An Open-Label, Randomized, Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of Pegcetacoplan in the Treatment of Post-Transplant Recurrence of C3G or IC-MPGN
Phase: PHASE2
Conditions: C3G, IC-MPGN, Renal Transplant, Complement 3 Glomerulopathy, Complement 3 Glomerulopathy (C3G), Dense Deposit Disease (DDD), Membranoproliferative Glomerulonephritis, Membranoproliferative Glomerulonephritis (MPGN), Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN), C3 Glomerulopathy, C3 Glomerulonephritis, Complement 3 Glomerulonephritis
Sponsor: Apellis Pharmaceuticals, Inc.

A pellis P har mace uticals, I nc
Pa ge 1 
C o nfi de ntial
P E G C E T A C O P L A N  (A P L‑ 2 ) 
A P L 2 -C 3 G -2 0 4
A N O P E N -L A B E L, R A N D O MI Z E D, C O N T R O L L E D, 
P H A S E 2 S T U D Y T O E V A L U A T E T H E S A F E T Y A N D 
E F FI C A C Y O F P E G C E T A C O P L A N I N T H E 
T R E A T M E N T O F P O S T -T R A N S P L A N T R E C U R R E N C E 
O F C 3 G O R I C‑ M P G N
Re g ul at or y A ge nc y I de ntifier N u m ber(s)
E u dra C T:  2 0 2 0‐ 0 0 2 6 3 7‐ 1 5
S P O N S O R’ S A P P R O V A L
T he pr ot oc ol has bee n a p pr o ve d b y A pellis P har m ace uticals, I nc. 
A pelli s P har mace uticals, I nc
1 0 0 5t h A ve n ue 
Walt ha m, M A 0 2 4 5 1
0 3 Fe br uar y 2 0 2 2 
A me n d me nt  3 
A me n d me nt N u m ber
P P D
C CI
P P D

Pe gcet ac o pl a n  (A P L‑ 2 ) 
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C o nfi de nti al  
I N V E S TI G A T O R’ S A G R E E M E N T 
 
I ha ve recei ve d a n d rea d t he i n vesti gat or’s br oc h ure f or pe gcetac o pla n  (A P L‑ 2 ). I ha ve r ea d t he 
A P L 2 -C 3 G - 2 0 4 pr ot oc ol a n d a gree t o c o n d uct t he st u d y as o utli ne d. I a gr ee t o mai ntai n t he 
c o nfi de ntialit y of all i nf or mati o n recei ve d or de vel o pe d i n c o n necti o n  wit h t his pr ot oc ol.  
 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
 
Pri nte d Na me of I n vesti gat or  
 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
 
Si g nat ure of I n vesti gat or  
 
  
  
  
  
  
  
 
Date  
 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
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0 3 Fe br uar y 2 0 2 2 
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C o nfi de nti al  
P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E S  
D O C U M E N T HI S T O R Y  
D oc u me nt  
A p pr o v al d ate 
A m e n d m e nt 3  
0 3 Fe br uar y 2 0 2 2  
A m e n d m e nt 2  
0 1 Marc h 2 0 2 1  
A m e n d m e nt 1  
2 7  Ma y  2 0 2 0 
Ori gi nal Pr ot oc ol  
2 9 Ma y  2 0 1 9 
P r ot oc ol A me n d me nt 3  
O ver all R ati o n ale f or t he A me n d me nt:  
T he pr ot oc ol was a me n de d t o m o dif y t he eli gi bilit y criteria i n or der t o i m pr o ve s u bject 
recr uit me nt a n d e nr ollme nt a n d t o re d uce t he d ur ati o n of t he f oll o w -u p peri o d, t h us ali g ni n g wit h 
ot her ne p hr ol o g y cli nical trials at A pellis.  
A d diti o nal re visi o ns were ma de t o  clarif y st ud y acti vities  a n d pr oce d ur es a n d  t o ali g n wit h 
c urre nt c o m pa n y practices , a n d mi n or f or matti n g a n d st ylistic r e visi o ns wer e ma de t o ali g n wit h 
c urre nt te m plates a n d a n y i de ntifie d t y p o gr a p hical or ot her mi n or err ors wer e c orr ecte d; t hese ar e 
n ot i de ntifie d i n di vi d uall y  i n t he descri pti o ns bel o w. 
Desc ri pti o n of c h a n ge 
Se cti o n(s) affe cte d b y c h a n ge  
Re m o ve d eli gi bilit y re q uire me nt f or pr ot ei n uri a of at le ast 1  g/ da y i n a 
2 4- h o ur uri ne c olle cti o n . 
S y n o psis , Secti o n  6. 2 , Se cti o n 7. 1. 1  
Re d uc e d e G F R eli gi bil it y re q uire me nt fro m  at le ast 3 0 m L/ mi n/ 1. 7 3  m2 
to at  le ast 1 5  m L/ mi n/ 1. 7 3  m2. 
S y n o psis , Secti o n 6. 2 , Se cti o n 7. 1. 1  
Re d uc e d d urati o n of f oll o w -u p peri o d fr o m 2 4  we e ks t o 8  wee ks ; bec a use 
t he effe cti ve half-life of s u bc uta ne o us pe gecta c o pla n at t he d oses use d i n 
t his st u d y is a p pr o xi m at el y 8 t o 1 0 da ys, t his is s uffi ci e nt t o c o ver t he 
was h o ut peri o d. 
S y n o psis , Secti o n  6. 1 , Fi g ure 1 , 
Se cti o n  6 . 2, Sc he d ul e of Acti vities 
(T a bl e  1, T a bl e  2), S e cti o n 9. 3 , 
Se cti o n  9 . 4, Secti o n 1 5. 2. 1 0  
(T a bl e  8, T a bl e  9) 
C ha n ge d se c o n dar y effic ac y e n d p oi nt of t he pr o p orti o n of s u bj ects wit h a 
5 0 % re d ucti o n i n pr ot ei n uria a n d sec o n dar y effi ca c y e n d p oi nt of t he 
pr o p orti o n of s u bje cts wit h n or m ali zati o n of pr otei n uria t o e x pl orat or y 
e n d p oi nts; t hese e n d p oi nts will n o w be e val uate d i n s u bje cts wit h 
baseli ne pr ot ei n uri a a b o ve t he u p per li mit of n or mal  at b ot h W ee k  1 2 a n d 
W ee k  5 2 . Up date d st atisti cal a nal yses t o ali g n wit h t his c ha n ge.  
S y n o psis , Secti o n 5. 2. 1 , Secti o n 1 2. 3  
Re or ga niz e d prese nt ati o n of e n d p oi nts f or i m pr o ve d clarit y , i ncl u di n g 
re m o val of disc ussi o n of e x pl orat or y e n d p oi nts fr o m s y n o psis. Ali g ne d 
prese nt ati o n of statistic al a nal yses wit h prese nt at i o n of e n d p oi nts. 
S y n o psis , Secti o n 5. 2. 1 , Secti o n 1 2  
A d de d e x pl orat or y e n d p oi nts of C 3 G hist ol o gi c i n de x acti vit y sc ore a n d 
c hr o ni cit y sc ore . 
Se cti o n  5. 2. 1. 3  
Re d uc e d c olle cti o n a n d a nal ysis of sa m ples f or t he m eas ure m e nt of C 3 
ne p hritic fact or.  
Sc he d ul e of Acti vities ( Ta ble  1), 
Se cti o n  1 5 . 1. 1 (T a bl e  7 ), 
Se cti o n  1 5. 2. 1 0  (T a ble  8, Ta ble  9, 
T a bl e  1 0) 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
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0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 4 
 
C o nfi de nti al  
Desc ri pti o n of c h a n ge 
Se cti o n(s) affe cte d b y c h a n ge  
Re d uc e d t he fre q ue nc y of c oll ecti o n of a nti dr u g a nti b o d y sa m ples i n t he 
l o n g-ter m e xte nsi o n peri o d ( Part B of t he st u d y) as t his will be s uffi ci e nt 
t o effecti vel y m o nit or i m m u n o ge ni c res p o nses.  
Se cti o n  1 5. 1. 1  (T a bl e  7 ), 
Se cti o n  1 5. 2. 1 0  (T a ble  1 0) 
A d de d disc ussi o n of C O VI D -1 9 vac ci nati o n t o C O VI D -1 9 ris k miti gati o n 
se cti o n a n d C O VI D-1 9 a p pe n di x. 
Se cti o n  4. 4. 1 , Se cti o n 1 5. 2. 5  
A d de d eli gi bilit y crit eri o n e xcl u di n g s u bje cts wit h k n o w n or s us pe cte d 
here ditar y fr uct ose i nt ol era nc e.  
S y n o psis , Secti o n 7. 1. 2  
A d de d w or di n g descri bi n g s hi p pi n g of  i n vesti gati o nal pr o d uct a n d/ or 
ot her st u d y s u p plies dire ctl y t o t he s u bje ct  t o m ai n b o d y of pr ot oc ol a n d 
re m o ve d fr o m C O VI D c o nti n uit y a p pe n di x.  
Se cti o n  8. 4 , Secti o n  1 5. 2   
U p date d esti mate of a p pr o xi mate bl o o d v ol u m e t o be c oll ecte d d uri n g t he 
st u d y. 
Se cti o n  1 0. 1 8  
Re vise d disc ussi o n of se verit y of a d verse e ve nts t o re m o ve g ui da nc e o n 
re p orti n g c ha n ges i n se verit y; t his g ui da nce will be pr o vi de d i n ot her 
st u d y d oc u m e ntati o n.  
Se cti o n  1 1. 2. 2  
 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
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C o nfi de nti al  
1.  
S Y N O P SI S  
Title of St u d y:  
A n O pe n -La bel, Ra n d o miz e d, C o ntr oll e d, P hase 2 St u d y t o E val uat e t he Safet y 
a n d E ffi ca c y of Pe gc et ac o pl a n i n t he Tre at me nt of P ost-Tra ns pl a nt Re c urre nc e of 
C 3 G or I C‑ M P G N  
P r ot oc ol N u m be r:  
A P L 2 - C 3 G-2 0 4  
P h ase of De vel o p me nt:  
P hase  2 
O bjecti ves:  
P ri m ar y: 
T o e val uate t he effic ac y of pe gc eta c o pla n i n i m pr o vi n g t he u n derl yi n g 
pat h o p h ysi o l o g y of c o m pl e m e nt 3 gl o m er ul o pat h y ( C 3 G)/i m m u ne c o m pl e x 
m e m bra n o pr oliferati ve gl o m er ul o ne p hritis (I C -M P G N) after 1 2  wee ks of 
treat m e nt. 
Se c o n d ar y:  
•  
T o e val uate t he effect of pe gc et ac o pl a n  o n ke y cli nic al m a nifest ati o ns of 
t he dise ase after 5 2 we e ks of tre at me nt.  
•  
T o e val uate t he safet y of pe gceta c o pl a n  f or u p t o 5 2  we e ks i n patie nts 
wit h rec urre nt C 3 G/I C -M P G N i n a re nal all o graft.  
St u d y E n d p oi nts:  
P ri m ar y Effic ac y E n d p oi nt:  
T he pri mar y effi ca c y e n d p oi nt is t he pr o p orti o n of s u bje cts wit h re d ucti o n i n C 3c 
st ai ni n g o n re nal bi o ps y after 1 2 wee ks of treat m e nt wit h pe gc eta c o pla n.  
Se c o n d ar y Effic ac y E n d p o i nts: 
T he sec o n dar y effi ca c y e n d p oi nts are as f oll o ws:  
•  
T he pr o p orti o n of s u bj ects wit h re d ucti o n i n C 3c stai ni n g o n re nal bi o ps y 
after 5 2 we e ks of tre at me nt  
•  
T he pr o p orti o n of s u bj ects wit h st a biliz ati o n or i m pr o ve m ent i n esti m ate d 
gl o mer ul ar filtrati o n rat e (e G F R), o ver ti m e  
•  
T he pr o p orti o n of s u bj ects wit h st a biliz ati o n or i m pr o ve m e nt of ser u m 
creati ni ne c o nc e ntrati o n  o ver ti me  
•  
C ha n ges fr o m baseli ne bi o ps y i n C 3c stai ni n g o ver ti m e  
•  
C ha n ges a n d perc e nt a ge c ha n ges fr o m baseli ne i n e G F R a n d ser u m 
creati ni ne c o nc e ntrati o n o ver ti me  
S afet y E n d p oi nts:  
T he safet y e n d p oi nts are as f oll o ws:  
•  
T he n u m ber a n d i nci de nce of tre at me nt -e mer ge nt a d verse e ve nts 
( T E A Es) 
•  
T he c ha n ge fr o m baseli ne i n vital si g ns me as ure m e nts a n d cli nic al 
l a b orat or y test a n d E C G res ults 
St u d y Desi g n:  
T his P hase  2, m ultic e nt er, o pe n -la bel, ra n d o miz e d, c o ntr olle d st u d y is desi g ne d t o 
e val uat e t he safet y a n d effic ac y of pe gc et ac o pla n i n patie nts w h o ha ve p ost -
tra ns pl a nt re c urre nce of C 3 G or I C-M P G N. T here will be u p t o 1 2  s u bj ects 
e nr oll e d i n t his st u d y. T here are 3  peri o ds of t his st u d y:  
P art A, C or e St u d y:  
•  
Scre e ni n g peri o d: u p t o a n 8 -we e k w ee k scre e ni n g peri o d, d uri n g w hi c h a 
scre e ni n g re nal all o graft bi o ps y will oc c ur 
•  
Mai n peri o d: a 5 2 -wee k st u d y peri o d t hat c o ntai ns 2  p orti o ns ( C o ntr oll e d 
a n d N o nc o ntr olle d) d uri n g w hi c h s u bj ects will be ra n d o mi ze d t o eit her 
Gr o u p 1 or Gr o u p  2 at t he W ee k  1 st u d y visit:  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
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C o nfi de nti al  
o  
C o ntr olle d p orti o n: W ee ks  1 -1 2 of t he st u d y  
 
Gr o u p 1: U p t o 9  s u bje cts will be ra n d o mize d t o t his 
treat m e nt gr o u p a n d will re cei ve pe gc et ac o pla n 
treat m e nt t hr o u g h o ut t he e ntire st u d y; bi o psies will 
oc c ur at We e k  1 2.  
 
Gr o u p 2: U p t o 3  su bje cts will be ra n d o mize d t o t his 
treat m e nt gr o u p a n d t he y will n ot re cei ve pe gc et ac o pl a n 
treat m e nt d uri n g t he C o ntr oll e d P orti o n; bi o psi es will 
oc c ur at We e k  1 2.  
o  
N o nc o ntr oll e d p orti o n: We e ks  1 3-5 2 of t he st u d y 
 
Gr o u p 1: S u bj ects  will c o nti n ue t o rec ei ve 
pe gceta c o pla n treat m e nt; bi o psies will oc c ur at 
W ee k  5 2.  
 
Gr o u p 2: S u bj ects w ill rec ei ve pe gceta c o pl a n treat m e nt 
f oll o wi n g t heir W ee k 1 2  re nal all o graft bi o ps y; bi o psies 
will occ ur at We e k  5 2.  
•  
F oll o w- u p peri o d: a n 8- we e k f oll o w -u p peri o d  
P art B, L o n g -Te r m E xte nsi o n:  
A n y s u bje ct w h o, i n t he o pi ni o n of t he i n vesti gat or, is e x perie nci n g cli nical be nefit 
fr o m pe gc et ac o pl a n a d mi nistrati o n ma y partici pate i n Part B, a l o n g -ter m 
e xte nsi o n, i n or der t o c o nti n ue t o re cei ve treat m e nt wit h pe gcet ac o pl a n u ntil it is 
c o m m erciall y a vail a bl e f or t he disease u n der st u d y. If i n vit e d t o parti ci pate, t he 
s u bj ect ca n e nter Part B as s o o n as t heir 5 2-we e k treat m e nt peri o d has e n de d a n d 
d oes n ot nee d t o partici pate i n t he 8- wee k f oll o w -u p peri o d.  
Sel ecti o n of S u bje cts:  
I ncl usi o n Crite ri a:  
I n di vi d uals m ust me et all of t he f oll o win g crit eri a at scre e ni n g visits t o be i ncl u de d 
i n t he st u d y: 
1.  At le ast 1 8  ye ars o f a ge at scre e ni n g 
2.  M ust ha ve cli ni cal a n d pat h ol o gi c e vi de nce of rec urre nt C 3 G or I C -
M P G N, a s e vi de nce d b y all of t he f oll o wi n g: 
a. A dia g n osis of C 3 G or I C -M P G N, wit h  at le ast 2 +  stai ni n g f or 
C 3c i n t he re nal all o graft, c o nfir m e d b y a c e ntral pat h ol o gist, 
base d o n t he scree ni n g re nal all o graft bi o ps y  
b.  C 3 G or I C -M P G N m ust be pri m ar y a n d n ot sec o n dar y t o a n ot her 
c o n diti o n (e g, i nfecti o n, m ali g na nc y, m o n ocl o nal ga m m o pat h y,  
a ut oi m m u nit y, c hr o nic a nti b o d y -me diate d reje cti o n, c hr o nic 
t hr o m b oti c mi cr oa n gi o pat h y, or a me dic ati o n)  
3.  St a ble ( n ot i m pr o vi n g) or w orse ni n g dise ase, i n t he o pi ni o n of t he 
i n vesti gat or, i n t he 2 m o nt hs pre ce di n g t he first d ose of pe gcet ac o pl a n  
4.  e G F R ≥1 5  m L / mi n/ 1. 7 3 m 2, c al c ul at e d b y t he C hr o ni c Ki d ne y Disease–
E pi de mi ol o g y C oll a b orati o n ( C K D -E PI) cre ati ni ne e q uati o n f or a d ults  
5.  N o m ore t ha n 5 0 % gl o mer ul oscler osis or i nt erstiti al fi br osis o n t he 
scre e ni n g re nal all o graft bi o ps y 
6.  St a ble re gi me n f or rec urre nt C 3 G/I C-M P G N f or at le ast 4  we e ks pri or t o 
t he scre e ni n g re nal all o graft bi o ps y a n d fr o m t he ti me of t he scre e ni n g 
re nal all o graft bi o ps y u ntil ra n d o mi zati o n 
7.  Ha ve rec ei ve d re q uire d va cci nati o ns a gai nst N. me ni n giti dis , 
S. p ne u m o ni ae , a n d H.  i nfl uenz ae  (t y pe B) or a gre e t o re cei ve 
va cci nati o ns if a p plic a bl e va cci nati o n rec or ds are n ot a vail a bl e. 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
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C o nfi de nti al  
Va c ci nati o n is m a n dat or y u nless d oc u m e nt e d e vi de nce e xists t hat s u bje cts 
are n o nres p o n ders t o vac ci nati o n.  
8.  W o me n of c hil d be ari n g p ot e ntial, defi ne d as a n y w o me n w h o ha ve 
e x peri e nce d m e narc he a n d w h o are n ot per m a ne ntl y st erile or 
p ost me n o pa usal, m ust e ac h ha ve a ne gati ve bl o o d pre g na nc y test at 
scre e ni n g (a n d ne gati ve uri ne pre g na nc y at Visit 4) a n d m ust a gre e t o use 
pr ot oc ol- defi ne d m et h o ds of c o ntrac e pti o n fr o m scre e ni n g t hr o u g h 
1 2 wee ks after rec ei vi n g l ast d ose of pe gceta c o pla n  
9.  Me n m ust a gree t o use pr ot oc ol -defi ne d m et h o ds of c o ntra ce pti o n a n d 
a gree t o refrai n fr o m d o nati n g se me n fr o m scree ni n g t hr o u g h 1 2  we e ks 
after re cei vi n g last d ose of pe gceta c o pl a n  
1 0.  W illi n g a n d a bl e t o pr o vi de writt e n i nf or m e d c o nse nt  
1 1.  A bl e t o u n dersta n d a n d willi n g t o c o m pl y wit h all sc he d ul e d pr oc e d ures 
a n d ot her re q uire me nts of t he st u d y i n t he o pi ni o n of t he i n vesti gat or 
1 2.  Willi n g a n d a bl e t o self -a d mi nist er pe gceta c o pl a n or ha ve a n i de ntifie d 
c are gi ver w h o c a n perf or m t he a d mi nistrati o n  
E xcl usi o n Criteri a:  
I n di vi d uals m eeti n g a n y of t he f oll o wi n g crit eri a at scree ni n g or baseli ne are 
i neli gi ble t o partici pate i n t his st u d y: 
1.  A bs ol ute ne utr o p hil c o u nt < 1 0 0 0  c ells/ m m 3 d uri n g scree ni n g ( n ot 
i ncl u di n g Da y 1) 
2.  Pre vi o us tre at me nt wit h pe gc et ac o pl a n  
3.  E vi de nc e of rej ecti o n o n t he scre e ni n g re nal all o graft bi o ps y t hat re q uires 
treat m e nt 
4.  Di a g n osis or hist or y of HI V, he patitis  B, or he pa titis C i nfe cti o n or 
p ositi ve ser ol o g y at scree ni n g i n dic ati ve of i nfe cti o n wit h a n y of t hese 
vir uses 
5.  W ei g ht m ore t ha n 1 0 0  k g at scre e ni n g 
6.  H y perse nsiti vit y t o pe gc et ac o pla n or a n y of the e xci pi e nts  
7.  Hist or y of me ni n g oc oc cal dise ase  
8.  Mali g na nc y, e xce pt f or t he f oll o wi n g:  
a. C ure d basa l or s q ua m o us cell s ki n c a nc er 
b.  C urati vel y tre at e d i n sit u disease  
c. Mali g na nc y free a n d off tre at me nt f or ≥5  ye ars  
9.  Si g nifi ca nt re nal dise ase i n t he re nal all o graft sec o n dar y t o a n ot her 
c o n diti o n (e g, i nfecti o n, m ali g na nc y, m o n ocl o nal ga m m o pat h y, rej ecti o n, 
or a m e di cati o n) t hat w o ul d , i n t he o pi ni o n of t he i n vesti gat or, c o nf o u n d 
i nter pret ati o n of t he st u d y res ults 
1 0.  Partici pati o n i n a n y ot her i n vesti gati o nal dr u g tri al or e x p os ure t o ot her 
i n vesti gati o nal a ge nt, de vi ce, or pr oc e d ure wit hi n 3 0  da ys or 5  half -li ves 
fr o m t he l ast d ose of t he i n vesti gati o nal a ge nt ( w hic he ver is l o n ger) pri or 
t o scree ni n g 
1 1.  W o me n w h o are pre g na nt, or w h o are c urre ntl y breastfe e di n g  
1 2.  I na bilit y t o c o o perate or a n y c o n diti o n t hat, i n t he o pi ni o n of t he 
i n vesti gat or, c o ul d i ncrease t he s u bj ect’s ris k b y parti ci pati n g i n t he st u d y 
or c o nf o u n d t he o ut c o m e of t he st u d y  
1 3.  E vi de nc e of dr u g or al c o h ol a b use or de pe n de nce, i n t he o pi ni o n of t he 
i n vesti gat or  
1 4.  K n o w n or s us pecte d here dit ar y fr uct ose i nt olera nce.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 8 
 
C o nfi de nti al  
Pl a n ne d S a m ple Si ze:  
U p t o 1 2  s u bje cts t o be e nr olle d 
I n vesti g ati o n al T her a p y: 
Pe gcet ac o pl a n ( A P L -2) 1 0 8 0  m g t wi c e/ we e k a d mi nistere d via s u bc uta ne o us 
i nf usi o n ( 2 0 m L)  
Tr e at me nt D ur ati o n:  
Part A: E ac h s u bje ct will ha ve u p t o a n 8 -wee k scree ni n g peri o d t o be f oll o we d b y 
a 5 2-we e k p eri o d, d uri n g w hic h ti me Gr o u p 1 will ha ve pe gcet ac o pl a n 
a d mi nistrati o n f or all 5 2 wee ks a n d Gr o u p  2 will rec ei ve pe gc eta c o pla n 
a d mi nistrati o n o nl y f oll o wi n g t he We e k  1 2 bi o ps y t hr o u g h t he re mai n der of t he 
m ai n peri o d of t he st u d y. All s u bj ects t he n e nt er t he 8- wee k f oll o w -u p peri o d o r 
t he l o n g-ter m e xte nsi o n ( Part B).  
T otal d urati o n of parti ci pati o n: u p t o 6 8 wee ks ( n ot i ncl u di n g t he l o n g -t er m 
e xte nsi o n) 
St atistic al Met h o ds a n d 
Pl a n ne d A n al yses:  
Gi ve n t he e x pl orat or y nat ure of t he st u d y, n o f or m al st atisti cal h y p ot heses testi n g 
will be pe rf or m e d, t heref ore t he sa m ple siz e is n ot base d u p o n st atisti cal p o wer of 
t he st u d y. 
T he f oll o wi n g re prese nt t he a nal ysis sets t o be a nal yze d: scree ne d, i nt e nt -t o-tre at 
(I T T), safet y, p har m ac o ki netic, a n d p har m ac o d y na mic. T he s pe cific assess me nts 
are o utli ne d bel o w. 
Effi c ac y Assess me nts : 
A n al ysis of P ri m ar y Effic ac y E n d p oi nt:  T he pr o p orti o n of s u bj ects wit h 
re d ucti o n i n C 3c stai ni n g o n re nal bi o ps y after 1 2 we e ks o n st u d y will be 
t a b ul at e d. N o f or mal st atisti cal h y p ot hesis t esti n g will be perf or me d. 
A n al ysis of Sec o n d ar y Effi c ac y E n d p oi nts:  C ha n ges fr o m baseli ne bi o ps y i n 
C 3c st ai ni n g o ver ti me will be s u m marize d b y treat m e nt gr o u p. T he pr o p orti o n of 
s u bj ects wit h re d ucti o n i n C 3c stai ni n g o n re nal bi o ps y after 5 2 wee ks of treat m e nt 
will b e ta b ul at e d.  
C ha n ges a n d perc e nt a ge c ha n ges i n e G F R a n d ser u m cre ati ni ne  c o nc e ntrati o n o ver 
ti me will be s u m m ari ze d b y tre at me nt gr o u p. Esti m ate d gl o m er ul ar filtrati o n rat e 
a n d ser u m creati ni ne c o nc e ntrati o n will be me as ure d at baseli ne a n d at ea c h 
p ostra n d o mi zati o n assess me nt. T he pr o p orti o n of s u bj ects wit h sta biliz ati o n or 
i m pr o ve m e nt i n ea c h para m et er will be ta b ul at e d. A sta ble or i m pr o ve d e G F R will 
be defi ne d as n o m ore t ha n a 2 5 % de cre ase i n e G F R relati ve t o baseli ne. A st a bl e 
or i m pr o ve d ser u m cre ati ni ne  c o nce ntrati o n will be defi ne d as n o i ncrease or a n 
i ncre ase of n o m ore t ha n 2 5 % fr o m baseli ne. 
Assess me nt of S afet y: 
T he n u m ber a n d i nci de nce of T E A Es ( b ot h seri o us a n d n o nseri o us) as well as t he 
n u m ber a n d i nci de nc e of disc o nti n uati o ns d ue t o T E A Es will be ta b ul ate d.  
T he a d verse e ve nt s u m m ari es will be prese nte d acr oss all s u bj ects. All a d verse 
e ve nts will be liste d b y s u bje ct, al o n g wit h i nf or m ati o n re gar di n g o nset, d urati o n, 
se verit y, relati o ns hi p t o st u d y dr u g, acti o n t a ke n wit h st u d y dr u g, tre at me nt of 
e ve nt, a n d o utc o me. I n a d diti o n, t he n u m ber a n d i nci de nc e of rej ecti o n e pis o des 
a n d graft l oss i n e ac h gr o u p will be ta b ul at e d.  
C ha n ges fr o m baseli ne i n cli ni cal la b orat or y t ests will be s u m mariz e d usi n g 
descri pti ve  statistics b y visit a n d n o mi nal ti m e p ost d ose.  
C ha n ges fr o m baseli ne i n vital si g ns will be s u m m ari ze d b y visit usi n g descri pti ve 
st atistics.  
C ha n ges fr o m baseli ne i n el ectr ocar di o gra m para meters will be s u m mariz e d b y 
visit usi n g des cri pti ve statistics.  
C ha n ges i n p h ysic al e xa mi nati o ns will be descri be d i n a dat a listi n g.  
 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 9 
 
C o nfi de nti al  
2.  
T A B L E O F C O N T E N T S, LI S T O F T A B L E S, A N D LI S T O F 
FI G U R E S  
TI T L E P A G E  .............................................................................................................................. 1 
S P O N S O R’ S A P P R O V A L  ......................................................................................................... 1 
I N V E S TI G A T O R’ S A G R E E M E N T ........................................................................................... 2 
P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E S  ....................................................... 3 
1.  
S Y N O P SI S  ............................................................................................................... 5  
2.  
T A B L E O F C O N T E N T S, LI S T O F T A B L E S, A N D LI S T O F FI G U R E S  ................ 9 
3.  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F T E R M S  ........................... 1 7  
4.  
I N T R O D U C TI O N .................................................................................................. 1 9 
4. 1.  
C 3 G a n d I C -M P G N a n d U n met Me dical Nee d  ....................................................... 1 9 
4. 2.  
St u d y Rati o nale  ...................................................................................................... 2 0 
4. 2. 1.  J ustificati o n of D ose ......................................................................................... 2 0 
4. 3.  
S u m mar y of Cli nical E x perie nce Wit h Pe gcetac o pla n  ............................................. 2 1 
4. 4.  
Cli nical Ris ks/ Be n efits of Pe gcetac o pla n  ................................................................ 2 1 
4. 4. 1.  C O VI D -1 9 Ris k Miti gati o n Meas ur es  ............................................................... 2 2 
5.  
S T U D Y O BJ E C TI V E S A N D E N D P OI N T S  ........................................................... 2 4 
5. 1.  
St u d y O bjecti ves  ..................................................................................................... 2 4 
5. 1. 1.  Pri mar y O bjecti ve  ............................................................................................. 2 4 
5. 1. 2.  Sec o n dar y O bjecti ves  ........................................................................................ 2 4 
5. 1. 3.  E x pl orat or y O bjecti ves  ..................................................................................... 2 4 
5. 2.  
St u d y E n d p oi nts  ..................................................................................................... 2 4 
5. 2. 1.  Effic ac y E n d p oi nts ............................................................................................ 2 4 
5. 2. 1. 1.  
Pri mar y Efficac y E n d p oi nt  .................................................................... 2 4 
5. 2. 1. 2.  
Sec o n dar y Efficac y E n d p oi nts  ............................................................... 2 4 
5. 2. 1. 3.  
E x pl orat or y Efficac y E n d p oi nts  ............................................................. 2 5  
5. 2. 2.  Safet y E n d p oi nts  ............................................................................................... 2 5  
5. 2. 3.  P K E n d p oi nts  .................................................................................................... 2 5  
5. 2. 4.  P D E n d p oi nts  .................................................................................................... 2 6 
5. 2. 5.  I m m u n o ge nicit y E n d p oi nts ............................................................................... 2 6 
6.  
I N V E S TI G A TI O N A L P L A N ................................................................................. 2 7  
6. 1.  
Descri pti o n of O verall St u d y Desi g n a n d Pla n  ........................................................ 2 7  
6. 2.  
St u d y Desi g n  .......................................................................................................... 2 8 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 1 0 
 
C o nfi de nti al  
6. 2. 1.  Scree ni n g Peri o d  ............................................................................................... 2 9 
6. 2. 2.  Mai n Peri o d  ...................................................................................................... 2 9 
6. 2. 3.  Part B: L o n g -T er m E xte nsi o n  ........................................................................... 3 0 
6. 2. 4.  F oll o w- u p Peri o d  .............................................................................................. 3 0 
6. 2. 5.  E n d of St u d y  ..................................................................................................... 3 0 
7.  
S T U D Y P O P U L A TI O N  ......................................................................................... 3 1 
7. 1.  
Selecti o n  of St u d y P o p ulati o n  ................................................................................. 3 1 
7. 1. 1.  I ncl usi o n Criteria .............................................................................................. 3 1 
7. 1. 2.  E xcl usi o n Criteria  ............................................................................................. 3 2 
7. 1. 3.  A p pr o ve d Met h o ds of C o ntr ace pti o n ................................................................. 3 2 
7. 2.  
Disc o nti n uati o ns a n d S u bjects L ost t o F oll o w - u p .................................................... 3 3 
7. 2. 1.  E arl y Treat me nt Disc o nti n uati o n a n d St u d y Wit h dr a wal  ................................... 3 3 
7. 2. 2.  Reas o ns f or Disc o nti n uati o n  ............................................................................. 3 3 
7. 2. 3.  Li ver T o xicit y  ................................................................................................... 3 4 
7. 2. 4.  S u bje cts L ost t o F oll o w -u p Pri or t o Last Sc he d ule d Visit  .................................. 3 5  
7. 2. 5.  Re place me nt of S u bjects  ................................................................................... 3 5  
8.  
T R E A T M E N T S  ...................................................................................................... 3 6 
8. 1.  
Details of St u d y Treat me nts  .................................................................................... 3 6 
8. 2.  
D osa ge Selecti o n  .................................................................................................... 3 6 
8. 3.  
I n vestigati o nal Pr o d uct A d mi nistr ati o n  ................................................................... 3 6 
8. 4.  
La beli n g, Pac ka gi n g, I nf usi o n S u p plies, a n d St or a ge a n d Ha n dli n g ......................... 3 7  
8. 4. 1.  La beli n g ............................................................................................................ 3 7  
8. 4. 2.  Pac ka gi n g  ......................................................................................................... 3 7  
8. 4. 3.  I nf usi o n S u p plies .............................................................................................. 3 7  
8. 4. 4.  St ora ge a n d Ha n dli n g  ........................................................................................ 3 7  
8. 5.  
Meas ures t o Mi ni mize Bias: St u d y Tr eat me nt Assi g n me nt  ..................................... 3 8 
8. 5. 1.  Met h o d of St u d y Treat me nt Assi g n me nt  ........................................................... 3 8 
8. 6.  
I n vesti gati o nal Pr o d uct Acc o u nta bilit y ................................................................... 3 8 
8. 7.  
S u bject C o m plia nce  ................................................................................................ 3 9 
8. 8.  
Pri or a n d C o nc o mita nt Me dicati o ns a n d Pr oce d ur es  ............................................... 3 9 
8. 8. 1.  E m piric A nti bi otic Treat me nt f or P ossi ble I nf ecti o n  ......................................... 3 9 
9.  
S T U D Y P R O C E D U R E S  ........................................................................................ 4 0 
9. 1.  
Scree ni n g  ................................................................................................................ 4 8 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 1 1 
 
