A Phase 2, Randomized, Double-blind, Placebo-controlled, Dose-finding Study to Evaluate the Efficacy and Safety of ALXN2050 in Adult Participants With Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN)
Phase: PHASE2
Conditions: Lupus Nephritis, Immunoglobulin A Nephropathy, IgAN, LN
Sponsor: Alexion Pharmaceuticals, Inc.

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1 Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 of 1 5 2  
Ale xi o n C o nfi de ntial  
TI T L E P A G E  
Pr ot oc ol Title: A P has e  2, Ra n d o mize d, D o u ble- bli n d, Place b o-c o ntr olle d, D ose-fi n di n g St u d y 
t o E val uate t he Efficac y a n d Safet y of A L X N 2 0 5 0 i n A d ult Partici pa nts wit h Pr oliferati ve L u p us 
Ne p hritis ( L N) or I m m u n o gl o b uli n A Ne p hr o pat h y (I g A N) 
Ale xi o n Pr ot oc ol N u m ber:  A L X N 2 0 5 0 -N E P H - 2 0 1 
Astr a Ze nec a D C o de:  D 7 8 4 5 C 0 0 0 0 1 
A m e n d m e nt N u m ber:  3. 0 
C o m p o u n d:  A L X N 2 0 5 0  
St u d y P h ase:  2 
Brief Title:  P hase  2 St u d y of A L X N 2 0 5 0 i n Pr oliferati ve L u p us N e p hritis ( L N) or 
I m m u n o gl o b uli n A Ne p hr o pat h y (I g A N) 
S p o ns or N a m e:  Ale xi o n P har mace uticals, I nc.  
Le g al Re gistere d A d dress:  1 2 1 Sea p ort B o ule var d B ost o n, M A 0 2 2 1 0, U S A 
Re g ul at or y A ge nc y I de ntifier N u m ber(s)  
I N D: 1 5 3 0 6 8 
E u dr a C T:  2 0 2 1- 0 0 1 4 2 6- 2 2 
N C T:  N C T 0 5 0 9 7 9 8 9 
E U C T: 2 0 2 3- 5 0 4 8 2 5- 3 8 - 0 0 
Rele ase D ate:  2 1 Fe b  2 0 2 4 
S p o ns or Si g n at or y: 
 
Ale xi o n P har mace uticals, I n c.  
Date  
T he  d oc u me nt has b ee n e-si g ne d i n Vee v a. Please refer t o last pa ge f or si g nat ure details. 
Me dic al M o nit or C o nt a ct I nf or m ati o n c a n be f o u n d i n t he St u d y C o nt act List.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 2  of 1 5 2  
Ale xi o n C o nfi de ntial  
I N V E S TI G A T O R’ S A G R E E M E N T 
I h a ve r ea d t he st u d y pr ot oc ol a me n d me nt a n d a gree t o c o n d uct t he st u d y i n acc or d a nce wit h t his 
pr ot oc ol a me n d me nt, all a p plica ble g o ver n me nt re g ulati o ns, t he pri nci ples of t he I nter n ati o nal 
C o u ncil f or Har m o nisati o n of Tec h nical Re q uire me nts f or P har mace u ticals f or H u ma n Use 
(I C H) E 6 G ui deli ne f or G o o d Cli nical Practice ( G C P), a n d t he pri nci ples of t he W orl d Me dical 
Ass ociati o n Declarati o n of Helsi n ki. I als o a gree t o mai ntai n t he c o nfi de nti alit y of all 
i nf or mati o n recei ve d or d e vel o pe d i n c o n n ecti o n wit h t his pr ot oc ol a me n d me nt. 
 
 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Pri nte d Na me of I n v esti gat or  
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Si g nat ure of I n vesti gat or  
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Date  
 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 3  of 1 5 2  
Ale xi o n C o nfi de ntial  
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  
D ate  
A me n d me nt 2. 0  
3 1  Ma y  2 0 2 3  
A me n d me nt 1. 0  
1 7  Ma y  2 0 2 2  
Ori gi nal Pr ot oc ol  
0 3  J u n 2 0 2 1  
A m e n d m e nt 3. 0 ( 2 1  Fe b  2 0 2 4)  
T his a me n d me nt is c o nsi dere d t o be n o ns u bsta ntial  base d o n t he criteria set f ort h i n Article 1 0(a) 
of Directi ve 2 0 0 1/ 2 0/ E C of t he E ur o pea n Parlia me nt a n d t he C o u ncil of t he E ur o pea n U ni o n 
( E U) a n d i n t he E U Cli nical Trials Re g ulati o n ( C T R) 5 3 6/ 2 0 1 4 Article 2, 2 ( 1 3). 
O ver all R ati o n ale f or t he A m e n d m e nt:  
T he pri mar y r eas o n f or t his a me n d me nt is t o a d dress t he re q uire me nts f or tra nsiti o ni n g a cli nical 
st u d y u n der t he E U C T R. F urt her m o dificati o ns i ncl u de n o ns u bsta ntial c ha n ges, mi n or 
c orrecti o ns, a n d har m o ni ze d ter mi n ol o g y.  
Secti o n # a n d N a m e  
Descri pti o n of C h a n ge  
Brief R ati o n ale  
T hr o u g h o ut pr ot oc ol  
U p date d d oc u me nt date a n d versi o n.  
Ma de mi n or e dit orial a n d d oc u me nt 
f or matti n g re visi o ns i ncl u di n g c ha n ge i n 
secti o n n u m beri n g i n Secti o n 8. 
U p date d Gl o bal Dr u g Safet y ( G D S) t o 
Gl o bal Patie nt Safet y ( G P S).  
A d mi nistrati ve c ha n ges.  
F or clarit y.  
U p date d t he f or mat of t he a ut h or 
refere nce citati o n. 
T o ali g n wit h t he Ale xi o n St yle 
G ui de  
TI T L E P A G E a n d 
Secti o n  1. 1. S y n o psis  
C ha n ge d Astra Ze neca Pr ot oc ol N u m ber t o 
Astra Ze neca D C o de , a n d S h ort Title t o 
Brief Title . A d de d Re g ulat or y A ge nc y 
i de ntifier n u m bers i n t he s y n o psis. 
T o ali g n wit h E U C T R 
re q uire me nts. 
Secti o n 4. 4. E n d of St u d y 
Defi niti o n  
U p date d e n d of st u d y defi niti o n.  
T o ali g n wit h E U C T R 
re q uire me nts. 
Secti o n 6. 1. St u d y 
I nter ve nti o n(s) 
A d mi nistere d  
Re m o ve d “ NI M P” fr o m Ta ble  1 0.  
T o ali g n wit h E U C T R 
re q uire me nts. 
Secti o n 6. 4 St u d y 
I nter ve nti o n C o m plia nce 
A d de d “a n d i n t he e C R F”.  
A d mi nistrati ve c ha n ge t o c orrect 
err or i n P A 2. 0. 
Secti o n 6. 5. 3. All o we d 
C o nc o mita nt T hera p y 
(f or merl y: Bac k gr o u n d 
T hera pies)  
T hr o u g h o ut pr ot oc ol  
C ha n ge of ter mi n ol o g y: “ bac k gr o u n d 
t hera p y” t o “all o we d c o nc o mit a nt 
t her a p y”. 
T o ali g n wit h E U C T R 
re q uire me nts. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 4  of 1 5 2  
Ale xi o n C o nfi de ntial  
Secti o n # a n d N a m e  
Descri pti o n of C h a n ge  
Brief R ati o n ale  
Secti o n 6. 5. 4. A d diti o nal 
Sta n dar d of Care T hera p y 
(f or merl y: Resc ue T hera p y 
f or L N C o h ort) 
T hr o u g h o ut pr ot oc ol  
C ha n ge of ter mi n ol o g y: “resc ue t hera p y” t o 
“a d diti o n al st a n d ar d of c are t her a p y ”. 
T o ali g n wit h E U C T R 
re q uire me nts. 
Secti o n 6. 8. Treat me nt of 
O ver d ose (f or merl y: 
Secti o n  8. 4)  
Tra ns p ose d t he re p orti n g details f or a n 
e ve nt of o ver d ose or s us pecte d o ver d ose.  
T o ali g n wit h E U C T R 
re q uire me nts. 
Secti o n 8. 3. 4. Re g ulat or y 
Re p orti n g Re q uire me nts f or 
S A Es  
Descri be d re p orti n g re q uire me nts  
T o ali g n wit h E U C T R 
re q uire me nts. 
Secti o n 8. 3. 5. 1. Ti meli nes  
Delete d t he f oll o wi n g te xt: T he desi g nate d 
Ale xi o n re prese ntati ve w or ks wit h t he 
I n vesti gat or t o e ns ure t hat all rele va nt 
i nf or mati o n is c o m plete d wit hi n 1 (i nitial 
fatal/life t hreate ni n g or f oll o w-u p fatal/life 
t hreate ni n g) or 5 ( ot her seri o us i nitial a n d 
f oll o w u p) cale n dar da ys if t here is a n S A E 
ass ociate d wit h t he e ve nt of me dicati o n 
err or, dr u g a b use, or mis use a n d wit hi n 3 0 
da ys f or all ot her e ve nts.  
T o ali g n wit h t he c urre nt Ale xi o n 
pr ocesses.  
Secti o n 1 0. 1. 1. Re g ulat or y 
a n d Et hical C o nsi derati o ns 
A d de d details o n seri o us breac h (i ncl u di n g 
pers o nal data breac h) pre ve nti o n, 
i de ntificati o n, n otificati o n, a n d i m pact 
miti gati o n.  
T o ali g n wit h E U C T R 
re q uire me nts. 
Secti o n 1 0. 1. 5. Data 
Pr otecti o n  
U p date d a n d descri be d data pr otecti o n 
meas ures t o e ns ure patie nt i de ntit y re mai ns 
sec ure. 
T o ali g n wit h E U C T R 
re q uire me nts. 
Secti o n 1 0. 1. 7. Data Q ualit y 
Ass ura nce  
S pecifie d d oc u me nt rete nti o n peri o d at 
i n vesti gati ve site a n d at Ale xi o n. 
T o ali g n wit h E U C T R 
re q uire me nts. 
Secti o n 1 0. 4. Me dicati o n 
Err or, Dr u g A b use, a n d 
Dr u g Mis use  
U p date d te xt i n Me dicati o n Err or a n d a d de d 
refere nce t o Secti o n 6. 8 f or i nf or mati o n o n 
treat me nt of o ver d ose. 
T o ali g n wit h E U C T R 
re q uire me nts. 
A b bre viati o ns: C T R  =  Cli nical Trials Re g ulati o n; e C R F = el ectr o nic case re p ort f or m; E U  =  E ur o pea n U ni o n; 
L N  =  l u p us ne p hritis; NI M P = n o n-i n vesti gati o nal me dici nal pr o d uct; P A =  pr ot oc ol a me n d me nt  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1 Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 5 of 1 5 2  
Ale xi o n C o nfi de ntial  
T A B L E O F C O N T E N T S  
TI T L E P A G E  ................................................................................................................................... 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 
T A B L E O F C O N T E N T S  ................................................................................................................. 5 
LI S T O F T A B L E S  ......................................................................................................................... 1 2 
LI S T O F FI G U R E S  ....................................................................................................................... 1 3 
LI S T O F A B B R E VI A TI O N S  ........................................................................................................ 1 4 
1.  
P R O T O C O L S U M M A R Y  .......................................................................................... 1 8 
1. 1.  
S y n o psis ...................................................................................................................... 1 8  
1. 2.  
Sc he ma  ........................................................................................................................ 2 4 
1. 3.  
Sc he d ule of A cti vities  ................................................................................................. 2 5 
2.  
I N T R O D U C TI O N ...................................................................................................... 4 8 
2. 1.  
St u d y Rati o nale ........................................................................................................... 4 8  
2. 2.  
Bac k gr o u n d ................................................................................................................. 4 8  
2. 2. 1.  
L u p us Ne p hritis a n d I m m u n o gl o b uli n A Ne p hr o pat h y .............................................. 4 8  
2. 2. 2.  
A L X N 2 0 5 0  ................................................................................................................. 4 8 
2. 2. 3.  
Rati o nale f or E val u ati n g A L X N 2 0 5 0 i n Partici pa nts wit h L u p us Ne p hritis .............. 4 9  
2. 2. 4.  
Rati o nale f or E val u ati n g A L X N 2 0 5 0 i n Partici pa nts wit h I m m u n o gl o b uli n A 
Ne p hr o pat h y ............................................................................................................... 5 1  
2. 3.  
Be nefit/ Ris k Assess me nt  ............................................................................................ 5 2 
2. 3. 1.  
Ris k Assess me nt  ......................................................................................................... 5 2 
2. 3. 1. 1.  
C or o na vir us Disease 2 0 1 9 .......................................................................................... 5 3  
2. 3. 2.  
Be nefit Assess me nt  ..................................................................................................... 5 3 
2. 3. 3.  
O verall Be nefit: Ris k C o ncl usi o n  ............................................................................... 5 4 
3.  
O BJ E C TI V E S A N D E N D P OI N T S  ............................................................................ 5 5 
4.  
S T U D Y D E SI G N  ....................................................................................................... 5 8 
4. 1.  
O verall Desi g n  ............................................................................................................ 5 8 
4. 1. 1.  
Scree ni n g  .................................................................................................................... 5 8 
4. 1. 2.  
Bli n de d I nitial E val uati o n Peri o d  ............................................................................... 5 8 
4. 1. 3.  
Bli n de d E xte n de d Treat me nt Peri o d ........................................................................... 5 9  
4. 1. 4.  
O pe n -la bel E xt e nsi o n Peri o d ...................................................................................... 6 0 
4. 1. 5.  
Re m ote Visit O pti o ns i n Ti mes of E mer ge n c y  ........................................................... 6 0 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1 Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 6 of 1 5 2  
Ale xi o n C o nfi de ntial  
4. 2.  
Scie ntific Rati o nale f or St u d y Desi g n  ........................................................................ 6 1 
4. 2. 1.  
Rati o nale f or Pri mar y E n d p oi nt .................................................................................. 6 2  
4. 3.  
J ustificati o n f or D ose .................................................................................................. 6 3 
4. 4.  
Defi niti o n of St u d y Peri o ds a n d E n d of St u d y ........................................................... 6 3  
5.  
S T U D Y P O P U L A TI O N  ............................................................................................. 6 5 
5. 1.  
I n cl usi o n Criteria ........................................................................................................ 6 5 
5. 1. 1.  
I n cl usi o n Criteria f or B ot h C o h orts ............................................................................ 6 5 
5. 1. 2.  
I n cl usi o n Criteria S pecifi c f or L N C o h ort .................................................................. 6 5 
5. 1. 3.  
I n cl usi o n Criteria S pecifi c f or I g A N C o h ort .............................................................. 6 6 
5. 2.  
E xcl usi o n Criteria  ....................................................................................................... 6 6 
5. 2. 1.  
E xcl usi o n Criteria f or B ot h C o h orts ........................................................................... 6 6  
5. 2. 2.  
E xcl usi o n Criteria S pecific f or L N C o h ort ................................................................. 6 8  
5. 2. 3.  
E xcl usi o n Criteria S pecific f or I g A N C o h ort ............................................................. 6 9  
5. 3.  
Lifest yle C o nsi derati o ns ............................................................................................. 6 9  
5. 4.  
Scree n Fail ures  ............................................................................................................ 6 9 
6.  
S T U D Y I N T E R V E N TI O N  ........................................................................................ 7 0 
6. 1.  
St u d y I nter v e nti o n(s) A d mi nistere d ........................................................................... 7 0  
6. 1. 1.  
Bli n de d Treat me nt  ...................................................................................................... 7 1 
6. 1. 2.  
St u d y I nter v e nti o n(s) Pac ka gi n g a n d La beli n g ........................................................... 7 1  
6. 2.  
Pre parati o n/ Ha n dli n g/ St ora ge/ Acc o u nta bilit y ............................................................ 7 1  
6. 2. 1.  
Pre parati o n  .................................................................................................................. 7 1 
6. 2. 2.  
St ora ge a n d H a n dli n g ................................................................................................. 7 1  
6. 2. 3.  
Acc o u nta bilit y a n d Dis p osal ....................................................................................... 7 2  
6. 3.  
Meas ures t o Mi ni mize Bias: Ra n d o mizati o n a n d Bli n di n g  ........................................ 7 3 
6. 3. 1.  
Ra n d o mizati o n a n d Stratificati o n  ............................................................................... 7 3 
6. 3. 2.  
Bli n di n g ...................................................................................................................... 7 3  
6. 3. 3.  
U n bli n di n g .................................................................................................................. 7 3  
6. 4.  
St u d y I nter v e nti o n C o m plia nce .................................................................................. 7 4  
6. 5.  
Pri or a n d C o nc o mita nt T hera p y .................................................................................. 7 4  
6. 5. 1.  
All o we d Me dicati o ns a n d T hera p y ............................................................................. 7 5  
6. 5. 2.  
Disall o we d Me dicati o ns a n d T hera p y ........................................................................ 7 5  
6. 5. 3.  
All o we d C o nc o mita nt T hera p y ................................................................................... 7 6  
6. 5. 3. 1.  
All o we d C o nc o mita nt T hera p y f or L N C o h ort .......................................................... 7 6  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1 Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 7 of 1 5 2  
Ale xi o n C o nfi de ntial  
6. 5. 3. 2.  
All o we d C o nc o mita nt T hera p y f or I g A N C o h ort ....................................................... 7 9  
6. 5. 4.  
A d diti o nal Sta n dar d of Care T h era p y f or L N C o h ort ................................................. 7 9  
6. 5. 5.  
Vacci n ati o n a n d A nti bi otic Pr o p h yla xis ..................................................................... 8 0  
6. 6.  
D ose M o dificati o n ...................................................................................................... 8 0  
6. 7.  
I nter ve nti o n After t he E n d of t he St u d y ..................................................................... 8 1 
6. 8.  
Treat me nt of O v er d ose  ............................................................................................... 8 1 
7.  
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D 
P A R TI CI P A N T DI S C O N TI N U A TI O N/ WI T H D R A W A L  ....................................... 8 2 
7. 1.  
Disc o nti n uati o n of St u d y I nter ve nti o n........................................................................ 8 2  
7. 2.  
Partici pa nt Disc o nti n uati o n/ Wit h dra wal fr o m t he St u d y  ........................................... 8 3 
7. 3.  
L ost t o F oll o w- u p ....................................................................................................... 8 3  
8.  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  ...................................................... 8 5 
8. 1.  
Efficac y Assess me nts  ................................................................................................. 8 5 
8. 1. 1.  
2 4- H o ur Uri n e C ollecti o n f or Pr otei n uria ................................................................... 8 5  
8. 1. 1. 1.  
L N C o h ort ................................................................................................................... 8 5  
8. 1. 1. 2.  
I g A N C o h ort ............................................................................................................... 8 6 
8. 1. 2.  
S p ot Uri ne Sa m ple ( B ot h C o h orts) ............................................................................. 8 6  
8. 1. 3.  
Esti mate d Gl o mer ular Filtrati o n Rate ( B ot h C o h orts)  ................................................ 8 6 
8. 1. 4.  
He mat uria ( B ot h C o h orts) .......................................................................................... 8 7  
8. 1. 5.  
Al b u mi n ( L N C o h ort O nl y) ........................................................................................ 8 7  
8. 1. 6.  
Re nal Flar e ( L N C o h ort O nl y) .................................................................................... 8 7  
8. 1. 7.  
E xtrare n al S yste mic L u p us Er yt he mat os us Flare ( L N C o h ort O nl y) ......................... 8 8  
8. 1. 8.  
S u b o pti mal Res p o nse ( L N C o h ort O nl y) ................................................................... 8 9  
8. 1. 9.  
Treat me nt Fail ure ( L N C o h ort O nl y) ......................................................................... 8 9  
8. 1. 1 0.  
C o m plete a n d Partial Re nal Res p o nse ( L N C o h ort O nl y) .......................................... 8 9  
8. 1. 1 1.  
Partial Re missi o n (I g A N C o h ort O nl y) ...................................................................... 9 0  
8. 2.  
Safet y Assess me nts  ..................................................................................................... 9 0 
8. 2. 1.  
P h ysical E xa mi nati o ns ................................................................................................ 9 0  
8. 2. 2.  
Vital Si g ns  .................................................................................................................. 9 1 
8. 2. 3.  
Electr ocar di o gra ms  ..................................................................................................... 9 1 
8. 2. 4.  
Cli nical Safet y La b orat or y Assess me nts  .................................................................... 9 1 
8. 2. 4. 1.  
Vir us Ser ol o g y ............................................................................................................ 9 2  
8. 2. 4. 2.  
C he mistr y, He mat ol o g y a n d C oa g ulati o n ................................................................... 9 2  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1 Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 8 of 1 5 2  
Ale xi o n C o nfi de ntial  
8. 2. 4. 3.  
R o uti ne Uri nal ysis a n d Uri ne Se di me nt ..................................................................... 9 2  
8. 2. 4. 4.  
F ollicle Sti m ulati n g H or m o ne  .................................................................................... 9 2 
8. 2. 5.  
Pri or a n d C o nc o mita nt Me dicati o ns a n d Pr oce d ures .................................................. 9 2  
8. 2. 6.  
Pre g na nc y  ................................................................................................................... 9 3 
8. 2. 7.  
Partici pa nt Safet y Car d  ............................................................................................... 9 4 
8. 3.  
A d verse E v e nts a n d Seri o us A d verse E v e nts ............................................................. 9 4  
8. 3. 1.  
Ti me Peri o d a n d Fr e q ue n c y f or C ollecti n g A E a n d S A E I nf or mati o n ....................... 9 4  
8. 3. 2.  
Met h o d of Detecti n g A Es a n d S A Es .......................................................................... 9 4  
8. 3. 3.  
F oll o w- u p of A Es a n d S A Es ....................................................................................... 9 5  
8. 3. 4.  
Re g ulat or y Re p orti n g Re q uire me nts f or S A Es ........................................................... 9 5  
8. 3. 5.  
Me dicati o n Err or, Dr u g A b use, a n d Dr u g Mis use ...................................................... 9 5  
8. 3. 5. 1.  
Ti meli nes  .................................................................................................................... 9 5 
8. 3. 5. 2.  
Me dicati o n Err or ......................................................................................................... 9 6  
8. 3. 5. 3.  
Dr u g A b use ................................................................................................................. 9 6  
8. 3. 5. 4.  
Dr u g Mis use ................................................................................................................ 9 6  
8. 4.  
P har mac o ki netics  ........................................................................................................ 9 6 
8. 5.  
P har mac o d y na mics  ..................................................................................................... 9 6 
8. 6.  
Ge netics  ...................................................................................................................... 9 7 
8. 7.  
Bi o mar kers  .................................................................................................................. 9 7 
8. 7. 1.  
Bl o o d Bi o mar kers ....................................................................................................... 9 7  
8. 7. 2.  
Uri ne Bi o mar kers  ........................................................................................................ 9 7 
8. 7. 3.  
Ki d ne y Bi o ps y Bi o mar kers ......................................................................................... 9 7  
8. 7. 4.  
A d diti o nal Bi o mar ker Researc h  ................................................................................. 9 7 
8. 8.  
I m m u n o ge nicit y Assess me nts .................................................................................... 9 8 
8. 9.  
Healt h Ec o n o mics D ata a n d/ or Me dical Res o urce Utilizati o n  ................................... 9 8 
8. 1 0.  
Partici pa nt -re p orte d O utc o mes ................................................................................... 9 8 
8. 1 1.  
Ot her E x pl orat or y Assess me nts .................................................................................. 9 8  
8. 1 1. 1.  
A ut oa nti b o dies ( L N C o h ort O nl y) .............................................................................. 9 8  
8. 1 1. 2.  
S L E D AI – 2 K ( L N C o h ort O nl y) ................................................................................. 9 8  
8. 1 2.  
Ge ner al Assess me nts a n d Pr oce d ures  ......................................................................... 9 9 
8. 1 2. 1.  
I nf or me d C o nse nt ....................................................................................................... 9 9 
8. 1 2. 2.  
I n cl usi o n/ E xcl usi o n Criteria ....................................................................................... 9 9 
8. 1 2. 3.  
De m o gra p hics ............................................................................................................. 9 9  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1 Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 9 of 1 5 2  
Ale xi o n C o nfi de ntial  
8. 1 2. 4.  
Me dical Hist or y a n d L N a n d I g A N Hist or y ............................................................... 9 9  
8. 1 2. 5.  
Ki d ne y Bi o ps y ............................................................................................................ 9 9  
8. 1 2. 5. 1.  
Scree ni n g Ki d ne y Bi o ps y ........................................................................................... 9 9  
8. 1 2. 5. 2.  
Ki d ne y Bi o ps y D uri n g t he St u d y .............................................................................. 1 0 0  
8. 1 2. 5. 3.  
Ce ntral Pat h ol o g y La b or at or y ................................................................................... 1 0 0  
9.  
S T A TI S TI C A L C O N SI D E R A TI O N S  ..................................................................... 1 0 1 
9. 1.  
Statistical H y p ot heses  ............................................................................................... 1 0 1 
9. 2.  
Sa m ple Size Deter mi nati o n  ...................................................................................... 1 0 1 
9. 3.  
P o p ulati o ns f or A nal yses .......................................................................................... 1 0 2  
9. 4.  
Statistical A nal yses  ................................................................................................... 1 0 2 
9. 4. 1.  
E nr oll me nt a n d Dis p ositi o n ...................................................................................... 1 0 2  
9. 4. 2.  
De m o gra p hics, Bas eli ne C haracteristics, I ncl usi o n a n d E xcl usi o n Criteria, 
a n d Pr ot oc ol De viati o ns ............................................................................................ 1 0 3  
9. 4. 3.  
Me dical Hist or y  ........................................................................................................ 1 0 3 
9. 4. 4.  
Pri or a n d C o nc o mita nt Me dicati o ns ......................................................................... 1 0 3  
9. 4. 5.  
E xte nt of Dr u g E x p os ur e .......................................................................................... 1 0 3  
9. 4. 6.  
Efficac y A nal yses  ..................................................................................................... 1 0 3 
9. 4. 6. 1.  
A nal yses of Pri mar y Effi cac y E n d p oi nt ................................................................... 1 0 3  
9. 4. 6. 2.  
A nal yses of Sec o n d ar y Efficac y E n d p oi nt(s) ........................................................... 1 0 4  
9. 4. 6. 3.  
M ulti plicit y A dj ust me nt ............................................................................................ 1 0 5 
9. 4. 6. 4.  
A nal yses of E x pl or at or y E n d p oi nt(s) ....................................................................... 1 0 6  
9. 4. 7.  
Safet y A nal yses f or B ot h L N C o h ort a n d I g A N C o h ort ........................................... 1 0 6  
9. 4. 7. 1.  
A d verse E v e nts  ......................................................................................................... 1 0 6 
9. 4. 7. 2.  
P h ysical E xa mi nati o n a n d Vital Si g ns ...................................................................... 1 0 6  
9. 4. 7. 3.  
Cli nical La b orat or y Tests  ......................................................................................... 1 0 6 
9. 4. 7. 4.  
Electr ocar di o gra ms  ................................................................................................... 1 0 6 
9. 4. 8.  
P K/ P D A nal ysis f or B ot h L N C o h ort a n d I g A N C o h ort .......................................... 1 0 7  
9. 5.  
Pla n ne d A nal yses ...................................................................................................... 1 0 7  
9. 6.  
I nteri m A nal ysis ........................................................................................................ 1 0 7 
9. 7.  
Data M o nit ori n g C o m mittee  ..................................................................................... 1 0 8 
9. 8.  
Safet y Re vie w C o m mittee  ........................................................................................ 1 0 8 
1 0.  
S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S  ................................................................................................ 1 0 9 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1 Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 0  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 1.  
Re g ulat or y, Et hical, a n d St u d y O versi g ht C o nsi derati o ns ....................................... 1 0 9  
1 0. 1. 1.  
Re g ulat or y a n d Et hical C o nsi derati o ns .................................................................... 1 0 9  
1 0. 1. 2.  
Fi na ncial Discl os ur e  ................................................................................................. 1 1 0 
1 0. 1. 3.  
I nf or me d C o nse nt Pr ocess ........................................................................................ 1 1 0 
1 0. 1. 4.  
Recr uit me nt Strate g y  ................................................................................................ 1 1 1 
1 0. 1. 5.  
Data Pr otecti o n  ......................................................................................................... 1 1 1 
1 0. 1. 6.  
Disse mi nati o n of Cli nical St u d y Data  ...................................................................... 1 1 3 
1 0. 1. 7.  
Data Q ualit y Ass ur a nce  ............................................................................................ 1 1 3 
1 0. 1. 8.  
S o urce D oc u m e nts .................................................................................................... 1 1 4  
1 0. 1. 9.  
St u d y a n d Site Start a n d Cl os ure .............................................................................. 1 1 4  
1 0. 1. 1 0.  
P u blicati o n P olic y  ..................................................................................................... 1 1 5 
1 0. 1. 1 1.  
G o o d Cli nical Practice C o m plia nce .......................................................................... 1 1 6 
1 0. 2.  
Cli nical La b orat or y Tests  ......................................................................................... 1 1 7 
1 0. 3.  
A d verse E v e nts: Defi niti o ns a n d Pr oce d ures f or R ec or di n g, E val u ati n g, 
F oll o w- u p, a n d Re p orti n g ......................................................................................... 1 2 1  
1 0. 3. 1.  
Defi niti o n of A E ....................................................................................................... 1 2 1  
1 0. 3. 2.  
Defi niti o n of S A E ..................................................................................................... 1 2 2  
1 0. 3. 3.  
Rec or di n g a n d F oll o w- U p of A E a n d/ or S A E .......................................................... 1 2 3  
1 0. 3. 4.  
Re p orti n g of S A Es .................................................................................................... 1 2 5  
1 0. 3. 5.  
U ne x pect e d E ve nts ................................................................................................... 1 2 5  
1 0. 4.  
Me dicati o n Err or, Dr u g A b use, a n d Dr u g Mis use .................................................... 1 2 7  
1 0. 5.  
C o ntrace pti ve G ui da n ce a n d C ollecti o n of Pre g na nc y I nf or mati o n ......................... 1 2 9  
1 0. 5. 1.  
Defi niti o ns  ................................................................................................................ 1 2 9 
1 0. 5. 2.  
C o ntrace pti o n G ui da nce ........................................................................................... 1 2 9  
1 0. 5. 2. 1.  
G ui da nce f or Fe male Partici pa nts  ............................................................................. 1 3 0 
1 0. 5. 2. 2.  
G ui da nce f or Male Partici pa nts  ................................................................................ 1 3 1 
1 0. 5. 3.  
C ollecti o n of Pre g na nc y I nf or mati o n ....................................................................... 1 3 1  
1 0. 5. 3. 1.  
Male Partici pa nts wit h Part ners W h o B ec o me Pre g na nt  .......................................... 1 3 2 
1 0. 5. 3. 2.  
Fe male Partici pa nts W h o Bec o me Pre g na nt  ............................................................. 1 3 2 
1 0. 6.  
E x pl orat or y Bi o mar kers ............................................................................................ 1 3 4  
1 0. 7.  
S yste mic L u p us Er yt he mat os us Dia g n osis Classificati o n  ........................................ 1 3 5 
1 0. 8.  
Re vise d 2 0 1 8 I nter nati o n al S ociet y of Ne p hr ol o g y/ Re nal Pat h ol o g y S ociet y 
(I S N/ R P S) Classificati o n .......................................................................................... 1 3 6 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1 Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 1  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 9.  
I g A N Dia g n osis Classificati o n Criteria .................................................................... 1 3 7 
1 0. 1 0.  
Partici pa nt -re p orte d O utc o me I nstr u me nts ............................................................... 1 3 8 
1 0. 1 0. 1.  
E Q - 5 D- 5 L ( F or B ot h C o h orts) ................................................................................. 1 3 8 
1 0. 1 0. 2.  
S F - 3 6 ( F or B ot h C o h orts) ......................................................................................... 1 3 8 
1 0. 1 0. 3.  
F A CI T - F A TI G U E ( F or L N C o h ort O nl y) ................................................................ 1 3 8 
1 0. 1 1.  
C O VI D - 1 9 Ris k Assess me nt .................................................................................... 1 3 9 
1 0. 1 2.  
C O VI D -1 9 V acci n e Ris k Assess me nt  ...................................................................... 1 4 1 
1 0. 1 3.  
Re m ote S o urce Dat a Verificati o n D uri n g C O VI D - 1 9 Pa n de mic ............................. 1 4 2 
1 0. 1 4.  
Ma na ge me nt of Sei z ures  ........................................................................................... 1 4 3 
1 0. 1 5.  
Selecte d Me dicati o ns K n o w n t o L o wer t he Seiz ure T hres h ol d a n d/ or Ca us e 
Seiz ure  ...................................................................................................................... 1 4 5 
1 0. 1 6.  
List of I n hi bit ors, I n d ucers a n d S u bstrates of C Y P 3 A ............................................. 1 4 6  
1 0. 1 7.  
Pr ot oc ol A me n d me nt Hist or y ................................................................................... 1 4 7  
1 1.  
R E F E R E N C E S  ......................................................................................................... 1 4 8 
 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1 Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 2  of 1 5 2  
Ale xi o n C o nfi de ntial  
LI S T O F T A B L E S  
Ta ble  1: 
Sc he d ule of A cti vities D uri n g Scree ni n g a n d t h e Bli n de d I nitial E val uati o n 
Peri o d: Scree ni n g t o Wee k  2 6 Visit ( L N C o h ort) ...................................................... 2 6 
Ta ble  2: 
Sc he d ule of A cti vities D uri n g Scree ni n g a n d t h e Bli n de d I nitial E val uati o n 
Peri o d: Scree ni n g t o Wee k  2 6 Visit (I g A N C o h ort) ................................................... 3 2 
Ta ble  3: 
Sc he d ule of A cti vities D uri n g t he Bli n de d E xte n de d Treat me nt Peri o d: 
Wee k  3 4 t o Wee k 5 0 Visits ( L N C o h ort) ................................................................... 3 7 
Ta ble  4: 
Sc he d ule of A cti vities D uri n g t he Bli n de d E xte n de d Treat me nt Peri o d: 
Wee k  2 8 t o Wee k 5 0 Visits (I g A N C o h ort) ............................................................... 4 1 
Ta ble  5: 
Sc he d ule of A cti vities D uri n g t he O pe n-la b el E xte nsi o n Peri o d a n d Safet y 
F oll o w- u p Peri o d ( B ot h L N a n d I g A N C o h orts) ........................................................ 4 4  
Ta ble 6:  
P ote ntial Ris ks a n d Miti gati o n Strate gies  ................................................................... 5 2 
Ta ble  7: 
Ma p pi n g O bjecti ves t o E n d p oi nts .............................................................................. 5 5  
Ta ble  8: 
S u m mar y of Partici pa nts i n Eac h Treat me nt Gr o u p D uri n g t he Bli n de d 
I nitial E val uati o n Peri o d ............................................................................................. 5 9 
Ta ble  9: 
Scie ntific Rati o nale f or t he Desi g n of St u d y A L X N 2 0 5 0- N E P H - 2 0 1 ....................... 6 1 
Ta ble  1 0: St u d y I nter v e nti o ns ..................................................................................................... 7 0  
Ta ble  1 1: Bli n de d St u d y I nter ve nti o n fr o m Wee k 1 t o Wee k  5 0 i n A d diti o n t o All o we d 
C o nc o mita nt T hera p y ................................................................................................. 7 1  
Ta ble  1 2: C ortic oster oi d Ta per f or Partici pa nts wit h L u p us Ne p hritis ....................................... 7 8  
Ta ble  1 3: Pr ot oc ol-re q uire d L a b or at or y Assess me nts .............................................................. 1 1 7  
Ta ble  1 4: P ote ntial Ris ks a n d Miti gati o n Meas ures d u e t o C O VI D - 1 9 ................................... 1 3 9 
Ta ble  1 5: P ote ntial Ris ks a n d Miti gati o n Meas ures d u e t o C O VI D 1 9 V acci n e....................... 1 4 1  
Ta ble  1 6: List of Pr o hi bite d I n d ucers, I n hi bit ors a n d S u bstrates of C Y P 3 A............................ 1 4 6  
 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1 Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 3  of 1 5 2  
Ale xi o n C o nfi de ntial  
LI S T O F FI G U R E S  
Fi g ure 1:  
St u d y Desi g n Sc he matic ( L N C o h ort) ........................................................................ 2 4  
Fi g ure 2:  
St u d y Desi g n Sc he matic (I g A N C o h ort) .................................................................... 2 5  
Fi g ure 3:  
C o m ple me nt Pat h wa ys ............................................................................................... 4 9  
 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 4  of 1 5 2  
Ale xi o n C o nfi de ntial  
LI S T O F A B B R E VI A TI O N S  
T he f oll o wi n g a b bre vi ati o ns a n d ter ms are use d i n t his st u d y pr ot oc ol.  
A b bre vi ati o n or Ter m  
E x pl a n ati o n  
A C Ei  
a n gi ote nsi n -c o n verti n g e nz y me i n hi bit or  
A C R  
A merica n C olle ge of R he u mat ol o g y  
A E  
a d verse e ve nt  
A N C O V A  
a nal ysis of c o varia nce 
a nti-ds D N A  
a nti-d o u ble -stra n de d D N A 
a nti-H Bc  
he patitis B c ore a nti b o d y  
a nti-H Bs  
he patitis B s urface a nti b o d y  
A R B  
a n gi ote nsi n II rece pt or bl oc ker  
A P  
alter nati ve pat h wa y 
A U C  
area u n der t he c o nce ntrati o n -ti me c ur ve 
A U C 0 -2 4  
area u n der t he c o nce ntrati o n -ti me c ur ve fr o m ti me zer o t o 2 4 h o urs  
A x M P  
a u xiliar y me dici nal pr o d uct  
B b  
B b fra g me nt of c o m ple me nt fact or B  
bi d  
t wice dail y 
C 1 q  
c o m ple me nt c o m p o ne nt C 1 q  
C 3  
c o m ple me nt c o m p o ne nt 3  
C 3a  
c o m ple me nt c o m p o ne nt 3a 
C 4  
c o m ple me nt c o m p o ne nt 4  
C 5  
c o m ple me nt c o m p o ne nt 5  
C 5a  
c o m ple me nt c o m p o ne nt 5a  
C 5 b -9  
ter mi nal c o m ple me nt c o m ple x  
CI  
c o nfi de nce i nter val  
CI O M S  
C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical Scie nces  
C K D  
c hr o nic ki d ne y disease  
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 ma x  
ma xi m u m ( pea k) plas ma c o nce ntrati o n o bser ve d after dr u g 
a d mi nistrati o n  
C NI  
calci ne uri n i n hi bit or 
C O VI D -1 9  
c or o na vir us disease 2 0 1 9  
C P  
classical pat h wa y 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 5  of 1 5 2  
Ale xi o n C o nfi de ntial  
A b bre vi ati o n or Ter m  
E x pl a n ati o n  
C R R  
c o m plete re nal res p o nse  
C S R  
cli nical st u d y re p ort 
C T R  
Cli nical Trials Re g ulati o n  
C Y P 3 A  
c yt oc hr o me P 4 5 0, fa mil y 3, s u bfa mil y A  
D M C  
Data M o nit ori n g C o m mittee  
E C G  
electr ocar di o gra m 
e C R F 
electr o nic case re p ort f or m  
E D  
earl y disc o nti n uati o n  
E D C  
electr o nic data ca pt ure  
E E G  
electr oe nce p hal o gra m  
e G F R  
esti mate d gl o mer ular filtrati o n rate  
E Q -5 D -5 L  
E ur o pea n Q ualit y of Life Healt h 5 -ite m q uesti o n naire di me nsi o ns 5 le vel  
E S R D  
e n d-sta ge re nal disease  
E U L A R  
E ur o pea n Lea g ue A gai nst R he u matis m  
F A CI T  
F u ncti o nal Assess me nt of C hr o nic Ill ness T hera p y  
F A S  
F ull A nal ysis Set  
F B  
c o m ple me nt fact or B 
F D  
c o m ple me nt fact or D 
F H  
c o m ple me nt fact or H 
F S H  
f ollicle sti m ulati n g h or m o ne  
G C P  
G o o d Cli nical Practice  
G P S  
Gl o bal Patie nt Safet y  
G M R  
ge o metric mea n rati o  
H Bs A g  
he patitis B s urface a nti ge n  
H C V  
he patitis C vir us  
HI V  
h u ma n i m m u n o deficie nc y vir us  
h pf  
hi g h -p o wer fiel d  
H R T  
h or m o ne re place me nt t hera p y  
I B 
I n vesti gat or’s br oc h ure 
I C  
i m m u ne c o m ple x  
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 of Tec h nical Re q uire me nts f or 
P har mace uticals f or H u ma n Use  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 6  of 1 5 2  
Ale xi o n C o nfi de ntial  
A b bre vi ati o n or Ter m  
E x pl a n ati o n  
I E C  
I n de pe n de nt Et hics C o m mittee  
I g A 
i m m u n o gl o b uli n A 
I g A 1  
i m m u n o gl o b uli n A 1  
I g A N  
i m m u n o gl o b uli n A ne p hr o pat h y  
I g G 
i m m u n o gl o b uli n G 
I R B  
I nstit uti o nal Re vie w B oar d  
I R T 
i nteracti ve res p o nse tec h n ol o g y 
I S N/ R P S 
I nter nati o nal S ociet y of Ne p hr ol o g y/ Re nal Pat h ol o g y S ociet y 
I V  
i ntra ve n o us(l y)  
L N  
l u p us ne p hritis  
L P  
lecti n pat h wa y 
K DI G O  
Ki d ne y Disease I m pr o vi n g Gl o bal O utc o mes  
M A C  
me m bra ne attac k c o m ple x  
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
M M F  
m yc o p he n olate m ofetil  
M M R M  
mi xe d -effect m o del f or re peate d meas ures  
M P S  
m yc o p he n olic aci d s o di u m  
N K F  
Nati o nal Ki d ne y F o u n dati o n  
N O A E L  
n o o bser ve d a d verse effect le vel 
O L E  
O pe n -la bel E xte nsi o n 
P D  
p har mac o d y na mic(s)  
P K  
p har mac o ki netic(s)  
P R R  
partial re nal res p o nse  
Q o L  
q ualit y of life  
Q T  
i nter val bet wee n t he start of t he Q wa ve a n d t he e n d of t he T wa ve i n a n 
E C G  
Q Tc  
c orrecte d Q T i nter val  
Q Tc F  
Q T i nter val c orrecte d usi n g Fri dericia’s f or m ula  
R A S  
re ni n-a n gi ote nsi n s yste m  
R B C  
re d bl o o d cell  
r S D V 
re m ote s o urce data verificati o n  
R T S M  
Ra n d o mizati o n a n d Trial S u p pl y Ma na ge me nt  
s C 5 b-9  
s ol u ble C 5 b-9  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 7  of 1 5 2  
Ale xi o n C o nfi de ntial  
A b bre vi ati o n or Ter m  
E x pl a n ati o n  
S A E  
seri o us a d verse e ve nt  
S A P  
statistical a nal ysis pla n  
S D  
sta n dar d de viati o n  
S D V  
s o urce data verificati o n 
S F -3 6  
S h ort F or m ( 3 6) Healt h S ur ve y  
S G L T -2  
s o di u m-gl uc ose c otra ns p orter -2  
S L E  
s yste mic l u p us er yt he mat os us  
S L E D AI – 2 K  
S yste mic L u p us Er yt he mat os us Disease Acti vit y I n de x 2 0 0 0 Safet y of 
Estr o ge ns i n L u p us Er yt he mat os us Nati o nal Assess me nt ( S E L E N A) 
M o dificati o n  
S o A  
Sc he d ule of Acti vities  
S O C  
S yste m Or ga n Class  
S U S A R  
s us pecte d u ne x pecte d seri o us a d verse reacti o n  
T E A E  
treat me nt-e mer ge nt a d verse e ve nt  
T E S A E  
treat me nt-e mer ge nt seri o us a d verse e ve nt  
U A C R  
uri ne al b u mi n t o creati ni ne rati o  
U P C R  
uri ne pr otei n t o creati ni ne rati o  
U L N  
u p per li mit of n or mal  
W O C B P  
w o me n of c hil d beari n g p ote ntial  
 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1 Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 8  of 1 5 2  
Ale xi o n C o nfi de ntial  
1.  
P R O T O C O L S U M M A R Y  
1. 1.  
S y n o psis  
Pr ot oc ol Title:  A P has e  2, Ra n d o mize d, D o u ble- bli n d, Place b o-c o ntr olle d, D ose-fi n di n g St u d y 
t o E val uate t he Efficac y a n d Safet y of A L X N 2 0 5 0 i n A d ult Partici pa nts wit h Pr oliferati ve L u p us 
Ne p hritis ( L N) or I m m u n o gl o b uli n A Ne p hr o pat h y (I g A N) 
Brief Title:  P hase  2 St u d y of A L X N 2 0 5 0 i n Pr oliferati ve L u p us N e p hritis ( L N) or 
I m m u n o gl o b uli n A Ne p hr o pat h y (I g A N) 
Re g ul at or y A ge nc y I de ntifier N u m ber(s)  
I N D: 1 5 3 0 6 8 
E u dr a C T:  2 0 2 1- 0 0 1 4 2 6- 2 2 
N C T:  N C T 0 5 0 9 7 9 8 9 
E U C T: 2 0 2 3- 5 0 4 8 2 5- 3 8 - 0 0 
R ati o n ale:  A L X N 2 0 5 0 is a p ote nt, re versi ble, oral s mall m olec ule i n hi bit or of c o m ple me nt 
fact or D ( F D), w hic h is a n esse ntial c o m p o ne nt of t he c o m ple me nt alter n ati ve pat h wa y ( A P). 
T he c o m ple me nt s yste m is i n v ol ve d i n t he pat h o p h ysi ol o g y of pr oliferati ve L N a n d 
i m m u n o gl o b uli n A ne p hr o pat h y (I g A N). T he o bjecti ves of t his st u d y are t o e val uate t he efficac y 
a n d safet y of oral A L X N 2 0 5 0 c o m pare d t o place b o, de m o nstrate pr o of of c o nce pt f or efficac y of 
F D i n hi biti o n, a n d esta blis h a d ose i n patie nts wit h L N or I g A N.  
O bjecti ves a n d E n d p oi nts  
O bjecti ves  
E n d p oi nts  
Pri m ar y ( B ot h C o h orts)  
T o e val uate t he efficac y of A L X N 2 0 5 0 t o 
re d uce pr otei n uria i n partici pa nts wit h L N or 
I g A N 
Perce nta ge c ha n ge i n pr otei n uria fr o m baseli ne t o 
Wee k  2 6 ( base d o n 2 4-h o ur uri ne c ollecti o n[s])  
Sec o n d ar y ( B ot h C o h orts)  
T o e val uate t he efficac y of A L X N 2 0 5 0 t o 
i m pr o ve meas ures of ki d ne y f u ncti o n i n 
partici pa nts wit h L N or I g A N  
Perce nta ge c ha n ge i n pr otei n uria fr o m baseli ne t o 
Wee k  5 0 ( base d o n 2 4-h o ur uri ne c ollecti o n[s])  
Ac hie vi n g > 3 0 % a n d > 5 0 %  re d ucti o n i n pr otei n uria 
at Wee k 2 6 a n d Wee k  5 0 c o m pare d t o baseli ne ( base d 
o n 2 4- h o ur uri ne c ollecti o n[s] at eac h ti me p oi nt)  
C ha n ge fr o m baseli ne i n e G F R at Wee k  2 6 a n d 
Wee k  5 0 
Sec o n d ar y ( L N C o h ort O nl y)  
T o e val uate t he efficac y of A L X N 2 0 5 0 o n 
meas ures of ki d ne y f u ncti o n i n partici pa nts 
wit h L N  
Meeti n g t he criteria f or  C R R at Wee k  2 6 a n d Wee k  5 0 
(as defi ne d i n Secti o n 8. 1. 1 0 ) 
Meeti n g t he criteria f or  P R R at Wee k  2 6 a n d Wee k  5 0 
(as defi ne d i n Secti o n 8. 1. 1 0 ) 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1 Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 9  of 1 5 2  
Ale xi o n C o nfi de ntial  
O bjecti ves  
E n d p oi nts  
Ti me t o t he first occ urre nce of U P C R ≤ 0. 5  g/ g as 
meas ure d b y s p ot uri ne sa m ple  
Ac hie vi n g c ortic oster oi d ta per t o 7. 5  m g/ da y at 
Wee ks  1 2, 2 6, a n d 5 0 
E x perie nce of a Re nal Flare (as defi ne d i n 
Secti o n  8. 1. 6 ) t hr o u g h Wee k 5 0 
E x perie nce of a n E xtrare nal S L E Flare (as defi ne d i n 
Secti o n  8. 1. 7 ) t hr o u g h Wee k 5 0 
Meeti n g t he criteria f or Treat me nt Fail ure (as defi ne d 
i n Secti o n 8. 1. 9 ) t hr o u g h Wee k 5 0 
Meeti n g t he criteria f or S u b o pti mal Res p o nse t hr o u g h 
Wee k  5 0 
A bs ol ute val ues a n d c ha n ge fr o m baseli ne i n ser u m 
al b u mi n at Wee k  2 6 a n d Wee k  5 0 
Sec o n d ar y (I g A N C o h ort O nl y)  
T o e val uate t he efficac y of A L X N 2 0 5 0 o n 
meas ures of ki d ne y f u ncti o n i n partici pa nts 
wit h I g A N  
Meeti n g t he criteria f or  Partial Re missi o n at Wee k  2 6 
a n d Wee k 5 0 (as defi ne d i n Secti o n 8. 1. 1 1 ) 
P K/ P D ( B ot h C o h orts)  
T o c haracterize t he P K a n d P D of A L X N 2 0 5 0 
i n partici pa nts wit h L N or I g A N 
O bser ve d plas ma c o nce ntrati o ns of A L X N 2 0 5 0 o ver 
ti me 
A bs ol ute val ues a n d c ha n ge fr o m baseli ne i n plas ma 
B b c o nce ntrati o n a n d ser u m A P acti vit y o ver ti me 
S afet y ( B ot h C o h orts) 
T o c haracterize t he safet y a n d t olera bilit y of 
A L X N 2 0 5 0 i n partici pa nts wit h L N or I g A N 
I nci de nce of T E A Es a n d T E S A Es o ver ti me 
C ha n ges fr o m baseli ne i n la b orat or y assess me nts  
E x pl or at or y ( B ot h C o h orts)  
T o assess t he efficac y of A L X N 2 0 5 0 i n 
e x pl orat or y efficac y e n d p oi nts  
Perce nta ge c ha n ge i n pr otei n uria fr o m baseli ne t o 
Wee k  1 0 2 a n d Wee k 1 5 4 ( base d o n 2 4- h o ur uri ne 
c ollecti o n[s]) 
C ha n ge fr o m baseli ne i n e G F R at Wee k  1 0 2 a n d 
Wee k  1 5 4 
T o e val uate t he efficac y of A L X N 2 0 5 0 o n 
he mat uria i n partici pa nts wit h L N or I g A N  
Effect o n he mat uria as meas ure d b y  
•  
A bs ol ute val ue a n d c ha n ge fr o m baseli ne i n 
R B C i n uri ne fr o m baseli ne t o Wee k  2 6 a n d 
Wee k  5 0 
•  
Ac hie vi n g < 1 0 R B C/ h pf  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 2 0  of 1 5 2  
Ale xi o n C o nfi de ntial  
O bjecti ves  
E n d p oi nts  
T o assess q ualit y of life base d o n 
partici pa nt -re p orte d o utc o mes i n partici pa nts 
wit h L N or I g A N base d o n treat me nt wit h 
A L X N 2 0 5 0  
C ha n ge fr o m baseli ne i n S F -3 6 at Wee k  2 6 a n d 
Wee k  5 0  
C ha n ge fr o m baseli ne i n E Q -5 D -5 L at Wee k  2 6 a n d 
Wee k  5 0  
T o e val uate bi o mar kers s uc h as c o m ple me nt, 
a ut oi m m u ne, a n d re nal i n partici pa nts wit h 
L N or I g A N  
A bs ol ute val ues a n d c ha n ge fr o m baseli ne i n le vels of 
bi o mar kers i n bl o o d a n d uri ne o ver ti me  
E x pl or at or y ( L N C o h ort O nl y)  
T o assess t he efficac y of A L X N 2 0 5 0 i n 
e x pl orat or y efficac y e n d p oi nts  
Ti me t o t he first C R R or P R R ( usi n g s p ot U P C R)  
Meeti n g t he criteria f or O verall Re nal Res p o nse ( C R R 
or P R R) at Wee k  2 6 a n d Wee k  5 0  
Ti me t o t he first occ urre nce of U P C R  >  5 0 % decrease 
fr o m baseli ne ( usi n g s p ot U P C R) 
T o assess q ualit y of life base d o n 
partici pa nt -re p orte d o utc o mes 
C ha n ge fr o m baseli ne i n F A CI T -Fati g ue t otal sc ore at 
Wee k  2 6 a n d Wee k  5 0  
T o assess t he efficac y of A L X N 2 0 5 0 i n ot her 
e x pl orat or y e n d p oi nts 
Hist ol o g y c ha n ges fr o m baseli ne t o Wee k  5 0, if tiss ue 
is a vaila ble 
A bs ol ute val ues a n d c ha n ge fr o m baseli ne i n a nti -
ds D N A a n d a nti -C 1 q a nti b o dies at Wee k  2 6 a n d 
Wee k  5 0  
E x pl or at or y (I g A N C o h ort O nl y)  
T o assess t he efficac y of A L X N 2 0 5 0 i n 
e x pl orat or y efficac y e n d p oi nts  
Sl o pe of e G F R c o m p ute d fr o m baseli ne t o Wee k  2 6 
a n d Wee k 5 0  
A b bre viati o ns: A P  =  alter nati ve pat h wa y; a nti -C 1 q  =  a nti-C 1 q c o m ple me nt c o m p o ne nt  ; 
a nti-ds D N A  =  a nti-d o u ble -stra n de d D N A; B b =  B b fra g me nt of c o m ple me nt fact or  B; C R R  =  c o m plete re nal 
res p o nse; e G F R =  esti mate d gl o mer ular filtrati o n rate; E Q -5 D -5 L  =  E ur o pea n Q ualit y of Life Healt h 5 -ite m 
q uesti o n naire di me nsi o ns 5  le vel; F A CI T =  F u ncti o nal Assess me nt of C hr o nic Ill ness T hera p y; h pf  =  hi g h -p o wer 
fiel d; I g A N =  i m m u n o gl o b uli n A ne p hr o pat h y; L N =  l u p us ne p hritis; P D =  p har mac o d y na mic(s); 
P K  =  p har mac o ki netic(s); P R R = partial re nal res p o nse; R B C  =  re d bl o o d cell; S L E =  s yste mic l u p us 
er yt he mat os us; T E A E  =  treat me nt-e mer ge nt a d verse e ve nt; T E S A E  =  treat me nt-e mer ge nt seri o us a d verse e ve nt; 
S F -3 6  =  S h ort  F or m  ( 3 6) Healt h S ur ve y; U P C R =  uri ne pr otei n t o creati ni ne rati o  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1 Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 2 1  of 1 5 2  
Ale xi o n C o nfi de ntial  
O ver all Desi g n  
T his is a P hase  2, ra n d o mize d, d o u ble- bli n d, place b o-c o ntr olle d, m ultice nt er st u d y of 
A L X N 2 0 5 0 i n a d diti o n t o all o we d c o nc o mita nt t h era p y c o nsiste nt wit h t he sta n dar d of care i n 
a d ult partici pa nts ( ≥ 1 8 t o ≤ 7 5 years of a ge) wit h eit her L N or I g A N. 
•  Partici pa nts i n t he L N c o h ort m ust ha ve a dia g n osis of L N wit h a n acti ve flare bas e d 
o n ki d ne y bi o ps y , esti mate d gl o mer ular filtrati o n rate (e G F R) > 3 0 m L/ mi n/ 1. 7 3  m2, 
a n d pr otei n uria ( d efi ne d as uri ne pr otei n t o creati ni ne rati o [ U P C R] ≥ 1 g/ g fr o m o ne 
2 4- h o ur uri ne c ollecti o n). 
•  Partici pa nts i n t he I g A N c o h ort m ust ha ve a dia g n osis of I g A N base d o n ki d ne y 
bi o ps y, e G F R > 3 0 m L/ mi n/ 1. 7 3 m 2, a n d pr otei n uria defi ne d as mea n 
pr otei n ≥ 1 g/ 2 4 h o urs fr o m 2 vali d 2 4- h o ur uri ne c ollecti o ns ( Secti o n 8. 1. 1 ). 
Partici pa nts m ust ha ve bee n treate d wit h sta ble d oses of t he ma xi m u m t olerate d 
re ni n-a n gi ote nsi n s yste m ( R A S)-i n hi biti n g me dicati o ns a n d ha ve c o ntr olle d, sta ble 
bl o o d press ure ( < 1 4 0/ 9 0 m m H g) f or  ≥ 3 m o nt hs pri or t o Scree ni n g. 
All partici pa nts will c o nti n ue t o recei v e all o we d c o nc o mita nt t hera p y c o nsiste nt wit h t he 
sta n dar d of car e f or p artici pa nts wit h L N a n d I g A N t hr o u g h o ut t he st u d y. Partici pa nts i n t he L N 
c o h ort will recei ve a d diti o nal sta n dar d of care t hera p y i n t he e ve nt of a pr ot oc ol- defi ne d Re n al 
Flare or se vere E xtr are n al s yste mic l u p us er yt he mat os us ( S L E) Flare a n d after Wee k  2 6, f or 
S u b o pti mal Res p o nse. A p pr o ve d n o vel treat me nts f or L N ca n be use d p er t he I n vesti gat or’s 
discreti o n. H o we v er, if a d diti o nal sta n dar d of care t hera p y is i nitiate d, t he I n vesti gat or s h o ul d 
c o ns ult t he list of disall o we d me dicati o ns ( Secti o n  6. 5. 2 ). If a d diti o nal sta n dar d of care t h era p y is 
a pr o hi bite d me dicati o n, st u d y i nter ve nti o n s h o ul d be disc o nti n ue d at least 3 da ys pri or t o 
i nitiati o n of t he a d diti o nal sta n dar d of care t h era p y. 
Bli n de d I niti al E v al u ati o n Peri o d  
•  F or eac h disease c o h ort, partici pa nts will be ra n d o ml y assi g ne d i n a 3: 1: 3 rati o o n 
Da y  1 t o recei ve A L X N 2 0 5 0 1 8 0 m g t wice dail y ( bi d), A L X N 2 0 5 0 1 2 0 m g bi d, or 
place b o bi d t hr o u g h o ut t he Bli n de d I nitial E val u ati o n Peri o d ( 2 6 wee ks).  
•  F or t he I g A N c o h ort, partici pa nts assi g ne d t o t he place b o gr o u p o n Da y 1 will als o be 
assi g ne d t o t heir st u d y treat me nt f or t he Bli n de d E xte n de d Treat me nt Peri o d 
( A L X N 2 0 5 0 1 8 0 m g bi d or A L X N 2 0 5 0 1 2 0 m g bi d) i n a 1: 1 all ocati o n rati o at t he 
ti me of ra n d o mizati o n. 
Bli n de d E xte n de d Tre at m e nt Peri o d  
After c o m pleti o n of t he Bli n de d I nitial E val uati o n Peri o d ( Wee k  2 6), partici pa nts will c o nti n ue 
t o recei ve st u d y i nter v e nti o n d uri n g a Bli n de d E xte n de d Treat me nt Peri o d f or 2 4 wee ks as 
f oll o ws: 
•  Partici pa nts i n t he L N c o h ort will c o nti n ue t o recei ve t heir ra n d o mize d all ocati o n of 
st u d y i nter ve nti o n ( A L X N 2 0 5 0 1 8 0 m g, A L X N 2 0 5 0 1 2 0 m g, or place b o) bi d. After 
Wee k  2 6, a d diti o nal sta n dar d of care t h era p y f or p artici pa nts wit h S u b o pti mal 
Res p o nse is all o we d at t h e cli nical discreti o n of t h e I n vesti gat or i n c o n v ers ati o n wit h 
t he Me dical M o nit or. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1 Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 2 2  of 1 5 2  
Ale xi o n C o nfi de ntial  
•  Partici pa nts i n t he I g A N c o h ort ra n d o mize d t o t he A L X N 2 0 5 0 1 8 0 m g bi d or 
A L X N 2 0 5 0  1 2 0 m g bi d gr o u ps will c o nti n ue t o recei ve t h eir ra n d o mize d all ocati o n 
of st u d y i nter ve nti o n bi d. 
•  Partici pa nts i n t he I g A N c o h ort ra n d o mize d t o t he place b o gr o u p will recei ve eit her 
A L X N 2 0 5 0  1 8 0 m g  bi d ( n = 1 2) or A L X N 2 0 5 0  1 2 0 m g  bi d ( n = 1 2) as assi g ne d at 
t he ti me of ra n d o mizati o n. 
O pe n -L a bel E xte nsi o n Peri o d  
After c o m pleti o n of all assess me nts at t he e n d of t he Bli n de d E xte n de d Treat me nt Peri o d 
( Wee k 5 0 Visit), all parti ci pa nts will ha ve t he o p p ort u nit y t o e nter t he O pe n -la bel E xte nsi o n 
(O L E)  Peri o d f or u p t o 2 years ( 1 0 4 wee ks) if n o rele va nt si de effects (i n t he o pi ni o n of t he 
I n v esti gat or) are pr ese nt. 
D uri n g t he O L E Peri o d: 
•  Partici pa nts i n b ot h c o h orts recei vi n g A L X N 2 0 5 0 d uri n g t he Bli n de d I nitial 
E val uati o n Peri o d a n d t h e Bli n de d E xte n de d Treat me nt Peri o d will c o nti n ue t heir 
acti ve treat me nt at t he sa me d ose le vel. O nce a n o pti mal d ose is i de ntifie d ( base d o n 
t he 2 6 wee ks pri mar y a n al ysis) f or eac h c o h ort, all partici pa nts i n t hat c o h ort wit h at 
least 5 0 wee ks of st u d y treat me nt will recei ve t he o pti mal d ose of A L X N 2 0 5 0. 
•  Partici pa nts i n t he L N c o h ort ra n d o mize d t o t he pl ace b o gr o u p will n o l o n ger recei ve 
place b o a n d will c o nti n ue t o recei ve all o we d c o nc o mita nt t hera p y. T hese p artici pa nts 
will ha ve t he o pti o n t o recei ve A L X N 2 0 5 0 1 8 0 m g bi d or t he o pti mal d ose (if alrea d y 
i de ntifie d) if t he partici pa nt has a Re nal Flare as d efi ne d i n Secti o n 8. 1. 6  or  
S u b o pti mal Res p o nse as defi ne d i n Secti o n  8. 1. 8 . 
•  Perce nta g e c ha n g e i n pr otei n uria fr o m bas eli ne a n d c ha n ge fr o m baseli ne i n e G F R at 
Wee ks  1 0 2 a n d Wee k 1 5 4 will be assesse d as e x pl orat or y efficac y e n d p oi nts. Safet y 
a n d t olera bilit y will als o be e val uat e d c o nti n uall y t hr o u g h o ut t he O L E Peri o d. 
Discl os ure St ate m e nt:  T his is a parallel - gr o u p treat me nt st u d y wit h 3 ar ms t hat is partici pa nt 
a n d I n vesti gat or bli n de d d uri n g t he 2 6- wee k Bli n de d I nitial E val uati o n Peri o d a n d t he 2 4- w ee k 
Bli n de d E xte n de d Treat me nt Peri o d. 
N u m ber of P artici p a nts:  
A p pr o xi matel y 7 0 partici pa nts i n t he L N c o h ort a n d a p pr o xi matel y 5 6 parti ci pa nts i n t he I g A N 
c o h ort will be ra n d o ml y assi g ne d t o st u d y i nter ve nti o n. 
I nter ve nti o n Gr o u ps a n d D ur ati o n: 
T he st u d y c o nsists of a n u p t o 6- wee k Scree ni n g Peri o d, a 2 6- wee k Bli n de d I nitial E val u ati o n 
Peri o d, a 2 4- wee k Bli n de d E xte n de d Treat me nt Peri o d, a n d a n O L E Peri o d of u p t o 2 years.  I n 
a d diti o n, all partici pa nts will be f oll o we d f or safet y f or 3 0 da ys after t he last d ose of st u d y 
i nter ve nti o n. T h us, t he t otal treat me nt d urati o n is 1 5 4 wee ks, a n d t h e t otal st u d y d urati o n is u p t o 
1 6 4 wee ks.  
D at a M o nit ori n g C o m mittee:  Yes  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 2 3  of 1 5 2  
Ale xi o n C o nfi de ntial  
Et hic al C o nsi der ati o ns a n d Be nefit -Ris k Assess me nt  
T his st u d y will be c o n d ucte d as s pecifie d i n t his pr ot oc ol a n d i n acc or da n ce wit h t he f oll o wi n g:  
•  C o nse ns us et hical pri nci ples deri ve d fr o m i nter nati o nal g ui deli nes i ncl u di n g t he 
Declar ati o n of Helsi n ki a n d C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical 
Scie nces ( CI O M S) I nter n ati o nal Et hical G ui deli nes  
•  A p plica ble I C H G o o d Cli nical Practice ( G C P) G ui deli nes  
•  A p plica ble la ws a n d re g ulati o ns  
A t h or o u g h be nefit -ris k assess me nt has bee n p erf or me d f or A L X N 2 0 5 0. M eas ures will be ta ke n 
t o mi ni mize ris k t o st u d y partici pa nts. T he p ote nti al ris ks i de ntifie d i n ass ociati o n wit h 
A L X N 2 0 5 0 ar e j ustifie d b y t he a ntici pate d be n efits t hat ma y be aff or de d t o  partici pa nts wit h L N 
or I g A N ( A L X N 2 0 5 0 I n vesti gat or’s Br oc h ure [I B]).  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1 Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 2 4  of 1 5 2  
Ale xi o n C o nfi de ntial  
1. 2.  
Sc he m a  
T he st u d y desi g n sc he matic f or t he L N c o h ort is pr o vi de d i n  Fi g ure 1  an d f or t he I g A N c o h ort i n 
Fi g ure 2 . 
Fi g ure  1: 
St u d y Desi g n Sc he m atic ( L N C o h ort)  
 
