC117-LS) was generally well tolerated at all doses tested when 
administered IV or SC. The most frequently reported AEs within 28 days of study drug 
administration were Grade 1 upper respiratory infections (URIs; 9.7%), dizziness (4.7%), and 
nausea (4.7%).




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Figure 1-2.
Study YCO-0946: Anti-GS-5423 (Anti-3BNC117-LS) Antibody 
Response Titers
ADA = antidrug antibody
Analysis of samples from participants enrolled in Part B of the study is ongoing.
1.2.3.3.
Study YCO-0971: First-in-Human Study of GS-2872 (10-1074-LS) Alone and in 
Combination with GS-5423 (3BNC117-LS) in HIV-Infected and Uninfected 
Individuals
Study YCO-0971 is a Phase 1, dose escalation cohort study of GS-2872 administered IV or SC 
alone in HIV-uninfected individuals at SC doses of 140 or 280 mg or in combination with 
GS-5423 at doses ranging from 60 mg to 100 mg of GS-2872 and 200 mg to 240 mg of GS-5423 
and groups that received IV infusions (HIV-uninfected and PLWH) of either GS-2872 alone at 
doses ranging from 3 to 30 mg/kg, or GS-2872 in combination with GS-5423 at 30 mg/kg of 
each antibody. Participants were followed for 48 weeks following last antibody dose.
A total of 69 participants were enrolled in the study and treated with GS-2872 or a combination 
of GS-2872 and GS-5423; 44 received the antibodies SC and 25 received the antibodies IV. 
Safety Summary
Adverse Events
The occurrence of AEs was assessed at multiple time points following administration of the 
study products.
Systemic and local reactogenicity and nonreactogenicity AEs are summarized in Table 1-3. In 
total, there have been 101 AEs reported; 14 (13 were dosed SC) enrolled participants reported 
17 reactogenicity events within 2 weeks following study drug administration and all were 
Grade 1. These included erythema/skin discoloration (n = 2), pain (n = 3) and induration (n = 1) at 
administration site, headache (n = 4), feverishness (n = 3), malaise/fatigue (n = 3), and myalgia 
(n = 1).
There were 84 unsolicited AEs reported by enrolled participants. Of these, 27 AEs (32.1%) 
occurred within 4 weeks of study drug administration. Nine AEs (10.7%) were Grade 3: 
nephrolithiasis (n = 1), elevated blood pressure (n = 4), decrease in hemoglobin (n = 1), 
 
 
 
 
 
 
 
 
  
 
 
 
 
 


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proteinuria (n = 2), and increased left-sided weakness (also reported as an SAE; n = 1). Three 
participants with transient Grade 3 elevation in blood pressure on the day of study drug 
administration had preexisting history of hypertension. Ten AEs (11.9%) were Grade 2: 
musculoskeletal pain (n = 3), rash (n = 1), elevated systolic blood pressure (n = 1), gastroenteritis 
(n = 2), abdominal pain (n = 1), abscess (n = 1), and sciatica (n = 1). All other AEs (n = 66) were 
Grade 1, and of these, 6 were considered possibly, probably, or definitely related to study drug 
administration. The most common AEs were related to URIs, musculoskeletal pain, and 
symptoms of gastroenteritis. Overall, no dose-limiting toxicities have occurred during study 
follow-up.
One SAE of worsening left-sided weakness (Grade 3) was reported in a participant receiving 
GS-5423 and GS-2872 or placebo. The participant had a history of ischemic stroke with 
residual left-sided weakness, and a workup did not reveal an etiology. The SAE and the event 
were not considered related to study drug.
Table 1-3.
Study YCO-0971: Summary of Reported Adverse Events
Severity
Adverse Events
Mild
Moderate
Severe
Total No. Participants
Related AEs
Local Injection Site Reactions
SC Groups
Only (n = 44)
Erythema/skin discoloration
2
—
—
2
Induration
1
―
―
1
Pain
3
―
―
3
Systemic AEs Within 4 Weeks of Study Drug Administration
All Groups
(n = 69)
Feverishness
3
—
—
3
Headache
4
―
—
3
Myalgia
1
―
—
1
Malaise/fatigue
3
―
—
3
Abdominal pain
1
―
—
1
Decrease in hemoglobin
―
―
1
1
Elevated blood pressure
―
1
1
2
Upper respiratory infection 
symptoms
2
—
—
2
Systemic AEs After 4 Weeks of Study Drug Administration
Xerophthalmia
1
―
―
1
Total Reported Related 
AEs
21
1
2
―


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Severity
Adverse Events
Mild
Moderate
Severe
Total No. Participants
Not-Related AEs
Systemic AEs Within 4 Weeks of Study Drug Administration
Bacterial vaginosis
1
―
—
1
Candida vaginitis
1
―
—
1
Chest pain
1
―
—
1
Dizziness
1
―
—
1
Dyspepsia
1
―
—
1
Elevated blood pressure
1
―
2
3
Facial edema
1
―
—
1
Gastroenteritis
1
―
—
1
Musculoskeletal pain
2
―
—
2
Rash
―
1
—
1
Upper respiratory infection
7
―
—
7
Proteinuria
―
―
1
1
Systemic AEs After 4 Weeks of Study Drug Administration
Abdominal pain
―
1
―
1
Bacterial vaginosis
1
―
―
1
Chlamydia urethritis
1
―
―
1
Constipation
2
―
―
1
Dizziness
1
―
―
1
Elevated blood pressure
1
―
―
1
Flu-like symptoms
1
―
―
1
Folliculitis
1
―
―
1
Gastroenteritis
3
2
―
5
Hordeolum
1
―
―
1
Rash
1
―
―
1
Musculoskeletal contusions
2
―
—
2
Musculoskeletal pain
4
2
―
6
Nephrolithiasis
—
―
1
1
Proteinuria
1
1
2
4
Sciatica
1
1
―
2
Dental extraction
1
―
―
1
Toothache
1
―
―
1
Upper respiratory infection
12
―
―
14
 
 


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Severity
Adverse Events
Mild
Moderate
Severe
Total No. Participants
Skin laceration 
2
―
―
2
Syphilis
2
―
―
2
Abscess
―
1
―
1
Diarrhea
1
―
―
1
Earache
1
―
―
1
Gonorrhea
1
―
―
1
Laryngeal polyp removal
1
―
―
1
Hemiparesis
―
―
1
1
Viral syndrome
1
―
―
1
Total Reported Not-Related 
AEs
61
9
7
―
AE(s) = adverse event(s); SC = subcutaneous
Chemistry and hematology laboratory abnormalities of moderate or severe grade are summarized 
in Table 1-4. Laboratory abnormalities graded as severe were judged not related to study drug or 
procedures. 
Thyroid function tests were also monitored following study drug administration given findings 
on tissue cross-reactivity studies that showed binding of GS-2872 to thyroid human tissue. No 
significant changes from baseline in thyroid function tests (thyroid-stimulating hormone [TSH], 
triiodothyronine [T3], and free thyroxine [T4]) were noted 4 weeks after study drug 
administration. HIV serologies were checked 2 or 4 weeks after antibody administration to 
determine if antibody administration might cause a transient false-positive HIV test in 
HIV-uninfected participants. Indeterminate HIV serologies were measured in participants in the 
groups receiving study drug by IV administration and less commonly in participants receiving 
study drug through SC administration. All participants with indeterminate HIV serologies also 
had an HIV viral load performed, which was negative in all participants.


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Table 1-4.
Study YCO-0971: Postinfusion Laboratory Abnormalities of 
Moderate or Severe Grade (Maximum Severity Per Volunteer)
Postinfusion Laboratory 
Results
Number of Moderate 
Laboratory Abnormalities
Number of Severe 
Laboratory Abnormalities
Number of 
Life-Threatening 
Laboratory Abnormalities
Hematology
—
—
—
Hemoglobin
20
2
—
Total white blood cell 
count
1
—
—
Neutrophils
6
—
—
Lymphocytes
6
—
—
Platelets
1
—
—
Chemistry
—
—
—
Creatinine
—
—
—
AST
2
—
—
ALT
—
—
—
Total bilirubin
1
—
—
Direct bilirubin
—
—
—
ALT = alanine aminotransferase; AST = aspartate aminotransferase
Pharmacokinetics of GS-2872 (10-1074-LS) 
Preliminary concentration-time profiles of GS-2872 are presented in Figure 1-3 following a 
single dose of 10 or 30 mg/kg GS-2872 in healthy volunteers, or in PLWH who were ART 
suppressed. Preliminary analysis of GS-2872 PK in Study YCO-0971 suggests that its 
elimination half-life is approximately 80 days. 




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Table 1-5.
Study GS-US-200-4538: Solution Formulations and Doses
Formulation
Dose of LEN (Volume Injected)
300 mg/mL FA
300 mg (1 × 1 mL)
309 mg (1  1 mL)
927 mg (3  1 mL)
309 mg/mL LEN injection
927 mg (2  1.5 mL)
309 mg (1  2 mL)
155 mg/mL NaS
927 mg (3  2 mL)
300 mg/mL NaSP
900 mg (3  1 mL)
75 mg (1 × 1 mL)
75 mg/mL NaSP
225 mg (2 × 1.5 mL)
50 mg/mL NaSP
50 mg (1 × 1 mL)
FA = free acid; LEN = lenacapavir; NaS = LEN injection; NaSP = LEN injection with poloxamer
Pharmacokinetic samples will be collected for up to 450 days; safety and PK analyses are 
ongoing. Data from selected formulations are presented below in Table 1-6. 
Pharmacokinetic Results
Data available to date after administration of single doses of SC LEN injection, 309 mg/mL are 
presented in Figure 1-4. Based on available PK data, a slow initial release of LEN was observed; 
however, concentrations exceeding an inhibitory quotient (IQ) of 4 (4-fold higher than the 
protein-adjusted 95% effective concentration [paEC95] from MT-4 cells; 3.87 ng/mL) were 
observed for at least 26 weeks following a single 927-mg dose (Figure 1-4). Preliminary PK data 
through 28 weeks postdose suggest similar PK profiles following SC administration of a 927-mg 
dose administered as either 3 × 1.0 mL or 2 × 1.5 mL SC injections.




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Table 1-6.
Study GS-US-200-4538: Preliminary Pharmacokinetic Parameters for 
Subcutaneous LEN Injection, 309 mg/mL 
PK Parameter 
(Mean %CV)
309 mg (1 × 1.0 mL) 
(n = 8)
927 mg (3 × 1.0 mL) 
(n = 8)
927 mg (2 × 1.5 mL)
(n = 8)
AUCinf (h•ng/mL)
66,400 (27.8)
225,000 (33.6)
224,000 (31.5)
AUClast (h•ng/mL)
61,100 (28.8)
179,000 (53.4)
153,000 (47.6)
%AUCexp
8.06 (51.2)
5.79 (50.6)
21.5 (33.8)
Cmax (ng/mL)
17.7 (50.3)
67.0 (54.8)
61.2 (43.5)
Tmax (h)
[days]
2350 (1340, 3360)
[98]
1850 (1680, 2020)
[77]
2020 (1510, 2690)
[84.2]
Tlast (h)
[days]
8740 (8060, 8740)
[364]
6720 (4030, 6720)
[280]
4700 (4700, 4700)
[196]
t1/2 (h)
[days]
1810 (1640, 2250)
[75.4]
1190 (1120, 1420)
[49.6]
1550 (1180, 1920)
[64.7]
%CV = percentage coefficient of variation; LEN = lenacapavir; PK = pharmacokinetic; Q1 = first quartile; Q3 = third quartile
PK parameters presented to 3 significant digits as mean (%CV), except Tmax, Tlast, and t1/2: median (Q1, Q3).
Safety Results
In a preliminary blinded review of safety data as of 29 October 2019, of 60 participants who 
received SC LEN injection, 309 mg/mL or SC LEN injection, 300 mg/mL with poloxamer or SC 
LEN injection, 155 mg/mL or placebo, no deaths or Grade 4 AEs have been reported. 
A total of 57 of 60 participants (95%) had at least 1 AE during the study (Table 1-7). 
The most frequently reported AEs were injection site induration (n = 47; 78.3%), injection site 
pain (n = 33; 55%), injection site erythema (n = 31; 51.7%), injection site swelling (n = 23; 
38.3%), headache (n = 21; 35.0%), injection site bruising (n = 16; 26.7%), and injection site 
nodules (n = 8; 13.3%). Three participants experienced Grade 3 SAEs; 1 with Grade 3 
hypoxemia on Day 16, 1 with Grade 3 abscess on Day 225, and 1 with Grade 3 fracture tibia on 
Day 121. All SAEs were not attributed to study drug.
Grade 3 and 4 treatment-emergent laboratory abnormalities were reported in 15 participants. 
Laboratory abnormalities reported in > 1 participant were creatine kinase (CK) (n = 4; attributed 
to exercise or boxes lifting), aspartate aminotransferase (AST) (n = 2 with CK elevation 
attributed to exercise and boxes lifting), low-density lipoprotein cholesterol (n = 2), and urine 
blood (n = 9). All cases were determined by the investigator to be not clinically significant.


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Table 1-7.
Study GS-US-200-4538: Summary of Adverse Events in 
> 2 Participants by Preferred Term
Preferred Term
Cohort 5
LEN
309 mg 
(309 mg/mL 
NaS)/ 
Placebo
(n = 10)
Cohort 6
LEN
927 mg 
(309 mg/mL 
NaS)/ 
Placebo
(3 × 1.0 mL)
(n = 10)
Cohort 7
LEN
927 mg 
(309 mg/mL 
NaS)/ 
Placebo
(2 × 1.5 mL)
(n = 10)
Cohort 9
LEN
309 mg 
(155 mg/mL 
NaS)/ 
Placebo
(1 × 2 mL)
(n = 10)
Cohort 10
LEN
927 mg 
(155 mg/mL 
NaS)/ 
Placebo
(3 × 2 mL)
(n = 10)
Cohort 13
LEN
900 mg 
(300 mg/mL 
+ NaSP)/ 
Placebo
(3 × 1 mL)
(n = 10
Total
(n = 60)
Number (%) of 
Participants with Any 
Treatment-Emergent 
Adverse Event
7
10
10
10
10
10
57 (95)
Injection site 
induration
3 (30)
8 (80)
10 (100)
8 (80)
9 (90)
9 (90)
47 (78)
Injection site pain
—
6 (60)
8 (80)
3 (30)
8 (80)
8 (80)
33 (55)
Injection site 
erythema
1 (10)
5 (50)
4 (40)
6 (60)
8 (80)
7 (70)
31 (52)
Injection site 
swelling
—
4 (40)
4 (40)
4 (40)
6 (60)
5 (50)
23 (38)
Headache
3 (30)
4 (40)
3 (30)
3 (30)
5 (50)
3 (30)
21 (35)
Injection site 
bruising
—
3 (30)
1 (10)
2 (20)
5 (50)
5 (50)
16 (27)
Injection site nodule
2 (20)
3 (30)
—
3 (30)
—
—
8 (13)
Hypersensitivity
—
—
—
1 (10)
2 (20)
—
3 (5)
Injection site 
discoloration
—
—
—
2 (20)
1 (10)
—
3 (5)
Injection site 
pruritus
—
—
2 (20)
—
—
1 (10)
3 (5)
Nausea
1 (10)
1 (10)
—
1 (10)
—
—
3 (5)
Oropharyngeal pain
—
—
—
1 (10)
2 (20)
—
3 (5)
Upper respiratory 
tract infection
1 (10)
1 (10)
1 (10)
—
—
—
3 (5)
LEN = lenacapavir; NaS = LEN injection; NaSP = LEN injection with poloxamer
No notable changes from predose in vital signs (systolic blood pressure, diastolic blood pressure, 
pulse, temperature, and respiration rate) have been observed in the study. No clinically 
significant electrocardiogram (ECG) abnormalities have been reported during the study.


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1.2.4.2.
Study GS-US-200-4072
Study GS-US-200-4072 is an ongoing, Phase 1b, randomized, double-blinded, 
placebo-controlled, multicohort dose-ranging study evaluating the safety, tolerability, PK, and 
short-term antiviral activity of monotherapy with SC doses of a LEN free-acid suspension 
(100 mg/mL) in PLWH who are either ART naive or ART experienced but capsid inhibitor 
naive.
This study will enroll 5 cohorts of approximately 8 unique participants per cohort to receive LEN 
or placebo. Within each cohort (n = 8), participants are randomized in a 3:1 ratio to receive 
active LEN (n = 6) or placebo (n = 2). A single dose of LEN or placebo is administered as an 
SC injection in the abdomen on Day 1.
As of 20 November 2019, 39 participants have received SC LEN or placebo (3:1 ratio) at doses 
of 20, 50, 150, 450, and 750 mg.
Disposition and Baseline Characteristics
As of 20 November 2019, 39 participants were randomized and received a single dose of 
SC LEN or placebo. One participant who received a single dose of LEN 450 mg was lost to 
follow-up after Day 169. The median duration of follow-up (number of days between Day 1 and 
the last study date) was 225 days and ranged from 16 to 247 days across the 5 cohorts.
The majority of participants were male (89.7%; 35 participants), white (53.8%; 21 participants), 
and not Hispanic or Latino (84.6%; 33 participants). The median age was 33 years (range: 19 to 
65 years). The median (first quartile [Q1], third quartile [Q3]) baseline HIV-1 RNA was 
4.53 (4.3, 4.74) log10 copies/mL, and the median (Q1, Q3) CD4 cell count was 463 
(359, 614) cells/μL. The majority of participants were ART-naive (82.1%; 32 participants).
Virologic Efficacy Results
HIV-1 RNA levels decreased following initiation of study drug (Figure 1-5). The mean (SD) 
maximum HIV-1 RNA reductions from baseline through Day 10 were 1.35 (0.318), 1.79 (0.476), 
1.76 (0.203), 2.20 (0.468), and 2.26 (0.662) log10 copies/mL at doses of LEN 20, 50, 150, 450, 
and 750 mg, respectively. All participants who received ≥ 50 mg LEN had a > 1 log10 copies/mL 
reduction in their HIV-1 RNA through Day 10. Overall, antiviral activity was comparable across 
the dose range of 50 to 750 mg, but lower at the 20-mg dose.


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Figure 1-5.
Study GS-US-200-4072: Mean and 95% CIs Change From Baseline in 
HIV-1 RNA (log10 copies/mL) (Full Analysis Set)
BL = baseline; GS-6207 = lenacapavir
Pharmacokinetic Results
Preliminary PK data show that following 50-, 150-, 450-, and 750-mg doses of LEN SC 
suspension, mean LEN concentrations on Day 10 were 1.1- to 20.5-fold higher than the paEC95 
for wild-type HIV-1 based on the half-maximal effective concentration in MT-4 cells (IQ = 1.1, 
3.3, 9.9, and 20.5 for the 50-, 150-, 450-, and 750-mg doses, respectively).
Safety Results
As of 20 November 2019, no deaths, Grade 4 AEs, or AEs leading to study drug discontinuation 
had been reported. One participant experienced a Grade 3 SAE of atrial fibrillation, which 
occurred following methamphetamine use and was not considered related to study drug by the 
investigator. After the data cut, the same participant, who had a history of hypertension, 
hyperlipidemia, and tobacco abuse, experienced Grade 4 SAEs of coronary artery disease and 
acute myocardial infarction, Grade 3 AEs of unstable angina and angina pectoris, and a Grade 3 
SAE of noncardiac chest pain. All AEs and SAEs were considered not related to study drug by 
the investigator. Another participant experienced a Grade 2 SAE of small intestinal obstruction, 
which was considered not related to study drug by the investigator. 
No other SAEs or Grade 3 AEs were reported. Most participants (33 of 39; 84.6%) reported an 
AE. The most frequent AEs were injection site pain (48.7%), injection site erythema (28.2%), 
and injection site induration (20.5%).
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Eight participants (20.5%) had a Grade 3 or Grade 4 laboratory abnormality reported. The 
Grade 3 or 4 abnormalities reported for more than 1 participant were transient CK elevations 
(n = 3), attributed to recent exercise or carrying heavy bags; asymptomatic elevated amylase 
(n = 2); and urine blood attributed to menses (n = 2).
1.2.4.3.
Study GS-US-200-4071 
Study GS-US-200-4071 is a completed Phase 1 study in healthy volunteers that evaluated the 
safety, tolerability, and PK of single- and multiple-ascending doses of oral LEN as an oral liquid 
(solution)-filled capsule (50 mg/mL or 100 mg/mL) or tablet (50 mg or 300 mg). Single- and 
multiple-dose PK data from the 50 mg/mL solution-filled capsule, and single-dose PK data from 
the tablets are presented in Table 1-8. To reduce pill burden, the LEN tablet was the oral form 
used in this study.
This study was originally designed as a single- and multiple-ascending dose evaluation of 
solution in capsule formulations, with 10 days of washout between the single- and multiple-dose 
periods (Cohorts 1 and 2). Following receipt of PK data from these 2 cohorts suggesting the t1/2 
was longer than predicted, the study design was altered to administer a single-ascending dose.
Within each cohort, participants were randomized to receive LEN (n = 8) or placebo (n = 2); all 
study drugs were administered under fasted conditions unless otherwise specified. In Cohorts 1, 
2, and 5, capsules containing 50 mg/mL solution were evaluated at doses of 30, 100, and 300 mg, 
respectively. Following development of a tablet formulation, 50-mg and 300-mg tablets were 
assessed, and participants were randomized to receive LEN (n = 8) or placebo (n = 2) under 
fasted conditions. In addition, 2 cohorts received open-label 300-mg LEN tablets (n = 8) given 
with a high-fat, high-calorie meal, or with a low-fat, low-calorie meal. A brief description of all 
cohorts is presented in Table 1-8.
Table 1-8.
Study GS-US-200-4071: LEN Formulations and Doses Evaluated
Formulation Description
Dose (No. of Capsules/Fasting Status)
Single-dose solution in capsule
50 mg/mL
30 mg (1 capsule, fasted)
100 mg (3 capsules, fasted)
300 mg (8 capsules, fasted)
Multiple-dose solution in capsule
50 mg/mL
30 mg (1 capsule, fasted)
100 mg (3 capsules, fasted)
Single-dose tablet
50 mg
50 mg (1 tablet, fasted)
300 mg
300 mg (1 tablet, fasted)
900 mg (3 tablets, fasted)
1800 mg (6 tablets, fasted)
300 mg (1 tablet, high fat)a
300 mg (1 tablet, low fat)a
LEN = lenacapavir
a
High-fat meal included high-calorie count (~1000 kcal, ~50% fat), low-fat meal included low-calorie count (~400 kcal, 
~25% fat)




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Table 1-9.
Study GS-US-200-4071: Preliminary LEN Plasma Pharmacokinetic 
Parameters Following Single-Dose Administration of Oral LEN 
Solution in Capsule (50 mg/mL; n = 8 Per Cohort)
Parameter
Cohort 1; 30 mg (n = 8)
Cohort 2; 100 mg (n = 8)
Cohort 5; 300 mg (n = 8)
Cmax (ng/mL)
1.16 (23.9)
2.70 (55.4)
4.75 (52.4)
Tmax (hr) a
29.0
(4.00, 90.0)
26.0
(4.00, 96.0)
7.00
(4.00, 18.00)
AUClast (hr•ng/mL)b
147 (29.0)
319 (46.0)
1990 (52.0)
AUCinf (hr•ng/mL)
ND
ND
2280 (53.1)
%AUCexp (%)
ND
ND
11.6 (61.0)
AUC0-24 (hr•ng/mL)
17.6 (19.7)
34.8 (47.3)
75.7 (61.3)
t1/2a (days)
ND
ND
12.3 (10.7, 13.8)
%CV = percentage coefficient of variation; LEN = lenacapavir; ND = not determined due to insufficient PK sampling; 
PK = pharmacokinetic; Q1 = first quartile; Q3 = third quartile 
PK parameters are presented as Mean (%CV), and shown to 3 significant digits
a
Median (Q1, Q3)
b
AUClast calculated through Day 7 postdose for Cohorts 1 and 2 and through last currently available time point for Cohort 5 
LEN preliminary PK parameters after 10 daily oral doses of LEN (50 mg/mL solution in 
capsule) are presented in Table 1-10. Consistent with its half-life, following 10 days of multiple 
dosing, the mean LEN Cmax and AUC0-24 were at least 10-fold higher than after a single dose 
(Table 1-11).
Table 1-10.
Study GS-US-200-4071: Preliminary LEN Plasma Pharmacokinetic 
Parameters Following Multiple-Dose Oral Administration of 30 mg 
and 100 mg Solution in Capsule (50 mg/mL; n = 8 Per Cohort)
Parameter
Cohort 1; 30 mg (n = 8)
Cohort 2; 100 mg (n = 8)
50 mg/mL solution in capsule
Cmax (ng/mL)
12.2 (17.1)
41.3 (53.8)
tmax (hr)a
3.50 (1.89, 10.0)
4.00 (4.00, 10.5)
AUC0-24hr (hr•ng/mL)
232 (17.9)
843 (56.5)
%CV = percentage coefficient of variation; LEN = lenacapavir; PK = pharmacokinetic; Q1 = first quartile; Q3 = third quartile
PK parameters are presented as Mean (%CV), and shown to 3 significant digits 
a
Median (Q1, Q3)
LEN concentration-time profiles and preliminary PK parameters after administration of single 
doses of LEN oral tablets administered either under fasted conditions, or with a high-fat or 
low-fat meal, are presented in Figure 1-7 and Figure 1-8. Interim safety and PK data are 
available through at least 8 days postdose. Based on preliminary PK data, LEN exposures 
increased in a less than dose-proportional manner over the range of 50 to 1800 mg. Maximal 
concentrations (Cmax) of LEN were achieved approximately 4 to 8 hours postdose (Tmax), and 
LEN half-life (t1/2) is estimated to be approximately 12 days (Figure 1-7).