C o nfi de nti al  
9. 1. 1.  Rescree ni n g  ...................................................................................................... 4 8 
9. 1. 2.  Scree ni n g Pr oce d ures  ........................................................................................ 4 8 
9. 1. 2. 1.  
Visit  1 ................................................................................................... 4 8 
9. 1. 2. 2.  
Visit  2 ................................................................................................... 4 9 
9. 1. 3.  Re nal Bi o ps y  .................................................................................................... 4 9 
9. 1. 4.  Vacci nati o ns  ..................................................................................................... 4 9 
9. 1. 5.  Pr o p h ylactic A nti bi otics  .................................................................................... 5 0  
9. 2.  
Mai n Peri o d  ............................................................................................................ 5 1  
9. 2. 1.  Ra n d o miza ti o n Visit ......................................................................................... 5 1  
9. 2. 1. 1.  
I m me diatel y F oll o wi n g Ra n d o mizati o n, All S u bjects ............................ 5 1  
9. 2. 1. 2.  
Gr o u p 1 S u bjects O nl y  .......................................................................... 5 1  
9. 2. 1. 3.  
All S u bjects  ........................................................................................... 5 2  
9. 2. 2.  Pri mar y E n d p oi nt Bi o ps y at 1 2 Wee ks  .............................................................. 5 2  
9. 2. 3.  Visit  7 or 8 ( Wee k  1 2 or 1 4) .............................................................................. 5 2  
9. 2. 3. 1.  
Pri or t o Pe gcetac o pla n A d mi nistr ati o n  ................................................... 5 2  
9. 2. 3. 2.  
A d mi nistrati o n of Pe gcetac o pla n  ........................................................... 5 3  
9. 2. 3. 3.  
Gr o u p 2 S u bjects O nl y  .......................................................................... 5 3  
9. 2. 3. 4.  
All S u bjects  ........................................................................................... 5 3  
9. 2. 4.  Re mai ni n g Visits D uri n g Mai n Peri o d  .............................................................. 5 3  
9. 2. 4. 1.  
Pri or t o A d mi nistr ati o n of Pe gcetac o pla n  .............................................. 5 3  
9. 2. 4. 2.  
A d mi nistrati o n of Pe gcetac o pla n  ........................................................... 5 4  
9. 2. 4. 3.  
F oll o wi n g A d mi nistr ati o n of Pe gcetac o pla n  .......................................... 5 4  
9. 2. 5.  Wee k  5 2 Re nal Bi o ps y  ...................................................................................... 5 4  
9. 3.  
F oll o w- u p Peri o d  .................................................................................................... 5 4  
9. 4.  
E xit Visit  ................................................................................................................ 5 5  
9. 5.  
E arl y T er mi nati o n a n d E xit Visit  ............................................................................ 5 5  
9. 6.  
U nsc he d ule d F oll o w -u p Visits  ................................................................................ 5 6  
9. 7.  
Part B, L o n g -T er m E xte nsi o n  ................................................................................. 5 6  
9. 8.  
Safet y M o nit ori n g C o m mittee  ................................................................................. 5 6  
1 0.  
A S S E S S M E N T S  .................................................................................................... 5 7  
1 0. 1.  
Me dical Hist or y ...................................................................................................... 5 7  
1 0. 2.  
Pri or a n d C o nc o mita nt Me dicati o ns  ........................................................................ 5 7  
1 0. 3.  
Vital Si g ns  .............................................................................................................. 5 7  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 1 2 
 
C o nfi de nti al  
1 0. 4.  
P h ysical E xa mi nati o n  ............................................................................................. 5 8  
1 0. 5.  
Electr ocar di o gra ms  ................................................................................................. 5 8  
1 0. 6.  
2 4- H o ur Uri ne C ollecti o n  ....................................................................................... 5 8  
1 0. 7.  
Tri plicate First -M or ni n g S p ot Uri ne C ollecti o ns  ..................................................... 5 9  
1 0. 8.  
Ra n d o m S p ot Uri ne C ollecti o n  ............................................................................... 6 0 
1 0. 9.  
Re nal Bi o ps y  .......................................................................................................... 6 0 
1 0. 1 0.  Meas ure d Gl o mer ular Filtr ati o n Rate  ...................................................................... 6 0 
1 0. 1 1.  O p ht hal m ol o gic E val uati o n  .................................................................................... 6 0 
1 0. 1 2.  I nf usi o n Site/ P u m p Safet y Assess me nt ................................................................... 6 1 
1 0. 1 3.  La b orat or y Assess me nts  ......................................................................................... 6 1 
1 0. 1 4.  P har mac o ki netics  .................................................................................................... 6 3 
1 0. 1 4. 1.  
B l o o d Sa m ples ............................................................................................ 6 3 
1 0. 1 5.  P K A nal ytical Met h o d ol o g y  ................................................................................... 6 4 
1 0. 1 6.  P har mac o d y na mics  ................................................................................................. 6 4 
1 0. 1 7.  A nti dr u g A nti b o d y Assess m e nt ............................................................................... 6 4 
1 0. 1 8.  Bl o o d V ol u me f or St u d y Assess me nts  .................................................................... 6 4 
1 0. 1 9.  Pre g na nc y T ests  ...................................................................................................... 6 5  
1 1.  
A D V E R S E E V E N T S .............................................................................................. 6 6 
1 1. 1.  
Defi niti o ns  .............................................................................................................. 6 6 
1 1. 1. 1.  
A d verse E ve nts ........................................................................................... 6 6 
1 1. 1. 2.  
Seri o us A d verse E ve nts  ............................................................................... 6 6 
1 1. 1. 3.  
U ne x pecte d A d verse E ve nts  ........................................................................ 6 6 
1 1. 2.  
Rec or di n g a n d Re p orti n g A d verse E ve nts  ............................................................... 6 6 
1 1. 2. 1.  
Relati o ns hi p t o St u d y Dr u g  ......................................................................... 6 7  
1 1. 2. 2.  
Se verit y of E ve nts  ....................................................................................... 6 8 
1 1. 2. 3.  
Re p orti n g A d verse E ve nts t o Healt h A ut h orities, I nstit uti o nal Re vie w 
B oar ds, a n d Et hics C o m mittees  ................................................................... 6 8 
1 1. 3.  
Pre g na nc y  ............................................................................................................... 6 8 
1 1. 4.  
A b use, Mis use, O ver d ose, a n d Me dicati o n Err ors  ................................................... 6 9 
1 2.  
S T A TI S TI C A L A N A L Y SI S  ................................................................................... 7 0  
1 2. 1.  
Deter mi nati o n of Sa m ple Size ................................................................................. 7 0  
1 2. 2.  
A nal ysis Set  ............................................................................................................ 7 0  
1 2. 2. 1.  
Scree ne d Set  ............................................................................................... 7 0  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 1 3 
 
C o nfi de nti al  
1 2. 2. 2.  
I nte nt-t o-Treat Set  ....................................................................................... 7 0  
1 2. 2. 3.  
Safet y Set  .................................................................................................... 7 0  
1 2. 2. 4.  
P K Set  ......................................................................................................... 7 0  
1 2. 2. 5.  
P D Set  ......................................................................................................... 7 0  
1 2. 2. 6.  
Data Re vie w f or A nal ysis Set  ...................................................................... 7 1  
1 2. 3.  
Efficac y A nal ysis .................................................................................................... 7 1  
1 2. 3. 1.  
A nal ysis of Pri mar y Efficac y E n d p oi nt  ....................................................... 7 1  
1 2. 3. 2.  
A nal ysis of Sec o n dar y Efficac y E n d p oi nts  .................................................. 7 1  
1 2. 3. 3.  
A nal ysis of E x pl or at or y Efficac y E n d p oi nts  ................................................ 7 1  
1 2. 4.  
Safet y A nal ysis  ....................................................................................................... 7 2  
1 2. 5.  
P K A nal ysis  ............................................................................................................ 7 2  
1 2. 6.  
P D A nal ysi s ............................................................................................................ 7 2  
1 2. 7.  
I m m u n o ge nicit y A nal ysis ....................................................................................... 7 3  
1 2. 8.  
Ot her A nal yses  ....................................................................................................... 7 3  
1 2. 9.  
I nteri m A nal ysis ..................................................................................................... 7 3  
1 2. 1 0.  Saf et y M o nit ori n g C o m mittee  ................................................................................. 7 3  
1 3.  
S T U D Y M A N A G E M E N T  ..................................................................................... 7 4  
1 3. 1.  
A p pr o val a n d C o nse nt  ............................................................................................ 7 4  
1 3. 1. 1.  
Re g ulat or y G ui deli nes  ................................................................................. 7 4  
1 3. 1. 2.  
I nstit uti o nal Re vie w B oar d or I n de pe n de nt Et hics C o m mittee Re vie w ........ 7 4  
1 3. 1. 3.  
I nf or me d C o nse nt ........................................................................................ 7 4  
1 3. 2.  
Data Ha n dli n g  ........................................................................................................ 7 5  
1 3. 3.  
S o urce D oc u me nts .................................................................................................. 7 5  
1 3. 4.  
Rec or d Rete nti o n  .................................................................................................... 7 5  
1 3. 5.  
M o nit ori n g ............................................................................................................. 7 5  
1 3. 6.  
Q ualit y C o ntr ol a n d Q ualit y Ass ur a nce  ................................................................... 7 6  
1 3. 7.  
Pr ot oc ol A me n d me nt a n d Pr ot oc ol De viati o n  ......................................................... 7 6  
1 3. 7. 1.  
Pr ot oc ol A me n d me nt  .................................................................................. 7 6  
1 3. 7. 2.  
Pr ot oc ol De viati o ns  ..................................................................................... 7 6  
1 3. 8.  
Et hical C o nsi derati o ns  ............................................................................................ 7 7  
1 3. 9.  
C o nfi de ntialit y  ........................................................................................................ 7 7  
1 3. 1 0.  Cli nical Trials. g o v  ................................................................................................... 7 7  
1 3. 1 1.  St u d y T er mi nati o n  .................................................................................................. 7 7  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 1 4 
 
C o nfi de nti al  
1 3. 1 2.  F i na nci n g a n d I ns ura nce ......................................................................................... 7 7  
1 3. 1 3.  P u blicati o n P olic y/ Discl os ur e of Data  ..................................................................... 7 7  
1 4.  
R E F E R E N C E S  ....................................................................................................... 7 8  
1 5.  
A P P E N DI C E S  ........................................................................................................ 7 9  
A P P E N DI X  1.  
L O N G - TE R M E X T E N SI O N A C TI VI TI E S  ................................................ 8 0 
1 5. 1.  
Part B: L o n g -T er m E xte nsi o n  ................................................................................. 8 0 
1 5. 1. 1.  
Part B O ver vie w/ Rati o nale  .......................................................................... 8 0 
1 5. 1. 2.  
Part B St u d y Desi g n a n d Pr oce d ur es  ........................................................... 8 2 
1 5. 1. 3.  
Part B D ose Rati o nale  ................................................................................. 8 2 
1 5. 1. 4.  
Part B St u d y Treat me nts .............................................................................. 8 2 
1 5. 1. 4. 1.  
Part B I de ntit y of I n vesti gati o nal Pr o d uct  .............................................. 8 2 
1 5. 1. 4. 2.  
Part B Pe gcetac o pla n D osi n g  ................................................................. 8 2 
1 5. 1. 4. 3.  
Part B Pe gcetac o pla n A d mi nistr ati o n ..................................................... 8 3 
1 5. 1. 5.  
Part B La beli n g, Pac ka gi n g, St or a ge, a n d Ha n dli n g  ..................................... 8 3 
1 5. 1. 5. 1.  
Part B La beli n g  ..................................................................................... 8 3 
1 5. 1. 5. 2 . 
Part B Pac ka gi n g  ................................................................................... 8 3 
1 5. 1. 5. 3.  
Part B I nf usi o n S u p plies  ........................................................................ 8 3 
1 5. 1. 5. 4.  
Part B St ora ge a n d Ha n dli n g  ................................................................. 8 4 
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 1 5  
 
C o nfi de nti al  
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 1 6 
 
C o nfi de nti al  
LI S T O F T A B L E S  
T a ble  1: 
Sc he d ule of Acti vities f or Part A  ............................................................................ 4 1 
T a ble  2: 
First -M or ni n g Uri ne C ollecti o n Sc he d ule  ............................................................... 4 7  
T a ble  3: 
La b orat or y Assess me nts  ......................................................................................... 6 2 
T a ble  4: 
A p pr o xi mate Bl o o d V ol u me C ollecte d  ................................................................... 6 5  
T a ble  5:  
Defi niti o ns of A d verse E ve nt Relate d ness  .............................................................. 6 8 
T a ble  6: 
Se verit y of E ve nts  ................................................................................................... 6 8 
T a ble  7:  
Sc he d ule of Acti vities f or Part B, L o n g -T er m E xte nsi o n ( F oll o wi n g 
Wee k  5 2)  ................................................................................................................ 8 1 
T a ble  8: 
Re vise d C O VI D -1 9 Mi ni m u m Sc he d ule of Acti vities f or Part A ............................. 9 3 
T a ble  9: 
Re vise d C O VI D -1 9 Mi ni m u m First -M or ni n g Uri ne C ollecti o n Sc he d ule f or 
Part A  ..................................................................................................................... 9 8 
T a ble  1 0: Re vi se d C O VI D-1 9 Mi ni m u m Sc he d ule of Acti vities f or Part B, L o n g -T er m 
E xte nsi o n ( F oll o wi n g Wee k  5 2) .............................................................................. 9 9 
 
LI S T O F FI G U R E S  
Fi g ure 1:  
St u d y Desi g n  .......................................................................................................... 2 8 
 
 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 1 7  
 
C o nfi de nti al  
3.  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F T E R M S  
T he f oll o wi n g a b bre viati o ns a n d s pecialist ter ms ar e use d i n t his st u d y pr ot oc ol.  
A b b re vi ati o n 
Defi niti o n  
A CI P  
A d vis or y C o m mittee o n I m m u ni zati o n Pract ices 
A D A  
a nti dr u g a nti b o dies  
A E  
a d verse e ve nt  
A H 5 0  
5 0 % alter nati ve he m ol ytic c o m ple me nt pat h wa y acti vit y  
A L T  
ala ni ne a mi n otra nsferase  
A P  
alter nati ve pat h wa y  
A S T  
as partate a mi n otra nsferase  
C 3 G 
c o m ple me nt 3 gl o mer ul o pat h y 
C 3 G N  
C 3 gl o mer ul o ne p hritis 
C D C  
Ce nters f or Disease C o ntr ol a n d Pre ve nti o n  
C H 5 0  
5 0 % classical he m ol ytic c o m ple me nt pat h wa y acti vit y  
C K D -E PI  
C hr o nic Ki d ne y Disease – E pi de mi ol o g y C olla b orati o n  
C O VI D - 1 9 
c or o na vir us disease 2 0 1 9 
D D D  
de nse de p osit disease  
e C R F 
electr o nic case re p ort f or m  
E C G  
electr ocar di o gra m  
e G F R  
esti mate d gl o mer ular filtrati o n rate  
E S R D  
e n d-sta ge re nal disease 
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
F S H  
f ollicle-sti m ulati n g h or m o ne 
G C P  
g o o d cl i nical practice 
G F R  
gl o mer ular filtrati o n rate  
I B 
i n vesti gat or’s br oc h ure 
I C-M P G N  
i m m u ne c o mple x me m bra n o pr oliferati ve gl o mer ul o ne p hritis  
I C F 
i nf or me d c o nse nt f or m 
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n 
I E C 
i n de pe n de nt et hics c o m mittee 
I R B 
i nstit uti o nal re vie w b oar d 
I T T 
i nte nt-t o-treat 
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
P D  
p har mac o d y na mic 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 1 8 
 
C o nfi de nti al  
A b b re vi ati o n 
Defi niti o n  
P E G  
p ol yet h yle ne gl yc ol  
P K  
p har mac o ki netic 
P N H  
par o x ys mal n oct ur nal he m o gl o bi n uria  
S A E  
seri o us a d verse e ve nt 
S A P  
statistical a nal ysis pla n 
S C  
s u bc uta ne o us 
S D -O C T  
s pectral d o mai n o ptical c o here nce t o m o gra p h y 
S M C  
safet y m o nit ori n g c o m mittee 
S O P  
sta n dar d o perati n g pr oce d ure 
T E A E  
treat me nt-e mer ge nt a d v erse e ve nt  
u A C R  
uri ne al b u mi n -t o-creati ni ne rati o 
U L N  
u p per li mit of n or mal  
u P C R 
uri ne pr otei n- t o-creati ni ne rati o 
W O C B P  
w o me n of c hil d beari n g p ote ntial  
 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 1 9 
 
C o nfi de nti al  
4.  
I N T R O D U C TI O N 
T w o si milar diseases, c o m ple me nt c o m p o ne nt 3 gl o mer ul o pat h y ( C 3 G) a n d i m m u ne c o m ple x 
me m bra n o pr oliferati ve gl o mer ul o ne p hritis (I C -M P G N), will be st u die d i n t his pr ot oc ol. 
T his pr ot oc ol will st u d y s pecificall y pri mar y C 3 G or I C -M P G N. Patie nts wit h C 3 G a n d 
I C-M P G N sec o n d ar y t o a n ot her u n derl yi n g c o n diti o n or sit uati o n ( e g, i nf ecti o n, m o n ocl o nal 
ga m m o pat h y, mali g na nc y, or me dicati o n) will be e xcl u de d fr o m t his st u d y.  
4. 1.  
C 3 G a n d I C -M P G N a n d U n m et Me dic al Nee d  
C o m p o ne nt 3 gl o mer ul o pat h y is a disease i n w hic h t he c o m ple me nt s yste m, s pecificall y t he 
alter nati ve pat h wa y ( A P), is i n discri mi natel y o veracti ve, lea di n g t o e xcessi ve de p ositi o n of C 3 
brea k d o w n pr o d ucts i n t he gl o mer uli of t he ki d ne y a n d da ma ge t o t he re nal pare nc h y ma. 
T he  u n derl yi n g A P h y peracti vit y ca n be d ue t o vari o us fact ors, m ost c o m m o nl y, a n ac q uire d 
a ut oa nti b o d y w hic h sta bilizes t he A P C 3 or C 5 c o n vertase ( C 3 or C 5 ne p hritic fact or). T his  setti n g of 
A P h y peracti vit y lea d s t o u n bri dle d a n d u nc o ntr olle d C 3 acti vati o n, a n d a n e xcess of C 3 brea k d o w n 
pr o d ucts, w hic h are de p osite d i n t he gl o mer ular base me nt me m bra ne a n d, al o n g wit h t he 
i nfla m mat or y res p o nse, disr u pt t he n or mal gl o mer ular arc hitect ure a n d filtrati o n barrier. 
T he re are 2 s u bt y pes of C 3 G: de nse de p osit disease ( D D D) a n d C 3 gl o mer ul o ne p hritis ( C 3 G N), 
w hic h are  disti n g uis ha ble o nl y b y re nal bi o ps y. T he cli nical pr ese ntati o n, f eat ur es, a n d disease 
c o urse are si milar bet wee n t he 2 s u bt y pes. N ota ble disti ncti o ns bet wee n  t he 2 s u bt y pes ar e t hat 
D D D te n ds t o prese nt earlier i n life t ha n C 3 G N ( me dia n a ges of dia g n osis f or D D D a n d C 3 G N 
are 1 2 a n d 2 6 years ol d, res pecti vel y), a n d t hat D D D is als o ass ociate d wit h e xtr ar e nal 
ma nifestati o ns, s uc h as ac q uire d partial li p o d ystr o p h y a n d mac ular de ge ner ati o n. T he i nci de nce 
of C 3 G N is a b o ut 3 -f ol d greater t ha n t hat of D D D (Me djer al -T h o mas et al. 2 0 1 4 ; 
Ser vais  et al. 2 0 1 2 ; L u et a l. 2 0 1 2). 
Alt h o u g h I C -M P G N is t y picall y c o nsi dere d a disti nct pat h ol o gic e ntit y fr o m C 3 G, t he  u n derl yi n g 
pat h o p h ysi ol o g y a n d cli nical c o urse of t he 2 pri mar y diseases are re mar ka bl y si milar 
(N oris  et al. 2 0 1 9 ; H olle e t al. 2 0 1 8). As i n C 3 G, patie nts wit h pri mar y I C-M P G N ofte n ha ve 
e vi de nce of A P h y peracti vit y, i ncl u di n g t he prese nce of ge netic or ac q uire d ca uses of A P 
d ysre g ulati o n. I n t hese patie nts, u nc o ntr olle d C 3 acti vati o n a n d gl o mer ular de p ositi o n of C 3 
brea k d o w n pr o d ucts is als o o bser ve d, si milar t o C 3 G. T he o nl y pat h ol o gic disti ncti o n fr o m C 3 G is 
t hat t he gl o mer ular C 3 de p ositi o n i n I C-M P G N is acc o m pa nie d b y i m m u n o gl o b uli n de p ositi o n. 
T he  c o m m o n cli nical ma nifestati o ns of pri mar y I C-M P G N are t he sa me as t h ose of C 3 G a n d ot her 
gl o mer ul o ne p hriti des — pr otei n uria, he mat uria, h y perte nsi o n, a n d re d uce d gl o mer ular filtrati o n rate. 
It is i m p orta nt t o n ote t hat t he ter m “i m m u n o gl o b uli n-ass ociate d me m bra n o pr oliferati ve 
gl o me r ul o ne p hritis” ma y be a m ore a p pr o priate ter m; h o we ver, i n a n eff ort t o be c o nsiste nt wit h t he 
maj orit y of t he literat ure, t he ter m I C -M P G N is use d t hr o u g h o ut t his pr ot oc ol.  
U nf ort u natel y, t here are n o a p pr o ve d or pr o ve n t hera pies t o pre ve nt or re verse disease pr o gressi o n i n 
eit her C 3 G or I C-M P G N. Si milar t o ot her gl o mer ular diseases, disease ma na ge me nt i ncl u des 
n o ns pecific meas ures t o ma na ge pr otei n uria, h y perte nsi o n, h y perli pi de mia, e de ma, a n d ot her facets 
of gl o mer ular a n d c hr o nic ki d ne y disease. Des pite t hese vari o us meas ures, t he pr o g n osis f or b ot h 
pri mar y C 3 G a n d I C -M P G N is p o or, wit h a p pr o xi matel y 5 0 % of patie nts pr o gressi n g t o e n d -sta ge 
re nal disease ( E S R D) wit hi n 5-1 0  years of dia g n osis. W hile re nal tra ns pla ntati o n is a n o pti o n f or 
t hese patie nts, disease rec urre nce is n ot u nc o m m o n a n d ca n lea d t o graft l oss. I n dee d, u p t o 5 0 % of 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 
 
C o nfi de nti al  
C 3 G patie nts l ose t heir re nal all o grafts d ue t o disease rec urre nce ( Me djeral -T h o mas et al. 2 0 1 4 ; 
Z ha n g et al . 2 0 1 4; Pic keri n g et al. 2 0 1 3 ; L u et al. 2 0 1 2 ; O k pec hi et al. 2 0 1 4 ). T heref ore, t hese are 
diseases  wit h a hi g h u n met me dical nee d, es peciall y f or a t hera p y t hat tar gets t he u n derl yi n g 
pat h o p h ysi ol o g y of t he disease a n d is a ble t o pre ve nt or re verse disease pr o gressi o n.  
4. 2.  
St u d y R ati o n ale  
T here are n o t hera pies a p pr o ve d t o pre ve nt or r e verse disease pr o gr essi o n i n C 3 G or I C -M P G N. 
Si milar t o ot her gl o mer ular diseases, disease ma na ge me nt i ncl u des n o ns pecific meas ur es t o 
ma na ge pr otei n uria, h y perte nsi o n, h y perli pi de mia, e de ma, a n d ot her f acets of gl o mer ular a n d 
c hr o nic ki d ne y disease. Des pite t hese vari o us meas ur es, t he pr o g n osis of C 3 G a n d I C -M P G N is 
p o or as patie nts ca n pr o gress t o E S R D ( Me djer al -T h o mas et al. 2 0 1 4 ; Z ha n g et al . 2 0 1 4; 
Pic keri n g et al. 2 0 1 3 ; L u et al. 2 0 1 2 ; O k pec hi et al. 2 0 1 4 ). 
Re nal tra ns pla ntati o n is a n o pti o n f or patie nts w h o r eac h E S R D, b ut t he i nci de nce of disease 
rec urre nce is hi g h, wit h u p t o 5 0 % of patie nts l osi n g t heir r e nal all o gr afts d ue t o d isease 
rec urre nce (Me djeral -T h o mas et al. 2 0 1 4 ; Z ha n g et al . 2 0 1 4; Pic keri n g et al. 2 0 1 3 ; 
L u  et al.  2 0 1 2). T heref ore, a t hera p y t hat ca n pr otect t he ki d ne ys, nati ve or tr a ns pla nte d, 
fr o m o n g oi n g da ma ge  d ue t o c o m ple me nt h y per acti vit y w o ul d be hi g hl y desir a ble.  
As a n i n hi bit or of C 3 a n d its fra g me nt, C 3 b, pe gcetac o pla n ( A P L -2) has t he p ot e ntial t o a d dress t he 
u n derl yi n g disease pat h o p h ysi ol o g y of c o m ple me nt h y peracti vit y i n C 3 G a n d I C -M P G N. 
S pecificall y, b y i n hi biti n g C 3, it is e x pecte d t hat pe gcetac o pla n will halt t he i na p pr o priate a n d 
e xcessi ve C 3 acti vati o n t hat c haracterizes t hese diseases. A d diti o nall y, b y i n hi biti n g C 3 b, 
pe gcetac o pla n i n hi bits t he acti vit y of t he A P C 3 c o n vertase ( w het her it is sta bilize d b y ne p hritic 
fact ors or n ot) t hr o u g h a sec o n d c o m ple me ntar y mec ha nis m of acti o n o n t o p of t he i n hi biti o n of C 3 
as a s u bstrate i n t he c o m ple me nt casca de. T hese 2 c o m ple me ntar y mec ha nis ms will pre ve nt f urt her 
de p ositi o n of C 3 brea k d o w n pr o d ucts i n t he gl o mer uli, aff or di n g t he o p p ort u nit y f or t he ki d ne y t o 
rec o ver b y cleari n g e xisti n g de p osits a n d res ol vi n g i nfla m mati o n. T his re nal rec o ver y w o ul d be 
e x pecte d, i nitiall y, t o yiel d re d ucti o ns i n pr otei n uria, a n d ulti matel y, t o res ult i n pr ol o n ge d re nal 
s ur vi val. T heref ore, pe gcetac o pla n is a p ote ntiall y lif e-alteri n g t her a p y f or C 3 G a n d I C -M P G N.  
A n o n g oi n g st u d y, A P L 2 -2 0 1, is st u d yi n g pe gcetac o pla n i n patie nts wit h C 3 G w h o ha ve n ot 
u n der g o ne a re nal tra ns pla nt. Preli mi nar y data fr o m t he A P L 2 -2 0 1 st u d y i n dicate t hat pe gcetac o pla n 
is a ble t o tar get t he c o m ple me nt h y peracti vit y of C 3 G. T he s p o ns or n o w ai ms t o st u d y t he safet y a n d 
efficac y of pe gcetac o pla n i n patie nts wit h rec urre n ce of C 3 G or I C-M P G N i n a re nal all o graft.  
T his st u d y will e x pl ore t he safet y a n d bi ol o gic acti vit y of pe gcetac o pla n i n patie nts wit h C 3 G or 
I C-M P G N rec ur re nce p ost-tra ns pla ntati o n. Re nal bi o psies will be o btai ne d at m ulti ple ti me 
p oi nts t o assess t he a bilit y of pe gcetac o pla n t o r e d uce t he a m o u nt of C 3c gl o mer ular de p ositi o n, 
o ne of t he hist ol o gic hall mar ks of t hese diseases. T his fi n di n g, al o n g wit h i ncr eases i n i ntact 
ser u m C 3, w o ul d pr o vi de str o n g e vi de nce t hat pe gcetac o pla n is a d dr essi n g t he u n derl yi n g 
pat h o p h ysi ol o g y of t he disease b y pre ve nti n g e xcessi ve pr o d ucti o n of C 3 br ea k d o w n pr o d ucts, 
a n d t heir s u bse q ue nt de p ositi o n i nt o t he ki d ne y.  
4. 2. 1.  
J ustific ati o n of D ose  
T he d osi n g re gi me n f or a d ults will be 1 0 8 0  m g S C t wic e wee kl y. T his d osi n g r e gi me n is 
i nte n ded t o res ult i n s yste mic e x p os ur es of pe gcetac o pla n si milar t o t h ose see n i n t he o n g oi n g 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 2 1 
 
C o nfi de nti al  
P hase  2 st u d y i n patie nts wit h c o m ple me nt -me diate d gl o mer ul o pat hies, St u d y A P L 2 - 2 0 1, 
a n d t he o n g oi n g P hase 3 st u d y i n patie nts wit h par o x ys mal n oct ur nal he m o gl o bi n uria ( P N H), 
St u d y A P L 2 -3 0 2, i n w hic h pe gcetac o pla n has bee n ge ner all y saf e a n d well t oler ate d.  
M o deli n g -base d si m ulati o ns were perf or me d usi n g a n a d ult p o p ulati o n p har mac o ki netics (P K ) 
m o del i nc or p orati n g pe gcetac o pla n ser u m c o nce ntrati o n -ti me data fr o m 1 0 clinical st u dies 
(fi ve P hase  1 st u dies i n healt h y v ol u nteers, o ne s pecial -p o p ulati o n st u d y i n a d ults wit h se vere re nal 
i m pair me nt, t hree P hase  1 b/ 2a st u dies i n a d ult P N H patie nts, a n d o ne P hase  3 st u d y 
[St u d y  A P L 2 -3 0 2; data u p t o Wee k  1 6]) i n healt h y a d ults a n d i n patie nts wit h P N H. M o deli n g of 
e x p os ure i n hi g h b o d y wei g ht s u bjects ( > 1 0 0  k g) res ults pre dicte d e x p os ur es at least 1 5 % l o wer t ha n 
t hat f or a refere nce 7 0 -k g s u bject; s u bjects > 1 0 0  k g will t heref ore be e xc l u de d fr o m t he st u d y. 
4. 3.  
S u m m ar y of Cli nic al E x perie nce Wit h P e gcet ac o pl a n  
Pe gcetac o pla n is bei n g st u die d i n St u d y A P L 2 -2 0 1, a n o n g oi n g P hase  2 st u d y t hat i ncl u des 
patie nts wit h 1 of 4  gl o mer ular diseases: C 3 G, i m m u n o gl o b uli n A ne p hr o pat h y, pri mar y 
me m bra n o us ne p hr o pat h y, or l u p us ne p hritis. Pr eli mi nar y data fr o m t he first 3 C 3 G patie nts i n 
t his st u d y i n dicate t hat pe gcetac o pla n is a ble t o tar get t he c o m ple me nt h y per acti vit y of C 3 G as 
well as r e d uce pr otei n uria i n patie nts wit h C 3 G.  
Cli nical data is als o a vail a ble fr o m 5 c o m plete d st u dies wit h pe gcetac o pla n i n patie nts wit h P N H  
( P hase 1 b: St u dies A P L -C P 0 5 1 4 a n d A P L 2 -C P -P N H - 2 0 4; P hase  2a: St u d y A P L 2 - 2 0 2; P hase  3: 
St u d ies A P L 2 - 3 0 2 a n d A P L 2 - 3 0 8). Res ults fr o m t hese st u dies i n dicate t hat pe gcetac o pla n ma y 
be effect i ve i n pr o vi di n g br oa d c o ntr ol of i ntr a vasc ular a n d e xtr a vasc ular he m ol ysis, 
as e vi de nce d b y t he f oll o wi n g: i ncrease d a n d sta ble he m o gl o bi n le vels, i m pr o ve me nt i n 
F u ncti o nal Assess m e nt of C hr o nic Ill ness T her a p y – Fati g ue Scale sc or e, n or malizati o n of lactat e 
de h y dr o ge nase, n or malizati o n of a bs ol ute r etic ul oc yte c o u nt, n or malizati o n of t otal bilir u bi n 
le vels, re d ucti o n i n C 3 fra g me nt o ps o nizati o n, a n d i ncr ease d n u m bers of P N H r e d bl o o d cells.  
Pe gcetac o pla n at d oses of 3 6 0 m g/ da y a n d 1 0 8 0  m g t wice wee kl y has bee n ge ner all y saf e a n d 
well t olerate d w he n a d mi nistere d via s u bc uta ne o us ( S C) i nf usi o n, i ncl u di n g t o patie nts wit h C 3 G 
a n d ot her gl o mer ular diseases. N o e x pecte d seri o us a d verse dr u g r eacti o ns ha ve bee n i de ntifie d, 
a n d n o deat hs ha ve occ urre d t hat are c o n si der e d r elate d t o tr eat me nt wit h pe gcetac o pla n. 
Refer t o t he latest versi o n of t he pe gcetac o pla n i n vesti gat or’s br oc h ur e (I B) f or t he o ver all 
ris k-be nefit  assess me nt a n d t he m ost c urr e nt i nf or mati o n r e gar di n g t he dr u g meta b olis m, P K, 
efficac y, a n d safet y of pe gcetac o pla n.  
4. 4.  
Cli nic al Ris ks/ Be nefits of Pe gcet ac o pl a n  
Pe gcetac o pla n has t he p ote ntial t o a d dr ess t he u n derl yi n g disease pat h o p h ysi ol o g y of 
c o m ple me nt h y peracti vit y i n C 3 G a n d I C-M P G N, a n d, t her ef or e, t o pr o vi de be nefit i n t hese 
diseases wit h a hi g h u n met me dical nee d.  
T he safet y of s u bc uta ne o us pe gcetac o pla n a d mi nistr ati o n has bee n st u die d i n m ulti ple P hase  2 
a n d 3 st u dies f or C 3 G a n d P N H, wit h a n acce pta ble saf et y pr ofile t o date. N o net heless, a n u m ber 
of safet y m o nit ori n g practices are bei n g e m pl o ye d b y t his pr ot oc ol t o e ns ur e s u bject saf et y, 
i ncl u di n g p h ysical e xa mi nati o n, vital si g ns m o nit ori n g, electr ocar di o gr a ms ( E C Gs), he mat ol o g y 
(i ncl u di ng c oa g ulati o n), ser u m c he mistr y, a n d uri nal ysis at s pecifie d i nter vals, as well as pr o m pt 
re p orti n g of a d verse e ve nts ( A Es). 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 2 2 
 