a T he o pti mal d ose le v el will b e i d e ntifie d b ase d o n t h e res ults of t h e Wee k  2 6 Pri mar y A n al ysis f or eac h c o h ort. O n ce i d e ntifie d, 
all partici pa nts o n acti v e treat me nt i n t h at c o h ort w h o h a v e at least 5 0  wee ks of treat me nt will recei ve t h e selecte d o pti mal d ose 
f or t he re mai n d er of t h e st u d y. 
b Partici pa nts will recei v e a d diti o n al sta n d ar d of care t h era p y i n t h e e v e nt of a pr ot o c ol -d efi n e d Re n al Flare, or se v ere E xtrare nal 
S L E Flare. A p pr o v e d n o v el treat me nts f or L N ca n b e use d p er t h e I n v esti g at or’s discreti o n. After Wee k 2 6, a d diti o n al sta n dar d 
of care t hera p y f or p artici p a nts wit h S u b o pti mal Res p o nse is all o we d at t h e cli nical discreti o n of t h e I n v esti g at or i n 
c o n versati o n wit h t h e Me dical M o nit or. H o we v er, if a C NI is use d, A L X N 2 0 5 0 will n ee d t o b e disc o nti n u e d 3  d a ys pri or t o 
C NI a d mi nistra ti o n. 
c After c o m pleti o n of t h e Bli n d e d E xte n d e d Treat me nt Peri o d, p artici p a nts i n t h e place b o gr o u p will o nl y recei v e all o we d 
c o nc o mita nt t h era p y d uri n g t h e O p e n‑la b el E xte nsi o n Peri o d a n d will h a v e t h e o pti o n t o recei v e A L X N 2 0 5 0 1 8 0  m g bi d or t he 
o pti mal d ose (if alrea d y i d e ntifie d) if t h e p artici p a nt h as a Re n al Flare as d efi n e d i n Secti o n  8. 1. 6  or  S u b o pti mal Res p o nse as 
defi ne d i n Secti o n  8. 1. 8 . 
A b bre viati o ns: bi d  = t wice d ail y; C NI = calci n e uri n i n hi bit or; L N  = l u p us n e p hritis; S L E = s yste mic l u p us er yt h e mat os us 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1 Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 2 5  of 1 5 2  
Ale xi o n C o nfi de ntial  
Fi g ure  2: 
St u d y Desi g n Sc he m atic (I g A N C o h ort)  
 
a T he o pti mal d ose le v el will b e i d e ntifie d b ase d o n t h e res ults of t h e Wee k  2 6 Pri mar y A n al ysis f or eac h c o h ort. O n ce i d e ntifie d, 
all partici pa nts i n t h at c o h ort w h o h a v e at least 5 0 wee ks of treat me nt will recei v e t h e selecte d o pti mal d ose f or t h e re mai n der 
of t he st u d y.  
b At ra n d o mizati o n, p artici p a nts assi g n e d t o t h e place b o gr o u p will als o b e assi g n e d t o t h eir st u d y treat me nt f or t h e Bli n d e d 
E xte n de d Treat me nt Peri o d ( A L X N 2 0 5 0 1 2 0  m g bi d or A L X N 2 0 5 0 1 8 0  m g bi d) i n a 1: 1 all o cati o n rati o. After c o m pleti o n of 
t he Bli n de d I nitial E v al u ati o n Peri o d ( Wee k 2 6), t h ese p artici p a nts will c o nti n u e o n A L X N 2 0 5 0 treat me nt d uri n g t h e Bli n de d  
E xte n de d Treat me nt Peri o d.  
A b bre viati o ns: bi d  = t wice d ail y; I g A N = i m m u n o gl o b uli n A n e p hr o p at h y 
1. 3.  
Sc he d ule of Acti vities  
T he Sc he d ule of Acti vities ( S o A) is pr o vi de d as f oll o ws: 
•  Scree ni n g Peri o d a n d Bli n de d I nitial E val uati o n Peri o d: Scree ni n g t o Wee k 2 6 
( Da y 1 8 3) Visit ( L N c o h ort i n Ta ble  1 an d I g A N c o h ort i n  Ta ble  2) 
•  Bli n de d E xte n de d Treat me nt Peri o d ( L N c o h ort i n  Ta ble  3 an d I g A N c o h ort i n 
Ta ble  4) 
•  O pe n -la bel E xt e nsi o n Peri o d a n d Safet y F oll o w- u p Peri o d ( b ot h L N a n d I g A N 
c o h orts i n  Ta ble  5) 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 2 6  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 1: 
Sc he d ule of Acti vities D uri n g Scree ni n g a n d t he Bli n de d I niti al E v al u ati o n Peri o d: Scree ni n g t o Wee k  2 6 
Visit ( L N C o h ort)  
Peri o d  
Scree n -
i n g 
I niti al E v al u ati o n Peri o d  
 