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Safety Results
LEN tablets were generally safe and well tolerated across all treatment groups. A total of 9 of 
56 participants (16.1%) had at least 1 AE reported. The most commonly reported AEs were 
headache (n = 3; 5.4%) and back pain (n = 2; 3.6%). No other AEs were reported by more than 
1 participant. No Grade 3 or 4 AEs, deaths, SAEs, pregnancy, or AEs leading to permanent 
discontinuation of study drug were reported in any treatment group.
In a preliminary blinded review of safety data as of 03 September 2019, when all participants 
who had received LEN solution in capsules or placebo-to-match had completed or discontinued 
the study, the safety profile was similar to that observed with the tablets. The only AE reported 
for > 1 participant was headache (6.7%; 2 participants).
Dosing with LEN was generally safe and well tolerated in this study, with no notable differences 
in the overall safety profile of LEN administered as capsules or tablets. Overall, headache was 
the most common AE in participants who received LEN tablets; however, headache occurred at 
similar frequency in participants who received placebo tablets. 
1.3.
Rationale for This Study
Advances in ART have led to significant improvements in morbidity and mortality among 
PLWH by suppressing viral replication, preserving immunologic function, and averting disease 
progression to AIDS. While combination ART for the treatment of HIV-1 infection has been 
largely successful in reducing the morbidity and mortality associated with HIV disease, there 
remains a significant medical need for new well-tolerated therapies that take into consideration 
the limitations of daily oral pills and provide new options for long-acting treatment.
A combination of 2 potent bNAbs, 3BNC117 and 10-1074, which target nonoverlapping 
epitopes on HIV envelope, can control viral replication in people with virus sensitivity to both 
bNAbs {Mendoza 2018} with subsequent virologic rebound (VR) a median of 21 weeks after 
stopping ART, after antibody concentrations declined. Two of 15 participants did not have 
detectable plasma HIV-1 viremia at 30 weeks, compared with historical data suggesting a 
median time to rebound of 2.3 weeks in participants undergoing analytical treatment interruption 
(ATI). This suggests that engagement of the host immune system by bNAbs may contribute to 
enhanced control of HIV-1 replication after antibody plasma concentrations decline and the 
bNAbs no longer exert a direct neutralizing effect on the virus. Fc engineering has extended the 
half-life of the antibodies 3BNC117 and 10-1074 without alteration to the Fab domain, which 
enables GS-5423 (formerly 3BNC117-LS) and GS-2872 (formerly 10-1074-LS) to maintain 
plasma concentrations in a predicted therapeutic range for 6 months. 
Due to the diversity of the HIV-1 virus Env, an estimated 50% of clade B viruses are sensitive to 
both antibodies, and more than 90% of tested isolates are sensitive to either 3BNC117 or 
10-1074. Combining the bNAbs GS-5423 and GS-2872 with LEN, a potent selective inhibitor of 
HIV-1 capsid with predicted breadth encompassing 100% of HIV viruses, is hypothesized to 
augment the breadth of the regimen, increase the barrier to resistance and durability of the study 
regimen which also provides the potential benefits of antibody mediated engagement of the host 


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immune system in controlling HIV-1. The PK of each study regimen component also enables 
dosing once in 6 months.
Pilot Cohort
The patient population that could benefit from a regimen of GS-5423, GS-2872, and LEN has 
not been defined. Utilizing bNAb phenotypic sensitivity testing may aid in identifying PLWH 
who will benefit, but the optimal criteria (eg, an IC90 threshold) for determining sensitivity to 
GS-5423 and GS-2872 remain undefined. In addition, prior studies have reported similar 
suppression rates whether bNAb sensitivity was a requisite for inclusion or no screening was 
performed. Therefore the applicability of these assays to clinical treatment with bNAbs has not 
been firmly established. The PhenoSense mAb assay (Monogram Biosciences), used to 
determine study eligibility, uses pseudoviruses derived from proviral DNA in PBMCs and may 
not fully characterize an individual’s HIV-1 reservoir. Even with viruses that have lower 
susceptibility in the phenotypic assay (IC90 > 2 µg/mL), it is expected that the bNAbs will 
contribute to the overall regimen efficacy because  systemic bNAb concentrations are maintained 
well above 10 ug/mL at 6 months. Using a combination of 2 bNAbs that target non-overlapping 
epitopes also has an additive effect, and may have a synergistic effect on potency, thus 
neutralizing viruses that have low susceptibility to individual bNAbs {Kong 2015, Wagh 2018}. 
For these reasons, the Pilot Cohort with sensitivity to only one bNAb (GS-5423 or GS-2872) by 
protocol criteria, will explore safety and efficacy of the full study regimen in the presence of 
lower sensitivity to one bNAb. Screened participants with decreased susceptibility to both 
bNAbs will be excluded to limit the risk of LEN monotherapy. Results from the Pilot Cohort will 
inform which potential patient populations could be safely and effectively treated by the study 
regimen LEN plus GS-5423 and GS-2872.
Enrollment into the optional Pilot Cohort will be gated by the Gilead Data Review Committee 
(GDRC) assessment of safety and efficacy data from the Primary Cohort after 20 participants 
have completed follow-up through Week 12. The Pilot Cohort will have the same treatments and 
assessments as the Primary Cohort.
Developing safe and effective therapeutic options that maintain virologic suppression and 
facilitate adherence over a lifetime of therapy for PLWH remains a priority. For many 
individuals, including some who struggle with daily oral pills, newer study drugs are needed to 
control viral replication, preserve immune function, and prevent clinical progression. In all 
PLWH, the ideal goal of therapy remains complete and durable viral suppression. 
1.4.
Rationale for Dose Selection of GS-5423 and GS-2872
Dose selection for GS-5423 (3BNC117-LS) and GS-2872 (10-1074-LS) in this study is 
supported by antiviral activity, PK, and safety data from the non-LS forms of each antibody, 
3BNC117 and 10-1074, in a Phase 1b proof-of-concept (POC) study in HIV+ participants 
{Mendoza 2018}, as well the PK and safety data in healthy volunteers and participants with HIV 
of the LS forms of each antibody from the ongoing studies, YCO-0946 and YCO-0971. 


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In the Phase 1b POC study {Mendoza 2018}, MCA-906, the activity of the combination of 
3BNC117 and 10-1074 in the setting of ATI was evaluated. In this study, participants who were 
sensitive to both antibodies (n = 9) maintained viral suppression for a median of 21 weeks after 
the last dose of the antibodies. An exploratory PK/pharmacodynamic (PD) analysis of these data 
suggest that in sensitive participants, virologic suppression was maintained when 3BNC117 and 
10-1074 concentrations were > 10 µg/mL and > 100 µg/mL, respectively. Virologic 
breakthrough occurred when the concentrations of the less potent antibody, 3BNC117, fell below 
10 µg/mL. 
Based on the location of the amino acid substitutions to generate the LS forms of each antibody, 
as well as delays in time to infection observed in a nonhuman primate disease challenge model 
(refer to the 3BNC117-LS IB and 10-1074-LS IB), it is anticipated that the 10-1074-LS and 
3BNC117-LS antibodies will demonstrate similar antiviral activity to the unmodified forms, at 
the same target concentrations.
Single doses of GS-5423 and GS-2872 were shown to be safe and well tolerated up to 30 mg/kg 
in Studies YCO-0946 and YCO-0971. Preliminary PK data from Study YCO-0946 suggest 
GS-5423 (3BNC117-LS) has a t1/2 of approximately 54 days, and IV administration of GS-5423 
30 mg/kg is anticipated to maintain concentrations > 10 µg/mL for 26 weeks. Preliminary PK 
data from Study YCO-0971 suggest GS-2872 (10-1074-LS) has a t1/2 of approximately 80 days, 
and IV administration of GS-2872 10 mg/kg and 30 mg/kg are anticipated to maintain 
concentrations > 10 µg/mL and > 100 µg/mL, respectively, for 26 weeks. 
Based on these data and analyses, GS-5423 will be administered at 30 mg/kg in both treatment 
groups of this study, targeting a concentration of > 10 µg/mL throughout the 6 months, and 
GS-2872 will be administered at 10 mg/kg in Treatment Group 1, and 30 mg/kg in Treatment 
Group 2, targeting > 10 µg/mL and > 100 µg/mL, respectively, throughout the 6 months. The 
proposed dose range for GS-2872 allows for sufficient dose separation to evaluate the antiviral 
activity of GS-2872 at 10 mg/kg and 30 mg/kg in combination with GS-5423 30 mg/kg and LEN 
927 mg SC. 
1.5.
Rationale for Dose Selection of LEN
The dose and formulation selection for LEN in this study is supported by antiviral activity, PK, 
and safety data from the ongoing Phase 1b POC study (GS-US-200-4072) in treatment-naive 
(TN) and treatment-experienced (TE) but capsid inhibitor-naive PLWH, as well as PK and safety 
data from the two Phase 1 studies in healthy volunteers (GS-US-200-4538 and 
GS-US-200-4071).
In the Phase 1b POC study (GS-US-200-4072), potent antiviral activity of LEN was 
demonstrated; the mean maximum HIV-1 RNA decline over 10-day monotherapy after single 
SC doses of 50 to 750 mg was 1.8 to 2.3 log10 copies/mL. All participants achieved at least 
1 log10 copies/mL decline in their HIV-1 RNA at Day 10. Day 10 antiviral activity was 
comparable across a dose range of single doses of 50 to 750 mg. At these doses, mean (%CV) 
LEN concentrations on Day 10 were 1.1- to 20.5-fold higher (ie, IQ = 1.1-20.5) than the paEC95 
for wild type HIV-1 (paEC95 = 3.87 ng/mL in MT-4 cells).


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Based on these data and the safety data available to date, the proposed LEN regimen for both 
treatment groups targets an exposure whereby the lower bound of the 90% CI of the Ctrough is at 
least 4-fold higher than the paEC95 (ie, IQ4 based on paEC95 from MT-4 cells; 15.5 ng/mL) 
starting within a few days of dosing initiation, and maintained through Week 26.
1.6.
Risk/Benefit Assessment for the Study
Potential risks associated with the study include unknown AEs, including injection site reaction 
with SC administration of LEN, and infusion reactions including ADA-mediated reactions from 
GS-5423 and GS-2872. Passive administration of anti–HIV-1 bNAbs, including GS-5423 and 
GS-2872, as well as the original bNAbs on which they are based (3BNC117 and 10-1074), have 
been previously evaluated in humans. As observed with other mAbs, anti–HIV-1 bNAbs were 
generally considered safe and well tolerated, and infusion reactions were more common for 
mAbs that contained murine elements, compared with fully human mAbs like GS-5423 and 
GS-2872. Clinical monitoring for possible immunologic symptoms will be conducted during and 
immediately following bNAb infusion, and study sites are required to: have appropriate 
supportive medications available, including, but not limited to, diphenhydramine, 
acetaminophen, and glucocorticoids during IV infusions; and to follow a protocol-specified 
management plan for infusion-related reactions. A limited number of participants will be 
enrolled (N = approximately 20) and an early safety review will assess the safety and tolerability 
of the investigational regimen. An additional optional Pilot Cohort (N = up to 20) of previously 
screened participants whose results have been reviewed centrally for genotypic sensitivity may 
be added after Gilead Data Review Committee (GDRC) review.
In general, risks include those associated with frequent clinic visits and laboratory blood draws, 
and the associated pain and discomfort of multiple phlebotomies. Strategies to mitigate any 
potential risks include close monitoring of laboratory values as well as AEs. Parameters for 
monitoring of AEs will be well defined and closely followed.
A potential risk of virologic breakthrough with exposure to suboptimal therapeutic 
concentrations of the study regimen or unrecognized preexisting resistance to both bNAbs and/or 
LEN could lead to HIV-1 developing resistance to one or more study drugs. Data are limited to 
inform whether resistance testing to bNAbs will minimize the risk of enrolling participants with 
preexisting resistance to both bNAbs. Strategies to mitigate the risk include frequent assessments 
of HIV-1 RNA to ensure that virologic breakthrough is rapidly identified, thus limiting the time 
during which drug resistance mutations could emerge. Participants must be taking standard 
first-line ART at baseline and not have any significant resistance to approved ART classes. Each 
component of the study regimen is from a novel class without any known or predicted 
cross-resistance with currently approved ART, thus the development of resistance to any 
component of the study regimen would have limited impact on a participant’s future treatment 
options. 
The potential direct benefits of the study include a long-acting regimen that is administered once 
in 6 months rather than daily, thus freeing participants from the requirement of daily adherence 
to ensure efficacy. Participants may benefit from the novel regimen due to enhanced engagement 
of the immune system from bNAb therapy, which may result in reduction of the latent viral 


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reservoir and/or improved immunologic control of HIV-1. Potential benefits to participants 
include the use of bNAbs, which may result in reduced risk of end-organ toxicities associated 
with some ART, and the participant’s contribution to understanding the safety and tolerability of 
a novel long-acting treatment strategy including the PK of the regimen and contributions to 
helping develop new classes of ART with potential application for HIV-1 treatment, prevention, 
and cure. 
Considering the above, the benefit-risk balance for this study is considered positive.
During a pandemic, additional potential risks to participants may include adequate study drug 
availability, interruptions to the study visit schedule, and adherence to protocol-specified safety 
monitoring or laboratory assessments. Refer to Appendix 7 for further details on the risks and 
risk mitigation strategy.
1.7.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


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2.
OBJECTIVES
The primary objective of this study is as follows:

To evaluate the safety and tolerability of a combination of the bNAbs GS-5423 and GS-2872 
in combination with the HIV capsid inhibitor LEN 
The secondary objectives of this study are as follows:

To evaluate efficacy of the study regimens determined by the proportion of participants 
maintaining virologic suppression (HIV-1 RNA < 50 copies/mL) at Week 26

To evaluate the PK of GS-5423, GS-2872, and LEN

To evaluate immunogenicity of GS-5423 and GS-2872

To evaluate the emergence of resistance to the components of the study regimens
The exploratory objectives are as follows:

To evaluate changes in HIV reservoir 

To evaluate changes in immune biomarkers


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3.
STUDY DESIGN
3.1.
Endpoints
Study endpoints will be assessed in the Primary Cohort excluding the optional Pilot Cohort. 
Exploratory analysis may be conducted for the optional Pilot Cohort as applicable. 
The primary endpoint of this study is as follows:

Incidence of treatment-emergent SAEs through Week 26
The secondary endpoints of this study are as follows:

Proportion of participants with HIV-1 RNA < 50 copies/mL at Week 26 as defined by the 
Food and Drug Administration (FDA)-defined snapshot algorithm

Proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 26 as defined by the 
FDA-defined snapshot algorithm

Proportion of participants with positive anti–GS-5423 or anti–GS-2872 antibodies at 
Week 26

Change from baseline in CD4+ cell counts at Week 26 

Treatment-emergent resistance to study drugs through Week 26

Incidence of treatment-emergent SAEs through Week 26, and treatment-emergent AEs 
through Week 26

PK parameters for GS-5423, GS-2872, and LEN (and metabolites, if applicable) as 
appropriate: AUC0-t, AUClast, t1/2, Cmax, Tmax, Tlast, Ct through Week 52
The other endpoints of interest are as follows:

Changes from baseline in HIV-1 reservoir in peripheral blood mononuclear cell (PBMC) at 
postbaseline visits

Changes from baseline in HIV-1 specific T-cell response, immune cell phenotyping and 
proliferation, gene expression, antibody profiling, and soluble proteins levels (eg, cytokines, 
chemokines, inflammatory markers, etc).


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3.2.
Study Design
This protocol describes a randomized, blinded, POC Phase 1b study to evaluate the safety and 
efficacy of a single dose each of long-acting regimen of LEN, GS-5423, and GS-2872 in adults 
with HIV-1 infection who are virologically suppressed on oral ART.
An overview of the study design is described below and shown in Figure 3-1.
Figure 3-1.
Study Schema
ART = antiretroviral therapy; ET = early termination; LEN = lenacapavir; PK = pharmacokinetic(s); SC = subcutaneous
3.3.
Study Treatments
This study will enroll approximately 20 participants (Primary Cohort). After GDRC review 
(Section 5.1.3), an optional Pilot Cohort of up to 20 additional participants may be added. 
Participants in the Primary Cohort and in the optional Pilot Cohort will be randomized in a 
1:1 ratio to one of the following 2 treatment groups based on the dose of GS-2872 as follows:
Treatment Group 1: 
Oral LEN for loading 600 mg followed by LEN 927 mg SC on Day 1; oral LEN for loading 
600 mg on Day 2 
GS-5423 30 mg/kg, administered via IV infusion over 60 minutes on Day 1 (after LEN SC 
injection)
GS-2872 10 mg/kg, administered via IV infusion over 60 minutes on Day 1 (after GS-5423 
infusion)
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
  
 
 
 
 
 
 
 
  
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 


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Treatment Group 2: 
Oral LEN for loading 600 mg followed by LEN 927 mg SC on Day 1; oral LEN for loading 
600 mg on Day 2
GS-5423 30 mg/kg, administered via IV infusion over 60 minutes on Day 1 (after LEN SC 
injection)
GS-2872 30 mg/kg, administered via IV infusion over 60 minutes on Day 1 (after GS-5423 
infusion)
There is no stratification for randomization for the Primary Cohort.
For the optional Pilot Cohort, randomization will be stratified by the antibody (GS-5423 or 
GS-2872) to which the participant is sensitive. 
All participants will discontinue their background oral ARV regimen 1 day prior to receiving 
study drugs on Day 1. 
At Week 26, all participants will resume their baseline regimen of once daily oral ART (or 
compatible regimen selected by the investigator) and return to the clinic for visits at Weeks 38 
and 52.
Unblinded treatment assignments will be provided to the investigators after all participants are 
back on their baseline ARVs (or compatible regimen selected by the investigator) at Week 26 or 
have discontinued the study, and the Week 26 analysis has been completed.
3.4.
Duration of Treatment
Duration of study drug treatment is approximately 26 weeks. 
3.5.
End of Study
The end of study will be when the last participant has completed their final visit in the study.
3.6.
Poststudy Care 
Once a participant has completed their study participation, the long-term care of the participant 
will return to the responsibility of their primary treating physicians. 
3.7.
Source Data
The source data for this study will be obtained from electronic data capture (EDC), central 
laboratory, specialty laboratory (eg, for PK/ADA and/or PD data), and interactive response 
technology (IRT) data.


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3.8.
Biomarker Testing 
3.8.1.
Biomarker Samples to Address the Study Objectives 
The following biological specimens will be collected from all participants who have provided 
consent to participate in this study and may be used to evaluate the association of systemic 
and/or tissue-based biomarkers with study drug response (including efficacy and/or AEs) and 
dosage selection, and to better understand the biological pathways, biology of HIV-1 infection or 
related diseases, and/or the validation of a companion diagnostic for HIV cure. Because 
biomarker science is a rapidly evolving area of investigation, and AEs in particular are difficult 
to predict, it may not be possible to specify prospectively all tests that may be done on the 
specimens provided. The specific analyses will include but may not be limited to the biomarkers 
and assays listed below. The testing outlined below is based upon the current state of scientific 
knowledge. It may be modified during or after the end of the study to remove tests no longer 
indicated and/or to add new tests based upon new state-of-the-art knowledge. 

Samples will be collected to measure biomarkers that may include but will not be limited to 
HIV-1 specific T-cell response, immune cell phenotyping, gene expression, antibody 
profiling, and soluble proteins levels (eg, cytokines, chemokines, inflammatory markers, etc.) 
at the following time points: baseline (Day 1 predose), and Weeks 4, 26, 38, and 52. 
Fc-gamma receptor (FcgR) single nucleotide polymorphisms (SNPs) will be evaluated using 
samples collected at the Day 1 visit.
Samples collected for biomarker assessments will be destroyed no later than 15 years after the 
end of study or per country requirements. 
3.8.2.
Biomarker Samples for Optional Future Research 
In addition to the study-specific informed consent to be signed by each study participant, 
participants will be required to document consent if they agree to allow the use of the remainder 
of their already collected biomarker and PK specimens for optional future research, in 
accordance with applicable regulations.
The specimens consented for optional future research may be used to advance development of 
the drug and/or increase our knowledge and understanding of the biology of the disease under 
investigation and related diseases. These specimens may also be used to study the association of 
biomarkers with biological pathways, disease pathogenesis, progression and/or treatment 
outcomes, including efficacy, AEs, and the processes of drug absorption and disposition. In 
addition, these specimens may be used to develop biomarker and/or diagnostic assays and 
establish the performance characteristics of these assays. The analysis of optional future research 
specimens may facilitate the design of new pharmaceutical agents and the development of 
diagnostic tests, which may allow for individualized drug therapy for patients in the future.
The specimens used for optional future research will be destroyed no later than 15 years after the 
end of study or per country requirements. 


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3.8.3.
Biomarker Samples for Optional Genomic Research 
In addition to the study-specific informed consent to be signed by each study participant, 
participants will be required to document consent if they agree to provide additional samples for 
optional genomic research. Additional samples will be obtained from participants who agree to 
participate and provide their additional specific consent. These samples should be collected at the 
Day 1 visit, before administration of the first dose of study drug, but may be collected at any 
time during the study or at a separate poststudy visit, if necessary. 
The specimens collected for optional future genomic research may be used to advance the 
development of the drug and/or increase our knowledge and understanding of the biology of the 
disease under investigation, or related diseases. These specimens may also be used to study the 
association of biomarkers with biological pathways, disease pathogenesis, progression and/or 
treatment outcomes, including efficacy, AEs, and the processes of drug absorption and 
disposition. In addition, these specimens may be used to develop biomarker and/or diagnostic 
assays and establish the performance characteristics of these assays. The collection and analysis 
of optional genomic research specimens may facilitate the design of new pharmaceutical agents 
and the development of diagnostic tests, which may allow for individualized drug therapy for 
patients in the future.
The samples collected for optional genomic research will be destroyed no later than 15 years 
after the end of the study or per country requirements.
3.9.
Optional Pharmacokinetic Substudy
In addition to the study-specific informed consent to be signed by each study participant, 
participants will be required to document consent if they agree to provide samples for the 
Optional PK Substudy. 
Plasma PK samples for LEN will be collected in a subset of participants (approximately 
n = 14 evaluable; approximately n = 7 from each treatment group).
Optional PK assessments will occur on the assigned days as outlined in Section 6.7.1 and 
Appendix 2.


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4. 
PARTICIPANT POPULATION 
4.1. 
Number of Participants and Participant Selection 
Approximately 20 participants who meet all the eligibility criteria will be enrolled in the Primary 
Cohort. After GDRC review (Section 5.1.3), an optional Pilot Cohort of up to 20 additional 
participants may be added.  
4.1.1. 
Participant Replacement 
Participants who discontinue before the end of study will not be replaced. 
4.2. 
Inclusion Criteria 
Participants must meet all of the following inclusion criteria to be eligible for participation in this 
study:  
1) The ability to understand and sign a written informed consent form (ICF), which must be 
obtained prior to initiation of study procedures; 
2) Between 18 and 65 years of age, inclusive, at screening; 
3) Plasma HIV-1 RNA < 50 copies/mL at screening; 
4) On first-line ART for ≥ 2 years prior to screening. A change in ART regimen ≥ 28 days prior 
to screening for reasons other than virologic failure (VF) (eg, tolerability, simplification, 
drug-drug interaction profile) is allowed; 
5) Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 18 months preceding the screening 
visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of 
detection is ≥ 50 copies/mL). Unconfirmed virologic elevations of ≥ 50 copies/mL (transient 
detectable viremia, or “blip”) prior to screening are acceptable; 
6) Proviral phenotypic sensitivity to both GS-5423 and GS-2872 at screening by the 
PhenoSense mAb Assay (Monogram Biosciences) for inclusion in the Primary Cohort; 
sensitivity at screening by the PhenoSense mAb Assay (Monogram Biosciences) to 1 mAb, 
either GS-5423 or GS-2872, within 18 months prior to enrollment for inclusion in the 
optional Pilot Cohort  
- 
In both cohorts, GS-5423 sensitivity is defined as 90% inhibitory concentration 
(IC90) ≤ 2 µg/mL; GS-2872 sensitivity is defined as IC90 ≤ 2 µg/mL; 
7) CD4+ count nadir ≥ 350 cells/µL; 
8) Screening CD4+ count ≥ 500 cells/µL; 


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9) Availability of a fully active alternative ART regimen, in the opinion of the investigator, in 
the event of discontinuation of the current ART regimen with development of resistance; 
10) Normal ECG (if abnormal, determined by the investigator to be not clinically significant); 
11) Adequate renal function: 
Estimated glomerular filtration rate (eGFR)  70 mL/min according to the Cockcroft-Gault 
formula {Cockcroft 1976}: 
Male:  
(140 − age in years)  (weight in kg)  CLcr (mL/min) 
 
 
72  (serum creatinine in mg/dL) 
Female: 
(140 – age in years)  (weight in kg)  0.85  CLcr (mL/min) 
 
 
72  (serum creatinine in mg/dL) 
where, CLcr = creatinine clearance; 
12) Alanine aminotransferase (ALT) and AST ≤ 5  upper limit of normal (ULN); 
13) Alkaline phosphatase within normal limits; 
14) Total bilirubin  1.5 mg/dL, or normal direct bilirubin; 
15) Adequate hematologic function (absolute neutrophil count  750/mm3; platelets 
 50,000/mm3; and hemoglobin  8.5 g/dL). Those with chronic neutropenia with no clinical 
significance can enroll at investigator discretion; 
16) Females of childbearing potential (as defined in Appendix 5) must have a negative serum 
pregnancy test at screening and negative urine pregnancy test at Day 1 prior to study drug 
administration; 
17) Male and female participants of childbearing potential who engage in heterosexual 
intercourse must agree to utilize protocol-specified method(s) of contraception as described 
in Appendix 5; 
18) Female participants must refrain from egg donation and in vitro fertilization during study 
participation and until at least 700 days following the last dose of study drugs; 
19) Male participants must refrain from sperm donation during treatment and until the end of the 
protocol-defined follow-up period. 


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4.3.
Exclusion Criteria
Participants who meet any of the following exclusion criteria are not eligible to be enrolled in 
this study:
1) Prior receipt of any anti–HIV-1 mAbs (including ibalizumab);
2) Have been treated with immunosuppressant therapies or chemotherapeutic agents 
(eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies) 
within 4 weeks of study screening or have an anticipated need for such treatment during the 
study;
3) Breastfeeding female;
4) Documented historical resistance to any component of the participant’s current ART 
regimen;
5) Participation in any other clinical study, including observational studies, without prior 
approval from the sponsor;
6) Hepatitis C virus (HCV) antibody positive and HCV RNA detectable; 
7) Chronic hepatitis B virus (HBV) infection, as determined by either:

Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV 
core antibody status, at the screening visit, or 

Positive HBV core antibody and negative HBV surface antibody, regardless of HBV 
surface antigen status, at the screening visit;
8) Active, serious infections (other than HIV-1 infection) requiring systemic antibiotic or 
antifungal therapy within 42 days prior to Day 1;
9) Have poor venous access that would limit phlebotomy or IV infusion of study treatments;
10) Have a history of any of the following:

Opportunistic infection or illness indicative of Stage 3 HIV disease (refer to Appendix 6);

Known hypersensitivity to the study drug, the metabolites, or formulation excipient;

Have an implanted defibrillator or pacemaker;

Malignancy within the past 5 years (prior to screening) or ongoing malignancy, other 
than basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma; 

Substance abuse or a psychiatric or medical condition that could, in the opinion of the 
investigator, compromise the participant’s ability to participate in the study.


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization, Blinding and Treatment Codes Access
5.1.1.
Randomization
Participants will be assigned a screening number in the IRT system at the time of consent.
Once eligibility has been confirmed, the investigator or designee will randomize the participant 
using the IRT system. Once a participant number has been assigned to a participant, it will not be 
reassigned to any other participant. The participant number assignment and randomization must 
be performed in clinic at the Day 1 visit provided that all screening procedures have been 
completed and participant eligibility has been confirmed.
Participants in the Primary Cohort who meet all eligibility criteria will be randomized in a 
1:1 ratio to Treatment Group 1 or Treatment Group 2. Participants in the Pilot Cohort who meet 
all eligibility criteria will be randomized in a 1:1 ratio to Treatment Group 1 or Treatment 
Group 2. 
There is no stratification for randomization for the Primary Cohort.
For the optional Pilot Cohort, randomization will be stratified by the antibody (GS-5423 or 
GS-2972) to which the participant is sensitive.
The IRT will assign a study drug bottle or vials at the Day 1 visit for each participant.
5.1.2.
Blinding
This study is designed as a randomized and blinded study, where Gilead personnel and site 
pharmacist will be unblinded while the investigational site(s) and participants participating in the 
study will remain blinded during the randomized phase. To mitigate the risks of inadvertently 
releasing the treatment information, Gilead staff will only be provided with the unblinded 
information when there is a need to access such information for data analysis to support safety 
and efficacy monitoring. Should Gilead staff receive unblinding information, they will maintain 
the confidentiality of the unblinded information, and will not communicate the information to 
blinded sites, or participants as specified in Gilead standard operating procedures (SOPs). 
5.1.3.
Planned Interim Unblinding
Additionally, to assess the safety and efficacy of the bNAbs GS-5423 and GS-2872 in 
combination with the HIV capsid inhibitor LEN for planning and development of the study 
regimen, an internal GDRC will be assembled. The GDRC will review participant-level data.
The GDRC will review the Week 12 data and other ad hoc analysis, if needed (see Section 0).