C o nfi de nti al  
I nf usi o n site/ p u m p safet y will be assesse d d uri n g cli nical visits, a n d a n y si g nifica nt fi n di n g fr o m 
t he assess me nt will be re p orte d as a n A E (see Secti o n  1 0. 1 0 ). T he v ol u me of bl o o d pla n ne d f or 
c ollectio n fr o m eac h s u bject o ver t he c o urse of t he st u d y will be mi ni mize d i n or der t o l i mit t he 
i m pact o n t he o verall healt h of t hese a ne mic s u bjects.  
S yste mic c o m ple me nt i n hi biti o n mi g ht pr e dis p ose i n di vi d uals t o i nf ecti o ns ca use d b y 
e nca ps ulat e d or ga nis ms, i ncl u di n g Stre pt oc occ us p ne u m o ni ae , Neisseri a me ni n giti dis , 
a n d H ae m o p hil us i nfl ue n z ae. Vacci nati o ns a gai nst t hese or ga nis ms will be ta ke n t o mi ni mize 
p ote ntial ris k of i nfecti o n. Use of pr o p h ylactic a nti bi otics is all o we d, at t he discr eti o n of t he 
i n vesti gat or, a n d s h o ul d ta ke i nt o c o nsi der ati o n t he le vel of i m m u n os u p pr essi o n, c o m ple me nt 
le vels, a n d ti mi n g of vacci nati o n relati ve t o pe gcetac o pla n start, as well as l ocal pr actices. 
B o d y te m perat ure a n d vital si g ns will be m o nit or e d peri o dicall y, a n d r ele va nt bl o o d par a meters 
m o nit ore d re g ularl y t hr o u g h o ut t he st u d y t o assess f or si g ns of i nf ecti o n. T he s u bject will be 
c o u nsele d re gar di n g t his p ote ntial ris k f or i nf ecti o n a n d gi ve n a patie nt saf et y wallet car d i n t he 
e ve nt of a n e mer ge nc y. T he i n vesti gat or s h o ul d be c o ntacte d i m me diatel y i n t he e ve nt of a 
s us pecte d i nfecti o n f or g ui da nce o n a p pr o priate acti o n t o be ta ke n.  
A pellis is n ot c urre ntl y a ware of a n y e vi de nce ass ociati n g pe gcetac o pla n use wit h s pecific ris ks 
or c o m plica ti o ns of c or o na vir us disease 2 0 1 9 ( C O VI D-1 9). A pellis r ec o g nizes t he nee d t o 
c o nsi der t he p u blic healt h ris ks of the C O VI D -1 9 pa n de mic wit hi n t he c o nte xt of c o n d ucti n g a 
cli nical trial. Beca use t hese ris ks ma y c ha n ge as t he pa n de mic e v ol ves a n d ma y var y base d o n 
ge o gra p hic l ocati o n, A pellis will c o nti n ue t o e val uate t he ris ks a n d be nefits ar o u n d st u d y c o n d uct 
o n a n o n g oi n g a n d s u bject - b y-s u bject basis. 
4. 4. 1.  
C O VI D -1 9 Ri s k Miti g ati o n Me as ures 
A pellis is n ot c urre ntl y a ware of a n y e vi de nce ass ociati n g pe gcetac o pla n use wit h s pecific ris ks 
or c o m plica ti o ns of C O VI D-1 9. A pellis r ec o g nizes t he nee d t o c o nsi der t he p u blic healt h r is ks of 
t he C O VI D-1 9 pa n de mic wit hi n t he c o nte xt of c o n d ucti n g a cli nical trial. Beca use t hese ris ks 
ma y c ha n ge as t he pa n de mic e v ol ves a n d ma y var y o n t he basis of ge o gr a p hic l ocati o n, A pellis 
will c o nti n ue t o e val uate t he ris k/ be nefit ar o u n d st u d y c o n d uct o n a n o n g oi n g a n d 
s u bject- b y-s u bje ct basis. 
I n t he e ve nt t hat a n i n vesti gati ve site is cl ose d or s u bject is u na ble or u n willi n g t o tr a vel d ue t o 
C O VI D -1 9 a n d if,  i n t he o pi ni o n of t he i n vesti gat or, it is i n t he s u bject’s best i nter est t o c o nti n ue 
i n t he st u d y, t he f oll o wi n g miti gati o n meas ur es ma y be i m ple me nte d f or t he st u d y a n d utilize d if 
dee me d necess ar y a n d a ut h orize d b y t he s p o ns or, i ncl u di n g b ut n ot li mite d t o:  
•  I n l ocati o ns w here h o me n ursi n g ser vices ma y be utilize d, a h o me n ursi n g ve n d or 
ma y be set u p t o c o m plete assess me nts at a s u bject’s h o me.  
•  A mi ni mize d sc he d ule of acti vities is pr ese nte d i n T a ble  8, T a ble  9, a n d T a ble  1 0 of 
A p pe n di x 3 .  
•  A n y acti vities n ot perf or me d beca use of C O VI D - 1 9 –r elated r estricti o ns will be 
i de ntifie d i n the electr o nic data ca pt ur e s yste m.  
•  A n y c ha n ge i n C O VI D -1 9 stat us ( ser ol o g y or a nti ge n), if a vaila ble, will be ca pt ur e d 
se paratel y i n t he electr o nic data ca pt ur e s yste m.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 2 3 
 
C o nfi de nti al  
•  W here a p plica ble, rele va nt st u d y d oc u me ntati o n will be u p date d a n d c o m m u nicate d 
t o healt h aut h orities a n d/ or i nstit uti o nal r e vie w b oar ds (I R Bs)/i n de pe n de nt et hics 
c o m mittees (I E Cs) as re q uir e d.  
A pellis is c urre ntl y n ot a ware of a n y c o ntr ai n dicati o ns t o vacci nati o n ( of a n y m o dalit y) a n d 
c o nc urre nt  treat me nt wit h pe gcetac o pla n. I n t he a bse nce of data, A pellis c urr e ntl y r ec o m me n ds 
t hat t he decisi o n t o vacci nate st u d y partici pa nts a gai nst C O VI D-1 9 s h o ul d be ma de b y t he 
i n vesti gat or a n d t he s u bject, wit h c o nsi der ati o n of l ocal a n d nati o nal vacci nati o n 
rec o m me n dati o ns a n d a be nefit-ris k assess ment. Vacci nati o n a gai nst C O VI D -1 9 is n ot 
ma n dat or y f or c o nti n ue d st u d y partici pati o n.  
T hese meas ures are descri be d i n detail i n  A p pe n di x 3 .  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 2 4 
 
C o nfi de nti al  
5.  
S T U D Y O B J E C TI V E S A N D E N D P OI N T S  
5. 1.  
St u d y O bjecti ves  
5. 1. 1.  
P ri m ar y O bjecti ve  
T he pri mar y o bjecti ve of t his st u d y is t o e val uate t he efficac y of pe gcetac o pla n i n i m pr o vi n g t he 
u n derl yi n g pat h o p h ys i ol o g y of C 3 G/I C-M P G N after 1 2  wee ks of tr eat me nt.  
5. 1. 2.  
Sec o n d ar y O bjecti ves  
T he sec o n d ar y o bjecti ves of t he st u d y ar e as f oll o ws:  
•  t o e val uate t he effect of pe gcetac o pla n o n ke y cli nical ma nif estati o ns of t he disease 
after 5 2 w ee ks of treat me nt 
•  t o e val uate t he safet y of pe gcetac o pla n f or u p t o 5 2 wee ks i n p atie nts wit h r ec urr e nt 
C 3 G/I C -M P G N i n a re nal all o gr aft 
5. 1. 3.  
E x pl or at or y O bjecti ves  
T he e x pl orat or y o bjecti ves are t o c haracterize t he a d diti o nal cli nical, la b or at or y, a n d hist ol o gic 
fi n di n gs of C 3 G/I C-M P G N i n res p o nse t o pe gcetac o pla n, i ncl u di n g pe gcetac o pla n  P K , 
p har mac o d y na mics ( P D), a n d i m m un o ge nic it y i n patie nts wit h C 3 G/I C-M P G N . 
5. 2.  
St u d y E n d p oi nts  
5. 2. 1.  
Effic ac y E n d p oi nts  
5. 2. 1. 1.  
P ri m ar y E ffic ac y E n d p oi nt  
T he pri mar y efficac y e n d p oi nt is t he pr o p orti o n of s u bjects wit h r e d ucti o n i n C 3c stai ni n g o n 
re nal bi o ps y after 1 2 wee ks of treat me nt wit h pe gcetac o pla n.  
5. 2. 1. 2.  
Sec o n d ar y Effic ac y E n d p oi nts  
T he sec o n dar y efficac y e n d p oi nts are as f oll o ws: 
•  T he pr o p orti o n of s u bjects wit h r e d ucti o n i n C 3c stai ni n g o n r e nal bi o ps y after 
5 2  wee ks o f treat me nt 
•  T he pr o p orti o n of s u bjects wit h sta bilizati o n or i m pr o ve me nt i n esti mate d gl o mer ular 
filtrati o n rate (e G F R) o ver ti me  
•  T he pr o p orti o n of s u bjects wit h sta bilizati o n or i m pr o ve me nt of ser u m cr eati ni ne  
c o nce ntrat i o n o ver ti me  
•  C ha n ges fr o m baseli ne bi o ps y i n C 3c stai ni n g o ver ti me  
•  C ha n ges  a n d perce nta ge c ha n ges fr o m baseli ne i n e G F R a n d ser u m cr eati ni ne 
c o nce ntrati o n o ver ti me 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 2 5  
 
C o nfi de nti al  
5. 2. 1. 3.  
E x pl or at or y E ffic ac y E n d p oi nts  
T he e x pl orat or y efficac y e n d p oi nts are as f oll o ws:  
•  F or s u bjects wit h baseli ne pr otei n uria a b o ve t he u p per li mit of n or mal ( U L N ), the 
pr o p orti o n of s u bjects ac hie vi n g at least a 5 0 % r e d ucti o n i n pr otei n uria o ver ti me 
•  F or s u bjects wit h baseli ne pr otei n uria a b o ve t he U L N , the pr o p o rti o n of s u bjects 
ac hie vi n g c o m plete cli nical r e missi o n of pr otei n uria after 1 2  a n d 5 2 wee ks of 
treat me nt, defi ne d as n or malizati o n of pr otei n uria 
•  C ha n ges a n d perce nta ge c ha n ges i n pr otei n uria o ver ti me  
•  C ha n ge o ver  ti me i n a d diti o nal ke y bi o ps y f eat ur es, i ncl u di n g: 
− Gl o mer ular m yel oi d cell i nfiltr ati o n  
− Gl o mer ular macr o p ha ge i nfiltr ati o n ( as meas ur e d b y C D 6 8 stai ni n g)  
− Gl o mer ular cresce nts (i n s u bjects wit h cr esce nts)  
− Mesa n gial e x pa nsi o n a n d h y per cell ularit y  
− De p osits b y electr o n micr osc o p y  
− Acti vit y sc ore ( base d o n C 3 G hist ol o gic i n de x)  
− C hr o nicit y sc o re ( base d o n C 3 G hist ol o gic i n de x)  
•  O p ht hal m ol o g y e n d p oi nts :  
− C ha n ge i n ma xi m u m dr use n size  at Wee k 5 2  
− N u m ber  of i nter me diate or lar ge druse n at baseli ne a n d Wee k  5 2  
5. 2. 2.  
S afet y E n d p oi nts  
T he safet y e n d p oi nts are as f oll o ws:  
•  T he n u m ber a n d i nci de nce of tr eat me nt -e mer ge nt AEs  
•  T he c ha n ge fr o m baseli ne i n vital si g ns meas ur e me nts a n d cli nical la b or at or y test a n d 
E C G res ults  
I n a d diti o n, t he f oll o wi n g e x pl orat or y saf et y e n d p oi nts will be e val uate d : 
•  T he n u m ber  a n d i nci de nce of r ejecti o n e pis o des i n eac h gro u p  
•  T he n u m ber a n d i nci de nce of gr aft l oss  i n eac h gr ou p  
5. 2. 3.  
P K  E n d p oi nts  
T he P K  en d p oi nts are as f oll o ws:  
•  Pe gcetac o p la n ser u m c o nce ntr ati o ns o ver ti me 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 2 6 
 
C o nfi de nti al  
5. 2. 4.  
P D  E n d p oi nts  
T h e P D  e n d p oi nts are as f oll o ws: 
•  C ha n ge i n c o m ple me nt bi o mar kers ( 5 0 % classical he m ol ytic c o m ple me nt pat h wa y 
acti vity [ C H 5 0] a n d 5 0 % alter nati ve he m ol ytic c o m ple me nt pat h w a y acti vit y 
[ A H 5 0]) o ver ti me  
A d diti o nal c o m ple me nt c o m p o ne nts ma y be meas ur e d, as n ote d i n T a ble  3 a n d Secti o n  1 0. 1 6 , 
a n d e val uated as e x pl orat or y e n d p oi nts.  
5. 2. 5.  
I m m u n o ge nicit y E n d p oi nts 
T he i m m u n o ge nicit y e n d p oi nts are as f oll o ws:  
•  T he i nci de nce of a nti-pe gcetac o pl a n a nti b o dies a n d i nci de nce of a nti-P E G a nti b o dies 
(i ncl u di n g treat me nt-e mer ge nt a n d tr eat me nt - b o oste d r es p o nses) t hr o u g h o ut t he 
treat me nt a n d f oll o w-u p peri o ds  
 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 2 7  
 
C o nfi de nti al  
6.  
I N V E S TI G A TI O N A L P L A N 
6. 1.  
Des cri pti o n of O ver all St u d y Desi g n a n d Pl a n  
T his P hase  2, m ultice nter, o pe n -la bel, r a n d o mize d, c o ntr olle d cli nical st u d y is desi g ne d t o 
e val uate t he safet y a n d efficac y of pe gcetac o pla n i n patie nts w h o ha ve p ost -tr a ns pla nt r ec urr e nce 
of C 3 G or I C -M P G N. T here will be u p t o 1 2  s u bjects e nr olle d i n t his st u d y. T her e ar e 3 mai n 
peri o ds of t his st u d y f or Part A,  t he c or e st u d y.  
•  Scree ni n g peri o d: a n u p t o 8 -wee k scr ee ni n g peri o d, d uri n g w hic h t he scr ee ni n g r e nal 
all o graft bi o ps y will occ ur 
•  Mai n peri o d: a 5 2 -wee k st u d y pe ri o d t hat c o ntai ns 2 p orti o ns ( c o ntr olle d a n d 
n o nc o ntr olle d) d uri n g w hic h s u bjects will be r a n d o mize d t o eit her Gr o u p  1 or 
Gr o u p 2 at t he Wee k  1 visit:  
− C o ntr olle d p orti o n: Wee ks  1-1 2 of t he st u d y  
 Gr o u p 1: U p t o 9  s u bjects will be r a n d o mize d t o t his tr eat me nt gr o u p 
a n d will recei ve pe gcetac o pla n tr eat me nt t hr o u g h o ut t he e ntir e st u d y; 
bi o psies will occ ur at Wee k  1 2 
 Gr o u p 2: U p t o 3  s ubjects will be r a n d o mize d t o t his tr eat me nt gr o u p 
a n d will n ot recei ve pe gcetac o pla n tr eat me nt d uri n g t he c o ntr olle d p orti o n; 
bi o psies will occ ur at Wee k  1 2 
− N o nc o ntr olle d p orti o n: Wee ks  1 3-5 2 of t he  st u d y 
 Gr o u p 1: S u bjects will c o nti n ue t o r ecei ve pe gcetac o pla n tr eat me nt; 
bi o ps ies will occ ur at Wee k 5 2  
 Gr o u p 2: S u bjects will r ecei ve pe gcetac o pla n tr eat me nt f oll o wi n g t heir 
Wee k  1 2 re nal all o gr aft bi o psies; bi o psies will occ ur at Wee k  5 2  
•  F oll o w- u p peri o d: a n 8- w ee k f oll o w-u p peri o d  
A n y s u bject w h o, i n t he o pi ni o n of t he i n vesti gat or, is e x perie nci n g cli nical be nefit fr o m 
pe gcetac o pl a n a d mi nistrati o n ma y partici pate i n Part B, a l o n g -ter m e xte nsi o n, i n or der t o 
c o nti n ue t o recei ve treat me nt wit h pe gcetac o pla n u ntil it is c o m mer ciall y a vaila ble f or t he 
disease u n der st u d y. If i n vite d t o partici pate, t he s u bject ca n e nter Part B as s o o n as his/ her 
5 2 -wee k treat me nt peri o d has e n de d a n d d oes n ot nee d t o partici pate i n t he 8- wee k f oll o w - u p 
peri o d. See t he a p pe n dices ( Secti o n  1 5 ) f or details a b o ut Part B. 
Fi g ure 1  prese nts t he st u d y desi g n.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4 Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc
Pa ge 2 8 
C o nfi de nti al
Fi g ure  1: 
St u d y Desi g n
A b bre viati o n: R = ra n d o miz ati o n. 
6. 2.
St u d y Desi g n
T his is a n o pe n -la bel, ra n d o mize d, c o ntr olle d, P hase 2 st u d y c o nsisti n g of a si n gle c o h ort of u p 
t o 1 2 s u bjects wit h cli nical a n d pat h ol o gic e vi de nce of r ec urr e nt C 3 G or I C-M P G N i n a r e nal 
all o graft. S u bjects will be ra n d o mize d 3: 1 t o Gr o u p 1 ( pe gcetac o pla n tr eat me nt t hr o u g h o ut t he 
mai n peri o d) or Gr o u p 2 ( n o pe gcetac o pla n tr eat me nt f or t he first 1 2 wee ks of t he mai n peri o d, 
f oll o we d b y pe gcetac o pla n treat me nt), r es pecti vel y. T he visit sc he d ule will be t he sa me, 
re gar dless of ra n d o mizati o n. 
Pat h ol o gic e vi de nce of disease rec urr e nce r e quir es a bi o ps y -base d dia g n osis of C 3 G or 
I C-M P G N i n t he re nal all o graft, c o nfir me d b y a st u d y pat h ol o gist. T he dia g n osis nee d n ot be t he 
sa me i n t he nati ve ki d ne y a n d t he re nal all o gr aft; f or e xa m ple, a s u bject wit h C 3 G i n t he nati ve 
ki d ne y a n d I C -M P G N p ost
tra ns pla nt is still eli gi ble f or t he st u d y. 
S u bjects wit h eit her pree xisti n g disease r ec urr e nce or u p o n i nitial i de ntificati o n of cli nica l a n d 
pat h ol o gic  rec urre nce of disease will be i n vite d t o e nter scr ee ni n g. S u bjects m ust als o ha ve a n 
e G F R of at least 1 5 m L/ mi n/ 1. 7 3  m2 a n d n o m or e t ha n 5 0 % fi br osis o n r e nal bi o ps y. 
T he st u d y will re q uire a t otal of 3 re nal all o gr aft bi o psies, d uri n g sc r ee ni n g, Wee k 1 2, 
a n d  Wee k 5 2. Fle xi bilit y has bee n b uilt i n f or eac h bi o ps y as descri be d bel o w:
•
Scree ni n g re nal all o graft bi o ps y: m ust occ ur wit hi n 4 wee ks le a di n g u p t o t he da y of 
ra n d o mizati o n 
−
A n o nst u d y bi o ps y ma y be use d as t he baseli ne bi o ps y pr o vi de d it meets t h e 
f oll o wi n g criteria:

it was perf or me d n o m or e t ha n 1 2 wee ks pri or t o Wee k  1 

t he s u bject has r e mai ne d cli nicall y sta ble si nce t he bi o ps y wit h n o 
c ha n ges i n me dicati o n r e gi me ns t hat w o ul d be e x pecte d t o si g nifica ntl y 
alter t he baseli ne bi o ps y fi n di n gs

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 2 9 
 
C o nfi de nti al  
 t he pri or bi o ps y is a vaila ble f or ce ntr al pat h ol o g y re vie w a n d i ncl u des 
all t he r e q uire d c o m p o ne nts of a st u d y baseli ne bi o ps y (see Secti o n  1 0. 9  
f or m ore details) 
•  Wee k  1 2 re nal all o graft bi o ps y: m ust occ ur at a ti me p oi nt bet wee n Wee ks  1 2 a n d 1 4, 
i ncl usi ve; Gr o u p 2 s u bjects ca n n ot be gi n pe gcetac o pla n a d mi nistr ati o n u ntil after t he 
bi o ps y occ urs  
•  Wee k  5 2 re nal a ll o graft bi o ps y: m ust occ ur at a ti me p oi nt bet wee n Wee ks  4 8 a n d 5 2, 
i ncl usi ve, b ut after c o m pleti o n of t he 2 4-h o ur uri ne c ollecti o n sc he d ule d f or Wee k  4 8. 
I n t he e ve nt t hat a s u bject has a bi o ps y f or cli nical ca use wit hi n t he ti me fr a me all o we d f or a 
st u d y bi o ps y, t his cli nical bi o ps y ma y be a ble t o ser ve as o ne of t he pr ot oc ol bi o psies, pr o vi de d it 
i ncl u des all re q uire d c o m p o ne nts f or t his st u d y. If it is n ot a ble t o ser ve as a pr ot oc ol bi o ps y, 
t he n i nf or mati o n fr o m t hat bi o ps y s h o ul d still be c ollecte d wit hi n t he st u d y data base, if possi ble.  
After c o m pleti o n of t he 5 2 -wee k mai n pe ri o d, a n y s u bject w h o, i n t he o pi ni o n of t he i n vesti gat or, 
is e x perie nci n g cli nical be nefit fr o m pe gcetac o pla n a d mi nistr ati o n will be i n vite d t o partici pate 
i n Part B, t he l o n g-ter m e xte nsi o n, i n or der t o c o nti n ue t o r ecei ve tr eat me nt wit h pe gcetac o pla n 
u ntil it is c o m merciall y a vaila ble f or t he disease u n der st u d y (see Secti o n  1 5 ). T h ose w h o d o n ot 
c o nti n ue o n pe gce tac o pla n i n t he l o n g-ter m e xte nsi o n pr ot oc ol will e nter a f oll o w-u p peri o d of a 
mi ni m u m of 8 wee ks.  
6. 2. 1.  
Scree ni n g P eri o d  
T he scree ni n g peri o d will occ ur i n 2  sta ges, s uc h t hat all assess me nts descri be d at Visit  1 m ust 
occ ur bef ore t h ose i n V isit 2. T his e ns ur es t hat t he m or e i n vasi ve pr oce d ur es ( vacci nati o ns a n d 
bi o ps y of re nal all o graft) d o n ot occ ur u nless t he s u bject is eli gi ble b y all ot her criteria. 
Vacci nati o ns f or N. me ni n giti dis , S. p ne u m o ni ae , a n d H.  i nfl ue nz a s h o ul d be a d mi nister e d at 
least 2 wee ks pri or t o ra n d o mizati o n; h o we ver, i n t he e ve nt t hat a n e x pe diti o us st u d y start is 
warra nte d, t he vacci nati o n sc he d ule ma y be a dj uste d. I n ge ner al, a d mi nistr ati o n of vacci nati o ns 
i m me diatel y after t he re nal bi o ps y ma y be a n efficie nt wa y t o ma na ge t he assess m e nts of Visit  2.  
S u bjects s h o ul d be o n sta ble d oses of all me dicati o ns r ele va nt t o t heir r e nal disease f or at least 
4 wee ks pri or  t o t he scree ni n g re nal all o gr aft bi o ps y a n d fr o m t he ti me of t he scr ee ni n g r e nal 
all o graft bi o ps y u ntil ra n d o mizati o n. C ha n ges t o t he baseli ne tr eat me nt r e gi me n s h o ul d be 
mi ni mize d t o t he greatest e xte nt p ossi ble a n d ma de o nl y w he n r e q uir e d f or t he well -bei n g of t he 
s u bject. See Secti o n  8. 8  ( C o nc o mita nt Me dicati o ns) f or f urt her g ui da nce. 
6. 2. 2.  
M ai n  P eri o d 
A ll s u bjects w h o e nter t he mai n peri o d will be r a n d o mize d i nt o eit her Gr o u p 1 or Gr o u p  2. 
T he m ai n peri o d will be s u b di vi de d i nt o t he c o ntr olle d ( Wee ks  1-1 2) a n d n o nc o ntr olle d 
( Wee ks 1 3-5 2) p orti o ns. S u bjects i n Gr o u p  1 will recei ve pe gcetac o pla n tr eat me nt d uri n g b ot h 
t he c o ntr olle d a n d n o nc o ntr olle d p orti o ns of t he mai n peri o d. S u bjects i n Gr o u p 2 will n ot 
recei ve pe gcetac o pla n treat me nt d uri n g t he c o ntr olle d p orti o n, b ut f oll o wi n g t heir Wee k 1 2 
bi o ps y, t he y t o o will be gi n recei vi n g pe gcetac o pla n tr eat me nt d uri n g t he n o nc o ntr olle d p orti o n.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 3 0 
 
C o nfi de nti al  
As wit h t he scree ni n g peri o d, c ha n ges t o t he baseli ne tr eat me nt r e gi me n s h o ul d be mi ni mize d t o 
t he greatest e xte nt p ossi ble a n d ma de o nl y w he n r e q uir e d f or t he well -bei n g of t he s u bject. 
See  Secti o n  8. 8  ( C o nc o mita nt Me dicati o ns) f or f urt her g ui da nce.  
Pe gcetac o pl a n treat me nt, t he ti mi n g o f w hic h is i n dicate d base d o n Gr o u p 1 or 2 r a n d o mizati o n 
assi g n me nt, will c o nsist of t wice -wee kl y S C d osi n g of 1 0 8 0  m g pe gcetac o pla n, self -a d mi nister e d 
at h o me, wit h t he e xce pti o n of sc he d ule d cli nic visits. F or t he first d ose of pe gcetac o pla n o nl y, 
t he site staff will assist i n a d mi nisteri n g pe gcetac o pla n. At s u bse q ue nt cli nic visits, s u bjects will 
self-a d mi nister pe gcetac o pla n i n t he pr ese nce of t he site staff a n d u n der g o vari o us saf et y a n d 
efficac y assess me nts b y q ualifie d site staff, as i n dic ate d i n t he Sc he d ule of Acti vities ( T a ble  1).  
Use of pr o p h ylactic a nti bi otics is all o we d, at t he discr eti o n of t he i n vesti gat or, a n d s h o ul d ta ke 
i nt o c o nsi derati o n t he le vel of i m m u n os u p pr essi o n, c o m ple me nt le vels, a n d ti mi n g of 
vacci nati o n relati ve t o pe gcetac o pla n start, as well as l ocal pr actices.  
6. 2. 3.  
P art B: L o n g -Ter m E xte nsi o n  
At Visit  1 6 ( Wee k  5 2), a n y s u bject w h o, i n t he o pi ni o n of t he i n vesti gat or, is e x perie nci n g 
cli nical be nefit fr o m pe gcetac o pla n a d mi nistr ati o n will be i n vite d t o partici pate i n Part B, 
t he l o n g-ter m e xte nsi o n, i n or der t o c o ntin ue t o r ecei ve tr eat me nt wit h pe gcetac o pla n u ntil it is 
c o m merciall y a vaila ble f or t he disease u n der st u d y. S u bjects w h o elect t o e nter t he l o n g -ter m 
e xte nsi o n s h o ul d c o m plete st u d y pr oce d ur es as o utli ne d i n t he a p pe n dices ( Secti o n  1 5  a n d 
T a ble  7 ). If t he y e nter Part B, t he y d o n ot nee d t o partici pate i n t he f oll o w-u p peri o d.  
6. 2. 4.  
F oll o w -u p P eri o d  
After c o m pleti o n of t he mai n peri o d, if a s u bject d oes n ot e nter Part B, t he l o n g -ter m e xtensi o n, 
t he y will nee d t o c o m plete t he 8- wee k f oll o w -u p peri o d.  
A d diti o nall y, f or t h ose s u bjects w h o disc o nti n ue t he mai n per i o d b ut ar e willi n g t o r e mai n i n t he 
st u d y, t he y s h o ul d c o nti n ue i n t he st u d y b y be gi n ni n g t he f oll o w-u p peri o d. De pe n di n g o n t he 
ti mi n g of pe gcetac o pla n disc o nti n uati o n, s o me assess me nts pla n ne d f or Visits 1 5 a n d 1 6 ma y 
als o be necessar y.  
6. 2. 5.  
E n d of St u d y  
A s u bje ct will ha ve f ulfille d t he re q uir e me nts f or st u d y c o m pleti o n if/ w he n t he s u bject has 
c o m pleted all st u d y peri o ds, i ncl u di n g t he 8- wee k f oll o w -u p peri o d as i n dicate d i n t he Sc he d ule 
of Acti vities ( T a ble  1). 
T he e n d of t he st u d y will be w he n t he last s ubject  has c o m plete d t heir  last visit as i n dicate d i n 
t he Sc he d ule of Acti vities (T a ble  1) or t he earl y ter mi nati o n a n d e xit visits as i n dicate d i n t he 
Part B S ch e d ule of Acti vities ( T a ble  7 ) or has wit h dr a w n fr o m t he st u d y as descri be d i n 
Secti o n  7. 2  or as re q ueste d b y t he s p o ns or.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 3 1 
 
C o nfi de nti al  
7.  
S T U D Y P O P U L A TI O N  
T his st u d y ai ms t o e nr oll patie nts wit h pri mar y C 3 G or I C -M P G N w h o ha ve ha d a 
p ost- tra ns pla nt rec urre nce of t heir disease i n t heir re nal all o gr aft. T he i ncl usi o n a n d e xcl usi o n 
criteria bel o w f urt her i de ntif y t he p o p ulati o n t o be st u die d. A d diti o nal i nf or mati o n r elate d t o 
disc o nti n uati o ns a n d s u bjects l ost t o f oll o w -u p is pr ese nte d i n Sec ti o n 7. 2 . 
7. 1.  
Selecti o n of St u d y P o p ul ati o n  
7. 1. 1.  
I ncl usi o n Criteri a 
I n di vi d uals m ust meet all of t he f oll o wi n g criteria at scr ee ni n g visits t o be i ncl u de d i n t he st u d y: 
1.  At lea st 1 8 years of a g e at scree ni n g  
2.  M ust ha ve cli nical a n d pat h ol o gic e vi de nce of r ec urr e nt C 3 G or I C -M P G N, as  e vi de nce d 
b y all of t he f oll o wi n g:  
a. A dia g n osis of C 3 G or I C -M P G N, w it h at least 2 + stai ni n g f or C 3c i n t he re nal all o graft, 
c o nfir me d b y a ce ntral pat h ol o gist, base d o n t he scree ni n g re nal all o graft bi o ps y  
b.  C 3 G or I C -M P G N m us t be pri mar y a n d n ot sec o n dar y t o a n ot her c o n diti o n 
(e g, i nfecti o n, mali g na nc y, m o n ocl o nal ga m m o pat h y, a ut oi m m u nit y, c hr o nic 
a nti b o d y-me diate d rejecti o n, c hr o nic t hr o m b otic micr oa n gi o pat h y, or a me dicati o n)  
3.  Sta ble ( n ot i m pr o vi n g) or w orse ni n g disease, i n t he o pi ni o n of t he i n vesti gat or, i n t he 
2 m o nt hs prec e di n g t he first d ose of pe gcetac o pla n  
4.  e G F R ≥1 5  m L/ mi n/ 1. 7 3  m2, calc ulate d b y t he C hr o nic Ki d ne y Disease– E pi de mi ol o g y 
C olla b orati o n ( C K D -E PI) creati ni ne e q uati o n f or a d ults  
5.  N o m ore t ha n 5 0 % gl o mer ul oscler osis or i nterstitial fi br osis o n t he scr ee ni n g r e nal bi o ps y  
6.  Sta ble re gi me n f or rec urre nt C 3 G/I C -M P G N f o r at least 4 wee ks pri or t o t he scree ni n g re nal 
all o graft bi o ps y a n d fr o m t he ti me of t he scree ni n g re nal all o graft bi o ps y u ntil ra n d o mizati o n 
7.  Ha ve  recei ved re q uired vacci nati o ns a gai nst N. me ni n giti dis , S. p ne u m o ni ae , 
a n d H.  i nfl ue nz ae (t y pe B) or a gr ee t o r ecei ve vacci nati o ns if a p plica ble vacci nati o n 
rec or ds are n ot a vaila ble. Vacci nati o n is ma n dat or y u nless d oc u me nte d e vi de nce e xists 
t hat s u bjects are n o nres p o n ders t o vacci nati o n. 
8.  W o me n of c hil d beari n g p ote ntial ( W O C B P), defi ne d as a n y w o me n w h o ha ve 
e x peri e nce d me narc he a n d w h o ar e n ot per ma ne ntl y sterile or p ost me n o pa usal, m ust ha ve 
a ne gati ve bl o o d pre g na nc y test at scr ee ni n g ( a n d ne gati ve uri ne pr e g na nc y at Visit  4) 
a n d m ust a gree t o use pr ot oc ol -defi ne d met h o ds of c o ntr ace pti o n fr o m scr ee ni n g t hr o u g h 
1 2 wee ks after recei vi n g last d ose of pe gcetac o pla n  
9.  Me n m ust a gree t o use pr ot oc ol -defi ne d me t h o ds of c o ntrace pti o n a n d a gree t o refrai n fr o m 
d o nati n g se me n fr o m scree ni n g t hr o u g h 1 2  wee ks after recei vi n g last d ose of pe gcetac o pla n  
1 0.  Willi n g a n d a ble t o pr o vi de writte n i nf or me d c o nse nt  
1 1.  A ble t o u n dersta n d a n d  willi n g t o c o m pl y wit h all sc he d ule d pr oce d ur es a n d ot her 
re q uire me nts of t he st u d y i n t he o pi ni o n of t he i n vesti gat or 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 3 2 
 
C o nfi de nti al  
1 2.  Willi n g a n d a ble t o self -a d mi nister pe gcetac o pla n or ha ve a n i de ntifie d car e gi ver w h o ca n 
perf or m t he a d mi nistrati o n  
7. 1. 2.  
E xcl usi o n Criteri a  
I n di vi d uals meeti n g a n y of t he f oll o wi n g criteria at scr ee ni n g or baseli ne ar e i neli gi ble t o 
partici pate  i n t his st u d y: 
1.  A bs ol ute ne utr o p hil c o u nt < 1 0 0 0  cells/ m m 3 d uri n g scr ee ni n g ( n ot i ncl u di n g Da y  1)  
2.  Pre vi o us treat me nt wit h pe gcetac o pla n  
3.  E vi de nce of rejecti o n o n t he scr ee ni n g r e nal all o graft bi o ps y t hat r e q uir es tr eat me nt  
4.  Dia g n osis or hist or y of HI V, he patitis B, or he patitis C i nf ecti o n or p ositi ve ser ol o g y at 
scree nin g i n dicati ve of i nfecti o n wit h a n y of t hese vir uses  
5.  Wei g ht m ore t ha n 1 0 0  k g at scree ni n g 
6.  H y perse nsiti vit y t o pe gcetac o pla n or t o a n y of t he e xci pie nts 
7.  Hist or y of me ni n g oc occal disease  
8.  Mali g na nc y, e xce pt f or t he f oll o wi n g:  
a.  C ure d basal or s q ua m o us cell s ki n ca ncer  
b.  C urati vel y treate d i n sit u disease  
c.  Mali g na nc y free a n d off treat me nt f or  ≥5  years  
9.  Si g nif ica nt re nal disease i n t he r e nal all o gr aft sec o n dar y t o a n ot her c o n diti o n 
(e g, i nfecti o n, mali g na nc y, m o n ocl o nal ga m m o pat h y, r ejecti o n, or a me dicati o n) t hat 
w o ul d , i n t he o pi ni o n of t he i n vesti gat or, c o nf o u n d i nter pr etati o n of t he st u d y r e s ults 
1 0.  Partici pati o n i n a n y ot her i n vesti gati o nal dr u g trial or e x p os ur e t o ot her i n vesti gati o nal 
a ge nt, de vi ce, or pr oce d ure wit hi n 3 0  da ys or 5  half -li ves fr o m t he last d ose of t he 
i n vesti gati o nal a ge nt ( w hic he ver is l o n ger) pri or t o scr ee ni n g peri o d 
1 1.  W o me n w h o are pre g na nt or w h o ar e c urr e ntl y br eastf ee di n g  
1 2.  I na bilit y t o c o o perate or a n y c o n diti o n t hat, i n t he o pi ni o n of t he i n vesti gat or, c o ul d i ncrease 
t he s u bject’s ris k b y partici pati n g i n t he st u d y or c o nf o u n d t he o utc o me of t he st u d y 
1 3.  E vi de nce of dr u g or  alc o h ol a b use or de pe n de nce, i n t he o pi ni o n of t he i n vesti gat or  
1 4.  K n o w n or s us pecte d here ditar y fr uct ose i nt oler a nce.  
7. 1. 3.  
A p p r o ve d Met h o ds of C o nt r ace pti o n  
A w o ma n is c o nsi dere d t o be of c hil d beari n g p ote ntial f oll o wi n g me nar c he a n d u ntil bec o mi n g 
p ost me n o pa usa l, u nless per ma ne ntl y sterile. Per ma ne nt sterilizati o n met h o ds i ncl u de 
h ysterect o m y, bilateral sal pi n gect o m y , a n d bilater al o o p h or ect o m y. A p ost me n o pa usal state is 
defi ne d as n o me nses f or 1 2  m o nt hs wit h o ut a n alter nati ve me dical ca use.  
A p pr o ve d met h o ds of c o ntrace pti o n i ncl u de:  
•  C o m bi ne d (estr o ge n a n d pr o gest o ge n c o ntai ni n g) h or m o nal c o ntr ace pti o n ass ociate d 
wit h i n hi bi ti o n of o v ulati o n: 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 3 3 
 