N otes  
Visit  
1 
2 
3 
4 
5 
6 
7 
8 
9 
E v al u ati o n 
f o r Re n al 
Fl a re a n d 
E xtr are n al 
S L E Fl are 
Assess me nt 
Visit a 
U nsc he d ule d visits c a n be perf or me d 
as nee de d. A n E D Visit is re q uire d if 
p artici p a nt disc o nti n ues st u d y e arl y.  
Wee k  
U p t o  
6 W 
 
W 2 
W 4 
W 8 
W 1 2 
W 1 6 
W 2 0 
W 2 6/  
E D b 
D a ys a n d Wi n d o w  
D  -4 2 t o 
- 1 
D 1  
 
D 1 5  
± 3 
D 2 9  
± 3 
D 5 7  
± 5 
D 8 5  
± 5 
D 1 1 3  
± 5 
D 1 4 1  
± 5 
D 1 8 3  
± 5 
Ge ner al Assess m e nts/ Pr o ce d ur es  
I nf or me d c o nse nt 
X 
 
 
 
 
 
 
 
 
 
 
I ncl usi o n/e xcl usi o n 
X 
X 
 
 
 
 
 
 
 
 
C o nfir m eli gi bilit y pri or t o first d ose of 
st u d y i nter ve nti o n at Da y 1; partici pa nts 
ma y be rescree ne d.  
De m o gra p hics  
X 
 
 
 
 
 
 
 
 
 
 
Me dical hist or y  
X 
 
 
 
 
 
 
 
 
 
 
L N hist or y/ dia g n osis  
X 
 
 
 
 
 
 
 
 
 
 
D oc u me ntati o n of ki d n e y 
bi o ps y  
X 
 
 
 
 
 
 
 
 
 
Bi o ps y o btai ne d  ≤ 6 m o nt hs pri or t o 
Scree ni n g or d uri n g Scree ni n g. Se n d 
l ocal pat h ol o g y re p ort a n d micr osc o p y 
sli des t o Ce ntral Pat h ol o g y La b orat or y 
( Secti o n 8. 1 2. 5 ). 
Vacci nati o n or c o nfir mati o n of 
vacci nati o n a g ai nst Neisseri a 
me ni n giti dis c 
X 
 
 
 
 
 
 
 
 
 
Pr o p h ylactic a nti bi otics f or at least 
2 wee ks p ost vacci nati o n if  < 2 wee ks 
pri or t o first d ose. ( Secti o n  6. 5. 5 ). 
Pri or L N t hera p y  
X 
 
 
 
 
 
 
 
 
 
Rec or d c ortic oster oi d a n d M M F usa ge 
( Secti o n 6. 5. 3. 1 ). 
Wei g ht
 
X 
X 
 
 
 
 
 
 
X 
 
 
Hei g ht  
X 
 
 
 
 
 
 
 
 
 
 
Pre g na nc y test ( W O C B P o nl y)  
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Ser u m tests re q uire d at Scree ni n g a n d 
E D; uri ne tests at all ot her visits. 
( Secti o n 8. 2. 6 ) 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 2 7  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 1: 
Sc he d ule of Acti vities D uri n g Scree ni n g a n d t he Bli n de d I niti al E v al u ati o n Peri o d: Scree ni n g t o Wee k  2 6 
Visit ( L N C o h ort)  
Peri o d  
Scree n -
i n g 
I niti al E v al u ati o n Peri o d  
 
N otes  
Visit  
1 
2 
3 
4 
5 
6 
7 
8 
9 
E v al u ati o n 
f o r Re n al 
Fl a re a n d 
E xtr are n al 
S L E Fl are 
Assess me nt 
Visit a 
U nsc he d ule d visits c a n be perf or me d 
as nee de d. A n E D Visit is re q uire d if 
p artici p a nt disc o nti n ues st u d y e arl y.  
Wee k  
U p t o  
6 W 
 
W 2 
W 4 
W 8 
W 1 2 
W 1 6 
W 2 0 
W 2 6/  
E D b 
D a ys a n d Wi n d o w  
D  -4 2 t o 
- 1 
D 1  
 
D 1 5  
± 3 
D 2 9  
± 3 
D 5 7  
± 5 
D 8 5  
± 5 
D 1 1 3  
± 5 
D 1 4 1  
± 5 
D 1 8 3  
± 5 
F S H test d 
X 
 
 
 
 
 
 
 
 
 
O nl y f or fe males w h o are n ot W O C B P 
( Secti o n 8. 2. 4. 4 ). 
HI V, H C V, a n d H B V  
X 
 
 
 
 
 
 
 
 
 
 
Dis pe nse partici p a nt safet y 
car d  
X 
 
 
 
 
 
 
 
 
 
I nstr uct partici pa nts t o carr y safet y car d 
at all ti mes a n d bri n g it t o sc he d ule d 
visits ( Secti o n  8. 2. 7 ). 
Effic ac y Assess m e nts  
2 4 -h o ur uri ne c ollecti o n e 
X 
 
 
 
 
 
 
 
X 
X 
O ne c ollecti o n is nee de d as s o o n as 
p ossi ble d uri n g Scree ni n g. T w o se parate 
c ollecti o ns m ust be o btai ne d wit hi n 
2 wee ks pri or t o t he Wee k  2 6 Visit. 
( Secti o n 8. 1. 1. 1 ). 
M or ni n g s p ot uri n e sa m ple  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
T w o c o nsec uti ve s p ot uri ne sa m ples at 
Wee k 1 6 ( Secti o n  8. 1. 2 ). 
e G F R ( m eas ure d b y ser u m 
creati ni ne)  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
At Wee k  2 6, t he first creati ni ne sa m ple 
f or e G F R will be o btai ne d wit hi n 2 wee ks 
pri or t o Wee k 2 6 st u d y visit a n d t he 
sec o n d creati ni ne sa m ple will be o btai ne d 
o n t he st u d y visit da y ( Secti o n 8. 1. 3 ). 
Pre d ose bl o o d sa m ple f or 
ser u m cli nical c o m ple me nt 
tests 
X 
X 
X 
 
X 
 
X 
 
X 
X 
Secti o n  1 0. 2 . 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 2 8  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 1: 
Sc he d ule of Acti vities D uri n g Scree ni n g a n d t he Bli n de d I niti al E v al u ati o n Peri o d: Scree ni n g t o Wee k  2 6 
Visit ( L N C o h ort)  
Peri o d  
Scree n -
i n g 
I niti al E v al u ati o n Peri o d  
 
N otes  
Visit  
1 
2 
3 
4 
5 
6 
7 
8 
9 
E v al u ati o n 
f o r Re n al 
Fl a re a n d 
E xtr are n a l 
S L E Fl are  
Asse ss ment 
Visit a 
U nsc he d ule d visits c a n be perf or me d 
as nee de d. A n E D Visit is re q uire d if 
p artici p a nt disc o nti n ues st u d y e arl y.  
Wee k  
U p t o  
6 W 
 
W 2 
W 4 
W 8 
W 1 2 
W 1 6 
W 2 0 
W 2 6/  
E D b 
D a ys a n d Wi n d o w  
D  -4 2 t o 
- 1 
D 1  
 
D 1 5  
± 3 
D 2 9  
± 3 
D 5 7  
± 5 
D 8 5  
± 5 
D 1 1 3  
± 5 
D 1 4 1  
± 5 
D 1 8 3  
± 5 
M o nit or f or Re n al Flare a n d/ or 
E xtrare nal S L E Flare a 
 
C o nti n u o us m o nit ori n g  
X 
Refer t o Secti o n  8. 1. 6  a n d Secti o n  8. 1. 7  
f or defi niti o ns. D oc u me nt use of 
a d diti o nal sta n dar d of care t hera p y  a n d/ or 
re peat bi o ps y, if a p plica ble 
( Secti o n 6. 5. 4 ). 
S afet y Assess m e nts  
P h ysical e xa mi n ati o n, 
i ncl u di n g ne ur ol o gical 
assess me nts f 
X 
X 
 
 
 
 
 
 
X 
 
Secti o n  8. 2. 1 . 
A b bre viate d P E  
 
 
X 
X 
X 
X 
X 
X 
 
 
Vital si g ns  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital si g ns t o be ta ke n pre d ose  at cli nic 
visits ( Secti o n  8. 2. 2 ). 
E C G f or L N patie nts o n 
h y dr o x yc hl or o q ui n e  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Secti o n  8. 2. 3 . 
E C G f or L N patie nts n ot o n 
h y dr o x yc hl or o q ui n e  
X 
X 
 
 
 
 
 
 
X 
 
Pri or me dicati o ns a n d 
pr oce d ures  
X 
 
 
 
 
 
 
 
 
 
Secti o n  8. 2. 5 . 
C o nc o mita nt me dicati o ns a n d 
N P T P  
 
C o nti n u o us m o nit ori n g  
X 
Secti o n  6. 5  a n d Secti o n  8. 2. 5 .  
All o we d c o nc o mita nt L N 
t hera p y 
 
C o nti n u o us m o nit ori n g  
X 
See details o n c ortic oster oi d ta per i n 
Secti o n  6. 5. 3. 1 . 
A d verse e ve nts  
C o nti n u o us m o nit ori n g  
X 
Secti o n  1 0. 3 . 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 2 9  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 1: 
Sc he d ule of Acti vities D uri n g Scree ni n g a n d t he Bli n de d I niti al E v al u ati o n Peri o d: Scree ni n g t o Wee k  2 6 
Visit ( L N C o h ort)  
Peri o d  
Scree n -
i n g 
I niti al E v al u ati o n Peri o d  
 
N otes  
Visit  
1 
2 
3 
4 
5 
6 
7 
8 
9 
E v al u ati o n 
f o r Re n al 
Fl a re a n d 
E xtr are n al 
S L E Fl are 
Assess me nt 
Visit a 
U nsc he d ule d visits c a n be perf or me d 
as nee de d. A n E D Visit is re q uire d if 
p artici p a nt disc o nti n ues st u d y e arl y.  
Wee k  
U p t o  
6 W 
 
W 2 
W 4 
W 8 
W 1 2 
W 1 6 
W 2 0 
W 2 6/  
E D b 
D a ys a n d Wi n d o w  
D  -4 2 t o 
- 1 
D 1  
 
D 1 5  
± 3 
D 2 9  
± 3 
D 5 7  
± 5 
D 8 5  
± 5 
D 1 1 3  
± 5 
D 1 4 1  
± 5 
D 1 8 3  
± 5 
Pre d ose bl o o d sa m ple f or 
cli nical c he mistr y, h e mat ol o g y, 
a n d c oa g ulati o n 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Secti o n  8. 2. 4. 2  a n d  Secti o n  1 0. 2 . 
Uri nal ysis a n d uri n e se di me nt  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Secti o n  8. 2. 4. 3  a n d  Secti o n  1 0. 2 . 
Partici pa nt safet y car d re vie w  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
C o nfir m partici pa nts carr y safet y car d at 
all ti mes ( Secti o n  8. 2. 7 ). 
P K a n d P D Assess m e nts g 
Pre d ose bl o o d sa m ple f or P K  
 
X 
X 
X 
X 
X 
X 
 
X 
X 
See f o ot n ote f or sa m pli n g ti me p oi nts.  
Pre d ose bl o o d sa m ple f or B b 
a n d A P acti vit y 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
P ost d ose bl o o d sa m ple f or P K  
 
X 
X 
 
 
 
 
 
 
 
P ost d ose bl o o d sa m ple f or B b 
a n d A P acti vit y 
 
X 
X 
 
 
 
 
 
 
 
E x pl or at or y Assess m e nts  
E Q -5 D -5 L  
 
X 
 
 
X 
 
X 
 
X 
 
If p ossi ble, c o m plete t he P R Os pri or t o 
pr oce d ures a n d i nter ve nti o n 
a d mi nistrati o n ( Secti o n  8. 1 0 ). 
S F -3 6  
 
X 
 
 
X 
 
X 
 
X 
 
F A CI T- Fati g ue  
 
X 
 
 
X 
 
X 
 
X 
 
S L E D AI -2 K  
 
X 
 
 
 
 
 
 
X 
X 
Re q uire d at Da y  1 a n d Wee k  2 6/ E D; 
perf or m as nee de d f or e val uati o n of 
E xtrare nal S L E Flare ( Secti o n  8. 1. 7 ). 
Bl o o d a n d uri n e sa m ples f or 
bi o mar kers  
X 
X 
X 
 
X 
 
X 
 
X 
X 
C ollect pre d ose o n i n -cli nic d osi n g da ys 
(Secti o n  1 0. 2 ). 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 3 0  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 1: 
Sc he d ule of Acti vities D uri n g Scree ni n g a n d t he Bli n de d I niti al E v al u ati o n Peri o d: Scree ni n g t o Wee k  2 6 
Visit ( L N C o h ort)  
Peri o d  
Scree n -
i n g 
I niti al E v al u ati o n Peri o d  
 
N otes  
Visit  
1 
2 
3 
4 
5 
6 
7 
8 
9 
E v al u ati o n 
f o r Re n al 
Fl a re a n d 
E xtr are n al 
S L E Fl are 
Assess me nt 
Visit a 
U nsc he d ule d visits c a n be perf or me d 
as nee de d. A n E D Visit is re q uire d if 
p artici p a nt disc o nti n ues st u d y e arl y.  
Wee k  
U p t o  
6 W 
 
W 2 
W 4 
W 8 
W 1 2 
W 1 6 
W 2 0 
W 2 6/  
E D b 
D a ys a n d Wi n d o w  
D  -4 2 t o 
- 1 
D 1  
 
D 1 5  
± 3 
D 2 9  
± 3 
D 5 7  
± 5 
D 8 5  
± 5 
D 1 1 3  
± 5 
D 1 4 1  
± 5 
D 1 8 3  
± 5 
Bl o o d sa m ple f or 
a ut oa nti b o dies  
X 
X 
 
 
 
 
 
 
X 
X 
Secti o n  1 0. 2 . 
O pti o nal ki d ne y bi o ps y h 
 
 
 
 
 
 
 
 
 
X 
Se n d l ocal pat h ol o g y re p ort a n d 
micr osc o p y sli des t o t he Ce ntral 
Pat h ol o g y La b orat or y ( Secti o n  8. 1 2. 5. 3 ). 
St u d y I nter ve nti o n  
Ra n d o mizati o n  
 
X 
 
 
 
 
 
 
 
 
Re vie w eli gi bilit y pri or t o ra n d o mizati o n.  
M or ni n g d ose a d mi nistere d i n -
cli nic 
 
X 
X 
X 
X 
X 
X 
X 
X i 
 
A d mi nister after all ot her re q uire d 
tests/ pr oce d ures. 
St u d y i nter ve nti o n c o m plia n ce 
a n d acc o u nta bilit y 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Partici pa nts o n st u d y i nter ve nti o n s h o ul d 
bri n g all u n use d st u d y i nter ve nti o n at 
eac h cli nic visit f or ta blet c o u nti n g.  
St u d y i nter ve nti o n dis p e nsi n g  
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Partici pa nts o n st u d y i nter ve nti o n will be 
pr o vi de d wit h s ufficie nt st u d y 
i nter ve nti o n t o last u ntil t heir ne xt st u d y 
visit (e xce pt at E D).  
a Re nal Flare (as d efi n e d i n Secti o n  8. 1. 6 ) a n d/ or se v ere E xtrare n al S L E Flare (as d efi n e d i n Secti o n 8. 1. 7 ) ma y o cc ur at a n y ti me d uri n g t he st u d y. E val uati o n of Re nal Flare 
re q uires t hat U P C R fr o m t h e m or ni n g s p ot uri n e c ollecti o n is c o nfir me d b y a ce ntral la b U P C R b ase d o n 2 4-h o ur uri n e c ollecte d wit hi n 2 wee ks, as well as 2  ser u m creati ni ne 
sa m ples o btai n e d wit hi n a 2 wee k p eri o d. E v al u ati o n of Re n al a n d E xtrare n al S L E Flares m ust b e p erf or me d as s o o n as p ossi ble u p o n n otificati o n t o t he I n vesti gat or of s y m pt o m 
o nset. If Re nal Flare or E xtrare n al S L E Flare o cc urs b et wee n sc h e d ule d visits, o nl y t h e assess me nts f or t h e Re n al Flare/ E xtrare nal S L E Flare Visit are nee de d. If Re nal Flare or 
E xtrare nal S L E Flare o cc urs o n a sc h e d ule d visit, all sc h e d ule d assess me nts s h o ul d b e p erf or me d f or t h at visit as well as a n y  a d diti o nal assess me nts re q uire d f or t he e val uati o n of 
t he flare. 
b F or partici pa nts w h o disc o nti n u e st u d y i nter v e nti o n pri or t o Wee k  5 0, e v er y eff ort s h o ul d b e ma d e t o h a v e t h e p artici p a nt c o nti n ue t he st u d y visits as per t he S o A t hr o u g h t he 
Wee k 5 0. A Safet y F oll o w -u p Visit s h o ul d b e p erf or me d 3 0  d a ys after t h e last d ose of st u d y i nter v e nti o n. If t h e p artici p a nt d oes n ot a gree t o c o nti n ue wit h t he st u d y visits after 
st u d y i nter ve nti o n is disc o nti n u e d, t h e E D Visit s h o ul d b e p erf or me d as s o o n as p ossi ble, a n d a Safet y F oll o w -u p Visit s h o ul d be perf o r me d 3 0 da ys after t he last d ose of st u d y 
i nter ve nti o n (refer t o Ta ble  5 for t h e Safet y F oll o w -u p Visit pr o ce d ures.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 3 1  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 1: 
Sc he d ule of Acti vities D uri n g Scree ni n g a n d t he Bli n de d I niti al E v al u ati o n Peri o d: Scree ni n g t o Wee k  2 6 Visit 
( L N C o h ort) 
c T o re d uce t he ris k of me ni n g o c o ccal i nfecti o n ( Neisseri a me ni n giti dis ), all p artici p a nts m ust b e v acci n ate d a g ai nst me ni n g oc occal i nfecti o n wit hi n 3 years or bef ore t he 
a d mi nistrati o n of st u d y i nter v e nti o n o n Da y 1. Partici p a nts w h o i nitiate st u d y i nter v e nti o n less t h a n 2 wee ks after recei vi n g  a me ni n g oc occal vacci ne m ust recei ve treat me nt wit h 
a p pr o priate pr o p h ylactic a nti bi otics u ntil at least 2 wee ks after v acci n ati o n ( Secti o n  6. 5. 5 ). 
d F S H test nee d n ot b e d o n e if d o c u me ntati o n c o nfir mi n g p ost me n o pa usal stat us is a v aila ble ( Secti o n  8. 2. 4. 4 ). 
e Re nal Flare re q uires a 2 4 -h o ur uri n e c ollecti o n f or c o nfir mati o n ( Secti o n  8. 1. 1 ). 
f Perf or m a s y m pt o m b ase d n e ur ol o gic e x a mi n ati o n if p artici p a nt h as c o m plai nts or cli nical fi n di n gs attri b uta ble t o t h e C N S a n d  if p ositi ve f or fi n di n gs, f ull ne ur ol o gic 
e xa mi nati o n t o b e p erf or me d at eac h assess me nt ti me p oi nt.  
g Pre d ose:  c ollect wit hi n 0. 5 h pre d ose o n i n dicate d i n -cli nic d osi n g d a ys. P ost d ose:  a p pr o xi matel y 5 0 %  p artici p a nt i n eac h treat me nt ar m will be assi g ne d t o P K/ P D sa m ple 
c ollecti o n at 2  ± 0. 5  h, 4  ± 0. 5  h, a n d 6  ± 0. 5  h p ost d ose o n Da y  1 a n d at 2  ± 0. 5  h, 4  ± 0. 5  h, 6  ± 0. 5  h p ost d ose at Wee k  2. F or t he ot her a p pr o xi mate 5 0 %  of partici pa nt, sa m ples 
will be c ollecte d at 2  ± 0. 5  h p ost d ose o n Da y  1 a n d 2  ± 0. 5  h p ost d ose at Wee k  2 ( Secti o n 8. 4  a n d Secti o n  8. 5 ) 
h Partici pa nts ma y recei v e a ki d n e y bi o ps y f or cli nical reas o ns or f or e v al u ati o n of a Re n al Flare (as d efi n e d i n Secti o n  8. 1. 6 ) at t he discreti o n of t he I n vesti gat or. T he l ocal 
pat h ol o g y re p ort a n d micr osecti o n sli d es fr o m ki d n e y bi o psies p erf or me d at ot h er ti mes d uri n g t h e st u d y pri or t o Wee k  2 6 s h o ul d als o be se nt t o t he Ce ntral Pat h ol o g y 
La b orat or y f or re vie w as s o o n as p ossi ble.  
i T he pri mar y efficac y e n d p oi nt assess me nt will b e o btai n e d pri or t o d osi n g o n Da y  1 8 3. D osi n g o n Da y  1 8 3 is t h e start of t he Bli n de d E xte n de d Treat me nt Peri o d.  
N ote: If p ossi ble, all assess m e nts s h o ul d be perf o r m e d pri o r t o a d mi nistr ati o n of st u d y i nter v e nti o n o n i n -cli nic d osi n g d a ys, u nless ot her wise s pecifie d . 
A b bre viati o ns: A P  = alter n ati v e pat h wa y; B b  = B b fra g me nt of c o m ple me nt fact or  B; C N S  = ce ntral n er v o us s yste m; D  = da y; E C G  = electr ocar di o gra m; E D  = earl y 
disc o nti n uati o n; e G F R  = esti mate d gl o mer ular filtrati o n rate; E Q -5 D -5 L  = E ur o p ea n Q u alit y of Life Healt h 5 -ite m q u esti o n naire di me nsi o ns 5 le vel; F A CI T = F u ncti o nal 
Assess me nt of C hr o nic Ill n ess T hera p y; F S H  = f ollicle sti m ulati n g h or m o n e; H B V = h e p atitis B vir us; H C V  = h e p atitis C vir us; HI V  = h u ma n i m m u n o deficie nc y vir us; 
L N  = l u p us n e p hritis; M M F = myc o p h e n olate m ofetil; N P T P  = n o n p h ar mac ol o gic t h era pies a n d pr o ce d ures; P D  = p h ar mac o d y na mics; P E  = p h ysical e xa mi nati o n; 
P K  = p har mac o ki n etics; P R O  = partici p a nt -re p orte d o utc o me; S L E = s yste mic l u p us er yt h e mat os us; S F-3 6  = S h ort F or m ( 3 6) Healt h S ur ve y; S L E D AI -2 K  = S yste mic L u p us 
Er yt he mat os us Disease Acti vit y I n d e x  2 0 0 0 Safet y of Estr o g e ns i n L u p us Er yt h e mat os us Nati o n al Assess m e nt ( S E L E N A) M o dificati o n; S o A = Sc he d ule of Acti vities; 
U P C R  = uri ne pr otei n t o creati ni ne rati o; W  = wee k(s); W O C B P  = w o me n of  c hil d b eari n g p ote ntial 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 3 2  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 2: 
Sc he d ule of Acti vities D uri n g Scree ni n g a n d t he Bli n de d I niti al E v al u ati o n Peri o d: Scree ni n g t o Wee k  2 6 Visit 
(I g A N C o h ort) 
Peri o d  
Scree n -
i n g 
I niti al E v al u ati o n Peri o d 
N otes  
Visit  
1 
2 
3 
4 
5 
6 
7 
U nsc he d ule d visits c a n be perf or me d as nee de d. A n E D Visit 
is re q uire d if p artici p a nt disc o nti n ues st u d y e arl y. 
Wee k  
U p t o  
6 W 
 
W 2 
W 6 
W 1 2 
W 1 8 
W 2 6/  
E D a 
D a ys a n d Wi n d o w  
D - 4 2 t o 
- 1 
D 1  
 
D 1 5  
± 3 
D 4 3  
± 5 
D 8 5  
± 5 
D 1 2 7  
± 5 
D 1 8 3  
± 5 
Ge ner al Assess m e nts/ Pr o ce d ur es  
I nf or me d c o nse nt 
X 
 
 
 
 
 
 
 
I ncl usi o n/e xcl usi o n 
X 
X 
 
 
 
 
 
C o nfir m eli gi bilit y pri or t o first d ose of st u d y i nter ve nti o n at 
Da y 1; p artici pa nts ma y be rescree ne d.  
De m o gra p hics  
X 
 
 
 
 
 
 
 
Me dical hist or y  
X 
 
 
 
 
 
 
 
I g A N hist or y/ dia g n osis 
X 
 
 
 
 
 
 
 
D oc u me ntati o n of ki d n e y bi o ps y  
X 
 
 
 
 
 
 
Ki d n e y bi o ps y perf or me d d uri n g or pri or t o Scree ni n g (a n y ti me 
pri or t o Da y  1). Se n d l ocal pat h ol o g y re p ort a n d micr osc o p y 
sli d es t o Ce ntral Pat h ol o g y ( Secti o n 8. 1 2. 5 ). 
Pri or I g A N t hera p y  
X 
 
 
 
 
 
 
Rec or d A C Ei/ A R B usa ge ( Secti o n  8. 2. 5 ). 
Vacci nati o n or c o nfir mati o n of 
vacci nati o n a g ai nst  
N me ni n giti dis b 
X 
 
 
 
 
 
 
Pr o p h ylactic a nti bi otics f or at least 2  wee ks p ost vacci nati o n 
if < 2 wee ks pri or t o first d ose. ( Secti o n  6. 5. 5 ). 
Wei g ht
 
X 
X 
 
 
 
 
X 
 
Hei g ht  
X 
 
 
 
 
 
 
 
HI V, H C V, a n d H B V  
X 
 
 
 
 
 
 
 
Pre g na nc y test ( W O C B P o nl y) 
X 
X 
X 
X 
X 
X 
X 
Ser u m tests re q uire d at Scree ni n g a n d E D; uri ne tests at all 
ot h er visits ( Secti o n  8. 2. 6 ). 
F S H test c 
X 
 
 
 
 
 
 
O nl y f or fe males w h o are n ot W O C B P ( Secti o n  8. 2. 4. 4 ). 
Dis pe nse partici p a nt safet y car d  
X 
 
 
 
 
 
 
I nstr u ct partici pa nts t o carr y safet y car d at all ti mes a n d bri n g t o 
sc h e d ule d visits ( Secti o n 8. 2. 7 ). 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 3 3  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 2: 
Sc he d ule of Acti vities D uri n g Scree ni n g a n d t he Bli n de d I niti al E v al u ati o n Peri o d: Scree ni n g t o Wee k  2 6 Visit 
(I g A N C o h ort) 
Peri o d  
Scree n -
i n g 
I niti al E v al u ati o n Peri o d 
N otes  
Visit  
1 
2 
3 
4 
5 
6 
7 
U nsc he d ule d visits c a n be perf or me d as nee de d. A n E D Visit 
is re q uire d if p artici p a nt disc o nti n ues st u d y e arl y. 
Wee k  
U p t o  
6 W 
 
W 2 
W 6 
W 1 2 
W 1 8 
W 2 6/  
E D a 
D a ys a n d Wi n d o w  
D - 4 2 t o 
- 1 
D 1  
 
D 1 5  
± 3 
D 4 3  
± 5 
D 8 5  
± 5 
D 1 2 7  
± 5 
D 1 8 3  
± 5 
Effic ac y Assess m e nts  
2 4 -h o ur uri ne c ollecti o n  
X 
 
 
 
 
 
X 
T w o se p arate, c o m plete, a n d vali d 2 4 -h o ur uri ne c ollecti o ns are 
re q uire d d uri n g Scree ni n g a n d wit hi n 2 wee ks pri or t o t he 
Wee k  2 6 Visit. ( Secti o n  8. 1. 1. 2 ). 
M or ni n g s p ot uri n e sa m ple  
X 
X 
X 
X 
X 
X 
X 
T w o c o nsec uti ve s p ot uri ne sa m ples at Wee k 1 8 ( Secti o n 8. 1. 2 ). 
e G F R ( m eas ure d b y ser u m 
creati ni ne)  
X 
X 
X 
X 
X 
X 
X 
 
Pre d ose bl o o d sa m ple f or ser u m 
cli nical c o m ple me nt tests 
X 
X 
X 
 
X 
X 
X 
Secti o n  1 0. 2 .  
S afet y Assess m e nts  
P h ysical e xa mi n ati o n, i n cl u di n g 
ne ur ol o gical assess m e nts d 
X 
X 
 
 
 
 
X 
Secti o n  8. 2. 1 . 
A b bre viate d P E  
 
 
X 
X 
X 
X 
 
Vital si g ns  
X 
X 
X 
X 
X 
X 
X 
Vital si g ns t o be ta ke n pri or t o d osi n g at cli nic visits 
( Secti o n 8. 2. 2 ). 
E C G 
X 
X 
 
 
 
 
X 
Secti o n  8. 2. 3 . 
Pri or me dicati o ns a n d 
pr oce d ures  
X 
 
 
 
 
 
 
Secti o n  8. 2. 5 . 
C o nc o mita nt me dicati o ns a n d 
N P T P  
 
C o nti n u o us m o nit ori n g  
Secti o n  6. 5  a n d Secti o n  8. 2. 5 . 
All o we d c o nc o mita nt I g A N 
t hera p y 
 
C o nti n u o us m o nit ori n g  
Secti o n  6. 5. 3. 2 . 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 3 4  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 2: 
Sc he d ule of Acti vities D uri n g Scree ni n g a n d t he Bli n de d I niti al E v al u ati o n Peri o d: Scree ni n g t o Wee k  2 6 Visit 
(I g A N C o h ort) 
Peri o d  
Scree n -
i n g 
I niti al E v al u ati o n Peri o d 
N otes  
Visit  
1 
2 
3 
4 
5 
6 
7 
U nsc he d ule d visits c a n be perf or me d as nee de d. A n E D Visit 
is re q uire d if p artici p a nt disc o nti n ues st u d y e arl y. 
Wee k  
U p t o  
6 W 
 
W 2 
W 6 
W 1 2 
W 1 8 
W 2 6/  
E D a 
D a ys a n d Wi n d o w  
D - 4 2 t o 
- 1 
D 1  
 
D 1 5  
± 3 
D 4 3  
± 5 
D 8 5  
± 5 
D 1 2 7  
± 5 
D 1 8 3  
± 5 
A d verse e ve nts  
C o nti n u o us m o nit ori n g  
Secti o n  1 0. 3 . 
Pre d ose bl o o d sa m ple f or 
cli nical c he mistr y, h e mat ol o g y, 
a n d c oa g ulati o n 
X 
X 
X 
X 
X 
X 
X 
Secti o n  8. 2. 4. 2  a n d Secti o n  1 0. 2 . 
Uri nal ysis a n d uri n e se di me nt  
X e 
X 
X 
X 
X 
X 
X 
Secti o n  8. 2. 4. 3  a n d  Secti o n  1 0. 2 . 
Partici pa nt safet y car d re vie w  
 
X 
X 
X 
X 
X 
X 
C o nfir m partici pa nts carr y safet y car d at all ti mes 
( Secti o n 8. 2. 7 ). 
P K a n d P D Assess m e nts f 
Pre d ose bl o o d sa m ple f or P K  
 
X 
X 
X 
X 
X 
X 
See f o ot n ote f or sa m pli n g ti me p oi nts.  
Pre d ose bl o o d sa m ple f or B b 
a n d A P acti vit y 
 
X 
X 
X 
X 
X 
X 
P ost d ose  bl o o d sa m ple f or P K  
 
X 
X 
 
 
 
 
P ost d ose bl o o d sa m ple f or B b 
a n d A P acti vit y 
 
X 
X 
 
 
 
 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 3 5  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 2: 
Sc he d ule of Acti vities D uri n g Scree ni n g a n d t he Bli n de d I niti al E v al u ati o n Peri o d: Scree ni n g t o Wee k  2 6 Visit 
(I g A N C o h ort) 
Peri o d  
Scree n -
i n g 
I niti al E v al u ati o n Peri o d 
N otes  
Visit  
1 
2 
3 
4 
5 
6 
7 
U nsc he d ule d visits c a n be perf or me d as nee de d. A n E D Visit 
is re q uire d if p artici p a nt disc o nti n ues st u d y e arl y. 
Wee k  
U p t o  
6 W 
 
W 2 
W 6 
W 1 2 
W 1 8 
W 2 6/  
E D a 
D a ys a n d Wi n d o w  
D - 4 2 t o 
- 1 
D 1  
 
D 1 5  
± 3 
D 4 3  
± 5 
D 8 5  
± 5 
D 1 2 7  
± 5 
D 1 8 3  
± 5 
E x pl or at or y Assess m e nts  
E Q -5 D -5 L  
 
X 
 
X 
X 
 
X 
If p ossi ble, c o m plete t he P R Os pri or t o pr oce d ures a n d 
i nter v e nti o n a d mi nistrati o n ( Secti o n 8. 1 0 ). 
S F -3 6  
 
X 
 
X 
X 
 
X 
Bl o o d a n d uri n e sa m ples f or 
bi o mar kers  
X 
X 
X 
 
X 
X 
X 
C ollect pre d ose o n i n -cli nic d osi n g da ys ( Secti o n  1 0. 2 ). 
St u d y I nter ve nti o n  
Ra n d o mizati o n  
 
X 
 
 
 
 
 
Re vie w eli gi bilit y pri or t o ra n d o mizati o n.  
M or ni n g d ose a d mi nistere d i n -
cli nic 
 
X 
X 
X 
X 
X 
X g 
A d mi nister d ose after all ot her re q uire d tests/ pr oce d ures.  
St u d y i nter ve nti o n c o m plia n ce 
a n d acc o u nta bilit y 
 
X 
X 
X 
X 
X 
X 
Partici p a nts o n st u d y i nter ve nti o n s h o ul d bri n g all u n use d st u d y 
i nter v e nti o n at eac h cli nic visit f or ta blet c o u nti n g. 
St u d y i nter ve nti o n dis p e nsi n g 
 