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The membership, conduct, and meeting schedule of the internal unblinded team will be 
documented in the GDRC Charter and as specified in Gilead SOPs. After the GDRC review of 
Week 12 data of primary cohort, the optional Pilot Cohort may be enrolled on the 
recommendation of the GDRC. 
5.1.4. 
Procedures for Breaking Treatment Codes 
In the event of a medical emergency where breaking the blind is required to provide medical care 
to the participant, the investigator may obtain treatment assignment directly from the IRT system 
for that participant. Gilead recommends but does not require that the investigator contact the 
Gilead medical monitor before breaking the blind. Treatment assignment should remain blinded 
unless that knowledge is necessary to determine participant emergency medical care. The 
rationale for unblinding must be clearly explained in source documentation along with the date 
on which the treatment assignment was obtained. The investigator is requested to contact the 
Gilead medical monitor promptly in case of any treatment unblinding. 
Blinding of study treatment is critical to the integrity of this clinical study and therefore, if a 
participant’s treatment assignment is disclosed to the investigator, the participant will have study 
treatment discontinued. All participants will be followed until study completion unless consent to 
do so is specifically withdrawn by the participant.  
All participants will receive the same 3 active study drugs, with the only difference being the 
dose of GS-2872. Unblinding for medical care is not expected. 
5.2. 
Description and Handling of Lenacapavir, GS-5423, and GS-2872 
5.2.1. 
Formulation 
5.2.1.1. 
Lenacapavir 
Lenacapavir tablets, 300 mg, are capsule-shaped, film-coated beige tablets, debossed with “GSI” 
on one side of the tablet and “62L” on the other side of the tablet. Each tablet core contains the 
equivalent of 300 mg LEN free acid in the form of LEN sodium salt. In addition to the active 
ingredient, LEN tablets, 300 mg, contain the following inactive ingredients: microcrystalline 
cellulose, mannitol, poloxamer 407, copovidone, croscarmellose sodium, magnesium stearate, 
polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide, iron oxide red, iron oxide black, 
and iron oxide yellow. 
Lenacapavir injection, 309 mg/mL, is a clear, yellow to brown solution for SC injection. In 
addition to the active ingredient (LEN sodium), LEN injection, 309 mg/mL, contains the 
following inactive ingredients: polyethylene glycol 300 and water for injection. 
5.2.1.2. 
GS-5423 
GS-5423 solution for infusion, 150 mg/mL, 1 mL/vial drug product will be supplied as a sterile, 
preservative-free, colorless to brownish yellow solution for IV administration. The drug product 
is composed of 150 mg/mL GS-5423 in histidine, acetate, trehalose, methionine, and 
polysorbate 20 at pH 5.2.  


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5.2.1.3.
GS-2872
GS-2872 solution for infusion, 150 mg/mL, 1 mL/vial, or 2 mL/vial drug product will be 
supplied as a sterile, preservative-free, colorless to brownish yellow solution for IV 
administration. The drug product is composed of 150 mg/mL GS-2872 in histidine, acetate, 
trehalose, methionine, and polysorbate 20 at pH 5.5.
5.2.2.
Packaging and Labeling
5.2.2.1.
Lenacapavir
Lenacapavir tablets, 300 mg, are packaged in white, high density polyethylene (HDPE) bottles. 
Each bottle contains either 4 or 5 tablets, silica gel desiccant, and polyester packing material. 
Each bottle is enclosed with a white, continuous thread, child-resistant polypropylene screw cap 
fitted with an induction-sealed, and aluminum-faced liner.
Lenacapavir injection, 309 mg/mL, is supplied as a sterile solution packaged in a single-use clear 
vial fitted with a rubber stopper and an aluminum flip-off seal.
5.2.2.2.
GS-5423
GS-5423 solution for infusion, 150 mg/mL, 1 mL/vial drug product is filled in single-use 2R, 
Type I clear glass vials, with coated elastomeric stoppers, capped with polypropylene flip-off 
caps with aluminum overseals.
5.2.2.3.
GS-2872
GS-2872 solution for infusion, 150 mg/mL, 1 mL/vial, or 2 mL/vial drug product is filled in 
single-use 2R, Type I clear glass vials, with coated elastomeric stoppers, capped with 
polypropylene flip-off caps with aluminum overseals.
Study drugs to be distributed to centers in the US shall be labeled to meet applicable 
requirements of the US FDA and/or other local regulations.
5.2.3.
Storage and Handling
Until administration and dispensation to the participants, all study drugs should be stored in a 
securely locked area, accessible only to authorized site personnel. To ensure the stability and 
proper identification, study drugs should not be stored in a container other than the container in 
which they were supplied. Consideration should be given to handling, preparation, and disposal 
through measures that minimize drug contact with the body. Appropriate precautions should be 
followed to avoid direct eye contact or exposure when handling.


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5.2.3.1.
Lenacapavir
Lenacapavir tablets, 300 mg, should be stored below 30°C (86°F). Storage conditions are 
specified on the study drug label. 
Lenacapavir injection, 309 mg/mL should be stored below 30°C (86°F) and protected from light. 
Storage conditions are specified on the study drug label.
5.2.3.2.
GS-5423
GS-5423 solution for infusion, 150 mg/mL, 1 mL/vial drug product, should be stored at 2-8°C 
and protected from light. Storage conditions are specified on the study drug label. 
5.2.3.3.
GS-2872
GS-2872 solution for infusion, 150 mg/mL, 1 mL/vial, or 2 mL/vial drug product, should be 
stored at 2-8°C and protected from light. Storage conditions are specified on the study drug label. 
5.3.
Dosage and Administration of GS-5423, GS-2872, and Lenacapavir
On Day 1, all participants will receive the following study regimen: 
Oral LEN 600 mg will be administered orally (PO) with approximately 240 mL water, 
without regard to food.
LEN 927 mg SC will be administered within 30 minutes after oral LEN for loading, as 
2 SC injections at separate injection sites in the abdomen, within 15 minutes. 
GS-5423 30 mg/kg IV infusion will be administered immediately following (up to 1 hour 
after) the last SC LEN injection.
GS-2872 10 mg/kg or 30 mg/kg (depending upon treatment group assignment) IV 
infusion will be administered at least 15 minutes following, and up to 1 hour after, the 
completion of GS-5423 IV infusion per Table 5-1.
On Day 1, all study drugs should be administered on the same day (ie, no visit window is 
permitted for Day 1 study drug administration).
On Day 2, all participants will self-administer oral LEN for loading 600 mg with approximately 
240 mL water, without regard to food, at approximately the same time as the oral LEN dose for 
loading on Day 1.
Dose and administration of LEN, GS-5423, and GS-2872 for Treatment Groups 1 and 2 are 
described below. 


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Table 5-1.
Treatment Table 
Study Day
Treatment Group 1
Treatment Group 2
Day 1
LEN 600 mg (two 300 mg tablets, PO)
LEN 927 mg (two 1.5 mL injections, SC)
GS-5423 30 mg/kg (IV infusion)
GS-2872 10 mg/kg (IV infusion)
LEN 600 mg (two 300 mg tablets, PO)
LEN 927 mg (two 1.5 mL injections, SC)
GS-5423 30 mg/kg (IV infusion)
GS-2872 30 mg/kg (IV infusion)
Day 2
LEN 600 mg (two 300 mg tablets, PO)
LEN 600 mg (two 300 mg tablets, PO)
IV = intravenous; LEN = lenacapavir; PO = per oral; SC = subcutaneous
Supportive medications, including but not limited to diphenhydramine, acetaminophen, and 
steroids, will be available in the clinic settings during the IV infusions.
Study drug infusion will be temporarily stopped if an infusion-related adverse reaction occurs. 
Symptom severity will be evaluated, and supportive medications provided as clinically indicated. 
Study drug infusion may be slowed and resumed after symptoms have resolved if approved by 
the investigator. If the symptoms, in the judgment of the investigator, compromise the ability to 
continue study-specific procedures and are considered to not be in the participant’s best interests, 
or recurrent symptoms prevent completion of infusion, the infusion will be permanently 
discontinued.
The exact time of study drug administrations must be recorded in the source document. For 
additional information, refer to the study Pharmacy Manual.
5.4.
Prior and Concomitant Medications
Clinical data indicate LEN is a substrate of P-glycoprotein (P-gp) transporters, and an inhibitor 
of cytochrome P450 enzyme (CYP) 3A enzymes (moderate), breast cancer resistance protein 
(BCRP), and P-gp transporters. In vitro data suggest LEN is also a substrate of CYP3A and 
uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) enzymes. Concomitant use of LEN 
with some medications or herbal/natural supplements that are inhibitors or inducers of CYP3A, 
UGT1A1, or P-gp may result in increased or decreased LEN exposure, respectively. 
Concomitant use of LEN with some medications or herbal/natural supplements that are 
substrates of CYP3A, P-gp, or BCRP may result in increased exposure of these medications.
Representative medications listed in Table 5-2 and herbal/natural supplements are currently 
excluded or should be used with caution while participating in this study; this table is not 
exhaustive. Any medication that is not on the list should be reviewed by Gilead prior to 
screening and throughout the study. Vitamins, acetaminophen, ibuprofen, and hormonal 
medications are allowed during the study period. Participants should discontinue disallowed 
concomitant medications 30 days prior to initiation of study drug, unless otherwise specified.
Vaccinations should not be administered within 14 days prior to infusion of GS-5423 and 
GS-2872 at Day 1.


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Table 5-2.
List of Representative Medications that are Prohibited or To Be Used 
with Caution due to the Potential for Drug-Drug Interaction with 
LEN
Medication Class
Prohibited Medications
Use Discouraged and To Be Used With 
Caution
Anticoagulants
—
Dabigatran etexilate: monitoring and/or dose 
reduction may be needed for certain 
populations per prescribing information
Anticonvulsants
Carbamazepine, oxcarbazepine, 
phenobarbital, phenytoin
—
Antimycobacterials
Rifampin, rifabutin, rifapentine
—
Antiretroviral agents
Any ARV not part of the study 
treatment regimen
—
Digoxin
—
Digoxin: concomitant use may result in 
increased levels of digoxin; use with caution 
and with appropriate monitoring of serum 
digoxin levels
Ergot derivatives
Ergotamine, ergonovine, 
dihydroergotamine, 
methylergonovine, ergometrine
—
Herbal/natural 
supplements
St. John’s wort, echinacea, milk 
thistle (ie, silymarin), Chinese herb 
sho-saiko-to 
(or Xiao-Shai-Hu-Tang)
—
3-Hydroxy-3-
methylglutaryl-coenzyme 
A (HMG-CoA) reductase 
inhibitors
—
Concentrations of some statins may increase 
with LEN. Start with the lowest dose and 
titrate to clinical response. For each of the 
following statins, the maximum allowed 
dose is:
Simvastatin: 10 mg
Lovastatin: 20 mg
Atorvastatin: 40 mg
Careful monitoring for signs and symptoms 
of muscle weakness or myopathy, 
including rhabdomyolysis.
Phosphodiesterase-5 
inhibitors
—
Sildenafil, vardenafil, tadalafil: It is 
recommended that a single dose of sildenafil 
no more than 25 mg in 48 hours, vardenafil 
no more than 2.5 mg in 72 hours, or tadalafil 
no more than 10 mg in 72 hours be 
coadministered.
Sedatives/hypnotics
—
Midazolam, triazolam
Systemic corticosteroids
All agents, including 
dexamethasone*
—
ARV = antiretroviral; LEN = lenacapavir
*
Single dose hydrocortisone for treatment of infusion reaction is permitted


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Medications to treat disease conditions excluded from the protocol are not listed under this 
concomitant medication section and are disallowed in the study. Medications for malignancy are 
not included in the table.
Should participants have a need to initiate treatment with any disallowed concomitant 
medication, the medical monitor must be consulted prior to initiation of the new medication. In 
instances where disallowed medication is initiated prior to discussion with Gilead, the 
investigator must notify Gilead as soon as they are aware of the use of the medication.
5.5.
Accountability for Investigational Medicinal Product 
The investigator is responsible for ensuring adequate accountability of all used and unused study 
drug, (vials and bottles). This includes acknowledgment of receipt of each shipment of study 
drug (quantity and condition). All used and unused study drug vials and bottles dispensed to 
participants must be returned to the site.
Each study site must keep accountability records that capture:

The date received and quantity of study drug (vials and bottles)

The date, participant number, and the study drug kit number dispensed

The date, quantity of used and unused study drug (bottles) returned, along with the initials of 
the person recording the information
5.5.1.
Investigational Medicinal Product Return or Disposal
Gilead recommends that used and unused study drug supplies be destroyed at the site. If the site 
has an appropriate SOP for drug destruction as determined by Gilead, the site may destroy used 
(empty or partially empty) and unused study drug supplies in accordance with that site’s 
approved SOP. A copy of the site’s approved SOP will be obtained by Gilead for the electronic 
trial master file (eTMF). If study drug is destroyed on site, the investigator must maintain 
accurate records for all study drugs destroyed. Records must show the identification and quantity 
of each unit destroyed, the method of destruction, and the person who disposed of the study drug. 
Upon study completion, copies of the study drug accountability records must be filed at the site. 
Another copy will be returned to Gilead. 
If the site does not have an appropriate SOP for drug destruction, used and unused study drug 
supplies are to be sent to the designated disposal facility for destruction. The study monitor will 
provide instructions for return.
The study monitor will review study drug supplies and associated records at periodic intervals.
For both disposal options listed above, the unblinded study monitor must first perform drug 
accountability during a monitoring visit.


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6.
STUDY PROCEDURES
The study procedures to be conducted for each participant enrolled in the study are presented in 
tabular form in Appendix 2 and described in the text that follows. 
The investigator must document any deviation from the protocol procedures and notify the 
Gilead or the contract research organization (CRO).
6.1.
Participant Enrollment and Treatment Assignment
Entry into screening does not guarantee enrollment into the study. In order to manage the total 
study enrollment, Gilead, at its sole discretion, may suspend screening and/or enrollment at any 
site or study-wide at any time.
Once the ICF has been obtained, all screening and eligibility tests and assessments have been 
assessed, and study eligibility has been confirmed, participants will be randomized to receive 
study drug on Day 1.
Participants will receive the study treatments as described in Section 5.3.
6.2.
Pretreatment Assessments
6.2.1.
Screening 
Due to the extended laboratory processing time of the bNAb sensitivity testing (up to 
approximately 10 weeks), the screening visit for the Primary Cohort will be performed in 2 parts. 
For the optional Pilot Cohort, participants will be selected by the sponsor from the previously 
screened/failed participants in the Primary Cohort and will directly proceed to Screening Part 2 
(no need to repeat Screening Part 1).
The following will be performed and documented at screening:
Part 1:

Obtain written informed consent

Obtain medical history

Review of AEs and concomitant study drugs

Obtain laboratory sample for bNAb sensitivity testing 


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Part 2: To be performed once results of bNAb sensitivity testing are reviewed and participant is 
deemed eligible to proceed.

Assess any changes in medical history, AEs, and concomitant medications

Complete physical examination

Vital signs (blood pressure, pulse, respiration rate, and temperature)

Weight

Height

ECG 

Obtain laboratory samples as described in Section 6.7
(Note: results obtained > 28 days before Day 1 will require a retest and confirmation)
Participants meeting all of the inclusion criteria and none of the exclusion criteria will return to 
the clinic within 28 days after the Screening Part 2 visit for the Day 1 visit. Participants must 
continue to take their prior treatment regimen up to 1 day prior to the Day 1 visit.
From the time of obtaining informed consent through the first administration of study drug, all 
SAEs, as well as any AEs related to protocol-mandated procedures, must be recorded on the AEs 
electronic case report form (eCRF). All other untoward medical occurrences observed during the 
screening period, including exacerbation or changes in medical history, are to be considered 
medical history. See Section 7 Adverse Events and Toxicity Management for additional details.
6.3.
Randomization
Once eligibility has been confirmed prior to or during the Day 1 visit, the investigator or 
designee will randomize the participant using IRT. The participant number assignment and 
randomization must be performed in clinic at the Day 1 visit provided that all screening 
procedures have been completed and participant eligibility has been confirmed.
There is no stratification for randomization for the Primary Cohort.
For the optional Pilot Cohort, randomization will be stratified by the antibody (GS-5423 or 
GS-2872) to which the participant is sensitive. 


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6.4.
Treatment Assessments
6.4.1.
Day 1 
The following procedures are to be completed at the Day 1 visit prior to study drug dosing:

Review of inclusion/exclusion criteria to confirm eligibility

Review of AEs and changes in concomitant medications

Complete physical examination 

Vital signs (blood pressure, pulse, respiration rate, and temperature) 

Weight

ECG 

Obtain laboratory samples as described in Section 6.7
After Day 1 assessments:

Participants will receive study treatment consisting of oral and SC LEN followed by 
GS-5423, then GS-2872, each administered as separate IV infusions
Infusion of GS-2872 will begin at least 15 minutes following, and up to 1 hour after, the 
completion of GS-5423 IV infusion
Participants will remain in a monitored clinical setting for at least 30 minutes after 
completion of GS-2872 infusion
Vital signs (blood pressure, pulse, respiration rate, and temperature) will be recorded 
30 minutes (± 10 minutes) after completion of GS-2872 infusion 

Participant will be dispensed oral LEN tablets 
6.4.2.
Day 2 

Participant will self-administer 2 tablets of LEN (2 × 300 mg) orally at home at 
approximately the same time as Day 1. The site will confirm dosing with participants and 
document in the source document.

Participants in the Optional PK Substudy will dose in the clinic and samples will be obtained 
as described in Section 6.7.1.

Review of AEs and changes in concomitant medications


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6.4.3.
Day 8

Participants in the Optional PK Substudy will visit the clinic for substudy sample collection

Review of AEs and changes in concomitant medications
6.4.4.
Weeks 4, 12, 26, 38, and 52

Review of AEs and changes in concomitant medications

Focused physical examination 

ECG at Weeks 26 and 52 

Weight

Vital signs (blood pressure, pulse, respiration rate, and temperature) 

Obtain laboratory samples as described in Section 6.7

At Week 26, all participants will resume their baseline background oral ARV regimen 
(or compatible regimen selected by the investigator). 
6.4.5.
Weeks 8, 16, 20, and 24 

Review of AEs and changes in concomitant medications

Obtain laboratory samples as described in Section 6.7
6.5.
Early Termination
If a participant discontinues their participation prior to Week 26, an Early Termination (ET) visit 
will be performed. 
The following will be performed at the ET visit:

Review of AEs and changes in concomitant medications

Complete physical examination 

Weight

Vital signs (blood pressure, pulse, respiration rate, and temperature)

Obtain laboratory samples as described in Section 6.7

Counsel participant regarding the importance of continuing a complete ARV therapy in 
accordance to standard of care, and refer patient to an appropriate HIV treatment facility


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However, if there are any abnormal laboratory results indicating there is a possible or probable 
causal relationship with the study drug, every attempt should be made to keep the participant in 
the study and repeat those laboratory tests weekly (or as often as deemed prudent by the 
investigator) until the abnormality is resolved, returns to baseline, or is otherwise explained.
The participant will be asked to continue attending the scheduled study visits through the 
Week 52 visit. 

If the participant decides to discontinue the study regimen but continues to attend study visits 
through Week 52, no other follow-up visits are required.

If the participant decides to discontinue the study regimen and does not continue to attend 
study visits through Week 52, the post-ET 30-, 90-, and 180-Day follow-up visits are 
required. Refer to Section 6.5.1. The post-ET 180-Day follow-up visit may be conducted via a 
phone call per the investigator’s discretion. 
Any post-ET 90-Day follow-up visit occurring after the date the Week 52 visit would have 
occurred may be conducted via a phone call per the investigator’s discretion. 
If this is not possible or acceptable to the participant or investigator, the participant may be 
withdrawn from the study.
6.5.1.
Post-Early Termination 30-Day, 90-Day, and 180-Day Follow-up Visits
The assessments below will be completed for participants who are required to complete the 
post-ET 30-, 90-, and 180-Day follow-up visits as noted in Section 6.7. 
Follow-up visits will be scheduled based on the date of the ET visit. For scheduling the 
follow-up visits, a ±6-day window may be used.
The following evaluations are to be completed during a phone call and in-clinic for follow-up 
visits:

Review of AEs and changes in concomitant medications
The following evaluations are to be completed at the in-clinic follow-up visits:

Review of AEs and changes in concomitant medications

Focused physical examination

Weight

Vital signs (blood pressure, pulse, respiration rate, and temperature)

Obtain laboratory samples as described in Section 6.7


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
At the post-ET 30-, 90-, and 180-Day follow-up visits, as applicable, if there are any 
abnormal laboratory results indicating that there is a possible or probable causal relationship 
with the study drug(s), every attempt should be made to repeat those laboratory tests weekly 
(or as often as deemed prudent by the investigator) until the abnormality is resolved, returns 
to baseline, or is otherwise explained. If this is not possible or acceptable to the participant or 
investigator, the participant may be withdrawn from the study.

If there are any AEs, every attempt should be made to keep the participant in the study and 
should be followed up until resolution or until the AE is stable, if possible. Gilead may 
request that certain AEs be followed beyond the protocol-defined follow-up period.
6.6.
Criteria for Discontinuation of Study Treatment
Study drug may be discontinued in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree and would not allow for subsequent study regimen 
administration

Unacceptable toxicity, as defined in the toxicity management section of the protocol, or 
toxicity that, in the judgment of the investigator, compromises the ability to continue 
study-specific procedures or is considered not to be in the participant’s best interest

VF; refer to Section 6.8

Participant request to discontinue for any reason

Participant noncompliance with any of the study drugs

Pregnancy during the study; refer to Appendix 5

Discontinuation of the study at the request of Gilead, a regulatory agency or an institutional 
review board (IRB) or independent ethics committee (IEC)
6.7.
Clinical Laboratory Assessments
Blood and urine samples will be collected throughout the study as outlined below, within 
Section 6, and in Appendix 2.
6.7.1.
Blood Samples
Blood sample collection for the following laboratory analyses will be performed as specified:

Proviral DNA phenotype by the PhenoSense mAb Assay DNA at Monogram Biosciences at 
screening (Part 1) 

Bulk viral outgrowth phenotype at screening for subsequent testing

Proviral DNA genotype at screening for subsequent testing 


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
Hematology profile: complete blood count (CBC) with differential and platelet count at 
screening, Day 1, Weeks 4, 12, 26, 38, 52, ET, and post-ET follow-up visits

Chemistry profile: alkaline phosphatase, AST, ALT, gamma-glutamyltransferase (GGT), 
total bilirubin, direct and indirect bilirubin, total protein, albumin, lactate dehydrogenase 
(LDH), creatine phosphokinase (CPK), bicarbonate, blood urea nitrogen (BUN), calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, amylase 
(reflex lipase testing is performed in participants with total amylase  1.5  ULN) at 
screening, Day 1, Weeks 4, 12, 26, 38, 52, ET, and post-ET follow-up visits

Coagulation (prothrombin time, partial thromboplastin time, international normalized ratio) 
at screening

Thyroid function: TSH, T3, and free T4 at screening, Day 1, Weeks 4, 12, 26, 38, and 52

CD4+ cell count, CD8+ cell count, and CD4/CD8 ratio at screening, Day 1, Weeks 4, 12, 
26, 38, 52, ET, and post-ET follow-up visits

eGFR according to the Cockcroft-Gault formula for CLcr at screening, Day 1, Weeks 4, 12, 
26, 38, 52, ET, and post-ET follow-up visits
Male: (140 – age in years)  (weight in kg)  CLcr (mL/min)
72  (serum creatinine in mg/dL)
Female:(140 – age in years)  (weight in kg)  0.85  CLcr (mL/min)
72  (serum creatinine in mg/dL)

Serum follicle-stimulating hormone (FSH) test (required for female participants < 54 years of 
age who have stopped menstruating for ≥ 12 months but do not have documentation of 
ovarian hormonal failure; see Appendix 5) at screening

Serum pregnancy test (females of childbearing potential only) at screening, Weeks 4, 12, 
38, 52, ET, and post-ET follow-up visits). If the test is positive at screening, the participant 
will not be randomized. 

HBV and HCV serology: HBV surface antigen, HBV core antibody, and HBV surface 
antibody; HCV serology, with reflex to HCV RNA if positive at screening

HIV-1 RNA at all visits (except Days 2-8)

HIV reservoir assay on Day 1 (predose) and at Week 52

Plasma storage samples for virology testing at all visits (except screening, Days 2-8)

Immune biomarker collection on Day 1 (predose), and at Weeks 4, 26, 38, and 52 


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
PK serum samples for GS-5423 and GS-2872 will be collected in all participants as 
follows:
Note: PK samples obtained on Day 1 should be drawn from a separate catheter in the 
opposite arm from the one used for GS-5423 and GS-2872 IV infusion to avoid 
contamination.
The exact time of study drug administration and the exact time points (date and time) of 
collection of plasma samples must be carefully recorded. Serum PK samples for GS-5423 
and GS-2872 will be collected at the following time points for all participants:
Day 1: 0 hour (predose, ≤ 30 minutes prior to dosing of oral LEN for loading), within 
5 minutes after the end of the first antibody infusion (GS-5423) and within 5 minutes 
after the end of the second antibody infusion (GS-2872)
A single anytime sample at Weeks 4, 8, 12, 16, 20, 24, 26, 38, and 52
In case of ET prior to Week 52, applicable study drug single PK samples will be collected.

PK plasma samples for LEN will be collected in all participants as follows: 
PK samples should be drawn from a separate catheter in the opposite arm from the one used 
for GS-5423 and GS-2872 IV infusion to avoid contamination.
Day 1: 0 hour (predose, ≤ 30 minutes prior to dosing of oral LEN for loading), within 
5 minutes after the end of the first antibody infusion (GS-5423) and within 5 minutes 
after the end of the second antibody infusion (GS-2872)
A single anytime sample at Weeks 4, 8, 12, 16, 20, 24, 26, 38, and 52
In case of ET prior to Week 52, applicable study drug single PK samples will be 
collected.

Optional PK Substudy:
If participants provide specific separate consent, plasma samples for LEN will be collected at 
the following times in a subset of participants who will dose in clinic on Day 2 
(approximately n = 14 evaluable and n = 7 from each treatment group): 
Day 1: 0 hour (predose, ≤ 30 minutes prior to dosing of oral LEN for loading), within 
5 minutes after the end of the first antibody infusion (GS-5423) and within 5 minutes 
after the end of the second antibody infusion (GS-2872), 4 hours after oral LEN dose for 
loading, and 8 hours after oral LEN dose for loading
■
The time points for Day 1 collection are the same for both plasma PK for LEN and 
the Optional PK Substudy; make sure to only collect once on Day 1 (predose), within 
5 minutes after the end of the first antibody infusion (GS-5423), and within 5 minutes 
after the end of the second antibody infusion (GS-2872)


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Day 2: 0 hour (predose, ≤ 30 minutes prior to dosing of oral LEN for loading), and single 
anytime sample between 1 and 6 hours after oral LEN dose for loading
Day 8: single anytime sample

Immunogenicity Assessment:
Serum samples will be drawn on Day 1 (predose), Weeks 4, 12, 26, 38, and 52 

Pharmacodynamic Biomarkers: 
PBMC, whole blood, serum, and plasma samples will be collected on Day 1 (predose), 
Weeks 4, 26, 38, and 52 for exploratory analysis, which may include HIV-1 specific 
T-cell response, immune cell phenotyping, gene expression, antibody profiling, and 
soluble proteins (eg, cytokines, chemokines, inflammatory markers, etc.). FcgR SNP will 
be evaluated using samples collected at the Day 1 visit. 
If consent for pharmacogenomic testing is obtained, then a sample is to be collected for 
optional pharmacogenomic testing. This sample should be collected at the Day 1 visit but 
may be collected at any time during the study or at a separate study visit, if necessary.
6.7.2.
Urine Samples
Urine samples will be collected for the following laboratory analyses at every study visit, unless 
otherwise specified:

Urinalysis: including color and clarity, specific gravity, pH, glucose, ketones, bilirubin, 
urobilinogen, blood, nitrite, leukocyte esterase and microscopic (if microscopic elements are 
seen), urine protein, albumin, creatinine, phosphate, calcium, magnesium, and uric acid at 
screening, Day 1, Weeks 4, 12, 26, 38, 52, ET, and post-ET follow-up visits

Urine pregnancy test predose (females of childbearing potential only) on Day 1.
If the test is positive, confirmatory serum test should be performed and study drug dosing 
should be delayed until results obtained
6.7.3.
Blood and Urine Storage Samples
Any residual blood and urine samples collected at all visits (except the screening and ET visits) 
will be frozen and stored. These stored blood and urine samples may be used by Gilead or its 
research partners for HIV-1 genotyping/phenotyping assays or their development, for retesting 
the amount of HIV-1 in the blood, for measurement of antiviral drug levels in the blood, or for 
future testing to learn more about how the study drug has worked against HIV-1 or clinical 
laboratory testing to provide additional safety data. No human genetic testing will be performed 
without expressed consent of study participants. At the conclusion of this study, these samples 
may be retained in storage by Gilead for a period up to 15 years.