C o nfi de nti al  
− oral, i ntra va gi nal, or tra ns der mal  
•  Pr o gest o ge n- o nl y h or m o nal c o ntr ace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n:  
− oral , i njecta ble, or i m pla nta ble 
•  I ntra uteri ne de vice 
•  I ntra uteri ne h or m o ne -releasi n g s yste m 
•  Bilateral t u bal occl usi o n  
•  Vasect o m ize d part ner (pr ovi de d t h at  t he p art ner is t he s ole sex u al p art ner of t he 
W O C B P tri al p artici p a nt a n d t h at t he v asect o mize d p art ner h as  receive d me dic al 
assess me nt of t he s ur gic al s uccess ) 
•  Se x ual a bsti ne nce ( defi ne d as r efr ai ni n g fr o m heter osex u al i nterc o urse d uri n g t he 
e ntire peri o d of risk ass oci ate d wit h st u dy tre at me nts ) 
•  Male c o n d o m wit h or wit h o ut s per mici de ( f or m ale st u d y s u bj ects wit h f e m ale 
p art ners of c hil d be ari n g p ot e nti al o nl y ) 
N ote: Se x ual a bsti ne nce is o nl y acce pte d w he n it is t he preferre d a n d us ual lifest yle of t he s u bject.  
S u bjects m ust a gree t o use a n a p pr o ve d met h o d of c o ntr ace pti o n d uri n g t he st u d y a n d f or 
1 2 w ee ks aft er t heir last d ose of st u d y dr u g.  
7. 2.  
Disc o nti n u ati o ns a n d S u bjects L ost t o F oll o w -u p  
7. 2. 1.  
E arl y Tre at me nt Disc o nti n u ati o n a n d St u d y Wit h dr a w al  
A s u bject ma y wit h dra w fr o m t he st u d y at a n y ti me, f or a n y r eas o n, wit h o ut pr ej u dice t o his/ her 
f ut ure me dical care b y t he p h ysicia n or at t he i nstit uti o n. T he i n vesti gat or or s p o ns or ma y 
wit h dra w t he s u bject at a n y ti me (e g, i n t he i nter est of t he s u bject’s saf et y). If a s u bject 
disc o nti n ues or is wit h dra w n fr o m st u d y tr eat me nt f or a n y r eas o n, t he st u d y site m ust 
i m me diatel y n otif y t he me dical m o nit or.  
O nce a s u bject is wit h dra w n fr o m t he st u d y, t he s u bject ma y n ot r ee nter t he st u d y.  
S u bjects w h o disc o nti n ue st u d y treat me nt pri or t o t he e n d of t he mai n peri o d s h o ul d u n der g o all 
f oll o w-u p visit s a n d pr oce d ures t hr ou g h t he e xit visit u nless t he y are u n willi n g or u na ble or c o nse nt 
has bee n wit h dra w n. S u bjects w h o wis h t o f ull y wit h dra w fr o m t he st u d y bef or e c o m pleti o n s h o ul d 
be e nc o ura ge d t o c o m plete t he earl y ter mi nati o n visit as descri be d i n Secti o n  9. 5 . 
7. 2. 2.  
Re as o ns f or  Disc o nti n u ati o n 
T he date of a n d reas o n f or treat me nt disc o nti n uati o n m ust be deter mi ne d b y t he i n vesti gat or a n d 
rec or de d i n t he s u bject’s me dical recor d. If it is deter mi ne d t hat t her e was m or e t ha n o ne r eas o n 
f or t he disc o nti n uati o n, eac h reas o n s h o ul d be d oc u me nte d i n t he s o ur ce d oc u me nt, a n d t he m ost 
cli nicall y rele va nt reas o n, as deter mi ne d b y t he i n vesti gat or, s h o ul d be i de ntifie d. Tr eat me nt ma y 
b e disc o nti n ue d a n d/ or a s u bject’s partici pati o n i n t he st u d y ma y be disc o nti n ue d f or a n y of t he 
f oll o wi n g reas o ns: 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 3 4 
 
C o nfi de nti al  
•  A n y seri o us a d verse e ve nt ( S A E), cli nicall y si g nifica nt A E, se ver e la b or at or y 
a b n or malit y, i nterc urre nt ill ness, ot her me dical c o n diti o n (i ncl u di n g i nf ecti o ns), 
or circ u msta nce t hat i n dicates t o t he i n vesti gat or t hat c o nti n ue d partici pati o n is n ot i n 
t he best i nterest of t he s u bject 
•  S u bject wit h dra wal of c o nse nt: At a n y ti me, a s u bject’s partici pati o n i n t he st u d y ma y 
be ter mi nate d at his/ her re q uest or o n t he basis of t he i n vesti gat or’s cli nical j u d g me nt. 
T he reas o n f or s u bject wit h dr a wal will be n ote d i n t he s u bject’s s o ur ce d oc u me nt.  
• S u bject fails t o a d here t o t he pr ot oc ol re q uir e me nts (e g, dr u g n o nc o m plia nce, fail ure t o 
ret ur n f or defi ne d n u m ber of visits)  
•  S u bject is l ost t o f oll o w -u p: t he s u bje ct st o p pe d c o mi n g f or visits, a n d st u d y 
pers o n nel were u na ble t o c o ntact t he s u bject  
•  T er mi nati o n of t he st u d y b y t he s p o ns or or r e g ulat or y a ut h orities  
•  Li ver t o xicit y (refer t o Secti o n  7. 2. 3  f or f urt her details) 
•  Pre g na n c y, as i n dicate d i n Secti o n  1 1. 3  
•  Fail ure t o meet ra n d o mizati o n criteria  
A n y s u bject  w h o disc o nti n ues treat me nt earl y or is wit h dr a w n fr o m t he st u d y earl y d ue t o a 
treat me nt-e mer ge nt a d verse e ve nt ( T E A E), w het her seri o us or n o nseri o us, will be f oll o we d u ntil 
t he T E A E res ol ves (ret ur ns t o n or mal or baseli ne val ues) or sta bilizes or u ntil it is j u d ge d b y t he 
i n vesti gat or t o n o l o n ger be cli nicall y si g nifica nt. 
If c o nse nt is wit h dra w n, n o f urt her st u d y e val uati o ns ar e t o be perf or me d a n d n o atte m pts ar e t o 
be ma de t o c ol lect a d diti o nal data. 
A d diti o nall y, t he s p o ns or ma y st o p t he st u d y at a n y ti me f or saf et y, r e g ulat or y, le gal, or ot her 
reas o ns ali g ne d wit h g o o d cli nical practice ( G C P). T his st u d y ma y be ter mi nate d at t he discr eti o n 
of t he s p o ns or or a n y re g ulat or y a ge nc y. A n i n vesti gat or ma y elect t o disc o nti n ue or st o p t he 
st u d y at his/ her st u d y site f or a n y reas o n, i ncl u di n g saf et y or l o w e nr oll me nt. 
7. 2. 3.  
Li ver T o xi cit y 
Dr u g treat me nt c o nti n uati o n will be e val uate d i n case of a n y si g ns of p ossi ble dr u g -i n d uce d 
he patic i nj ur y as f oll o ws:  
Dr u g treat me nt will be disc o nti n ue d i m me diatel y if eit her:  
•  ala ni ne a mi n otra nsferase ( A L T) or as partate a mi n otr a nsf er ase ( A S T) is > 3 × t he U L N  
a n d (t otal bilir u bi n is > 2 × t he U L N or i nter nati o nal n or malize d r ati o is > 1. 5)  
or 
•  A L T or A S T is > 8 × t he U L N  
D r u g treat me nt will be wit h hel d if eit her : 
•  A L T or A S T is > 5 × t he U L N  
or  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 3 5  
 
C o nfi de nti al  
•  A L T or A S T is > 3 × t he U L N wit h t he a p pear a nce of f ati g ue, na usea, v o miti n g, 
ri g ht u p per q ua dra nt pai n or te n der ness, f e ver, r as h, a n d/ or e osi n o p hilia ( > 5 %)  
Dr u g treat me nt will be per ma ne ntl y disc o nti n ue d a n d t he s u bject wit h dr a w n fr o m t he st u d y if t he 
c o n ditio n persists f or m ore t ha n 2  wee ks.  
If t he s u bject is n ot wit h dra w n fr o m t he st u d y, dr u g tr eat me nt ma y be r es u me d w he n b ot h A L T 
a n d A S T are less t ha n 1. 5 × U L N.  
A n y p ossi ble he patic a b n or malities will be m o nit or e d wit h r e peat testi n g at a fr e q ue nc y of at 
least e ver y 7 2  h o urs. Fre q ue nc y of retesti n g will decr ease t o wee kl y or less o nce a b n or malities 
sta bilize. Re peat testi n g will disc o nti n ue o nce a b n or malities ar e n o l o n ger detecte d. 
Ca uses f or t he si g nifica nt li ver test a b n or malities will be i n vesti gate d  (e g, ac ute viral he patitis, 
E pstei n -Barr vir us, c yt o me gal o vir us, her pes si m ple x vir us, t o x o plas m osis, varicella, a n d par v o vir us), 
a n d s u bjects will be f oll o we d u p u ntil all a b n or malities ret ur n t o n or mal or t o t he baseli ne state.  
W or k u p will als o i ncl u de c o nsi derati o n of alc o h olic a n d a ut oi m m u ne he patitis, he pat o biliar y 
dis or ders ( e g, gallst o nes), n o nalc o h olic steat o he patitis, car di o vasc ular ca uses ( e g, ri g ht -si de d 
heart fail ure), a n d c o nc o mita nt me dicati o ns or s u p ple me nts.  
7. 2. 4.  
S u bjects L ost t o F oll o w -u p P ri or t o L ast Sc he d ule d Visit  
A mi ni m u m of 3 d oc u me nte d atte m pts m ust be ma de t o c o ntact a n y s u bjects l ost t o f oll o w -u p at 
a n y ti me p oi nt pri or t o t he last sc he d ule d c o ntact ( office visit or tele p h o ne c o ntact). At least 1 of 
t hese d oc u me nte d atte m pts m ust i ncl u de a writte n c o m m u nicati o n se nt t o t he s u bject’s last 
k n o w n a d dress via c o urier or mail ( wit h a n ac k n o wle d g me nt of r ecei pt r e q uest) as ki n g t hat t he 
s u bject ret ur n t o t he site f or fi nal safet y e val uati o ns a n d t o r et ur n a n y i n vesti gati o nal pr o d uct. 
7. 2. 5.  
Re pl ace me nt  of S u bjects 
S u bjects w h o disc o nti n ue treat me nt earl y or wit h dra w fr o m t he st u d y earl y f or r eas o ns n ot 
relate d to t he safet y of pe gcetac o pla n ma y be r e place d at t he s p o ns or’s discr eti o n t o e ns ur e t hat 
t he o bjecti ves of t he st u d y are met. S u bjec ts assi g n e d t o tr eat me nt w h o disc o nti n ue or wit h dr a w 
fr o m t he st u d y ma y be re place d u ntil 1 2 s u bjects c o m plete Wee k 5 2 of t he st u d y.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 3 6 
 
C o nfi de nti al  
8.  
T R E A T M E N T S  
8. 1.  
Det ails of St u d y Tre at m e nts  
T he test pr o d uct is pe gcetac o pla n, w hic h will be pr o vi de d as a sterile s ol uti o n of pe gcetac o pla n 
1 0 8 0 m g/ 2 0 m L i n acetate -b uffere d s or bit ol, s u p plie d i n st o p per e d glass vials. 
A d diti o nal i nf or mati o n is pr o vi de d i n t he pe gcetac o pla n I B.  
8. 2.  
D os a ge Selecti o n  
T he d ose of pe gcetac o pla n is 1 0 8 0  m g t wice per wee k via S C i nf usi o n ( 2 0  m L) d uri n g t he mai n 
peri o d of Part A ( wit h d osi n g n ot be gi n ni n g f or Gr o u p  2 u ntil Wee k  1 3) a n d d uri n g Part B.  
As  n ote d i n Secti o n  4. 2. 1 , this st u d y uses t he sa me 1 0 8 0 m g t wi ce wee kl y d osi n g sc he d ule  
c urre ntl y use d i n t he P hase 3 st u dies i n patie nts wit h P N H . T his d ose was als o e val uate d i n 
St u d y A P L 2 - 2 0 1, a P hase 2 st u d y t hat e nr olle d patie nts wit h C 3 G.  
Gr o u p 1 s u bjects will recei ve t heir i nitial d oses of pe gcetac o pla n at t he sc he d ule d cli nic visit o n 
Da y  1 a n d will  c o nti n ue t o recei ve t heir pe gcetac o pla n ( 1 0 8 0 m g/ 2 0  m L t wice a wee k) o n Da y  1 
a n d Da y 4 of eac h treat me nt wee k u ntil Wee k  5 2 if t he y d o n ot e nter Part B; h o we ver, if t he y d o 
e nter Part B, t he treat me nt sc he d ule will c o nti n ue as d uri n g Part A.  
Gr o u p  2 s u bjects will recei ve t heir i nitial d oses of pe gcetac o pla n  after t he Wee k 1 2 re nal bi o ps y 
(see Sc he d ule of Acti vities [ Ta ble  1]) a n d will c o nti n ue t o recei ve pe gcetac o pla n ( 1 0 8 0 m g/ 2 0  m L 
t wice a wee k) o n Da y 1 a n d Da y  4 of eac h treat me nt wee k u ntil Wee k  5 2 if t he y d o n ot e nter Part B; 
h o we ver, if t he y d o e nter Part B , t he treat me nt sc he d ule will c o nti n ue as d uri n g Part A. 
D osi n g diaries will be utilize d f or pe gcetac o pla n a n d are t o be c o m plete d f or eac h d ose a d mi nistere d 
at t he clinic or o utsi de re g ular cli nic visits. S u bjects s h o ul d i deall y mai ntai n a c o nsiste nt d osi n g 
sc he d ule a n d s h o ul d n ot dela y or defer d osi n g. Misse d d oses will be ha n dle d o n a case- b y-case basis 
bet wee n t he i n vesti gat or a n d me dical m o nit or, wit h t he ge neral a p pr oac h bei n g t o a d mi nister a 
misse d d ose as s o o n as n otice d, u nless t he ne xt d ose has alrea d y bee n a d mi nistere d.  
8. 3.  
I n vesti g ati o n al Pr o d uct A d mi nistr ati o n 
I n vesti gati o nal pr o d uct, pe gcetac o pla n, will be a d mi nister e d as a 2 0-m L S C i nf usi o n.  
T he preferre d site of i nf usi o n will be t he a b d o me n. If a d mi nistr ati o n i nt o t he a b d o me n is n ot 
feasi ble, alter nati ve a p pr o priate sites ar e acce pta ble (see p har mac y ma n ual f or m or e details). 
Researc h n urses or ot her a p pr o priatel y q ualifie d r esear c h pers o n nel will a d mi nister t he S C 
i nf usi o ns (as nee de d) a n d will q ualif y a n d s u per vise t he self-a d mi nistr ati o n ( or c ar e gi ver 
a d mi nistrati o n). T hese q ualifie d pers o n nel will be ma de a vaila ble f or a mi ni m u m of 6  da ys o n 
treat me nt ( 2 d oses) t o e ns ure t he s u bject has bee n q ualifie d t o c o n d uct self -a d mi nistr ati o n; 
d urati o n c o ul d be s h orte ne d if q ualificati o n ha p pe ns s o o ner. D uri n g q ualificati o n, t he s u bject 
( or care gi ver) m ust de m o nstrate t o t he r esear c h pers o n nel t heir a bilit y t o saf el y a n d eff ecti vel y 
a d mi nister st u d y dr u g usi n g t he i nf usi o n p u m p. F oll o wi n g self -a d mi nistr ati o n q ualificati o n, 
s u bjects ma y self-a d mi nister t he S C i nf usi o ns wit h o ut s u per visi o n. O nce q ualifie d, t he s u bject 
will c o nti n ue t o self -a d mi nister i nf usi o ns at t he cli nic o n t h ose da ys w he n a cli nic visit occ urs 
a n d at a n off -site l ocati o n c o n ve nie nt t o t he s u bject o n all ot her da ys. Self-a d mi nistr ati o n 
c on d ucte d at t he cli nic will be s u per vise d t o e ns ur e t hat t he s u bject c o nti n ues t o r e mai n 
c o m plia nt wit h t he a d mi nistrati o n g ui deli nes.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 3 7  
 
C o nfi de nti al  
N O T E: If t he s u bject re q uires f urt her tr ai ni n g, t he self -a d mi nistr ati o n q ualificati o n peri o d ma y 
be e xte n de d be y o n d 6  da y s o n treat me nt ( 2 d oses). Self -a d mi nistr ati o n ma y als o be c o n d ucte d b y 
a me m ber of t he s u bject’s h o use h ol d or f a mil y me m ber, etc, w h o will u n der g o t he sa me 
q ualificati o n criteria b y t he i n -h o me me dical pr of essi o nal ( q ualificati o n is n ot i nte n de d t o be 
restricte d t o t he s u bject). Please refer t o t he p har mac y ma n ual f or f urt her details r e gar di n g 
self-a d mi nistrati o n q ualificati o n.  
8. 4.  
L a beli n g, P ac k a gi n g, I nf usi o n S u p plies, a n d St or a ge a n d H a n dli n g  
8. 4. 1.  
L a beli n g  
La bels c o ntai ni n g st u d y i nf or mati o n a n d pac k i de ntificati o n ar e a p plie d t o t he i n vesti gati o nal 
pr o d uct(s) c o ntai ner.  
All i n vesti gati o nal pr o d uct is la bele d wit h a mi ni m u m of t he f oll o wi n g: pr ot oc ol n u m ber, d osa ge 
f or m (i ncl u di n g pr o d uct na me a n d q ua ntit y i n pac k), r o ute of a d mi nistr ati o n, dir ecti o ns f or use, 
st ora ge c o n diti o ns, batc h n u m ber a n d/ or pac ka gi n g r ef er e nce, t he state me nts r e q uir e d per l ocal 
re g ulati o ns (e g, “ F or cli nical trial use o nl y”), a n d na me a n d a d dr ess of t he s p o ns or. 
S pace is all ocate d o n t he la bel s o t hat t he site r e pr ese ntati ve ca n r ec or d a u ni q ue s u bject  
i de ntifier a n d date dis pe nse d b y t he site t o t he s u bject. 
A d diti o nal la bels ma y, o n a case -b y -case basis, be a p plie d t o t he i n vesti gati o nal pr o d uct i n or der t o 
satisf y nati o nal, l ocal, or i nstit uti o nal re q uire me nts b ut m ust n ot d o a n y of t he f oll o wi n g: c o ntra dict 
t he cli nical st u d y la bel, o bsc ure t he cli nical st u d y la bel, i de ntif y t he st u d y s u bject b y na me. 
A d diti o nal la bels ma y n ot be a d de d wit h o ut t he s p o ns or’s pri or f ull a gr ee me nt.  
8. 4. 2.  
P ac k a gi n g 
In vesti gati o nal pr o d uct is s u p plie d i n 2 0 -m L glas s vials. Please refer t o t he p har mac y ma n ual 
f or details.  
C ha n ges t o s p o ns or -s u p plie d pac kagi n g pri or t o d osi n g ma y n ot occ ur wit h o ut f ull a gr ee me nt, 
i n a d va nce, b y t he s p o ns or.  
8. 4. 3.  
I nf usi o n S u p plies 
T he s p o ns or w ill s u p pl y s yri n ges, vial a da pters, i nf usi o n sets, a n d a m b ulat or y s yri n ge i nf usi o n 
p u m ps, as re q uire d. Refer t o t he p har mac y ma n ual f or f urt her details.  
8. 4. 4.  
St or a ge a n d H a n dli n g  
T he i n vesti gati o nal pr o d uct s h o ul d be st or e d r efri ger ate d at 2 - 8 ° C, b ot h at h o me a n d i n t he 
cli nic. T e m perat ure m o nit ori n g is re q uir e d at t he i n vesti gat or site ( or d oc u me nte d st or a ge 
l ocati o n) t o e ns ure t hat t he i n vesti gati o nal pr o d uct is mai ntai ne d wit hi n a n esta blis he d 
te m perat ure ra n ge.  
T he i n vesti gat or or a p pr o priatel y q ualifie d site staff will be r es p o nsi ble f or t he f oll o wi n g:  
•  e ns uri n g t hat t he i n vesti gati o nal pr o d uct is st or e d i n a sec ur e, li mite d -access l ocati o n 
at t he site 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 3 8 
 
C o nfi de nti al  
− li mite d res p o nsi bilit y ma y be dele gate d t o t he p har mac y or me m ber of t he st u d y 
tea m, b ut t his dele gati o n m ust be d oc u me nte d  
•  e ns uri n g t hat t he te m perat ur e is m o nit or e d t hr o u g h o ut t he d ur ati o n of t he st u d y a n d 
t hat rec ords are mai ntai ne d  
A p har macist or a p pr o priatel y q ualifie d desi g nate d pers o n will be r es p o nsi ble f or t he f oll o wi n g:  
•  st ori n g t he i n vesti gati o nal pr o d uct a p pr o priatel y 
•  dis pe nsi n g t he vials of i n vesti gati o nal pr o d uct t o t he s u bject  
•  e nterin g t he u ni q ue s u bject i de ntifier o n t he i n vesti gati o nal pr o d uct b ottle/cart o n 
la bels as the y are distri b ute d  
W he n t he s u bject recei ves t he i n vesti gati o nal pr o d uct fr o m t he site, it s h o ul d be tr a ns p orte d i n a 
s p o ns or-a p pr o ve d bag or b o x c o ntai ni n g pr e vi o usl y te m per at ur e -c o n diti o ne d c ol d plates t o 
e ns ure t hat t he st ora ge te m perat ure ( 2 - 8 ° C) is mai ntai ne d. T e m per at ur e m o nit ori n g will n ot be 
re quire d d uri n g tra ns p ort or at t he s u bject’s r esi de nce, b ut a l o g will be ke pt f or e ver y i nf usi o n t o 
e ns ure t hat all i n vesti gati o nal pr o d uct was ke pt r efri ger ate d.  
Wit h sp o ns or pri or a p pr o val, in vesti gat i o nal pr o d uct a n d/ or a ncillar y s u p plies ma y be s hi p pe d fr o m 
t he st u d y site t o a s u bject’s desi g nate d l ocati o n. S uc h s hi p me nts will o nl y be i m ple me nte d at sites 
w here t his acti vit y is a p pr o ve d b y t he I R B/ E C a n d healt h a ut h orit y (if re q uire d). S u bject c o nse nt will 
be re q uire d pri or t o a n y s u bject i nf or mati o n bei n g pr o vi de d t o a c o urier. T he res p o nsi bilit y t o ret ur n 
b ot h e m pt y vials a n d a n y u n use d i n vesti gati o nal pr o d uct s hall re mai n u nc ha n ge d.  
8. 5.  
Me as ures t o Mi ni mize Bi as: St u d y Tre at m e nt Assi g n m e nt  
Ra n d o mizati o n will occ ur t hr o u g h t he i nter acti ve res p o nse tec h n ol o g y s yste m.  
8. 5. 1.  
Met h o d of S t u d y Tre at m e nt Assi g n m e nt 
All s u bjects w h o meet all t he i ncl usi o n criteria a n d n o ne of t he e xcl usi o n criteria will be e nr olle d 
i n t he st u d y, u ntil s uc h ti me t hat u p t o 1 2 s u bjects ha ve bee n e nr olle d i n t he st u d y. S u bjects will 
t he n be ra n d o mize d t hr o u g h t he i nter acti ve r es p o nse tec h n ol o g y s yste m t o eit her Gr o u p 1 
( pe gcetac o pla n) or Gr o u p 2 (c o ntr ol). F oll o wi n g c o m pleti o n of t he mai n peri o d, all s u bjects will 
e nter t he f oll o w -u p peri o d u nless t he y e nter t he s p o ns or -pla n ne d l o n g -ter m e xtensi o n pr ot oc ol.  
8. 6.  
I n vesti g ati o n al Pr o d uct Acc o u nt a bilit y 
I n vesti gat ors will be pr o vi de d wit h s ufficie nt a m o u nts of t he i n vesti gati o nal pr o d uct t o carr y o ut 
t his pr ot oc ol f or t he a gree d n u m ber of s u bjects. T he i n vesti gat or or desi g nee will ac k n o wle d ge 
recei pt of t he i n vesti gati o nal pr o d uct, d oc u me nti n g s hi p me nt c o nte nt a n d c o n diti o n. Acc ur ate 
rec or ds of all i n vesti gati o nal pr o d uct dis pe nse d, use d, r et ur ne d, a n d/ or destr o ye d m ust be 
mai ntai ne d. T he i n vesti gat or is res p o nsi ble f or e ns uri n g t he r etrie val of all r et ur na ble st u d y 
s u p plies fr o m s u bjects. 
At t he c o ncl usi o n of t he st u d y, a n y u n use d i n vesti gati o nal pr o d uct will eit her be destr o ye d at t he 
i n vesti gator site or be ret ur ne d t o t he s p o ns or or desi g nee f or destr ucti o n, a n d destr ucti o n will be 
d oc u me nte d a p pr o priatel y. If n o s u p plies r e mai n, t his f act will be d oc u me nte d a p pr o priatel y.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 3 9 
 
C o nfi de nti al  
8. 7.  
S u bject C o m pli a nce  
S u bjects m ust be i nstr ucte d t o bri n g t heir e m pt y/ u n use d i n vesti gati o nal pr o d uct pac ka gi n g t o 
e ver y visit. T he p har macist/ n o mi nate d pers o n will r ec or d details o n  t he dr u g acc o u nta bilit y f or m. 
8. 8.  
Pri or a n d C o nc o mit a nt Me dic ati o ns a n d Pr oce d ures  
All me dicati o ns a d mi nistere d a n d pr oce d ur es perf or me d wit hi n 1 2  wee ks of scr ee ni n g will be 
c ollecte d as pri or me dicati o ns a n d pr oce d ur es. Me dicati o ns a d mi nister e d a n d pr oce d ur e s 
perf or me d fr o m t he ti me of i nf or me d c o nse nt t hr o u g h t he e n d - of-st u d y visit ar e r e gar de d as 
c o nc o mita nt a n d will be d oc u me nte d. Use of rit u xi ma b, beli m u ma b, ec uliz u ma b, 
a n d ra v uliz u ma b d uri n g t he st u d y (a n d/ or wit hi n 2 4 wee ks pri or t o t he first d ose of 
pe gcetac o pla n) m ust be disc usse d wit h t he s p o ns or f or c o nsi der ati o n a n d a p pr o val.  
S u bjects s h o ul d be o n sta ble d oses of all me dicati o ns rele va nt t o t heir re nal disease f or at least 
4 wee ks pr i or t o t he scree ni n g re nal all o graft bi o ps y u ntil t he e n d of t he st u d y. D uri n g t he st u d y, 
i ncl u di n g t he scree ni n g peri o d, c ha n ges t o t he baseli ne treat me nt re gi me ns (i ncl u di n g me dicati o ns, 
dietar y restricti o ns, a n d lifest yle m o dificati o ns) s h o ul d be mi ni mize d t o t he e xte nt p ossi ble a n d ma de 
o nl y w he n re q uire d f or t he well -bei n g of t he s u bject. H o we ver,  i n t he setti n g of a n ac ute cresce ntic 
gl o mer ul o ne p hritis at t he ti me of st u d y e ntr y, ster oi d treat me nt ma y be i nitiate d al o n g wit h, or ar o u n d 
t he sa me ti me as, pe gcetac o pla n treat me nt, if dee me d necessar y b y t he i n vesti gat or.  
If t he s u bject is i n a p ost-tra ns plant ti me fra me i n w hic h i m m u n os u p pressi o n or ot her 
tra ns pla nt-relate d me dicati o n a dj ust me nts are a ntici pate d, t hese a dj ust me nts s h o ul d still occ ur, 
a d heri n g t o t he ce nter’s sta n dar d pr ot oc ol f or p ost -tra ns pla nt care. F or all s u bjects, t he pla n f or 
p ost -tra ns pla nt i m m u n os u p pressi o n f or t he d urati o n of t he st u d y s h o ul d be d oc u me nte d pri or t o 
ra n d o mizati o n. A n y de viati o n d uri n g t he st u d y fr o m t he pres pecifie d pla n s h o ul d be d oc u me nte d 
wit h a j ustific ati o n f or t he c ha n ge. S u bjects wit h e vi de nce of rejecti o n o n t he scree ni n g bi o ps y t hat 
re q uires treat me nt will nee d t o u n der g o t heir a ntirejecti o n treat me nt, a n d t he n ca n be rec o nsi dere d f or 
pe gcetac o pla n d osi n g, b ut will nee d t o meet all ot her st u d y eli gi bilit y criteria, i ncl u di n g a scree ni n g 
bi o ps y t hat is wit hi n t he desi g nate d assess me nt wi n d o w, t o ser ve as t he baseli ne (refer t o 
Secti o n  9. 1. 3  f or f urt her details). S u bjects wit h e vi de nce of s u bcli nical rejecti o n o n t he scree ni n g 
bi o ps y ma y pr oc ee d wit h pe gcetac o pla n treat me nt, at t he discreti o n of t he i n vesti gat or, pr o vi de d n o 
treat me nt is i nitiate d f or t he rejecti o n. 
8. 8. 1.  
E m piric A nti bi otic Tre at m e nt f or P ossi ble I nf ecti o n  
B o d y te m perat ure, vital si g ns, a n d rele va nt bl o o d par a meters will be m o nit or e d r e g ularl y 
t hr o u g h o ut t he stu d y t o assess f or si g ns of i nf ecti o n. T he i n vesti gat or s h o ul d be c o ntacte d 
i m me diatel y i n t he e ve nt of a s us pecte d i nf ecti o n f or g ui da nce o n a p pr o priate acti o n t o be ta ke n. 
Acti o n t o be ta ke n ma y i ncl u de e m piric a d mi nistr ati o n of a br oa d -s pectr u m a nti bi otic t o c o ver 
p ossi ble seri o us i nfecti o ns, s uc h as me ni n g oc occ us.  
 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 4 0 
 
C o nfi de nti al  
9.  
S T U D Y P R O C E D U R E S  
T a ble  1 o utli nes t he ti mi n g of pr oce d ur es a n d assess me nts t o be perf or me d t hr o u g h o ut Part A of 
t he st u d y, o nce writte n i nf or me d c o nse nt has bee n o btai ne d fr o m t he s u bject. Secti o n  1 0. 1 3  
s pecifies la b orat or y assess me nt sa m ples t o be o btai ne d. T he sc he d ule of visit dates s h o ul d be 
esta blis he d, eit her pri or t o or at t he ti me of scr ee ni n g t o all o w s u bjects a n o p p ort u nit y t o asse ss 
w het her t here are li kel y t o be si g nifica nt c o nflicts wit h ot her acti vities or pla n ne d a bse nces. 
T o  t he e xte nt p ossi ble, s u bjects will be e x pecte d t o a d her e t o t he visit sc he d ule, a n d a n y 
resc he d uli n g of visits m ust be a gree d, i n a d va nce, wit h t he i n vesti gat or a n d s p o ns or. 
T he i n vesti gat or ma y, at his/ her discreti o n, arr a n ge f or a s u bject t o ha ve a n u nsc he d ule d 
assess me n t, es peciall y i n t he case of A Es t hat r e q uir e f oll o w-u p or ar e c o nsi der e d b y t he 
i n vesti gat or t o be p ossi bl y relate d t o t he use of st u d y dr u g. T he u nsc he d ule d visit pa ge i n t he 
e C R F m ust be c o m plete d.  
St u d y disc o nti n uati o n pr oce d ures are descri be d i n Secti o n  7. 2. 1 . 
Details r e gar di n g partici pati o n i n Part B, t he l o n g -ter m e xtensi o n, ar e pr o vi de d i n t he a p pe n dices 
(Secti o n  1 5 ). 
 