X 
X 
X 
X 
X 
X 
Partici p a nts o n st u d y i nter ve nti o n will be pr o vi de d wit h 
s ufficie nt st u d y i nter ve nti o n t o last u ntil t heir ne xt st u d y visit 
(e x ce pt at E D). 
a F or partici pa nts w h o disc o nti n u e st u d y i nter v e nti o n pri or t o Wee k  5 0, e v er y eff ort s h o ul d b e ma d e t o h a v e t h e p artici p a nt c o nti n ue t he st u d y visits as per t he S o A t hr o u g h t he 
Wee k 5 0. A Safet y F oll o w -u p Visit s h o ul d b e p erf or me d 3 0  d a ys after t h e last d ose of st u d y i nter v e nti o n. If t h e p artici p a nt d oes n ot a gree t o c o nti n ue wit h t he st u d y visits after 
st u d y i nter ve nti o n is disc o nti n u e d, t h e E D Visit s h o ul d b e p erf or me d as s o o n as p ossi ble, a n d a Safet y F oll o w -u p Visit s h o ul d be perf or me d 3 0 da ys after t he last d ose of st u d y 
i nter ve nti o n. Refer t o Ta ble  5 for t h e Safet y F oll o w -u p Visit pr o ce d ures.  
b T o re d uce t he ris k of me ni n g o c o ccal i nfecti o n ( N me ni n giti dis ), all p artici p a nts m ust b e v acci n ate d a g ai nst me ni n g o c o ccal i nfecti o n wit hi n 3 years or bef ore t he a d mi nistrati o n of 
st u d y i nter ve nti o n o n Da y 1. Partici p a nts w h o i nitiate st u d y i nter v e nti o n less t h a n 2 wee ks after recei vi n g a me ni n g o c o ccal v acci ne m ust recei ve treat me nt wit h a p pr o priate 
pr o p h ylactic a nti bi otics u ntil at least 2 wee ks after v acci n ati o n ( Secti o n  6. 5. 5 ). 
c F S H test nee d n ot b e d o n e if d o c u me ntati o n c o nfir mi n g p ost me n o pa usal stat us is a v aila ble ( Secti o n  8. 2. 4. 4 ). 
d Perf or m a s y m pt o m b ase d n e ur ol o gic e x a mi n ati o n if p artici p a nt h as c o m plai nts or cli nical fi n di n gs attri b uta ble t o t h e C N S a n d  if p ositi ve f or fi n di n gs, f ull ne ur ol o gic 
e xa mi nati o n t o b e p erf or me d at eac h assess me nt ti me p oi nt.  
e F or partici pa nts i n t h e I g A N c o h ort, eli gi bilit y f or h e mat uria ca n b e d eter mi n e d via t h e l o cal la b orat or y.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 3 6  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 2: 
Sc he d ule of Acti vities D uri n g Scree ni n g a n d t he Bli n de d I niti al E v al u ati o n Peri o d: Scree ni n g t o Wee k  2 6 Visit 
(I g A N C o h ort) 
f Pre d ose : c ollect wit hi n 0. 5 h pre d ose o n i n dicate d i n -cli nic d osi n g d a ys. P ost d ose:  a p pr o xi matel y 5 0 % p artici p a nt i n eac h treat me nt ar m will be assi g ne d t o P K/ P D sa m ple 
c ollecti o n at 2  ± 0. 5  h, 4  ± 0. 5  h, 6  ± 0. 5  h p ost d ose o n Da y  1 a n d at 2  ± 0. 5  h, 4  ± 0. 5  h, 6  ± 0. 5  h p ost d ose at Wee k  2. F or t he ot her a p pr o xi matel y 5 0 % of partici pa nt, sa m ples 
will be c ollecte d at 2  ± 0. 5  h p ost d ose o n Da y  1 a n d 2  ± 0. 5  h p ost d ose at Wee k  2 ( Secti o n 8. 4  a n d Secti o n  8. 5 ). 
g T he pri mar y efficac y e n d p oi nt assess me nt will b e o btai n e d pri or t o d osi n g o n Da y  1 8 3. D osi n g o n Da y  1 8 3 is t h e start of t he Bli n de d E xte n de d Treat me nt Peri o d.  
N ote: If p ossi ble, all assess m e nts s h o ul d be perf o r m e d pri o r t o a d mi nistr ati o n of st u d y i nter v e nti o n o n i n -cli nic d osi n g d a ys, u nless ot her wise s pecifie d.  
A b bre viati o ns: A C Ei  = a n gi ote nsi n -c o n v erti n g e n z y me i n hi bit or; A P  = alter n ati v e p at h wa y; A R B  = a n gi ote nsi n II rece pt or bl oc ker; B b  = B b fra g me nt of c o m ple me nt fact or  B; 
C N S  = ce ntral n er v o us s yste m; D  = d a y; E C G  = electr o car di o gra m; E D  = earl y disc o nti n u ati o n; e G F R  = esti mate d gl o mer ular filtrati o n rate; E Q -5 D -5 L  = E ur o pea n Q ualit y of 
Life Healt h 5 -ite m q u esti o n n aire di me nsi o ns 5 le v el; F S H = f ollicle sti m ulati n g h or m o n e; H B V = h e p atitis B vir us; H C V  = he patitis C vir us; HI V  = h u ma n i m m u n o deficie nc y 
vir us; I g A N = i m m u n o gl o b uli n A n e p hr o p at h y; N P T P  = n o n p h ar mac ol o gic t h era pies a n d pr o ce d ures; P D  = p h ar mac o d y na mics; P E  = p h ysical e xa mi nati o n; 
P K  = p har mac o ki n etics; P R O  = partici p a nt -re p orte d o utc o me; S F -3 6  = S h ort F or m ( 3 6) Healt h S ur v e y; S o A  = Sc h e d ule of Acti vities; W  = wee k(s); W O C B P  = w o me n of 
c hil d beari n g p ote ntial 
 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 3 7  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 3: 
Sc he d ule of Acti vities D uri n g t he Bli n de d E xte n de d Tre at me nt Peri o d: Wee k  3 4 t o Wee k 5 0 Visits ( L N C o h ort) 
Peri o d  
E xte n de d Tre at m e nt Peri o d  
 
N otes  
Visit  
1 0  
1 1  
1 2  
E v al u ati o n f o r 
Re n al Fl a re, 
E xtr a re n al S L E 
Fl a re, a n d 
S u b o pti m al 
Res p o nse 
Assess m e nt Visit a 
U nsc he d ule d visits c a n be perf or me d as nee de d. A n E D 
Visit is re q uire d if p artici p a nt disc o nti n ues st u d y e arl y.  
Wee k  
W 3 4 
W 4 2 
W 5 0/ E D
b 
D a ys a n d Wi n d o w  
D 2 3 9  
± 7 
D 2 9 5  
± 7 
D 3 5 1  
± 7 
Ge ner al Assess m e nts/ Pr o ce d ur es  
Wei g ht
 
 
 
X 
 
 
Pre g na nc y test ( W O C B P o nl y)  
X 
X 
X 
 
Ser u m pre g na nc y test re q uire d at E D; uri ne pre g na nc y tests 
at all ot her visits ( Secti o n  8. 2. 6 ). 
Effic ac y Assess m e nts  
2 4 -h o ur uri ne c ollecti o n  
 
 
X 
X a 
T w o se parate 2 4 -h o ur uri ne c ollecti o ns re q uire d wit hi n 
2 wee ks pri or t o t he Wee k 5 0 Visit ( Secti o n  8. 1. 1 ). Re nal 
Flare a n d S u b o pti mal Res p o nse re q uire a 2 4 -h o ur uri ne 
c ollecti o n f or c o nfir mati o n ( Secti o n  8. 1. 6  a n d Secti o n 8. 1. 8 ) 
M or ni n g s p ot uri n e sa m ple  
X 
X 
X 
X 
Secti o n  8. 1. 2  
e G F R ( m eas ure d b y ser u m creati ni n e)  
X 
X 
X 
X 
At Wee k  5 0, t he first creati ni ne sa m ple f or e G F R will be 
o btai ne d wit hi n 2  wee ks pri or t o Wee k 5 0 st u d y visit a n d 
t he sec o n d creati ni ne sa m ple will be o btai ne d o n t he st u d y 
visit da y  ( Secti o n 8. 1. 3 ). 
Pre d ose bl o o d sa m ple f or ser u m cli nical 
c o m ple me nt tests  
X 
X 
X 
X 
Secti o n  1 0. 2   
M o nit or f or Re n al Flare a n d/ or E xtrare n al 
S L E Flare a n d/ or S u b o pti mal Res p o nse  a 
C o nti n u o us m o nit ori n g  
X 
Refer t o Secti o n  8. 1. 6 , Secti o n  8. 1. 7 , a n d Secti o n 8. 1. 8  f or 
d efi niti o ns. D oc u me nt use of a d diti o nal sta n dar d of care 
t hera p y a n d/ or re peat bi o ps y, if a p plica ble ( Secti o n 6. 5. 4 ). 
S afet y Assess m e nts  
P h ysical e xa mi n ati o n,  i n cl u di n g ne ur ol o gical 
assess me nts c 
 
 
X 
 
Secti o n  8. 2. 1 . 
A b bre viate d P E  
X 
X 
 
 
Vital si g ns  
X 
X 
X 
X 
Vital si g ns t o be ta ke n pre d ose at cli nic visits 
( Secti o n 8. 2. 2 ). 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 3 8  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 3: 
Sc he d ule of Acti vities D uri n g t he Bli n de d E xte n de d Tre at me nt Peri o d: Wee k  3 4 t o Wee k 5 0 Visits ( L N C o h ort) 
Peri o d  
E xte n de d Tre at m e nt Peri o d  
 
N otes  
Visit  
1 0  
1 1  
1 2  
E v al u ati o n f o r 
Re n al Fl a re, 
E xtr a re n al S L E 
Fl a re, a n d 
S u b o pti m al 
Res p o ns e 
Assess m e nt  Visita 
U nsc he d ule d visits c a n be perf or me d as nee de d. A n E D 
Visit is re q uire d if p artici p a nt disc o nti n ues st u d y e arl y.  
Wee k  
W 3 4 
W 4 2 
W 5 0/ E D
b 
D a ys a n d Wi n d o w  
D 2 3 9  
± 7 
D 2 9 5  
± 7 
D 3 5 1  
± 7 
E C G f or L N patie nts o n h y dr o x y c hl or o q ui n e  
X 
X 
X 
X 
Secti o n  8. 2. 3 . 
E C G f or L N patie nts n ot o n 
h y dr o x yc hl or o q ui n e  
 
 
X 
 
C o nc o mita nt me dicati o ns a n d N P T P  
C o nti n u o us m o nit ori n g  
X 
Secti o n  6. 5  a n d Secti o n  8. 2. 5 . 
All o we d c o nc o mita nt L N t h era p y  
C o nti n u o us m o nit ori n g  
X 
See details o n c ortic oster oi d ta per i n Secti o n  6. 5. 3. 1 . 
A d verse e ve nts  
C o nti n u o us m o nit ori n g  
X 
Secti o n  1 0. 3 .  
Pre d ose bl o o d sa m ple f or cli nical c h e mistr y, 
h e mat ol o g y, a n d c o a g ulati o n  
X 
X 
X 
X 
Secti o n  8. 2. 4. 2  a n d Secti o n  1 0. 2 .  
Uri nal ysis a n d uri n e se di me nt  
X 
X 
X 
X 
Secti o n  8. 2. 4. 3  a n d Secti o n  1 0. 2 . 
Partici pa nt safet y car d re vie w  
X 
X 
X 
X 
C o nfir m partici pa nts carr y safet y car d at all ti mes 
( Secti o n 8. 2. 7 ). 
P D a n d P K Assess m e nts  
Pre d ose bl o o d sa m ples f or P K  
X 
X 
X 
X 
Secti o n  8. 4 .  
Pre d ose bl o o d sa m ple f or B b a n d A P acti vit y  
X 
X 
X 
X 
Secti o n  8. 5 .  
E x pl or at or y Assess m e nts  
S F -3 6  
X 
X 
X 
 
P R Os t o be perf or me d as earl y as p ossi ble d uri n g visits 
( Secti o n 8. 1 0 ). 
E Q -5 D -5 L  
X 
X 
X 
 
F A CI T- Fati g ue  
X 
X 
X 
 
S L E D AI -2 K  
  
 
X 
X 
Re q uire d at Wee k  5 0/ E D, perf or m as nee de d f or e val uati o n 
of E xtrare nal S L E Flare ( Secti o n  8. 1. 7 ). 
Bl o o d a n d uri n e sa m ples f or bi o mar k ers  
X 
X 
X 
X 
C ollect pre d ose o n i n -cli nic d osi n g da ys ( Secti o n 1 0. 2 ). 
Bl o o d sa m ple f or a ut o a nti b o dies  
 
 
X 
X 
Secti o n  1 0. 2 . 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 3 9  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 3: 
Sc he d ule of Acti vities D uri n g t he Bli n de d E xte n de d Tre at me nt Peri o d: Wee k  3 4 t o Wee k 5 0 Visits ( L N C o h ort) 
Peri o d  
E xte n de d Tre at m e nt Peri o d  
 
N otes  
Visit  
1 0  
1 1  
1 2  
E v al u ati o n f o r 
Re n al Fl a re, 
E xtr a re n al S L E 
Fl a re, a n d 
S u b o pti m al 
Res p o nse 
Assess m e nt Visit a 
U nsc he d ule d visits c a n be perf or me d as nee de d. A n E D 
Visit is re q uire d if p artici p a nt disc o nti n ues st u d y e arl y.  
Wee k  
W 3 4 
W 4 2 
W 5 0/ E D
b 
D a ys a n d Wi n d o w  
D 2 3 9  
± 7 
D 2 9 5  
± 7 
D 3 5 1  
± 7 
O pti o nal ki d ne y bi o ps y d 
 
 
X 
X 
Se n d l ocal pat h ol o g y re p ort a n d micr osc o p y sli des t o t he 
Ce ntral Pat h ol o g y La b orat or y ( Secti o n  8. 1 2. 5. 3 ). 
St u d y I nter ve nti o n e 
M or ni n g d ose a d mi nistere d i n -cli nic 
X 
X 
X 
 
A d mi nister after all ot her re q uire d tests/ pr oce d ures.  
St u d y i nter ve nti o n c o m plia n ce a n d 
acc o u nta bilit y 
X 
X 
X 
 
Partici pa nts o n st u d y i nter ve nti o n s h o ul d bri n g all u n use d 
st u d y i nter ve nti o n at eac h cli nic visit f or ta blet c o u nti n g. 
St u d y i nter ve nti o n dis p e nsi n g  
X 
X 
X 
 
Partici pa nts o n st u d y i nter ve nti o n will be pr o vi de d wit h 
s ufficie nt st u d y i nter ve nti o n t o last u ntil t heir ne xt st u d y 
visit (e xce pt at E D).  
a Re nal Flare (as d efi n e d i n Secti o n  8. 1. 6 ), a n d E xtrare n al S L E Flare (as d efi n e d i n Secti o n 8. 1. 7 ) ma y o cc ur at a n y ti me d uri n g t he st u d y. S u b o pti mal Res p o nse (as defi ne d i n 
Secti o n  8. 1. 8 ) ma y o cc ur after Wee k 2 6. E v al u ati o n of Re n al Flare re q uires a U P C R fr o m a s p ot uri n e sa m ple t h at is c o nfir me d o n a 2 4 -h o ur uri ne c ollecti o n, as well as 2  ser u m 
creati ni ne sa m ples o btai n e d wit hi n a 2 -wee k p eri o d. E v al u ati o n of Re n al a n d E xtrare n al S L E Flares m ust b e p erf or me d as s o o n as p ossi ble u p o n n otificati o n t o t he I n v esti gat or 
of s y m pt o m o nset or lac k of res p o nse (after Wee k  2 6). If Re n al Flare or E xtrare n al S L E Flare or S u b o pti mal Res p o nse (after Wee k  2 6) occ urs bet wee n sc he d ule d visits, o nl y t he 
assess me nts f or t h e Re n al Flare/ E xtrare n al S L E Flare/ S u b o pti mal Res p o nse (after Wee k  2 6) Visit are n ee d e d. If Re n al Flare or E xtrare nal S L E Flare or S u b o pti mal Res p o nse 
(after Wee k 2 6) o cc urs o n a sc h e d ule d visit, all sc h e d ule d assess m e nts s h o ul d b e p erf or me d f or t h at visit as well as a n y a d diti o nal asses s me nts re q uire d f or t he e val uati o n of t he 
flare or lac k of res p o nse (after Wee k 2 6).  
b F or partici pa nts w h o disc o nti n u e st u d y i nter v e nti o n pri or t o Wee k  5 0, e v er y eff ort s h o ul d b e ma d e t o h a v e t h e p artici p a nt c o nti n ue t he st u d y visits as per t he S o A t hr o u g h t he 
Wee k 5 0. A Safet y F oll o w -u p Visit s h o ul d b e p erf or me d 3 0 d a ys after t h e last d ose of st u d y i nter v e nti o n. If t h e p artici p a nt d oes n ot a gree t o c o nti n ue wit h t he st u d y visits after 
st u d y i nter ve nti o n is disc o nti n u e d, t h e E D Visit s h o ul d b e p erf or me d as s o o n as p ossi ble, a n d a Safet y F oll o w - -u p Visit s h o ul d be perf or me d 3 0 da ys after t he last d ose of st u d y 
i nter ve nti o n. Refer t o Ta ble  5 for t h e Safet y F oll o w -u p Visit pr o ce d ures.  
c Perf or m a s y m pt o m b ase d n e ur ol o gic e x a mi n ati o n if p artici p a nt h as c o m plai nts or cli nical fi n di n gs attri b uta ble t o t h e C N S a n d  if p ositi ve f or fi n di n gs, f ull ne ur ol o gic 
e xa mi nati o n t o b e p erf or me d at eac h assess me nt ti me p oi nt.  
d Partici pa nts will b e as k e d t o u n d er g o a n o pti o n al re p eat ki d n e y bi o ps y after c o m pleti o n of t h e Bli n de d E xte n d e d Treat me nt Peri o d. If a partici pa nt a grees t o a re peat re nal bi o ps y, 
it s h o ul d be p erf or me d at t h e Wee k 5 0 Visit or wit hi n 4  wee ks ( b y Wee k  5 4).  
e D uri n g t he Bli n d e d E xte n d e d Treat me nt Peri o d, partici p a nts i n t h e L N c o h ort will c o nti n u e t o recei ve t h eir ra n d o mize d all ocati o n of st u d y i nter ve nti o n.  
N ote: If p ossi ble, all assess m e nts s h o ul d be perf o r m e d pri o r t o a d mi nistr ati o n of st u d y i nter v e nti o n o n i n -cli nic d osi n g d a ys, u nless ot her wise s pecifie d.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  F e b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 4 0  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble  3:  
Sc he d ule of Acti vities D uri n g t he Bli n de d E xte n de d Tre at me nt Peri o d: Wee k  3 4 t o Wee k  5 0 Visits ( L N C o h ort)  
A b bre viati o ns: A P  =  alter n ati v e pat h wa y; B b  =  B b fra g me nt of c o m ple me nt fact or  B; C N S  =  ce ntral n er v o us s yste m; D  =  da y; E C G  =  electr ocar di o gra m; E D  =  earl y 
disc o nti n uati o n; e G F R  =  esti mate d gl o mer ular filtrati o n rate; E Q -5 D -5 L  =  E ur o p ea n Q u alit y of Life Healt h 5 -ite m q u esti o n naire di me nsi o ns 5 le vel; F A CI T =  F u ncti o nal 
Assess me nt of C hr o nic Ill n ess T hera p y; L N  =  l u p us n e p hritis; N P T P =  n o n p h ar mac ol o gic t h era pies a n d pr o ce d ures; P D  =  p har mac o d y na mics; P E  =  p h ysical e xa mi nati o n; 
P K  =  p har mac o ki n etics; P R O  =  partici p a nt -re p orte d o utc o me; S F-3 6  =  S h ort F or m ( 3 6) Healt h S ur v e y; S L E  =  s yste mic l u p us er yt he mat os us; S L E D AI-2 K  =  S yste mic L u p us 
Er yt he mat os us Disease Acti vit y I n d e x  2 0 0 0 Safet y of Estr o g e ns i n L u p us Er yt h e mat os us Nati o n al Assess m e nt ( S E L E N A) M o dificati o n; S o A  =  Sc he d ule of Acti vities; 
U P C R  =  uri ne pr otei n t o creati ni ne rati o; W  =  wee k; W O C B P  =  w o me n of c hil d b eari n g p ote ntial  
 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 4 1  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 4: 
Sc he d ule of Acti vities D uri n g t he Bli n de d E xte n de d Tre at me nt Peri o d: Wee k  2 8 t o Wee k 5 0 Visits (I g A N C o h ort) 
Peri o d  
E xte n de d Tre at m e nt Peri o d  
N otes  
Visit  
8 
9 
1 0  
1 1  
1 2  
U nsc he d ule d visits c a n be perf or me d as nee de d. A n E D 
Visit is re q uire d if p artici p a nt disc o nti n ues st u d y e arl y.  
Wee k  
W 2 8 
W 3 2 
W 3 8 
W 4 2 
W 5 0/ 
E D a 
D a ys a n d Wi n d o w  
D 1 9 7  
± 7 
D 2 2 5  
± 7 
D 2 6 7  
± 7 
D 2 9 5  
± 7 
D 3 5 1  
± 7 
Ge ner al Assess m e nts/ Pr o ce d ur es  
Wei g ht
 
 
 
 
 
X 
 
Pre g na nc y test ( W O C B P o nl y)  
X 
X 
X 
X 
X 
Ser u m pre g na nc y test re q uire d at E D; uri ne pre g na nc y tests at 
all ot her visits ( Secti o n 8. 2. 6 ). 
Effic ac y Assess m e nts  
2 4 -h o ur uri ne c ollecti o n  
 
 
 
 
X 
T w o se parate 2 4 -h uri ne c ollecti o ns re q uire d wit hi n 2  wee ks 
pri or t o t he Wee k  5 0 Visit ( Secti o n  8. 1. 1. 2 ). 
M or ni n g s p ot uri n e sa m ple  
X 
X 
X 
X 
X 
Secti o n  8. 1. 2 . 
e G F R ( m eas ure d b y ser u m creati ni n e)  
X 
X 
X 
X 
X 
 
Pre d ose bl o o d sa m ple f or ser u m cli nical c o m ple me nt 
tests 
X 
X 
X 
X 
X 
Secti o n  1 0. 2 .  
S afet y Assess m e nts  
P h ysical e xa mi n ati o n,  i n cl u di n g ne ur ol o gical 
assess me nts b 
 
 
 
 
X 
Secti o n  8. 2. 1 . 
A b bre viate d P E  
X 
X 
X 
X 
 
Vital si g ns  
X 
X 
X 
X 
X 
Vital si g ns t o be ta ke n pre d ose at cli nic visits ( Secti o n  8. 2. 2 ). 
E C G 
 
 
 
 
X 
Secti o n  8. 2. 3 . 
C o nc o mita nt me dicati o ns a n d N P T P  
 
C o nti n u o us m o nit ori n g  
Secti o n  6. 5  an d Secti o n  8. 2. 5 . 
All o we d c o nc o mita nt I g A N t h era p y  
 
C o nti n u o us m o nit ori n g  
Secti o n  6. 5. 3. 2 .  
A d verse e ve nts  
 
C o nti n u o us m o nit ori n g  
Secti o n  1 0. 3 .  
Pre d ose bl o o d sa m ple f or cli nical c h e mistr y, 
h e mat ol o g y, a n d c o a g ulati o n  
X 
X 
X 
X 
X 
Secti o n  8. 2. 4. 2  a nd Secti o n  1 0. 2 . 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 4 2  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 4: 
Sc he d ule of Acti vities D uri n g t he Bli n de d E xte n de d Tre at me nt Peri o d: Wee k  2 8 t o Wee k 5 0 Visits (I g A N C o h ort) 
Peri o d  
E xte n de d Tre at m e nt Peri o d  
N otes  
Visit  
8 
9 
1 0  
1 1  
1 2  
U nsc he d ule d visits c a n be perf or me d as nee de d. A n E D 
Visit is re q uire d if p artici p a nt disc o nti n ues st u d y e arl y.  
Wee k  
W 2 8 
W 3 2 
W 3 8 
W 4 2 
W 5 0/ 
E D a 
D a ys a n d Wi n d o w  
D 1 9 7  
± 7 
D 2 2 5  
± 7 
D 2 6 7  
± 7 
D 2 9 5  
± 7 
D 3 5 1  
± 7 
Uri nal ysis a n d uri n e se di me nt  
X 
X 
X 
X 
X 
Secti o n  8. 2. 4. 3  a nd Secti o n  1 0. 2 .  
Partici pa nt safet y car d re vie w  
X 
X 
X 
X 
X 
C o nfir m partici pa nts carr y safet y car d at all ti mes 
( Secti o n 8. 2. 7 ). 
P K a n d P D Assess m e nts  
Pre d ose bl o o d sa m ples f or P K  
X 
X 
X 
X 
X 
Secti o n  8. 4 . 
Pre d ose bl o o d sa m ple f or B b a n d A P acti vit y  
X 
X 
X 
X 
X 
Secti o n  8. 5 . 
E x pl or at or y Assess m e nts  
S F -3 6  
 
 
X 
 
X 
P R Os t o be perf or me d as earl y as p ossi ble d uri n g visits.  
E Q -5 D -5 L  
 
 
X 
 
X 
Bl o o d a n d uri n e sa m ples f or bi o mar k ers  
X 
X 
X 
X 
X 
C ollect pre d ose o n i n -cli nic d osi n g da ys ( Secti o n  1 0. 2 ). 
St u d y I nter ve nti o n c 
M or ni n g d ose a d mi nistere d i n -cli nic 
X 
X 
X 
X 
X 
A d mi nister d ose after all ot her re q uire d tests/ pr oce d ures.  
St u d y i nter ve nti o n c o m plia n ce a n d acc o u nta bilit y  
X 
X 
X 
X 
X 
Partici pa nts o n st u d y i nter ve nti o n s h o ul d bri n g all u n use d 
st u d y i nter ve nti o n at eac h cli nic visit f or ta blet c o u nti n g. 
St u d y i nter ve nti o n dis p e nsi n g  
X 
X 
X 
X 
X 
Partici pa nts o n st u d y i nter ve nti o n will be pr o vi de d wit h 
s ufficie nt st u d y i nter ve nti o n t o last u ntil t heir ne xt st u d y visit 
(e xce pt at E D). 
a F or partici pa nts w h o disc o nti n u e st u d y i nter v e nti o n pri or t o Wee k  5 0, e v er y eff ort s h o ul d b e ma d e t o h a v e t h e p artici p a nt c o nti n ue t he st u d y visits as per t he S o A t hr o u g h t he 
Wee k 5 0. A Safet y F oll o w -u p Visit s h o ul d b e p erf or me d 3 0 d a ys after t h e last d ose of st u d y i nter v e nti o n. If t h e p artici p a nt d oes n ot a gree t o c o nti n ue wit h t he st u d y visits after 
st u d y i nter ve nti o n is disc o nti n u e d, t h e E D Visit s h o ul d b e p erf or me d as s o o n as p ossi ble, a n d a Safet y F oll o w -u p Visit s h o ul d be perf or me d 3 0 da ys after t he last d ose of st u d y 
i nter ve nti o n. Refer t o Ta ble  5 for t h e Safet y F oll o w -u p Visit pr o ce d ures.  
b Perf or m a s y m pt o m b ase d n e ur ol o gic e x a mi n ati o n if p artici p a nt h as c o m plai nts or cli nical fi n di n gs attri b uta ble t o t h e C N S a n d  if p ositi ve f or fi n di n gs, f ull ne ur ol o gic 
e xa mi nati o n t o b e p erf or me d at eac h assess me nt ti me p oi nt.  
c D uri n g t he Bli n d e d E xte n d e d Treat me nt Peri o d, partici p a nts i n t h e I g A N place b o gr o u p will s witc h t o recei v e eit h er A L X N 2 0 5 0 1 8 0  m g bi d or A L X N 2 0 5 0 1 2 0  m g bi d. 
Partici pa nts i n t h e I g A N c o h ort ra n d o mize d t o acti v e treat me nt will c o nti n u e t o recei v e t h eir ra n d o mize d all o cati o n of st u d y i nter ve nti o n. 
N ote: If p ossi ble, all assess m e nts s h o ul d be perf o r m e d pri o r t o a d mi nistr ati o n of st u d y i nter v e nti o n o n i n -cli nic d osi n g d a ys, u nless ot her wise s pecifie d.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  F e b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 4 3  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble  4:  
Sc he d ule of Acti vities D uri n g t he Bli n de d E xte n de d Tre at me nt Peri o d: Wee k  2 8 t o Wee k  5 0 Visits (I g A N 
C o h ort)  
A b bre viati o ns: A P  =  alter n ati v e pat h wa y; B b  =  B b fra g me nt of c o m ple me nt fact or  B; bi d  =  t wice dail y; C N S =  ce ntral n er v o us s yste m; D  =  da y; E C G  =  electr ocar di o gra m; 
E D  =  earl y disc o nti n u ati o n; e G F R  =  esti mate d gl o mer ular filtrati o n rate; E Q -5 D -5 L  =  E ur o p ea n Q ualit y of Life Healt h 5 -ite m q uesti o n naire di me nsi o ns 5 le vel; 
I g A N =  i m m u n o gl o b uli n A n e p hr o p at h y; N P T P  =  n o n p h ar mac ol o gic t h era pies a n d pr o ce d ures; P D  =  p h ar mac o d y n a mics; P E  =  p h ysical e xa mi nati o n; P K  =  p har mac o ki netics; 
P R O  =  partici p a nt -re p orte d o utc o me; S F -3 6  =  S h ort F or m ( 3 6) Healt h S ur v e y; S o A = Sc h e d ule of Acti vities; W  =  wee k (s); W O C B P  =  w o me n of c hil d beari n g p ote ntial  
 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 4 4  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 5: 
Sc he d ule of Acti vities D uri n g t he O pe n -l a bel E xte nsi o n Peri o d a n d S afet y F oll o w-u p Peri o d ( B ot h L N a n d I g A N 
C o h orts) 
Peri o d  
A d h o c 
visit a  
O pe n -l a bel E xte nsi o n Peri o d 
 
S afet y 
F oll o w -u p 
Peri o d  
N otes  
Wee k  
After  
W 5 0 
W 6 3 
W 7 6 
W 8 9 
W 1 0 2  
W 1 1 5  
W 1 2 8  
W 1 4 1  
W 1 5 4/  
E D b 
E v al u ati o n 
f or Re n al 
Fl are, 
E xtr are n al 
S L E Fl are, 
a n d 
S u b o pti m al 
Res p o nse 
Assess me nt 
Visit  
( L N o nl y)c  
4  wee ks 
p ost l ast 
d ose  
U nsc he d ule d visits c a n be 
perf or me d as nee de d. A n E D 
Visit is re q uire d if p artici p a nt 
disc o nti n ues st u d y e arl y  
D a ys a n d Wi n d o w  
 
D 4 4 2  
± 1 4  
D 5 3 3  
± 1 4  
D 6 2 4  
± 1 4  
D 7 1 5  
± 1 4  
D 8 0 6  
± 1 4  
D 8 9 7  
± 1 4  
D 9 8 8  
± 1 4  
D 1 0 7 9  
± 1 4  
3 0  ( ± 3) 
d a ys p ost 
l ast d ose 
Ge ner al Assess m e nts/ Pr o ce d ur es  
Wei g ht
 
 
 
 
 
 
 
 
 
X 
 
 
 
Pre g na nc y test ( W O C B P o nl y)  
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Ser u m test re q uire d at E D; 
uri ne tests at all ot her visits 
( Secti o n 8. 2. 6 ). 
Effic ac y Assess m e nts  
2 4 -h o ur uri ne c ollecti o n  
 
 
 
 
X 
 
 
 
X 
X 
 
O btai n o ne 2 4 -h o ur uri ne 
c ollecti o n; Secti o n  8. 1. 1  
M or ni n g s p ot uri n e sa m ple  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Secti o n  8. 1. 2 . 
M o nit or f or Re nal Flare a n d/ or 
E xtrare nal S L E Flare a n d/ or 
S u b o pti mal Res p o nse  ( L N 
o nl y)  
 
C o nti n u o us m o nit ori n g  
X 
 
Refer t o Secti o n  8. 1. 6 , 
Secti o n  8. 1. 7 , a n d Secti o n 8. 1. 8  
f or defi niti o ns. D oc u me nt use 
of a d diti o nal sta n dar d of care 
t hera p y a n d/ or re peat bi o ps y, if 
a p plica ble ( Secti o n  6. 5. 4 ). 
Bl o o d sa m ples f or 
a ut oa nti b o dies ( L N o nl y) 
 
 
 
 
 
 
 
 
 
X 
 
Secti o n  1 0. 2 . 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 4 5  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 5: 
Sc he d ule of Acti vities D uri n g t he O pe n -l a bel E xte nsi o n Peri o d a n d S afet y F oll o w-u p Peri o d ( B ot h L N a n d I g A N 
C o h orts) 
Peri o d  
A d h o c 
visit a  
O pe n -l a bel E xte nsi o n Peri o d 
 
S afet y 
F oll o w -u p 
Peri o d  
N otes  
Wee k  
After  
W 5 0 
W 6 3 
W 7 6 
W 8 9 
W 1 0 2  
W 1 1 5  
W 1 2 8  
W 1 4 1  
W 1 5 4/  
E D b 
E v al u ati o n 
f or Re n al 
Fl are, 
E xtr are n al 
S L E Fl are, 
a n d 
S u b o pti m al 
Res p o nse 
Assess me nt 
Visit  
( L N o nl y)c  
4  wee ks 
p ost l ast 
d ose  
U nsc he d ule d visits c a n be 
perf or me d as nee de d. A n E D 
Visit is re q uire d if p artici p a nt 
disc o nti n ues st u d y e arl y  
D a ys a n d Wi n d o w  
 
D 4 4 2  
± 1 4  
D 5 3 3  
± 1 4  
D 6 2 4  
± 1 4  
D 7 1 5  
± 1 4  
D 8 0 6  
± 1 4  
D 8 9 7  
± 1 4  
D 9 8 8  
± 1 4  
D 1 0 7 9  
± 1 4  
3 0  ( ± 3) 
d a ys p ost 
l ast d ose 
S afet y Assess m e nts  
P h ysical e xa mi n ati o n, 
i ncl u di n g ne ur ol o gical 
assess me nts d 
 
 
 
 
 
 
 
 
X 
 
 
Secti o n  8. 2. 1 . 
A b bre viate d P E  
 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
E C G ( o nl y f or L N p atie nts 
recei vi n g h y dr o x y c hl or o q ui n e) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Secti o n  8. 2. 3   
Vital si g ns  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital si g ns t o be ta ke n pri or t o 
d osi n g at cli nic visits 
( Secti o n 8. 2. 2 ). 
C o nc o mita nt me dicati o ns a n d 
N P T P  
 
C o nti n u o us m o nit ori n g  
X 
X 
Secti o n  6. 5  a n d Secti o n  8. 2. 5 .  
All o we d c o nc o mita nt L N or 
I g A N t hera p y 
 
C o nti n u o us m o nit ori n g  
X 
X 
Secti o n  6. 5. 3. 1  an d 
Secti o n  6. 5. 3. 2 .  
A d verse e ve nts  
 