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6.8.
Management of Virologic Rebound and Virologic Failure
Virologic failure is defined as having a rebound of HIV-1 RNA ≥ 200 copies/mL at 
2 consecutive visits on or before Week 26, at Week 26, or at study drug discontinuation. 
Participants who meet criteria for VF will have samples sent for genotypic and phenotypic 
testing, will restart their baseline ARV regimen (or compatible regimen selected by the 
investigator), and will continue study follow-up but will not receive additional doses of the study 
regimen. 
6.8.1.
Virologic Rebound 
Participants who meet the criteria listed below will be considered to have VR (see Figure 6-1):

At any post-Day 1 visit, a rebound in HIV-1 RNA ≥ 50 copies/mL that is subsequently 
confirmed at the following scheduled or unscheduled visit; OR

Any participant with HIV RNA ≥ 50 copies/mL at study discontinuation or Week 26
At any post-Day 1 visit, if the HIV-1 RNA is ≥ 50 and < 200 copies/mL, a reflex HIV-1 RNA 
repeat test will be conducted on stored plasma samples by the study central laboratory, if 
available. If the repeat result is < 50 copies/mL, participants will resume scheduled study visits. 
If the repeat result is ≥ 50 copies/mL, participants will be asked to return to the clinic for a 
scheduled or unscheduled HIV-1 RNA retest (approximately 2 to 3 weeks after the date of the 
last test that resulted in HIV-1 RNA ≥ 50 copies/mL) for confirmation.

HIV-1 RNA < 50 copies/mL at the confirmation visit: participants will resume scheduled 
study visits

HIV-1 RNA ≥ 200 copies/mL at one visit except at study discontinuation or Week 26: 
participants will be asked to return to the clinic for a scheduled or unscheduled HIV-1 RNA 
(within 2 to 3 weeks after the date of last HIV-1 RNA) and resume scheduled study visits 
until confirmation results are available

Participants with HIV-1 RNA ≥ 200 copies/mL at two consecutive visits or at study 
discontinuation or Week 26 meet criteria for VF, refer to Section 6.8.2.

Participants with HIV-1 RNA between ≥ 50 and < 200 copies/mL at both the confirmation 
visit and the previous test, must be discussed with medical monitor.
6.8.2.
Virologic Failure 
Participants who meet the criteria listed below will be considered to have VF:


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
Participants with HIV-1 RNA ≥ 200 copies/mL on 2 consecutive visits will be considered to 
have VF. The blood sample from the confirmation visit will be the primary sample used for 
HIV-1 genotypic and phenotypic testing of capsid and env for study drugs (LEN, GS-5423, 
and GS-2872) and genotypic testing of RT, PI, and/or IN genes for the baseline ART 
regimen. Samples collected at baseline will be used for comparison of genotypic and 
phenotypic testing of study drugs at VF. The participant will be restarted on their baseline 
ART regimen (or compatible regimen selected by the investigator) and continue on study 
follow-up but will not receive additional doses of the study regimen. Participants will return 
for an unscheduled visit, 4 weeks after restarting their baseline ART regimen (or compatible 
regimen selected by the investigator) to confirm virologic suppression.

Participants with HIV-1 RNA ≥ 200 copies/mL at study discontinuation or Week 26 will be 
considered to have VF. The blood sample from the last visit or Week 26 with HIV-1 
RNA ≥ 200 (ie, not confirmable) will be the primary sample used for HIV-1 genotypic and 
phenotypic testing. The participant will be restarted on their baseline ART regimen 
(or compatible regimen selected by the investigator) and continue on study follow-up but will 
not receive additional doses of the study regimen. Participants will return for a unscheduled 
visit 4 weeks after restarting their baseline ART regimen (or compatible regimen selected by 
the investigator) to confirm virologic suppression. 

Participants with ongoing HIV-1 RNA ≥ 50 copies/mL but who do not meet criteria for VF 
must be discussed with the medical monitor.
For participants who are off study drug but remain on study, it will be the investigator’s 
discretion to manage VR.
Figure 6-1.
Virologic Rebound Schema
VF = virologic failure
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 


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6.9.
End of Study
The end of this study will be when the last participant has completed their final visit.
6.10.
Poststudy Care 
Once a participant has completed their study participation, the long-term care of the participant 
will return to the responsibility of their primary treating physicians.
6.11.
Sample Storage
The stored biological samples may be used by Gilead or its research partner for future testing to 
provide additional data to answer questions that relate to the main study. At the end of this study, 
these samples may be retained in storage by Gilead for a period up to 15 years or per country 
requirements. If participants provide additional specific consent, residual PK samples may be 
destroyed no later than 15 years after the end of the study or per country requirements. 


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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events and Serious Adverse Events
7.1.1.
Adverse Events
An AE is any untoward medical occurrence in a clinical study participant administered a study 
drug which does not necessarily have a causal relationship with the study drug. An AE can 
therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated 
with the use of a study drug, whether or not the AE is considered related to the study drug. 
Adverse events may also include pretreatment or posttreatment complications that occur as a 
result of protocol-specified procedures or special situations (Section 7.1.3). 
An AE does not include the following:

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion. 
The condition that led to the procedure may be an AE and must be reported.

Preexisting diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (eg, hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae (Section 7.1.3)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the ICF is signed and not related to a protocol-associated procedure is not an AE but 
rather considered to be preexisting and should be documented as medical history.
Preexisting events that increase in severity or change in nature after study drug initiation or 
during or as a consequence of participation in the clinical study will also be considered AEs.
7.1.2.
Serious Adverse Events
An SAE is defined as an event that, at any dose, results in the following:

Death

A life-threatening situation (Note: The term “life-threatening” in the definition of “serious” 
refers to an event in which the participant was at risk of death at the time of the event; it does 
not refer to an event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization


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
Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: Such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the participant or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. 
7.1.3.
Study Drugs and Gilead Concomitant Therapy Special Situations Reports
Special situation reports (SSRs) include all reports of medication error, abuse, misuse, overdose, 
occupational exposure, drug interactions, exposure via breastfeeding, unexpected benefit, 
transmission of infectious agents via the product, counterfeit of falsified medicine, and 
pregnancy regardless of an associated AE. 
Medication error is any unintentional error in the prescribing, dispensing, preparation for 
administration or administration of a study drug while the medication is in the control of a health 
care professional, patient, or consumer. Medication errors may be classified as a medication error 
without an AE, which includes situations of missed dose, medication error with an AE, 
intercepted medication error, or potential medication error.
Abuse is defined as persistent or sporadic intentional excessive use of a study drug by a 
participant.
Misuse is defined as any intentional and inappropriate use of a study drug that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a study 
drug given per administration or cumulatively which is above the maximum recommended dose 
as per protocol or in the product labeling (as it applies to the daily dose of the participant in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the participant has taken the excess dose(s). Overdose cannot be established 
when the participant cannot account for the discrepancy, except in cases in which the 
investigator has reason to suspect that the participant has taken the additional dose(s).
Occupational exposure is defined as exposure to a study drug as a result of one’s professional or 
nonprofessional occupation.
Drug interaction is defined as any drug/drug, drug/food, or drug/device interaction.


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Unexpected benefit is defined as an unintended therapeutic effect where the results are judged to 
be desirable and beneficial. 
Transmission of infectious agents is defined as any suspected transmission of an infected agent 
through a Gilead study drug.
Counterfeit or falsified medicine: Any study drug with a false representation of (a) its identity, 
(b) its source, or (c) its history.
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified sub investigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Study Drugs and Procedures
The investigator or qualified sub investigator is responsible for assessing the relationship to 
study drug) using clinical judgment and the following considerations:

No: Evidence exists that the AE has an etiology other than the study drug. For SAEs, an 
alternative causality must be provided (eg, preexisting condition, underlying disease, 
intercurrent illness, concomitant medication).

Yes: There is reasonable possibility that the AE may have been caused by the study drug).
It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of AE reporting. 
The relationship to study procedures (eg, invasive procedures such as venipuncture, biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the AE has an etiology other than the study procedure.

Yes: The AE occurred as a result of protocol procedures (eg, venipuncture).
7.2.2.
Assessment of Severity 
The severity of AEs will be graded using the Division of AIDS (DAIDS) Table for Grading the 
Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017 (Appendix 4). For 
each episode, the highest grade attained should be reported as defined in the toxicity grading 
scale. 
The Common Terminology Criteria for Adverse Events (CTCAE) Version 5 grading scale will 
be used to grade AEs determined to be infusion reactions.


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7.3. 
Investigator Reporting Requirements and Instructions  
7.3.1. 
Requirements for Collection Prior to Study Drug Initiation 
After informed consent, but prior to initiation of study drug, the following types of events must 
be reported on the applicable eCRFs: all SAEs and AEs related to protocol-mandated procedures. 
7.3.2. 
Adverse Events 
Following initiation of study drug, collect all AEs, regardless of cause or relationship, until the 
end of the protocol-defined posttreatment follow-up period and report them on the eCRFs as 
instructed. 
All AEs should be followed up until resolution or until the AE is stable, if possible. Gilead may 
request that certain AEs be followed beyond the protocol-defined follow-up period. 
7.3.3. 
Serious Adverse Events 
All SAEs, regardless of cause or relationship, that occurs after the participant first consents to 
participate in the study (ie, signing the ICF) and throughout the duration of the study, including 
the posttreatment follow-up visit, must be reported on the applicable eCRFs and Global Patient 
Safety (GLPS) as instructed below in this section. This also includes any SAEs resulting from 
protocol-associated procedures performed after ICF is signed. 
Any SAEs and deaths that occur throughout the duration of the study, including the 
protocol-required posttreatment follow-up period, regardless of causality, should also be 
reported.  
Investigators are not obligated to actively seek SAEs after the protocol-defined follow-up period; 
however, if the investigator learns of any SAEs that occur after the protocol-defined follow-up 
period has concluded and the event is deemed relevant to the use of study drug, the investigator 
should promptly document and report the event to Gilead GLPS. 
Instructions for reporting SAEs are described in Section 7.4.1. 
7.3.4. 
Study Drug Special Situations Reports 
All study drug SSRs that occur from study drug initiation and throughout the duration of the 
study, including the posttreatment follow-up visit, must be reported to GLPS (Section 7.4.2). 
Adverse events and SAEs resulting from SSRs must be reported in accordance to the AE and 
SAE reporting guidance (Section 7.4). 


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7.3.5. 
Concomitant Therapy Reports 
7.3.5.1. 
Gilead Concomitant Therapy Special Situations Report 
Special situation reports involving a Gilead concomitant therapy (not considered study drug), 
that occurs after the participant first consents to participate in the study (ie, signing the informed 
consent) and throughout the duration of the study, including the posttreatment follow-up visit, 
must be reported to Gilead GLPS utilizing the paper SSR (Section 7.4.2). 
7.3.5.2. 
Non-Gilead Concomitant Therapy Report 
Special situations involving non-Gilead concomitant medications does not need to be reported on 
the SSR form; however, for special situations that result in AEs due to a non-Gilead concomitant 
medication, the AE should be reported on the AE form.  
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation. 
All clinical sequelae in relation to these SSRs will be reported as AEs or SAEs at the same time 
using the AE eCRF and/or the SAE report form. Details of the symptoms and signs, clinical 
management, and outcome will be reported, when available. 
7.4. 
Reporting Process for Serious Adverse Events and Special Situation Reports 
7.4.1. 
Serious Adverse Event Reporting Process 
 For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be transmitted by email or fax when requested and applicable. 
Transmission of such documents should occur without personal participant identification, 
maintaining the traceability of a document to the participant identifiers. 
 Additional information may be requested to ensure the timely completion of accurate safety 
reports. 
 Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the participant’s eCRF and the SAE narrative section of the Safety 
Report Form eCRF. 
7.4.1.1. 
Electronic Serious Adverse Event Reporting Process 
 Site personnel will record all SAE data on the applicable eCRFs and from there transmit the 
SAE information to Gilead GLPS within 24 hours of the investigator’s knowledge of the 
event from ICF signature throughout the duration of the study, including the 
protocol-required posttreatment follow-up period.  


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
If it is not possible to record and transmit the SAE information electronically, record the SAE 
on the paper SAE reporting form and transmit within 24 hours:
Gilead GLPS
Email: 
 
or
Fax: 

If an SAE has been reported via a paper form because the eCRF database has been locked, no 
further action is necessary. If the database is not locked, any SAE reported via paper must be 
transcribed as soon as possible on the applicable eCRFs and transmitted to GLPS.
7.4.2.
Special Situations Reporting Process 
7.4.2.1.
Electronic Special Situations Reporting Process for Study Drug

Site personnel will record all SSR data on the applicable eCRFs and from there transmit the 
SSR information to Gilead GLPS from study drug initiation throughout the duration of the 
study, including the protocol-required posttreatment follow-up period. 

If for any reason it is not possible to record the SSR information electronically, record the 
SSR on the paper special situation reporting form and transmit to:
Gilead GLPS
Email: 
 
or
Fax: 

If an SSR has been reported via a paper form because the eCRF database has been locked, no 
further action is necessary. If the database is not locked, any SSR reported via paper must be 
transcribed as soon as possible on the applicable eCRFs and transmitted to GLPS. 

See Section 7.4.2.2 for instructions on reporting special situations with Gilead concomitant 
medications. 
PPD
PPD
PPD
PPD


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7.4.2.2.
Reporting Process for Gilead Concomitant Medications

Special situations that involve Gilead concomitant medications that are not considered study 
drug must be reported within 24 hours of the investigator’s knowledge of the event to Gilead 
GLPS utilizing the paper special situations report form to:
Gilead GLPS
Email: 
 
or
Fax: 

Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.

Special situations involving non-Gilead concomitant medications do not need to be reported 
on the SSR form; however, special situations that result in AEs due to a non-Gilead 
concomitant medication, must be reported as an AE.
7.4.2.3.
Pregnancy Reporting Process

The investigator should report pregnancies in female study participants and/or female 
partners of male participants that are identified after initiation of study drug and throughout 
the study, including the poststudy drug follow-up period, to Gilead GLPS using the 
pregnancy report form within 24 hours of becoming aware of the pregnancy. Contact details 
for transmitting the pregnancy report form are as follows:
Gilead GLPS
Email: 
 
or
Fax: 

The pregnancy itself is not considered an AE, nor is an induced elective abortion to terminate 
a pregnancy without medical reasons.

All other premature terminations of pregnancy (eg, a spontaneous abortion, an induced 
therapeutic abortion due to complications or other medical reasons) must be reported within 
24 hours as an SAE, as described in Section 7.4.1. The underlying medical reason for this 
procedure should be recorded as the AE term.

A spontaneous abortion is always considered to be an SAE and will be reported as described 
in Section 7.4.1. Furthermore, any SAE occurring as an adverse pregnancy outcome 
poststudy must be reported to the Gilead GLPS.
PPD
PPD
PPD
PPD


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
The participant should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome of the pregnancy/partner pregnancy should be reported to Gilead 
GLPS using the pregnancy outcome report form. If the end of the pregnancy/partner 
pregnancy occurs after the study has been completed, the outcome should be reported 
directly to Gilead GLPS. Gilead GLPS contact information is as follows: email: 
 and fax: 
 

Refer to Appendix 5 for Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements.
7.5.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the European Union (EU) Clinical Trials Directive (2001/20/EC) and 
relevant updates, and other country-specific legislation or regulations, Gilead may be required to 
expedite to worldwide regulatory agencies reports of SAEs which may be in the form of 
line-listings, serious adverse drug reactions (SADRs), or suspected unexpected serious adverse 
reactions (SUSARs). In accordance with the EU Clinical Trials Directive (2001/20/EC), Gilead 
or a specified designee will notify worldwide regulatory agencies and the relevant IEC in 
concerned member states of applicable SUSARs as outlined in current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the IB or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study drug. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy. 
7.6.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, and urinalysis) that 
require medical or surgical intervention or lead to study drug interruption, modification, or 
discontinuation must be recorded as an AE, as well as an SAE, if applicable. In addition, 
laboratory or other abnormal assessments (eg, ECG, x-rays, vital signs) that are associated with 
signs and/or symptoms must be recorded as an AE or SAE if they meet the definition of an AE 
or SAE as described in Sections 7.1.1 and 7.1.2. If the laboratory abnormality is part of a 
syndrome, record the syndrome or diagnosis (eg, anemia), not the laboratory result (ie, decreased 
hemoglobin).
Severity should be recorded and graded according to the DAIDS toxicity grading scale, 
Version 2.1 (Appendix 4). For AEs associated with laboratory abnormalities, the event should be 
graded on the basis of the clinical severity in the context of the underlying conditions; this may 
or may not be in agreement with the grading of the laboratory abnormality.
The CTCAE Version 5 grading scale will be used to grade AEs determined to be infusion-related 
reactions or cytokine release syndrome (see Table 7-1).
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Table 7-1.
The Common Terminology Criteria for Adverse Events (CTCAE) 
Version 5 Grading Scale
General Disorders and Administration Site Conditions
CTCAE Term
Grade 
1
Grade 
2
Grade 
3
Grade 
4
Grade 
5
Infusion-related 
reaction
Mild transient 
reaction; infusion 
interruption not 
indicated; 
intervention not 
indicated
Therapy or 
infusion 
interruption 
indicated but 
responds promptly 
to symptomatic 
treatment 
(eg, antihistamines, 
NSAIDS, 
narcotics, 
IV fluids); 
prophylactic 
medications 
indicated for 
≤ 24 hours
Prolonged 
(eg, not rapidly 
responsive to 
symptomatic 
medication and/or 
brief interruption 
of infusion); 
recurrence of 
symptoms 
following initial 
improvement; 
hospitalization 
indicated for 
clinical sequelae
Life-threatening 
consequences; 
urgent 
intervention 
indicated
Death
Definition: A disorder characterized by adverse reaction to the infusion of pharmacological or biological 
substances.
Cytokine release 
syndrome
Fever with or 
without 
constitutional 
symptoms
Hypotension 
responding to 
fluids; hypoxia 
responding to < 
40% O2
Hypotension 
managed with one 
pressor; hypoxia 
requiring ≥ 40% 
O2
Life-threatening 
consequences; 
urgent 
intervention 
indicated
Death
Definition: A disorder characterized by fever, tachypnea, headache, tachycardia, hypotension, rash, and/or 
hypoxia caused by the release of cytokines.
Navigational Note: Also consider reporting other organ dysfunctions including neurological toxicities such as: 
Psychiatric disorders: Hallucinations or Confusion; Nervous system disorders: Seizure, Dysphasia, Tremor, or 
Headache.
IV = intravenous; NSAIDs = nonsteroidal antiinflammatory drugs
7.7.
Toxicity Management 
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 3, and as outlined below:
Grade 3 or 4 clinically significant laboratory abnormalities should be confirmed by repeat testing 
as soon as possible, and preferably within 3 calendar days after receipt of the original test results.
Treatment-emergent toxicities will be noted by the investigator and brought to the attention of 
the Gilead medical monitor, and the appropriate course of action will be discussed and decided. 
Whether or not considered treatment-related, all participants experiencing AEs must be 
monitored periodically until symptoms subside, any abnormal laboratory values have resolved or 
returned to baseline levels or they are considered irreversible, or until there is a satisfactory 
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Any questions regarding toxicity management should be directed to the Gilead medical monitor.
All clinical sequelae in relation to these SSRs will be reported as AEs or SAEs at the same time 
using the AE eCRF and/or the SAE report form. Details of the symptoms and signs, clinical 
management, and outcome will be reported, when available.
7.7.1.
Management of Adverse Events of Injection Site Reactions of Grade 3 or 
Higher or Persisting for More than 26 Weeks
In clinical studies of SC LEN, Grade 3 or higher AEs of injections site reactions (ISRs) were 
uncommon. Some participants experienced AEs of injection site nodule and induration, which 
decreased in size over 6 months or longer. For AEs of ISRs related to SC LEN administered 
from a borosilicate vial that are Grade 3 or higher or persisting for more than 26 weeks, 
particularly nodule and/or induration, the investigator must contact the Medical Monitor and 
obtain consultation with an independent dermatologist to evaluate the ISRs. 
If clinically indicated as determined by the independent dermatologist, a biopsy of the SC 
injection site may be performed. The histopathology should be reviewed by an independent 
dermatopathologist; if a dermatopathologist is not locally available, the histopathology may be 
reviewed by an otherwise medically qualified person. 
Photographic documentation of the ISRs that meet the criteria above is recommended, if 
possible, but is not mandatory. If obtained, the documentation may be shared by the investigator 
with the independent dermatologist or dermatopathologist and may be requested by the sponsor. 
7.7.2.
Management of Other Toxicities
Unless otherwise specified in Section 7.7, toxicities will be managed according to the guidelines 
below.

All clinically significant Grade 3 and 4 laboratory abnormalities should be repeated within 
3 calendar days to confirm toxicity grade. Confirmation of toxicity grade is required prior to 
the next dose of investigational medicinal product for any Grade 3 and 4 laboratory 
abnormality that in the opinion of the investigator is clinically significant and may pose a risk 
to the participant’s safety.

Clinical events and clinically significant laboratory abnormalities will be graded according to 
the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities (refer 
to Appendix 4).
Any questions regarding toxicity management should be directed to the Gilead medical monitor.
7.7.2.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event Management of 
Clinical and Laboratory Adverse Events

Grade 1 or 2 laboratory abnormality or clinical event
Continue investigational medicinal product at the discretion of the investigator.


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7.7.2.2.
Grades 3 Laboratory Abnormality or Clinical Event

For Grade 3 clinically significant laboratory abnormality or clinical event, investigational 
medicinal product may be continued if the event is considered to be unrelated to 
investigational medicinal product.

For a Grade 3 clinical event, or clinically significant laboratory abnormality confirmed by 
repeat testing, that is considered to be related to investigational medicinal product, 
investigational medicinal product should be withheld until the toxicity returns to ≤ Grade 2.

If a laboratory abnormality recurs to ≥ Grade 3 following rechallenge with investigational 
medicinal product and is considered related to investigational medicinal product, then 
investigational medicinal product should be permanently discontinued, and the participant 
managed according to local practice including switching to an effective alternative ARV 
regimen with consideration of the long duration of exposure of investigational medicinal 
products and the risk of resistance if viremic. Recurrence of laboratory abnormalities 
considered unrelated to investigational medicinal product may not require permanent 
discontinuation.
7.7.2.3.
Grade 4 Laboratory Abnormality or Clinical Event
For a Grade 4 clinical event or clinically significant Grade 4 laboratory abnormality confirmed 
by repeat testing that is considered related to investigational medicinal product, investigational 
medicinal product should be permanently discontinued, and the participant managed according to 
local practice including switching to an effective alternative ARV regimen with consideration of 
the long duration of exposure of investigational medicinal products and the risk of resistance if 
viremic. The participant should be followed as clinically indicated until the laboratory 
abnormality returns to baseline or is otherwise explained, whichever occurs first. A clinically 
significant Grade 4 laboratory abnormality that is not confirmed by repeat testing should be 
managed according to the algorithm for the new toxicity grade.
Investigational medicinal product may be continued without dose interruption for a clinically 
nonsignificant Grade 3-4 laboratory abnormality (eg, CK elevation after strenuous exercise, or 
triglyceride elevation that is nonfasting or that can be medically managed) or a Grade 3-4 clinical 
event considered unrelated to investigational medicinal product.
7.8.
Safety Assessment Committee 
Per Gilead’s signal management and unblinding process, an internal Safety Assessment 
Committee can be requested to review unblinded clinical study for safety reasons. Members of 
the Safety Assessment Committee are not directly involved in conduct of the study. The Safety 
Assessment Committee provides recommendations to relevant safety committees (per Gilead’s 
signal management process) whether further actions are necessary to protect participants 
involved in the LEN development program.


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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
Study endpoints will be assessed in the Primary Cohort excluding the optional Pilot Cohort. 
Exploratory analysis may be conducted for the optional Pilot Cohort as applicable.
The primary objective of this study is as follows:

To evaluate the safety and tolerability of a combination of the bNAbs GS-5423 and GS-2872 
in combination with the HIV capsid inhibitor LEN 
The secondary objectives of this study are as follows:

To evaluate efficacy of the study regimens determined by the proportion of participants 
maintaining virologic suppression (HIV-1 RNA < 50 copies/mL) at Week 26 

To evaluate the PK of GS-5423, GS-2872, and LEN

To evaluate immunogenicity of GS-5423 and GS-2872

To evaluate the emergence of resistance to the components of the study regimens
The exploratory objectives are as follows:

To evaluate changes in HIV reservoir 

To evaluate changes in immune biomarkers
8.1.2.
Primary Endpoint
The primary endpoint of this study is as follows:

Incidence of treatment-emergent SAEs through Week 26
8.1.3.
Secondary Endpoints
The secondary endpoints of this study are as follows:

Proportion of participants with HIV-1 RNA < 50 copies/mL at Week 26 as defined by the 
FDA-defined snapshot algorithm

Proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 26 as defined by the 
FDA-defined snapshot algorithm


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
Proportion of participants with positive anti–GS-5423 or anti–GS-2872 antibodies at 
Week 26

Change from baseline in CD4+ cell counts at Week 26 

Treatment-emergent resistance to study drugs through Week 26

Incidence of treatment-emergent SAEs through Week 26, and treatment-emergent AEs 
through Week 26 

PK parameters for GS-5423, GS-2872, and LEN (and metabolites, if applicable) as 
appropriate: AUC0-t, AUClast, t1/2, Cmax, Tmax, Tlast, Ct through Week 52
8.1.4.
Other Endpoints of Interest
Other endpoints of interest are as follows:

Changes from baseline in HIV-1 reservoir in PBMC at postbaseline visits

Changes from baseline in HIV-1 specific T-cell response, immune cell phenotyping and 
proliferation, gene expression, antibody profiling, and plasma soluble proteins levels 
(eg, cytokines, chemokines, etc).
8.2.
Planned Analyses
8.2.1.
Interim Analysis 
Prior to the final analysis, interim analyses will be conducted. The results from these analyses 
may be submitted to scientific meetings and for publications and to regulatory agencies to seek 
guidance for the overall clinical development program.
8.2.1.1 
Gilead Data Review Committee Analysis
The GDRC will review the progress, unblinded safety and efficacy data of this study while the 
study is ongoing. The GDRC will convene after all participants enrolled in the Primary Cohort 
have completed their Week 12 visit or prematurely discontinued from the study. 
No formal stopping rules will be used by the GDRC for safety outcomes. Rather, a clinical 
assessment will be made to determine if the nature, frequency, and severity of AEs associated 
with a study regimen warrant the early termination of the study in the best interest of the 
participants. Based on safety and preliminary efficacy, the GDRC will determine whether the 
optional Pilot Cohort will be implemented. 
In addition, the GDRC may review unblinded safety and efficacy data on an ad hoc basis when 
there is a need for safety or efficacy monitoring. Refer to the GDRC Charter for additional 
details.