 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 4 5  
 
C o nfi de nti al  
B.  S u bj ects will self -a d mi nist er S C pe gc et ac o pl a n aft er re cei vi n g a p pr o pri at e trai ni n g a n d si g n -off b y a rese arc h n urse or ot her pers o n nel i n t heir first tre at me nt 
we e k. D uri n g site visits s u bj ects will self -a d mi nist er pe gcetac o pla n at t he site, wit h t he e xce pti o n of t he ver y first d ose. Gr o u p  2 s u bj ects will be trai ne d o n 
self-a d mi nistrati o n of pe gceta c o pl a n a n d rec ei ve t heir s u p pl y of pe gc et ac o pl a n at t he ne xt sc he d ul e d cli ni c visit ( Visit  7 or 8) f oll o wi n g t heir bi o psies.  
C.  Visit  2 m ust oc c ur at l east 7  da ys aft er  Visit 1 a n d at l east 1 4  da ys pri or t o t he Da y  1 d osi n g date; t he vac ci nati o ns a n d bi o ps y ca n occ ur a n y ti me aft er 
c o nfir mati o n of eli gi bilit y base d o n Visit  1 dat a.  
D.  S pe cific i ncl usi o n/ e xcl usi o n criteria will be m eas ure d d uri n g scre e ni n g, a n d s o me of t he m re q uire c o nfir mati o n pri or t o a n y acti vit ies of Da y 1. Se e t he 
i ncl usi o n/ e xcl usi o n criteria i n Se cti o n 7  f or f urt her detail. 
E.  Va c ci nati o ns a gai nst  N. me ni n giti dis , S.  p ne u m o ni ae, a n d H.  i nfl ue nz ae are m a n dat or y, u nl ess d oc u me nte d e vi de nc e e xists t hat s u bje cts ha ve rec ei ve d all 
re c o m m e n de d vac ci nes or are n o nres p o n ders t o va cci nati o n. A n y re q uire d vac ci nes s h o ul d be a d mi nistere d d uri n g scre e ni n g ( Da y –1 4), a n d a n y re q uire d 
b o ost ers s h o ul d be a d mi nist ere d at Visit  6 ( Da y  5 6), u nless a n alter nati ve vac ci nati o n sc he d ul e has be e n a gree d wit h t he m e di cal m o nit or , as descri be d i n 
Se cti o n  9. 1. 4 . S u bje cts w h o wit h dra w fr o m t he st u d y pri or t o a sc he d ule d vac ci ne b o ost er, as rec o m m e n de d b y t he c urre nt A d vis or y C o m mitt ee o n 
I m m u niz ati o n Practi ces a d ult i m m u ni zati o n sc he d ule, will be offere d t he o p p ort u nit y t o ret ur n t o t he site t o recei ve t he b o ost er. Va cci nati o n ser u m sa m pl es 
(f or a nti b o d y titer) will be c olle ct e d pri or t o s u bje ct re cei vi n g vac ci nati o ns o n t hat st u d y visit. 
F.  F ull p h ysic al e xa mi nati o n will o nl y be perf or me d at St u d y W ee ks – 4, 1, a n d 5 2. Bri ef p h ysi cal e xa mi nati o ns will be c o n d ucte d at all ot her cli nic visits, as 
n ot e d. A s y m pt o m -dri ve n p h ysic al e xa mi nati o n ma y be perf or m e d at ot her ti mes, at t he i n vesti gat or’s discreti o n. B o d y hei g ht (c m) will be m eas ure d d uri n g 
scre e ni n g o nl y a n d wei g ht ( k g) will be m eas ure d t hr o u g h o ut st u d y, d uri n g brief a n d f ull p h ysi cal e xa mi nati o ns. E de ma s h o ul d be assesse d at e ver y visit.  
G.  W ee k  1 2 bi o ps y m us t occ ur at a ti m e p oi nt bet wee n We e ks 1 2 a n d 1 4, i ncl usi ve; Gr o u p  2 s u bj ects ca n n ot be gi n pe gceta c o pl a n a d mi nistrati o n u ntil after t he 
bi o ps y occ urs. W ee k  5 2 bi o ps y m ust occ ur at a ti me p oi nt bet we e n W ee ks  4 8 a n d 5 2, i ncl usi ve, b ut after c o m pleti o n of t he 2 4 -h o ur uri ne c olle cti o n 
sc he d ul e d f or W ee k 4 8.  
H.  Bet we e n site visits, s u bje cts will be i nstr ucte d t o re p ort a n y i nf usi o n site re acti o n t o  t he st u d y staff. P u m p use safet y assess m e nt will be perf or m e d b y 
li ce nse d he alt h care pr ofessi o nal (i e, i n vesti gat or or n urse) wit hi n 3 0 mi n ut es f oll o wi n g st u d y dr u g a d mi nistrati o n at all cli nic visits a n d d uri n g at -h o m e 
q ualific ati o n. Se e Ma n ual of Pr oc e d ures f or m ore det ails.  
I. 
W he n pe gceta c o pla n is a d mi nist ere d at t he st u d y sit e, vit al si g ns will be me as ure d wit hi n 2  h o urs pri or t o i nf usi o n , bef ore ve ni p u nct ure a n d E C G . F oll o wi n g 
t he first i nf usi o n, vit al si g ns will be m eas ure d a gai n at 3 0 mi n ut es ( ± 5  mi n utes) aft er d osi n g. F or s u bje cts i n Gr o u p  2, vit al si g ns will be m eas ure d o nc e at 
e ac h visit d uri n g t he c o ntr olle d peri o d. F or all e val uati o ns, bl o o d press ure a n d he art rat e s h o ul d be e val uate d aft er t he s u b je ct has be e n resti n g i n a se at e d, 
re c u m be nt, or s u pi ne p ositi o n f or at le ast 5 mi n ut es.  
J. 
T he 2 4 -h o ur uri ne c olle cti o n re q uires c oll ecti o n of 2 4  h o urs of uri ne i n a p o oli n g c o nt ai ner f oll o wi n g t he first uri nar y o ut p ut o n t hat da y (first uri nar y o ut p ut 
is disc ar de d). T he scree ni n g 2 4-h o ur uri ne c olle cti o n s h o ul d be d o ne f oll o wi n g Visit  1. C o urier arra n ge me nts will be m a de b y sit e pers o n nel t o pic k u p uri ne 
c o ntai ners fr o m s u bj ect’s h o me. T his c olle cti o n s h o ul d be d o ne pri or t o t he re nal bi o ps y.  
K.  Uri ne pr ot ei n -t o-cre ati ni ne rati o sa m pl es (first urinar y o ut p ut f or t he da y) s h o ul d be c olle ct e d o n 3  c o nse c uti ve da ys, e ver y 2 we e ks, t hr o u g h o ut t he st u d y. 
O n wee ks of sc he d ul e d cli ni c visits, sa m pl es will be br o u g ht wit h s u bje ct d uri n g t he site visit. O n we e ks w he n n o cli nic visi t is sc he d ul e d, c o urier ser vic e 
will be arra n ge d f or uri ne sa m ple pic k u p a n d deli ver y t o t he sit e.  
L.  T he Da y  1 tri pli cat e first -m or ni n g uri ne sa m ples s h o ul d be c olle cte d bef ore t he first d ose of pe gc etac o pla n (e g, Da y – 2, Da y – 1, a n d Da y  1) a n d are re q uire d 
f or ra n d o miz ati o n. 
M.  Se e l a b orat or y assess m e nts ( T a bl e  3) f or m ore det ails.  
N.  D uri n g t he c o ntr oll e d peri o d, P K a n d A D A sa m ples will be c olle cte d fr o m s u bj ects i n Gr o u p  1 o nl y.  
O.  S u bj ects w h o disc o nti n ue d osi n g will ne e d t o ha ve A D A sa m pl es c olle cte d at 6 a n d 1 2  we e ks af t er t he last tre at me nt. S u bje cts w h o test p ositi ve f or 
a nti -pe gcet ac o pl a n pe pti de or a nti -P E G a nti b o di es at a n y ti me will be f oll o we d u p wit h A D A sa m pl es bei n g c olle ct e d e ver y 6  m o nt hs u ntil t he a nti b o d y 
l e vels re vert t o baseli ne. 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 4 6 
 
C o nfi de nti al  
P.  Me as u re d G F R is a n o pti o nal assess m e nt w hi c h, if d o ne, s h o ul d perf or me d at 2 ti me p oi nts: o nce o n Da y 1, or wit hi n 4  we e ks bef ore Da y  1, a n d a gai n at 
1 ti me p oi nt bet we e n W ee k 4 8 a n d W ee k  5 2, i ncl usi ve. Meas ure d G F R s h o ul d o nl y be d o ne at sites w here it is r o ut i nel y perf or m e d, as per t he site’s sta n dar d 
pr ot oc ol. 
Q.  C K D -E PI creati ni ne e q uati o n; t he C K D -E PI creat i ni ne-c yst ati n C e q uati o n (if c o nfir m ati o n re q uire d).  
R.  Ser u m F S H t o be perf or me d o n w o me n o nl y (see l a b orat or y m a n ual f or m ore details).  
S.  O p ht hal m ol o gi c e val uati o ns are o pti o nal a n d will be perf or me d at sel ect e d sit es. If t hese e val uati o ns are perf or m e d , s u bj ects s h o ul d ha ve a baseli ne 
e val uati o n, i ncl u di n g a basi c o p ht hal m ol o gi c e xa mi nati o n, S D -O C T, a n d c ol or f u n d us p h ot o gra p h y, at a n a p pr o ve d o p ht hal m ol o gi c c li ni cal sit e at a n y ti me 
d uri n g t he scree ni n g peri o d. F or t h ose s u bje cts wit h dr use n pri or t o pe gc et ac o pl a n a d mi nistrati o n, a f oll o w -u p o p ht hal m ol o gi c e val uati o n, i ncl u di n g a basi c 
o p ht hal m ol o gic e xa mi nati o n, S D -O C T, a n d c ol or f u n d us p h ot o gra p h y, s h o ul d occ ur at a c o n ve nie nt ti m e p oi nt bet wee n W ee k  4 2 a n d Wee k  5 2 of t he st u d y.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 4 8 
 
C o nfi de nti al  
9. 1.  
Scree ni n g  
S u bjects wit h eit her pree xisti n g disease r ec urr e nce or u p o n i nitial i de ntificati o n of cli nical a n d 
pat h ol o gic rec urre nce of disease will be i n vite d t o e nter scr ee ni n g. S u bjects will be scr ee ne d t o 
c o nfir m t hat t he s u bject selecti o n criteria f or t he st u d y ha ve bee n met. I nf or me d c o nse nt will be 
o btai ne d at scree ni n g pri or t o t he c o n d uct of a n y st u d y -r elate d pr oce d ur es.  
A scree n fail ure is defi ne d as a s u bject w h o has pr o vi de d writte n i nf or me d c o nse nt, f aile d t o 
meet at least o ne of t he i ncl usi o n criteria a n d/ or met at least o ne  of t he e xcl usi o n criteria, a n d n ot 
bee n ra n d o mize d or a d mi nistere d i n vesti gati o nal pr o d uct(s).  
A s u bject s h o ul d n ot ha ve a Visit  2 u nless t he y m eet t he st u d y criteria. 
F or all s u bjects, t he pla n f or p ost -tra ns pla nt i m m u n os u p pr essi o n f or t he d ur ati o n of t he st u d y 
s h o ul d be d oc u me nte d pri or t o ra n d o mizati o n. A n y de viati o n d uri n g t he st u d y fr o m t he 
pres pecifie d pla n s h o ul d be d oc u me nte d wit h a j ustificati o n f or t he c ha n ge.  
9. 1. 1.  
Rescre e ni n g  
In di vi d uals w h o c o nse nt t o partici pate i n t he st u d y b ut w h o d o n ot i nitia ll y meet all t he 
re q uire me nts as o utli ne d i n t he i ncl usi o n a n d e xcl usi o n criteria ar e n ot a ble t o be e nr olle d; 
h o we ver, t hese i n di vi d uals ma y be hel d i n t he scr ee ni n g peri o d at t he discr eti o n of t he 
i n vesti gat or u ntil s uc h ti me t hat t he y ar e a ble t o be e nr olle d. I n t his case, a d diti o nal scr ee ni n g 
visits a n d/ or re peat scree ni n g assess me nts ma y be c o n d ucte d, as nee de d, t o esta blis h eli gi bilit y.  
I n t he e ve nt t hat rescree ni n g occ urs, a n d t he s u bject has n ot r e mai ne d i n t he scr ee ni n g peri o d, 
t he i n di vi d ual is req uire d t o rec o nse nt a n d m ust be assi g ne d a ne w i de ntificati o n n u m ber.  
9. 1. 2.  
Scree ni n g P r o ce d ures 
9. 1. 2. 1.  
Visit  1 
T he f oll o wi n g assess me nts will be perf or me d a n d i nf or mati o n c ollecte d d uri n g Visit  1: 
•  I nf or me d c o nse nt re vie we d a n d si g ne d, b ot h f or t he st u d y a n d f or t he bi o psies 
•  De m o gra p hics 
•  Me dica l hist or y 
•  Re vie w  of i ncl usi o n/e xcl usi o n criteria 
•  Re vie w  of c o nc o mita nt me dicati o ns 
•  P h ysica l e xa mi nati o n, f ull 
•  1 2- lea d E C G  
•  Dis pe ns e 2 4-h o ur uri ne c ol lecti o n c o ntai ner 
•  Dis pe nse 3 uri ne pr otei n -t o-cr eati ni ne r ati o ( u P C R) c o ntai ners f or c o nsec uti ve 
c ollecti o n 
•  Arra n ge h o me u P C R c o urier pic k u p  
•  Uri na l ysis assess me nt 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 4 9 
 
C o nfi de nti al  
•  Bl o o d sa m ples f or la b orat or y assess me nts 
•  e G F R 
•  A E c olle cti o n 
9. 1. 2. 2.  
Vis it 2  
T he f oll o wi n g assess me nts will be perf or me d a n d i nf or mati o n c ollecte d d uri n g Visit  2: 
•  Re vie w  of i ncl usi o n/e xcl usi o n criteria 
•  Vacci nati o n  
•  Re vie w  of c o nc o mita nt me dicati o ns 
•  P h ysica l e xa mi nati o n, brief 
•  C ollec t 3 u P C R c o ntai ners fr o m pr e vi o us visit 
•  Dis pe ns e 3 u P C R c o ntai ners f or c o nsec uti ve c ollecti o n  
•  Arra n ge  h o me u P C R c o urier pic k u p 
•  Uri na l ysis assess ment 
•  Bl o o d sa mples f or la b orat or y assess me nts  
•  e G F R 
•  U ri ne pre g na nc y test, if a p plica ble  
•  A E c olle cti o n 
•  P ost -trans pla nt i m m u n os u p pr essi o n pla n f or t he d ur ati o n of t he st u d y s h o ul d be 
d oc u me nte d ( pri or t o ra n d o mizati o n)  
•  Re nal bi o ps y (see Secti o n  9. 1. 3  bel o w f or f urt her details) 
9. 1. 3.  
Re n al Bi o p s y 
T he scree ni n g re nal all o graft bi o ps y s h o ul d be c o n d ucte d d uri n g t he scr ee ni n g peri o d a n d m ust 
occ ur wit hi n 4  wee ks lea di n g u p t o t he da y of r a n d o mizati o n. H o we ver, a n o nst u d y bi o ps y ma y 
be use d as t he scree ni n g bi o ps y pr o vi de d it meets all t he f oll o wi n g criteria:  
•  it was perf or me d n o m ore t ha n 1 2 wee ks pri or t o Wee k  1 
•  t he s u bject has re mai ne d cli nicall y sta ble si nce t he bi o ps y wit h n o c ha n ges i n 
me dicati o n re gi me ns t hat w o ul d be e x pecte d t o si g nifica ntl y alter t he scr ee ni n g r e nal 
all o graft bi o ps y fi n di n gs  
•  t he pri or bi o ps y is a vaila ble f or ce ntr al pat h ol o g y re vie w a n d i ncl u des all t he r e q uir e d 
c o m p o ne nts of  a st u d y scr ee ni n g r e nal all o gr aft bi o ps y  
9. 1. 4.  
V acci n ati o ns  
S u bjects will be re q uire d t o be vacci nate d as f oll o ws o n t he basis of  A d vis or y  C o m mittee o n 
I m m u nizati o n Practices ( A CI P) rec o m me n dati o ns f or a d ults wit h c o m ple me nt deficie ncies 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 5 0  
 
C o nfi de nti al  
a n d/ or i m m u n oc o m pr o misi n g c o n diti o ns ( a vaila ble at 
htt ps:// w w w. c dc. g o v/ vacci nes/sc he d ules/ hc p/i mz/a d ult-c o n diti o ns. ht ml).  
•  N. me ni n giti dis t y pes A, C, W, a n d Y : First d ose at least 2 wee ks pri or t o start of 
pe gcetac o pla n wit h sec o n d d ose 2  m o nt hs later, a n d t he n b o osters e ver y 5  years.  
•  N. me ni n giti dis  t y pe B: First d ose at least 2 wee ks pri or t o start of pe gcetac o pla n wit h 
a sec o n d d ose after at lea st 1 m o nt h. First b o oster d ose 1  year later, a n d t he n 
a d diti o nal b o oster d oses e ver y 2 t o 3  years.  
•  S. p ne u m o ni ae : P C V 1 3 an d/ or P P S V 2 3 as per A CI P g ui deli nes f or a d ults wit h 
i m m u n oc o m pr o misi n g c o n diti o ns. 
•  H. i nfl ue nz ae  t y pe B: D ocu me ntati o n of c hil d h o o d vac ci nati o n or 1 d ose at least 
2 wee ks pri or t o start of pe gcetac o pla n d osi n g.  
Vacci nati o n is ma n dat or y u nless d oc u me nte d e vi de nce e xists t hat s u bjects ha ve r ecei ve d all 
rec o m me n ded vacci nes or are n o nres p o n ders t o vacci nati o n. F or s u bjects w h o d o n ot ha ve t h is 
d oc u me nte d e vi de nce, t he re q uire d missi n g vacci nati o n(s) will be a d mi nister e d as nee de d t o 
bri n g t he s u bjects u p t o date. T he i n vesti gat or s h o ul d disc uss wit h t he me dical m o nit or a n y 
i n di vi d ual s u bject circ u msta nces rele va nt t o t he vacci nati o n r e q uir e me nts or t hat w o ul d ma ke t he 
a b o ve sc he d ule n ot p ossi ble or reas o na ble. O n a n o n g oi n g basis, i ncl u di n g u p o n e ntr y i nt o 
Part  B, t he l o n g -ter m e xte nsi o n, s u bjects s h o ul d be r ee val uate d f or t he nee d f or a n y vacci nati o ns 
base d o n A CI P rec o m me n dati o ns.  
Vacci nati o n at least 2  wee ks pri or t o t he first d ose of pe gcetac o pla n is pr ef err e d; h o we ver, 
t he vacci nati o n sc he d ule ma y be a dj uste d wit h writte n a p pr o val fr o m t he me dical m o nit or a n d 
vacci nati o ns ma y occ ur u p t o 2  wee ks after i nitiati o n of tr eat me nt wit h pe gcetac o pla n. 
S u bjects  vacci nate d after i nitiati o n of tr eat me nt wit h pe gcetac o pla n m ust r ecei ve pr o p h ylactic 
a nti bi otics as descri be d i n Secti o n  9. 1. 5 . 
Vacc i nati o n ser u m sa m ples will be c ollecte d o n t he da y of vacci nati o n pri or t o r ecei vi n g 
vacci nati o ns o n t hat st u d y visit. T hese sa m ples will be a nal yze d f or a nti b o d y titer i n t he e ve nt 
t hat t he s u bject has a p ositi ve i nfecti o n f or S.  p ne u m o ni ae, N.  me ni n giti dis, or H.  i nfl ue nz ae.  
S u bjects w h o wit h dra w fr o m t he st u d y pri or t o a sc he d ule d vacci ne b o oster, as r ec o m me n de d b y 
t he c urre nt A CI P a d ult i m m u nizati o n sc he d ule, will be off er e d t he o p p ort u nit y t o r et ur n t o t he 
site t o r ecei ve t he b o oster.  
9. 1. 5.  
P r o p h yl a ctic A nti bi otics 
S u bjects w h o recei ve t heir i nitial vacci nati o ns after i nitiati o n of treat me nt wit h pe gcetac o pla n will be 
re q uire d t o recei ve a nti bi otic pr o p h yla xis u ntil at least 1 4  da ys after vacci nati o n. T he  c h oice of 
pr o p h ylactic a nti bi otic is at t he discreti o n of t he treati n g i n vesti gat or a n d wit h a p pr o val fr o m t he 
me dical m o nit or. F oll o wi n g t his or f or a n y s u bject w h o d oes n ot re q uire vacci nati o n, pr o p h ylactic 
a nti bi otic t hera p y is all o we d at t he discreti o n  of t he tr eati n g i n vesti gat or. T he use of pr o p h ylactic 
a nti bi otics s h o ul d be i n acc or da nce wit h l ocal treat me nt g ui deli nes f or s u bjects w h o are recei vi n g 
treat me nt wit h a c o m ple me nt i n hi bit or a n d s h o ul d ta ke i nt o c o nsi derati o n t he le vel of 
i m m u n os u p pressi on a n d c o m ple me nt le vels, as well as l ocal practices.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 5 1  
 
C o nfi de nti al  
9. 2.  
M ai n Peri o d  
T his 5 2 -wee k mai n peri o d is di vi de d i nt o a c o ntr olle d p orti o n ( Wee ks  1-1 2) a n d a n o nc o ntr olle d 
p orti o n ( Wee ks  1 3-5 2) a n d will be c o m plete d b y all s u bjects. T h ose s u bjects w h o ar e 
ra n d o mize d t o Gr o u p 1 will recei ve pe gcetac o pla n a d mi nistr ati o n t hr o u g h o ut t he e ntir e mai n 
peri o d. T h ose s u bjects w h o are ra n d o mize d t o Gr o u p  2 will n ot r ecei ve pe gcetac o pla n 
a d mi nistrati o n d uri n g t he c o ntr olle d p orti o n b ut will be gi n pe gcetac o pla n tr eat me nt d uri n g t he 
n o nc o ntr olle d p orti o n (f oll o wi n g t he Wee k  1 2 bi o ps y). D uri n g t he desi g nate d peri o d of 
pe gcetac o pla n a d mi nistrati o n ( w hic h diff ers base d o n r a n d o mizati o n assi g n me nt), s u bjects will 
recei ve 1 0 8 0 m g pe gcetac o pla n S C i nf usi o ns ( 2 0  m L) t wice wee kl y.  
9. 2. 1.  
R a n d o miz at i o n Visit  
T he f oll o wi n g assess me nts will be perf or me d a n d i nf or mati o n c ollecte d at t he r a n d o mizati o n 
visit ( Visit  3,  St u d y Da y 1), as o utli ne d i n t he Sc he d ule of Acti vities ( T a ble  1).  
Ra n d o mizati o n m ust occ ur at t he o utset of t his visit t o deter mi ne tr eat me nt gr o u p. T he o nl y 
la b orat or y assess me nt t hat w o ul d pre ve nt r a n d o mizati o n is a p ositi ve pr e g na nc y test. 
Please n ote t he fe w ite ms t hat are s p ecific t o t he treat me nt gr o u p t o w hic h t he s u bject is 
ra n d o mize d. Gr o u p 2 s u bjects d o n ot r ecei ve pe gcetac o pla n a d mi nistr ati o n d uri n g t he c o ntr olle d 
p orti o n b ut will be gi n t o recei ve pe gcetac o pla n a d mi nistr ati o n d uri n g t he n o nc o ntr olle d p orti o n, 
f oll o wi n g t he Wee k 1 2 bi o ps y.  
9. 2. 1. 1.  
I m me di atel y F oll o wi n g R a n d o miz ati o n, All S u bj ects 
•  Re vie w  i ncl usi o n/e xcl usi o n criteria, c o nfir m eli gi bilit y 
•  Re vie w  of c o nc o mita nt me dicati o ns 
•  P h ysica l e xa mi nati o n, f ull 
•  1 2- lea d E C G 
•  C ollec t 3 u P C R c o ntai ners fr o m pr e vi o us visit 
•  Arra n ge  h o me u P C R c o urier pic k u p 
•  Uri na l ysis assess me nt 
•  Bl o o d sa m ples f or la b orat or y assess me nts 
•  e G F R 
•  A E c olle cti o n 
•  Vital si g n  meas ure me nts 
9. 2. 1. 2.  
Gr o u p  1 S u bjec ts O nl y 
•  P K c ollecti o n: c ollect after bl o o d sa m ple dr a ws a n d bef or e d osi n g 
•  Dis pe ns e i n vesti gati o nal pr o d uct a n d i n f usi o n materials 
•  Trai n s u bject t o perf or m h o me i nf usi o n  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 5 2  
 
C o nfi de nti al  
•  A d mi nister pe gcetac o pla n t o s u bjects  
•  I nf usi o n site/ p u m p safet y assess me nt 
•  A d diti o n al vital si g n meas ur e me nt at 3 0  mi n utes ( ± 5  mi n utes) after d osi n g  
9. 2. 1. 3.  
All S u bj ects 
•  Dis pe nse 3 u P C R  c o ntai ner s f or c o nsec uti ve c ollecti o n 
9. 2. 2.  
P ri m ar y E n d p oi nt Bi o ps y at 1 2 Wee ks  
T he Wee k  1 2 re nal all o graft bi o ps y m ust occ ur at a ti me p oi nt bet wee n Wee ks  1 2 a n d 1 4, i ncl usi ve; 
Gr o u p  2 s u bjects ca n n ot be gi n pe gcetac o pla n a d mi nistrati o n u ntil after t he bi o ps y occ urs. It is 
i m p orta nt t o n ote t hat t he 2 4-h o ur uri ne c ollecti o n s h o ul d occ ur f or all s u bjects pri or t o t he re nal 
bi o ps y a n d f or Gr o u p  2, pri or t o t he i nitiati o n of pe gcetac o pla n; gi ve n t his, t he  Wee k  8 visit s h o ul d 
i ncl u de t he se n di n g h o me of a 2 4-h o ur uri ne c ollecti o n c o ntai ner wit h all s u bjects.  
9. 2. 3.  
Visit  7 or 8 ( W ee k 1 2 or 1 4)  
De pe n di n g o n w he n t he Gr o u p  2 s u bject s r ecei ve t heir Wee k 1 2 r e nal bi o psies 
(see Secti o n  9. 2. 2 ), t he f oll o wi n g will occ ur at eit her Visit 7 or 8 ( Wee k 1 2 or 1 4). T he f oll o wi n g 
assess me nts will be perf or me d a n d i nf or mati o n c ollecte d as n ote d a b o ve, as o utli ne d i n t he 
Sc he d ule of Acti vities ( T a ble  1). Please n ote t he f e w ite ms t hat ar e s pecific t o tr eat me nt gr o u p; 
Gr o u p 1 will  n ot ha ve t o d o all t he sa me assess me nts as Gr o u p 2. 
9. 2. 3. 1.  
P ri or t o P e g cet ac o pl a n A d mi nist r ati o n 
•  Re vie w of c o nc o mita nt me dicati o ns  
•  P h ysica l e xa mi nati o n, brief 
•  1 2- lea d E C G 
•  C ollec t 3 u P C R c o ntai ners fr o m pr e vi o us visit 
•  Arra n ge  h o me u P C R c o urier pic k u p 
•  Uri na l ysis assess me nt 
•  Bl o o d sa m ples f or la b orat or y assess me nts 
•  e G F R 
•  β – h u ma n c h or i o nic g o na d otr o pi n, if a p plica ble 
•  A E c o llecti o n 
•  Vital si g n  meas ure me nts 
•  P K c oll ecti o n ( pre d ose)  
•  Dis pe n se i n vesti gati o nal pr o d uct a n d i nf usi o n materials 
•  Trai n s u bject t o perf or m h o me i nf usi o n ( Gr o u p  2 o nl y)  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 5 3  
 
C o nfi de nti al  
9. 2. 3. 2.  
A d mi nis tr ati o n of P e gcet ac o pl a n 
•  A d mi nister pe gcetac o pla n t o s u bjects ( Gr o u p  2 o nl y; Gr o u p  1 ca n self -a d mi nister) 
•  I nf usi o n site/ p u m p safet y assess me nt 
9. 2. 3. 3.  
Gr o u p  2 S u bje cts O nl y 
•  A d diti o nal vital si g n meas ur e me nt at 3 0  mi n utes ( ± 5  mi n utes) after d osi n g  
9. 2. 3. 4.  
All S u bj ects 
•  Dis pe nse 3 u P C R c o ntai ners f or c o nsec uti ve c ollecti o n  
9. 2. 4.  
Re m ai ni n g  Visits D uri n g M ai n P eri o d 
F or all of  t he re mai ni n g visits of t he mai n peri o d, all s u bjects, r e gar dless of r a n d o mizati o n, 
will  e x peri e nce t he sa me assess me nt acti vities, as o utli ne d i n t he Sc he d ule of Acti vities 
(T a ble  1). A n y discre pa ncies/a d diti o ns ar e n ote d wit h a n asteris k ( *).  
9. 2. 4. 1.  
P ri or t o A d mi nistr ati o n of P e gcet ac o pl a n  
•  Vacci nati o n * ( St u d y Wee k  8 o nl y)  
•  Re vi e w of c o nc o mita nt me dicati o ns  
•  P h ysica l e xa mi nati o n * 
− brief, e xce pt f or Visit  1 6, w hic h is f ull 
•  1 2- lea d E C G 
•  C ollec t 3 u P C R c o ntai ners fr o m pr e vi o us visit 
•  Arra n ge  h o me u P C R c o urier pic k u p 
•  Uri na l ysis assess me nt 
•  Bl o o d sa m ples f or la b orat or y assess me nts 
•  e G F R 
•  U ri ne pre g na nc y test, if a p plica ble * 
− β – h u ma n c h ori o nic g o na d otr o pi n at Visit  1 6 o nl y, if  a p plica ble 
•  A E c ollecti o n  
•  Vital si g n  meas ure me nts 
•  P K c oll ecti o n ( pre d ose)  
•  Dis pe ns e 2 4-h o ur uri ne c ol lecti o n c o ntai ner ( Wee k 2 0 f or Wee k  2 4 c ollecti o n a n d 
Wee k  4 2 f or Wee k  4 8 c ollecti o n) *  
•  Dis pe nse i n vesti gati o nal pr o d uct a n d i nf usi o n materials  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 5 4  
 
C o nfi de nti al  
9. 2. 4. 2.  
A d mi n istrati o n of P e gcet ac o pl a n  
•  Pe gcetac o pla n a d mi nistrati o n  
•  I nf usi o n site/ p u m p safet y assess me nt 
9. 2. 4. 3.  
F ol l o wi n g A d mi nistr ati o n of P e gcet ac o pl a n  
•  Dis pe nse 2 4 -h o ur uri ne c ol lecti o n c o ntai ner * ( Wee k 8 f or Wee k  1 2 c ollecti o n; 
Wee k  2 0 f or Wee k  2 4 c ollecti o n; Wee k  4 2 f or Wee k  4 8 c ollecti o n o nl y)  
•  Dis pe nse u P C R c o ntai ners f or c o nsec uti ve c ollecti o n e ver y 2  wee ks, per  t he 
f oll o wi n g c o ntai ner dis persal sc he d ule: 
− Dis pe nse 3 c o ntai ners ( visits s pace d e ver y 2  wee ks): Wee k s 1, 2, 1 2, 1 4, 5 2  
− Dis pe nse 6 c o ntai ners ( visits s pace d e ver y 4  wee ks): Wee k s 4, 8, 1 6, 2 0, 4 8  
− Dis pe nse 9 c o ntai ners ( visits s pace d e ver y 6  wee ks): Wee k s 2 4, 3 0, 3 6, 4 2  
9. 2. 5.  
Wee k  5 2 Re n al Bi o ps y  
T he Wee k  5 2 bi o ps y m ust  occ ur at a ti me p oi nt bet wee n Wee ks 4 8 a n d 5 2, i ncl usi ve.  
9. 3.  
F o ll o w-u p Peri o d  
All s u bjects w h o c o m plete st u d y treat me nt a n d d o n ot e nter Part B, t he l o n g -ter m e xte nsi o n, 
will  ret ur n t o t he i n vesti gat or site f or f oll o w-u p visits f or 8 wee ks, w her e assess me nts will be 
perf or me d as per t he Sc he d ule of Acti vities ( T a ble  1), a n d w her e t he visit wi n d o w all o wa nces 
are als o pr o vi de d.  
S u bjects w h o disc o nti n ue treat me nt earl y a n d d o n ot elect t o c o nti n ue t heir partici pati o n i n t he 
st u d y will co m plete a f oll o w -u p visit 2 wee ks after disc o nti n uati o n of tr eat me nt a n d als o t he e xit 
visit, 6  wee ks t hereafter.  
T he f oll o wi n g assess me nts will be perf or me d d uri n g t his peri o d, as o utli ne d i n t he Sc he d ule of 
Acti vities ( T a b le 1): 
•  Pr oc ure 3 pre vi o usl y c ollecte d c o nsec uti ve u P C R sa m ples  
− Arra n ge c o urier pic k u p f or all e ver y 2 -wee k tri plicate u P C R sa m ples d uri n g 
wee ks wit h o ut cli nic visits  
•  P h ysical e xa mi nati o n, brief  
•  C o nc o mita nt me dicati o ns r e vie w  
•  I nf usi o n site/ p u m p safet y assess me nt  
•  Bl o o d sa m ples f or la b orat or y assess me nts 
•  A nti – p e gcetac o p la n pe pti de/a nti-P E G cir c ulati n g a nti b o dies c ollecti o n  
•  e G F R assess me nt  
•  Uri nal y sis c ollecti o n  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 5 5  
 
C o nfi de nti al  
•  Uri ne pre g na nc y test  
•  A E re vi e w 
•  Vital si g n s 
•  1 2- lea d E C G 
•  P K sa m p le c ollecti o n 
•  Dis pe ns e u P C R c o ntai ners f or c o nsec uti ve c ollecti o n e ver y 2  wee ks, per  t he 
f oll o wi n g c o ntai ner dis persal sc he d ule:  
− Dis pe nse 3 c o ntai ners ( visits s pace d e ver y 2  wee ks): Wee k s 5 4, 5 6  
− Dis pe nse 9 c o ntai ners ( visits s pace d e ver y 6  wee ks): Wee k s 5 8, 6 4, 7 0  
•  Dis pe nse 2 4 -h o ur uri ne c ol lecti o n c o ntai ner 
9. 4.  
E xit Visit  
All s u bjects will ret ur n t o t he cli nic facilit y f or t he e xit visit, 8 wee ks f oll o wi n g t he fi nal d ose of 
pe gcetac o pla n, o n Da y  4 2 0 ( or s o o ner if t he s u bject disc o nti n ues pri or t o Wee k 5 2).  
St u d y partici pati o n f or eac h s u bject will be c o ncl u de d f oll o wi n g c o m pleti o n of t he e xit visit. If a 
s u bject wit h dra ws fr o m t he st u d y pri or t o t he sc he d ule d e xit visit, all e xit visit assess me nts s h o ul d be 
perf or me d at t he s u bject’s fi nal visit t o t he cli nic, i ncl u di n g c ollecti o n of bl o o d sa m ples f or P K a n d/ or 
P D assess me n ts, as well as a p ost d ose a nti ge nicit y sa m ple, if n ot yet c ollecte d. 
T he e xit visit pr oce d ures are liste d i n t he Sc he d ule of Acti vities ( T a ble  1): 
•  Arra n ge c o urier ser vice t o pic k u p 2 4 -h o ur ur i ne c ollecti o n t o deli ver t o site 
•  Pr oc ure 3 pre vi o usl y c ollecte d c o nsec uti ve u P C R sa m ples t o site  
•  Bl o o d sa m ples f or la b orat or y assess me nts (see Sc he dule of Acti vities [ T a ble  1] 
f or details)  
•  C o nc o mita nt me dicati o ns  
•  A E re vi e w 
•  A nti – pe g cetac o pla n/a nti -P E G ci r c ulati n g a nti b o dies assa y 
•  e G F R assess me nt  
•  Uri nal y sis (see Sc he d ule of Acti vities [T a ble  1] f or details) 
•  Vital si g ns  
•  1 2- lea d E C G 
•  P K sa m p le 
9. 5.  
E arl y Ter mi n ati o n a n d E xit Visit  
S u bjects w h o disc o nti n ue treat me nt earl y a n d d o n ot elect t o c o nti n ue t heir partici pati o n i n t he st u d y 
will c o m plete a n earl y ter mi nati o n visit. If t he earl y ter mi nati o n visit is pri or t o Wee k  4 8, t he n all 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 5 6  
 