C o nti n u o us m o nit ori n g  
X 
X 
Secti o n  1 0. 3 .  
Bl o o d sa m ple f or cli nical 
c he mistr y, he mat ol o g y, a n d 
c oa g ulati o n 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Secti o n  8. 2. 4. 2  an d 
Secti o n  1 0. 2 . 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 4 6  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 5: 
Sc he d ule of Acti vities D uri n g t he O pe n -l a bel E xte nsi o n Peri o d a n d S afet y F oll o w-u p Peri o d ( B ot h L N a n d I g A N 
C o h orts) 
Peri o d  
A d h o c 
visit a  
O pe n -l a bel E xte nsi o n Peri o d 
 
S afet y 
F oll o w -u p 
Peri o d  
N otes  
Wee k  
After  
W 5 0 
W 6 3 
W 7 6 
W 8 9 
W 1 0 2  
W 1 1 5  
W 1 2 8  
W 1 4 1  
W 1 5 4/  
E D b 
E v al u ati o n 
f or Re n al 
Fl are, 
E xtr are n al 
S L E Fl are, 
a n d 
S u b o pti m al 
Res p o nse 
Assess me nt 
Visit  
( L N o nl y)c  
4  wee ks 
p ost l ast 
d ose  
U nsc he d ule d visits c a n be 
perf or me d as nee de d. A n E D 
Visit is re q uire d if p artici p a nt 
disc o nti n ues st u d y e arl y  
D a ys a n d Wi n d o w  
 
D 4 4 2  
± 1 4  
D 5 3 3  
± 1 4  
D 6 2 4  
± 1 4  
D 7 1 5  
± 1 4  
D 8 0 6  
± 1 4  
D 8 9 7  
± 1 4  
D 9 8 8  
± 1 4  
D 1 0 7 9  
± 1 4  
3 0  ( ± 3) 
d a ys p ost 
l ast d ose 
Uri nal ysis a n d uri n e se di me nt  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Secti o n  8. 2. 4. 3  an d 
Secti o n  1 0. 2 . 
Partici pa nt safet y car d re vie w  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
C o nfir m partici pa nts carr y 
safet y car d at all ti mes 
( Secti o n 8. 2. 7 ). 
St u d y I nter ve nti o n e 
St u d y i nter ve nti o n c o m plia n ce 
a n d acc o u nta bilit y 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Partici pa nts o n st u d y 
i nter ve nti o n s h o ul d bri n g all 
u n use d st u d y i nter ve nti o n at 
eac h cli nic visit f or ta blet 
c o u nti n g. 
St u d y i nter ve nti o n dis p e nsi n g  
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Partici pa nts o n st u d y 
i nter ve nti o n will be pr o vi de d 
wit h s ufficie nt st u d y 
i nter ve nti o n t o last u ntil t heir 
ne xt st u d y visit (e xce pt at 
W 1 5 4 a n d E D).  
a A d h oc visit is o nl y a p plica ble f or L N p atie nts w h o are recei vi n g h y dr o x y c hl or o q ui n e: W h e n p atie nts are s witc h e d fr o m 1 2 0 m g t o 1 8 0 m g after Wee k 5 0, or w he n place b o 
patie nts w h o are o n all o we d c o n c o mita nt t h era p y i nitiate A L X N 2 0 5 0 at a n y d ose d u e t o a Re n al Flare, a d diti o n al E C G nee ds t o be o btai ne d at a n a d h oc visit 2 wee ks ( ± 7 da ys) 
after t he d ose i nitiati o n or d ose escalati o n.  
b F or partici pa nts w h o disc o nti n u e st u d y i nter v e nti o n pri or t o t h e e n d of t h e O p e n -la b el E xte nsi o n Peri o d, t h e E D Visit s h o ul d be perf or me d as s o o n as p ossi ble a n d a Safet y 
F oll o w -u p Visit s h o ul d b e p erf or me d 3 0 d a ys after t h e last d ose of st u d y i nter v e nti o n.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 4 7  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 5: 
Sc he d ule of Acti vities D uri n g t he O pe n -l a bel E xte nsi o n Peri o d a n d S afet y F oll o w-u p Peri o d ( B ot h L N a n d I g A N 
C o h orts) 
c Re nal Flare (as d efi n e d i n Secti o n  8. 1. 6 ), E xtrare n al S L E Flare (as d efi n e d i n Secti o n 8. 1. 7 ) ma y o cc ur at a n y ti me d uri n g t he st u d y a n d S u b o pti mal Res p o nse (as defi ne d i n 
Secti o n  8. 1. 8 ) after Wee k 2 6. E v al u ati o n of Re n al Flare re q uires a U P C R fr o m a s p ot uri n e sa m ple t h at is c o nfir me d o n a 2 4 -h o ur uri ne c ollecti o n, as well as 2 ser u m creati ni ne 
sa m ples o btai n e d wit hi n a 2-wee k p eri o d. E v al u ati o n of Re n al a n d E xtrare n al S L E Flares or S u b o pti mal Res p o nse m ust be perf or me d as s o o n as p ossi ble u p o n n otificati o n t o t he 
I n vesti gat or of s y m pt o m o nset or lac k of res p o nse. If Re n al Flare or E xtrare n al S L E Flare or S u b o pti mal Res p o nse o cc urs bet wee n sc he d ule d visits, o nl y t he assess me nts f or t he 
Re nal Flare/ E xtrare n al S L E Flare/ S u b o pti mal Res p o nse Visit are nee d e d. If Re n al Flare or E xtrare n al S L E Flare or S u b o pti mal Res p o nse occ urs  o n a sc he d ule d visit, all 
sc he d ule d assess me nts s h o ul d b e p erf or me d f or t h at visit as well as a n y a d diti o n al assess me nts re q uire d f or t h e e v al u ati o n of t he flare or lac k of res p o nse. 
d Perf or m a s y m pt o m b ase d n e ur ol o gic e x a mi n ati o n if p artici p a nt h as c o m plai nts or cli nical fi n di n gs attri b uta ble t o t h e C N S a n d  if p ositi ve f or fi n di n gs, f ull ne ur ol o gic 
e xa mi nati o n t o b e p erf or me d at eac h assess me nt ti me p oi nt.  
e I n t he L N c o h ort, place b o p atie nts will recei v e o nl y all o we d c o n c o mita nt t h era p y. F or all ot h er p atie nts i n b ot h c o h orts, see Fi g ure  1 an d  Fi g ure  2. 
N ote: If p ossi ble, all assess m e nts s h o ul d be perf o r m e d pri o r t o a d mi nistr ati o n of st u d y i nter v e nti o n o n i n-cli nic d osi n g d a ys, u nless ot her wise s pecifie d.  
A b bre viati o ns: C N S  = ce ntral n er v o us s yste m; D  = d a y; E C G  = electr o car di o gra m; E D  = earl y disc o nti n u ati o n; I g A N  = i m m u n o gl o b uli n A ne p hr o pat h y; L N  = l u p us ne p hritis; 
N P T P  = n o n p h ar mac ol o gic t h era pies a n d pr o ce d ures; P E  = p h ysical e x a mi n ati o n; S L E  = s yste mic l u p us er yt h e mat os us; U P C R = uri ne pr otei n t o creati ni ne rati o; W  = wee k; 
W O C B P = w o me n of c hil d b eari n g p ote ntial  
 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 4 8  of 1 5 2  
Ale xi o n C o nfi de ntial  
2.  
I N T R O D U C TI O N 
2. 1.  
St u d y R ati o n ale  
A L X N 2 0 5 0 is a p ote nt, r e versi ble, or al s mall m olec ule i n hi bit or of F D, w hic h is a n esse ntial 
c o m p o ne nt of t he c o m ple me nt A P. T he c o m ple me nt s yste m is i n v ol ve d i n t he pat h o p h ysi ol o g y 
of pr olifer ati ve L N a n d I g A N. T he o bjecti ves of t his st u d y are t o e val uate t he effi cac y a n d safet y 
of oral A L X N 2 0 5 0 c o m p are d t o place b o, de m o nstrate pr o of of c o n ce pt f or efficac y of F D 
i n hi biti o n, a n d esta blis h a n eff ecti ve d ose t h at a d dresses o n g oi n g u n met me dical nee d i n patie nts 
wit h L N or I g A N w h o ar e treate d wit h all o we d c o nc o mita nt t hera p y c o nsiste nt wit h t he sta n dar d 
of car e . 
2. 2.  
B ac k gr o u n d  
2. 2. 1.  
L u p us Ne p hritis a n d I m m u n o gl o b uli n A Ne p hr o p at h y  
C hr o nic ki d ne y disease ( C K D) has bec o me a w orl d wi de p u blic healt h iss ue d ue t o its hi g h 
i nci de nce, p o or pr o g n osis, a n d s u bsta ntial ec o n o mic b ur de n. W he n n ot pr o perl y dia g n ose d a n d 
ma na ge d, C K D ca n lea d t o a d verse o utc o m es, i ncl u di n g e n d -sta ge re nal dis ease ( E S R D)  
(L v, 2 0 1 9 ). Des pite a d va nces i n i m m u n os u p pressi ve treat me nts, certai n t y p es of 
gl o mer ul o ne p hritis s uc h as L N a n d I g A N c o nti n u e t o res p o n d p o orl y t o treat me nt, res ulti n g i n 
C K D o ver ti me. T her e has bee n s o me pr o gress i n ter ms of a p pr o v e d treat me nts f or patie nts wit h 
L N wit h 2 rece nt a p pr o v als i n t he U S, ie, beli m u ma b a n d v ocl os p ori n. At 2  years, beli m u ma b 
s h o we d a c o m plete re n al res p o nse ( C R R) of 3 0. 0 % vs 2 0. 0 % c o m pare d t o place b o (F urie, 2 0 2 0 ). 
At 1  year, v ocl os p ori n s h o we d a C R R of 4 0. 8 % vs 2 2. 5 % c o m pare d t o place b o (Arrie ns, 2 0 2 0 ). 
H o we ver, t here re mai ns a si g nifica nt u n met nee d f or i nter ve nti o ns t hat w o ul d all o w m ore n o vel, 
defi niti ve, a n d t olera ble treat me nts f or p atie nts wit h L N as well as f or patie nts wit h I g A N, 
partic ularl y i n t h ose w h o are at ris k of pr o gressi ve ki d ne y diseas e.  
T he pat h o p h ysi ol o g y of gl o mer ular diseas es s uc h as L N a n d I g A N i n v ol ves a c o m ple x o verl a p 
of a b n or mal cell ular i m m u ne res p o nse, l oss of h u m oral i m m u ne t olera nce, a berra nt c oa g ul ati o n, 
a n d s yste mic i nfla m mati o n. D ysre g ulati o n of t he A P of c o m ple me nt, eit her  b y direct A P 
acti vati o n or via t he A P -me diate d a m plificati o n of c o m ple me nt classical pat h wa y ( C P) a n d lecti n 
pat h wa y ( L P), h as e mer g e d as a n a d diti o nal dri vi n g fact or t hat i nter pl a ys wit h t hese pat h wa ys i n 
L N a n d I g A N (L u ka ws k a, 2 0 1 8 ; T h ur ma n, 2 0 0 6 ). T he narr o w vessels a n d hi g h perf usi o n i n t he 
ki d ne y ma ke t his or ga n p artic ularl y s usce pti ble t o i m m u ne c o m ple x (I C) de p ositi o n a n d 
c o nse q ue nt c o m ple me nt -me diate d i nj ur y. Hist ol o gic e vi de nce of c o m ple m e nt de p ositi o n 
o bser ve d i n ki d ne y bi o ps y sa m ples fr o m patie nts wit h eit her L N or I g A N s u g gests a pat h ol o gical 
r ole. Ser u m/ plas ma le vels of c o m ple me nt c o m p o n e nts wit hi n a n d d o w nstrea m of t he A P (e g, 
c o m ple me nt c o m p o ne nt 3 [ C 3] a n d t he me m bra ne attac k c o m ple x [ M A C]) c orrel ate wit h disease 
acti vit y a n d res p o nse t o treat me nt, partic ularl y i n patie nts wit h L N (Gali n d o -Iz q uier d o, 2 0 2 1; 
T h ur ma n, 2 0 1 5 ). 
2. 2. 2.  
A L X N 2 0 5 0  
A L X N 2 0 5 0 is a n or all y acti ve, s mall m olec ule, c o m ple me nt F D i n hi bit or t hat is i n de vel o p me nt 
f or t he treat me nt of c o m ple me nt-me diate d diseas es. A seri ne pr otease, F D catal yzes t he clea va ge 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 4 9  of 1 5 2  
Ale xi o n C o nfi de ntial  
of c o m ple me nt fact or B ( F B) t o pr o d uce t he B b fra g me nt of c o m ple me nt fact or B ( B b), a n 
e nz y matic c o m p o n e nt of A P C 3 a n d c o m ple me nt c o m p o ne nt 5 ( C 5) c o n vertases. A L X N 2 0 5 0 
acts b y bi n di n g re versi bl y t o F D, bl oc ki n g its seri ne pr oteas e acti vit y a n d t here b y i n hi biti n g A P 
acti vati o n a n d t he r es ulti n g pr o d ucti o n of C 3 clea va ge fra g me nts, a na p h yl at o xi ns of c o m ple me nt 
c o m p o ne nts 3a a n d  5a ( C 3a a n d C 5a), a n d d o w nstrea m M A C c o m ple x (Fi g ure  3). In a d diti o n, 
alt h o u g h F D i n hi biti o n d oes n ot i n hi bit c o m p o ne nts s pecific t o t he C P or L P of c o m ple me nt, it 
will re d uce t he pr o d ucti o n of C 3 clea va g e fra g me nts a n d d o w nstrea m M A C f or mati o n i nitiate d 
t hr o u g h t hese 2 pat h wa ys via i n hi biti o n of t he a m plificati o n of acti vati o n (H ar b oe, 2 0 0 4 ). 
Fi g ure  3:  
C o m ple m e nt P at h w a ys 
 