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8.2.2.
Primary Analysis 
The unblinded primary analysis will be conducted after all participants in the Primary Cohort 
have completed Week 26 visit or prematurely discontinued from the study.
8.2.3.
Final Analysis
The final analysis will be performed after all participants have completed the study or 
prematurely discontinued from the study, outstanding data queries have been resolved or 
adjudicated as unresolvable, and the data have been cleaned and finalized. The final analysis will 
include data from the Primary Cohort and may include data from the optional Pilot Cohort.
8.3.
Analysis Conventions
8.3.1.
Analysis Sets
8.3.1.1.
All Randomized
The primary analysis set for by-participant listings is defined as the All Randomized Analysis 
Set, which will include all participants who are randomized into the study.
8.3.1.2.
Efficacy
The primary analysis set for efficacy analysis is defined as the Full Analysis Set, which will 
include all randomized participants who have received at least one dose of the complete long 
acting study drug regimen (ie, SC LEN + GS-5423 and GS-2872). 
8.3.1.3.
Safety
The primary analysis set for safety analyses is defined as the Safety Analysis Set, which will 
include all randomized participants who have received at least one dose of study drug. 
All data collected during study will be included in the safety summaries.
8.3.1.4.
Pharmacokinetics
8.3.1.4.1.
Pharmacokinetic (PK) Substudy Analysis Set
The PK Substudy Analysis Set, which will include all randomized participants who are enrolled 
into the Optional PK Substudy, have received at least 1 dose of study drug, and have at least 
1 nonmissing concentration value reported by the PK laboratory for corresponding analytes (eg, 
LEN or metabolites, if applicable). 
8.3.1.4.2.
Pharmacokinetic (PK) Analysis Set
The PK Analysis Set, which will include all randomized participants who have received at least 
1 dose of study drug, and have at least 1 nonmissing concentration value reported by the PK 


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laboratory for the corresponding analytes (eg, GS-5423, GS-2872, LEN and metabolites, if 
applicable).
8.3.1.5.
Immunogenicity
The Immunogenicity Analysis Set will include all randomized participants who have received at 
least 1 dose of study drug and have had at least 1 nonmissing value for each immunogenicity 
evaluation (eg, anti–GS-5423 or anti–GS-2872).
8.3.2.
Data Handling Conventions
Natural logarithm transformation for key PK parameters, such as AUC and Cmax will be applied 
for PK analysis, as appropriate.
For summary statistics, PK concentration values below the limit of quantitation (BLQ) will be 
treated as zero at predose and one-half the lower limit of quantitation (LLOQ) for postdose time 
points.
Laboratory data that are continuous in nature but are less than the LLOQ or above the upper limit 
of quantitation (ULQ) will be imputed to the value of the lower or upper limit minus or plus 
1 significant digit, respectively (eg, if the result of a continuous laboratory test is < 20, a value of 
19 will be assigned).
Missing data can have an impact upon the interpretation of the study data. In general, values for 
missing data will not be imputed. However, a missing pretreatment laboratory result would be 
treated as normal (ie, no toxicity grade) for the laboratory abnormality summary.
8.4.
Demographic and Baseline Characteristics Analysis
Demographic and baseline measurements will be summarized using standard descriptive 
methods by treatment group. 
Demographic summaries will include sex, race/ethnicity, and age. Baseline data will include a 
summary of body weight, height, body mass index, and HIV-1 infection. 
8.5.
Efficacy Analysis
The proportion of participants with HIV-1 RNA < 50 copies/mL at Weeks 26 as defined by the 
FDA-defined snapshot algorithm will be summarized by treatment group and overall using the 
Full Analysis Set. The 95% CIs will be constructed on the exact method. These efficacy 
endpoints will be compared between treatment groups by Fisher exact test.
The proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Weeks 26 as defined by the 
FDA-defined snapshot algorithm will also be summarized by treatment group and overall in a 
similar manner. 


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The change from baseline in CD4+ cell count at Weeks 26 will be summarized by treatment 
group using descriptive statistics. Treatment-emergent resistance to study drugs will be 
summarized by treatment group.
8.6.
Safety Analysis
All safety data collected on or after the date that study drug was first dispensed up to the end of 
the protocol-defined follow-up period will be summarized by treatment group using Safety 
Analysis Set. Data for the pretreatment will be included in data listings. For participants who 
discontinue from only the oral LEN, only data collected up to 60 days after the last dose of the 
oral tablet will be included in the data summary.
8.6.1.
Extent of Exposure
A participant’s extent of exposure to study drug data will be generated from the study drug 
administration data. Exposure data will be listed. 
8.6.2.
Adverse Events
Clinical and laboratory AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). System organ class (SOC), high-level group term (HLGT), high-level 
term (HLT), preferred term, and lower-level term (LLT) will be attached to the clinical database.
Events will be summarized on the basis of the date of onset for the event. Any 
treatment-emergent AEs will be defined as any AE that begins on or after the date of first dose of 
study drug up to the end of the protocol-defined follow-up period. For participants who 
discontinue from only the oral LEN, only AEs collected up to 60 days after the last dose date 
will be considered treatment-emergent.
Summaries (number and percentage of participants) of treatment-emergent AEs (by SOC and 
preferred term) by treatment group will be provided. Additional summaries will include 
summaries for AEs by grade, investigator’s assessment of relationship to study drug, and effect 
on study drug dosing. 
8.6.3.
Laboratory Evaluations
Selected laboratory data will be summarized using only observed data. Data and change from 
baseline at all scheduled time points will be summarized by treatment group.
Graded laboratory abnormalities will be defined using the grading scheme in the DAIDS toxicity 
grading scale, Version 2.1 (Appendix 4).
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
one toxicity grade from baseline at any time postbaseline through the duration of the study, will 
be summarized by treatment group. If baseline data are missing, then any graded abnormality 
(ie, at least a Grade 1) will be considered treatment-emergent.


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Laboratory abnormalities that occur before the first dose of study drug will be included in a data 
listing.
8.6.4.
Other Safety Evaluations
Vital signs and ECG data will be summarized by treatment group.
8.7.
Adjustments for Multiplicity
No adjustments are planned.
8.8.
Pharmacokinetic Analysis 
Serum or plasma concentrations of each analyte (eg, GS-5423, GS-2872, and LEN [and 
metabolites, if applicable]) will be summarized by nominal sampling time and treatment using 
descriptive statistics for PK Substudy Analysis Set or PK Analysis Set as appropriate. 
Pharmacokinetic parameters (AUC0-t, AUClast, t1/2, Cmax, Tmax, Tlast, Ct, as appropriate) will be 
listed and summarized using descriptive statistics (eg, sample size, arithmetic mean, geometric 
mean, coefficient of variation %, SD, median, Q1, Q3, minimum, and maximum) by treatment 
group or overall, as appropriate. Serum or plasma concentrations of each analyte over time will 
be plotted in semi-logarithmic and linear formats as mean ± SD, and median (Q1, Q3), 
respectively.
8.9.
Immunogenicity Analysis
Immunogenicity to GS-5423 and GS-2872 will be evaluated based upon the incidence of 
anti-GS-5423 antibody and anti–GS-2872 antibody formation, respectively. The number and 
percentage of participants positive or negative for anti–GS-5423 antibody and anti–GS-2872 
antibody at each specified time point will be summarized, and supporting data including 
treatment, nominal visits, actual date and time of sampling, and anti–GS-5423 antibody and 
anti-GS-2872 antibody results will be included in a listing.


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8.10.
Sample Size
Although the sample size in this study is determined based on practical considerations and past 
experience with similar types of studies, assuming the 2 treatment groups have a similar 
virologic suppression rate, a total of 20 participants in the Primary Cohort will provide at least 
35% power to show the lower bound of 95% CI for Week 26 virologic response rate (HIV-1 
RNA < 50 copies/mL as defined by the FDA-defined snapshot algorithm) is greater than 83%. It 
was assumed that the virologic response rate at Week 26 was 95% (based on Gilead studies 
GS-US-380-1844 and GS-US-380-4030), 12% was a clinically tolerable margin for Phase 1b 
studies, and a one-sided exact test with a significance level 0.025 was used. The sample size and 
power calculations were made using the statistical software package PASS (Version 14, NCSS, 
LLC; Kaysville, Utah, USA). 
The estimated 95% CI for possible range of VF rate is provided in Table 8-1. For example, with 
1 VF event occurrence (5% estimated VF rate), a sample size of 20 participants can provide 
95% confidence that the true VF rate is unlikely to be higher than 24.9%.
Table 8-1.
Estimated Virologic Failure Rate and its 95% CIs (from the Clopper-
Pearson Exact CI) Based on Number of Virologic Failure Event in 
Each Group or in Total
Sample Size
20
Number of VF Events
0
1
2
3
4
Estimate of Incidence of VF (%)
0.0
5.0
10.0
15.0
20.0
Lower Bound of 95% CI (%)
0.0
0.1
1.2
3.2
5.7
Upper Bound of 95% CI (%)
16.8
24.9
31.7
37.9
43.7
VF = virologic failure
Software: SAS® Version 9.4. (SAS Institute Inc., Cary, NC, USA)
A total of approximately 20 participants in the Primary Cohort will provide reasonable 
assessment of safety and the descriptive PK profile throughout the study. A total of up to 
20 participants in the optional Pilot Cohort is based on practical considerations. 


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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with International Council 
for Harmonisation (of Technical Requirements for Pharmaceuticals for Human Use) (ICH) 
E6(R2) addendum to its guideline for GCP and applicable laws and regulations.
9.1.2.
Financial Disclosure
The investigator and subinvestigators will provide prompt and accurate documentation of their 
financial interest or arrangements with Gilead, or proprietary interests in the study drug during 
the course of a clinical study. This documentation must be provided prior to the investigator’s 
(and any subinvestigator’s) participation in the study. The investigator and subinvestigator agree 
to notify Gilead of any change in reportable interests during the study and for 1 year following 
completion of the study. Study completion is defined as the date when the last participant 
completes the protocol-defined activities.
9.1.3.
Institutional Review Board/Independent Ethics Committee Review and 
Approval
The investigator (or Gilead as appropriate according to local regulations) will submit this 
protocol, ICF, and any accompanying material to be provided to the participant (such as 
advertisements, participant information sheets, or descriptions of the study used to obtain 
informed consent) to an IRB/IEC. The investigator will not begin any study participant activities 
until approval from the IRB/IEC has been documented and provided as a letter to the 
investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IRB/IEC any modifications made to the protocol or any accompanying material to be 
provided to the participant after initial IRB/IEC approval, with the exception of those necessary 
to reduce immediate risk to study participants.
9.1.4.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study before undertaking any study-related procedures. The investigator 
must use the most current IRB- or IEC-approved ICF for documenting written informed consent. 
Each ICF (or assent as applicable) will be appropriately signed and dated by the participant or 
the participant’s legally authorized representative, and the person conducting the consent 
discussion, and also by an impartial witness if required by IRB or IEC or local requirements. 


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The ICF will inform participants about genomic testing and/or planned sample retention. In 
addition to the study-specific ICF to be signed by each participant participating in the study, 
participants will be required to document agreement to provide additional samples or to allow the 
use of the remainder of their already collected specimens for optional future research, in 
accordance with applicable regulations. In addition to the study-specific ICF to be signed by 
each participant participating in the study, participants will be required to document agreement to 
provide additional samples for optional genomic research. The results of the tests done on the 
samples will not be given to the participant or the investigator.
9.1.5.
Confidentiality
The investigator must ensure that participants’ anonymity will be strictly maintained and that 
their identities are protected from unauthorized parties. Only an identification code and any other 
unique identifier(s) as allowed by local law (such as year of birth) will be recorded on any form 
or biological sample submitted to Gilead or the laboratory. Laboratory specimens must be 
labeled in such a way as to protect participant identity while allowing the results to be recorded 
to the proper participant. Refer to specific laboratory instructions. NOTE: The investigator must 
keep a screening log with details for all participants screened and enrolled in the study, in 
accordance with the site procedures and regulations. Participant data will be processed in 
accordance with all applicable regulations. 
The investigator agrees that all information received from Gilead, including but not limited to the 
IB, this protocol, case report forms (CRFs)/eCRFs, the study drug information, and any other 
study information, remain the sole and exclusive property of Gilead during the conduct of the 
study and thereafter. This information is not to be disclosed to any third party (except employees 
or agents directly involved in the conduct of the study or as required by law) without prior 
written consent from Gilead. The investigator further agrees to take all reasonable precautions to 
prevent the disclosure by any employee or agent of the study site to any third party or otherwise 
into the public domain.
9.1.6.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following 2 categories: (1) investigator’s study file, and 
(2) participant clinical source documents.
The investigator’s study file will contain the protocol/amendments, paper or electronic 
completed participant CRFs, and governmental approval with correspondence, the ICF(s), drug 
records, staff curriculum vitae and authorization forms, and other appropriate documents and 
correspondence.


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The required source data should include sequential notes containing at least the following 
information for each participant:

Participant identification

Documentation that participant meets eligibility criteria, ie, medical history, physical 
examination, and confirmation of diagnosis (to support inclusion and exclusion criteria)

Documentation of the reason(s) a consented participant is not enrolled

Participation in study (including study number)

Study discussed and date of informed consent

Dates of all visits

Documentation that protocol-specific procedures were performed

Results of efficacy parameters, as required by the protocol

Start and end date (including dose regimen) of study drug, including dates of dispensing and 
return

Record of all AEs and other safety parameters (start and end date, and including causality 
and severity), and documentation that adequate medical care has been provided for any AE

Concomitant medication (including start and end date, dose if relevant; dose changes)

Date of study completion and reason for early discontinuation, if it occurs
All clinical study documents must be retained by the investigator for at least 2 years or according 
to local laws, whichever is longer, after the last approval of a marketing application in an ICH 
region (ie, US, Europe, or Japan) and until there are no pending or planned marketing 
applications in an ICH region; or, if no application is filed or if the application is not approved 
for such indication, for 2 years after the investigation is discontinued and regulatory authorities 
have been notified. Investigators may be required to retain documents longer if specified by 
regulatory requirements, by local regulations, or by an agreement with Gilead. The investigator 
must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
participant, appropriate copies should be made for storage away from the site.


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9.1.7.
Case Report Forms
An eCRF casebook will be completed by an authorized study personnel member whose training 
for this function is completed in the EDC system unless otherwise directed. The eCRF casebook 
will only capture the data required per the protocol schedule of events and procedures, unless 
collected by a nonelectronic data capture vendor system (eg, central laboratory). The 
Inclusion/Exclusion Criteria and Enrollment eCRFs should be completed only after all data 
related to eligibility are available. Data entry should be performed in accordance with the eCRF 
Completion Guidelines provided by the sponsor. Subsequent to data entry, a study monitor may 
perform source data verification. System-generated or manual queries will be issued in the EDC 
system as data discrepancies are identified by the study monitor or Gilead personnel who 
routinely review the data for completeness, correctness, and consistency. The site investigator, 
site coordinator, or other designee is responsible for responding to the queries in a timely 
manner, within the system, either by confirming the data as correct or updating the original entry, 
and providing the reason for the update (eg, data entry error). Original entries as well as any 
changes to data fields will be stored in the audit trail of the system. Regular oversight by the 
principal investigator of the data entered into the EDC system is expected to occur on an ongoing 
basis throughout the study to ensure quality and completeness. At a minimum, before any 
interim, final, or other time points (as instructed by Gilead), the investigator will apply his/her 
electronic signature to confirm that the forms have been reviewed and that the entries accurately 
reflect the information in the source documents. At the conclusion of the study, Gilead will 
provide the site investigator with a read-only archive copy of the data entered. This archive must 
be stored in accordance with the records retention requirements outlined in Section 9.1.6.
9.1.8.
Investigator Inspections
The investigator will make available all source documents and other records for this study to 
Gilead’s appointed study monitors, to IRBs/IECs, or to regulatory authority or health authority 
inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study participants, 
may be made only by Gilead. The investigator must submit all protocol modifications to the in 
accordance with local requirements and receive documented approval before modifications can 
be implemented.


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9.2.2.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency(ies) when 
applicable and in accordance with local regulatory requirements. Gilead will ensure that the 
report meets the standards set out in the ICH Guideline for Structure and Content of Clinical 
Study Reports (ICH E3). Note that an abbreviated report may be prepared in certain cases. For 
studies with sites in countries following the EU Regulation No. 536/2014, a CSR will be 
submitted within 1 year (6 months for pediatric studies, in accordance with Regulation [EC] 
No. 1901/2006) after the global end of study (as defined in Section 3.5).
Investigators in this study may communicate, orally present, or publish study data in scientific 
journals or other scholarly media in accordance with the Gilead clinical trial agreement.
9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol (eg, attendance at investigator meetings). If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to federal and state agencies any 
expenses paid or reimbursed for such services, including any clinical study payments, meal, 
travel expenses or reimbursements, consulting fees, and any other transfer of value.
9.3.2.
Access to Information for Monitoring
The monitor is responsible for routine review of the CRF/eCRF at regular intervals throughout 
the study to verify adherence to the protocol and the completeness, consistency, and accuracy of 
the data being entered on them. The monitor should have access to any participant records 
needed to verify the entries in the CRF/eCRF. The investigator agrees to cooperate with the 
monitor to ensure that any problems detected through any type of monitoring (central, on-site) 
are resolved.
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead medical monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both Gilead and the investigator reserve the right to terminate the study at any time. Should this 
be necessary, both parties will arrange discontinuation procedures and notify the participants, 
appropriate regulatory authority, and IRB In terminating the study, Gilead and the investigator 
will ensure that adequate consideration is given to the protection of the participants’ interests.


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10.
REFERENCES
Bar-On Y, Gruell H, Schoofs T, Pai JA, Nogueira L, Butler AL, et al. Safety and Antiviral 
Activity of Combination HIV-1 Broadly Neutralizing Antibodies in Viremic Individuals. 
Nat Med 2018;24:1701-7.
Burton DR, Mascola JR. Antibody responses to envelope glycoproteins in HIV-1 infection. 
Nature immunology 2015;16 (6):571-6.
Caskey M, Klein F, Lorenzi JC, Seaman MS, West AP, Jr., Buckley N, et al. Viraemia 
suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. 
Nature 2015;522 (7557):487-91.
Caskey M, Schoofs T, Gruell H, Settler A, Karagounis T, Kreider EF, et al. Antibody 10-1074 
suppresses viremia in HIV-1-infected individuals. Nat Med 2017;23 (2):185-91.
Claborn KR, Meier E, Miller MB, Leffingwell TR. A Systematic Review Of Treatment Fatigue 
Among HIV-Infected Patients Prescribed Antiretroviral Therapy. Psychology, health & 
medicine 2015;20 (3):1-11.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 
1976;16:31-41.
Kong R, Louder MK, Wagh K, Bailer RT, deCamp A, Greene K, et al. Improving neutralization 
potency and breadth by combining broadly reactive HIV-1 antibodies targeting major 
neutralization epitopes. J Virol 2015;89 (5):2659-71.
Mendoza P, Gruell H, Nogueira L, Pai JA, Butler AL, Millard K, et al. Combination Therapy 
With Anti-HIV-1 Antibodies Maintains Viral Suppression. Nature 2018;561:479-84.
Mouquet H, Scharf L, Euler Z, Liu Y, Eden C, Scheid JF, et al. Complex-type N-glycan 
recognition by potent broadly neutralizing HIV antibodies. Proc Natl Acad Sci U S A 
2012;109 (47):E3268-77.
Niessl J, Baxter AE, Mendoza P, Jankovic M, Cohen YZ, Butler AL, et al. Combination anti-
HIV-1 antibody therapy is associated with increased virus-specific T cell immunity. Nat 
Med 2020;26 (2):222-7.
Nishimura Y, Gautam R, Chun TW, Sadjadpour R, Foulds KE, Shingai M, et al. Early antibody 
therapy can induce long-lasting immunity to SHIV. Nature 2017;543 (7646):559-63.
Scheid JF, Mouquet H, Ueberheide B, Diskin R, Klein F, Oliveira TY, et al. Sequence and 
structural convergence of broad and potent HIV antibodies that mimic CD4 binding. 
Science 2011;333 (6049):1633-7.
Schneider E, Whitmore S, Glynn KM, Dominguez K, Mitsch A, McKenna MT. Revised 
surveillance case definitions for HIV infection among adults, adolescents, and children 
aged <18 months and for HIV infection and AIDS among children aged 18 months to 
<13 years--United States, 2008. MMWR Recomm Rep 2008;57 (RR-10):1-12.
UNAIDS. Fact Sheet - Global HIV Statistics 2021.  2021:
Wagh K, Seaman MS, Zingg M, Fitzsimons T, Barouch DH, Burton DR, et al. Potential of 
conventional & bispecific broadly neutralizing antibodies for prevention of HIV-1 
subtype A, C & D infections. PLoS pathogens 2018;14 (3):e1006860.


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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table
Appendix 3.
Management of Clinical and Laboratory Adverse Events
Appendix 4.
Toxicity Grading Scale for Severity of Adverse Events and Laboratory 
Abnormalities
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements
Appendix 6.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines)
Appendix 7.
Pandemic Risk Assessment and Mitigation Plan




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Appendix 2.
Study Procedures Table
Treatment Visits Window
(± 3 Days)
Follow-up Visits 
Window
(± 6 Days)
Study Procedure
Screeninga
Day 1
Day 2
Day 8
Wk 4
Wk 8
Wk 12
Wk 16
Wk 20
Wk 24
Wk 26
Wk 38
Wk 52
ET
Post-ET 
30-, 90-, 
and 180- 
Day FUb 
Written Informed Consent
X
Medical History 
X
Review Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Review AEs 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Complete Physical 
Examination
X
X
X
Focused Physical 
Examination
X
X
X
X
X
X
Height 
X
Weight 
X
X
X
X
X
X
X
X
X
Vital Signsc
X
X
X
X
X
X
X
X
X
Proviral DNA Phenotype
X
Bulk Viral Outgrowth 
Phenotype and Proviral DNA 
Genotype
X
Chemistry
X
X
X
X
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
X
X
Coagulation 
X
Thyroid Function 
X
X
X
X
X
X
X
CD4+, CD8+ Cell Count, 
CD4/CD8 Ratio
X
X
X
X
X
X
X
X
X


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Treatment Visits Window
(± 3 Days)
Follow-up Visits 
Window
(± 6 Days)
Study Procedure
Screeninga
Day 1
Day 2
Day 8
Wk 4
Wk 8
Wk 12
Wk 16
Wk 20
Wk 24
Wk 26
Wk 38
Wk 52
ET
Post-ET 
30-, 90-, 
and 180- 
Day FUb 
Serum Pregnancy Test
X
X
X
X
X
X
X
FSHd
X
Urinalysis
X
X
X
X
X
X
X
X
X
Urine Pregnancy Test
X
HBV & HCV Serology
X
HIV-1 RNA 
X
X
X
X
X
X
X
X
X
X
X
X
X
HIV-1 Genotype/Phenotypee
HIV Reservoir Assay 
X
X
eGFR
X
X
X
X
X
X
X
X
X
ECG
X
X
X
X
Immune Biomarker 
Collection
X
X
X
X
X
Plasma Storage Samples for 
Virology Testing
X
X
X
X
X
X
X
X
X
X
X
X
Immunogenicity Assessment 
Serum Sample
X
X
X
X
X
X
PD Biomarkers: PBMC, 
Whole Blood, Serum, Plasma
X
X
X
X
X
Serum PK samples (GS-5423 
& GS-2872)f
X
X
X
Plasma PK Sample for LENg
X
X
X
Single PK Sample (GS-5423 
& GS-2872)
X
X
X
X
X
X
X
X
X


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Treatment Visits Window
(± 3 Days)
Follow-up Visits 
Window
(± 6 Days)
Study Procedure
Screeninga
Day 1
Day 2
Day 8
Wk 4
Wk 8
Wk 12
Wk 16
Wk 20
Wk 24
Wk 26
Wk 38
Wk 52
ET
Post-ET 
30-, 90-, 
and 180- 
Day FUb 
Single Plasma PK Sample for 
LEN
X
X
X
X
X
X
X
X
X
Optional PK Substudy 
Sample 
X
X
X
Randomization
X
LEN Oral Administrationh
X
X
LEN SC Administrationi
X
GS-5423 IV Infusion 
Administrationi
X
GS-2872 IV Infusion 
Administrationi
X
Optional Pharmacogenomic 
Samplej
a.
For the Primary Cohort, screening procedures will be conducted in 2 parts: Part 2 will be performed once results of bNAb sensitivity testing from Part 1 are reviewed and 
participant is deemed eligible to proceed. For the optional Pilot Cohort, participants will be selected by the sponsor from the previously screened/failed participants in the 
Primary Cohort and will directly proceed to Screening Part 2 (no need to repeat Screening Part 1).
b.
Refer to Section 6.5.1 for Post-ET 30-, 90-, and 180-Day follow-up visits.

Counsel participant regarding the importance of continuing a complete ARV therapy in accordance to standard of care, and refer patient to an appropriate HIV treatment 
facility.
c.
Vital signs: blood pressure, pulse, respiration rate, and temperature. On Day 1, vital signs should be recorded prior to start of study drug administration and 30 minutes 
(± 10 minutes) after completion of the GS-2872 infusion.
d.
Serum FSH test (required for female participants < 54 years of age who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal 
failure; see Appendix 5)
e.
HIV-1 genotype and phenotype testing for participants with virologic failure. Refer to Section 6.8.2.
f.
PK serum samples will be collected in all participants for GS-5423 and GS-2872 as follows: 

The exact time of study drug administration and the exact time points (date and time) of collection of plasma samples must be carefully recorded.

Day 1: 0 hour (predose, ≤ 30 minutes prior to dosing of oral LEN for loading), within 5 minutes after the end of the first antibody infusion (GS-5423) and within 
5 minutes after the end of the second antibody infusion (GS-2872)

For ET visit, only single PK sample collection is required


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g.
PK plasma samples for LEN will be collected in all participants as follows: 

PK samples should be drawn from a separate catheter in the opposite arm from the one used for GS-5423 and GS-2872 IV infusion to avoid contamination.

Day 1: 0 hour (predose, ≤ 30 minutes prior to dosing of oral LEN for loading), within 5 minutes after the end of the first antibody infusion (GS-5423) and within 
5 minutes after the end of the second antibody infusion (GS-2872)

For ET visit, only single PK sample collection is required
h.
Participants will take oral LEN for loading on Day 1 at the clinic and self-administer on Day 2 at home, unless participating in the Optional PK Substudy.
i.
On Day 1, participants will receive study treatment consisting of oral and SC LEN, followed by GS-5423, then GS-2872, each administered as separate IV infusions. Infusion 
of GS-2872 will begin at least 15 minutes following, and up to 1 hour after, the completion of GS-5423 IV infusion. Participants will remain in a monitored clinical setting for 
at least 30 minutes after completion of GS-2872 infusion, and vital signs will be recorded 30 minutes (± 10 minutes) after completion of GS-2872 infusion. For the Day 1 
visit, all study drugs are to be administered on the same day. On Day 2, the participant will self-administer 2 tablets of oral LEN for loading (2 × 300 mg) at home at 
approximately the same time oral LEN for loading was administered on Day 1.
j.
If consent for optional pharmacogenomic testing is obtained, then a sample is to be collected at the Day 1 visit, but may be collected at any time during the study or at a 
separate poststudy visit, if necessary.


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Appendix 3.
Management of Clinical and Laboratory Adverse Events
Grade 3 or 4 laboratory abnormalities include drop in platelets to < 50,000/mm3.
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 


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Appendix 4.
Toxicity Grading Scale for Severity of Adverse Events and 
Laboratory Abnormalities
The Division of AIDS (DAIDS) scale is available at the following location: 
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf


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Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Definitions
a. Definition of Childbearing Potential
For the purposes of this study, a female born participant is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming postmenopausal, unless the 
participant is permanently sterile or has medically documented ovarian failure. 
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause. In 
addition, women of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle-stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female participant of any age.
b. Definition of Male Fertility
For the purposes of this study, a male born participant is considered of fertile after the initiation 
of puberty unless the participant is permanently sterile by bilateral orchidectomy or medical 
documentation.
2) Contraception Requirements for Female Participants
a) Study Drug Effects on Pregnancy and Hormonal Contraception
Nonclinical toxicity studies of lenacapavir (LEN, GS-6207) have demonstrated no adverse effect 
on fertility or embryo-fetal development. However, there are no clinical studies of LEN in 
pregnant women. Based on the available in vitro induction data, a drug-drug interaction with 
LEN and hormonal contraceptives that are not taken orally is not expected. Therefore, a barrier 
method with contraceptive steroids that are not taken orally is permitted in this study. However, 
LEN has insufficient data to exclude the possibility of a clinically relevant interaction with oral 
hormonal contraception that results in reduced contraception efficacy. Therefore, oral 
contraceptive steroids are not recommended as a contraceptive method either solely or as a part 
of a contraceptive regimen.
GS-2872 and GS-5423 are contraindicated in pregnancy as their teratogenicity/fetotoxicity 
profile is unknown. A reduction in the clinical efficacy of hormonal contraception is not 
expected as GS-2872 and GS-5423 are not cytokine modulators. As protein biologics, GS-2872 
and GS-5423 are not expected to be genotoxic but genotoxicity has not been evaluated in these 
compounds and so conservative contraceptive requirements are used in this study. Refer to the 
latest version of the investigator’s brochure (IB) for additional information.