C o nfi de nti al  
assess me nts fr o m Wee k 4 8, i n a d diti o n t o a re nal bi o ps y, s h o ul d be d o ne, if p ossi ble. A n  a d diti o nal 
e xit visit s h o ul d occ ur 6 wee ks after t he earl y ter mi nati o n visit. If t he earl y ter mi nati o n is d uri n g t he 
f oll o w-u p peri o d, t he n all t he assess me nts fr o m t he e xit visit s h o ul d be perf or me d.  
9. 6.  
U nsc he d ule d F oll o w -u p Visits  
All s u bjects will be as ke d t o ret ur n t o t he cli nical facilit y f or a d diti o nal f o ll o w-u p visits, 
if c o nsi dere d necessar y b y t he i n vesti gat or.  
U nsc he d ule d f oll o w -u p visits ma y i ncl u de, b ut ar e n ot li mite d t o, a n y of t he pr oce d ur es liste d i n 
t he Sc he d ule of Acti vities (T a ble  1). 
9. 7.  
P art B, L o n g -Ter m E xte nsi o n  
T he a p pe n dices ( Secti o n  1 5 ) pr o vi de t he details r e gar di n g t he Part B, t he l o n g-ter m e xte nsi o n. 
9. 8.  
S afet y M o nit ori n g C o m mittee  
A safet y m o nit ori n g c o m mittee ( S M C) will r e vie w c u m ulati ve saf et y/t oler a bilit y data 
(e g, p h ysical e xa mi nati o ns, E C Gs, vital si g ns, cli nical la b or at or y tests, a n d A Es). T he S M C will 
ha ve t he res p o nsi bilit y t o c o n d u ct a t h or o u g h saf et y assess me nt at r e g ular pr e defi ne d i nter vals 
d uri n g t he treat me nt peri o d of t he st u d y.  
T he first S M C meeti n g will be sc he d ule d 4  m o nt hs aft er t he first s u bject is d ose d wit h st u d y dr u g a n d 
at f urt her 4-m o nt hl y i nter vals u ntil all s u bjects c o m plete t he mai n peri o d. A n a d h oc S M C data 
re vie w ma y be rec o m me n de d b y t he S M C or re q ueste d b y t he s p o ns or at a n y ti me d uri n g t he st u d y. 
T he re mit, r oles, a n d res p o nsi bilities of t he S M C will be s pecifie d i n a se par ate S M C c harter.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 5 7  
 
C o nfi de nti al  
1 0.  
A S S E S S M E N T S  
Safet y assess me nts are t o be perf or me d at pr ot oc ol -s pecifie d visits, as s pecifie d i n t he Sc he d ule of 
Acti vities ( Ta ble  1) f or Part A; assess me nts s pecific t o Part B, t he l o n g-ter m e xtensi o n, are pr o vi de d 
i n t he a p pe n dices (Secti o n  1 5 ). If dee me d necessar y, a d diti o nal safet y meas ure me nts will be 
perf or me d,  at t he discreti o n of t he i n vesti gat or. 
1 0. 1.  
Me dic al Hist or y  
Me dical hist or y will be rec or de d at scree ni n g. I n vesti gat ors s h o ul d d oc u me nt t he occ urre nce, si g ns, 
a n d s y m pt o ms of t he s u bject’s pree xisti n g c o n diti o ns, i ncl u di n g all pri or si g nifica nt ill nesses, u p t o 
a n d i ncl u di n g 3 years bef ore scree ni n g. A d diti o nal pr ee xisti n g c o n diti o ns prese nt at t he ti me w he n 
i nf or me d c o nse nt is gi ve n u p t o t he ti me of first d osi n g are t o be re gar de d as c o nc o mita nt. Me dical 
hist or y will i ncl u de alc o h ol c o ns u m pti o n a n d s m o ki n g hist or y, if a p plica ble.  
Ill nesses first occ urri n g or detecte d d uri n g t he st u d y a n d/ or w orse ni n g of a c o nc o mita nt ill ness 
d uri n g t he st u d y  are t o be d oc u me nte d as A Es i n acc or da nce wit h Secti o n  1 1 .  
A d diti o nall y, de m o gra p hic data will be c ollecte d f or all s u bjects a n d will i ncl u de date of birt h or 
a ge, acc or di n g t o a p plica ble re g ulati o ns, se x, et h nicit y, etc.  
A detaile d me dical hist or y wit h re gar d t o disease i n dicati o n ( C 3 G or I C -M P G N) will b e 
re q ueste d a n d will i ncl u de pri or s ur geries, r e nal bi o psies, h os pitalizati o ns, dial ysis, 
tra ns pla ntati o n, la b orat or y data, a n d e xtr ar e nal ma nif estati o ns of t he disease. T his i nf or mati o n 
will be rec or de d o n a detaile d disease -s pecific e C R F. A vaila ble disease me dical hist or y f or t he 
3 years prece di n g scree ni n g will be re q ueste d. S u b missi o n of a d diti o nal hist orical data  is 
e nc o ura ge d, w he n a vaila ble.  
1 0. 2.  
Pri or a n d C o nc o mit a nt Me dic ati o ns  
All pri or a n d c o nc o mita nt me dicati o ns f or at least 1 2  wee ks pri or t o scr ee ni n g s h o ul d be 
c ollecte d at t he i nitial scree ni n g visit. All disease -s pecific t her a p y f or t he pr ece di n g 3 years 
s h o ul d als o be c ollecte d, a n d c ollecti o n of a d diti o nal disease-s pecific me dicati o n hist or y is 
e nc o ura ge d, w he n a vaila ble. T he pla n f or p ost -tr a ns pla nt i m m u n os u p pr essi o n f or t he d ur ati o n of 
t he st u d y s h o ul d be d oc u me nte d pri or t o r a n d o mizati o n.  
1 0. 3.  
Vit al Si g ns  
Vit al si g ns ( b o d y te m perat ure, res pirati o n rate, heart rate, a n d s yst olic a n d diast olic bl o o d press ure 
meas ure me nts) will be e val uate d at t he visits i n dicate d i n t he Sc he d ule of Acti vities ( Ta ble  1). 
All  vital si g ns  will be meas ure d after t he s u bject has bee n resti n g i n a sitti n g p ositi o n f or at least 
5  mi n utes, e xce pt w he n t he y are s u pi ne or se mirecli ne d beca use of st u d y pr oce d ures a n d/ or A Es, 
or  if dee me d necessar y b y t he i n vesti gat or. Bl o o d press ur e meas ure me nts are t o be ta ke n i n t he sa me 
ar m f or t he d urati o n of t he st u d y. B o d y wei g ht ( wit h o ut s h oes) will be rec or de d w he ne ver vital si g ns 
are rec or de d; hei g ht ( wit h o ut s h oes) will be rec or de d at scree ni n g o nl y.  
Vital si g ns meas ure me nts will be re peate d if cli nicall y si g nifica nt or if mac hi ne/e q ui p me nt err ors 
occ ur. O ut - of-ra n ge bl o o d press ure, r es pir at or y r ate, or heart r ate meas ur e me nts will be r e peate d, 
at t he i n vesti gat or’s discreti o n. A n y c o nfir me d, cli nicall y si g nifica nt vital si g ns meas ur e me nts 
m ust be rec or de d as A Es.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 5 8  
 
C o nfi de nti al  
W he n pe gcetac o pla n is a d mi nistere d at t he st u d y site, vital si g ns will be meas ur e d wit hi n 2  h o urs 
pri or t o i nf usi o n, bef ore ve ni p u nct ure a n d E C G. F oll o wi n g t he first i nf usi o n, vital si g ns w ill be 
meas ure d a gai n at 3 0  mi n utes ( ± 5  mi n utes) after d osi n g. F or s u bjects i n Gr o u p  2, vital si g ns will 
be meas ure d o nce at eac h visit d uri n g t he c o ntr olle d peri o d.  
1 0. 4.  
P h ysic al E x a mi n ati o n  
All f ull p h ysical e xa mi nati o ns, perf or me d b y t he i n vesti gat or or des i g nee, will i ncl u de, at a 
mi ni m u m, assess me nt of t he f oll o wi n g: ge ner al, hea d, ears, e yes, n ose, t hr oat, de ntiti o n, t h yr oi d 
(e n d ocri ne), heart, c hest, l u n gs, a b d o me n, s ki n, e xtr e mities, bac k/ nec k, m usc ul os keletal, 
a n d l y m p h n o des.  
Brief p h ysical e xa mi nati o ns will i nc l u de ge ner al a p pear a nce, heart, l u n gs, a b d o me n, e xtr e mities, 
a n d wei g ht a n d are t o be perf or me d at all visits w her e a f ull p h ysical e xa mi nati o n d oes n ot occ ur. 
E de ma will be assess e d at eac h visit.  
A d diti o nal s y m pt o m -dri ve n p h ysica l e xa mi nati o ns ma y be perf or me d at a n y ti me, as dee me d 
necess ar y b y t he i n vesti gat or.  
See t he Sc he d ule of Acti vities ( T a ble  1) f or t he details r e gar di n g w hic h t y pe of p h ysical 
e xa mi nati o n s h o ul d be gi ve n at eac h visit.  
1 0. 5.  
Electr oc ar di o gr a ms  
All 1 2 -lea d E C Gs will be meas ure d o nce, pri or t o d osi n g, at t he ti me p oi nts o utline d i n t he 
Sc he d ule of Acti vities (T a ble  1). T he E C G will be ta ke n w he n t he s u bject has bee n r esti n g i n t he 
s u pi ne p ositi o n f or 1 0 mi n utes i n a q uiet e n vir o n me nt a n d pri or t o a n y bl o o d sa m pli n g 
pr oce d ures, u nless s pecifie d at ti me p oi nts after ti me d bl o o d sa m pli n g pr oce d ur es.  
All E C Gs will be rec or de d at t he sites usi n g t he e q ui p me nt pr o vi de d b y t he ve n d or perf or mi n g 
t he ce ntralize d E C G a nal ysis. 
T he E C Gs w ill be classifie d as n or mal, ha vi n g a n ot cli nicall y si g nifica nt a b n or malit y, or ha vi n g 
a cli nicall y si g nifica nt a b n or malit y. I n a d diti o n, E C G par a meters of ve ntric ular r ate, P R i nter val, 
Q R S d urati o n, a n d Q T i nter val (c orrecte d usi n g Fri dericia’s met h o d a n d u nc orr ecte d) will be 
re vie we d f or eli gi bilit y a n d o n g oi n g saf et y. 
Please see t he p har mac y ma n ual f or f urt her details o n E C G c ollecti o n a n d r e p orti n g.  
1 0. 6.  
2 4 -H o ur Uri ne C ollecti o n  
A 2 4 -h o ur uri ne c ollecti o n is defi ne d as c ollecti o n of all uri nar y v oi ds f or a  2 4 -h o ur peri o d. 
T he  2 4 -h o ur uri ne c ollecti o n s h o ul d be gi n f oll o wi n g t he ( discar de d) first uri nar y o ut p ut f or t he da y. 
S u bjects will be pr o vi de d a c o ntai ner f or 2 4 -h o ur uri ne c ollecti o n t hat will be u n derta ke n at h o me.  
T here will be fi ve 2 4 -h o ur uri ne c ol lecti o ns:  
•  Wee k  1 (scree ni n g): will be use d t o deter mi ne eli gi bilit y f or st u d y e ntr y, as well as t o 
assess c ha n ges i n pr otei n uria o ver t he c o urse of t he st u d y, t o be o btai ne d pri or t o t he 
re nal bi o ps y b ut n o m ore t ha n 4 wee ks bef or e r a n d o mizati o n  
•  Wee k  1 2 ( pri or t o  the re nal bi o ps y)  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 5 9  
 
C o nfi de nti al  
•  Wee k  2 4  
•  Wee k  4 8 ( pri or  t o t he re nal bi o ps y) 
•  Wee k  7 6 (f or s u bjects w h o d o n ot e nter Part B)  
If me nses are occ urri n g at t he sc he d ule d ti me of a 2 4-h o ur uri ne c oll ecti o n, t he n t he c ollecti o n s h o ul d 
be dela ye d u ntil c o m pleti o n of me nses, wit h t his i nf or mati o n rec or de d i n t he s u bject’s s o urce 
d oc u me nt. Uri ne will nee d t o be st ore d at 2 - 8 ° C (ie, i n refri gerat or). C o urier arra n ge me nts will be 
ma de b y t he site t o pic k u p t he c ollecti o n c o ntai ner fr o m t he s u bjects a n d ret ur n it t o t he site. 
T otal  uri ne v ol u me, t otal pr otei n c o nce ntrati o n, t otal al b u mi n c o nce ntrati o n, a n d t otal creati ni ne 
c o nce ntrati o n of t he 2 4-h o ur uri ne c ollecti o n will be meas ure d, wit h calc ulati o n of t otal pr otei n 
e xcreti o n, t otal al b u mi n e xcreti o n, t otal cr eati ni ne e xcreti o n, a n d u P C R a n d uri ne 
al b u mi n-t o-creati ni ne rati o ( u A C R) base d o n t he 2 4 -h o ur c ollecti o n.  
1 0. 7.  
Tri plic ate First -M or ni n g S p ot Uri ne C ollecti o ns  
Tri plicate first -m or ni n g s p ot uri ne c ollecti o n is defi ne d as a c ollecti o n of first -m or ni n g uri ne o n 
3 c o nsec uti ve m or ni n gs, wit h eac h m or ni n g c ollecte d i nt o a se par ate c o ntai ner. 
Tri plicate  first-m or ni n g s p ot uri ne sa m ples s h o ul d be c ollecte d e ver y 2  wee ks t hr o u g h o ut t he 
mai n peri o d of st u d y, a n d, f or s u bjects w h o d o n ot e nter Part B, t he l o n g -ter m e xte nsi o n, t hr o u g h 
t he f oll o w-u p peri o d . Tri plicate first -m or ni n g s p ot uri ne sa m ples s h o ul d be c ollecte d e ver y 
6 wee ks i n t he l o n g-ter m e xte nsi o n.  
At eac h sc he d ule d cli nic visit, t he site will dis pe nse t he n u m ber of s p ot uri ne c o ntai ners nee de d 
pri or t o t he  ne xt sc he d ule d visit (see T a ble  2). F or c ollecti o n wee ks i n w hic h t her e is a sc he d ule d 
cli nic visit, su bjects will ret ur n t he tri plicate s p ot uri ne c ollecti o ns at t he visit. O n wee ks w her e 
n o cli nic visit is sc he d ule d, a c o urier ser vice will be arr a n ge d t o pic k u p sa m ples fr o m t he 
s u bject’s h o me f or deli ver y t o t he cli nic.  
It is i m p orta nt t hat eac h of t hese c ollecti o ns r e pr ese nt t he first uri nar y o ut p ut u p o n a wa ke ni n g, 
after a n e xte n de d peri o d of rest. I n t he e ve nt t hat a s u bject has a n at y pical slee p/ wa ke sc he d ule, 
t he a p pr o priate ti mi n g f or t hese s p ot uri ne c ollecti o ns ma y n ot be m or ni n g. I n t his case, 
t he ti mi n g of t he c ollecti o n s h o ul d be a dj uste d t o e ns ur e c ollecti o n of t he first uri nar y o ut p ut 
after a n e xte n de d peri o d of rest (e g, at least 6  h o urs), a n d t he alter nate ti mi n g s h o ul d  be r ec or de d 
i n t he s u bject’s s o urce d oc u me nt. After c ollecti o n, t he uri ne sa m ples m ust be st or e d at 2- 8 ° C 
(ie, i n refri gerat or). Uri ne pr otei n, al b u mi n, a n d creati ni ne c o nce ntr ati o ns s h o ul d be meas ur e d o n 
all s p ot uri ne sa m ples, wit h calc ulati o n of u P C R a n d u A C R val ues.  If me nses ar e r e peate dl y 
occ urri n g at t he sc he d ule d ti mes of a tri plicate first m or ni n g uri ne c ollecti o n, t he c ollecti o n dates 
s h o ul d be a dj uste d t o a v oi d c ollecti o n d uri n g me nses t o t he e xte nt p ossi ble, wit h t his i nf or mati o n 
rec or de d i n t he s u bject’s s o urce d oc u me nt. 
T he sc he d ule f or t he tri plicate first -m or ni n g s p ot ur i ne c ollecti o ns is as f oll o ws: 
u P C R c ollecti o n sc he d ule:  
•  Dis pe nse u P C R c o ntai ners f or c o nsec uti ve c ollecti o n e ver y 2  wee ks, per  t he 
f oll o wi n g c o ntai ner dis persal sc he d ule: 
− Dis pe nse 3 c o ntai ners ( visits s pace d e ver y 2  wee ks): Wee k s 1, 2, 1 2, 1 4, 5 2, 
5 4,  5 6  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 6 0 
 
C o nfi de nti al  
− Dis pe nse 6 c o ntai ners ( visits s pace d e ver y 4 wee ks): Wee k s 4, 8, 1 6, 2 0, 4 8  
− Dis pe nse 9 c o ntai ners ( visits s pace d e ver y 6  wee ks): Wee k s 2 4, 3 0, 3 6, 4 2, 5 8, 
6 4, 7 0  
1 0. 8.  
R a n d o m S p ot Uri ne C ollecti o n  
At eac h cli nic visit, s u bjects will be as ke d t o s u b mit a uri ne sa m ple. As t his sa m ple will n ot  
necess aril y reflect a s pecific ti me of da y, it is c o nsi der e d a “r a n d o m” s p ot uri ne sa m ple, s o as t o 
disti n g uis h it fr o m t he first -m or ni n g s p ot c ollecti o ns. After c ollecti o n, t he uri ne sa m ples m ust be 
st ore d at 2- 8 ° C (ie, i n a refri gerat or). Uri ne pr otei n, al b u mi n, a n d cr eati ni ne c o nce ntr ati o ns 
s h o ul d be meas ure d o n all s p ot uri ne sa m ples, wit h calc ulati o n of u P C R a n d u A C R val ues.  
1 0. 9.  
Re n al Bi o ps y  
A perc uta ne o us bi o ps y of t he re nal all o gr aft will be o btai ne d at t he ti mes i n dicate d i n t he 
Sc he d ule of Acti vities  (T a ble  1). T he pr oce d ur e s h o ul d be perf or me d acc or di n g t o t he l ocal 
sta n dar d practices at t he site, i ncl u di n g use of a nest hesia/se dati o n, pr e pr oce d ur e e va l uati o n 
(e g, la b orat or y testi n g pri or t o re nal bi o ps y), a n d p ost pr oce d ur e o bser vati o n a n d m o nit ori n g. 
T he re nal bi o ps y m ust i ncl u de a de q uate material f or li g ht micr osc o p y ( 7 or m or e gl o mer uli), 
i m m u n ofl u oresce nce micr osc o p y ( 3 or m or e gl o mer uli), a n d electr o n micr osc o p y ( 2 or m or e 
gl o mer uli). Re nal bi o ps y sa m ples s h o ul d be ha n dle d a n d pr ocesse d as per t he pat h ol o g y ma n ual. 
All re nal pat h ol o g y will be re vie we d b y t he ce ntr al pat h ol o g y la b or at or y, w hic h will be bli n de d 
t o treat me nt assi g n me nt. 
As a re mi n der, if a c oa g ulati o n pa nel is perf or me d f or a n y r eas o n, i ncl u di n g as a pr e bi o ps y 
assess m e nt, t he use of silica rea ge nts f or t his test s h o ul d be a v oi de d i n s u bjects tr eate d wit h 
pe gcetac o pla n.  
1 0. 1 0.  
Me as ure d Gl o m er ul ar Filtr ati o n R ate  
Meas ure d gl o mer ular filtrati o n rate ( G F R) is a n o pti o nal assess me nt t hat ma y be d o ne b y a site 
t hat r o uti nel y perf or ms t his assess me nt. I n t his case, t he site s h o ul d f oll o w its sta n dar d pr oce d ur e 
f or meas ure d G F R (a n d d oc u me nt t he pr oce d ur e wit hi n t he s u bject’s s o ur ce d oc u me nt) at 1 ti me 
p oi nt pri or t o t he first pe gcetac o pla n d ose ( b ut n o m or e t ha n 4  wee ks pri or t o t he first d ose) a n d 
at 1 ti me p oi nt bet wee n Wee k 4 8 a n d Wee k  5 2, i ncl usi ve.  
1 0. 1 1.  
O p ht h al m ol o gic E v al u ati o n  
O p ht hal m ol o gic e val uati o n is a n o pti o nal assess me nt a n d will be perf or me d  at selecte d sites. 
If t hese e val uati o ns are perf or me d, s u bjects s h o ul d ha ve a baseli ne  e val uati o n, i ncl u di n g a basic 
o p ht hal m ol o gic e xa mi nati o n, s pectral d o mai n o ptical c o her e nce t o m o gr a p h y ( S D -O C T), 
a n d c ol or f u n d us p h ot o gra p h y, at a n a p pr o ve d o p ht hal m ol o gic cli nical site at a n y ti me d uri n g t he 
scree ni n g peri o d. F or t h ose s u bjects wit h dr use n pri or t o pe gcetac o pla n a d mi nistr ati o n, 
a f oll o w-u p o p ht hal m ol o gic e val uati o n, i ncl u di n g a basic o p ht hal m ol o gic e xa mi nati o n, S D -O C T, 
a n d c ol or f u n d us p h ot o gra p h y, s h o ul d occ ur at a c o n ve nie nt ti me p oi nt bet wee n Wee k  4 2 a n d 
Wee k  5 2 of t he st u d y. T he S D -O C T a n d c ol or f u n d us p h ot o gr a p h y will be ac q uir e d usi n g a 
sta n dar dize d pr ot oc ol, perf or me d b y r ea di n g ce nter certifie d i ma gers o n r e gister e d e q ui p me nt, 
a n d will be tra ns mitte d t o a ce ntral rea di n g ce nter f or e val uati o n. T he basic o p ht hal m ol o gic 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 6 1 
 
C o nfi de nti al  
e xa mi nati o n s h o ul d i ncl u de best -c orrecte d vi s ual ac uit y, i ntr a oc ular pr ess ur e, a n d a dilate d 
f u n d us e xa m wit h c o m me nt o n prese nce or a bse nce of pi g me nt, dr use n, he m orr ha ge, atr o p h y, 
or ot her e vi de nce of mac ular de ge nerati o n.  
1 0. 1 2.  
I nf usi o n Site/ P u m p S afet y Ass ess m e nt 
O n t he da ys of cli nical visits, p u m p use saf et y will be assesse d wit hi n 3 0  mi n utes after st u d y 
dr u g a d mi nistrati o n. T his tec h ni q ue e val uati o n will be perf or me d b y a p h ysicia n or ot her 
lice nse d healt h care pr o vi der (e g, st u d y n urse), as dele gate d b y t he i n vesti gat or. T he s u bject will 
be as ke d a b o ut a n y iss ues relate d t o p u m p use.  
S u bjects will be i nstr uct e d t o n otif y t he i n vesti gat or or ot her st u d y pers o n nel if a n i nf usi o n site 
reacti o n occ urs after self-a d mi nistrati o n of pe gcetac o pla n. All cli nicall y si g nifica nt fi n di n gs 
relate d t o i nf usi o n pr oce d ures will be r ec or de d as A Es. 
1 0. 1 3.  
L a b or at or y Assess m e nts  
La b ora t or y assess me nt sa m ples (T a ble  3) ar e t o be o btai ne d at desi g nate d visits as detaile d i n t he 
Sc he d ule  of Acti vities (T a ble  1). 
 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 6 2 
 
C o nfi de nti al  
T a ble  3 : 
L a b or at or y Assess me nts  
H e m at ol o g y 
Se r u m c he mistr y  
Uri ne st u di es  
H b  
He mat ocrit  
Pl atelet c o u nt  
R B C c o u nt  
W B C c o u nt wit h differe ntial  
 
 
Al b u mi n 
A L T  
A L P  
A S T  
Bi car b o nate 
Bilir u bi n (t otal, dire ct, a n d 
i n dire ct) 
B U N  
C 3 
C 4 
C alci u m 
C hl ori de 
Cre ati ni ne 
Cre ati ne ki nase  
Esti m at e d gl o mer ul ar filtrati o n 
rate ( usi n g C KD -E PI f or m ula)  
G G T  
Gl uc ose  
H D L  
L D H  
L D L  
P h os p h or us 
P ot assi u m  
S o di u m 
Tri gl yceri des 
T otal c h ol est er ol  
T otal pr ot ei n  
Uri c aci d  
 
Uri nal ysis 
•  
Bl o o d 
•  
Bilir u bi n 
•  
Gl uc ose  
•  
Ket o nes  
•  
L e u k oc yt e esterase  
•  
Mi cr osc o pic e xa mi nati o n of uri ne 
se di me nt, i ncl u di n g f or prese nc e 
of R B Cs, W B Cs, a n d casts, will 
be perf or me d o n all uri nal yses  
•  
Nitrit e  
•  
p H 
•  
Pre g na nc y, w he n a p plic a ble  
•  
Pr ot ei n 
•  
S pe cific gra vit y  
•  
Ur o bili n o ge n 
 
S p ot uri ne s (first-m or ni n g a n d r a n d o m) 
•  
A C R  
•  
P C R  
•  
T otal al b u mi n c o nce ntrati o n  
•  
T otal cre ati ni ne c o nce ntrati o n  
•  
T otal pr ot ei n c o nc e ntrati o n  
 
2 4- h o ur uri ne  
•  
A C R  
•  
P C R  
•  
T otal al b u mi n c o nce ntrati o n  
•  
T otal cre ati ni ne c o nce ntrati o n  
•  
T otal pr ot ei n c o nc e ntrati o n  
•  
T otal v ol u me  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 6 3 
 
C o nfi de nti al  
T a ble  3 : 
L a b or at or y Assess me nts  
H e m at ol o g y 
Se r u m c he mistr y  
Uri ne st u di es  
a P T T 
Fi bri n o ge n 
I N R 
F S H ( p ost me n o pa usal w o me n)  
H Bs A g  
H b c A b 
H C V  
HI V  
Ser u m pre g na nc y test , w he n 
a p pli ca ble 
Ser u m p e gceta c o pl a n  
c o nce ntrati o n 
C o m pl e m e nt pr ofil e:  
( A H 5 0, C H 5 0, C 3a, C 3 b/i C 3 b, 
C 5a, a n d C 5 b - 9) 
C 3 ne p hritic fact or  
A nti – pe gceta c o pla n 
pe pti de/ a nti – p ol yet h yle ne 
gl yc ol a nti b o d y  
 
Ser u m sa m ples will be c oll ecte d f or 
a nal ysis of a nti b o d y titers t o Neisseri a 
me ni n giti dis  (t y pes A, C, W, Y, a n d B), 
P C V 1 3 or P P S V 2 3, a n d t he Hi b 
va cci nati o n.  
A b bre viati o ns: A C R  = al b u mi n-t o-creati ni ne rati o; A H 5 0 = 5 0 % alter nati ve he m ol ytic c o m ple me nt pat h wa y acti vit y; 
A L P  = al kali ne p h os p hatase; A L T = ala ni ne a mi n otra nsferase; a P T T  = acti vate d partial t hr o m b o plasti n ti me; 
A S T  = as partate a mi n otra nsferase; B U N = bl o o d urea nitr o ge n; C H 5 0  = 5 0 % classical he m ol ytic c o m ple me nt pat h wa y 
acti vit y; C K D-E PI  = C hr o nic Ki d ne y Disease – E pi de mi ol o g y C olla b orati o n; F S H  = f ollicle-sti m ulati n g h or m o ne; 
G G T  = γ-gl uta m yltra nsfer ase; H b = he m o gl o bi n ; Hb c A b = he patitis B c ore a nti b o d y; H b s A g = he patitis B s urface 
a nti ge n; H C V = he patitis C; H D L  = hi g h -de nsit y li p o pr otei ns; Hi b  = H ae m o p hil us i nfl ue nz ae  t y pe B vacci ne; 
HI V  = h u ma n i m m u n o deficie nc y vir us; I N R  = i nter nati o nal n or malize d rati o; L D H = lactate de h y dr o ge nase; 
L D L  = l o w-de nsit y li p o pr otei ns; P C R  = pr otei n -t o-creati ni ne rati o; P C V 1 3 = p ne u m oc occal c o nj u gate vacci ne; 
P P S V 2 3  = p ne u m oc occal p ol ysacc hari de vacci ne 2 3; R B C  = re d bl o o d cell; W B C = w hite bl o o d cell.  
A.  T he use of sili ca rea ge nts i n c oa g ulati o n pa nels s h o ul d be a v oi de d i n s u bj ects tre at e d wit h pe gc et ac o pla n.  
B.  Ser u m sa m ples will o nl y be a nal yze d i n t he e ve nt t hat t he s u bj ect has a p ositi ve i nfe cti o n f or 
Stre pt oc o c c us p ne u m o ni ae, Neisseri a  me ni n giti dis , or H ae m o p hil us i nfl ue nz ae . 
Bl o o d a n d uri ne sa m ples will be a nal yze d at a ce ntral la b orat or y facilit y. Uri ne sa m ples will be 
a nal yze d b y di pstic k a n d a micr osc o pic a nal ysis. All la b orat or y re p orts m ust be re vie we d, si g ne d, 
a n d date d b y t he i n vesti gat or. A le gi ble c o p y of all re p orts m ust be file d wit h t he s u bject’s me dical 
rec or d (s o urce d oc u me nt) f or t hat visit. A n y la b orat or y test res ult c o nsi dere d b y t he i n vesti gat or t o be 
cli nicall y si g nifica nt s h o ul d be c o nsi dere d a n A E (cli nicall y si g nifica nt A Es i ncl u de t h ose t hat 
re q uire a n i nter ve nti o n). Cli nicall y si g nifica nt a b n or mal val ues occ urri n g d uri n g t he st u d y will be 
f oll o we d u p u ntil re peat test res ults ret ur n t o n or mal, sta bilize, or are n o l o n ger cli nicall y si g nifica nt. 
1 0. 1 4.  
P h ar m ac o ki netics  
1 0. 1 4. 1.  
 
Bl o o d S a m ples  
Bl o o d sa m ples f or P K assess me nt of pe gcetac o pla n will be c ollecte d via dir ect ve ni p u nct ur e at 
t he ti me p oi nts deli neate d i n t he Sc he d ule of Acti vities (T a ble  1). 
P K sa m ples will be ta ke n pre d ose at all ot her visits.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 6 4 
 
C o nfi de nti al  
I nstr ucti o ns f or c ollecti o n, ha n dli n g, pr ocessi n g, st or a ge, a n d s hi p pi n g of sa m ples will be 
pr o vi de d i n a se parate la b orat or y refer e nce ma n ual pri or t o st u d y i nitiati o n.  
1 0. 1 5.  
P K  A n al ytic al Met h o d o l o g y 
T he c o nce ntrati o n of st u d y dr u g will be deter mi ne d fr o m t he ser u m sa m ples usi n g a vali date d 
a nal ytical met h o d. Details of t he met h o d vali dati o n a n d sa m ple a nal ysis will be i ncl u de d wit h t he 
fi nal cli nical st u d y re p ort. 
1 0. 1 6.  
P h ar m ac o d y n a mics 
Bl o o d sa m ple f o r P D assess me nt of pe gcetac o pla n will be c ollecte d via dir ect ve ni p u nct ur e at t he 
ti me p oi nts deli neate d i n t he Sc he d ule of Acti vities (T a ble  1) t o assess c o m ple me nt acti vati o n 
( C 3, C 4, A H 5 0, C H 5 0, C 3a, C 3 b/i C 3 b, C 5a, a n d s C 5 b- 9).  
I nstr ucti o ns f or c ollecti o n, ha n dli n g, pr ocessi n g, st or a ge, a n d s hi p pi n g of sa m ples will be 
pr o vi de d i n a se parate la b orat or y refer e nce ma n ual pri or t o st u d y i nitiati o n.  
1 0. 1 7.  
A nti d r u g A nti b o d y Ass ess m e nt  
A nti dr u g a nti b o dies ( A D A) i ncl u de b ot h a nti – pe gcetac o pla n pe pti de a n d a nti -P E G a nti b o dies. 
T he  pr o p ose d A D A sa m pli n g sc he d ule was esta blis he d t o ca pt ure t he A D A si g nal at baseli ne, al o n g 
wit h a n y p ote ntial earl y o nset a n d t he d y na mic pr ofile (tra nsie nt or persiste nt) of a nti b o d y f or mati o n.  
S u bjects w h o disc o nti n ue d osi n g will nee d t o ha ve A D A sa m pl es c ollecte d 6  a n d 1 2 wee ks 
f oll o wi n g t heir last treat me nt. 
Sa m ples t hat test p ositi ve will be c har acterize d b y assa y s t hat will deter mi ne a nti b o d y titer a n d 
meas ure ne utralizi n g ca pacit y. A n y titer t hat is at least 4- f ol d gr eater t ha n baseli ne is c o nsi dere d 
treat me nt b o oste d. S u bjects w h o ha ve a tr eat me nt -e mer ge nt or tr eat me nt - b o oste d a nti dr u g 
a nti b o dy res p o nse  at a n y ti me will be f oll o we d u p wit h A D A sa m ples bei n g c ollecte d e ver y 
6 m o nt hs u ntil t he a nti b o d y le vels are c o nsi der e d t o be ne gati ve. A nti b o d y l e vels will be 
c o nsi dere d t o be ne gati ve w he n t he y r e vert t o baseli ne or a n y titer t hat is less t ha n a 4-f ol d 
i ncrease fr o m t he baseli ne titer.  
1 0. 1 8.  
Bl o o d V ol u m e f or St u d y Ass ess m e nts  
T a ble  4 prese nts t he a p pr o xi mate bl o o d v ol u me t o be c ollecte d f or t his st u d y. See t he la b or at or y 
ma n ual f or  a d diti o nal details re gar di n g t he bl o o d v ol u me r e q uir e d t hr o u g h o ut t his st u d y.  
 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 6 5  
 
C o nfi de nti al  
T a ble  4 : 
A p pr o xi m ate Bl o o d V ol u m e C ollect e d  
S a m pl e t y pe 
A p pr o xi m ate 
v ol u m e per  
visit  
( m L) 
C ollecti o ns 
d uri n g 
scree ni n g 
C ollecti o ns 
d uri n g m ai n 
peri o d  
C ollecti o ns 
d uri n g 
f ollo w -u p  
A p pr o xi m ate 
v ol u m e o ver  
c o urse of st u d y 
( m L) 
Scr ee ni n g la b or at or y saf et y t ests 
(i ncl u di n g he m at ol o g y, ser u m 
c he mistr y, c oa g ulati o n ser ol o g y), 
F S H (f or p ost m e n o pa usal f e m al e 
s u bjects o nl y) 
2 5  
1 
0 
0 
2 5  
O n -st u d y ser u m c he mistr y 
1 1 
1 
1 4 
3 
1 9 8 
O n -st u d y he m at ol o g y 
4 
1 
1 4 
3 
7 2  
O n -st u d y c oa g ul ati o n 
3 
1 
1 4 
3 
5 4  
P K sa m pl es  
4 
0 
1 4 
3 
6 8 
C o m pl e m e nt pr ofil e  
1 0 
0 
1 4 
3 
1 7 0  
C 3 ne p hritic f act or  
2 
1 
0 
0 
2 
I m m u n o ge nicit y (a nti dr u g 
a nti b o di es) 
5  
0 
8 
2 
5 0  
Vacci nati o n titer sa m ple 
7  
1 
1 
0 
1 4 
A p pr o xi m ate bl o o d v ol u me per visit ( m L): 
2 5 -2 7  
3 2 -4 4  
3 2 -- 3 7 
 