A b bre viati o ns: C  = c o m ple me nt c o m p o ne nt; F B  = c o m ple me nt fact or B; F D  = c o m ple me nt fact or D; 
M A C  = me m bra ne attac k c o m ple x  
S o urce: A da pte d fr o m   (Merle, 2 0 1 5a ; Merle, 2 0 1 5 b ; Y ua n, 2 0 1 7 ) 
A detaile d descri pti o n of t he c he mistr y, p har mac ol o g y, efficac y, a n d s afet y of A L X N 2 0 5 0 is 
pr o vi de d i n t he I n vesti gat or’s Br oc h ure (I B). 
2. 2. 3.  
R ati o n ale f or E v al u ati n g A L X N 2 0 5 0 i n P artici p a nts wit h L u p us Ne p hritis 
L u p us ne p hritis occ urs i n a p pr o xi matel y 5 0 % of p atie nts wit h S L E ( Al maa ni, 2 0 1 9 ; M orales,  
2 0 2 1 ), a n a ut oi m m u ne dis or der ca use d b y l oss of t olera nce t o self-a nti ge ns, t he pr o d ucti o n of 
a ut oa nti b o dies, a n d de p ositi o n of c o m ple me nt-fi xi n g I Cs i n i nj ure d tiss ues  
(Ba o, 2 0 1 5 ). T he dia g n osis of L N is deter mi ne d b y ki d ne y bi o ps y acc or di n g t o t he 
2 0 1 8 I nter nati o nal S ociet y of Ne p hr ol o g y/ Re nal P at h ol o g y S ociet y (I S N/ R P S) n o me nclat ure a n d 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 5 0  of 1 5 2  
Ale xi o n C o nfi de ntial  
classificati o n re vise d fr o m t he 2 0 0 3 re p ort (Baje ma, 2 0 1 8 ; Mar k o witz, 2 0 0 7 ). I n t otal, t here are 
6 classes of L N: Classes  I t o VI (Mar k o witz, 2 0 0 7 ). T he s u bset of p atie nts wit h S L E t hat de vel o p 
L N ha ve t he w orst pr o g n osis. L u p us ne p hritis lea di n g t o C K D is a n i n de pe n de nt maj or ris k 
fact or f or o ver all m ortalit y a n d m or bi dit y attri b ute d t o car di o vasc ul ar diseases  
(Gas par ott o, 2 0 2 0 ). Wit h c urre nt i n d ucti o n a n d m ai nte na nce t hera pi es, t he 5-year m ort alit y is 
a p pr o xi matel y 2 0 %, a n d t he ris k of de vel o pi n g E S R D at 5, 1 0, a n d 1 5 years is 1 1 %, 1 7 %, a n d 
2 2 %, res pecti vel y  
(Te kt o ni d o u, 2 0 1 6 ). Rec urre nce of L N after treat me nt ( Re nal Flare) o cc urs wit hi n 1 year i n u p t o 
2 5 % of patie nts a n d is ass ociate d wit h i ncrease d ris k of C K D pr o gressi o n ( Al maa ni, 2 0 1 7 ). 
T he pat h o p h ysi ol o g y of L N i n v ol ves m ulti ple o verla p pi n g pat h wa ys w here c o m ple me nt ser v es 
as a me diat or of a n a b n or mal i m m u ne res p o nse ( B a o, 2 0 1 5 ; Pic keri n g, 2 0 0 0 ). I m m u ne 
c o m ple xes ca n acti vate t he c o m ple me nt C P b y direct i nteracti o n wit h c o m ple me nt c o m p o ne nt 1 q 
( C 1 q) i n t he C 1 c o m ple x; f urt her acti vati o n b y t he A P- me diate d a m plificati o n l o o p c o ntri b utes t o 
t he o verall acc u m ulati o n of c o m ple me nt acti vati o n pr o d ucts a n d t he res ulti n g i nfla m mat or y 
res p o nse a n d tiss ue i nj ur y. T he ter mi nal c o m ple m e nt c o m p o ne nts ( C 5a a n d ter mi nal c o m ple me nt 
c o m ple x [ C 5 b- 9]) tri g g er ac ute cell ular i nfla m mat or y res p o nses t hr o u g h acti vati o n of i nterle u ki n 
a n d c yt o ki ne si g nali n g. C o m ple me nt als o ser ves t o fi x i m m u n o gl o b uli ns a n d I Cs i n t he ki d ne y 
(T h ur ma n, 2 0 2 0 ). I n fact, c o m ple me nt a n d c o m ple me nt s plit pr o d ucts are a pr o mi ne nt hist ol o gic 
fi n di n g i n ki d ne y bi o psies of patie nts wit h L N (Biesec ker, 1 9 8 1 ; Wils o n, 2 0 1 9 ). Ser u m le vels of 
t hese a ut oi m m u ne a n d c o m ple me nt bi o mar kers are li n ke d wit h disease acti vit y  
(Bir mi n g ha m, 2 0 1 0 ; Dall' Era, 2 0 1 1 ). D ecreas es i n C 3, c o m ple me nt c o m p o ne nt 4 ( C 4), a n d C 1 q 
are ass o ciate d wit h de n o v o L N a n d L N fl ares. Li k e wise, le vels of c o m ple me nt bi o mar kers 
c orrel ate wit h disease acti vit y i n S L E (Ki m, 2 0 1 9 ; S o n g, 2 0 1 7 ). I n fact, t he p har mac o d y n a mic 
( P D) mar ker of A L X N 2 0 5 0, plas ma c o m ple me nt fact or B b, is si g nifica ntl y ele vate d i n patie nts 
wit h acti ve L N w he n c o m pare d t o patie nts wit h L N i n cli nical re missi o n, acti ve S L E wit h o ut 
L N, a n d n or mal c o ntr ols. Lastl y, plas ma B b le vel si g nifica ntl y c orrel ates wit h ki d ne y disease 
acti vit y i n dices a n d is a ris k fact or f or a d verse ki d ne y o utc o mes ( S o n g, 2 0 1 7 ). 
Rest ori n g c o m ple me nt re g ulati o n ma y i m pr o ve re nal res p o nses t hr o u g h ac ute a nti- i nfla m mat or y 
effects a n d lasti n g effects o n I C de p ositi o n- me diat e d i nj ur y i n t he ki d ne y. T he c o ntri b uti o n of 
A P  acti vit y t o L N pat h o p h ysi ol o g y has bee n de m o nstrate d i n m o use m o dels  
(Elli ott, 2 0 0 4 ; Gr oss ma n, 2 0 1 6 ; Wata na b e, 2 0 0 0 ) a n d f urt her s u p p orte d b y s ol u ble bi o mar ker 
pr ofiles a n d t he c o m p ositi o n of re nal de p ositi o n i n patie nts wit h L N (Bir mi n g ha m, 2 0 1 7 ; Ki m,  
2 0 2 0 ; L u ka ws ka, 2 0 1 8 ; S o n g, 2 0 1 7 ). Rest ori n g A P re g ulati o n ma y i m pr o ve re nal res p o nses 
t hr o u g h ac ute a nti-i nfl a m mat or y eff ects a n d lasti n g effects o n I C de p ositi o n- me diate d i nj ur y i n 
t he ki d ne y. He nce, F D i n hi biti o n is pr o misi n g f or b ot h i n d ucti o n treat me nt f or acti ve 
pr oliferati ve L N a n d mai nte na nce tr eat me nt of c hr o nic L N (L u ka ws ka, 2 0 1 8 ; T h ur ma n, 2 0 0 6 ). 
T he A merica n C olle ge of R he u mat ol o g y ( A C R) a n d j oi ntl y t he E ur o pea n Lea g ue A g ai nst 
R he u matis m ( E U L A R) a n d E ur o pea n Re n al Ass o ciati o n- E ur o pea n Dial ysis a n d Tra ns pla nt 
Ass ociati o n ( E R A- E D T A) rec o m me n d i m m u n os u p pressi o n treat me nt f or Class III, I V, III/ V, 
a n d I V/ V L N, als o calle d “ pr olifer ati ve” L N (Bertsias, 2 0 1 2 ). T he g ui deli n es a gree o n i n d ucti o n 
treat me nt wit h gl uc oc orti c oi ds pl us M M F or l o w- d ose c ycl o p h os p ha mi de. F or mai nte na n ce 
t hera p y, t he g ui deli nes a gree o n M M F or azat hi o pri ne, wit h or wit h o ut l o w d ose gl uc oc ortic oi ds 
(Bertsias, 2 0 1 2 ). I n p atie nts wit h L N, t he mai n g oal of t hera p y is pre ve nti o n of C K D 
pr o gressi o n, pre v e nti o n of E S R D, a n d i m pr o ve d s ur vi val. Lac k of ac hie v e me nt of re missi o n, i n 
pa rtic ular c o m plete re missi o n, is o ne of t he maj or ris k fact ors f or t he pr o gressi o n of re nal 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 5 1  of 1 5 2  
Ale xi o n C o nfi de ntial  
disease. He n ce, s h ort -ter m C R R a n d partial re nal res p o nse ( P R R) are use d t o assess t he effi cac y 
of sta n dar d of car e a n d n o vel t hera pies. After 6 t o 1 2 m o nt hs of treat me nt, o nl y 1 0 % t o 4 0 % of 
patie nts ac hie ve a C R R wit h sta n dar d of care (Pari k h, 2 0 1 6 ). 
Rece nt a p pr o v als i n t he U S of beli m u ma b a n d v ocl os p ori n re prese nt pr o gress i n t he treat me nt of 
L N. Res ults at 2 years s h o we d a C R R of 3 0. 0 % f or beli m u ma b vs 2 0. 0 % f or place b o  
(F urie, 2 0 2 0 ). F or v ocl os p ori n, C R R was 4 0. 8 % c o m pare d t o 2 2. 5 % f or place b o at o ne year  
(Arrie ns, 2 0 2 0 ). H o we v er, a si g nifica nt nee d e xists f or t hera pi es t hat yiel d fast a n d d ura bl e 
res p o nses, wit h hi g h c o m plete res p o nse rates, al o n g wit h re d uce d n ee d f or ster oi ds a n d/ or 
i m m u n os u p pressa nts i n patie nts wit h L N. 
2. 2. 4.  
R ati o n ale f or E v al u ati n g A L X N 2 0 5 0 i n P artici p a nts wit h I m m u n o gl o b uli n A 
Ne p hr o p at h y  
I m m u n o gl o b uli n A ne p hr o pat h y (I g A N), als o k n o w n as Ber ger’s diseas e, is t he m ost c o m m o n 
gl o bal pri mar y gl o mer ul o ne p hr o pat h y t hat ca n pr o gress t o re nal fail ure. I m m u n o gl o b uli n A 
ne p hr o pat h y is a lifel o n g disease lea di n g t o C K D a n d pr o gresses t o E S R D i n 3 0 % t o 4 0 % of 
patie nts o ver t he c o urse of 2 0 t o 3 0 years (Lai, 2 0 1 6 ). Patie nts i nitiall y prese nt wit h he mat uria 
a n d h y perte nsi o n, a n d pr otei n uria de vel o ps as t he disease pr o gresses. Dia g n osis of I g A N is ma de 
b y re nal bi o ps y de m o nstr ati n g i m m u n o gl o b uli n A (I g A) i m m u n ofl u ores ce n ce i n t he gl o mer uli, 
us uall y c o d o mi na nt wit h C 3 acc or di n g t o t he O xf or d Classificati o n n o me nclat ure  
(K DI G O, 2 0 1 7 ; Riz k, 2 0 1 9 ; Tri marc hi, 2 0 1 7 ). 
T he pat h o p h ysi ol o g y of I g A N is relate d t o t he o v er pr o d ucti o n of u n der- gl y c os ylate d 
i m m u n o gl o b uli n A 1 (I g A 1), w hic h acc u m ulates i n t he ki d ne y gl o mer uli. H o we ver, a berra nt 
galact os ylati o n al o ne is i ns ufficie nt t o i n d uce re nal i nj ur y; gl yca n- s pecific I g A a n d 
i m m u n o gl o b uli n G (I g G) a ut oa nti b o dies t hat rec o g nize t he u n der- galact os ylate d I g A 1 m olec ule 
li kel y als o c o ntri b ute. T his pr ocess lea ds t o t he l ocal i nfla m mati o n a n d c o m ple me nt acti vati o n i n 
t he ki d ne y (O ort wij n, 2 0 0 8 ). B ot h t he A P a n d L P c o m ple me nt pat h wa ys m a y be acti vate d, 
lea di n g t o ge ner ati o n of a na p h ylat o xi ns of C 3a a n d C 5a, a n d t he M A C C 5 b- 9, wit h s u bse q ue nt 
pr o m oti o n of i nfla m mat or y me diat ors ( L u ka ws ka, 2 0 1 8 ; Maillar d, 2 0 1 5 ; T h ur ma n, 2 0 0 6 ). C 4 
a n d C 3 c o m ple xes a n d acti vate d C 3 pr o d ucts are ele vate d i n u p t o 3 0 % of p atie nts wit h I g A N. 
Acti vate d C 3 pr o d ucts ar e ass ociate d wit h ele vate d le vels of pr otei n uria a n d he mat uria c o m pare d 
t o patie nts wit h I g A N w h o ha ve n or mal le v els of t hese pr o d ucts, a n d c orrel ate wit h deteri orati o n 
of re nal f u n cti o n ( Z wir n er, 1 9 9 7 ). C o m ple me nt acti vit y o n ki d ne y bi o ps y a n d circ ulati n g 
c o m ple me nt pr otei ns ar e ass ociate d wit h diseas e acti vit y a n d pr o gressi o n of C K D. E vi de nce f or 
A P i n v ol ve me nt has bee n esta blis he d i n t he c o de p ositi o n wit h I g A of pr o p er di n a n d of re g ulat ors 
of A P C 3  c o n vertase st a bilit y i ncl u di n g c o m ple me nt fact or H ( F H) a n d fact or  H-relate d pr otei n- 5 
( F H R 5) (M e djer al - T h o m as, 2 0 1 4; Riz k, 2 0 1 9 ). F urt her s u p p ort has arise n fr o m t he ass ociati o n of 
I g A N pat h o ge n esis wit h circ ulati n g le vels of t he F H R pr otei ns, a n d wit h t he i de ntificati o n of 
b ot h pr otecti ve a n d pat h o ge nic varia nts i n t he C F H  l oc us w hic h affect e x pressi o n or acti vit y of 
F H a n d F H -relate d pr otei ns (T ortaja da, 2 0 1 9 ). T o get her t hese fi n di n gs s u g gest a r ole of 
c o m ple me nt i n t he pat h o p h ysi ol o g y a n d t he pr o g n ostic val ue of c o m ple me nt bi o mar kers i n I g A N 
(Riz k, 2 0 1 9 ). A ni mal st u dies de m o nstrate t hat a b erra ntl y gl yc os ylate d I g A c o m ple xes wit h C 3 b 
a n d F B ar e c o d e p osite d i n gl o mer uli ( Has hi m ot o, 2 0 1 2 ). T his is s u p p orte d i n h u ma ns t hr o u g h 
data de m o nstrati n g ele v ate d messe n ger ri b o n uclei c aci d ( m R N A) tra nscri pt e x pressi o n of F D 
a n d pr o per di n i n gl o mer uli relati ve t o ot her ki d ne y fracti o ns ( S o n g, 1 9 9 8 ). 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 5 2  of 1 5 2  
Ale xi o n C o nfi de ntial  
Fact or  D i n hi biti o n is a p ote ntial tar get f or treat me nt of patie nts wit h I g A N at hi g h ris k of 
pr o gressi o n t o ki d ne y disease ( Riz k, 2 0 1 9 ) (ie, si g nifica nt pr otei n uria d es pite o pti mal R A S 
bl oc ka de) ( Reic h, 2 0 0 7 ). Fact or D i n hi biti o n bl oc ks c o m ple me nt A P acti vati o n directl y a n d 
te m pers c o m ple me nt acti vati o n via ot her pat h wa ys t hr o u g h i n hi biti o n of t he a m plificati o n l o o p, 
lea di n g t o pre ve nti o n of t he d o w nstrea m m olec ular a n d cell ular c o nse q u e nces, a n d s u bse q ue ntl y 
has p ote n tial f or t her a pe utic efficac y i n patie nts wit h I g A N. 
Treat me nts f or I g A N i ncl u de R A S bl oc ki n g a ge nts, s uc h as a n gi ote nsi n-c o n verti n g e nz y me 
( A C E) i n hi bit ors ( A C Eis) or a n gi ote nsi n II rece pt or bl oc kers ( A R Bs). T hese t hera pies are ai me d 
at c o ntr olli n g bl o o d press ure a n d pr eser vi n g ki d ne y f u ncti o n t hr o u g h decreasi n g i ntra gl o mer ular 
press ure, w hi c h i n t ur n re d uces pr otei n uria. T hese treat me nts are i ns ufficie nt i n preser vi n g re n al 
f u ncti o n i n patie nts wit h I g A N, as a hi g h pr o p orti o n still s uffer fr o m pr o gressi ve C K D a n d 
E S R D (K DI G O, 2 0 2 0 ). Patie nts wit h baseli ne h y perte nsi o n (P u g h, 2 0 1 9 ) a n d 
pr otei n uria > 1 g/ da y (Reic h, 2 0 0 7 ) ar e at i ncrease d ris k f or re n al disease pr o gressi o n.  
2. 3.  
Be nefit/ Ris k Assess m e nt  
2. 3. 1.  
Ris k Assess m e nt  
P ote ntial ris ks ass ociate d wit h partici pati o n i n t his st u d y a n d ris k miti gati o n meas ures are 
prese nte d i n  Ta bl e  6. 
T a ble 6:  
P ote nti al Ris ks a n d Miti g ati o n Str ate gies 
P ote nti al Ris ks of 
Cli nic al Si g nific a nce  
S u m m ar y of D at a/ R ati o n ale f or 
Ris k  
Miti g ati o n Str ate g y 
St u d y I nter ve nti o n  
Me ni n g oc occal i nfecti o n  Partici pa nts recei vi n g Fact or  D 
c o m ple me nt i n hi bit or t hera p y 
ma y ha ve a n i ncrease d ris k of 
i nfecti o ns, partic ularl y Neisseri a 
me ni n giti dis.  
All partici pa nts m ust be vacci nate d 
a gai nst me ni n g oc occal disease wit hi n 
3 years pri or t o, or at t he ti me of, 
i nitiati n g t he st u d y i nter ve nti o n. 
Partici pa nts w h o i nitiate st u d y 
i nter ve nti o n less t ha n 2 wee ks after 
recei vi n g a me ni n g oc occal vacci ne 
m ust recei ve treat me nt wit h 
a p pr o priate pr o p h ylactic a nti bi otics 
u ntil at least 2  wee ks after vacci nati o n.  
Partici pa nts m ust carr y t he Patie nt 
Safet y Car d dis pe nse d at t he Da y  1 
Visit at all ti mes t o pr o m ote ra pi d 
rec o g niti o n of a n y p ote ntial si g ns or 
s y m pt o ms of i nfecti o n. 
Seiz ure  
C o n v ulsi o ns a n d/ or 
electr oe nce p hal o gra m 
a b n or malities ha ve bee n o bser ve d 
d uri n g n o ncli nical re peat- d ose 
t o xic ol o g y st u dies. Refer t o 
Partici pa nts wit h hist or y of seiz ures 
are e xcl u de d. Pr oce d ures s pecifie d i n 
Secti o n  1 0. 1 4  are t o be f oll o we d if a 
s us pecte d seiz ure occ urs. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 5 3  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 6:  
P ote nti al Ris ks a n d Miti g ati o n Str ate gies 
P ote nti al Ris ks of 
Cli nic al Si g nific a nce  
S u m m ar y of D at a/ R ati o n ale f or 
Ris k  
Miti g ati o n Str ate g y 
Secti o n  4. 3  f or i nf or mati o n o n t he 
safet y mar gi n. 
Ot her  
Pre g na nc y 
e x p os ure/lactati o n 
N o st u dies of A L X N 2 0 5 0 ha ve 
bee n c o n d ucte d i n pre g na nt 
w o me n. T here are n o data 
a vaila ble o n e xcreti o n of 
A L X N 2 0 5 0 i n breast mil k.  
Pre g na nc y testi n g will be c o n d ucte d as 
s pecifie d i n t he Sc he d ule of Acti vities 
( Secti o n 1. 3 ). A ne gati ve ser u m 
pre g na nc y test ( Scree ni n g Visit) a n d a 
ne gati ve uri ne pre g na nc y test ( Da y 1) 
are re q uire d pri or t o ra n d o mizati o n.  
If a pre g na nc y is re p orte d d uri n g t he 
st u d y, safet y f oll o w- u p will be 
perf or me d ( Secti o n  1 0. 5 ). 
Pre g na nt or n ursi n g w o me n are 
e xcl u de d fr o m partici pati n g i n t his 
cli nical st u d y. Partici pa nts m ust use a 
hi g hl y effecti ve or acce pta ble  met h o d 
of c o ntrace pti o n d uri n g t he st u d y a n d 
f oll o wi n g t he final d ose of st u d y 
i nter ve nti o n ( Secti o n 1 0. 5 ). 
2. 3. 1. 1.  
C or o n a vir us Dise ase 2 0 1 9 
T he C O VI D - 1 9 p a n de mi c is acti ve i n ma n y c o u ntries at t he ti me of t his pr ot oc ol a me n d me nt. 
Gi ve n t his u ni q ue circ u msta nce, s pecific c o nsi derati o n has bee n gi ve n t o t he ris ks a n d be n efits of 
t he st u d y as t he y relate t o C O VI D- 1 9, a n d t h e gl o bal a n d l ocal c h a nges t hat e xist as a res ult of 
t he pa n de mic. T his assess me nt is descri be d i n Secti o n 1 0. 1 1 . T he ris k assess me nt f or C O VI D- 1 9 
vacci nati o n is descri be d i n Secti o n  1 0. 1 2 . 
2. 3. 2.  
Be nefit Assess m e nt  
L N a n d I g A N ar e lifel o n g diseases t hat lea d t o pr o gressi ve l oss of ki d ne y f u ncti o n. As ki d ne y 
f u ncti o n decli nes, patie nts ma y s uffer t h e m or bi dit y a n d m ortalit y ass ociate d wit h a d va nce d 
C K D, dial ysis, a n d ki d ne y tra ns pla nt. W hile t here has bee n s o me pr o gress i n ter ms of a p pr o v e d 
treat me nts f or p atie nts wit h L N ( beli m u ma b a n d v ocl os p ori n) a n d I g A N ( b u des o ni de), t here 
re mai ns a si g nifica nt u n met nee d f or n o v el i nter v e nti o ns w hic h w o ul d all o w m ore defi niti ve 
treat me nts f or L N as well as disease-s p ecific treat me nts f or patie nts wit h I g A N, partic ularl y i n 
patie nts w h o are at ris k of pr o gressi ve ki d n e y disease. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 5 4  of 1 5 2  
Ale xi o n C o nfi de ntial  
Base d o n its mec ha nis m of acti o n ( Secti o n  2. 2. 2 ), A L X N 2 0 5 0 ma y pr o vi de a n effi caci o us 
treat me nt t o patie nts wit h L N or I g A N, rare diseas es wit h a lar ge u n m et cli nical nee d. P ote ntial 
be nefits of partici pati n g i n t his cli nical st u d y i ncl u de:  
•  M ore fr e q ue nt r o uti ne assess me nts/ pr oce d ures (e g, p h ysical e xa mi nati o ns a n d vital 
si g ns assess me nts) at pres pecifie d st u d y visits 
•  P ote ntial cli nical i m pr o ve me nt a n d decrease d ris k of ki d ne y disease pr o gressi o n 
2. 3. 3.  
O ver all Be nefit: Ris k C o ncl usi o n  
Ta ki n g i nt o acc o u nt t he hi g h u n met nee d f or effecti ve t hera pies f or patie nts wit h L N or I g A N, 
t he o utc o mes of t hese p atie nt p o p ulati o ns wit h c urre ntl y a vaila ble care, al o n g wit h t he meas ures 
ta ke n t o mi ni mize ris k t o partici pa nts i n t his st u d y, t he p ote ntial ris ks of partici pati n g i n t he st u d y 
are j ustifie d b y t he a ntici pate d be nefits. 
M ore detaile d i nf or mati o n a b o ut t he p ote ntial be n efits a n d p ote ntial ris ks of A L X N 2 0 5 0 ma y b e 
f o u n d i n t he A L X N 2 0 5 0 I B. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 5 5  of 1 5 2  
Ale xi o n C o nfi de ntial  
3.  
O B J E C TI V E S A N D E N D P OI N T S  
T a ble 7: 
M a p pi n g O bjecti ves t o E n d p oi nts  
O bjecti ves  
E n d p oi nts  
Pri m ar y ( B ot h C o h orts)  
T o e val uate t he efficac y of A L X N 2 0 5 0 t o 
re d uce pr otei n uria i n partici pa nts wit h L N or 
I g A N 
Perce nta ge c ha n ge i n pr otei n uria fr o m baseli ne t o 
Wee k  2 6 ( base d o n 2 4-h o ur uri ne c ollecti o n[s])  
Sec o n d ar y ( B ot h C o h orts)  
T o e val uate t he efficac y of A L X N 2 0 5 0 t o 
i m pr o ve meas ures of ki d ne y f u ncti o n i n 
partici pa nts wit h L N or I g A N  
Perce nta ge c ha n ge i n pr otei n uria fr o m baseli ne t o 
Wee k  5 0 ( base d o n 2 4-h o ur uri ne c ollecti o n[s])  
Ac hie vi n g > 3 0 % a n d > 5 0 %  re d ucti o n i n pr otei n uria 
at Wee k 2 6 a n d Wee k  5 0 c o m pare d t o baseli ne ( base d 
o n 2 4- h o ur uri ne c ollecti o n[s] at eac h ti me p oi nt)  
C ha n ge fr o m baseli ne i n e G F R at Wee k  2 6 a n d 
Wee k  5 0 
Sec o n d ar y ( L N C o h ort O nl y)  
T o e val uate t he efficac y of A L X N 2 0 5 0 o n 
meas ures of ki d ne y f u ncti o n i n partici pa nts 
wit h L N  
Meeti n g t he criteria f or  C R R at Wee k  2 6 a n d Wee k  5 0 
(as defi ne d i n Secti o n 8. 1. 1 0 ) 
Meeti n g t he c riteria f or P R R at Wee k  2 6 a n d Wee k 5 0 
(as defi ne d i n Secti o n  8. 1. 1 0 ) 
Ti me t o t he fi rst occ urre nce of U P C R ≤ 0. 5  g/ g as 
meas ure d b y s p ot uri ne sa m ple  
Ac hie vi n g c or tic oster oi d ta per t o 7. 5 m g / da y at 
Wee ks  1 2, 2 6, a n d 5 0 
E x perie nce of a Re nal Flare (as defi ne d i n 
Secti o n  8. 1. 6 ) t hr o u g h Wee k 5 0 
E x perie nce of a n E xtrare nal S L E Flare (as defi ne d i n 
Secti o n  8. 1. 7 ) t hr o u g h Wee k 5 0 
Meeti n g t he criteria f or Treat me nt Fail ure (as defi ne d 
i n Secti o n 8. 1. 9 ) t hr o u g h Wee k 5 0 
Meeti n g t he criteria f or S u b o pti mal Res p o nse t hr o u g h 
Wee k  5 0 
A bs ol ute val ues a n d c ha n ge fr o m baseli ne i n ser u m 
al b u mi n at Wee k  2 6 a n d Wee k  5 0 
Sec o n d ar y (I g A N C o h ort O nl y)  
T o e val uate t he efficac y of A L X N 2 0 5 0 o n 
meas ures of ki d ne y f u ncti o n i n partici pa nts 
wit h I g A N  
Meeti n g t he criteria f or Partial Re missi o n at Wee k  2 6 
a n d Wee k 5 0 (as defi ne d i n Secti o n 8. 1. 1 1 ) 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 5 6  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble  7 : 
M a p pi n g O bjecti ves t o E n d p oi nts  
O bjecti ves  
E n d p oi nts  
P K/ P D ( B ot h C o h orts)  
T o c haracterize t he p har mac o ki netics ( P K) 
a n d p har mac o d y na mics ( P D) of A L X N 2 0 5 0 
i n partici pa nts wit h L N or I g A N 
O bser ve d plas ma c o nce ntrati o ns of A L X N 2 0 5 0 o ver 
ti me 
A bs ol ute val ues a n d c ha n ge fr o m baseli ne i n plas ma 
B b c o nce ntrati o n a n d ser u m A P acti vit y o ver ti me  
S afet y ( B ot h C o h orts)  
T o c haracterize t he safet y a n d t olera bilit y of 
A L X N 2 0 5 0 i n partici pa nts wit h L N or I g A N  
I nci de nce of T E A Es a n d T E S A Es o ver ti me 
C ha n ges fr o m baseli ne i n la b orat or y assess me nts  
E x pl or at or y ( B ot h C o h orts)  
T o assess t he efficac y of A L X N 2 0 5 0 i n 
e x pl orat or y efficac y e n d p oi nts  
Perce nta ge c ha n ge i n pr otei n uria fr o m baseli ne t o 
Wee k  1 0 2 a n d Wee k  1 5 4 ( base d o n 2 4 -h o ur uri ne 
c ollecti o n[s]) 
C ha n ge fr o m baseli ne i n e G F R at Wee k  1 0 2 a n d 
Wee k  1 5 4  
T o e val uate t he efficac y of A L X N 2 0 5 0 o n 
he mat uria i n partici pa nts wit h L N or I g A N  
Effect o n he mat uria as meas ure d b y  
•  
A bs ol ute val ue a n d c ha n ge fr o m baseli ne i n 
R B C i n uri ne fr o m baseli ne t o Wee k  2 6 a n d 
Wee k  5 0  
•  
Ac hie vi n g  <  1 0  R B C/ h pf  
T o assess q ualit y of life base d o n 
partici pa nt -re p orte d o utc o mes i n partici pa nts 
wit h L N or I g A N base d o n treat me nt wit h 
A L X N 2 0 5 0  
C ha n ge fr o m baseli ne i n S F -3 6 at Wee k  2 6 a n d 
Wee k  5 0  
C ha n ge fr o m baseli ne i n E Q -5 D -5 L at Wee k  2 6 a n d 
Wee k  5 0  
T o e val uate bi o mar kers s uc h as c o m ple me nt, 
a ut oi m m u ne, a n d re nal i n partici pa nts wit h 
L N or I g A N  
A bs ol ute val ues a n d c ha n ge fr o m baseli ne i n le vels of 
bi o mar kers i n bl o o d a n d uri ne o ver ti me  
E x pl or at or y ( L N C o h ort O nl y)  
T o assess t he efficac y of A L X N 2 0 5 0 i n 
e x pl orat or y efficac y e n d p oi nts  
Ti me t o t he first C R R or P R R ( usi n g s p ot U P C R)  
Meeti n g t he criteria f or O verall Re nal Res p o nse ( C R R 
or P R R) at Wee k  2 6 a n d Wee k  5 0  
Ti me t o t he first occ urre nce of U P C R  >  5 0 % decrease 
fr o m baseli ne ( usi n g s p ot U P C R) 
T o assess q ualit y of life base d o n 
partici pa nt -re p orte d o utc o mes 
C ha n ge fr o m baseli ne i n F A CI T -Fati g ue t otal sc ore at 
Wee k  2 6 a n d Wee k  5 0  
T o assess t he efficac y of A L X N 2 0 5 0 i n ot her 
e x pl orat or y e n d p oi nts 
Hist ol o g y c ha n ges fr o m baseli ne t o Wee k  5 0, if tiss ue 
is a vaila ble 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 5 7  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble  7 : 
M a p pi n g O bjecti ves t o E n d p oi nts  
O bjecti ves  
E n d p oi nts  
A bs ol ute val ues a n d c ha n ge fr o m baseli ne i n a nti -
ds D N A a n d a nti -C 1 q a nti b o dies at Wee k  2 6 a n d 
Wee k  5 0  
E x pl or at or y (I g A N C o h ort O nl y)  
T o assess t he efficac y of A L X N 2 0 5 0 i n 
e x pl orat or y efficac y e n d p oi nts  
Sl o pe of e G F R c o m p ute d fr o m baseli ne t o Wee k  2 6 
a n d Wee k 5 0  
A b bre viati o ns: A P  =  alter nati ve pat h wa y; a nti -C 1 q  =  a nti-C 1 q c o m ple me nt c o m p o ne nt  ; 
a nti-ds D N A  =  a nti-d o u ble -stra n de d D N A; B b =  B b fra g me nt of c o m ple me nt fact or  B; C R R  =  c o m plete re nal 
res p o nse; e G F R =  esti mate d gl o mer ular filtrati o n rate; E Q -5 D -5 L  =  E ur o pea n Q ualit y of Life Healt h 5 -ite m 
q uesti o n naire di me nsi o ns 5  le vel; F A CI T =  F u ncti o nal Assess me nt of C hr o nic Ill ness T hera p y; h pf  =  hi g h -p o wer 
fiel d; I g A N =  i m m u n o gl o b uli n A ne p hr o pat h y; L N =  l u p us ne p hritis; P D =  p har mac o d y na mic(s); 
P K  =  p har mac o ki netic(s); P R R = partial re nal res p o nse; R B C  =  re d bl o o d cell; S L E = s yste mic l u p us 
er yt he mat os us; T E A E  =  treat me nt-e mer ge nt a d verse e ve nt; T E S A E  =  treat me nt-e mer ge nt seri o us a d verse e ve nt; 
S F -3 6  =  S h ort  F or m  ( 3 6) Healt h S ur ve y; U P C R =  uri ne pr otei n t o creati ni ne rati o  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 5 8  of 1 5 2  
Ale xi o n C o nfi de ntial  
4.  
S T U D Y D E SI G N  
4. 1.  
O ver all Desi g n  
T his is a P hase  2, ra n d o mize d, d o u ble- bli n d, place b o-c o ntr olle d, m ultice nt er st u d y of 
A L X N 2 0 5 0 i n a d diti o n t o all o we d c o nc o mita nt t h era p y c o nsiste nt wit h t he sta n dar d of care i n 
a d ult partici pa nts ( ≥ 1 8 t o ≤ 7 5 years of a ge) wit h eit her L N or I g A N. 
•  Partici pa nts i n t he L N c o h ort m ust ha ve a dia g n osis of L N wit h a n acti ve flare bas e d 
o n ki d ne y bi o ps y , e G F R > 3 0 m L/ mi n/ 1. 7 3  m2, a n d pr otei n uria defi n e d as 
U P C R  ≥ 1 g/ g fr o m o ne 2 4- h o ur uri ne c ollecti o n. 
•  Partici pa nts i n t he I g A N c o h ort m ust ha ve a dia g n osis of I g A N base d o n ki d ne y 
bi o ps y, e G F R > 3 0 m L/ mi n/ 1. 7 3 m 2, a n d pr otei n uria defi ne d as mea n 
pr otei n ≥ 1 g/ 2 4 h o urs fr o m 2 vali d 2 4- h o ur uri ne c ollecti o ns ( Secti o n 8. 1. 1 ). 
Partici pa nts m ust ha ve bee n treate d wit h sta ble d oses of t he ma xi m u m t olerate d 
R A S -i n hi biti n g me dicati o ns a n d ha ve c o ntr olle d, sta ble bl o o d press ure 
( < 1 4 0/ 9 0 m m H g) f or  ≥ 3 m o nt hs pri or t o Scree ni n g. 
T he st u d y c o nsists of a n u p t o 6- wee k Scree ni n g Peri o d, a 2 6- wee k Bli n de d I nitial E val u ati o n 
Peri o d, a 2 4- wee k Bli n de d E xte n de d Treat me nt Peri o d, a n d a n O L E Peri o d of u p t o 2 years. 
U p o n c o m pleti o n of t he O L E Peri o d or if a p artici pa nt deci des t o wit h dra w fr o m t he st u d y, all 
partici pa nts will be f oll o we d f or s afet y f or 3 0 da ys after t he last d ose of st u d y i nter ve nti o n. T h us, 
t he t otal treat me nt d urati o n is 1 5 4 wee ks, a n d t he t otal st u d y d urati o n is u p t o 1 6 4 wee ks.  
All partici pa nts will c o nti n ue t o recei v e all o we d c o nc o mita nt t hera p y c o nsiste nt wit h t he 
sta n dar d of car e f or p artici pa nts wit h L N a n d I g A N t hr o u g h o ut t he st u d y. Partici pa nts i n t he L N 
c o h ort will recei ve a d diti o nal sta n dar d of care t hera p y i n t he e ve nt of a pr ot oc ol- defi ne d Re n al 
Flare or E xtrare nal S L E Flare a n d after Wee k  2 6, f or S u b o pti mal Res p o nse. A p pr o ve d n o vel 
treat me nts f or L N ca n b e use d per t he I n vesti gat or’s discreti o n. H o we v er, if a d diti o nal sta n dar d 
of car e t her a p y is i nitiate d, t he I n v esti ga t or s h o ul d c o ns ult t he list of disall o we d me dicati o ns 
( Secti o n 6. 5. 2 ). If t he a d diti o nal sta n dar d of care t hera p y is a pr o hi bite d me dicati o n, st u d y 
i nter ve nti o n s h o ul d be disc o nti n ue d at least 3 da ys pri or t o i nitiati o n of t he a d diti o nal sta n dar d of 
care t h era p y.  
See st u d y desi g n sc he matics i n  Fi g ure 1  an d  Fi g ure 2  for L N a n d I g A N c o h orts, res pecti vel y.  
4. 1. 1.  
Scree ni n g  
Partici pa nts will be scree ne d f or eli gi bilit y f or u p t o 6  wee ks d uri n g t he Scree ni n g Peri o d. F or 
partici pa nts i n t he L N  c o h ort, all scree ni n g la b orat or y assess me nts s h o ul d be perf or me d as s o o n 
as p ossi ble after si g ni n g of t he i nf or me d c o ns e nt f or m (I C F). All partici pa nts i n t he L N  c o h ort 
s h o ul d be ra n d o mize d as s o o n as p ossi ble o nce eli gi bilit y is c o nfir me d. 
4. 1. 2.  
Bli n de d I niti al E v al u ati o n Peri o d  
A p pr o xi matel y 1 2 6 a d ult partici pa nts wit h eit her L N or I g A N will be ra n d o mize d i nt o t he st u d y 
o n Da y 1 (a p pr o xi matel y 7 0 partici pa nts i n t he L N  c o h ort a n d a p pr o xi mat el y 5 6 partici pa nts i n 
t he I g A N c o h ort), as f oll o ws: 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 5 9  of 1 5 2  
Ale xi o n C o nfi de ntial  
•  F or eac h disease c o h ort, partici pa nts meeti n g eli gi bilit y criteria will be ra n d o ml y 
assi g ne d i n a 3: 1: 3 rati o t o recei v e A L X N 2 0 5 0 1 8 0 m g bi d, A L X N 2 0 5 0 1 2 0 m g bi d, 
or place b o bi d ( T a ble  8). 
•  F or t he I g A N c o h ort, partici pa nts assi g ne d t o t he place b o gr o u p will als o be assi g ne d 
t o t heir st u d y treat me nt f or t he Bli n de d E xte n de d Treat me nt Peri o d ( A L X N 2 0 5 0 
1 8 0 m g bi d or A L X N 2 0 5 0 1 2 0 m g bi d) i n a 1: 1 all ocati o n rati o at t he ti me of 
ra n d o mizati o n. 
T a ble 8: 
S u m m ar y of P artici p a nts i n E ac h Tre at me nt Gr o u p D uri n g t he Bli n de d 
I niti al E v al u ati o n Peri o d 
Tre at me nt Gr o u p  
L N C o h ort  
I g A N C o h ort 
A p pr o xi m ate N u m ber of 
P artici p a nts  
A p pr o xi m ate N u m ber of 
P artici p a nts  
A L X N 2 0 5 0 1 8 0 m g bi d 
3 0 
2 4 
A L X N 2 0 5 0 1 2 0 m g bi d 
1 0 
8 
Place b o bi d 
3 0 
2 4 
A b bre viati o ns: bi d  = t wice dail y; I g A N = i m m u n o gl o b uli n A ne p hr o pat h y; L N  = l u p us ne p hritis 
Stratificati o n will be perf or me d as f oll o ws:  
•  F or t he L N c o h ort: b y w het her c ortic oster oi d i n d ucti o n treat me nt was i nitiate d pri or 
t o Scree ni n g vers us d uri n g t he Scree ni n g Peri o d. 
•  F or t he I g A N c o h ort: b y mea n pr otei n uria ( 1 t o 2 g/ da y vers us > 2 g/ da y) fr o m 2 vali d 
2 4- h o ur uri ne c ollecti o ns d uri n g t he Scree ni n g Peri o d. 
After c o m pleti o n of t he Da y 1 Visit assess me nts, partici pa nts will recei ve t he first d ose of st u d y 
i nter ve nti o n pri or t o lea vi n g t he cli nic. Partici pa nts will c o nti n ue t o recei ve bi d d oses of st u d y 
i nter ve nti o n t hr o u g h o ut t he Bli n de d I nitial E val u ati o n Peri o d (Ta ble  1 1). 
4. 1. 3.  
Bli n de d E xte n de d Tre at me nt Peri o d  
After c o m pleti o n of t he Bli n de d I nitial E val uati o n Peri o d ( Wee k  2 6 Visit), partici pa nts will 
c o nti n ue t o recei ve st u d y i nter ve nti o n d uri n g a Bli n de d E xte n de d Treat me nt Peri o d f or 2 4 wee ks 
as f oll o ws: 
•  Partici pa nts i n t he L N c o h ort will c o nti n ue t o recei ve t heir ra n d o mize d all ocati o n of 
st u d y i nter ve nti o n ( A L X N 2 0 5 0 1 8 0 m g, A L X N 2 0 5 0 1 2 0 m g, or place b o) bi d. After 
Wee k  2 6, a d diti o nal sta n dar d of care t h era p y f or p artici pa nts wit h S u b o pti mal 
Res p o nse is all o we d at t h e cli nical discreti o n of t h e I n vesti gat or i n c o n v ers ati o n wit h 
t he Me dical M o nit or. 
•  Partici pa nts i n t he I g A N c o h ort ra n d o mize d t o acti ve treat me nt will c o nti n ue t o 
recei v e t heir r a n d o mize d all ocati o n of st u d y i nter v e nti o n ( A L X N 2 0 5 0 1 8 0 m g or 
A L X N 2 0 5 0  1 2 0 m g) bi d. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 6 0  of 1 5 2  
Ale xi o n C o nfi de ntial  
•  P artici pa nts i n t he I g A N c o h ort ra n d o mize d t o t he place b o gr o u p will recei ve eit her 
A L X N 2 0 5 0  1 8 0 m g  bi d or A L X N 2 0 5 0  1 2 0 m g  bi d as assi g ne d at t he ti me of 
ra n d o mizati o n. 
4. 1. 4.  
O pe n -l a bel E xte nsi o n Peri o d 
After c o m pleti o n of all assess me nts at t he e n d of t he Bli n de d E xte n de d Treat me nt Peri o d 
( Wee k 5 0 Visit), all parti ci pa nts will ha ve t he o p p ort u nit y t o e nter a n O L E Peri o d a n d recei ve 
A L X N 2 0 5 0 f or u p t o 2 y ears ( 1 0 4  wee ks) if n o rel e va nt si de effects (i n t he o pi ni o n of t he 
I n v esti gat or) a n d n o Treat me nt Fail ure ( L N c o h ort) are prese nt. D uri n g t he O L E Peri o d: 
•  Partici pa nts i n t he L N c o h ort ra n d o mize d t o t he acti ve treat me nt gr o u ps will c o nti n ue 
t o recei ve t h e sa me d osi n g re gi me n as assi g ne d d uri n g t he Bli n de d E xte n de d 
Treat me nt Peri o d.  
•  Partici pa nts i n t he L N c o h ort ra n d o mize d t o t he pl ace b o gr o u p will n o l o n ger recei ve 
place b o a n d will c o nti n ue t o recei ve all o we d c o nc o mita nt t hera p y al o ne. T hese 
pa rtici pa nts will ha ve t he o pti o n t o recei ve A L X N 2 0 5 0 1 8 0 m g bi d or t he o pti mal 
d ose (if alr ea d y i de ntifie d) if t he partici pa nt h as a Re nal Flare as defi ne d i n 
Secti o n  8. 1. 6  or  S u b o pti mal Res p o nse as defi ne d i n Secti o n 8. 1. 8 . 
•  Partici pa nts i n t he I g A N c o h ort will c o nti n ue t o recei ve t he sa m e d osi n g re gi me n as 
assi g ne d d uri n g t he Bli n de d E xte n de d Treat me nt Peri o d. 
•  Partici pa nts i n b ot h c o h orts recei vi n g A L X N 2 0 5 0 w h o c o m plete at least 5 0 wee ks of 
treat me nt will recei ve t he o pti mal d ose le vel of A L X N 2 0 5 0 ( 1 8 0 m g or 1 2 0 m g bi d) 
o nce a n o pti mal d ose is i de ntifie d base d o n res ults of t he pri mar y a n al ysis at Wee k 2 6 
a n d/ or Data M o nit ori n g C o m mittee ( D M C) re vie w of t he safet y a n d efficac y data. 
•  Perce nta g e c ha n g e i n pr otei n uria fr o m bas eli ne a n d c ha n ge fr o m baseli ne i n e G F R at 