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b) Contraception Requirements for Female Born Participants of Childbearing Potential
The inclusion of female born participants of childbearing potential requires using at least an 
acceptable effective contraceptive. They must have a negative serum pregnancy test at screening 
and a negative pregnancy test at the Day 1 visit prior to the dose of study drug. Pregnancy tests 
will be performed as defined by the study procedures in Appendix 2. In the event of a delayed 
menstrual period (over 1 month between menstruations), a pregnancy test must be performed to 
rule out pregnancy. This is even true for female born participants of childbearing potential with 
infrequent or irregular periods. Female born participants of childbearing potential must agree to 
1 of the following from screening until 700 days following the last dose of study drug:
Complete abstinence from intercourse of reproductive potential. Abstinence is an acceptable 
method of contraception only when it is in line with the participant’s preferred and usual 
lifestyle.
Or
Consistent and correct use of 1 of the following methods of birth control listed below:
Intrauterine device (IUD) with a failure rate of < 1% per year
Tubal sterilization
Essure® microinsert system (provided confirmation of success 3 months after procedure)
Vasectomy in the male born partner (provided that the partner is the sole sexual partner 
and had confirmation of surgical success 3 months after procedure)
Barrier methods (one female barrier and one male barrier must be used in combination):
■
Female barriers: Diaphragm with spermicide or Cervical cap with spermicide
■
Male barriers: Male condom (with or without spermicide)
Hormonal Methods that are not taken orally (each method must be used with a barrier 
method, preferably male condom):
■
Intrauterine hormone-releasing system (IUS) with a failure rate of < 1% per year
■
Injectable progesterone
■
Subdermal contraceptive implant
■
Transdermal contraceptive patch
■
Contraceptive vaginal ring


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Inclusion of methods of contraception in this list of permitted methods does not imply that the 
method is approved in any country or region. Methods should only be used if locally approved.
Female born participants must also refrain from egg donation and in vitro fertilization during 
treatment and until at least 700 days following the last dose of study drug.
3) Contraception Requirements for Male Participants
It is theoretically possible that a relevant systemic concentration may be achieved in a female 
partner from exposure of the male participant’s seminal fluid. Therefore, male participants with 
female partners of childbearing potential must use condoms during the study and until the end of 
the protocol-defined follow-up period. Additional contraception recommendations should also be 
considered if the female partner is not pregnant.
Male participants must also refrain from sperm donation during the study and until the end of the 
study protocol-defined follow-up period.
4) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (eg, calendar, ovulation, 
symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method. A female condom and a male condom should not be used 
together.
5) Procedures to be Followed in the Event of Pregnancy
Female participants will be instructed to notify the investigator if they become pregnant or 
suspect they are pregnant at any time from start of the study drug and throughout the study 
including the poststudy drug follow-up period. Study drug must be discontinued immediately, or 
interruption of study drug should be considered upon discussion with the medical monitor. 
Male participants whose partner has become pregnant or suspects she is pregnant from the start 
of study drug and throughout the study including the poststudy drug follow-up period needs to 
report the information to the investigator. Instructions for reporting pregnancy, partner 
pregnancy, and pregnancy outcome are outlined in Section 7.4.2.3.


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Appendix 6.
Definitions of Stage 3 Opportunistic Illnesses in HIV 
(CDC Guidelines)
Candidiasis of bronchi, trachea, or lungs
Candidiasis of esophagus
Cervical cancer, invasive
Coccidioidomycosis, disseminated or extrapulmonary
Cryptococcosis, extrapulmonary
Cryptosporidiosis, chronic intestinal ( 1 month duration)
Cytomegalovirus disease (other than liver, spleen or nodes)
Cytomegalovirus retinitis (with loss of vision)
Encephalopathy, HIV-related
Herpes simplex: chronic ulcer(s) ( 1 month duration); or bronchitis, pneumonitis or esophagitis
Histoplasmosis, disseminated or extrapulmonary
Isosporiasis, chronic intestinal ( 1 month duration)
Kaposi’s sarcoma
Lymphoma, Burkitt’s (or equivalent term)
Lymphoma, immunoblastic (or equivalent term)
Lymphoma, primary, of brain
Mycobacterium avium complex or Myobacterium kansasii, disseminated or extrapulmonary
Mycobacterium tuberculosis, of any site, pulmonary, disseminated or extrapulmonary
Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
Pneumocystis jirovecii (previously known as “Pneumocystis carinii) pneumonia
Pneumonia, recurrent
Progressive multifocal leukoencephalopathy
Salmonella septicemia, recurrent


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Toxoplasmosis of brain
Wasting syndrome attributed to HIV infection
CDC Stage-3-Defining Opportunistic Illnesses in HIV Infection - 2014 {Schneider 2008}


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Appendix 7.
Pandemic Risk Assessment and Mitigation Plan
During an ongoing pandemic, potential risks associated with participants being unable to attend 
study visits have been identified for this study. 
These risks can be summarized as follows:
1) Study drug supplies to sites:
Shipments of study drug could be delayed because of transportation issues. Without study 
drug participant would not be able to stay on the study drug as planned per protocol.
Mitigation plan: The sites' study drug inventory should be closely monitored. Site staff 
should notify Gilead or delegate if they foresee shortage in study drug inventory or if there is 
any interruption in local shipping service. Gilead will continue to monitor inventory at the 
study drug depot and study sites. Manual shipments will be triggered as necessary.
Participant safety monitoring and follow-up:
a) Participant may be unable or unwilling to come to the study site for their scheduled study 
visits as required per protocol.
Mitigation plan: For participants who may be unable or unwilling to visit the study site 
for their scheduled study visits as required per protocol, the PI or qualified delegate will 
conduct a virtual study visit, via phone or video conferencing, to assess the participant 
within target visit window date whenever possible. During the virtual study visit, the 
following information at minimum will be reviewed: 
i)
Confirm if participant has experienced any adverse events (AEs)/serious adverse 
events (SAEs)/special situations (including pregnancy) and follow-up on any 
unresolved AE/SAEs.
ii) Review current list of concomitant medications and document any new concomitant 
medications.
iii) Review study restrictions with the participant.
iv) Counsel the participant on the importance of obtaining the final safety laboratory 
assessments at their local lab. 


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b) Participant may be unable or unwilling to travel to the site for planned assessments (eg, 
safety blood draws); hence samples may not be sent for central laboratory analyses.
Mitigation plan: Local laboratories may be utilized as appropriate to monitor participant 
safety until the participant can return to the site for their regular scheduled and follow-up 
visits per protocol. Any laboratory assessments conducted at a local laboratory due to the 
pandemic will be documented accordingly. Pregnancy testing may be performed using a 
home urine pregnancy test if local laboratory pregnancy testing is not feasible.
Home health service provider may be utilized to perform protocol scheduled study visits 
at participant’s home as home healthcare visit to collect protocol-specified clinical 
laboratory samples and assessments, except for Screening, Day 1, Weeks 26, 52, and ET 
visits, if approved by site in compliance with local EC/IRB and national laws and 
regulations and participant’s consent.
c) Participants may be unable or unwilling to attend the study visit to sign an updated 
informed consent form (ICF) version.
Mitigation plan: The site staff will follow their approved consent process and remain in 
compliance with local EC/IRB and national laws and regulations. Remote consent will be 
allowed if has been approved by the local EC/IRB. The consent process will be 
documented and confirmed by normal consent procedure at the earliest opportunity.
Protocol and monitoring compliance:
d) Protocol deviations may occur, in case scheduled visits cannot occur as planned per 
protocol.
Mitigation plan: If it is not possible to complete a required procedure, an unscheduled 
visit should be conducted as soon as possible when conditions allow. The situation should 
be recorded and explained as a protocol deviation. Any missed participant visits or 
deviation to the protocol due to the pandemic must be reported in the eCRF and described 
in the clinical study report. Any virtual study visits that are conducted in lieu of clinic 
visits due to the pandemic will be documented as a protocol deviation related to the 
pandemic.
e) Monitors may be unable to carry out source data review (SDR) or source data verification 
(SDV), or study drug accountability or assess protocol and GCP compliance. This may 
lead to delays in SDV, an increase in protocol deviations, or under reporting of AEs.
Mitigation plan: The study monitor is to remain in close communication with the site to 
ensure data entry and query resolution. The study monitor is to reference the Study 
Monitoring Plan for guidance on how to conduct a remote monitoring visit. The study 
staff is to save and document all relevant communication in the study files. The status of 
sites that cannot accept monitoring visits and/or participants on site, must be tracked 
centrally and updated on a regular basis.


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Missing data and data integrity:
f)
There may be an increased amount of missing data due to participants missing 
visits/assessments. This could have an impact on the analysis and the interpretation of 
clinical study data. 
Mitigation plan: Implications of a pandemic on methodological aspects for the study will 
be thoroughly assessed and documented, and relevant actions will be taken as appropriate 
(ie, modification of the statistical analysis plan) and in compliance with Regulatory 
Authorities’ guidance. Overall, the clinical study report will describe the impact of the 
pandemic on the interpretability of study data. 
Risks will be assessed continuously, and temporary measures will be implemented to mitigate 
these risks as part of a mitigation plan, as described above. These measures will be 
communicated to the relevant stakeholders as appropriate and are intended to provide alternate 
methods that will ensure the evaluation and assessment of the safety of participants who are 
enrolled in this study. 
Since these potential risks are considered mitigated with the implementation of these measures, 
the expected benefit-risk assessment of study drug(s) in study participants remains unchanged.


protocol GS-US-536-5816 amendment 2
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
 eSigned 30-Mar-2022
18:30:31
PPD
PPD

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 1b Randomized, Blinded, Proof-of-Concept Study to 
Evaluate the Safety and Efficacy of Broadly Neutralizing 
Antibodies (bNAbs) GS-5423 and GS-2872 in Combination 
with Capsid Inhibitor Lenacapavir (GS-6207) in Virologically 
Suppressed Adults with HIV-1 Infection
Name of Test Drug:
Broadly Neutralizing Antibodies (bNAbs GS-5423 and 
GS-2872) +Lenacapavir (LEN; GS-6207)
Study Number:
GS-US-536-5816
Protocol Version (Date):
Amendment 2 (30 March 2022)
Analysis Type:
Week 26 Analysis 
Analysis Plan Version:
Version 1.0
Analysis Plan Date:
02 August 2022
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
 
PPD


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TABLE OF CONTENTS
TABLE OF CONTENTS................................................................................................................................................2
LIST OF IN-TEXT TABLES .........................................................................................................................................3
LIST OF ABBREVIATIONS.........................................................................................................................................4
1.
INTRODUCTION..................................................................................................................................................5
1.1.
Study Objectives........................................................................................................................................5
1.2.
Study Design .............................................................................................................................................5
1.3.
Sample Size and Power .............................................................................................................................8
2.
TYPE OF PLANNED ANALYSIS......................................................................................................................10
2.1.
Interim Analyses......................................................................................................................................10
2.1.1.
Gilead Data Review Committee (GDRC) Analysis ..............................................................10
2.1.2.
Primary Analysis ...................................................................................................................10
2.2.
Final Analysis..........................................................................................................................................10
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES.............................................................................11
3.1.
Analysis Sets ...........................................................................................................................................12
3.1.1.
All Randomized Analysis Set................................................................................................12
3.1.2.
Full Analysis Set....................................................................................................................12
3.1.3.
Per Protocol Analysis Set ......................................................................................................12
3.1.4.
Safety Analysis Set................................................................................................................13
3.2.
Participant Grouping ...............................................................................................................................13
3.3.
Strata and Covariates...............................................................................................................................14
3.4.
Examination of Participant Subgroups....................................................................................................14
3.5.
Multiple Comparisons .............................................................................................................................14
3.6.
Missing Data and Outliers.......................................................................................................................14
3.6.1.
Missing Data..........................................................................................................................14
3.6.2.
Outliers ..................................................................................................................................14
3.7.
Data Handling Conventions and Transformations ..................................................................................14
3.8.
Analysis Visit Windows..........................................................................................................................15
3.8.1.
Definition of Key Dates and Study Day................................................................................15
3.8.2.
Analysis Visit Windows........................................................................................................16
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window .................................................................................................................................18
4.
PARTICIPANT DISPOSITION ..........................................................................................................................19
4.1.
Participant Enrollment and Disposition...................................................................................................19
4.2.
Extent of Study Drug Exposure and Adherence......................................................................................20
4.2.1.
Duration of Exposure to Study Drug.....................................................................................20
4.2.2.
Adherence to Study Drug ......................................................................................................20
4.3.
Protocol Deviations .................................................................................................................................21
5.
BASELINE CHARACTERISTICS .....................................................................................................................22
5.1.
Demographics and Baseline Characteristics ...........................................................................................22
5.2.
Other Baseline Characteristics ................................................................................................................22
5.3.
Medical History.......................................................................................................................................22
6.
EFFICACY ANALYSES.....................................................................................................................................23
6.1.
Primary Efficacy Endpoint......................................................................................................................23
6.2.
Secondary Efficacy Endpoints ................................................................................................................24


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6.2.1.
Definition of the Secondary Efficacy Endpoints...................................................................24
6.2.2.
Analysis of the Secondary Efficacy Endpoints .....................................................................25
6.3.
Other Efficacy Endpoints ........................................................................................................................25
6.3.1.
Definition of the Other Efficacy Endpoints...........................................................................25
6.3.2.
Analysis of the Other Efficacy Endpoints.............................................................................25
6.4.
Changes from Protocol-Specified Efficacy Analyses .............................................................................26
7.
SAFETY ANALYSES.........................................................................................................................................27
7.1.1.
Adverse Event Dictionary .....................................................................................................27
7.1.2.
Adverse Event Severity .........................................................................................................27
7.1.3.
Relationship of Adverse Events to Study Drug.....................................................................27
7.1.4.
Serious Adverse Events.........................................................................................................27
7.1.5.
Treatment-Emergent Adverse Events....................................................................................28
7.1.6.
Summaries of Adverse Events and Deaths............................................................................29
7.1.7.
Additional Analysis of Adverse Events ................................................................................30
7.2.
Laboratory Evaluations ...........................................................................................................................31
7.2.1.
Summaries of Numeric Laboratory Results ..........................................................................32
7.2.2.
Graded Laboratory Values ....................................................................................................32
7.3.
Body Weight and Vital Signs..................................................................................................................34
7.4.
Prior and Concomitant Medications........................................................................................................34
7.4.1.
Nonstudy Drug Antiretroviral Medications...........................................................................34
7.4.2.
Prior and Concomitant Non-ARV Medications ....................................................................34
7.5.
Electrocardiogram Results.......................................................................................................................35
7.6.
Other Safety Measures ............................................................................................................................35
7.7.
Changes from Protocol-Specified Safety Analyses.................................................................................35
8.
REFERENCES.....................................................................................................................................................36
9.
SOFTWARE.........................................................................................................................................................37
10.
SAP REVISION...................................................................................................................................................38
11.
APPENDICES......................................................................................................................................................39
LIST OF IN-TEXT TABLES 
Table 1-1.
Estimated Virologic Failure Rate and its 95% CIs (from the Clopper-fPearson Exact 
CI) Based on Number of Virologic Failure Event in Each Group or in Total...........................9
Table 3-1.
Participants Excluded from Week 26 PP Analysis Set Due to Premature 
Discontinuation of Study Drug and/or Missing HIV-1 RNA Assessment in Week 26 
Analysis Window ....................................................................................................................13
Table 3-2.
Analysis Windows for HIV-1 RNA ........................................................................................17
Table 3-3.
Analysis Windows for CD4+ cell count, CD8+ cell count, Chemistry, Hematology, 
Urinalysis, Vital Signs, and Weight ........................................................................................17
Table 3-4.
Analysis Windows for ECG ....................................................................................................17


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LIST OF ABBREVIATIONS
AE
adverse event
B/F/TAF
Bictegravir/Emtricitabine/Tenofovir Alafenamide
BIC
Bictegravir
BLQ
below the limit of quantitation
BMI
body mass index
CI
confidence interval
CK
creatine kinase
CRF
case report form
CSR
clinical study report
DMC
data monitoring committee
ECG
Electrocardiogram
eGFRCG
estimated glomerular filtration rate using Cockcroft-Gault formula
FAS
Full Analysis Set
Hb
Hemoglobin
HLT
high-level term
ITT
intent to treat
LOQ
limit of quantitation
LPLV
last patient last visit
MedDRA
Medical Dictionary for Regulatory Activities
PBMC 
peripheral blood mononuclear cell
POC
Proof-of-Concept
PT
preferred term
PWH
people with HIV
Q1, Q3
first quartile, third quartile
SAP
statistical analysis plan
SC
subcutaneous 
SD
standard deviation
SE
standard error
SOC
system organ class
TAF
tenofovir alafenamide
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
TFV
tenofovir
TFV-DP
tenofovir diphosphate
WHO
World Health Organization


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) of Week 26 primary analysis for 
the primary cohort of Study GS-US-536-5816. A formal primary analysis will be performed 
when all participants in primary cohort have completed Week 26 visit or prematurely 
discontinued from study. 
This SAP is based on the study protocol amendment 2 dated 30 March 2022 and the electronic 
case report form (eCRF). The SAP will be finalized prior to data finalization for the Week 26 
primary analysis. 
1.1.
Study Objectives
The primary objective of this study is as follows:

To evaluate the safety and tolerability of a combination of the bNAbs GS-5423 and GS-2872 
in combination with the HIV capsid inhibitor LEN  
The secondary objectives of this study are as follows:

To evaluate efficacy of the study regimens determined by the proportion of participants 
maintaining virologic suppression (HIV-1 RNA < 50 copies/mL) at Week 26

To evaluate the PK of GS-5423, GS-2872, and LEN

To evaluate immunogenicity of GS-5423 and GS-2872

To evaluate the emergence of resistance to the components of the study regimens
The exploratory objectives are as follows:

To evaluate changes in HIV reservoir 

To evaluate changes in immune biomarkers
1.2.
Study Design
Design Configuration and Participant Population
This is a randomized, blinded, Proof of Concept (POC)  Phase 1b study to evaluate the safety 
and efficacy of a single dose each of long-acting (LA) regimen of LEN, GS-5423, and GS-2872 
in adults with HIV-1 infection who are virologically suppressed on oral antiretroviral therapy 
(ART).


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This study will enroll approximately 20 participants (Primary Cohort). After GDRC review 
(Section 2.1), an optional Pilot Cohort of up to 20 additional participants may be added. 
Participants in the Primary Cohort and in the optional Pilot Cohort will be randomized in a 
1:1 ratio to one of the following 2 treatment groups based on the dose of GS-2872 as follows:
Treatment Groups
Treatment Group 1: 
Oral LEN for loading 600 mg followed by LEN 927 mg SC on Day 1; oral LEN for loading 
600 mg on Day 2 
GS-5423 30 mg/kg, administered via IV infusion over 60 minutes on Day 1 (after LEN SC 
injection)
GS-2872 10 mg/kg, administered via IV infusion over 60 minutes on Day 1 (after GS-5423 
infusion)
Treatment Group 2: 
Oral LEN for loading 600 mg followed by LEN 927 mg SC on Day 1; oral LEN for loading 
600 mg on Day 2
GS-5423 30 mg/kg, administered via IV infusion over 60 minutes on Day 1 (after LEN SC 
injection)
GS-2872 30 mg/kg, administered via IV infusion over 60 minutes on Day 1 (after GS-5423 
infusion)
For the optional Pilot Cohort, randomization will be stratified by the antibody (GS-5423 or 
GS-2872) to which the participant is sensitive. 
All participants will discontinue their background oral antiretroviral (ARV) regimen 1 day prior 
to receiving study drugs on Day 1. 
At Week 26, all participants will resume their baseline regimen of once daily oral ART (or 
compatible regimen selected by the investigator) and return to the clinic for visits at Weeks 38 
and 52.
Unblinded treatment assignments will be provided to the investigators after all participants are 
back on their baseline ARVs (or compatible regimen selected by the investigator) at Week 26 or 
have discontinued the study, and the Week 26 analysis has been completed.


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Key Eligibility Criteria
HIV-1 infected participants who meet the following criteria:

Age between 18 and 65 years at screening

On first-line ART for ≥ 2 years prior to screening. A change in ART regimen ≥ 28 days prior 
to screening for reasons other than VF (eg, tolerability, simplification, drug-drug interaction 
profile) is allowed

No documented historical resistance to the current ART regimen

Plasma HIV-1 RNA < 50 copies/mL at screening

Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 18 months preceding the screening 
visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of 
detection is ≥ 50 copies/mL). Unconfirmed virologic elevations of ≥ 50 copies/mL (transient 
detectable viremia, or “blip”) prior to screening are acceptable.

Proviral phenotypic sensitivity by the PhenoSense mAb Assay DNA at Monogram 
Biosciences to both GS-5423 and GS-2872 at screening

CD4+ count nadir ≥ 350 cells/µL

Screening CD4+ count ≥ 500 cells/µL

Availability of a fully active alternative ART regimen, in the opinion of the investigator, in 
the event of discontinuation of the current ART regimen with development of resistance

No comorbid condition requiring ongoing immunosuppression

No evidence of current hepatitis B virus (HBV) infection 

No evidence of current hepatitis C virus (HCV) infection (prior infection cleared 
spontaneously or with treatment is acceptable)

No history of opportunistic infection or illness indicative of Stage 3 HIV disease
Schedule of Assessments
Due to the extended laboratory processing time for bNAb sensitivity testing, screening 
procedures for the Primary Cohort will be conducted in two parts. For the optional Pilot Cohort, 
participants will be selected from the previously screened/failed participants in the Primary 
Cohort and will directly proceed to Screening Part 2 (no need to repeat Screening Part 1).


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Screening Part 1: Assessment of medical history, adverse events (AEs), and concomitant 
medications will be performed. A blood sample to assess for bNAb sensitivity will be collected 
and analyzed to support eligibility and entry into Screening Part 2. 
Screening Part 2: Participants with proviral phenotypic sensitivity to either or both GS-5423 and 
GS-2872 will have the following assessments performed: changes in medical history, complete 
physical examination, vital signs, height, weight, electrocardiogram (ECG), and sample 
collection for laboratory analyses (hematology, chemistry, coagulation, thyroid function, 
urinalysis, serum pregnaancy test [for women of childbearing potential], serum 
follicle-stimulating hormone [FSH], HIV-1 RNA, CD4+ cell count, CD8+ cell count, CD4/CD8 
ratio, HBV and HCV serologies, and estimated glomerular filtration rate [eGFR]). Laboratory 
samples for proviral DNA genotype and bulk viral outgrowth phenotype will be collected at 
screening for subsequent testing.
Participants in the Primary Cohort who meet all eligibility criteria will be randomized in a 
1:1 ratio to Treatment Group 1 or Treatment Group 2. Participants in the Pilot Cohort who meet 
all eligibility criteria will be randomized in a 1:1 ratio to Treatment Group 1 or Treatment 
Group 2. Participants in both cohorts will return to the clinic within 28 days after the Screening 
Part 2 visit for the Day 1 visit.
There is no stratification for randomization for the Primary Cohort.
For the optional Pilot Cohort, randomization will be stratified by the antibody (GS-5423 or 
GS-2872) to which the participant is sensitive.
More details for study procedures could be found in Section 11 (Appendix 1). 
Study Duration
26 weeks. 
1.3.
Sample Size and Power
Although the sample size in this study is determined based on practical considerations and past 
experience with similar types of studies, assuming the 2 treatment groups have a similar 
virologic suppression rate, a total of 20 participants in the Primary Cohort will provide at least 
35% power to show the lower bound of 95% CI for Week 26 virologic response rate (HIV-1 
RNA < 50 copies/mL as defined by the United States (US) Food and Drug Administration 
(FDA)-defined snapshot algorithm {U. S. Department of Health and Human Services 2015}) is 
greater than 83%. It was assumed that the virologic response rate at Week 26 was 95% (based on 
Gilead studies GS-US-380-1844 and GS-US-380-4030), 12% was a clinically tolerable margin 
for Phase 1b studies, and a one-sided exact test with a significance level 0.025 was used. The 
sample size and power calculations were made using the statistical software package PASS 
(Version 14, NCSS, LLC; Kaysville, Utah, USA). 


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The estimated 95% CI for possible range of VF rate is provided in Table 1-1. For example, with 
1 VF event occurrence (5% estimated VF rate), a sample size of 20 participants can provide 
95% confidence that the true VF rate is unlikely to be higher than 24.9%.
Table 1-1.
Estimated Virologic Failure Rate and its 95% CIs (from the 
Clopper-fPearson Exact CI) Based on Number of Virologic Failure 
Event in Each Group or in Total
Sample Size
20
Number of VF Events
0
1
2
3
4
Estimate of Incidence of VF (%)
0.0
5.0
10.0
15.0
20.0
Lower Bound of 95% CI (%)
0.0
0.1
1.2
3.2
5.7
Upper Bound of 95% CI (%)
16.8
24.9
31.7
37.9
43.7
VF = virologic failure
Software: SAS® Version 9.4. (SAS Institute Inc., Cary, NC, USA)
A total of approximately 20 participants in the Primary Cohort will provide reasonable 
assessment of safety and the descriptive PK profile throughout the study. A total of up to 
20 participants in the optional Pilot Cohort is based on practical considerations.


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
Prior to the final analysis, interim analyses will be conducted. The results from these analyses 
may be submitted to scientific meetings and for publications and to regulatory agencies to 
seekguidance for the overall clinical development program.
2.1.1.
Gilead Data Review Committee (GDRC) Analysis
The GDRC will review the progress, unblinded safety and efficacy data of this study while the 
study is ongoing. The GDRC will convene after all participants enrolled in the Primary Cohort 
have completed their Week 12 visit or prematurely discontinued from the study. 
No formal stopping rules will be used by the GDRC for safety outcomes. Rather, a clinical 
assessment will be made to determine if the nature, frequency, and severity of AEs associated 
with a study regimen warrant the early termination of the study in the best interest of the 
participants. Based on safety and preliminary efficacy, the GDRC will determine whether the 
optional Pilot Cohort will be implemented. 
In addition, the GDRC may review unblinded safety and efficacy data on an ad hoc basis when 
there is a need for safety or efficacy monitoring. Refer to the GDRC Charter for additional 
details.
2.1.2.
Primary Analysis 
The unblinded primary analysis will be conducted after all participants in the Primary Cohort 
have completed Week 26 visit or prematurely discontinued from the study.
2.2.
Final Analysis
The final analysis will be performed after all participants have completed the study or 
prematurely discontinued from the study, outstanding data queries have been resolved or 
adjudicated as unresolvable, and the data have been cleaned and finalized. The final analysis will 
include data from the Primary Cohort and may include data from the optional Pilot Cohort. 