T ot al a p pr o xi m at e bl o o d v ol u m e f or st u d y ( m L): 
6 5 3 
A b br e vi ati o ns: F S H  = f olli cl e-sti m ul ati n g h or m o ne; P K = p har m ac o ki neti cs. 
N ot e: Re prese nts t he sta n dar d c oll ecti o n v ol u m e pl a n ne d o ver t he d ur ati o n of t he st u d y act ual v ol u me m a y var y. F or s u bj ects 
e nteri n g Part B, t he l o n g-t er m e xt e nsi o n, t he sa m pl e v ol u m es n ote d a b o ve will c o nti n ue t o be c ollect e d as descri be d i n Ta bl e  7 . 
1 0. 1 9.  
Pre g n a nc y Tests  
F or W O C B P, a ser u m pre g na nc y test will be perf or me d d uri n g scr ee ni n g, at Visit  1, a n d at t he 
e n d of t he treat me nt peri o d ( Visit 1 6). A uri ne pr e g na n c y test will als o be perf or me d at eac h site 
visit ( pr e d ose), if a p plica ble. S u bjects wit h a p ositi ve r es ult will be e xcl u de d or disc o nti n ue d 
fr o m t he st u d y. Uri ne pre g na nc y tests will be perf or me d at e ver y visit t hr o u g h o ut t he f oll o w- u p 
peri o d. Male s u bjects will be c o u nsele d t o a v oi d d o nati n g se me n d uri n g t he ti me bet wee n t he 
first scr ee ni n g a n d t he fi nal e xit visit a n d f or t he 1 2 wee ks after t heir last d ose of st u d y dr u g.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 6 6 
 
C o nfi de nti al  
1 1.  
A D V E R S E E V E N T S  
1 1. 1.  
Defi niti o ns  
1 1. 1. 1.  
A d verse E ve nts  
A n A E is a n y u nt o war d me dical occ urr e nce ass ociate d wit h t he use of a dr u g i n h u ma ns, w het her 
or n ot it is  c o nsi dere d dr u g relate d. A n A E ca n, t her ef or e, be a n y u nf a v or a ble a n d u ni nte n de d 
si g n, i ncl u di n g a cli nicall y si g nifica nt a b n or mal la b or at or y fi n di n g, s y m pt o m, or disease 
te m p orall y ass ociate d wit h t he use of a n i n vesti gati o nal pr o d uct, w het her or n ot c o nsi der e d 
relate d t o t he i n vesti gati o nal pr o d uct. 
A Es ca n be s p o nta ne o usl y re p orte d b y t he s u bject a n d/ or i n r es p o nse t o a n o pe n q uesti o n fr o m 
t he st u d y per s o n nel or re veale d b y o bser vati o n a n d will be r ec or de d d uri n g t he st u d y at t he 
i n vesti gati o nal site. All i de ntifie d A Es m ust be r ec or de d a n d descri be d i n t he s u bject’s 
s o urce d oc u me nt. 
Fl uct uati n g or n o nsi g nifica nt c ha n ges i n la b or at or y val ues d o n ot n ecessaril y q ualif y f or A E 
re p orti n g. If c ha n ges i n la b orat or y val ues are assesse d as cli nicall y si g nifica nt a n d/ or lea d t o 
disc o nti n uati o n of a d mi nistrati o n of i n vesti gati o nal pr o d uct, t he y s h o ul d be re p orte d as a n A E. 
If t hese la b orat or y val ues are li n ke d t o a dia g n osis, o nl y t he dia g n osis s h o ul d be re p orte d as a n A E.  
1 1. 1. 2.  
Seri o us A d verse E ve nts  
A n S A E is a n y A E or s us pecte d a d verse reacti o n t hat, i n t he vie w of t he i n vesti gat or, res ults deat h, 
is life t hreateni n g, re q uires i n patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n, 
res ults i n a persiste nt or si g nifica nt i nca pacit y or s u bsta ntial disr u pti o n of t he a bilit y t o c o n d uct 
n or mal life f u ncti o ns, or is a c o n ge nital a n o mal y or birt h defect. I m p orta nt me dical e ve nts t hat ma y 
n ot res ult i n deat h, be life t hreate ni n g *, or re q uire h os pitalizati o n ma y be c o nsi der e d seri o us w he n, 
acc or di n g t o a p pr o priate me dical j u d g me nt, t he y ma y je o par dize t he s u bject or ma y re q uir e me dical 
or s ur gical i nter ve nti o n t o pre ve nt o ne of t he o utc o mes liste d i n t he a b o ve defi niti o n. E xa m ples of 
i m p orta nt me dical e ve nts i ncl u de aller gic br o nc h os pas m re q uiri n g i nte nsi ve treat me nt i n a n 
e mer ge nc y r o o m or at h o me, bl o o d d yscrasias or c o n v ulsi o ns t hat d o n ot res ult i n i n patie nt 
h os pitalizati o n, or t he de vel o p me nt of dr u g de pe n de nc y or dr u g a b use.  
* Life  t hre ate ni n g is defi ne d as a n A E or s us pecte d a d verse r eacti o n t hat, i n t he vie w of eit her t he 
i n vesti gat or or s p o ns or, place d t he s u bject at i m me diate ris k of deat h as it occ urr e d. It d oes n ot 
i ncl u de a n A E or s us pecte d a d verse r eacti o n t hat, ha d it occ urr e d i n a m or e se ver e f or m, 
mi g ht ha ve ca use d deat h.  
1 1. 1. 3.  
U ne x pecte d A d verse E ve nts  
A n A E or s us pecte d a d verse reacti o n is c o nsi der e d “ u ne x pecte d” if it is n ot liste d i n t he r ef er e nce 
safet y i nfor mati o n secti o n of t he I B t hat is i n eff ect at t he ti me of e ve nt o nset.  
1 1. 2.  
Rec or di n g a n d Re p orti n g A d vers e E ve nts  
A Es a n d S A Es will be c ollecte d fr o m t he si g ni n g of t he i nf or me d c o nse nt f or m (I C F) u ntil t he 
e xit/earl y ter mi nati o n visit.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 6 7  
 
C o nfi de nti al  
All S A Es will be f oll o we d u ntil satisf act or y r es ol uti o n, u ntil baseli ne le vel is r eac he d, or u ntil 
t he S A E is c o nsi dere d b y t he i n vesti gat or t o be c hr o nic or t he s u bject is sta ble, as a p pr o priate. 
All S A Es t hat are s us pecte d of bei n g relate d t o st u d y tr eat me nt m ust be r e p orte d i m me diatel y t o 
t he s p o ns or if t he i n vesti gat or bec o mes a war e of t he m, r e gar dless of t he ti me si nce t he 
c o m pleti o n of t he cli nical trial.  
A n y e ve nts t hat occ ur pri or t o t he start of d osi n g will be cate g orize d as pr etr eat me nt e ve nts; 
e ve nts occ ur ri n g after t he start of d osi n g will be r ec or de d as T E A Es (t he start date of d osi n g a n d, 
t heref ore, cate g orizati o n of t he e ve nt will be de pe n de nt o n r a n d o mizati o n assi g n me nt).  
F or eac h A E, t he i n vesti gat or will e val uate a n d r e p ort t he o nset date ( a n d ti me, if a p plica ble), 
res ol uti o n date (a n d ti me, if a p plica ble), i nte nsit y, ca usalit y, acti o n ta ke n, seri o us ness criteria 
met (if a p plica ble), a n d w het her  or n ot t he s u bject disc o nti n ue d t he st u d y as a r es ult of t he e ve nt.  
If p ossi ble, t he o utc o me of a n y A E res ulti n g i n per ma ne nt disc o nti n uati o n or t hat was pr ese nt at 
t he e n d of t he st u d y s h o ul d be re p orte d. S u bjects e x perie nci n g A Es t hat ca use i nterr u pti o n or 
disc o nti n uati o n of i n vesti gati o nal pr o d uct a n d t h ose e x perie nci n g A Es t hat ar e pr ese nt at t he last 
visit or earl y ter mi nati o n visit s h o ul d r ecei ve f oll o w -u p as a p pr o priate.  
All S A Es m ust be re p orte d t o t he s p o ns or/ A pellis Saf et y b y c o m pleti n g t he S A E f or m wit hi n 
2 4 h o urs of t he i n vesti gat or or t heir re pr ese ntati ve bec o mi n g a war e of t he e ve nt, w het her or n ot 
t he e ve nt is dee me d treat me nt relate d. C o m plete d S A E f or ms s h o ul d be  e maile d t o 
Safet y @ A pellis. c o m .  
A Es will be c o de d i n acc or da nce wit h t he Me dic al Dicti o nar y f or Re g ulat or y Acti vities 
( Me d D R A). If k n o w n, t he dia g n osis of t he u n derl yi n g ill ness or dis or der s h o ul d be r ec or de d, 
rat her t ha n its i n di vi d ual s y m pt o ms. 
1 1. 2. 1.  
Rel ati o ns hi p t o St u d y Dr u g  
T he i n vesti gat or will re vie w eac h e ve nt a n d assess its r elati o ns hi p t o st u d y dr u g tr eat me nt 
( n ot relate d, u nli kel y relate d, p ossi bl y r elate d, or defi nitel y r elate d). T he date a n d ti me of o nset, 
ti me relati o ns hi p t o dr u g d osi n g, d urati o n, se verit y, acti o n ta ke n, a n d o utc o me 
(rec o vere d/res ol ve d, rec o vere d/res ol ve d wit h se q uelae, r ec o veri n g/r es ol vi n g, n ot r ec o ver e d/ n ot 
res ol ve d, fatal, or u n k n o w n) of eac h e ve nt will be n ote d. 
T a ble  5  s h o ul d be c o nsi dere d w he n e valuati n g t he  r elati o ns hi p of A Es/ S A Es t o st u d y tr eat me nt. 
 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 6 8 
 
C o nfi de nti al  
T a ble  5 : 
Defi niti o ns of A d verse E ve nt Rel at e d ness  
Cl assific ati o n  
Defi niti o n  
Defi nitel y relate d  
Str o n g e vi de nce of a ca usal relati o ns hi p; t he i nfl ue nce of ot her fact ors is 
u nli kel y. 
P ossi bl y relate d  
S o me e vi de nce of a ca usal relati o ns hi p, b ut ot her fact ors ma y ha ve ca use d or 
c o ntri b ute d t o t he e ve nt (e g, a n ot her ill ness or c o nc o mita nt treat me nt)  
U nli kel y relate d  
A ca usal relati o ns hi p is n ot a reas o na ble p o ssi bilit y, b ut it ca n n ot be c o m pletel y 
r ule d o ut wit h t he a vaila ble e vi de nce. 
N ot relate d  
N o e vi de nce of a ca usal relati o ns hi p  
1 1. 2. 2.  
Se verit y of E ve nts  
T he i n vesti gat or will re vie w eac h e ve nt a n d assess its se verit y. N ote t hat se verit y is a meas ur e of 
i nte nsit y, w hereas seri o us ness is defi ne d b y t he criteria i n Secti o n  1 1. 1. 2 . A n A E ca n be of 
se vere i nte nsit y b ut n ot be c o nsi dere d seri o us.   
T a ble  6 prese nts t he defi niti o ns t hat s h o ul d be c o nsi der e d w he n e val uati n g t he se verit y of A Es 
a n d S A Es.   
T a ble  6: 
Se verit y o f E ve nts 
S e verit y  
Defi niti o n/ Descri pti o n  
Mil d  
E ve nt res ults i n mil d or tra nsie nt disc o mf ort, n ot re q uiri n g i nter ve nti o n or treat me nt; 
d oes n ot li mi t or i nterfere wit h dail y acti vities (e g, i ns o m nia, mil d hea dac he). 
M o derate  
E ve nt is s ufficie ntl y disc o mf orti n g, s o as t o li mit or i nterfer e wit h dail y acti vities; 
ma y re q uir e i nter ve nti o nal treat me nt (e g, fe brile ill ness re q uiri n g oral me dicati o n).  
S e vere  
E ve nt res ults i n si g nifica nt s y m pt o ms t hat pre ve nts n or mal dail y acti vities; ma y 
re q uire h ospitalizati o n or i n vasi ve i nter ve nti o n (e g, a ne mia res ulti n g i n bl o o d 
tra nsf usi o n). 
1 1. 2. 3.  
Re p orti n g A d verse E ve nts  t o He alt h A ut h orities, I nstit uti o n al Re vie w B o ar ds, 
a n d Et hics C o m mittees  
T he s p o ns or has t he res p o nsi bilit y t o i nf or m c o ncer ne d healt h a ut h orities, I R Bs, I E Cs, 
a n d i n vesti gat ors a b o ut s us pecte d u ne x pecte d seri o us a d verse r eacti o ns i n li ne wit h G C P 
g ui da nce a n d a p plica ble re g ulat or y re q uir e me nts.  
If re q uire d, s pecific S A Es s h o ul d be r e p orte d t o t he c o ncer ne d I R B or I E C i n c o m plia nce wit h 
l ocal re q uire me nts. 
1 1. 3.  
Pre g n a nc y  
Alt h o u g h pre g na nc y is n ot a n A E, all pr e g na ncies a n d s us pecte d pr e g na ncies (i ncl u di n g a 
p ositi ve pre g na nc y test re gar dless of a ge or disease state) occ urri n g wit h a f e male s u bject or t he 
fe male part ner of a male s u bject m ust be f oll o we d t o c o ncl usi o n t o deter mi ne t heir o utc o mes a n d 
are c o nsi dere d i m me diatel y re p orta ble e ve nts.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 6 9 
 
C o nfi de nti al  
A n y pre g na nc y, s us pecte d pre g na nc y, or p ositi ve pre g na nc y t est m ust be re p orte d t o A pellis Safet y 
b y c o m pleti n g t he pre g na nc y re p ort f or m wit hi n 2 4 h o urs of t he i n vesti gat or or t heir re prese ntati ve 
bec o mi n g a ware of t he e ve nt. T he pre g na nc y re p ort f or m m ust be c o m plete d, si g ne d, a n d date d b y 
t he i n vesti gat or a n d su b mitte d via e mail t o Safet y @ A pellis.c o m .  
T he i n vesti gat or m ust f oll o w u p t he s u bject u ntil c o m pleti o n of t he pr e g na nc y a n d m ust r e p ort 
t he o utc o me of t he pre g na nc y (e g, deli ver y, ter mi nati o n, etc) a n d ne o natal stat us u p t o 1 2 m o nt hs 
after  deli ver y. A n a b n or mal o utc o me is defi ne d as t he birt h of a c hil d wit h persiste nt or 
si g nifica nt i nca pacit y or s u bsta ntial disr u pti o n of t he a bilit y t o c o n d uct n or mal lif e f u ncti o ns 
(f or merl y referre d t o as disa bilities), c o n ge nital a n o malies, or birt h def ects. I n t he e ve nt of a n 
a b n or mal o utc o me, a n S A E m ust be re p orte d usi n g t he S A E r e p ort f or m, as descri be d i n 
Secti o n  1 1. 2 . 
1 1. 4.  
A b use, Mis use, O ver d os e, a n d Me dic ati o n Err ors  
Occ urre nces of e ve nts of o ver d ose, dr u g mis use, dr u g a b use, a n d me dicati o n err or m ust be 
re p orte d t o A pellis Safet y.  
A b use of a me dici n al pr o d uct:  Persist e nt or s p ora dic, i nte nti o nal, e xcessi ve use of me dici nal 
pr o d ucts t hat is acc o m pa nie d b y har mf ul p h ysical or ps yc h ol o gical eff ects.  
Mis use:  I nte nti o nal a n d i na p pr o priate use of a me dici nal pr o d uct n ot i n acc or da nce wit h t he 
prescri be d or a ut h orize d d ose, r o ute of a d mi nistr ati o n, a n d/ or i nte n de d  i n dicati o n(s) or n ot wit hi n 
t he le gal stat us of its s u p pl y.  
O ver d ose:  A n y d ose a d mi ni stere d t o or ta ke n b y a s u bject ( acci de ntall y or i nte nti o nall y) t hat 
e xcee ds t he hi g hest dail y d ose or is at a hi g her fr e q ue nc y t ha n t hat descri be d  i n t he pr ot oc ol. 
Me di c ati o n Err or:  A n err or m a de i n pr escri bi n g, dis pe nsi n g, a d mi nistr ati o n, a n d/ or use of t he 
st u d y dr u g. Me dicati o n err ors are re p orta ble t o t he s p o ns or as defi ne d bel o w.  
•  T he dis pe nsi n g, a d mi nistrati o n, a n d/ or use of u nassi g ne d st u d y dr u g  
•  T he a d mi nistrati o n a n d/ or use of a n e x pir e d st u d y dr u g  
All A Es  or S A Es ass ociate d wit h dr u g a b use, mis use, o ver d ose, or me dicati o n err or m ust be 
re p orte d as a p pr o priate. T he i n vesti gat or, i n c o ns ultati o n wit h t he s p o ns or,  will deci de w het her a 
d ose is t o be c o nsi dere d a n o ver d ose. I n t he e ve nt of a n o ver d ose, t he act ual d ose a d mi nister e d 
m ust be rec or de d i n t he s u bject’s s o urce d oc u me nt . 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 7 0  
 
C o nfi de nti al  
1 2.  
S T A TI S TI C A L A N A L Y SI S  
A f or mal statistical a nal ysis pla n ( S A P) will be de vel o pe d a n d fi nalize d pri or t o l oc ki n g t he 
data base. T he f ull details of data prese ntati o ns a n d a nal yses will be pr o vi de d i n t he S A P. 
A d diti o nal statistical a nal yses ot her t ha n t h ose descri be d i n t his secti o n ma y be perf or me d if 
dee me d a p pr o priate a n d i ncl u de d i n t he S A P. A n y de viati o ns fr o m eit her t he fi nal S A P or t he 
pr ot oc ol will be disc usse d i n t he fi nal st u d y r e p ort.  
E n d p oi nts t hat are n ot bi o ps y relate d ( e g, pr otei n uria, c ha n ges i n ser u m C 3 le vels) will be 
s u m marize d b y visit. E n d p oi nts t hat ar e bi o ps y r elate d ( e g , gl o mer ular m yel oi d cell i nfiltr ati o n, 
gl o mer ular cresce nts) will be s u m marize d b y sc he d ule d r e nal bi o ps y assess me nt. C o nti n u o us 
data will be s u m marize d usi n g descri pti ve statistics ( e g, mea n a n d sta n dar d de viati o n), 
a n d cate g orical data will be s u m marize d usi n g fr e q ue nc y ta bles ( c o u nts a n d per ce nta ges).  
1 2. 1.  
Deter mi n ati o n of S a m ple Size  
Gi ve n t he e x pl orat or y nat ure of t he st u d y, n o f or mal statistical h y p ot hesis testi n g will be 
perf or me d; t heref ore, t he sa m ple size is n ot base d u p o n statistical p o wer of t he st u d y. 
U p t o 1 2  s u bjects will be e nr olle d i n t his st u d y. Beca use t hese c o m ple me nt-m e diate d 
g l o mer ul o pat hies are rare diseases, as ar e s u bjects w h o ha ve r ecei ve d a r e nal tr a ns pla nt, it ma y 
be diffic ult t o recr uit s u bjects. T he i nte nti o n is t o c ollect saf et y, P K, P D, a n d efficac y data t o 
s u p p ort t he pr o gress of pe gcetac o pla n i nt o f urt her cli nical st u dies. 
1 2. 2.  
A n al ysis Set  
1 2. 2. 1.  
Scree ne d Set  
T he scree ne d set will c o nsist of all s u bjects w h o ha ve si g ne d i nf or me d c o nse nt.  
1 2. 2. 2.  
I nte nt-t o-Tre at Set  
T h e i nte nt-t o-treat (I T T) set c o nsists of all s u bjects f or w h o m a r a n d o mizati o n n u m ber has 
bee n  assi g ne d. 
1 2. 2. 3.  
S afet y Set  
T he safet y set will i ncl u de all s u bjects w h o r ecei ve at least 1  d ose of pe g cetac o pla n , a n d s u bjects 
w h o are ra n d o mize d i nt o Gr o u p 2 .  
1 2. 2. 4.  
P K  Set  
T h e P K set will i ncl u de all s u bjects i n t he I T T set w h o r ecei ve pe gcetac o pla n a n d ha ve at least 
1 e val ua ble p ost d ose P K meas ure me nt.  
1 2. 2. 5.  
P D  Set  
T he P D set  will i ncl u de all s u bjects i n t he I T T set w h o r ecei ve pe gcetac o pla n a n d ha ve at least 
1 e val ua ble p ost d ose P D meas ure me nt.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 7 1  
 
C o nfi de nti al  
1 2. 2. 6.  
D at a Re vie w f or A n al ysis Set  
After all t he data ha ve bee n verifie d/c o de d/e nter e d i nt o t he data base, a r e vie w will be perf or me d 
t o defi ne t he a nal ysis sets. T he re vie w will als o c hec k t he q ualit y of t he data, i de ntif y o utliers, 
a n d ma ke decisi o ns re gar di n g data iss ues ( e g, missi n g val ues, wit h dr a wals, pr ot oc ol de viati o ns). 
After t he prea nal ysis re vie w, res ol uti o n of all iss ues, a n d d oc u me ntati o n of all decisi o ns, 
t he data base will be l oc ke d.  
1 2. 3.  
Effic ac y A n al ysis  
N o f or mal i nfere ntial statistics will be a p plie d t o data c ollecte d i n t he st u d y.  
1 2. 3. 1.  
A n al ysis of  P ri m ar y Effic ac y E n d p oi nt 
T he pr o p orti o n of s u bjects wit h re d ucti o n i n C 3c stai ni n g o n r e nal bi o ps y after 1 2  wee ks o n 
st u dy will be ta b ulate d. N o f or mal statistical h y p ot hesis testi n g will be p erf or me d. T he scr ee ni n g 
re nal all o graft bi o ps y will be ta ke n as defi ne d per Secti o n  9. 1. 3 . 
1 2. 3. 2.  
A n al ysis of  Sec o n d ar y Effic ac y E n d p oi nts 
C ha n ges fr o m baseli ne bi o ps y i n C 3c stai ni n g o ver ti me will be s u m marize d b y tr eat me nt gr o u p. 
T he pr o p orti o n o f s u bjects wit h re d ucti o n i n C 3c stai ni n g o n r e nal bi o ps y after 5 2  wee ks of 
treat me nt will be ta b ulate d.  
C ha n ges a n d perce nta ge c ha n ges i n e G F R a n d ser u m cr eati ni ne  c o nce ntr ati o n  o ver ti me will be 
s u m marize d b y treat me nt gr o u p. e G F R a n d ser u m cr eati ni ne  c o nce ntr ati o n  will be meas ur e d at 
baseli ne  a n d at eac h p ostra n d o mizati o n assess me nt. T he pr o p orti o n of s u bjects wit h sta bilizati o n 
or i m pr o ve me nt i n eac h para meter will be ta b ulate d. T he C hr o nic Ki d ne y Disease – E pi de mi ol o g y 
C olla b orati o n ( C K D -E PI) creati ni ne e q uati o n f or a d ults will be use d t o calc ulate e G F R, a n d a  
sta ble or i m pr o ve d e G F R will be defi ne d as n o m or e t ha n a 2 5 % decr ease i n e G F R r elati ve t o 
baseli ne.  A sta ble or i m pr o ve d ser u m cr eati ni ne  c o nce ntr ati o n  will be defi ne d as n o i ncr ease or 
a n i ncrease of n o m ore t ha n 2 5 % fr o m baseli ne . 
1 2. 3. 3.  
A n al ysis of E x pl or at or y Effic ac y E n d p oi nts  
C ha n ges a n d perce nta ge c ha n ges i n pr otei n uria o ver ti me i n s u bjects wit h baseli ne pr otei n uria 
a b o ve t he U L N  will be s u m marize d b y tr eat me nt gr o u p. Pr otei n uria will be calc ulate d usi n g t he 
mea n of t he 3  s p ot u P C R sa m ples c ollecte d f or baseli ne a n d t he s u bse q ue nt tr eat me nt visits. 
C ha n ges a n d perce nta ge c ha n ges i n pr otei n uria will als o be assesse d o n t he basis of  2 4- h o ur 
uri ne c ollecti o n. T he pr o p orti o n of s u bjects wit h baseli ne pr otei n uria a b o ve t he U L N wit h at 
least a 5 0 % re d ucti o n i n pr otei n uria will be ta b ulate d. T he pr o p orti o n of s u bjects wit h baseli ne 
pr otei n uria a b o ve t he U L N ac hie vi n g c o m plete cli nical r e missi o n of pr otei n uria after 1 2  a n d 
5 2  wee ks of treat me nt ( defi ne d as mea n tri plicate u P C R or 2 4 -h o ur uri ne pr otei n i n t he n or mal 
ra n ge) will be ta b ulate d.  
C ha n ges i n a d diti o nal ke y bi o ps y feat ur es o ver ti me (s uc h as gl o mer ular m yel oi d cell 
i nfiltrati o n) will be s u m marize d f or eac h bi o ps y assess me nt. 
Baseli ne  will be ta ke n as t he meas ure me nt cl osest t o b ut bef or e r a n d o mizati o n.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 7 2  
 
C o nfi de nti al  
C ha n ges i n o p ht hal m ol o gic feat ures o ver ti me (i ncl u di n g c ha n ges i n ma xi m u m dr use n size a n d 
i n t he n u m ber of i nter me diate or lar ge dr use n) will be s u m marize d f or s u bjects w h o ha ve b ot h 
b aseli ne a n d o n -st u d y o p ht hal m ol o gic e val uati o ns. 
1 2. 4.  
S afet y A n al ysis  
T E A Es are defi ne d as t h ose A Es t hat de vel o p or w orse n after t he first d ose of st u d y me dicati o n 
( or after ra n d o mizati o n i n Gr o u p 2) a n d u p t o 8 wee ks  be y o n d t he last d ose of st u d y me dicati o n. 
All re p orte d A Es will be c o de d usi n g Me d D R A a n d s u m marize d b y S yste m Or ga n Class a n d 
Preferre d T er m. T he n u m ber a n d i nci de nce of T E A Es ( b ot h seri o us a n d n o nseri o us) as well as 
t he n u m ber a n d i nci de nce of disc o nti n uati o ns d ue t o T E A Es will be ta b ulate d. 
T he A E s u m maries will be prese nte d acr oss all  s u bjects. All A Es will be liste d b y s u bject, al o n g 
wit h i nf or mati o n re gar di n g o nset, d urati o n, se verit y, r elati o ns hi p t o st u d y dr u g, acti o n ta ke n wit h 
st u d y dr u g, treat me nt of e ve nt, a n d o utc o me. I n a d diti o n, t he n u m ber a n d i nci de nce of r ejecti o n 
e pis o des a n d graft l oss will be ta b ulate d.  
C ha n ges fr o m baseli ne i n cli nical la b or at or y tests will be s u m marize d usi n g descri pti ve statistics 
b y visit a n d n o mi nal ti me p ost d ose. O ut - of-r a n ge val ues will be fla g ge d i n data listi n gs.  
C ha n ges fr o m baseli ne i n vital si g ns will be s u m marize d usi n g desc ri pti ve statistics b y visit.  
C ha n ges fr o m baseli ne i n E C G para meters will be s u m marize d usi n g descri pti ve statistics b y 
visit. Val ue s of p ote ntial cli nical si g nifica nce will be fla g ge d b y listi n gs.  
C ha n ges i n p h ysical e xa mi nati o ns will be descri be d i n a data listi n g.  
1 2. 5.  
P K  A n al ysis 
T he P K c o nce ntrati o ns will be e val uate d usi n g t he P K set.  
C o nce ntrati o ns will be s u m marize d usi n g descri pti ve statistics o ver ti me i n t he tr eat me nt gr o u p 
( pe gcetaco pla n gr o u p) a n d t he c o ntr ol gr o u p, starti n g at Wee k  1 2.  
I n di vi d ual s u bject c o nce ntrati o n-ti me data will be pl otte d a gai nst act ual sa m pli n g ti me. 
Me dia n  pr ofiles of t he c o nce ntrati o n -ti me data usi n g n o mi nal sa m pli n g ti mes will als o be 
prese nte d. B ot h li near -li near a n d li near-l o g pl ots will be pr ese nte d.  
P o p ulati o n P K a n d e x p os ure -res p o nse m o deli n g of t he saf et y a n d efficac y data will be descri be d 
i n a pe gcetac o pla n p o p ulati o n P K/ P D a nal ysis pla n. T he met h o ds will be base d o n t he F D A 
g ui da nce f or b ot h e x p os ure -res p o nse a n d p o p ulati o n P K ( F D A G ui da nce f or I n d ustr y P o p ulati o n 
P har mac o ki netics, F D A G ui da nce f or E x p os ur e -R es p o nse Relati o ns hi ps).  
1 2. 6.  
P D  A n al ysis  
T he P D e n d p oi nts will be e val uate d usi n g t he P D set.  
A bs ol ute val ues, c ha n ges fr o m baseli ne, a n d per ce nta ge c ha n ges fr o m baseli ne will be 
s u m marize d usi n g d escri pti ve statistics o ver ti me.  
I n di vi d ual s u bject ti me pr ofiles will be pl otte d a gai nst act ual sa m pli n g ti me. Me dia n pr ofiles 
o ver ti me,  usi n g n o mi nal sa m pli n g ti me, will als o be pr ese nte d. 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 7 3  
 
C o nfi de nti al  
1 2. 7.  
I m m u n o ge nicit y A n al ysis 
T he pr o p orti o n of s u bjects wit h treat ment- e mer ge nt or tr eat me nt - b o oste d a nti-pe gcetac o pla n 
pe pti de or a nti -P E G A D A res p o nse s will be ta b ulate d. A D A r es ults will be s u m marize d b y 
treat me nt gr o u p, usi n g a p pr o priate descri pti ve statistics.  
1 2. 8.  
Ot her A n al ys es  
De m o gra p hics, baseli ne c haracteristics, c o nc o mita nt me dicati o n, me dical hist or y, a n d st u d y 
me dicati o n e x p os ure will be s u m marize d.  
W orl d Healt h Or ga nizati o n a n d Me d D R A c o di n g dicti o naries will be use d f or t he c o nc o mita nt 
me dicati o ns  a n d me dical hist ories, res pecti vel y.  
1 2. 9.  
I nteri m A n al ysis  
N o i nteri m a nal yses are pla n ne d f or t he pri mar y e n d p oi nt.  
1 2. 1 0.  
S afet y M o nit ori n g C o m mittee  
As descri be d i n Secti o n  9. 8 , a n S M C  will r e vie w c u m ulati ve saf et y  a n d t olera bilit y data 
(e g, p h ysical e xa mi nati o ns, E C Gs, vital si g ns, cli nical la b or at or y tests, a n d A Es). T he S M C will 
ha ve t he res p o nsi bilit y t o c o n d uct a t h or o u g h saf et y assess me nt at r e g ular pr e defi ne d i nter vals 
d uri n g t he  treat me nt peri o d of t he st u d y. 
T he re mit, r oles, a n d res p o nsi bilities of t he S M C will be s pecifie d i n a se par ate S M C c harter.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 7 4  
 
C o nfi de nti al  
1 3.  
S T U D Y M A N A G E M E N T  
1 3. 1.  
A p pr o v al a n d C o nse nt  
1 3. 1. 1.  
Re g ul at or y G ui deli nes  
T his st u d y will be c o n d ucte d i n acc or da nce wit h t he acce pte d versi o n of t he Declar ati o n of 
Helsi n ki a n d/ or all rele va nt re g ulati o ns, i n c o m plia nce wit h I nter nati o nal C o u ncil f or 
Har m o nisati o n (I C H) a n d G C P a n d acc or di n g t o t he a p pr o priate r e g ulat or y r e q uir e me nts i n t he 
c o u ntries w here t he st u d y was c o n d ucte d.  
T he fi nal re p ort of t his st u d y will be writte n acc or di n g t o t he I C H E 3 G ui deli ne ( Str uct ur e a n d 
C o nte nt of Cl i nical St u d y Re p orts) as per t he I C H Har m o nize d Tri partite G ui da nce 
( Or ga nizati o n of t he C o mm o n T ec h nical D oc u me nt f or t he Re gistr ati o n of P har mace uticals f or 
H u ma n Use M 4 a n d t he I C H M 2 E x pert W or ki n g Gr o u p).  
1 3. 1. 2.  
I nstit uti o n al Re vie w B o ar d or I n de pe n de nt Et hics C o m mitt ee Re vie w  
T he st u d y pr ot oc ol, a n y a me n d me nts t o t he pr ot oc ol, t he I C F, t he I B, a n d  ot her st u d y -specific 
i nf or mati o n will be re vie we d a n d a p pr o ve d b y t he I R B or I E C. T he st u d y will n ot be i nitiate d 
u ntil t he I R B/I E C has a p pr o ve d t he pr ot oc ol or a m o dificati o n t her e of. All r ec or ds pertai ni n g t o 
I R B/I E C s u b missi o n a n d a p pr o val s h o ul d be ke pt i n t he site’s r e g ulat or y files a n d s p o ns or’s trial 
master file.  
T he I R B/ E R C m ust be c o nstit ute d a n d o perate i n acc or da nce wit h t he pri nci ples a n d re q uire me nts 
descri be d i n I C H G ui da nce E 6 a n d nati o nal a n d l ocal re g ulati o ns dee me d a p pr o priate.  
1 3. 1. 3.  
I nf or me d Co nse nt  
F or e ac h st u d y s u bject, writte n i nf or me d c o nse nt will be o btai ne d bef or e a n y pr ot oc ol -r elate d 
acti vities. As part of t his pr oce d ure, t he i n vesti gat or or desi g nee m ust e x plai n or all y a n d i n 
writi n g t he nat ure of t he st u d y; its p ur p ose, pr oce d ur es, a n d e x pecte d d ur ati o n; alter nati ve 
t hera p y a vaila ble; a n d t he be nefits a n d ris ks i n v ol ve d i n st u d y partici pati o n. T he s u bject s h o ul d 
be i nf or me d t hat he/s he ma y wit h dra w fr o m t he st u d y at a n y ti me, a n d t he s u bject will r ecei ve all 
i nf or mati o n t hat is re q uired b y l ocal r e g ulati o ns a n d I C H g ui deli nes. T he i n vesti gat or will 
pr o vi de t he s p o ns or or its re prese ntati ve wit h a c o p y of t he I E C/I R B -a p pr o ve d I C F bef or e t he 
start of t he st u d y. T he i n vesti gat or s hall r etai n t he ori gi nal, si g ne d I C F i n t he s u bject’s me dical 
rec or d a n d s hall pr o vi de t he s u bject wit h a c o p y of t he c o nse nt. 
If re q uire d b y l ocal or i nstit uti o nal p olic y, a bi o ps y c o nse nt f or m ma y als o be utilize d f or t he st u d y 
ki d ne y bi o ps y pr oc e d ures. T he bi o ps y -s pecific I C F s h o ul d be fr o m t he ce nter perf or mi n g t he bi o ps y, 
a n d it s h o ul d be re vie we d a n d si g ne d at t he sa me ti me as t he st u d y -s pecific I C F, c o veri n g t he 
s u bject’s c o nse nt t o all 3 st u d y bi o psies. T his bi o ps y-s pecific I C F is t o s pecificall y i ncl u de t he ris ks 
of t he bi o ps y pr oce d ure, t he pla n ne d a nest hesia f or t he bi o ps y, t he pla n ne d pre pr oce d ure e val uati o n, 
a n d t he pla n ne d o bser vati o n peri o d f oll o wi n g t he bi o ps y. Wit hi n a p pr o xi matel y 1  wee k of eac h 
bi o ps y pr oce d ure, t he s u bject s h o ul d be c o u nsele d a gai n re gar di n g t he bi o ps y ris ks, 
pla n ne d  a nest hesia, req uire d pre pr oce d ure la b orat or y val ues or tests, a n d o bser vati o n peri o d.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 7 5  
 