Wee ks  1 0 2 a n d Wee k 1 5 4 will be assesse d as e x pl orat or y efficac y e n d p oi nts. Safet y 
a n d t olera bilit y will als o be e val uat e d c o nti n uall y t hr o u g h o ut t he O L E Peri o d. 
After c o m pleti o n of t he st u d y or after E D, a Safet y F oll o w- u p Visit will be c o n d ucte d 3 0 da ys 
after t he l ast d ose of st u d y i nter ve nti o n. 
4. 1. 5.  
Re m ote Visit O pti o ns i n Ti mes of E mer ge nc y  
T o e ns ure partici pa nt saf et y a n d treat me nt c o nti n uit y i n ti mes of e mer ge nc y (e g, C O VI D- 1 9 
pa n de mic), t he f oll o wi n g will a p pl y w here partici pa nts are n ot a bl e t o reac h t he st u d y sites, a n d 
u ntil partici pa nts are a bl e t o res u me st u d y visits at t he site.  
Re m ote visit o pti o ns ma y be a vaila ble at t he I n vesti gat or’s discreti o n a n d o versi g ht, i n 
acc or d a nce wit h t he l ocal re g ulati o ns. Re m ote visit o pti o ns ma y i ncl u de visits c o n d ucte d at t he 
partici pa nt’s h o me, a n alter nati ve q ualifie d healt hcare facilit y, or virt uall y t hr o u g h p h o ne or 
vi de o c o nfere nce. All ass ess me nts f or t he st u d y visit da y s h o ul d be c o n d uct e d acc or di n g t o t he 
S o A ( Secti o n  1. 3 ), w he n e ver p ossi ble. I nf or mati o n a b o ut a d vers e e ve nts ( A Es), c o nc o mita nt 
me dicati o ns, all o we d c o n c o mita nt t hera pies, a n d disease -relate d si g ns or s y m pt o mat ol o g y m ust 
be se nt t o t he I n vesti gat or f or e v al uati o n o n t he da y of t he re m ote visit. I n case of a n y si g ns or 
s y m pt o ms i n dicati n g a seri o us a d verse e ve nt ( S A E), t he partici pa nt will nee d t o be e val uate d at 
t he st u d y site. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 6 1  of 1 5 2  
Ale xi o n C o nfi de ntial  
4. 2.  
Scie ntific R ati o n ale f or St u d y Desi g n  
J ustificati o n f or s pecific desi g n ele me nts is pr o vi de d i n Ta ble  9. 
T a ble 9:  
Scie ntific R ati o n ale f or t he Desi g n of St u d y A L X N 2 0 5 0- N E P H - 2 0 1 
Desi g n Ele me nt  
R ati o n ale 
Tar get p o p ulati o ns 
Gl o mer ular diseases s uc h as L N a n d I g A N  c o nti n ue t o 
res p o n d p o orl y t o treat me nt, res ulti n g i n C K D o ver ti me. 
W hile t here has bee n s o me pr o gress i n ter ms of a p pr o ve d 
treat me nts wit h 2 rece nt a p pr o vals i n s o me c o u ntries f or 
patie nts wit h L N (ie, beli m u ma b a n d v ocl os p ori n) a n d I g A N 
( b u des o ni de), there re mai ns a si g nifica nt u n met nee d f or n o vel 
i nter ve nti o ns w hic h w o ul d all o w m ore defi niti ve treat me nts 
f or L N as well as disease-s pecific treat me nts f or patie nts wit h 
I g A N, partic ularl y i n patie nts w h o are at ris k of pr o gressi ve 
ki d ne y disease.  
See Secti o n  2. 2. 3  an d Secti o n  2. 2. 4 . 
Ra n d o mize d, d o u ble- bli n d, 
place b o- c o ntr olle d 
A ra n d o mize d, d o u ble- bli n d, place b o- c o ntr olle d st u d y desi g n 
i n a d diti o n t o all o we d c o nc o mita nt t hera p y c o nsiste nt wit h t he 
sta n dar d of care is selecte d t o pr o vi de t he m ost r o b ust 
e vi de nce of t he efficac y of A L X N 2 0 5 0 o n cli nical res p o nse, 
disease pr o gressi o n, a n d safet y. Ra n d o mizati o n mi ni mizes t he 
effects of baseli ne differe nces a n d c o nf o u n di n g fact ors o n t he 
st u d y e n d p oi nts. T he use of a place b o c o m parat or all o ws f or 
t he tr ue treat me nt effect of A L X N 2 0 5 0 b y mi ni mizi n g t he ris k 
of selecti o n bias.  
Ra n d o mizati o n strat u m 
A si n gle ra n d o mizati o n strat u m was selecte d f or eac h c o h ort 
t o e ns ure e q ual distri b uti o n of baseli ne c haracteristics t hat 
ma y i m pact t he e n d p oi nts. See Secti o n  6. 3. 1 . 
Selecti o n of 2 d ose le vels 
( A L X N 2 0 5 0 1 8 0 m g bi d a n d 
A L X N 2 0 5 0 1 2 0 m g bi d) 
T he o pti mal d ose of A L X N 2 0 5 0 i n gl o mer ular diseases is n ot 
k n o w n. T h us, partici pa nts will be ra n d o mize d t o a hi g h - d ose 
gr o u p ( 1 8 0  m g bi d), a l o w-d ose gr o u p ( 1 2 0  m g bi d), or a 
place b o gr o u p i n a 3: 1: 3 all ocati o n rati o. T he pri mar y a nal ysis 
will c o m pare t he hi g h - d ose treat me nt gr o u p t o t he place b o 
treat me nt gr o u p. A s maller n u m ber of partici pa nts will be 
ra n d o mize d t o t he l o w- d ose treat me nt gr o u p t o c ollect 
s u p p orti ve data t hat will be s u m marize d descri pti vel y. Gi ve n 
t he u n k n o w n de gree of A P i n hi biti o n re q uire d t o ac hie ve 
cli nical efficac y i n t hese i n dicati o ns a n d t o e ns ure r o b ust A P 
i n hi biti o n i n a maj orit y of patie nts, 1 8 0 m g bi d was c h ose n f or 
t he hi g h- d ose gr o u p. See Secti o n 4. 3 . 
Pri mar y e n d p oi nt ( pr otei n uria) 
C ha n ge i n pr otei n uria is c o nsi dere d a vali d s urr o gate e n d p oi nt 
f or ki d ne y s ur vi val i n gl o mer ular diseases. See Secti o n 4. 2. 1 . 
Safet y e n d p oi nts 
T he safet y para meters bei n g e val uate d are c o m m o nl y use d i n 
cli nical st u dies per I C H a n d G C P g ui deli nes.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 6 2  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 9:  
Scie ntific R ati o n ale f or t he Desi g n of St u d y A L X N 2 0 5 0- N E P H - 2 0 1 
Desi g n Ele me nt  
R ati o n ale 
D urati o n of st u d y 
T he 2 6- wee k i nitial treat me nt d urati o n pr o vi des a de q uate ti me 
t o assess t he safet y a n d efficac y e n d p oi nts t o de m o nstrate 
pr o of of c o nce pt f or b ot h c o h orts i n a P hase 2 st u d y. 
T he E xte n de d Treat me nt Peri o d a n d O L E Peri o d will facilitate 
c ollecti o n of l o n git u di nal efficac y a n d a d diti o nal safet y data of 
A L X N 2 0 5 0 f or all partici pa nts. 
A b bre viati o ns: A P  = alter nati ve pat h wa y; bi d  = t wice dail y; C K D = c hr o nic ki d ne y disease; G C P  = G o o d Cli nical 
Practice; I C H  = I nter nati o nal C o u ncil f or Har m o nisati o n of Tec h nical Re q uire me nts f or P har mace uticals f or 
H u ma n Use; I g A N  = i m m u n o gl o b uli n A ne p hr o pat h y; L N  = l u p us ne p hritis; O L E = O pe n -la bel E xte nsi o n 
4. 2. 1.  
R ati o n ale f or Pri m ar y E n d p oi nt 
T he pri mar y e n d p oi nt f or t he st u d y is perce nt c h a n ge fr o m baseli ne t o Wee k 2 6 i n 2 4- h o ur 
pr otei n uria. C ha n ge i n pr otei n uria is c o nsi dere d a vali d s urr o gate e n d p oi nt f or ki d ne y s ur vi val i n 
gl o mer ular diseas es. C ha n ge i n pr otei n uria is als o a n acce pta ble e n d p oi nt f or cli nical st u dies as 
c o ncl u de d d uri n g a s cie ntific w or ks h o p facilitate d b y t he Nati o nal Ki d ne y F o u n dati o n ( N K F) i n 
c olla b orati o n wit h t he U S F o o d a n d Dr u g A d mi nistrati o n ( F D A) a n d t he E ur o pea n Me di ci nes 
A ge nc y ( E M A) i n 2 0 1 8 ( C ores h, 2 0 1 9 ). A decli ne i n pr otei n uria i n res p o ns e t o treat me nt is a 
str o n g pre dict or of ki d ne y s ur vi val (H e b ert, 2 0 0 1 ; Wil mer, 2 0 0 3 ) a n d a > 2 0 % t o 3 0 % relati ve 
treat me nt effect o v er sta n dar d of care i n c ha n ge i n pr otei n uria is c o nsi dere d cli nicall y rele va nt 
(Le ve y, 2 0 2 0 ). C ha n ges i n pr otei n uria bec o me e vi de nt bef ore tra diti o nal mar kers of ki d ne y 
s ur vi val (e g, E S R D, dial ysis, or tra ns pla nt); t h us, it is es peciall y usef ul t o detect si g ns of efficac y 
f or a pr o of- of-c o nce pt st u d y. Acc or di n gl y, t he effect of A L X N 2 0 5 0 o n t he perce nt a ge re d ucti o n 
of pr otei n uria at Wee k  2 6 c o m pare d t o bas eli ne w as selecte d as t he pri mar y e n d p oi nt f or t his 
st u d y. It is e x pecte d t hat 2 6 wee ks of treat me nt wit h A L X N 2 0 5 0 will pr o vi de partici pa nts w h o 
res p o n d t o F D i n hi biti o n s ufficie nt ti me t o ac hie v e re d ucti o n of pr otei n uria. 
C urre ntl y, t he m ost precise met h o d f or meas uri n g pr otei n uria is a c o m plete 2 4- h o ur uri ne 
c ollecti o n. 
Pr otei n uria is f urt her j ustifie d as a n e n d p oi nt i n t his P hase 2 st u d y beca use A L X N 2 0 5 0 has 
p ote ntial f or a nti-i nfla m mat or y eff ects t hat ma y b e de m o nstrate d t hr o u g h c ha n ges i n pr otei n uria. 
Pr otei n uria ma y als o res ult fr o m irre versi ble s carri n g of re nal tiss ue. T heref ore, t he prese nce of 
p ote ntiall y re versi ble a n d acti ve i nfla m mat or y ki d ne y disease is e ns ure d b y re q uiri n g he mat uria 
i n partici pa nts wit h I g A N, a n d acti ve Class III or I V L N o n ki d ne y bi o ps y i n partici pa nts wit h 
L N. A d diti o nall y, relati vel y preser v e d re nal f u ncti o n wit h a n e G F R of > 3 0 m L/ mi n/ 1. 7 3  m2 is 
re q uire d f or b ot h disease c o h orts. Fi nall y, alt h o u gh treat me nt res p o ns e i n patie nts wit h L N is 
tra diti o nall y defi ne d b y stratificati o n i nt o c o m plete a n d partial res p o nse, t h ere is n o c o ns e ns us 
defi niti o n acr oss g ui deli n es, a n d pr otei n uria is t he m ost i m p orta nt cli nical varia ble use d t o d efi ne 
res p o nse (Pari k h, 2 0 1 6 ). I n fact, a retr os p ecti ve a n al ysis of 1-year cli nical res p o nse metrics fr o m 
t he E ur o L u p us Ne p hritis Trial de m o nstrate d pr ot ei n uria < 8 0 0 m g/ da y at 1 year t o be t he b est 
pre dict or of g o o d l o n g-t er m re nal o utc o me. T h e a d diti o n of ser u m creati ni ne le vel a n d 
micr osc o pic he mat uri a di d n ot i m pr o ve t he pre dicti o n m o del ( Pari k h, 2 0 2 0 ). 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 6 3  of 1 5 2  
Ale xi o n C o nfi de ntial  
4. 3.  
J ustific ati o n f or D ose  
Cli nical p har mac o ki netics ( P K) a n d P D data h a ve bee n ge n erate d f or A L X N 2 0 5 0 i n 
si n gle-asce n di n g a n d m ulti ple-asce n di n g d ose st u dies i n healt h y v ol u nteers 
( St u dies A C H 2 2 8 - 0 0 1 a n d A C H 2 2 8- 0 0 2). I n t hes e cli nical st u dies, A L X N 2 0 5 0 de m o nstrate d a 
d ose- pr o p orti o nal i ncr eas e i n s yste mic e x p os ure f oll o wi n g si n gle- d ose a d mi nistrati o n a n d a 
greater t ha n d ose- pr o p orti o nal i ncreas e f oll o wi n g m ulti ple- d ose a d mi nistrati o n at stea d y state 
( Da ys 7 a n d 1 4) o ver t he d osi n g ra n ge of 4 0 m g bi d t o 2 0 0 m g bi d. Lar ge i nters u bject vari a bilit y 
was o bser v e d.  
F oll o wi n g m ulti ple - d ose a d mi nistrati o n of A L X N 2 0 5 0 ra n gi n g fr o m 4 0 m g bi d t o 2 0 0 m g bi d i n 
healt h y partici pa nts, P D acti vit y ( deter mi ne d b y A P i n hi biti o n i n t he A P Wiesla b assa y) 
i ncreas e d wit h i ncreasi n g d ose. T he 1 2 0 m g bi d d osi n g re gi me n pr o vi de d s ustai ne d A P i n hi biti o n 
( A P acti vit y < 1 0 %) i n h ealt h y partici pa nts w h ose A L X N 2 0 5 0 c o n ce ntrati o ns ac hie ve d t he 
9 0 % i n hi bit or y c o nce ntrati o n (I C 9 0) t hres h ol d t hr o u g h t he 1 2- h o ur d osi n g p eri o ds. T heref or e, 
1 2 0 m g bi d is selecte d as t he mi ni m u m t hera pe utic d ose. I n ters u bj ect vari a bilit y i n P K a n d 
P K - P D relati o ns hi p i n dicate d t hat a d ose hi g her t h a n 1 2 0 m g bi d (s uc h as 1 8 0 m g bi d) ma y be 
re q uire d t o e ns ure m ore partici pa nts reac h a n d m ai ntai n A L X N 2 0 5 0 c o n ce ntrati o n a b o ve t he 
t hres h ol d f or 9 0 % A P i n hi biti o n. I n a d diti o n, it is e x pecte d t h at F D b aseli ne le vels will be 
ele vate d i n patie nts w h o e x hi bit re d uce d ki d ne y f u ncti o n, w hic h w o ul d raise t he A L X N 2 0 5 0 
t hres h ol d c o nce ntr ati o n r e q uire d f or 9 0 % i n hi biti o n of A P acti vit y i n patie nts wit h eit her L N or 
I g A N. T heref ore, t he 1 8 0 m g bi d is selecte d as t he li kel y t hera pe utic d ose. 
I n a m ulti ple asce n di n g d ose st u d y, t he 1 2 0 a n d 2 0 0 m g bi d d ose re gi me ns were s afe a n d 
effecti ve, s h o wi n g a n a p pr o xi matel y 1 0-f ol d or greater s afet y mar gi n i n b ot h ma xi m u m plas ma 
c o nce ntr ati o n o bser ve d after st u d y i nter ve nti o n a d mi nistrati o n ( C ma x ) a n d t he area u n der t he 
c o nce ntr ati o n -ti me c ur ve fr o m ti me zer o t o 2 4 h o urs ( A U C0- 2 4) o ver t he e x p os ures ac hie v e d at 
t he n o o bser ve d a d vers e effect le vel ( N O A E L) fr o m n o ncli nical c hr o nic t o xic ol o g y st u dies (see 
A L X N 2 0 5 0 I B). I n a d diti o n, b ot h d osa ge re gi me ns pr o vi de d c o m plete ( > 9 0 %) a n d s ustai ne d 
i n hi biti o n of A P acti vit y t hr o u g h o ut t he 1 2- h o ur d osi n g i nter val. T heref ore, 1 2 0 m g bi d is 
selecte d as t h e mi ni m u m t hera pe utic d os a ge. 
Base d o n t he fa v ora ble cli nical safet y a n d t olera bilit y data fr o m t hese st u dies, a n d t he P K a n d P D 
c haracteri zati o n of A L X N 2 0 5 0, t he d osi n g re gi me ns of 1 2 0 m g bi d a n d 1 8 0 m g bi d are pr o p ose d 
f or t his d ose-fi n di n g st u d y i n partici pa nts wit h L N or I g A N. T h e e x p os ure ra n ge ge n erate d b y t h e 
pr o p ose d A L X N 2 0 5 0 1 2 0 m g bi d a n d 1 8 0 m g bi d d osi n g is e x pecte d t o be a de q uate t o esta blis h 
t he P K- P D relati o ns hi p i n partici pa nts wit h L N or I g A N, t here b y setti n g u p t he basis f or d ose 
selecti o n i n t he pla n ne d P hase 3 st u d y. 
T he o pti mal d ose will be i de ntifie d as t he d ose wit h t he best be nefit t o ris k rati o base d o n P K/ P D 
m o deli n g, safet y, a n d efficac y dat a. 
4. 4.  
Defi niti o n of St u d y Peri o ds a n d E n d of St u d y  
T he Scree ni n g Peri o d is u p t o 6 wee ks ( T a ble  1 [L N c o h ort] a n d Ta ble  2 [I g A N c o h ort]). 
T he Bli n de d I nitial E val u ati o n Peri o d is fr o m Da y  1 t o Wee k  2 6 (T a ble  1 [L N c o h ort] a n d 
Ta ble  2 [I g A N c o h ort]). 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 6 4  of 1 5 2  
Ale xi o n C o nfi de ntial  
T he Bli n de d E xte n de d Tr eat me nt Peri o d starts wit h d osi n g of st u d y i nter ve nti o n at t he Wee k 2 6 
( Da y 1 8 3) Visit a n d c o nti n ues t hr o u g h t he Wee k 5 0 ( Da y  3 5 1) Visit (T a ble  3 [L N c o h ort] a n d 
Ta ble  4 [I g A N c o h ort]). 
T he O L E Peri o d be gi ns after t he Wee k  5 0 Visit a n d c o nti n ues u p t o 2 years ( Ta ble  5). 
T he Safet y F oll o w- u p Peri o d is 4 wee ks aft er t he l ast d ose of st u d y i nter ve nti o n a n d i ncl u des a 
Safet y F oll o w- u p Visit 3 0  ( ± 3) da ys after t he last d ose.  
A partici pa nt is c o nsi der e d t o ha ve c o m plet e d t he st u d y: 
•  If he/s he has c o m plete d all peri o ds of t he st u d y, i ncl u di n g t he O L E Peri o d a n d t he last 
sc he d ule d pr o ce d ur e s h o w n i n t he S o A 
•  I n t he e ve nt t he st u d y is st o p pe d earl y, t he p artici p a nt has c o m plete d all a p plica ble 
peri o ds of t he st u d y, i ncl u di n g t he Earl y Disc o nti n uati o n ( E D) a n d Safet y F oll o w- u p 
Visits  
•  T he partici pa nt c o m plet es t he st u d y earl y beca use t he st u d y i nter ve nti o n is re gistere d or 
a p pr o ve d (i n acc or da nce wit h c o u ntr y- s pecifi c re g ulati o ns) 
Earl y ter mi nati o n or disc o nti n uati o n: A partici pa nt is c o nsi dere d t o ter mi nate earl y fr o m t he 
st u d y if t he partici pa nt is disc o nti n ue d fr o m t he st u d y d uri n g t he Bli n de d I nitial E val uati o n 
Peri o d, Bli n de d E xte n de d Treat me nt Peri o d, or O L E Peri o d. 
E n d of st u d y: T he e n d of st u d y is defi ne d as t he date of t he last visit of t he last partici pa nt i n t he 
st u d y or last sc he d ule d pr oce d ure s h o w n i n t he S o A f or t he last partici pa nt i n t he st u d y gl o ball y.  
Refer t o t he S o A i n Secti o n  1. 3 . 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 6 5  of 1 5 2  
Ale xi o n C o nfi de ntial  
5.  
S T U D Y P O P U L A TI O N  
Pr os pecti ve a p pr o v al of pr ot oc ol de viati o ns t o recr uit me nt a n d e nr oll me nt criteria, als o k n o w n as 
pr ot oc ol wai vers or e xe m pti o ns, is n ot per mitte d. 
5. 1.  
I ncl usi o n Criteri a 
A partici pa nt m ust meet all i ncl usi o n criteria t o be eli gi ble t o partici pate i n t he st u d y.  
5. 1. 1.  
I ncl usi o n Criteri a f or B ot h C o h orts 
A ge  
1.  Partici pa nt m ust be  ≥ 1 8 a n d ≤ 7 5 years of a ge  at t he ti me of si g ni n g t he i nf or me d 
c o nse nt. 
Se x  
2.  Male or fe m ale partici pa nt.  
3.  Fe male p artici pa nts of c hil d beari n g p ote ntial a n d male partici pa nts m ust f oll o w 
pr ot oc ol-s pecifi e d c o ntrace pti o n g ui da nce as descri be d i n Secti o n  1 0. 5. 2 . 
I nf or m e d C o nse nt 
4.  Ca pa ble of gi vi n g i nf or m e d c o nse nt (as descri be d i n Secti o n  1 0. 1. 3 ) w hic h i ncl u des 
c o m plia nce wit h t he r e q uire me nts a n d restri cti o ns liste d i n t he I C F a n d i n t his pr ot oc ol. 
V acci n ati o ns a n d A nti bi otics 
5.  Vacci n ate d a g ai nst me ni n g oc occal i nfecti o n ( Neisseri a me ni n giti dis ) wit hi n 3 years pri or 
t o, or at t he ti me of ra n d o mizati o n. Partici pa nts w h o i nitiate st u d y i nter ve nti o n < 2 wee ks 
after r ecei vi n g a me ni n g oc occal vacci ne m ust recei ve a p pr o priate pr o p h yl actic a nti bi otics 
u ntil at least 2  wee ks aft er t he vacci nati o n.  
Dise ase C h ar acteristi cs  
6.  L ocal pat h ol o g y re p ort fr o m t he ki d ne y bi o ps y ( Secti o n  8. 1 2. 5 ) use d f or eli gi bilit y m ust 
be a vaila ble.  
Pri or/ C o nc o mit a nt T her a p y  
7.  Partici pa nts o n s o di u m- gl uc ose c otra ns p orter- 2 ( S G L T - 2) i n hi bit ors (e g, e m pa glifl ozi n) 
m ust be o n a sta ble d ose f or ≥ 3 m o nt hs wit h n o pla n ne d c h a n ge i n d ose d uri n g t he 
Bli n de d Treat me nt Peri o ds (t hr o u g h Wee k 5 0). 
5. 1. 2.  
I ncl usi o n Criteri a S pecific f or L N C o h ort 
Dise ase C h ar acteristi cs  
8.  Cli nical dia g n osis of S L E b y 2 0 1 9 A C R a n d E U L A R criteria ( Secti o n  1 0. 7 ). 
9.  Dia g n osis of 2 0 1 8 Re vise d I S N/ R P S classificati o n (acti ve f o cal or diff use pr oliferati ve 
L N Class  III or I V; Secti o n 1 0. 8 ) c o nfir me d b y bi o ps y o btai ne d ≤ 6 m o nt hs pri or t o 
Scree ni n g or d uri n g Scree ni n g Peri o d. Partici pa nts ma y c o- e x hi bit Class  V disease. 
Partici pa nts wit h de n o v o or rela psi n g diseas e ma y be eli gi ble. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 6 6  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0.  Cli nicall y acti ve L N at Scree ni n g re q uiri n g/recei vi n g i m m u n os u p pressi o n i n d ucti o n 
treat me nt i n t he o pi ni o n of t he I n vesti gat or. 
1 1.  Pr otei n uria wit h U P C R  ≥ 1 g/ g base d o n o ne 2 4- h o ur uri ne c ollecti o n d uri n g t he 
Scree ni n g Peri o d. 
5. 1. 3.  
I ncl usi o n Criteri a S pecific f or I g A N C o h ort 
1 2.  Esta blis he d dia g n osis of pri mar y I g A N b ase d o n ki d ne y bi o ps y ( Secti o n  1 0. 9 ) o btai ne d 
a n y ti me pri or t o or d uri n g t he Scree ni n g Peri o d. 
1 3.  Mea n pr otei n uria ≥ 1 g/ d a y o n 2 c o m plete a n d v ali d 2 4- h o ur uri ne c ollecti o ns d uri n g t he 
Scree ni n g Peri o d. 
1 4.  F or partici pa nts wit h a ki d ne y bi o ps y perf or m e d > 1 year pri or t o Scree ni n g t hat was use d 
f or eli gi bilit y: 
•  Prese nce of he mat uri a as defi ne d b y a p ositi ve res ult f or bl o o d o n uri ne di pstic k 
or ≥ 1 0 re d bl o o d cells ( R B Cs)/ hi g h- p o wer fiel d ( h pf) micr osc o p y o n uri n e se di me nt 
( d oc u me nte d b y t he l ocal la b orat or y) d uri n g Scree ni n g Peri o d. Prese nce of he mat uria 
d oc u me nte d b y t he ce ntr al la b orat or y ma y als o be acce pta ble. 
1 5.  C o m plia nce wit h sta ble a n d o pti mal d ose of R A S i n hi bit or treat me nt i ncl u di n g ma xi m u m 
all o we d or t oler ate d A C E i n hi bit or a n d/ or A R B d ose f or ≥ 3 m o nt hs pri or t o Scree ni n g 
wit h n o e x pecte d c ha n ge i n d ose d uri n g t he Bli n de d Treat me nt Peri o ds (t hr o u g h 
Wee k  5 0) ( partici p a nts wit h esta blis he d i nt olera nce t o R A S i n hi bit ors ma y be i ncl u de d). 
1 6.  C o ntr olle d a n d sta ble bl o o d press ure ( defi ne d as < 1 4 0/ 9 0 m m H g) o ver t he past 3 m o nt hs 
pri or t o ra n d o mizati o n. 
5. 2.  
E xcl usi o n Criteri a  
5. 2. 1.  
E xcl usi o n Criteri a f or B ot h C o h orts 
A partici pa nt will be e x cl u de d fr o m t he st u d y if a n y of t he f oll o wi n g criteri a a p pl y. 
Dise ase C h ar acteristi cs  
1.  Esti mate d G F R  ≤ 3 0 m L/ mi n/ 1. 7 3 m2 d uri n g Scree ni n g calc ulate d b y 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)  
2.  F or partici pa nts wit h e G F R <  4 5 m L/ mi n/ 1. 7 3 m2 at Scree ni n g, prese nce of a n y of t he 
f oll o wi n g i n gl o mer uli o n m ost rece nt ki d ne y bi o ps y pri or t o or d uri n g t he Scree ni n g 
Peri o d: 
a. ≥ 5 0 % i nterstitial fi br osis a n d t u b ular atr o p h y 
b.  ≥ 5 0 % gl o mer ular scler osis 
c. ≥ 5 0 % acti ve cresce nt f or mati o n  
3.  C o nc o mita nt si g nifica nt re nal disease ot h er t ha n L N or I g A N o n t he m ost rece nt bi o ps y 
pri or t o or d uri n g t he Scr ee ni n g Peri o d 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 6 7  of 1 5 2  
Ale xi o n C o nfi de ntial  
4.  Hist or y of s oli d or ga n ( ki d ne y, heart, l u n g, s mall b o wel, pa ncreas, or li ver) or b o ne 
marr o w tra ns pl a nt, or pla n ne d tra ns pla nt d uri n g t h e Bli n de d E xte n de d Treat me nt Peri o d 
( 5 0 wee ks)  
Me dic al C o n diti o ns  
5.  S ple nect o m y or f u ncti o n al as ple nia 
6.  Hist or y of seiz ur e 
7.  K n o w n or s us pect e d c o m ple me nt deficie n c y, u nless attri b uta ble t o u n derl yi n g disease 
(ie, L N a n d I g A N)  
8.  Hist or y or prese n ce of a n y ris k fact ors f or T orsa d es de P oi ntes (e g, heart 
fail ure/car di o m y o pat h y or fa mil y hist or y of L o n g Q T S y n dr o me), a scree ni n g Q T i nter val 
c orrecte d usi n g Fri derici a's f or m ula ( Q Tc F) > 4 5 0 msec f or males a n d  > 4 7 0 msec f or 
fe males, or recei vi n g me dicati o ns k n o w n t o si g nifica ntl y pr ol o n g t he c orrecte d Q T 
i nter val ( Q Tc), e x ce pt f or h y dr o x yc hl or o q ui ne i n patie nts wit h L N 
9.  La b orat or y a b n or malities at Scree ni n g, i ncl u di n g: 
•  Ala ni ne a mi n otra nsf eras e ( A L T)  > 2 × t he u p p er li mit of n or mal ( U L N) 
•  Direct bilir u bi n  > 2 × U L N  
1 0.  He m o gl o bi n A 1 C at Scree ni n g > 7. 0 % 
1 1.  A n y ot her cli nicall y si g nifica nt la b orat or y a b n or m alit y t hat, i n t he o pi ni o n of t he 
I n v esti gat or, w o ul d ma ke t he partici pa nt i na p pr o priate f or t he st u d y or p ut t he partici pa nt 
at u n d ue ris k 
1 2.  I nstit uti o nalizati o n b y a d mi nistrati ve or c o urt or der or k n o w n me dical or ps yc h ol o gical 
c o n diti o n(s) or ris k fact or t hat, i n t he o pi ni o n of t he I n vesti gat or, mi g ht i nterfere wit h t he 
partici pa nt’s f ull partici p ati o n i n t he st u d y, p ose a n y a d diti o nal ris k f or t he partici pa nt, or 
c o nf o u n d t he ass ess me nt of t he partici pa nt or o ut c o me of t he st u d y 
1 3.  K n o w n or s us pect e d hist or y of dr u g or alc o h ol a b use or de pe n d e nce wit hi n 1 year pri or t o 
t he start of t he Scr ee ni n g Peri o d 
1 4.  Hist or y of h y perse nsiti vit y t o a n y i n gre die nt c o ntai ne d i n t he st u d y i nter ve nti o n, 
i ncl u di n g i na bilit y t o ta ke or t olerat e t he all o we d c o nc o mita nt t hera pies c o nsiste nt wit h 
t he sta n dar d of car e ( Secti o n 6. 5. 3 ), wit h t he e xce pti o n of R A S i n hi bit ors f or t he I g A N 
c o h ort (i ncl usi o n criteri o n 1 5). 
1 5.  Hist or y of mali g na nc y wit hi n 5 years pri or t o Scree ni n g wit h t he e xce pti o n of 
n o n mela n o ma s ki n ca ncer or carci n o ma i n sit u of t he cer vi x t hat h as bee n treate d wit h n o 
e vi de nce of rec urr e nce  
1 6.  E vi de nce of h e patitis B ( p ositi ve he patitis s urface a nti ge n [ H Bs A g] or p ositi ve c ore 
a nti b o d y (a nti- H Bc) wit h ne gati ve s urface a nti b o d y [a nti- H Bs]) or h e patitis C viral 
i nfecti o n ( he p atitis C vir us [ H C V] a nti b o d y p ositi ve, e xce pt f or patie nts wit h d oc u me nte d 
s uccessf ul treat me nt a n d d oc u me nte d s ustai ne d vir ol o gic res p o nse [ S V R]) at Scree ni n g 
1 7.  E vi de nce of h u m a n i m m u n o deficie nc y vir us ( HI V a nti b o d y p ositi ve) i nfecti o n at 
Scree ni n g  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 6 8  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 8.  B o ne marr o w i ns uffi cie n c y wit h a bs ol ute ne utr o p hil c o u nt < 1. 3 × 1 0 3/ μ L; 
t hr o m b oc yt o pe nia ( platel et c o u nt < 5 0, 0 0 0/ m m3) 
1 9.  Acti ve s yste mic bact erial, viral, or f u n gal i nfecti o n wit hi n 1 4 da ys pri or t o first d ose of 
st u d y i nter ve nti o n 
2 0.  Prese nce of fe v er as d o c u me nte d b y a te m perat ure  ≥ 3 8° C ( 1 0 0. 4° F) wit hi n 7 da ys pri or 
t o a d mi nistrati o n of st u d y i nter ve nti o n o n Da y 1 
2 1.  Hist or y of Neisseri a  me ni n giti dis  i nfecti o n 
Pri or/ C o nc o mit a nt T her a p y  
2 2.  C urre nt treat me nt wit h a bi ol o gic me dicati o n t hat ma y affect i m m u ne s yste m f u ncti o ni n g, 
or has st o p pe d treat me nt wit h a bi ol o gic me dicati o n t hat ma y affect i m m u ne s yste m 
f u ncti o ni n g, a n d 5 ter mi n al half-li ves of t he bi ol o gic me dicati o n ha ve n ot el a pse d b y t he 
ti me of t he Scree ni n g Visit, or treat me nt wit h beli m u ma b or rit u xi ma b ≤ 6 m o nt hs pri or 
t o Scree ni n g 
2 3.  A n y pre vi o us or c urre nt treat me nt wit h c o m ple me nt i n hi bit ors (e g, ec uliz u ma b, 
ra v uliz u ma b) 
2 4.  Use of k n o w n c yt o c hr o m e P 4 5 0, fa mil y 3, s u bfa mil y A ( C Y P 3 A) se nsiti ve s u bstrates, 
m o derate or str o n g C Y P 3 A i n d ucers, a n d/ or m o derate or str o n g C Y P 3 A i n hi bit ors fr o m 
2 wee ks or 5  h alf -li ves, w hic he ver is l o n ger, pri or t o t he first a d mi nistrati o n of st u d y 
i nter ve nti o n o n Da y 1 (r a n d o mizati o n). T he f ull list pr o vi de d i n Secti o n 1 0. 1 6 ) 
2 5.  Use of selecte d me dicati o ns k n o w n t o l o wer t he s eiz ure t hres h ol d a n d/ or ca use seiz ure. 
See Secti o n  1 0. 1 5  for list of me dicati o ns  
Pri or/ C o nc urre nt Cli nic al St u d y E x perie nce  
2 6.  Partici pati o n i n a n ot her i n vesti gati o nal dr u g or i n vesti gati o nal de vice st u d y wit hi n 
3 0 da ys bef or e i nitiati o n of st u d y i nter ve nti o n o n Da y 1 i n t his st u d y or wit hi n 
5 half -li ves of t hat i n vesti gati o nal pr o d uct, w hic he ver is great er 
Ot her E xcl usi o ns  
2 7.  Pre g na nt, breastfee di n g, or i nte n di n g t o c o ncei ve d uri n g t he c o urse of t he st u d y 
5. 2. 2.  
E xcl usi o n Criteri a S pecific f or L N C o h ort  
2 8.  Partici pa nts w h o ha ve i nitiate d a n y of t he f oll o wi n g treat me nts f or t he c urre nt acti ve L N 
flare: 
a. C ycl o p h os p ha mi de ≤ 6 m o nt hs pri or t o Scree ni n g 
b.  C NIs  ≤ 1 m o nt h pri or t o Scree ni n g 
c. A c u m ulati ve d ose of i ntr a ve n o us (I V) met h yl pre d nis ol o ne > 3 g 
d.  M yc o p he n olate m of etil > 2 g/ da y ( or e q ui val e nt) f or ≥ 8 c o nsec uti ve w ee ks pri or t o 
Scree ni n g  
e. Pre d nis o ne or pre d nis o n e e q ui vale nt ≥ 0. 5 m g/ k g/ da y f or ≥ 8 c o ns ec uti ve wee ks pri or 
t o Scree ni n g 
2 9.  U nc o ntr olle d h y pert e nsi o n (s yst olic bl o o d press ure > 1 6 0 m m H g or diast olic bl o o d 
press ure  > 1 1 0 m m H g) o n 2 or m ore meas ure me nts d uri n g t he Scree ni n g Peri o d 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 6 9  of 1 5 2  
Ale xi o n C o nfi de ntial  
3 0.  Pri or hist or y or cli nicall y acti ve S L E relat e d cere britis, seiz ures, str o ke, or str o ke 
s y n dr o me re q uiri n g treat me nt or cli nicall y acti ve pericar ditis 
3 1.  I n a bilit y t o ta ke or t olerat e t he all o we d c o nc o mita nt t hera pies c o nsiste nt wit h t he sta n dar d 
of car e.  
5. 2. 3.  
E xcl usi o n Criteri a S pecific f or I g A N C o h ort  
3 2.  Dia g n osis of ra pi d pr o gr essi ve gl o mer ul o ne p hritis as meas ure d b y e G F R l oss  ≥ 3 0 % o ver 
a peri o d of 3  m o nt hs pri or t o or d uri n g t he Scree ni n g Peri o d  
3 3.  Sec o n dar y eti ol o gies of I g A N (e g, S L E, cirr h osis, celiac disease)  
3 4.  Cli nicall y acti ve He n oc h -Sc h o nlei n p ur p ura (I g A vasc ulitis) re q uiri n g treat me nt  
3 5.  Pre d nis o ne or pre d nis o n e e q ui vale nt  >  2 0  m g/ da y f or  >  1 4  c o ns ec uti ve da ys or a n y ot her 
s yste mic i m m u n os u p pressi o n f or t he treat me nt of I g A N ≤ 6  m o nt hs pri or t o Scree ni n g  
3 6.  Bl o o d press ure of  ≥ 1 4 0/ 9 0  m m H g d uri n g t he Scree ni n g Peri o d c o nfir m e d o n 
2  meas ures  >  3 0  mi n utes a part  
3 7.  B o d y mass i n de x  ≥ 3 8 k g/ m 2 d uri n g Scree ni n g  
5. 3.  
Lifest yle C o nsi der ati o ns  
Certai n f o o ds s uc h as gra pefr uit ha ve b ee n s h o w n t o be i n hi bit ors of C Y P 3 A 4 e nz y me acti vit y. 
Partici pa nts s h o ul d refr ai n fr o m c o ns u mi n g t hese f o o ds a n d be vera ges fr o m 2  wee ks pri or t o t he 
first a d mi nistrati o n of st u d y i nter ve nti o n o n Da y 1 u ntil 2  wee ks after t h e fi nal d ose of st u d y 
i nter ve nti o n. 
5. 4.  
Scree n F ail ures  
Scree n f ail ures are defi ne d as partici pa nts w h o c o nse nt t o partici pate i n t he cli nical st u d y b ut are 
n ot s u bse q ue ntl y ra n d o ml y assi g ne d t o st u d y i nter ve nti o n. A mi ni mal set of scree n fail ure 
i nf or mati o n is re q uire d t o e ns ure tra ns p are nt re p orti n g of scree n fail ure partici pa nts t o meet t he 
C o ns oli date d Sta n dar ds of Re p orti n g Trials p u blis hi n g re q uire me nts a n d t o res p o n d t o q ueries 
fr o m re g ulat or y a ut h orities. Mi ni mal i nf or mati o n i ncl u des de m o gra p h y, scree n fail ure det ails 
(e g, faile d eli gi bilit y criteria), AEs, i ncl u di n g a n y S A Es, a n d a n y rel ate d c o nc o mita nt me dicati o n 
occ urri n g d uri n g t he Scree ni n g Peri o d.  
I n di vi d uals w h o d o n ot meet t he criteri a f or p arti ci pati o n i n t his st u d y (scree n fail ure) d ue t o a 
reas o n t hat is e x pecte d t o res ol ve or has res ol ve d, ma y be res cree ne d bas e d o n disc ussi o n a n d 
a gree m e nt bet wee n t he I n vesti gat or a n d t he Me di cal M o nit or.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 7 0  of 1 5 2  
Ale xi o n C o nfi de ntial  
6.  
S T U D Y I N T E R V E N TI O N 
St u d y i nter ve nti o n is defi ne d as a n y i n vesti gati o nal i nter ve nti o n(s), mar ket e d pr o d uct(s), 
place b o, or me di cal de vi ce(s) i nte n d e d t o be a d mi nistere d t o a st u d y partici pa nt acc or di n g t o t he 
st u d y pr ot oc ol. 
6. 1.  
St u d y I nter ve nti o n(s) A d m i nistere d 
T he i nter ve nti o ns i n t his st u d y are A L X N 2 0 5 0 a n d matc hi n g place b o. St u d y i nter ve nti o ns are 
prese nte d i n Ta bl e  1 0. All o we d c o nc o mita nt t hera pies are disc uss e d i n Secti o n 6. 5. 3. 1  an d 
Secti o n  6. 5. 3. 2  f or t he L N a n d I g A N c o h orts, res pecti vel y. 
T a b le 1 0: 
St u d y I nter ve nti o ns 
St u d y I nter ve nti o n 
N a me  
A L X N 2 0 5 0  
Pl ace b o  
D ose f or m ul ati o n 
Ta blet  
Ta blet  
P h ysic al descri pti o n  
R o u n d, w hite t o off- w hite fil m 
c oate d ta blet 
R o u n d, w hite t o off- w hite fil m c oate d 
ta blet 
U nit d ose stre n gt h(s)  
6 0 m g 
Place b o  
D os a ge le vels 
1 2 0 m g bi d or 1 8 0 m g t wice dail y 
N ot a p plica ble  
R o ute of 
a d mi nistr ati o n  
Oral  
Oral  
I M P or A x M P 
I M P  
I M P  
Use  
E x peri me ntal 
Place b o c o m parat or  
F or mer N a me 
A C H - 0 1 4 5 2 2 8 
N ot a p plica ble  
S o urci n g  
Ale xi o n P har mace uticals, I nc.  
Ale xi o n P har mace uticals, I nc.  
A b bre viati o ns: A x M P = a u xiliar y me dici nal pr o d uct; bi d = t wice dail y; I M P  = i n vesti gati o nal me dici nal pr o d uct 
Partici pa nts will ta ke st u d y i nter ve nti o n bi d (a d ose of 3 ta blets i n t he m or ni n g a n d a sec o n d 
[e ve ni n g] d os e of 3 ta blets a p pr o xi matel y 1 2 h o urs after t he m or ni n g d os e). D oses s h o ul d be 
ta ke n at a p pr o xi mat el y t he sa me ti me eac h da y. If a d ose is misse d, it s h o ul d be ta ke n wit hi n 
6 h o urs of t he ori gi nall y sc he d ule d ti me. After 6 h o urs, t he misse d d ose s h o ul d be s ki p pe d. I n 
eit her cas e, t he ne xt d ose s h o ul d be ta ke n acc or di n g t o t he ori gi nal d osi n g sc he d ule. I nf or mati o n 
o n misse d d oses s h o ul d be rec or de d i n t he electr o nic case re p ort f or m (e C R F). 
M ost d oses will be ta ke n o utsi de of t he cli nic. Partici pa nts will be pr o vi de d wit h s ufficie nt st u d y 
i nter ve nti o n t o last u ntil t heir ne xt st u d y visit. 
F or st u d y visits t hat re q uire P K sa m ple c ollecti o n, partici pa nts will be i nstr ucte d t o a bstai n fr o m 
ta ki n g t heir A L X N 2 0 5 0 d ose o n t he m or ni n gs of t heir st u d y visits s o t hat t he y ca n b e d ose d i n 
t he cli nic f oll o wi n g t he pr ot oc ol-re q uire d assess m e nts. At t he cli nic visit, partici pa nts will first 
ha ve bl o o d dra w n f or cli nical la b orat or y a n d ot her e val uati o ns as o utli ne d i n t he S o A 
( Secti o n 1. 3 ), t he n ta ke t he m or ni n g d ose of A L X N 2 0 5 0 assi g ne d f or t hat da y. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 7 1  of 1 5 2  
Ale xi o n C o nfi de ntial  
6. 1. 1.  
Bli n de d Tre at m e nt  
A L X N 2 0 5 0 a n d place b o ta blets will be i de ntical i n a p peara nce. T he bli n de d st u d y i nter ve nti o ns 
are s h o w n i n  T a ble  1 1. 
T a ble 1 1: 
Bli n de d St u d y I nter ve nti o n fr o m Wee k  1 t o Wee k 5 0 i n A d diti o n t o All o we d 
C o nc o mit a nt T her a p y 
Ti mi n g  
 