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of participants in each category will be presented; for continuous 
variables, the number of participants (n), mean, standard deviation (SD) or standard error (SE), 
median, first quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
All statistical tests will be 2-sided and performed at the 5% significance level unless otherwise 
specified.
By-participant listings will be presented for all participants in the All Randomized Analysis Set 
and sorted by participant identification (ID) number, visit date, and time (if applicable). Data 
collected on log forms, such as AEs, will be presented in chronological order within the 
participant. The treatment group to which participants were randomized will be used in the 
listings. Age, sex at birth, race, and ethnicity will be included in the listings, as space permits.
There are following 2 sets of analyses defined for this study. Data included in each analysis are 
defined as follows:
Long Acting (LA) Regimen Period Analysis
Long Acting (LA) Regimen Period Analysis includes efficacy (ie, HIV-1 RNA and CD4 cell 
count and percentage) and safety data collected during long acting regimen period from 
participants randomized and received at least one dose of the complete long acting study drug 
regimen (ie, SC LEN + GS-5423 and GS-2872). All data collected up to the last exposure date of 
LA regimen (defined in section 3.8.1) will be summarized except for data on AEs, death and 
concomitant medications. For AEs, death and concomitant medications, only data collected prior 
to the last exposure date of LA regimen will be included. For participants who did not restart 
ART on or before last study date or have missing ARV restart date, all data will be included.
Data included in this analysis will be used to assess the efficacy and safety data collected during 
the LA regimen period of the study. Results will be summarized by treatment group and overall.
Whole Study Period Analysis
Whole Study Period Analysis includes efficacy (ie, HIV-1 RNA and CD4 cell count and 
percentage) and safety data collected during whole study period from participants randomized 
and received at least one dose of study drug. For efficacy summary, all HIV-1 RNA and CD4 
data during the whole study will be included. For safety summary, (1) for participants who 
prematurely discontinued study or complete study, all safety data collected up to the last 
exposure date (defined in section 3.8.1) will be included; (2) for participants who were still on 
study: all available data will be included. 
Data included in this analysis will be used to assess the efficacy and safety data collected during 
the whole study period.  Results will be summarized by treatment group and overall.


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3.1.
Analysis Sets
Analysis sets define the participants to be included in an analysis. Analysis sets and their 
definitions are provided in this section. The analysis set will be identified and included as a 
subtitle of each table, figure, and listing.
For each analysis set, the number and percentage of participants eligible for inclusion will be 
summarized by treatment group and total.
A listing of reasons for exclusion from analysis sets will be provided by participant.
3.1.1.
All Randomized Analysis Set
The All Randomized Analysis Set includes all participants who were randomized into the study. 
This is the primary analysis set for by-participant listings.
3.1.2.
Full Analysis Set
The Full Analysis Set (FAS) includes all randomized participants who have received at least one 
dose of the complete long acting study drug regimen (ie, SC LEN + GS-5423 and GS-2872). 
This is the primary analysis set for efficacy analyses.
3.1.3.
Per Protocol Analysis Set
The Per Protocol (PP) Analysis Set includes all participants in the FAS excluding participants 
meeting any of the following criteria:
1) did not have on-treatment HIV-1 RNA in the Week 26 analysis window, except when 
missing is due to discontinuation of study drug for lack of efficacy as in Table 3-1. 
(Note: lack of efficacy is defined as having the check-box for Lack of Efficacy marked as the 
reason for premature study drug discontinuation on the study drug completion eCRF page.)
2) Received partial or missed doses on Day 1 or Day 2.
3) Prior receipt of any anti–HIV-1 mAbs (including ibalizumab).
4) Have been treated with immunosuppressant therapies or chemotherapeutic agents 
(eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies) 
within 4 weeks of study screening or have an anticipated need for such treatment during the 
study.


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Table 3-1.
Participants Excluded from Week 26 PP Analysis Set Due to 
Premature Discontinuation of Study Drug and/or Missing HIV-1 
RNA Assessment in Week 26 Analysis Window
HIV-1 RNA Data on Treatment Available in 
Week 26 Analysis Window
Discontinuation from Study Drug prior to or on the 
Upper Bound of Week 26 Analysis Window
Yes
No
Due to Lack of Efficacy
+
+
Yes
Due to Other Reasons
+
-
No
+
-
+ = Inclusion of Participants in Week 26 PP analysis set; - = Exclusion of Participants in Week 26 PP analysis set.
On-Treatment HIV-1 RNA data include all HIV-1 RNA data collected up to the earliest date of (196 days [28 weeks] after the 
dose date of complete long acting regimen, date of restarting ART).
The date of study drug premature discontinuation is the last exposure date of LA regimen for 
participants who prematurely discontinued study drug.
For the PP analysis, efficacy data up to the earliest date of (196 days [28 weeks] after the dose 
date of complete long acting regimen, date of restarting ART) will be included. 
The PP Analysis Set is the secondary analysis set for efficacy analysis.
3.1.4.
Safety Analysis Set
The Safety Analysis Set is the primary analysis set for safety analyses. Two safety analysis sets 
are defined for this study: 

The Safety Analysis Set includes all participants who were randomized and received at least 
1 dose of study drug. This is the primary analysis set for safety analyses for whole study 
period. This analysis set will also be used to describe baseline information.

The Safety Analysis Set for LA Regimen includes all randomized participants who have 
received at least one dose of the complete long acting study drug regimen 
(ie, SC LEN + GS-5423 and GS-2872). This is the primary analysis set for safety analyses 
for LA regimen period analysis.
3.2.
Participant Grouping
For analyses based on the All Randomized Analysis Set or the FAS, participants will be grouped 
according to the treatment group to which they were randomized. For all other analyses, 
participants will be grouped according to the actual treatment received. The actual treatment 
received will differ from the randomized treatment only when their actual treatment differs from 
randomized treatment for the entire treatment duration.


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Participants will be grouped as follows for table summary:  

Treatment Group 1: SC LEN + GS-5423 + GS-2872 10 mg/kg

Treatment Group 2: SC LEN + GS-5423 + GS-2872 30 mg/kg

Total Group: All participants from Teatment Groups 1 and 2 (for all tables and figure 
summary unless specified otherwise)
3.3.
Strata and Covariates
This study does not use a stratified randomization schedule when enrolling participants in 
primary cohort. 
3.4.
Examination of Participant Subgroups
There are no prespecified participant subgroupings for efficacy and safety analyses due to small 
sample size.
3.5.
Multiple Comparisons
Adjustments for multiplicity will not be made in this phase 1b trial.
3.6.
Missing Data and Outliers
3.6.1.
Missing Data
In general, missing data will not be imputed unless methods for handling missing data are 
specified. Exceptions are presented in this document.
For missing last dose date of study drug, imputation rules are described in Section 3.6. The 
handling of missing or incomplete dates for AE onset is described in Section 7.1.5.2., and for 
prior and concomitant medications in Section 7.4.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be conducted. All data will be included in the data analysis.
3.7.
Data Handling Conventions and Transformations
Only year of birth is collected in this study. The following conventions will be used for the 
imputation of date of birth when it is partially missing or not collected:

If year of birth is collected, “01 July” will be imputed as the day and month of birth

If year of birth is missing, date of birth will not be imputed


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In general, age collected at Day 1 (in years) will be used for analyses and presented in listings. If 
age at Day 1 is not available for a participant, age derived based on date of birth and the Day 1 
visit date will be used instead. If a randomized participant was not dosed with any study drug, 
the randomization date will be used instead of the Day 1 visit date. For screen failures, the date 
the first informed consent was signed will be used for the age derivation. Age required for 
longitudinal and temporal calculations and analyses (eg, estimates of creatinine clearance) will 
be based on age derived from date of birth and the date of the measurement or event, unless 
otherwise specified.
Non-PK data that are continuous in nature but are less than the lower limit of quantitation (LOQ) 
or above the upper LOQ will be imputed as follows:

A value that is 1 unit less than the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “ x” (where x is considered the LOQ). For example, if the 
values are reported as < 50 and < 5.0, values of 49 and 4.9, respectively, will be used to 
calculate summary statistics. An exception to this rule is any value reported as < 1 or < 0.1, 
etc. For values reported as < 1 or < 0.1, a value of 0.9 or 0.09, respectively, will be used to 
calculate summary statistics.

A value that is 1 unit above the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “> x” (where x is considered the LOQ). Values with decimal 
points will follow the same logic as above.

The LOQ will be used to calculate descriptive statistics if the datum is reported in the form of 
“≤ x” or “≥ x” (where x is considered the LOQ).
HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “<20 cp/mL HIV-1 RNA Detected” will 
be imputed as 19 copies/mL for analysis purposes. 
3.8.
Analysis Visit Windows
3.8.1.
Definition of Key Dates and Study Day
Study Day 1 is defined as the day when the first dose of any study drug was taken, as recorded 
on the Study Drug Administration eCRF (ie, oral LEN, SC LEN or infusion drugs [GS-5423, 
GS-2872]). 
Last Dose Date is defined as the latest dose date of any study drug as recorded on the Study 
Drug Administration eCRF (ie, oral LEN, SC LEN or infusion drugs (GS-5423, GS-2872) for 
participants who prematurely discontinued study drug or completed study drug according to 
Study Drug Completion eCRF. 
Study Days are calculated relative to Study Day 1 of study drug and derived as follows:

For postdose study days: Assessment Date – First Dose Date + 1

For days prior to the first dose: Assessment Date – First Dose Date


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Baseline Value is defined as the last value obtained on or prior to the first dose of study drug.
Last Study Date is the latest clinic visit dates, and/or the laboratory visit dates, and/or latest AE 
onset date and end date, whichever is latest, including the any follow-up visit dates, for 
participants who prematurely discontinued study or completed study according to the Study 
Completion eCRF.
Last Exposure Date is defined as follows for participants who prematurely discontinued study 
or complete study according to Study Completion eCRF (i.e. participant answered “No’ or “Yes” 
for “Did the participant complete the protocol-planned duration of the study” on Study 
Completion form): 

For participants who receive any injection or infusion, last exposure date is defined as last 
study date.  

For participants who do not receive any injection or infusion (i.e. for those who only receive 
oral LEN), last exposure date is defined as the earliest of the last dose date plus 60 days and 
the last study date.
This date is defined considering the prolonged exposure of LEN, GS-5423, and GS-2872 after 
the last dose date of LEN, GS-5423, and GS-2872 through the end of study.
Last Exposure Date of LA regimen is defined as follows for participants who prematurely 
discontinued study drug or complete study drug according to Study Drug Completion eCRF (i.e. 
participant answered “No’ or “Yes’ for “Did participant complete study drug dosing as specified 
per protocol” on Study Drug Completion form): 
1)  the earliest (last study date or ART restart date) for participants who prematurely 
discontinued study or complete study;
2)  the ART restart date for participants who were still on study. If the ART restart date is 
missing, the data cut date will be used to impute the last exposure date for participants who 
are still on study at the time of the data cut date. 
This date is defined considering the prolonged exposure of LEN, GS-5423, and GS-2872 after 
the last dose date of LEN, GS-5423, and GS-2872 through the ART restart date.
ART Restart Date is defined as the date resuming baseline oral ART or compatible regimen.
3.8.2.
Analysis Visit Windows
Participant visits might not occur on protocol-specified days. Therefore, for the purpose of 
analysis, observations will be assigned to analysis windows.
The analysis windows for HIV-1 RNA, CD4+ cell count, CD8+ cell count, CD4 %, Hematology, 
Chemistry, Lipid Panel, Urinalysis, Urine Chemistry, Urine Pregnancy Laboratory Tests, Vital 
Signs, Weight and ECG are provided in Table 3-2 to Table 3-4.


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Table 3-2.
Analysis Windows for HIV-1 RNA
Visit ID
Nominal Day
Lower Limit
Upper Limit
Day 1 (Baseline)
1
Week 4
28
2
42
Week 8
56
43
70
Week 12
84
71
98
Week 16
112
99
126
Week 20
140
127
154
Week 24
168
155
175
Week 26
182
176
224
Week 38
266
225
315
Week 52
364
316
413
Table 3-3.
Analysis Windows for CD4+ cell count, CD8+ cell count, Chemistry, 
Hematology, Urinalysis, Vital Signs, and Weight
Visit ID
Nominal Day
Lower Limit
Upper Limit
Day 1 (Baseline)
1
Week 4
28
2
56
Week 12
84
57
133
Week 26
182
134
224
Week 38
266
225
315
Week 52
364
316
413
Table 3-4.
Analysis Windows for ECG
Visit ID
Nominal Day
Lower Limit
Upper Limit
Day 1 (Baseline)
1
Week 26
182
2
273
Week 52
364
274
413


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3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window
Depending on the statistical analysis method, single values may be required for each analysis 
window. For example, change from baseline by visit usually requires a single value, whereas a 
time-to-event analysis would not require 1 value per analysis window.
If multiple valid, nonmissing measurements exist in an analysis window, records will be chosen 
based on the following rules if a single value is needed:

For baseline, the last nonmissing value on or prior to the first dose date of study drug will be 
selected, unless specified differently. If there are multiple records with the same time or no 
time recorded on the same day, the baseline value will be the average of the measurements 
for continuous data (except for HIV-1 RNA, see below), or the measurement with the lowest 
severity (eg, normal will be selected over abnormal for safety ECG findings) for categorical 
data.

For postbaseline values:
The record closest to the nominal day for that visit will be selected with the exception of 
CD4 cell counts and CD4% in which the latest record will be selected and HIV-1 RNA 
level (see below).
If there are 2 records that are equidistant from the nominal day, the later record will be 
selected.
If there is more than 1 record on the selected day, the average will be taken for 
continuous data (except for HIV-1 RNA, see below) and the worse severity will be taken 
for categorical data, unless otherwise specified.

For baseline HIV-1 RNA, the latest (considering both date and time) record(s) on or prior to 
the first dose date and time of study drug will be selected. For postbaseline HIV-1 RNA, the 
latest (considering both date and time) record(s) in the window will be selected. If both “HIV 
RNA Taqman 2.0” and “HIV RNA Repeat” (ie, the HIV-1 RNA result obtained from an 
additional aliquot of the original sample) are available with the same collection time, the 
results from the “HIV RNA Repeat” will be selected for analysis purposes; otherwise, if 
there are multiple “HIV RNA Taqman 2.0” records with the same collection time, the 
geometric mean will be taken for analysis purposes. 


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4.
PARTICIPANT DISPOSITION
4.1.
Participant Enrollment and Disposition
A summary of participant enrollment will be provided by treatment group and total for each 
country, investigator within a country, and overall. For each column, the denominator for the 
percentage calculation will be the total number of participants analyzed for that column. 
A summary of participant disposition will be provided by treatment group and total based on all 
screened participants. This summary will present the number of participants screened, the 
number of subjects who did not meet eligibility criteria and were not randomized, the number of 
participants who met all eligibility criteria but were not randomized with reasons participants not 
randomized, the number of participants randomized but never dosed (if applicable), number of 
participants in the Safety Analysis Set and the number of participants in each of the following 
categories as applicable: 

Completed study drug

Did not complete study drug with reasons for premature discontinuation of study drug

Continuing study 

Completed study

Did not complete the study with reasons for premature discontinuation of study
For summary, participants with study drug premature discontinuation are defined as 
participants who were  answered “No” to “Did subject complete study drug dosing as specified 
per protocol?”  and had a discontinuation reason other than “Investigator Discretion” (with 
comment of “Due to Clinical hold”) in Study Drug Completion eCRF).
Participants who prematurely discontinued study are defined as participants who answered 
‘No’ to “Did the subject complete the protocol-planned duration of the study?” in Study 
Completion eCRF)
For the status of study drug and study completion and reasons for premature discontinuation, the 
number and percentage of participants in each category will be provided. The denominator for 
the percentage calculation will be the total number of participants in the Safety Analysis Set 
corresponding to that column. In addition, a flowchart will be provided to depict the disposition.
The following by-participant listings will be provided by participant ID number in ascending 
order to support the above summary tables:

Reasons for premature study drug or study discontinuation


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4.2.
Extent of Study Drug Exposure and Adherence
Study drug administration and study drug dispensing information will be collected in the Study 
Drug Administration and Study Drug Accountability eCRFs. Extent of exposure to study drug 
will be examined by assessing the total duration of exposure to study drug and the level of 
adherence relative to the study drug if applicable.
4.2.1.
Duration of Exposure to Study Drug
Duration of exposure to study drug will be summarized for LA regimen period and the whole 
study period, respectively. Due to long acting feature of study drug, duration of follow-up to 
study drug will consider the prolonged exposure of LA study drug (ie, SC LEN, GS-5423, 
GS-2872) after the last dose date of study drug through the ART restart date or the end of study, 
respectively.
For long acting regimen period analysis, last exposure date of LA regimen is defined in 
Section 3.8.1 for participants who prematurely discontinued study drug or completed study drug. 
Duration of study drug exposure for long acting regimen period is defined as (the last exposure 
date of LA regimen – the first dose date + 1), and duration of exposure will be expressed in 
weeks using up to 1 decimal place (eg, 4.5 weeks). 
For whole study period analysis, last exposure date are defined in Section 3.8.1 for participants 
who prematurely discontinued study or completed study. For the calculation of the duration of 
exposure to study drug, the data cut date will be used to impute the last exposure date for 
participants who are still on study at the time of the data cut date. 
Duration of study drug exposure for the whole study period will be defined as (the last exposure 
date – the first dose date + 1), and duration of exposure will be expressed in weeks using up to 
1 decimal place (eg, 4.5 weeks). 
Duration of exposure will be summarized using descriptive statistics (n, mean, SD, median, Q1, 
Q3, minimum, and maximum) and as the number and percentage of participants exposed and 
remained through the following time periods: 1 day, 2 days, 4 weeks (28 days), 8 weeks 
(56 days), 16 weeks (112 days), 24 weeks (168 days), 26 weeks (182 days), 30 weeks (210 days), 
34 weeks (238 days), etc. Summaries will be provided based on the Safety Analysis Set for LA 
regimen period and for whole study period separately. No inferential statistics will be provided.
4.2.2.
Adherence to Study Drug
4.2.2.1.
Adherence to Oral Study Drug (Oral LEN)
The adherence to oral study drug will be computed based on pill counts. The numbers of pills of 
study drug dispensed and returned are captured on study drug accountability eCRF.


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Adherence (%) of oral study drug will be calculated as follows:
Adherence (%) =  100 ×
𝑇𝑜𝑡𝑎𝑙 No. of pills taken
Total No. of pills prescribed
The number of pills taken for the study drug = number of pills dispensed minus the number of 
pills returned. The number of pills prescribed is the number of pills dispensed.
For a record where the number of pills returned was missing (with “Yes” answered for “Was 
Bottle returned?” question), it is assumed the number of pills returned was zero. If the number of 
pills dispensed was missing or any study drug bottle was not returned or the bottle return status 
was unknown, all records for that study drug will be excluded from both denominator and 
numerator calculation.
Adherence will be calculated for each participant for the entire dosing period up to the date of 
permanent discontinuation of the study drug for participants who prematurely discontinued study 
drug or using all available data for participants ongoing by the data cut date. 
Descriptive statistics for adherence (n, mean, SD, median, Q1, Q3, minimum, and maximum) 
along with the number will be provided for participants who return at least 1 bottle of oral study 
drug, and who have calculable adherence in the Safety Analysis Set. No inferential statistics will 
be provided.
4.3.
Protocol Deviations 
Participants who did not meet the eligibility criteria for study entry, but enrolled in the study will 
be summarized. The summary will present the number and percentage of participants who did 
not meet at least 1 eligibility criterion and the number of participants who did not meet specific 
criteria based on the Safety Analysis Set. A by-participant listing will be provided for those 
participants who did not meet at least 1 eligibility (inclusion or exclusion) criterion.
Protocol deviations occurring after participants entered the study are documented during routine 
monitoring. The number and percentage of participants with important protocol deviations and 
number of important protocol deviations by deviation category (eg, eligibility criteria, informed 
consent) will be summarized by treatment group and total for the Safety Analysis Set. A 
by-participant listing will be provided for those participants with important protocol deviation.


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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
Participant demographic variables (ie, age, sex at birth, gender identity, sexual orientation, race, 
and ethnicity) and baseline characteristics (body weight [in kg], height [in cm], body mass index 
[BMI; in kg/m2]) will be summarized by treatment group and overall using descriptive statistics 
for continuous variables and using number and percentage of participants for categorical 
variables. The summary of demographic data will be provided for the Safety Analysis Set. 
Statistical comparison across treatment groups will be performed. For categorical data, the 
Cochran-Mantel-Haenszel (CMH) test will be used to compare across treatment groups. For 
continuous data, the 2-sided Wilcoxon rank sum test will be used to compare across treatment 
groups. 
A by-participant demographic and baseline characteristic listing, including the informed consent 
date, will be provided by participant ID number in ascending order.
5.2.
Other Baseline Characteristics
The following baseline disease characteristics will be summarized by treatment group and 
overall using descriptive statistics for participants in the Safety Analysis Set: 

HIV-1 RNA categories (copies/mL): (a) < 50, (b) ≥ 50

CD4 cell counts (/uL)

CD4 cell counts categories (/uL): (a) < 50, (b) ≥ 50 to < 200, (c) ≥ 200 to < 350, (d) ≥ 350 to 
< 500, and (e) ≥ 500

CD4 percentage (%)

Mode of infection (HIV risk factors)

HIV disease status

eGFRCG (mL/min)

Duration of baseline ARV medication
Statistical comparison across treatment groups will be conducted similarly as described for the 
demographic and baseline characteristics. A by-participant listing of other baseline characteristics 
will be provided by participant ID number in ascending order.
5.3.
Medical History
Medical history will be collected at screening. Medical history data will be coded and listed.


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6.
EFFICACY ANALYSES
Secondary endpoints of this study include efficacy endpoints as described below. For efficacy 
analysis, except for FDA-defined snapshot endpoints, two sets of analysis will be conducted 
unless otherwise specified: LA regimen period analysis and whole study period analysis. 
6.1.
Primary Efficacy Endpoint
6.1.1. Definition of the Primary Efficacy Endpoint
The primary efficacy endpoint of this study is  Proportion of participants with HIV-1 RNA 
≥ 50 copies/mL at Weeks 26 as defined by the FDA-defined snapshot algorithm 
{U. S. Department of Health and Human Services 2015}. 
6.1.2 US FDA-Defined Snapshot Algorithm
The analysis window at Week 26 is defined as from Study Day 176 to Study Day 224, inclusive. 
All HIV-1 RNA data collected on-treatment (ie, data collected up to the earliest date of 
(196 days [28 weeks] after the dose date of complete long acting regimen, date of restarting 
ART)) will be used in the US FDA-defined snapshot algorithm. Virologic outcome will be 
defined as the following categories:

HIV-1 RNA < 50 copies/mL: this includes participants who have the last available 
on-treatment HIV-1 RNA < 50 copies/mL in the Week 26 analysis window

HIV-1 RNA ≥ 50 copies/mL: this includes participants
a) Who have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 26 
analysis window, or
b) Who do not have on-treatment HIV-1 RNA data in the Week 26 analysis window and 
i)
Who discontinue study drug prior to or in the Week 26 analysis window due to lack 
of efficacy, or
ii) Who discontinue study drug prior to or in the Week 26 analysis window due to AE or 
death and have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL, or 
iii) Who discontinue study drug prior to or in the Week 26 analysis window due to 
reasons other than AE, death, or lack of efficacy and have the last available 
on-treatment HIV-1 RNA ≥ 50 copies/mL.


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
No Virologic Data in the Week 26 Window: this includes participants who do not have 
on-treatment HIV-1 RNA data in the Week 26 analysis window because of the following: 
a) Discontinuation of study drug prior to or in the Week 26 analysis window due to AE or 
death and the last available on-treatment HIV-1 RNA < 50 copies/mL, or
b) Discontinuation of study drug prior to or in the Week 26 analysis window due to reasons 
other than AE, death, or lack of efficacy and the last available on-treatment HIV-1 RNA 
< 50 copies/mL or,
c) Missing data during the window but on study drug.
The flowchart of the US FDA-defined snapshot algorithm is provided in Appendix 2.
The Week 26 virologic outcomes for the US FDA-defined snapshot algorithm will be listed.
Note, for switch trials, the US FDA-defined snapshot algorithm classifies participants who 
discontinue study drug due to AE or death and have the last available on-treatment HIV-1 RNA 
value ≥ 50 copies/mL in the “HIV-1 RNA ≥ 50 copies/mL” category. For treatment naïve study 
population, these participants will be classified in the “No Virologic Data in the Week 26 
Window” category.
6.1.3
Analysis of the Primary Efficacy Endpoint
The Primary analysis of the proportion of subjects with HIV-1 RNA ≥ 50 copies/mL as 
determined by the US FDA-defined snapshot algorithm at Week 26 will be based on the FAS. 
The point estimate of treatment difference in the percentage of participants with HIV-1 RNA ≥
 50 copies/mL and the associated 2-sided 95% CI will be constructed based on an unconditional 
exact method using 2 inverted 1-sided tests. 
The 2-sided Fisher’s exact test will also be used to compare the percentages of participants 
between treatment groups.
A secondary analysis based on the PP analysis set will also be performed. Subjects excluded 
from the PP analysis set will be determined before database lock.
6.2.
Secondary Efficacy Endpoints
6.2.1.
Definition of the Secondary Efficacy Endpoints
The secondary efficacy endpoints of this study are:

Proportion of participants with HIV-1 RNA < 50 copies/mL at Weeks 26 as defined by the 
FDA-defined snapshot algorithm

Change from baseline in CD4+ cell counts at Weeks 26 


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6.2.2.
Analysis of the Secondary Efficacy Endpoints
6.2.2.1.
Analysis of the Proportion of Subjects with HIV-1 RNA < 50 copies/mL as 
Determined by US FDA-defined Snapshot Algorithm
Proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 26 as determined by US 
FDA-defined snapshot algorithm will be analyzed based on the FAS and the PP analysis sets, 
similarly to the primary efficacy endpoint.
The analyses for the above endpoint will be conducted using the FAS and the PP analysis set, 
respectively.
6.2.2.2.
Analysis of CD4+ cell counts
The changes from baseline in CD4+ cell count at Week 26 and other visits will be summarized 
by treatment group and overall for FAS using descriptive statistics. The change from baseline in 
CD4+ cell count will also be summarized up to the visits with available data for each period 
analysis. 
The absolute values of CD4 cell counts will be also summarized by treatment group and overall 
similarly. The analyses of CD4 cell counts and their changes from baseline will be conducted 
using the FAS.
The mean and 95% CI of change from baseline in CD4+ cell count over time by treatment 
groups and overall will be plotted for the FAS.
CD4+ cell counts over time in individual participants will be plotted by treatment groups and 
overall.
6.3.
Other Efficacy Endpoints
6.3.1.
Definition of the Other Efficacy Endpoints

The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 26 as defined by 
2 different missing data imputation methods specified in Section 6.3.2.

The change from baseline in CD4 percentage (%) at Week 26
6.3.2.
Analysis of the Other Efficacy Endpoints
6.3.2.1.
Analysis of Proportion of Participants with HIV-1 RNA < 50 copies/mL by 
Missing = Failure and Missing = Excluded Approaches
Number and percentage of participants with HIV-1 RNA < 50 copies/mL by visit will be 
analyzed using the following 2 methods for imputing missing HIV-1 RNA values:

Missing = Failure (M = F): 
In this approach, missing data will be treated as virologic failure and summarized into the 
“missing” category (see list of HIV-RNA categories below). Results will be summarized by 
treatment group and total for all visits up to Week 26. 


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
Missing = Excluded (M = E): 
In this approach, missing data will be excluded in the computation of the percentages 
(ie, missing data points will be excluded from both the numerator and denominator in the 
computation). The denominator for percentages at a visit is the number of participants in the 
FAS with nonmissing HIV-1 RNA value at that visit. 
For both M = F and M = E analyses, the number and percentage of participants with HIV-1 RNA 
in the following categories will be summarized based on the FAS:

< 50 copies/mL 
< 20 copies/mL
■
< 20 copies/mL Not Detectable
■
< 20 copies/mL Detectable
20 to < 50 copies/mL 

50 to < 200 copies/mL 

200 to < 400 copies/mL 

400 to < 1000 copies/mL

≥ 1000 copies/mL 

Missing (only applicable to M = F analysis)
The proportion of participants with HIV-1 RNA < 50 copies/mL as defined by the 2 different 
missing data imputation methods will be analyzed using the same statistical method applied to 
the primary endpoint. In addition, the 95% CI of the proportion of participants with HIV-1 RNA 
< 50 copies/mL within each treatment will be provided using the Clopper-Pearson Exact method.
For the M = F analysis, results will be summarized by treatment group for all visits up to 
Week 26 and for LA regimen period analysis only. For the M = E analysis, results will be 
summarized by treatment group for all visits with available data for each period analysis.
For the M = F analysis, the proportion of subjects with HIV-1 RNA < 50 copies/mL will be
plotted by treatment group for all visits up to Week 26 using the FAS.
6.3.2.2.
Analysis of CD4% 
The change from baseline in CD4 percentage will be based on the FAS and summarized up to 
the visits with available data for each period analysis using descriptive statistics. 
6.4.
Changes from Protocol-Specified Efficacy Analyses
No change from protocol-specified efficacy analysis is planned. 