C o nfi de nti al  
If t here are a n y a me n d me nts t o t he a p pr o ve d pr ot oc ol t hat ma y dir ectl y aff ect t he s u bject’s 
decisi o n t o c o nti n ue partici pati o n i n t he st u d y, t he I C F will be a me n de d acc or di n gl y, a n d t he 
s u bject m ust re-si g n t he re vise d I E C/I R B-a p pr o ve d I C F. 
1 3. 2.  
D at a H a n dli n g  
T he i n vesti gat or m ust mai ntai n all d oc u me ntati o n relate d t o t his st u d y. All esse ntial d oc u me nts 
(as defi ne d i n I C H G ui deli ne E 6) a n d t he data ge nerate d i n c o n necti o n wit h t his st u d y, w it h t he 
ori gi nal c o p y of t he fi nal re p ort, will be retai ne d f or at least 5  years after t he last a p pr o val of a 
mar keti n g a p plicati o n i n a n I C H re gi o n a n d u ntil t her e are n o pe n di n g or c o nte m plate d mar keti n g 
a p plicati o ns i n a n I C H re gi o n or at least 5 years ha ve ela pse d si nce t he f or mal disc o nti n uati o n of 
cli nical de vel o p me nt of t he i n vesti gati o nal pr o d uct. T hese d oc u me nts s h o ul d be retai ne d f or a l o n ger 
peri o d if re q uire d b y t he a p plica ble re g ulat or y re q uir e me nts or b y a n a gree me nt wit h t he s p o ns or.  
It is t he res p o nsi bilit y of t he s p o ns or t o i nf or m t he i n vesti gat or/i nstit uti o n as t o w he n t hese 
d oc u me nts n o l o n ger nee d t o be retai ne d.  
1 3. 3.  
S o urce D oc u m e nts  
S o urce d oc u me nts are c o nsi dere d t o be all i nf or mati o n i n ori gi nal r ec or ds a n d certifie d c o pies of 
ori gi nal rec or ds of cli nical fi n di n gs, o bser vati o ns, data, or ot her acti vities i n a cli nical st u d y 
necess ar y f or t he rec o nstr ucti o n a n d e val uati o n of t he st u d y. T he i n vesti gat or will pr o vi de dir ect 
access t o s o urce d oc u me nts a n d/ or s o ur ce data i n t he f acilitati o n of t rial-r elate d m o nit ori n g, 
a u dits, re vie w b y I E Cs/I R Bs, a n d re g ulat or y i ns pecti o ns.  
T he i n vesti gat or/i nstit uti o n s h o ul d mai ntai n a de q uate a n d acc ur ate s o ur ce d oc u me nts a n d trial 
rec or ds t hat i ncl u de all perti ne nt o bser vati o ns o n eac h of t he site’s trial s u bjects. S o ur ce data 
s h o ul d be attri b uta ble, le gi ble, c o nte m p or a ne o us, ori gi nal, acc ur ate, a n d c o m plete. C ha n ges t o 
s o urce data s h o ul d be tracea ble, n ot o bsc ur e t he ori gi nal e ntr y, a n d be e x plai ne d, if necessar y.  
1 3. 4.  
Rec or d Rete nti o n  
St u d y rec or ds a n d s o urce d oc u me nts m ust be pr eser ve d f or at least 1 5  years after t he c o m pleti o n 
or disc o nti n uati o n of/ wit h dra wal fr o m t he st u d y, at least 2  years after t he dr u g bei n g st u die d has 
recei ve d its last a p pr o val f or sale, or at least 2 years after t he dr u g de vel o p me nt has st o p pe d, 
a n d i n acc or da nce wit h t he a p plica ble l ocal pri vac y la ws, w hic he ver is t he l o n ger ti me peri o d. 
T he i n vesti gat or a grees t o c o m pl y wit h all a p plica ble fe deral, state, a n d l ocal la ws a n d re g ulati o ns 
relati n g to t he pri vac y of patie nt healt h i nf or mati o n, i ncl u di n g, b ut n ot li mite d t o, t he  Sta n dar ds f or 
Pri vac y of I n di vi d uall y I de ntifia ble Healt h I nf or mati o n; Title 4 5 of t he U S C o de of Fe deral 
Re g ulati o ns, Parts  1 6 0 a n d 1 6 4; a n d t he Healt h I ns ur a nce P orta bilit y Acc o u nta bilit y Act of  1 9 9 6 
Pri vac y R ule. T he i n vesti gat or s hall e ns ure t hat st u d y s u bjects a ut h orize t he use a n d discl os ure of 
pr otecte d healt h i nf or mati o n i n acc or da nce wit h t he Healt h I ns ura nce P orta bilit y Acc o u nta bilit y Act 
of  1 9 9 6 Pri vac y R ule a n d i n a f or m satisfact or y t o t he s p o ns or.  
1 3. 5.  
M o nit ori n g  
O n -site m o nit ori n g will be perf or me d b y t he s p o ns or’s desi g nee f or t he d ur ati o n of t he st u d y. 
T he m o nit or will e ns ure t hat t he st u d y is c o n d ucte d, r ec or de d, a n d r e p orte d, i n acc or da nce wit h 
t he pr ot oc ol, sta n dar d o perati n g pr oce d ur es ( S O Ps), G C P, a n d t he a p plica ble r e g ulat or y 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 7 6  
 
C o nfi de nti al  
re q uire me nts. T he m o nit or will verif y t he acc ur ac y a n d c o m plete ness of t he e C R F e ntries, s o ur ce 
d oc u me nts, a n d ot her st u d y -relate d rec or ds a gai nst eac h ot her. T he i n vesti gat or will pr o vi de 
direct access t o s o urce data/ d oc u me nts f or st u d y -r elate d m o nit ori n g. It is i m p orta nt t hat t he 
i n vesti gat or a n d t he staff are a vaila ble at t hese visits. T he m o nit or will r ec or d t he date of eac h 
visit, wit h a s u m mar y of t he stat us a n d pr o gr ess of t he st u d y. Pr o p ose d acti o ns will be 
d oc u me nte d i n writi n g t o t he i n vesti gat or. 
1 3. 6.  
Q u alit y C o ntr ol a n d Q u alit y Ass ur a nce  
T he s p o ns or or its desi g nee will perf or m t he q ualit y ass ur a nce a n d q ualit y c o ntr ol acti vities of 
t his st u d y; h o we ver, res p o nsi bilit y f or t he acc ur ac y, c o m plete ness, sec urit y, a n d r elia bilit y of t he 
st u d y data prese nte d t o t he s p o ns or lies wit h t he i n vesti gat or ge ner ati n g t he data. 
Q ualit y c o ntr ol a n d q ualit y ass ura nce s yste ms are i m ple me nte d a n d mai ntai ne d usi n g writte n S O Ps 
fr o m t he i n vesti gati ve site, t he s p o ns or, a n d/ or its desi g nee t o e ns ure t hat t he st u d y is c o n d ucte d a n d 
data are ge nerate d, d oc u me nte d (rec or de d), a n d re p orte d i n c o m plia nce wit h t he pr ot oc ol, G C P, 
a n d t he a p plica ble re g ulat or y re q uire me nt(s), nati o nal a n d l ocal la ws, r ules, a n d re g ulati o ns. 
Q ualit y c o ntr ol c hec ks wil l be a p plie d at eac h sta ge of data ha n dli n g ( e g, e dit c hec ks) t o e ns ur e 
t hat all data are relia ble a n d ha ve bee n pr ocesse d c orr ectl y. 
T he s p o ns or will arra n ge a u dits as part of t he i m ple me ntati o n of q ualit y ass ura nce t o e ns ure t hat t he 
st u d y is bei n g co n d ucte d i n c o m plia nce wit h t he pr ot oc ol, S O Ps, G C P, a n d all a p plica ble re g ulat or y 
re q uire me nts. A u dits will be i n de pe n de nt of a n d se parate fr o m t he r o uti ne m o nit ori n g a n d q ualit y 
c o ntr ol f u ncti o ns. Q ualit y ass ura nce pr oce d ures will be perf or me d at st u d y sites  a n d d uri n g data 
ma na ge me nt t o ass ure t hat safet y a n d efficac y data are a de q uate a n d well d oc u me nte d.  
1 3. 7.  
Pr ot oc ol A m e n d m e nt a n d Pr ot oc ol De vi ati o n  
1 3. 7. 1.  
P r ot oc ol A me n d me nt  
A me n d me nts t o t he pr ot oc ol t hat e ntail c orr ecti o ns of t y p o gr a p hical err ors, clarificati o ns of 
c o nf usi n g w or di n g, c ha n ges i n st u d y pers o n nel, a n d mi n or m o dificati o ns t hat ha ve n o eff ect o n 
t he safet y of s u bjects or t he c o n d uct of t he st u d y will be classe d as a d mi nistr ati ve a me n d me nts 
a n d will be s u b mitte d t o t he I E C/I R B f or i nf or ma ti o n o nl y. T he s p o ns or will e ns ur e t hat 
ac k n o wle d g me nt is recei ve d a n d file d. A me n d me nts t hat ar e classe d as s u bsta ntial a me n d me nts 
m ust be s u b mitte d t o t he a p pr o priate re g ulat or y a ut h orities a n d t he I E Cs/I R Bs f or a p pr o val a n d 
will n ot be i m ple me nte d at si tes u ntil s uc h a p pr o vals ar e r ecei ve d, ot her t ha n i n t he case of a n 
ur ge nt safet y meas ure.  
1 3. 7. 2.  
P r ot oc ol De vi ati o ns  
S h o ul d a pr ot oc ol de viati o n occ ur, t he s p o ns or m ust be i nf or me d as s o o n as p ossi ble. Pr ot oc ol 
de viati o ns a n d/ or vi olati o ns a n d t he reas o ns t he y o cc urr e d will be i ncl u de d i n t he cli nical st u d y 
re p ort. Re p orti n g of pr ot oc ol de viati o ns t o t he I R B/I E C a n d i n acc or da nce wit h a p plica ble 
re g ulat or y a ut h orit y ma n dates is a n i n vesti gat or or c o ntr act r esear c h or ga nizati o n r es p o nsi bilit y. 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 7 7  
 
C o nfi de nti al  
1 3. 8.  
Et hic al C o nsi der ati o ns  
T his st u d y will be c o n d ucte d i n acc or da nce wit h t his pr ot oc ol; t he acce pte d versi o n of t he 
Declarati o n of Helsi n ki; all rele va nt fe der al r e g ulati o ns, as set f ort h i n Parts  5 0, 5 6, 3 1 2, S u b part 
D, of Title 2 1 of t he U S C o de of Fe der al Re g ulati o ns a n d E U 5 3 6/ 2 0 1 4, A n ne x 1, D, 1 7 ( a); 
a n d i n c o m plia nce wit h G C P g ui deli nes. 
I nstit uti o nal et hics c o m mittees/I R Bs will r e vie w a n d a p pr o ve t his pr ot oc ol a n d t he I C F. 
All  s u bjects are re q uire d t o gi ve writte n i nf or me d c o nse nt bef or e partici pati o n i n t he st u d y. 
1 3. 9.  
C o nfi de nti alit y  
C o nfi de ntialit y of s u bject’s i nf or mati o n m ust be mai ntai ne d, i n acc or da nce wit h nati o nal a n d 
l ocal pri vac y la ws. 
1 3. 1 0.  
Cli nic al Tri als. g o v  
T his st u d y has bee n liste d wit h Cli nical Trials. g o v, as r e q uir e d.  
1 3. 1 1.  
St u d y Ter mi n ati o n  
T he s p o ns or reser ves t he ri g ht  t o s us pe n d or disc o nti n ue t his st u d y f or a d mi nistr ati ve a n d/ or 
safet y reas o ns at a n y ti me. T he i n vesti gat or r eser ves t he ri g ht t o disc o nti n ue d osi n g s u bjects at 
a n y ti me f or safet y reas o ns.  
1 3. 1 2.  
Fi n a nci n g a n d I ns ur a nce  
A cli nical trial a gree me nt bet wee n t he i n vesti gat or/i nstit uti o n a n d t he s p o ns or will a d dr ess all 
fi na nce a n d i ns ura nce matters. 
1 3. 1 3.  
P u blic ati o n P olic y/ Dis cl os ure of D at a  
B ot h t he use of data a n d t he p u blicati o n p olic y are detaile d wit hi n t he cli nical st u d y a gree me nt. 
I ntellect ual pr o pert y ri g hts (a n d relate d matters) ge nerate d b y t he i n vesti gat or a n d ot hers perf or mi n g 
t he cli nical st u d y will be s u bject t o t he ter ms of a cli nical st u d y a gree me nt t hat will be a gree d 
bet wee n t he i nstit uti o n a n d t he s p o ns or or its desi g nee. Wit h res pect t o s uc h ri g hts, t he s p o ns or or its 
desi g nee will s olel y o w n all ri g hts a n d i nterests i n a n y materials, data, a n d  i ntellect ual pr o pert y ri g hts 
de vel o pe d b y i n vesti gat ors a n d ot hers perf or mi n g t he cli nical st u d y descri be d i n t his pr ot oc ol, 
s u bject t o t he ter ms of a n y s uc h a gree me nt. I n or der t o facilitate s uc h o w ners hi p, i n vesti gat ors will be 
re q uire d t o assi g n all s uc h i n ve nti o ns eit her t o t heir i nstit uti o n or directl y t o t he s p o ns or or its 
desi g nee, as will be set f ort h i n t he cli nical st u d y a gr ee me nt.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 7 8  
 
C o nfi de nti al  
1 4.  
R E F E R E N C E S  
H olle  J, Bere n ber g-G o ßler L, W u K, et al. O utc o me of me m br a n o pr olif er ati ve 
gl o mer ul o ne p hritis a n d C 3 -gl o mer ul o pat h y i n c hil dr e n a n d a d olesce nts. P e di atr Ne p hr ol . 
2 0 1 8; 3 3( 1 2): 2 2 8 9- 2 2 9 8. 
L u D F, M o o n M, La n ni n g L D, Mc Cart h y A M, S mit h RJ. Cli nical f eat ur es a n d o utc o mes of 
9 8 c hil dre n a n d a d ults wit h de nse de p osit disease. P e di atr Ne p hr ol . 2 0 1 2; 2 7( 5): 7 7 3-7 8 1.  
Me djeral -T h o mas N R, O’ S ha u g h ness y M M, O’ Re ga n J A, et al. C 3 gl o mer ul o pat h y: 
cli nic o pat h ol o gic feat ures a n d pre dict ors of o utc o me. Cli n J A m S oc Ne p hr ol . 2 0 1 4; 9(1): 4 6 -5 3.  
N oris M, D o na delli R, Re m uzzi G. A ut oi m m u ne a b n or malities of t he alter nati ve c o m ple me nt 
pat h wa y i n me m bra n o pr oliferati ve gl o mer ul o ne p hritis a n d C 3 gl o mer ul o pat h y. P e di atr Ne p hr ol . 
2 0 1 9; 3 4: 1 3 1 1- 1 3 2 3. D oi: 1 0. 1 0 0 7/s 0 0 4 6 7 - 0 1 8- 3 9 8 9- 0. 
O k pec hi I G, Dl a mi ni T A, D uffiel d M, Ra y ner B L, M ot uri G, S wa ne p oel C R. O utc o me of 
patie nts wit h pri mar y i m m u ne -c o m ple x t y pe mesa n gi oca pillar y gl o mer ul o ne p hritis ( M C G N) i n 
Ca pe T o w n S o ut h Africa. Pl o S O ne . 2 0 1 4; 9( 1 1):e 1 1 3 3 0 2. 
Pic keri n g M C, D’ A gati V D, Nester C M, et al. C 3 gl o mer ul o pat h y: c o nse ns us r e p ort. Ki d ney I nt . 
2 0 1 3; 8 4( 6): 1 0 7 9 - 1 0 8 9. 
Ser vais A, N oël L H, R o u me ni na L T, et al. Ac q uir e d a n d ge netic c o m ple me nt a b n or malities pla y 
a critical r ole i n de nse de p osit disease a n d ot her C 3 gl o mer ul o pat hies. Ki d ney I nt . 
2 0 1 2; 8 2( 4) : 4 5 4- 4 6 4. 
Z ha n g Y, Nester C, Marti n B, et al. Defi ni n g t he c o m ple me nt bi o mar ker pr ofile of C 3 
gl o mer ul o pat h y. Cli n J A m S oc Ne p hr ol . 2 0 1 4; 9( 1 1): 1 8 7 6- 1 8 8 2. 
 
 
 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 7 9  
 
C o nfi de nti al  
1 5.  
A P P E N DI C E S  
 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 8 0 
 
C o nfi de nti al  
A P P E N DI X  1. L O N G -T E R M E X T E N SI O N A C TI VI TI E S  
1 5. 1.  
P art B: L o n g -Ter m E xte n si o n 
T his a p pe n di x c o ntai ns o nl y i nf or mati o n t hat is s pecific t o t he desi g n a n d c o n d uct of Part B, t he 
l o n g-ter m e xte nsi o n. A n y pr ocesses, pr oce d ur e, or i nf or mati o n n ot descri be d i n t his a p pe n di x is 
i de ntical t o t hat descri be d t hr o u g h t he b o d y of t he mai n pr ot oc ol. 
1 5. 1. 1.  
P art B O v ervie w/ R ati o n ale  
F oll o wi n g Wee k  5 2 a n d t he c o m pleti o n of Part A (t he c or e st u d y), a n y s u bject w h o, i n t he 
o pi ni o n of t he i n vesti gat or, is e x perie nci n g cli nical be nefit fr o m pe gcetac o pla n a d mi nistr ati o n 
will be i n vite d t o partici pate i n Part B, t he l o n g -term e xte nsi o n, i n or der t o c o nti n ue t o r ecei ve 
treat me nt wit h pe gcetac o pla n u ntil it is c o m mer ciall y a vaila ble f or t he disease u n der st u d y. 
D osi n g will re mai n t he sa me t hr o u g h o ut Part A a n d Part B.  
T a ble  7  c o ntai ns t he Sc he d ule of Acti vities f or visits t hat will be c o n d ucte d d uri n g Part B, t he 
l o n g-ter m exte nsi o n.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 8 1 
 
C o nfi de nti al  
T a ble  7 : 
Sc he d ule of Acti vities f or P art B, L o n g -Ter m E xt e nsi o n ( F oll o wi n g 
Wee k  5 2)  
St u d y pe ri o d  
L o n g- ter m e xte nsi o n: Wee k 6 4 a n d be y o n d  
E T & e xit A  
St u d y Wee k  
6 4  
≥7 6 B  
 
St u d y D a y  
4 4 8  
5 3 2 B  
 
St u d y Visit  
1 7 B 
1 8 B B  
 
Visit wi n d o w ( ± d a ys)  
7 
7 
 
P h ysi c al e xa mi nati o n C  
X 
X 
X 
1 2- l ea d E C GD  
X 
 
X 
I nf usi o n site/ p u m p safet y assess m e ntE  
X 
X 
 
C o nc o mit a nt m e dic ati o ns  
X 
X 
X 
Vit al si g n me as ure me nts F 
X 
X 
X 
Uri nal ysis 
X 
X 
X 
Tri plic at e first -m or ni n g s p ot uri ne G  
( Dis pe nse u P C R c oll ecti o n c o nt ai ners/ arra n ge 
f or h o m e c o urier pic k u p) 
X 
X 
X 
Bl o o d H  
P K sa m pl e  
X 
X 
X 
A D A assa ys I 
X 
X I 
X 
He mat ol o g y a n d c he mistr y  
X 
X 
X 
C o m pl e m e nt pr ofil e  
X 
X 
X 
e G F R J 
X 
X 
X 
Pre g na nc y ( β -H C G a n d F S H)  
 
 
X 
Uri ne pre g na nc y test K  
X 
X 
X 
A d verse e ve nts 
X 
X 
X 
Dr u g dis pe nsati o n f or h o me a d mi nistrati o n  
X 
X 
 
A b bre viati o ns : β -H C G  = β – h u ma n c h ori o nic g o na d otr o pi n; A D A  = a nti dr u g a nti b o d y; C D K-E PI  = C hr o nic Ki d ne y 
Disease – E pi de mi ol o g y C olla b orati o n; E C G  = electr ocar di o gra m; e G F R = esti mate d gl o mer ular filtrati o n rate; 
E T  = earl y ter mi nati o n; F S H = f ollicle-sti m ulati n g h or m o ne; P K = p har mac o ki netics; u P C R  = uri ne pr otei n -t o-
creati ni ne rati o. 
A.  S u bjects w h o disc o nti n ue treat me nt earl y s h o ul d c o m plete a n E T visit i m me diatel y f oll o wi n g disc o nti n uati o n ( b ut n o 
later t ha n 6 wee ks after disc o nti n uati o n of treat me nt) a n d a n e xit visit 6  wee ks after t he E T visit.  
B.  F oll o wi n g Visit  1 8 B ( Wee k  7 6) s u bjects s h o ul d c o nti n ue t o sc he d ule visits at 1 2 -wee k i nter vals ( ± 7  da ys) i n defi nitel y 
u ntil t he s u bject disc o nti n ues or t he pe gcetac o pla n de vel o p me nt pr o gra m is ter mi nate d.  
C.  Brief p h ysical e xa mi nati o ns s h o ul d be perf or me d at eac h visit, b ut s y m pt o m -dri ve n p h ysic al e xa mi nati o ns ma y als o 
be perf or me d at vari o us u nsc he d ule d ti me p oi nts, if dee me d necessar y  b y t he pri mar y i n vesti gat or.  E de ma s h o ul d be 
assesse d at e ver y visit. 
D.  E C Gs are t o be perf or me d bef ore d osi n g a n d bef ore bl o o d sa m pli n g pr oce d ures.  
E.  Bet wee n site visits, s u bjects will be i nstr ucte d t o re p ort a n y i njecti o n site reacti o n t o t he st u d y c o or di na t or. 
F.  O n cli nic d osi n g da ys, vital si g ns will be meas ure d wit hi n 2  h o urs pri or t o d osi n g, bef ore ve ni p u nct ure a n d E C G 
assess me nts.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 8 2 
 
C o nfi de nti al  
G.  Starti n g at Visit  1 6 a n d c o nti n ui n g t hr o u g h t he l o n g -ter m e xte nsi o n, u P C R sa m ples (first uri nar y o ut p ut f or t he da y) 
s h o ul d be c ollecte d o n 3 c o nsec uti ve da ys, e ver y 6 wee ks, u ntil t he s u bject e xits t he st u d y. At e ver y cli nic visit, t he 
s u bject s h o ul d be distri b ute d 6 c ollecti o n c o ntai ners. F or c ollecti o ns t hat ha p pe n bet wee n visits a c o urier ser vice will 
be arra n ge d f or uri ne sa m ple pic k u p a n d deli ver y t o t he site.  
H.  Bl o o d sa m ples will be t a ke n bef ore d osi n g.  
I. 
F oll o wi n g Visit  1 8 B ( W ee k  7 6) , A D A sa m ples will be c olle ct e d e ver y 6 m o nt hs (i e, at alt er nate visits). 
F or  s u bje cts wit h p ositi ve a nti– pe gceta c o pla n  pe pti de a nti b o d y i n l ast d ose sa m pl es, a d diti o nal sa m ples will be 
c oll ect e d 6 a n d 1 2  m o nt hs after t he l ast d ose f or f urt her assess m e nts.  
J. 
C K D -E PI creati ni ne e q uati o n (see htt ps:// w w w. ni d d k. ni h. g o v); t he C K D -E PI creat i ni ne-c ystati n C e q uati o n 
(if c o nfir matio n re q uire d).  
K.  Uri ne pre g na nc y test s h o ul d be c o m plete d f or w o me n of c hil d be ari n g p ot e ntial pri or t o d osi n g.  
1 5. 1. 2.  
P art B St u d y Desi g n a n d P r oce d ures  
F oll o wi n g Visit  1 6 ( Wee k  5 2), s u bjects w h o elect t o c o nti n ue i n Part B, t he l o n g -ter m e xte nsi o n, 
will ret ur n t o t he site at 1 2 -wee k i nter vals u ntil pe gcetac o pla n is c o m mer ciall y a vaila ble f or t he 
disease u n der st u d y. S pecific assess me nts f or Part B ar e liste d i n T a ble  7 . 
T he vacci nati o n hist or y f or eac h s u bject s h o ul d be r e vie we d pri or t o e ntr y i nt o t he l o n g -ter m 
e xte nsi o n, as descri be d i n Secti o n  9. 1. 4 , a n d a n y a d diti o nal r e q uir e d vacci nati o ns s h o ul d be 
a d mi nistere d acc or di n g t o t he c urre nt A CI P g ui deli nes.  
S u bjects w h o disc o nti n ue treat me nt earl y s h o ul d c o m plete a n earl y ter mi nati o n visit i m me diatel y 
f oll o wi n g disc o nti n uati o n ( b ut n o later t ha n 6  wee ks after dis c o nti n uati o n of tr eat me nt) a n d 
1 e xit visit 6 wee ks after t he earl y ter mi nati o n visit, as o utli ne d i n T a ble  7 .  
1 5. 1. 3.  
P art B D ose  R ati o n ale 
T he l o n g -ter m e xte nsi o n mai ntai ns t he sa me d ose f or Part A, w hic h is descri be d i n Secti o n  8. 2 . 
1 5. 1. 4.  
P art B St u d y Tre at me nts  
T his secti o n c o ntai ns st u d y tre at me nt i nf or mati o n f or Part B, t he l o n g -ter m e xte nsi o n.  
1 5. 1. 4. 1.  P art B I de ntit y of I n vesti g ati o n al P r o d uct  
T he test pr o d uct is pe gcetac o pla n, w hic h will be pr o vi de d as a sterile s ol uti o n of pe gcetac o pla n 
( 5 4 m g/ m L) i n a cetate-b uffere d s or bit ol, s u p plie d i n st o p pere d glass vials. A d diti o nal i nf or mati o n 
re gar di n g t he i n vesti gati o nal pr o d uct is pr o vi de d i n t he pe gcetac o pla n I B. 
1 5. 1. 4. 2.  P art B P e gcet ac o pl a n D osi n g  
D osi n g will re mai n t he sa me as Part A: s u bjects will c o nti n ue t o r ecei ve S C i nf usi o ns 
pe gcetac o pla n  at a d osa ge of 1 0 8 0 m g t wice wee kl y.  
D osi n g diaries will be utilize d f or pe gcetac o pla n  a n d are t o be c om plete d f or eac h d ose a d mi nistere d 
at t he st u d y site or o utsi de of re g ular cli nic visits. S u bjects s h o ul d i deall y mai ntai n a c o nsiste nt 
d osi n g sc he d ule a n d s h o ul d n ot dela y or defer d osi n g. Misse d d oses will be ha n dle d o n a 
case-b y -case basis bet wee n t he i n vesti gat or a n d me dical m o nit or, wit h t he ge neral a p pr oac h bei n g t o 
a d mi nister a misse d d ose as s o o n as n otice d, u nless t he ne xt d ose has alrea d y bee n a d mi nistere d.  
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 8 3 
 
C o nfi de nti al  
1 5. 1. 4. 3.  P art B P e g cet ac o pl a n A d mi nist r ati o n 
Pe gcetac o pla n will be a d mi nistere d as  a 2 0-m L S C i nf usi o n. T he pr ef err e d site of i nf usi o n will 
be t he a b d o me n; h o we ver, if a s u bject d oes n ot t oler ate a d mi nistr ati o n t o t he a b d o me n, 
alter nati ve sites ma y be c o nsi dere d.  
S u bjects ma y c h o ose t o c o nti n ue t o self -a d mi nister pe gcetac o pla n i nf usi o ns at t he st u d y site o n 
sc he d ule d d osi n g da ys w he n a st u d y visit c oi nci des, alt h o u g h t his is n ot r e q uir e d. 
Self -a d mi nistrati o n c o n d ucte d at t he st u d y site will be s u per vise d t o e ns ur e t hat t he s u bject 
c o nti n ues t o re mai n c o m plia nt wit h t he a d mi nistr ati o n g ui deli nes.  
1 5. 1. 5.  
P art B L a be li n g, P ac k a gi n g, St or a ge, a n d H a n dli n g 
1 5. 1. 5. 1.  P art B L a be li n g 
La bels c o ntai ni n g st u d y i nf or mati o n a n d pac k i de ntificati o n ar e a p plie d t o t he i n vesti gati o nal 
pr o d uct(s) c o ntai ner.  
All i n vesti gati o nal pr o d uct is la bele d wit h a mi ni m u m of t he f oll o wi n g: pr ot oc ol n u m ber, d osa ge 
f or m (i ncl u di n g pr o d uct na me a n d q ua ntit y i n pac k), r o ute of a d mi nistr ati o n, dir ecti o ns f or use, 
st ora ge c o n diti o ns, batc h n u m ber, pac ka gi n g r ef er e nce, t he state me nts, “ F or cli nical trial use 
o nl y, ” a n d/ or “ C A U TI O N: Ne w D r u g —Li mite d b y Fe der al ( or U S) La w t o I n vesti gati o nal Use, ” 
a n d na me a n d a d dress of t he s p o ns or.  
S pace is all ocate d o n t he la bel s o t hat t he site r e pr ese ntati ve ca n r ec or d a u ni q ue s u bject 
i de ntifier a n d date dis pe nse d b y t he site t o t he s u bject. 
A d diti o na l la bels ma y, o n a case- b y-case basis, be a p plie d t o t he i n vesti gati o nal pr o d uct i n or der 
t o satisf y nati o nal, l ocal, or i nstit uti o nal r e q uir e me nts, b ut t he y m ust n ot: 
•  C o ntra dict t he cli nical st u d y la bel  
•  O bsc ur e t he cli nical st u d y la bel 
•  I de ntify t he st u d y s u bject b y na me  
A d diti o nal  la bels ma y n ot be a d de d wit h o ut t he s p o ns or’s pri or f ull a gr ee me nt. 
1 5. 1. 5. 2.  P art B P ac k a gi n g  
I n vesti gati o nal pr o d uct is s u p plie d i n 2 0-m L glass v ials. Please r ef er t o t he p har mac y ma n ual 
f or details .  
C ha n ges t o s p o ns or -s u p plie d pac kagi n g pri or t o d osi n g ma y n ot occ ur wit h o ut f ull a gr ee me nt, 
i n a d va nce, b y t he s p o ns or.  
1 5. 1. 5. 3.  P art B I nf usi o n S u p plies  
T he s p o ns or will s u p pl y s yri n ges, vial a da pters, i nf usi o n sets, a n d a m b ulat or y s yri n ge i nf usi o n 
p u m ps, as re q uire d. Refer t o t he p har mac y ma n ual f o r f urt her details. 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 8 4 
 
C o nfi de nti al  
1 5. 1. 5. 4.  P art B St or a ge a n d H a n dli n g  
T he i n vesti gati o nal pr o d uct s h o ul d be st or e d r efri ger ate d at 2 - 8 ° C, b ot h at h ome a n d i n t he 
cli nic. T e m perat ure m o nit ori n g is re q uir e d at t he i n vesti gat or site ( or d oc u me nte d st or a ge 
l ocati o n) t o e ns ure t hat t he i n vesti gati o nal pr o d uct is mai ntai ne d wit hi n a n esta blis he d 
te m perat ure ra n ge.  
T he i n vesti gat or or a p pr o priatel y q ualifie d site staff will be r es p o nsi ble f or t he f oll o wi n g:  
•  e ns uri n g t hat t he i n vesti gati o nal pr o d uct is st or e d i n a sec ur e, li mite d -acces s l ocatio n 
at t he site 
− li mite d res p o nsi bilit y ma y be dele gate d t o t he p har mac y or me m ber of t he st u d y 
tea m, b ut t his dele gati o n m ust be d oc u me nte d 
•  e ns uri n g t hat t he te m perat ur e is m o nit or e d t hr o u g h o ut t he d ur ati o n of t he st u d y a n d 
t hat rec ords are mai ntai n e d 
A p har macist or a p pr o priatel y q ualifie d desi g nate d pers o n will be r es p o nsi ble f or t he f oll o wi n g:  
•  st ori n g t he i n vesti gati o nal pr o d uct a p pr o priatel y 
•  dis pe nsi n g t he vials of i n vesti gati o nal pr o d uct t o t he s u bject  
•  e nterin g t he u ni q ue s u bject i de ntifier o n t he i n vesti gati o nal pr o d uct b ottle/cart o n 
la bels as the y are distri b ute d  
W he n t he s u bject recei ves t he i n vesti gati o nal pr o d uct fr o m t he site, it s h o ul d be tr a ns p orte d i n a 
s p o ns or-a p pr o ve d bag or b o x, c o ntai ni n g pr e vi o usl y te m per at ur e -c o n ditio ne d c ol d plates t o 
e ns ure t hat t he st ora ge te m perat ure ( 2 - 8 ° C) is mai ntai ne d. T e m per at ur e m o nit ori n g will n ot be 
re q uire d d uri n g tra ns p ort or at t he s u bject’s r esi de nce, b ut a l o g will be ke pt f or e ver y i nf usi o n t o 
e ns ure t hat all i n vesti gati o nal pr o d uct  was ke pt r efri ger ate d.  
 
 
 
 
 
 

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 8 5  
 
C o nfi de nti al  
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 8 6 
 
C o nfi de nti al  
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 8 7  
 
C o nfi de nti al  
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 8 8 
 
C o nfi de nti al  
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 8 9 
 
C o nfi de nti al  
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 9 0 
 
C o nfi de nti al  
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 9 1 
 
C o nfi de nti al  
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 9 2 
 
C o nfi de nti al  
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 9 3 
 
C o nfi de nti al  
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 9 4 
 
C o nfi de nti al  
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 9 5  
 
C o nfi de nti al  
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 9 6 
 
C o nfi de nti al  
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 9 7  
 
C o nfi de nti al  
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 9 8 
 
C o nfi de nti al  
 
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 9 9 
 
C o nfi de nti al  
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 1 0 0 
 
C o nfi de nti al  
 
 
 
 
C CI

Pe gcet ac o pl a n  (A P L‑ 2 ) 
A P L 2 - C 3 G-2 0 4  Pr ot oc ol A me n d me nt 3 
0 3 Fe br uar y 2 0 2 2 
A pellis P har ma ce utic als, I nc  
Pa ge 1 0 1 
 
C o nfi de nti al  
 
 
 
 
C CI