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7.
SAFETY ANALYSES
The primary objective of this study is to evaluate the safety and tolerability of a combination of 
the bNAbs GS-5423 and GS-2872 in combination with the HIV capsid inhibitor LEN, and the 
primary endpoint of this study is incidence of treatment-emergent SAEs through Week 26. The 
second endpoint of this study includes incidence of treatment-emergent AEs through Week 26.
Safety data will be summarized for participants in the Safety Analysis Set for the whole study 
period analysis and for participants in the Safety Analysis Set for LA regimen for LA regimen 
period analysis, separately, unless otherwise specified. All collected data will be included in data 
listings. 
7.1.1.
Adverse Event Dictionary
Clinical and laboratory AEs will be coded using the current version of the Medical Dictionary 
for Regulatory Activities (MedDRA). System organ class (SOC), high-level group term (HLGT), 
high-level term (HLT), preferred term (PT), and lower-level term (LLT) will be provided in the 
AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1, 2, 3, 4, or 5 according to toxicity 
criteria specified in the protocol. The severity grade of events for which the investigator did not 
record severity will be categorized as “missing” for tabular summaries and data listings. The 
missing category will be listed last in summary presentation.
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE eCRF to the 
question of “Related to Study Treatment.” Relatedness to each study drug is justified by 
investigator and recorded on AE eCRF, for example, relatedness to Oral LEN is which 
investigator selected “Related” on the AE eCRF to the question of “Related to Study Treatment 
Oral LEN”. Relatedness will always default to the investigator’s choice, not that of the medical 
monitor. Events for which the investigator did not record relationship to study drug will be 
considered related to study drug for summary purposes. However, by-participant data listings 
will show the relationship as missing.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if the AEs met the 
definitions of SAEs that were specified in the study protocol. SAEs captured and stored in the 
clinical database will be reconciled with the SAE database from the Gilead Global Patient Safety 
(GLPS) Department before data finalization.


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7.1.5.
Treatment-Emergent Adverse Events 
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent AEs (TEAEs) for whole study period analysis are defined as follows:

Any AEs leading to premature discontinuation of study drug, or

Any AEs with an onset date on or after the study drug start date and no later than the last 
exposure date after permanent discontinuation of the study
For LA regimen period analysis, the definition of TEAE is the same except the last exposure date 
of LA regimen after permanent discontinuation of the study instead of the last exposure date 
after permanent discontinuation of the study will be used for defining TEAEs.
7.1.5.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dose date of 
study drug, then the month and year (or year alone if month is not recorded) of onset determine 
whether an AE is treatment emergent. The event is considered treatment emergent as follows:

Participants who receive any injection or infusion drug: the AE onset date is the same as or 
after the month and year (or year) of the first dose date of study drug

Participants who do not receive any injection or infusion drug (for whole study period 
analysis): 
The AE onset is the same as or after the month and year (or year) of the first dose date of 
study drug, and
The AE onset date is the same as or before the month and year (or year) of the last 
exposure date 
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dose date of study drug, will be considered to be treatment emergent. In 
addition, an AE with the onset date missing and incomplete stop date with the same or later 
month and year (or year alone if month is not recorded) as the first dose date of study drug will 
be considered treatment emergent.
When calculating the duration of event or time to onset, the following imputation rule will be 
used:
Missing start month/day: Jan 1/first day of the month will be used unless this is before the start 
date of study drug; in this case the study drug start date will be used;
Missing stop month/day: Dec 31/last day of the month will be used, unless this is after the last 
study date; in this case the last study date will be used.


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7.1.6.
Summaries of Adverse Events and Deaths
Treatment-emergent AEs will be summarized based on the Safety Analysis Set or Safety 
Analysis Set for LA regimen, and will be summarized separately for the whole study period 
analysis and LA regimen period analysis. 
For each period analysis, a brief, high-level summary of the number and percentage of 
participants who experienced at least 1 TEAE in the categories described below will be provided 
by treatment group and total. All deaths observed in the period will also be included in this 
summary. The number and percentage of participants who experienced at least 1 TEAE will be 
provided and summarized by SOC and PT and by PT only for the following AE categories: 

TEAEs

TEAEs with Grade 3 or higher 

TEAEs with Grade 2 or higher 

TE treatment-related AEs

TE treatment-related AEs with Grade 3 or higher 

TE treatment-related AEs with Grade 2 or higher 

TE SAEs

TE treatment-related SAEs 

TEAEs leading to death (by SOC and PT only)

TEAEs leading to premature discontinuation of study drug

TEAEs leading to premature discontinuation of study 
Multiple events will be counted only once per participant in each summary. For summaries by 
SOC and PT, AEs will be summarized and listed first in alphabetical order of SOC and then by 
PT in descending order of total frequency within each SOC. For summarizes by PT only, AEs 
will be summarized and listed by PT in descending order of total frequency. For summaries by 
severity grade, the most severe grade will be used for those AEs that occurred more than once in 
an individual participant during the period. 


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In addition, data listings will be provided for the following:

All AEs

All SAEs

All Deaths

All AEs with severity of Grade 3 or higher 

All AEs leading to discontinuation of study drug

All AEs leading to discontinuation of study
For each listing, whether the event is treatment emergent will be indicated.
7.1.7.
Additional Analysis of Adverse Events
7.1.7.1.
Study Drug Related Injection Site Reactions and Infusion Related Reactions
Additional analysis of AEs will be performed for injection site reaction (ISR) and infusion 
related reaction (IRR), respectively, as defined per eCRF (ie, AE with“Yes’ answer to “Is this 
part of an infusion-related reaction?” or “Is this part of an injection site reaction?” in AE CRF, 
respectively). The following summaries will be provided for LA regimen period analysis only.

Number of participants received any injection or infusion    

Number and percentage of participants with study drug related ISRs or IRRs   

Number and percentage of participants with study drug related ISRs or IRRs by grade 

Number and percentage of participants with study drug related ISRs or IRRs by PT 
The denominator for the percentage calculation will be based on the number of participants 
received at least one injection or infusion in Safety Analysis Set . 
Duration of the ISR will also be calculated and summarized. Duration of a given ISR event is 
defined as the ISR stop date minus the ISR onset date plus 1 day. For ISRs with ongoing stop 
date, stop date will be imputed as last study date or data cut date, whichever is the earliest. 
Duration of ISR events in days will be summarized by PT and overall using descriptive statistics.  
Duration of a given IRR event is defined as the IRR stop date minus the IRR onset date plus 
1 day, and duration of IRR will be listed also.
By-participant listings for ISRs orIRRs will be provided.


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7.1.7.2.
Study Drug Related Injection Site Induration and Nodules
Percentage of ongoing and resolved study drug releated “Injection Site Induration” (one of 
preferred terms of ISR) will be summarized at both subject-level and event-level. 
For the subject-level summary, if a subject had more than one injection site indurations, the 
subject will be counted in the “Ongoing” category  unless all study drug releated injection site 
induration events have been resolved. 
For the event-level summary, duration of the resolved events will be summarized using 
descriptive statistics.
Study drug related “Injection Site Nodules” (another preferred term of ISR)  will be summarized 
in the same manner as defined for study drug releated injection site induration.
A by-subject listing for study drug related injection site induration and nodules and the 
corresponding duration will be provided.
7.2.
Laboratory Evaluations
Summaries of laboratory data will be provided for the whole study period and LA regimen 
period analysis, respectively. Laboratory data collected during the study will be analyzed and 
summarized using both quantitative and qualitative methods.
For whole study period analysis, summaries of laboratory data will be provided for the Safety 
Analysis Set and will include data collected up to the last exposure date for subjects who have 
permanently discontinued study, or all available data at the time of the database snapshot for 
subjects who were ongoing on study at the time of an interim analysis.
For LA regimen analysis, summaries of laboratory data will be provided for the Safety Analysis 
Set for LA regimen and will include data collected up to the last exposure date of LA regimen 
for subjects who have permanently discontinued study drug, or all available data at the time of 
the database snapshot for subjects who were ongoing on study drug at the time of an interim 
analysis.
Calcium Corrected for Albumin
Calcium corrected for albumin will be calculated and summarized for the study. The following 
formula will be used when both serum calcium and albumin results for a given blood drawn are 
available and serum albumin value is < 4.0 g/dL. 
Calcium corrected for albumin (mg/dL) = serum calcium (mg/dL) + 0.8 × (4.0 – albumin (g/dL))
Toxicity grading for calcium will be applied based on the corrected values.


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Estimated Glomerular Filtration Rate
The following formulae will be used to calculate the estimated glomerular filtration rate using 
Cockcroft-Gault formula (eGFRCG):
eGFRCG (mL/min) = [(140 – age (yrs)) × weight (kg) × (0.85 if female)] / (SCr (mg/dL) × 72),
where weight is total body mass in kilograms and SCr is serum creatinine.
The analysis will be based on values reported in conventional units. When values are below the 
LOQ, they will be listed as such, and the closest imputed value will be used for the purpose of 
calculating summary statistics as specified in Section 3.7. 
No formal statistical testing is planned.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group for selected laboratory test as follows:

Baseline values 

Values at each postbaseline visit 

Change from baseline at each postbaseline visit 
A baseline laboratory value will be defined as the last measurement obtained on or prior to the 
date of first dose of study drug. Change from baseline to a postbaseline visit will be defined as 
the visit value minus the baseline value. The mean, median, Q1, Q3, minimum, and maximum 
values will be displayed to the reported number of digits; SD values will be displayed to the 
reported number of digits plus 1.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3.
7.2.2.
Graded Laboratory Values
The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 
dated July 2017, will be used to assign toxicity grades (0 to 4) to laboratory results for analysis. 
Grade 0 includes all values that do not meet the criteria for an abnormality of at least Grade 1. 
For laboratory tests with criteria for both increased and decreased levels, analyses for each 
direction (ie, increased, decreased) will be presented separately.
For triglycerides, LDL (4th generation), and cholesterol, toxicity grading scale is for fasting test 
values, so nonfasting lipid results (or lipid results without a known fasting status) will not be 
graded or summarized by toxicity grades.


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7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
For whole study period analysis, treatment-emergent laboratory abnormalities are defined as 
values that increase at least 1 toxicity grade from baseline at any postbaseline visit, up to last 
exposure date for participants who permanently discontinued study, or the last available date in 
the database snapshot for participants who were still on study at the time of an interim analysis. 
For LA regimen period analysis, treatment-emergent laboratory abnormalities are defined as 
values that increase at least 1 toxicity grade from baseline at any postbaseline visit, up to last 
exposure date of LA regimen for participants who permanently discontinued study drug, or the 
last available date in the database snapshot for participants who were still on treatment at the 
time of an interim analysis. 
If the relevant baseline laboratory value is missing, any abnormality of at least Grade 1 observed 
at any postbaseline visit will be considered treatment emergent.
7.2.2.2.
Summaries of Laboratory Abnormalities
Laboratory data that are categorical will be summarized using the number and percentage of 
participants in the study with the given response at baseline and each scheduled postbaseline 
visit, for the whole study period and LA regimen period, separately.
The following summaries (number and percentage of participants) for treatment-emergent 
laboratory abnormalities will be provided by lab test and treatment group, for the whole study 
period and LA regimen period, seperatly; participants will be categorized according to the most 
severe postbaseline abnormality grade for a given lab test:

Graded laboratory abnormalities 

Grade 3 or 4 laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of participants 
with nonmissing postbaseline values. 
A by-participant listing of treatment-emergent laboratory abnormalities and treatment-emergent 
Grade 3 or 4 laboratory abnormalities, respectively, will be provided by participant ID number 
and visit in chronological order. This listing will include all test results that were collected 
throughout the study for the lab test of interest, with all applicable severity grades and abnormal 
flags displayed.


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7.3.
Body Weight and Vital Signs
Descriptive statistics will be provided for the whole study period and LA regimen period by 
treatment group and total for body weight, BMI and vital signs as follows:

Baseline value

Values at each postbaseline visit 

Change from baseline at each postbaseline visit 
A baseline value will be defined as the last available value collected on or prior to the first dose 
date of study drug. Change from baseline to a postbaseline visit will be defined as the 
postbaseline value minus the baseline value. 
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3. No formal statistical testing is planned.
A by-participant listing of vital signs will be provided by participant ID number and visit in 
chronological order. Body weight, height, and BMI will be included in the vital signs listing, if 
space permits. If not, they will be provided separately.
7.4.
Prior and Concomitant Medications
Medications collected at screening and during the study will be coded using the current version 
of the World Health Organization (WHO) Drug dictionary. The WHO preferred name and drug 
code will be attached to the clinical database.
7.4.1.
Nonstudy Drug Antiretroviral Medications
Any nonstudy drug ARV medications used prior to, during, or after the study (if collected) will 
be listed. No inferential statistics will be provided.
Antiretroviral medications at baseline will be summarized by ARV category and drug name. 
Antiretroviral medications at baseline are defined as the ARV medications taken on or up to 2 
day prior to first dose date of study drug. 
7.4.2.
Prior and Concomitant Non-ARV Medications
Concomitant non-ARV medications are defined as non-ARV medications taken while a subject 
took study drug. Use of concomitant medications from Study Day 1 up to the last exposure date 
for whole study period analysis and last exposure date for LA regimen for LA regimen period 
analysis,  will be summarized (number and percentage of subjects) by treatment group and total, 
and by preferred name. Multiple drug use (by preferred name) will be counted only once per 
subject. The summary will be sorted alphabetically by preferred drug name. For drugs with the 
same frequency, sorting will be done alphabetically.


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If the start or stop date of non-ARV medications is incomplete, the month and year (or year 
alone, if month is not recorded) of the start or stop date will be used to determine whether the 
non-ARVs are concomitant or not. The medication is concomitant if the month and year of the 
start or stop (or year of the start or stop, if month is not recorded) of the medication does not 
meet either of the following criteria:
The month and year of start of the medication is after the last exposure date (or last exposure 
date for LA regimen for LA regimen period analysis)
The month and year of stop of the medication is before the first dose date of study drug
If the start and stop date of non-ARV medications are complete, the start date is not after last 
exposure date and the stop date is not before first dose date, or the non-ARV medications are 
marked as ongoing and start date is on or before last exposure date, the non-ARV medications 
are concomitant.
Summaries of non-ARV concomitant medications will be based on the Safety Analysis Set. No 
formal statistical testing is planned. A by-subject listing for all non-ARV concomitant 
medications including prior medication will be listed and sorted by subject ID number and 
administration date in chronological order.
7.5.
Electrocardiogram Results
The investigators’ assessment of ECG results are collected. 
A shift table of the investigators’ assessment of ECG results at each scheduled postbaseline visit 
compared with baseline values will be presented by treatment group using the following 
categories: normal; abnormal, not clinically significant; abnormal, clinically significant; or 
missing. The number and percentage of subjects in each cross-classification group of the shift 
table will be presented. Subjects with a missing value at baseline or postbaseline will not be 
included in the denominator for percentage calculation. No inferential statistics will be provided.
A by-subject listing for ECG assessment results will be provided by subject ID number and visits 
in chronological order. 
7.6.
Other Safety Measures
A data listing will be provided for participants experiencing pregnancy during the study. 
7.7.
Changes from Protocol-Specified Safety Analyses
No change from protocol-specified safety analyses is planned.


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8.
REFERENCES
U. S. Department of Health and Human Services, Food and Drug Administration (FDA), Center 
for Drug Evaluation and Research (CDER). Human Immunodeficiency Virus-1 
Infection: Developing Antiretroviral Drugs for Treatment. Guidance for Industry. 
Silver Spring, MD.  November, 2015.


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9.
SOFTWARE
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA.
nQuery Advisor(R) Version 7.0. Statistical Solutions, Cork, Ireland.
Phoenix WinNonlin® 7.0 Pharsigh Corporation, Princeton, NJ, USA. 


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10.
SAP REVISION
Revision Date
(DD MMM YYYY)
Section
Summary of Revision
Reason for Revision


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11.
APPENDICES
Appendix 1.
Study Procedures Table
Appendix 2.
Flowchart of US FDA-defined Snapshot Algorithm (for  Long Acting Switch Trial)
Appendix 3.
Programming Specifications


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Appendix 1.
Study Procedures Table
Treatment Visits Window
(± 3 Days)
Follow-up Visits 
Window
(± 6 Days)
Study Procedure
Screeninga
Day 1
Day 2
Day 8
Wk 4
Wk 8
Wk 12
Wk 16
Wk 20
Wk 24
Wk 26
Wk 38
Wk 52
ET
Post-ET 
30-, 90-, 
and 180- 
Day FUb 
Written Informed Consent
X
Medical History 
X
Review Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Review AEs 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Complete Physical 
Examination
X
X
X
Focused Physical 
Examination
X
X
X
X
X
X
Height 
X
Weight 
X
X
X
X
X
X
X
X
X
Vital Signsc
X
X
X
X
X
X
X
X
X
Proviral DNA Phenotype
X
Bulk Viral Outgrowth 
Phenotype and Proviral DNA 
Genotype
X
Chemistry
X
X
X
X
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
X
X
Coagulation 
X
Thyroid Function 
X
X
X
X
X
X
X
CD4+, CD8+ Cell Count, 
CD4/CD8 Ratio
X
X
X
X
X
X
X
X
X


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Treatment Visits Window
(± 3 Days)
Follow-up Visits 
Window
(± 6 Days)
Study Procedure
Screeninga
Day 1
Day 2
Day 8
Wk 4
Wk 8
Wk 12
Wk 16
Wk 20
Wk 24
Wk 26
Wk 38
Wk 52
ET
Post-ET 
30-, 90-, 
and 180- 
Day FUb 
Serum Pregnancy Test
X
X
X
X
X
X
X
FSHd
X
Urinalysis
X
X
X
X
X
X
X
X
X
Urine Pregnancy Test
X
HBV & HCV Serology
X
HIV-1 RNA 
X
X
X
X
X
X
X
X
X
X
X
X
X
HIV-1 Genotype/Phenotypee
HIV Reservoir Assay 
X
X
eGFR
X
X
X
X
X
X
X
X
X
ECG
X
X
X
X
Immune Biomarker 
Collection
X
X
X
X
X
Plasma Storage Samples for 
Virology Testing
X
X
X
X
X
X
X
X
X
X
X
X
Immunogenicity Assessment 
Serum Sample
X
X
X
X
X
X
PD Biomarkers: PBMC, 
Whole Blood, Serum, Plasma
X
X
X
X
X
Serum PK samples (GS-5423 
& GS-2872)f
X
X
X
Plasma PK Sample for LENg
X
X
X
Single PK Sample (GS-5423 
& GS-2872)
X
X
X
X
X
X
X
X
X


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Treatment Visits Window
(± 3 Days)
Follow-up Visits 
Window
(± 6 Days)
Study Procedure
Screeninga
Day 1
Day 2
Day 8
Wk 4
Wk 8
Wk 12
Wk 16
Wk 20
Wk 24
Wk 26
Wk 38
Wk 52
ET
Post-ET 
30-, 90-, 
and 180- 
Day FUb 
Single Plasma PK Sample for 
LEN
X
X
X
X
X
X
X
X
X
Optional PK Substudy 
Sample 
X
X
X
Randomization
X
LEN Oral Administrationh
X
X
LEN SC Administrationi
X
GS-5423 IV Infusion 
Administrationi
X
GS-2872 IV Infusion 
Administrationi
X
Optional Pharmacogenomic 
Samplej
a.
For the Primary Cohort, screening procedures will be conducted in 2 parts: Part 2 will be performed once results of bNAb sensitivity testing from Part 1 are reviewed and 
participant is deemed eligible to proceed. For the optional Pilot Cohort, participants will be selected by the sponsor from the previously screened/failed participants in the 
Primary Cohort and will directly proceed to Screening Part 2 (no need to repeat Screening Part 1).
b.
Refer to Section 6.5.1 for Post-ET 30-, 90-, and 180-Day follow-up visits.

Counsel participant regarding the importance of continuing a complete ARV therapy in accordance to standard of care, and refer patient to an appropriate HIV treatment 
facility.
c.
Vital signs: blood pressure, pulse, respiration rate, and temperature. On Day 1, vital signs should be recorded prior to start of study drug administration and 30 minutes 
(± 10 minutes) after completion of the GS-2872 infusion.
d.
Serum FSH test (required for female participants < 54 years of age who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal 
failure; see Appendix 5)
e.
HIV-1 genotype and phenotype testing for participants with virologic failure. Refer to Section 6.8.2.
f.
PK serum samples will be collected in all participants for GS-5423 and GS-2872 as follows: 

The exact time of study drug administration and the exact time points (date and time) of collection of plasma samples must be carefully recorded.

Day 1: 0 hour (predose, ≤ 30 minutes prior to dosing of oral LEN for loading), within 5 minutes after the end of the first antibody infusion (GS-5423) and within 
5 minutes after the end of the second antibody infusion (GS-2872)

For ET visit, only single PK sample collection is required


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g.
PK plasma samples for LEN will be collected in all participants as follows: 

PK samples should be drawn from a separate catheter in the opposite arm from the one used for GS-5423 and GS-2872 IV infusion to avoid contamination.

Day 1: 0 hour (predose, ≤ 30 minutes prior to dosing of oral LEN for loading), within 5 minutes after the end of the first antibody infusion (GS-5423) and within 
5 minutes after the end of the second antibody infusion (GS-2872)

For ET visit, only single PK sample collection is required
h.
Participants will take oral LEN for loading on Day 1 at the clinic and self-administer on Day 2 at home, unless participating in the Optional PK Substudy.
i.
On Day 1, participants will receive study treatment consisting of oral and SC LEN, followed by GS-5423, then GS-2872, each administered as separate IV infusions. Infusion 
of GS-2872 will begin at least 15 minutes following, and up to 1 hour after, the completion of GS-5423 IV infusion. Participants will remain in a monitored clinical setting for 
at least 30 minutes after completion of GS-2872 infusion, and vital signs will be recorded 30 minutes (± 10 minutes) after completion of GS-2872 infusion. For the Day 1 
visit, all study drugs are to be administered on the same day. On Day 2, the participant will self-administer 2 tablets of oral LEN for loading (2 × 300 mg) at home at 
approximately the same time oral LEN for loading was administered on Day 1.
j.
If consent for optional pharmacogenomic testing is obtained, then a sample is to be collected at the Day 1 visit, but may be collected at any time during the study or at a 
separate poststudy visit, if necessary.




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The dose date of complete long acting regimen refers to the date of dosing with complete long 
acting drugs (GS-5423, GS-2872, and SC LEN) (ie, Day 1). 
Participants with study drug premature discontinuation are defined as participants who were 
answered “No” to “Did subject complete study drug dosing as specified per protocol?”  and had 
a discontinuation reason other than “Investigator Discretion” (with comment of “Due to Clinical 
hold”) in Study Drug Completion eCRF). 
The date of study drug premature discontinuation is the last exposure date of LA regimen for 
participants who prematurely discontinued study drug.


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Appendix 3.
Programming Specifications
1) SAS codes for the treatment comparison for demographics and baseline characteristics tables.
CMH test for nominal variable (Y), the p-value from the general association test should be 
used for nominal variables:
proc freq;
tables trt * Y /cmh; /*general association test*/
run;
CMH test for ordinal variable (Y), the p-value from the row mean score test should be used 
for ordinal variables:
proc freq;
tables trt * Y / cmh2 ; /*row mean score test*/
run;
Wilcoxon rank sum test for continuous variable (Y), the p-value from the normal 
approximation two-sided test should be used for continuous variables:
proc npar1way wilcoxon;
class trt; 
var Y;
run;
2) Efficacy analyses:
a) For categorical efficacy response (eg, Participants with HIV-1 RNA < 50 copies/mL or 
Participants with HIV-1 RNA ≥ 50 copies/mL as determined by US FDA-defined 
snapshot algorithm, M=F, or M=E Analyses): the proportion difference between 
two treatment groups and its 95% CIs are calculated based on the an unconditional exact 
method using 2 inverted 1-sided tests in SAS v9.3 or above. 
b) The following SAS code will be used to compute cell counts and confidence interval. 
data example;
input  grp trt01a $  outcome $ count ;
datalines;
1       Treat-A        2-Fail        1     
1       Treat-A        1-Succ      189     
1       Treat-B        2-Fail        4     
1       Treat-B        1-Succ       88     
run;
proc freq data = example;
table trt01a*outcome /riskdiff(CL=(exact)) alpha=0.05;
weight count; exact RISKDIFF(METHOD=SCORE);


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output out=ciexact(keep=_RDIF1_ XL_RDIF1 XU_RDIF1 _RSK11_  _RSK21) riskdiff;
run;
data final(keep=A1 B1 Estimate LowerCL UpperCL ocharc1);
set ciexact;
label Estimate ="Percentage Difference"
LowerCL = "95% Lower Confidence Limit"
UpperCL = "95% Upper Confidence Limit"
A1 = "Percentage of Success in Treat-A"
B1 = "Percentage of Success in Treat-B";
Estimate=100*_RDIF1_;
LowerCL = 100*XL_RDIF1;
UpperCL = 100*XU_RDIF1;
A1 = 100*_RSK11_;
B1 = 100*_RSK21_;
ocharc1 = right(compress(put(Estimate,8.1)) || '% (' || compress(put(LowerCL,8.1)) || '% 
to ' || compress(put(UpperCL,8.1)) || '%)');
run;
c) The 95% CI for percentage estimate of HIV-1 RNA < 50 copies/mL for each treatment is 
calculated based on the Clopper-Pearson exact method.
d) Fisher’s exact test for categorical efficacy response (eg, HIV-1 RNA < 50 copies/mL by 
US FDA-defined snapshot algorithm), where trtgrp is the treatment, and response is the 
categorical efficacy response. P-value from 2-sided Fisher’s exact test should be used 
proc freq data=adeff;
tables trtgrp*response/fisher; /*p value from Fisher’s exact 
test*/
run;
e) For figures, if at a visit where n (sample size) for any treatment group <= 5, data for that 
treatment group will not be displayed at the visit in figure (except the Kaplan-Meier 
figure), but all data will be included in the corresponding table summary.
f)
All screened subjects refer to all subjects who are screened (ie, with nonmissing 
screening date) and have a screening number. For summaries the same subject is counted 
only once. DOB and other demographic information such as sex, race, ethnicity, country, 
and initials will be used to identify unique screened subjects.
g) Screen failure subjects are the subjects who were screened and answered “No” for any 
inclusion criteria or “Yes” for any exclusion criteria regardless of which version of 
protocol the subject was consent to, or subjects who have missing answer to any 
inclusion or exclusion criteria.
h) Baseline ARV medication is defined as:


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Using the ARV raw dataset, include all prior ARVs (where ARV.CMSCAT =’Prior 
ARV”), taken on or up to 2 day prior to first dose date (or randomization date if not 
treated), i.e. End date of ARV >= first dose date -2.
i)
For last dose date calculation:
For participants who receive injection or infusion, the last dose date is defined as the 
latest nonmissing end date of the study drug used.
For participants who do not receive injection or infusion, the last dose date is defined as 
the last dose date of oral LEN.
If the date of last dose is incomplete or missing (eg, due to lost to follow-up), the latest 
nonmissing study drug start dates the clinic visit dates, and the laboratory visit dates 
excluding the dates of any follow-up visits will be used to impute the last dose date.


GS US-536-5816-Week26-SAP
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
 eSigned
04-Aug-2022
02:11:25
 eSigned 05-Aug-2022
00:00:34
PPD
PPD
PPD
PPD