D ose Gr o u p  
A L X N 2 0 5 0  
1 2 0 m g bi d  
A L X N 2 0 5 0  
1 8 0 m g bi d  
Pl ace b o  
M or ni n g d ose 
6 0 m g 
6 0 m g 
Place b o  
6 0 m g 
6 0 m g 
Place b o  
Place b o  
6 0 m g 
Place b o  
A p pr o xi matel y 1 2 h o urs i nter val 
E ve ni n g d ose 
6 0 m g 
6 0 m g 
Place b o  
6 0 m g 
6 0 m g 
Place b o  
Place b o  
6 0 m g 
Place b o  
A b bre viati o n: bi d  = t wice dail y 
6. 1. 2.  
St u d y I nter ve nti o n(s) P ac k a gi n g a n d L a beli n g  
St u d y i nter ve nti o n will be pr o vi de d i n ta m per pr o of c o ntai ners t hat will be la bele d acc or di n g t o 
c o u ntr y-s pecific re g ul ati o ns. At a mi ni m u m, t he c o ntai ner will be la bele d wit h: 
•  Pr ot oc ol n u m ber 
•  L ot n u m ber/e x pir y date 
•  Ale xi o n na me a n d a d dress 
•  I nstr u cti o ns f or use a n d st ora ge 
6. 2.  
Pre p ar ati o n/ H a n dli n g/ St or a ge/ Acc o u nt a bilit y  
6. 2. 1.  
Pre p ar ati o n  
T he st u d y i nter ve nti o n will be pr o vi de d b y Ale xi o n; n o s pecific pre p arati o n i nstr ucti o ns are 
re q uire d. 
6. 2. 2.  
St or a ge a n d H a n dli n g  
A L X N 2 0 5 0 a n d mat c hi n g place b os m ust be st ore d at r o o m te m perat ure ( 1 5° C t o 3 0° C; 5 9° F t o 
8 6° F). 
St u d y i nter ve nti o n will be s hi p pe d directl y t o eac h i n vesti gati o nal site. T he I n v esti gat or or 
desi g nee m ust c o nfir m a p pr o priate te m perat ure c o n diti o ns ha ve bee n mai ntai ne d d uri n g tra nsit 
f or all st u d y i nter ve nti o n recei v e d a n d t hat a n y dis cre pa n cies are re p orte d a n d res ol ve d bef ore 
dis pe nsati o n of t he st u d y i nter ve nti o n. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 7 2  of 1 5 2  
Ale xi o n C o nfi de ntial  
O nl y partici pa nts e nr olle d i n t he st u d y ma y recei v e t he st u d y i nter ve nti o n a n d o nl y a ut h orize d 
site staff ma y s u p pl y or a d mi nister t he st u d y i nter ve nti o n. All st u d y i nter ve nti o n m ust be st ore d 
i n a sec ur e, e n vir o n me nt all y c o ntr olle d, a n d m o nit ore d ( ma n ual or a ut o mat e d) area i n acc or d a nce 
wit h t he la bele d st ora g e c o n diti o ns wit h access li mite d t o t he I n v esti gat or a n d a ut h orize d site 
staff. 
6. 2. 3.  
Acc o u nt a bilit y a n d Dis p os al 
T he I n vesti gat or, i nstit uti o n, or t he hea d of t he me dical i nstit uti o n ( w here a p plica ble) is 
res p o nsi ble f or st u d y i nter ve nti o n acc o u nt a bilit y, rec o nciliati o n, a n d rec or d mai nte na nce (ie, 
recei pt, r ec o n ciliati o n, a n d fi nal dis p ositi o n rec or ds). 
•  T his res p o nsi bilit y i ncl u des t he re p orti n g of a n y te m perat ure e xc ursi o ns a n d pr o d uct 
c o m plai nts t o  Ale xi o nI M P T E @ale xi o n.c o m  an d  pr o d uctc o m plai nts @ale xi o n.c o m  
wit hi n 1  b usi ness da y of a ware ness. 
A pr o d uct c o m pl ai nt is defi ne d as a ny writte n, electr o nic, or or al c o m m u ni c ati o n t h at 
alle ges deficie ncies r el ate d t o t he i de ntity, q u ality, d ur a bility, reli a bility, us a bility, 
s afety, effective n ess, or p erf or m a nce of a pr o d uct or cli nic al st u dy m ateri al a n d/ or its 
p ack a gi n g c o m p o n e nts after it is h as bee n rele ase d f or distri b uti o n t o a n e n d 
c ust o mer t h at affects t he perf or m a nce of s uc h pr o d uct. 
•  T he I n vesti gat or m ust mai ntai n a de q uate rec or ds of dr u g dis pe nsati o n t hr o u g h o ut t he 
st u d y. At a mi ni m u m, dr u g dis pe nsati o n acti vities m ust i ncl u de rec or di n g t he date, l ot 
n u m ber, q ua ntit y of ta blets a d mi nistere d t o eac h p artici pa nt, a n d i nf or m ati o n a b o ut 
a n y use d, u n use d, or e x pire d c o ntai ners t hat are destr o ye d at t he site or ret ur ne d t o 
Ale xi o n. 
•  At t he c o ncl usi o n or ter mi nati o n of t he st u d y, after fi nal acc o u nt a bilit y f or st u d y 
i nter ve nti o n i n ve nt or y has bee n perf or me d b y Al e xi o n or desi g nee, t he I n v esti gat or 
m ust e ns ure use d, u n use d, or e x pire d c o ntai ners at t he site are ret ur ne d t o Al e xi o n or 
desi g nee i n acc or d a nce wit h Ale xi o n i nstr ucti o ns or destr o ye d if t he site h as 
a p pr o priate facilities a n d writte n pr oce d ures t o dis p ose of st u d y i nter ve nti o n. 
•  T he p har macist or ot her desi g nate d i n di vi d ual will mai ntai n rec or ds of st u d y 
i nter ve nti o n deli vere d t o t he st u d y site, t he i n ve nt or y at t he st u d y site, t he distri b uti o n 
t o a n d use b y eac h partici pa nt, a n d t he ret ur n of m aterials t o t he s p o ns or f or st ora ge or 
dis p osal/ destr ucti o n of materials at t he st u d y site. T hese rec or ds s h o ul d i ncl u de dates, 
q ua ntities, batc h/serial n u m bers, e x pirati o n dates, i n- cli nic te m perat ure l o g, a n d 
u ni q ue c o de n u m bers assi g ne d t o t he st u d y i nter ve nti o n a n d st u d y partici pa nts. 
•  T he I n vesti gat or will mai ntai n rec or ds t hat a de q uatel y d oc u me nt t hat t he partici pa nts 
were a d mi nistere d t he c orrect st u d y treat me nt kits a n d rec o n cile t he pr o d u cts recei v e d 
fr o m t he dr u g dis pe nsi n g ce nter. I n vesti gati o nal pr o d uct will n ot be ret ur ne d t o t he 
s p o ns or or dis p ose d of u ntil acc o u nta bilit y has bee n f ull y m o nit ore d. 
F urt her g ui d a nce re gar di n g pre par ati o n, ha n dli n g, st ora ge, a n d acc o u nt a bilit y a n d i nf or mati o n 
f or t he fi nal dis p ositi o n of u n use d st u d y i nter ve nti o n is pr o vi de d i n t he P har mac y Ma n u al.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 7 3  of 1 5 2  
Ale xi o n C o nfi de ntial  
6. 3.  
Me as ures t o Mi ni mize Bi as: R a n d o miz ati o n a n d Bli n di n g  
6. 3. 1.  
R a n d o miz ati o n a n d Str atific ati o n 
All partici pa nts will be ra n d o mize d o n Da y  1 usi n g a ce ntralize d i nteracti v e res p o nse tec h n ol o g y 
(I R T) aft er t he I n v esti gat or has verifi e d t hat t he y are eli gi ble t o partici pate i n t he st u d y. After 
Scree ni n g, eli gi ble partici pa nts will be assi g ne d t o a treat me nt ar m b y stratifie d ra n d o mizati o n. 
F or eac h disease c o h ort, partici pa nts meeti n g eli gi bilit y criteria will be ra n d o ml y assi g ne d i n a 
3: 1: 3 rati o t o recei ve A L X N 2 0 5 0 1 8 0 m g bi d, A L X N 2 0 5 0 1 2 0 m g bi d, or place b o bi d, 
res pecti vel y (Ta ble  8) d uri n g t he Bli n de d I nitial E val uati o n Peri o d. T he L N c o h ort will c o nti n ue 
wit h t he sa me treat me nt all ocati o n d uri n g t he Bli n de d E xte n de d Treat me nt Peri o d. F or t he I g A N 
c o h ort, partici pa nts assi g ne d t o t he place b o gr o u p will als o be assi g ne d t o t heir acti ve st u d y 
treat me nt f or t he Bli n de d E xte n de d Treat me nt Peri o d ( A L X N 2 0 5 0 1 2 0 m g bi d or A L X N 2 0 5 0 
1 8 0 m g bi d) i n a 1: 1 all ocati o n rati o at t he ti me of i nitial ra n d o mizati o n.  
T he ra n d o mizati o n strat u m f or t he L N c o h ort is as f oll o ws: 
•  C ortic oster oi d i n d ucti o n treat me nt i nitiate d ( pri or t o scree ni n g, d uri n g Scree ni n g 
Peri o d) 
T he ra n d o mizati o n strat u m f or t he I g A N c o h ort is as f oll o ws: 
•  Mea n pr otei n uria fr o m 2 vali d 2 4- h o ur uri ne c ollecti o ns ( 1 t o 2 g/ da y vers us > 2 g/ da y) 
6. 3. 2.  
Bli n di n g  
All i n vesti gati o nal site pers o n nel, ot her staff directl y ass ociate d wit h t he c o n d uct of t he st u d y, 
a n d all partici pa nts will be bli n de d t o treat me nt assi g n me nt d uri n g t he Bli n de d I nitial E val uati o n 
Peri o d a n d t he Bli n de d E xte n de d Treat me nt Peri o d. T he d o u b le- bli n d will be mai ntai ne d b y 
usi n g i de ntical st u d y treat me nt kits a n d la bels f or all partici pa nts. T he place b o ta blet will ha ve a n 
i de ntical a p peara n ce t o t hat of A L X N 2 0 5 0. T h e ra n d o mizati o n c o de will b e mai ntai ne d b y t he 
I R T pr o vi d er. Select Al e xi o n staff will be u n bli n de d f or t he pri mar y a n al ysis at Wee k 2 6. All 
partici pa nts, I n vesti gat ors, a n d site pers o n nel will re mai n bli n de d t o treat m e nt assi g n me nt fr o m 
Da y  1 t hr o u g h t he e n d of t he Bli n de d E xte n de d Treat me nt Peri o d (ie, Wee k 5 0). After 
c o m pleti o n of all assess me nts at t he e n d of t he Bli n de d E xte n de d Treat me nt Peri o d, partici pa nts 
will be gi n recei vi n g o pe n-la bel treat me nt d uri n g t he O L E Peri o d a n d t heref ore, partici p a nts, 
I n v esti gat ors, a n d site pers o n nel will n o l o n ger be bli nde d t o t he i nitial treat me nt assi g n me nt. 
K n o wle d ge of t h e i nitial treat me nt assi g n me nt d uri n g t he O L E Peri o d is n ot e x pecte d t o i m pact 
t he data i nte grit y as t he pri mar y a n d ke y s ec o n dar y e n d p oi nts ha ve alrea d y bee n c ollecte d a n d 
d ue t o t he o bjecti ve nat ur e of t hese e n d p oi nts. 
6. 3. 3.  
U n bli n di n g  
D uri n g t he Bli n de d I nitial E val uati o n Peri o d a n d t he Bli n de d E xte n de d Treat me nt Peri o d , 
u n bli n di n g s h o ul d o nl y be c o nsi der e d f or t he s afet y of t he partici pa nt. I n case of a n e m er ge n c y, 
t he I n v esti gat or has t he s ole res p o nsi bilit y f or deter mi ni n g if u n bli n di n g of a patie nt’s 
i nter ve nti o n assi g n me nt is warr a nte d. Partici pa nt s afet y m ust al wa ys be t h e first c o nsi derati o n i n 
ma ki n g s uc h a deter mi nati o n. If t he I n vesti gat or d eci des t hat u n bli n di n g is warra nte d, t he 
I n v esti gat or will be a ble t o u n bli n d t he partici pa nt’s treat me nt all ocati o n directl y usi n g t he I R T. 
If a partici pa nt’s i nter v e nti o n assi g n me nt is u n bli n de d, t he S p o ns or m ust be n otifie d wit hi n 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 7 4  of 1 5 2  
Ale xi o n C o nfi de ntial  
2 4  h o urs after brea ki n g t he bli n d. T he date a n d reas o n t hat t he bli n d was br o ke n m ust be 
rec or d e d i n t he s o urce d o c u me ntati o n. 
I n t he e ve nt of a s us pect e d u ne x pecte d s eri o us a d v erse reacti o n ( S U S A R), t he bli n d will be 
br o ke n f or t hat s p ecific p artici pa nt o nl y. T he bli n d will be mai ntai ne d f or p ers o ns res p o nsi ble f or 
t he o n g oi n g c o n d uct of t he st u d y (e g, m o nit ors, I n vesti gat ors) a nd t h ose res p o nsi ble f or data 
a nal ysis a n d i nter pr etati o n of res ults, s uc h as bi o m etrics pers o n n el.  
U n bli n de d i nf or mati o n will o nl y be accessi ble t o t h ose w h o are i n v ol ve d i n safet y re p orti n g t o 
Healt h A ut h orities, I E Cs, a n d/ or I R Bs.  
A n y partici pa nt w h o is u n bli n de d d uri n g t he bli n de d peri o ds will be wit h dra w n fr o m t he st u d y.  
I n v esti gat ors will recei ve o nl y bli n de d i nf or mati o n u nless u n bli n de d i nf or mati o n is j u d ge d 
necessar y f or s afet y r eas o ns.  
6. 4.  
St u d y I nter ve nti o n C o m pli a nce  
W he n partici p a nts are d ose d at t he i n vesti gati o nal site, t he y will recei ve st u d y i nter ve nti o n 
directl y fr o m t he I n v esti gat or or desi g nee, u n der m e dical s u per visi o n. T he d ate a n d ti me of eac h 
d ose a d mi nistere d i n t he cli nic will be rec or de d i n t he s o urce d o c u me nts a n d i n t he e C R F.  
W he n partici p a nts self -a d mi nister st u d y i nter ve nti o n at h o me, c o m plia nce wit h t he st u d y 
i nter ve nti o n will be assesse d b y direct q uesti o ni n g a n d c o u nti n g of ret ur n e d ta blets d uri n g t he 
ne xt i n -cli nic visit a n d rec or de d i n t he s o urce d oc u me nts. De viati o n(s) fr o m t he prescri be d 
d osa ge re gi me n s h o ul d b e rec or de d.  
A rec or d of t he q u a ntit y of st u d y i nter ve nti o n dis pe nse d a n d a d mi nistere d t o/ta ke n b y eac h 
partici pa nt m ust be mai ntai ne d a n d r ec o ncile d wit h st u d y i nter ve nti o n rec or ds pr o vi de d t o t he 
i n vesti gati o nal site. I nter ve nti o n start a n d st o p dates, i ncl u di n g dates f or pl a n ne d a n d u n pla n n e d 
i nter ve nti o n dela ys a n d/ or d ose re d u cti o ns will als o be rec or de d. 
6. 5.  
Pri or a n d C o nc o mit a nt T her a p y  
A n y me dicati o n (i ncl u di n g o ver -t he-c o u nter or prescri pti o n me dici nes, vita mi ns, a n d/ or her bal 
s u p ple me nts), vacci n es, or ot her s pecific cate g ori es of i nterest t hat t he p artici pa nt is recei vi n g at 
t he ti me of e nr oll me nt or recei v es d uri n g t he st u d y m ust be rec or d e d al o n g wit h: 
•  Reas o n f or use  
•  Dates of a d mi nistrati o n, i ncl u di n g start a n d e n d dates  
•  D osa ge i nf or m ati o n i ncl u di n g d ose a n d fre q ue nc y  
N o n p har mac ol o gic treat me nts a n d t hera pies t hat t he partici pa nt recei v es d uri n g t he cli nical st u d y 
m ust be rec or d e d al o n g wit h:  
•  Reas o n f or use  
•  Dates of a d mi nistrati o n, i ncl u di n g start a n d e n d dates  
•  Dia g n ostics a d mi nistere d, if a p plica ble  
•  W het her t he treat me nt is o n g oi n g  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 7 5  of 1 5 2  
Ale xi o n C o nfi de ntial  
T he Me dical M o nit or s h o ul d be c o ntacte d if t h ere are a n y q u esti o ns re gar di n g c o nc o mita nt or 
pri or t hera p y. 
6. 5. 1.  
All o we d Me dic ati o ns a n d T her a p y  
All o we d c o nc o mita nt t hera p y is disc usse d i n Secti o n  6. 5. 3. 1  (L N c o h ort) a n d Secti o n  6. 5. 3. 2  
(I g A N c o h ort).  
A n y me dicati o n or t her a p y (i ncl u di n g o ver-t he- c o u nter or pres cri pti o n me dici nes, vacci n es, 
vita mi ns, a n d/ or her bal s u p ple me nts) dee me d n ecessar y f or t he partici p a nt’s care d uri n g t he 
st u d y, or f or t he treat me nt of a n y A E, al o n g wit h a n y ot her me dicati o ns, ot h er t ha n t h ose liste d as 
disall o we d me dicati o ns i n Secti o n  6. 5. 2 , ma y be gi ve n at t he discreti o n of t he I n vesti gat or. 
H o we ver, it is t he res p o nsi bilit y of t he I n vesti gat or t o e ns ure t hat det ails re gar di n g t he 
me dicati o n are rec or de d o n t he e C R F ( Secti o n  8. 2. 5 ). 
If a de q u ate bl o o d press ur e c o ntr ol is n ot ac hie v e d d uri n g t he st u d y, partici pa nts ma y recei ve 
a d diti o nal a nti h y perte nsi ve a ge nts, b ut n ot a ge nts t hat affect pr otei n uria d uri n g t he st u d y t hr o u g h 
Wee k  5 0. It is r ec o m me n de d t hat n o nster oi dal a nti-i nfla m mat or y dr u gs ( N S AI Ds) n ot be 
i nitiate d d uri n g t he st u d y d ue t o t he p ossi bilit y of a d verse effects o n re nal f u ncti o n. H o we ver, 
t hese ca n b e use d if i n dicate d f or s y m pt o matic relief f or a s h ort peri o d of ti me ( u p t o a ma xi m u m 
of 7 da ys per t h e la bele d usa ge; if a n  i ncreas e d d ose/treat me nt d urati o n is re q uire d, t he 
I n v esti gat or m ust disc uss wit h t he S p o ns or). 
F or partici pa nts i n t he L N c o h ort o nl y: 
•  P ne u m ocystis p ne u m o ni a  pr o p h yla xis is all o we d at t he discreti o n of t he I n v esti gat or. 
•  Treat me nt wit h a nti malarial a ge nts s uc h as h y dr o x yc hl or o q ui ne are str o n gl y 
rec o m me n de d u nl ess c o ntrai n dicate d. 
•  Meas ures t o pr e ve nt a n d treat oste o p or osis are e n c o ura ge d d uri n g t he st u d y; t hese 
meas ures ma y i ncl u d e a n y, or all, of t he f oll o wi n g: calci u m car b o n ate or citrate, 
Vita mi n D, a n d bis p h os p h o nates. 
•  I m m u n os u p pr essi ve dr u gs f or a d diti o nal sta n dar d of care t hera p y are all o w e d. 
6. 5. 2.  
Dis all o we d Me dic ati o ns a n d T her a p y  
Partici pa nts i n b ot h c o h orts are pr o hi bite d fr o m recei vi n g a n y of t he f oll o wi n g me dicati o ns a n d 
t hera pies d uri n g t he e ntir e d urati o n of st u d y partici pati o n: 
•  E x peri me ntal i nter ve nti o ns or t hera pies 
•  A c o m ple me nt i n hi bit or (e g, ec uliz u ma b, ra v uliz u ma b) 
•  Ne w use or m o difi cati o n of t he d ose of S G L T- 2 i n hi bit ors ( u p t o 5 0 wee ks)  
•  Ne w use or m o difi cati o n of t he d ose of R A S i n hi bit or or direct re ni n a nta g o nist 
treat me nt ( u p t o 5 0 wee ks)  
•  K n o w n C Y P 3 A se nsiti ve s u bstrates, m o derate or str o n g C Y P 3 A i n d ucers, a n d/ or 
m o derate or str o n g C Y P 3 A i n hi bit ors are pr o hi bite d t hr o u g h o ut t he st u d y, u ntil 
1 wee k after t he fi nal a d mi nistrati o n of st u d y i nter ve nti o n (see Secti o n  1 0. 1 6  f or a f ull 
list of t hese me dicati o ns) 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 7 6  of 1 5 2  
Ale xi o n C o nfi de ntial  
•  Selecte d me dicati o ns k n o w n t o l o wer t he seiz ure t hres h ol d a n d/ or ca use sei z ure 
s h o ul d n ot be ta ke n c o nc o mita ntl y (see Secti o n 1 0. 1 5  for a f ull list of t hese 
me dicati o ns)  
•  Me dicati o ns k n o w n t o si g nifica ntl y pr ol o n g t he c orrect e d Q T i nter v al ( Q T c), wit h t he 
e xce pti o n of h y dr o x y c hl or o q ui ne i n patie nts wit h L N 
I n t he e ve nt t hat a p artici pa nt recei ves a pr o hi bite d me dicati o n a n d/ or t hera p y, t he I n vesti gat or 
will c o nsi der t he disc o nti n uati o n of st u d y i nter ve nti o n ( Secti o n  7. 1 ). S G L T- 2 i n hi bit ors, R A S 
i n hi bit ors, a n d direct re ni n a nta g o nists are pr o hi bit e d b ut ma y be c o nsi dere d wit h o ut 
disc o nti n uati o n of st u d y i nter ve nti o n base d o n t he disc ussi o n a n d a p pr o val of t he I n vesti gat or 
a n d Me dical M o nit or. 
Partici pa nts i n t he I g A N c o h ort ar e als o pr o hi bite d fr o m recei vi n g a n y of t he f oll o wi n g 
me dicati o ns a n d t her a pies d uri n g t he e ntire d urati o n of st u d y partici pati o n: 
•  H y dr o x yc hl or o q ui ne 
•  I m m u n os u p pr essi ve a ge nts (e g, M M F) 
•  S yste mic c ortic oster oi ds f or  > 1 4 c o ns ec uti ve da ys (s h ort-ter m ster oi d c o urse 
f or ≤ 1 4 da ys f or m e dical c o n diti o ns n ot relate d t o I g A N or s ur g er y are per mitte d) 
F or partici pa nts i n t he L N c o h ort, escalati o n of i m m u n os u p pressi o n is all o we d f or 
pr ot oc ol- defi ne d R e nal, E xtrare n al Flares, a n d S u b o pti mal Res p o nse (after Wee k  2 6). C NIs 
i ncl u di n g, b ut n ot li mite d t o v ocl os p ori n, are pr o hi bite d. If a C NI is use d as a d diti o nal sta n dar d 
of car e t her a p y per t h e cli nical j u d g me nt of t he I n vesti gat or, A L X N 2 0 5 0 will nee d t o be 
disc o nti n ue d 3 da ys pri or t o C NI a d mi nistrati o n. H o we ver, t he partici p a nt ca n re m ai n i n t he 
st u d y a n d c o nti n ue t he st u d y visits as per t he S o A. 
A n y me dicati o ns n ot s pecifie d i n t his secti o n, t hat re mai n a c o n cer n t o t he I n vesti gat or s h o ul d be 
disc usse d wit h t he Me dical M o nit or. 
6. 5. 3.  
All o we d C o nc o mit a nt T her a p y 
T he all o we d c o n c o mita nt t hera p y c o nsiste nt wit h t he sta n dar d of care e m pl o ye d i n t his pr ot oc ol 
are c o nsiste nt wit h cli nical st u dies i n patie nts wit h L N (R o vi n, 2 0 1 9 ) a n d I g A N (Ra ue n, 2 0 1 5 ). 
6. 5. 3. 1.  
All o we d C o nc o mit a nt T her a p y f or L N C o h ort 
D uri n g t he c o urs e of t he st u d y, partici pa nts i n t he L N c o h ort will recei ve all o we d c o nc o mita nt 
t hera p y c o nsiste nt wit h t he sta n dar d of care f or i n d ucti o n a n d mai nte na nce treat me nt of L N. 
•  F or partici pa nts w h o ha v e n ot starte d c ortic ost er oi d i n d ucti o n treat me nt pri or t o 
Scree ni n g:  
− Partici pa nts will recei ve a c u m ulati ve d ose of 1  g of met h yl pre d nis ol o ne I V 
a d mi nistere d i n 1  or m ulti ple di vi de d d oses or oral e q ui vale nt d uri n g t he 
Scree ni n g Peri o d ( pri or t o Da y 1).  
− D uri n g t he Scree ni n g Peri o d a n d n o later t ha n D a y 2, all partici pa nts will recei ve 
oral c ortic oster oi ds wit h pre d nis o ne or pre d nis o ne e q ui vale nt wit h starti n g d oses 
as o utli ne d i n  Ta ble  1 2. T he starti n g mi ni m u m a n d ma xi m u m d oses all o we d are 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 7 7  of 1 5 2  
Ale xi o n C o nfi de ntial  
3 0 m g/ da y a n d 6 0 m g/ da y, res pecti vel y. A c ortic oster oi d ta per will c o m me nce at 
Wee k  2 ( Da y  1 4). Fr o m Wee k  1 2 t o Wee k 2 6, t he tar get d ose is 7. 5 m g/ da y. 
F oll o wi n g Wee k 2 6, p artici pa nts ma y re mai n o n 7. 5 m g/ da y or c o nti n ue t o ta per 
at t he cli nical discreti o n of t he I n vesti gat or u ntil Wee k  4 6. Fr o m Wee k 4 6 t o 
Wee k  5 0, t he d os e of c ortic oster oi ds m ust n ot be c ha n ge d. 
− D uri n g t he Scree ni n g Peri o d a n d n o later t ha n D a y 1, partici pa nts will recei ve a 
c u m ulati ve d ose of 1 t o 1. 5 g/ da y of M M F a n y ti m e after c o m pleti o n of t he 
I V met h yl pre d nis ol o ne d uri n g t he Scree ni n g Peri o d a n d n o later t ha n D a y 1. T he 
d ose ca n be a d mi nistere d i n m ulti ple di vi de d d oses. Partici pa nts will c o nti n ue t o 
recei v e 1 t o 1. 5 g/ da y f or 1 wee k.  
− After r ecei vi n g 1 t o 1. 5 g/ da y f or 1 wee k, t he d ose will be titrate d per t he 
discreti o n of t he I n v esti gat or t o a c u m ulati ve d ose u p t o 3 g/ da y of M M F n o later 
t ha n b y Wee k  4 ( Da y  2 8). T he d ose ca n be a d mi nistere d i n m ulti ple di vi de d 
d oses. Partici pa nts will c o nti n ue t o recei ve 1. 5 t o 3 g/ da y of M M F u ntil Wee k 5 0, 
after w hi c h it ma y be decrease d or disc o nti n ue d base d o n t he I n vesti gat ors’ 
j u d g me nt a n d t he K DI G O cli nical practice g ui deli nes (K DI G O, 2 0 1 2 ). 
•  F or partici pa nts w h o ha v e i nitiate d c ortic oster oi d i n d ucti o n treat me nt pri or t o 
Scree ni n g a n d d o n ot meet E xcl usi o n Criteri o n  2 8  (Secti o n  5. 2 ): 
− If t he partici p a nt alrea d y recei v e d met h yl pre d nis ol o ne I V ≥ 1 g or e q ui vale nt oral 
c ortic oster oi d i n d ucti o n a n d is recei vi n g M M F ≥ 2 g/ da y pri or t o Scree ni n g, t he n 
met h yl pre d nis ol o ne I V will n ot be gi ve n. T he partici pa nt ma y c o nti n ue t he 
c urre nt M M F d ose d uri n g Scree ni n g, a n d d uri n g t he Bli n de d I nitial E val u ati o n 
Peri o d t he d ose of M M F s h o ul d be a dj uste d t o ac hie ve 1. 5 t o 3 g/ da y n o lat er t ha n 
Da y  2 8 ( Wee k  4). M M F will be c o nti n ue d at 1. 5 t o 3 g/ da y u ntil Wee k  5 0, after 
w hic h it ma y be decreas e d or disc o nti n ue d base d o n t he I n v esti gat or’s j u d g me nt 
a n d t he K DI G O cli nical practice g ui d eli nes (K DI G O, 2 0 1 2 ). 
− If t he partici p a nt alrea d y recei v e d met h yl pre d nis ol o ne I V ≥ 1 g or e q ui vale nt oral 
c ortic oster oi d i n d ucti o n a n d is recei vi n g M M F < 2 g/ da y pri or t o Scree ni n g, t he n 
met h yl pre d nis ol o ne I V will n ot be gi ve n, a n d t he M M F d ose will be i ncrease d 
d uri n g t he Scree ni n g Peri o d ( n o later t ha n D a y 1) t o a c u m ulati ve d ose of 1 t o 
1. 5 g/ da y. Partici pa nts will c o nti n ue t o recei ve 1 t o 1. 5 g/ da y f or 1 wee k, after 
w hic h t he M M F d ose will be i ncreas e d per t h e discreti o n of t he I n v esti gat or t o 1. 5 
t o 3 g/ da y t o be ac hie v e d n o later t ha n Wee k 4 ( D a y  2 8). T hese d oses ca n be 
a d mi nistere d i n m ulti ple di vi de d d oses. Partici pa nts will c o nti n ue t o recei v e 1. 5 t o 
3 g/ da y u ntil Wee k 5 0, after w hic h it ma y be decrease d or disc o nti n ue d bas e d o n 
t he I n v esti gat or’s j u d g me nt a n d t he K DI G O cli nical practice g ui deli nes  
(K DI G O, 2 0 1 2 ). 
− If a partici pa nt is alrea d y recei vi n g pre d nis o ne or pre d nis o ne e q ui val e nt, t he d ose 
will be c o nti n ue d u ntil Da y 2, at w hic h ti me pre d nis o ne or pre d nis o ne e q ui vale nt 
s h o ul d be a d mi nistere d (t he mi ni m u m a n d ma xi m u m d oses all o we d are 
3 0 m g/ da y a n d 6 0 m g/ da y, res pecti vel y) as o utli ne d i n  Ta ble  1 2. The pre d nis o ne 
d ose will be ta per e d starti n g at Wee k  2 ( Da y  1 4) acc or di n g t o t he sc h e d ule. Fr o m 
Wee k  1 2 t o Wee k 2 6, t he tar get d ose is 7. 5 m g/ da y. F oll o wi n g Wee k 2 6, 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 7 8  of 1 5 2  
Ale xi o n C o nfi de ntial  
partici pa nts ma y re m ai n o n 7. 5 m g/ da y or c o nti n ue t o ta per at t he cli nical 
discreti o n of t he I n v esti gat or u ntil Wee k 4 6. Fr o m Wee k 4 6 t o Wee k 5 0, t h e d ose 
of c ortic oster oi ds m ust n ot be c ha n ge d. 
T a ble 1 2: 
C ortic ost er oi d T a per f o r P artici p a nts wit h L u p us Ne p hritis  
St u d y Wee k  
Pre d nis o ne D ose or E q ui v ale nt D ose ( m g/ d a y)  
≤ 6 0 k g 
6 1 t o 8 0 k g 
8 1 t o 1 0 0 k g 
≥ 1 0 0 k g 
Scree ni n g t o 
Wee k  2a 
3 0 
4 0 
5 0 
6 0 
2 
2 5 
3 5 
4 0 
5 0 
4 
2 5 
3 0 
3 0 
4 0 
6 
2 0 
2 5 
2 0 
3 0 
8 
1 5 
2 0 
1 5 
2 0 
1 0 
1 0 
1 5 
1 0 
1 0 
1 2 b 
7. 5 
7. 5 
7. 5 
7. 5 
a Wei g ht at Scree ni n g will be use d f or d osi n g, a n d t his wei g ht cate g or y will be use d t hr o u g h o ut t he st u d y. T he 
mi ni m u m a n d ma xi m u m starti n g d oses of pre d nis o ne are 3 0  m g a n d 6 0  m g, res pecti vel y.  
b Fr o m Wee k  1 2 t o Wee k  2 6, t he tar get d ose is 7. 5  m g/ da y. F oll o wi n g Wee k  2 6, partici pa nts ma y re mai n o n 
7. 5  m g/ da y or c o nti n ue t o ta per at t he cli nical discreti o n of t he I n vesti gat or u ntil Wee k  4 6. Fr o m Wee k  4 6 t o 
Wee k  5 0, t he d ose of c ortic oster oi ds m ust n ot be c ha n ge d.  
•  A n e q ui vale nt d ose of e nteric-c o ate d m yc o p he n olic aci d s o di u m ( M P S) ma y be use d 
i nstea d of M M F (i e, a 3 6 0 m g d ose M P S is e q ui vale nt t o a 5 0 0 m g d ose of M M F). 
•  I n v esti gat ors ma y a dj ust t he d osa ge of M M F d ue t o t olera nce or A Es. If t he 
partici pa nt’s s y m pt o ms res ol ve, t he I n vesti gat or s h o ul d atte m pt t o i ncrease M M F ( or 
e q ui vale nt) t o t he g oal le vel of 1. 5 t o 3 g/ da y. If s y m pt o ms ret ur n, t he n t he partici pa nt 
s h o ul d be c o nti n ue d o n t he hi g hest t olera ble d ose. 
•  C ha n ges t o t he d ose of M M F a n d t he j ustificati o n will be d oc u me nte d i n t he e C R F. 
Ot her c o nsi derati o ns re g ar di n g t he c ortic oster oi d ta per: 
•  All partici pa nts will ha ve a sc he d ule d c ortic oster oi d ta per starti n g o n Da y 1 4. 
Partici pa nts will re d uce t heir pre d nis o ne d os e acc or di n g t o t heir baseli ne b o d y wei g ht 
o ver 1 0 wee ks u ntil t he d ose is 7. 5 m g/ da y b y Wee k 1 2 (Ta ble  1 2). Fr o m Wee k 1 2 t o 
Wee k  2 6, t he t ar get d ose is 7. 5 m g/ da y. F oll o wi n g Wee k 2 6, p artici pa nts m a y re mai n 
o n 7. 5 m g/ da y or c o nti n ue t o ta per at t he cli nical discreti o n of t he I n v esti gat or u ntil 
Wee k  4 6. Fr o m Wee k 4 6 t o Wee k  5 0, t he d ose of c ortic oster oi ds m ust n ot be 
c ha n ge d. 
•  De viati o ns fr o m t he sc h e d ule d c ortic oster oi d ta p er f or a n y reas o n ot her t ha n Re nal 
Flare or E xtrare nal S L E Flare will c o nf o u n d i nter pretati o n, s o e ver y atte m pt s h o ul d 
be ma de t o a d h ere t o t he ta peri n g sc he d ul e.  
•  If disease is t o o cli nicall y acti ve i n t he o pi ni o n of t he I n vesti gat or t o be gi n t he 
c ortic oster oi d ta per aft er Wee k  2, t he n t h e partici p a nt ma y c o nti n ue t o recei ve his or 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 7 9  of 1 5 2  
Ale xi o n C o nfi de ntial  
her i nitial c ortic oster oi d d ose f or u p t o a n a d diti o nal 2 8 da ys. Si milarl y, partici pa nts 
w h o ha ve start e d t he ta per a n d w h ose disease is t o o cli nicall y acti ve t o c o nti n ue 
ta peri n g ma y r e mai n at t he sa me ta per d ose ac hie ve d f or u p t o a n a d diti o nal 2 8 da ys. 
Fail ure t o ac hie ve t h e c ortic oster oi d ta per b y Wee k  1 2 will n ot be c o nsi dere d as 
Treat me nt Fail ure a n d will be ca pt ure d as a sec o n dar y e n d p oi nt. 
•  H o we ver, t he pre d nis o n e d ose ma y N O T be i n crease d be y o n d t he ta p er d ose ac hie v e d 
u nless t he partici pa nt meets t he pr ot oc ol- defi ne d criteria f or Re n al Flare 
( Secti o n 8. 1. 6 ) a n d/ or se vere E xtrare n al S L E Flare ( Secti o n 8. 1. 7 ), i n w hic h case 
t hese partici pa nts will recei ve a d diti o nal sta n dar d of care t hera p y a n d will be i ncl u de d 
as treat me nt f ail ures.  
6. 5. 3. 2.  
All o we d C o nc o mit a nt T her a p y f or I g A N C o h ort 
T he all o we d c o n c o mita nt t hera pies f or partici pa nts i n t he I g A N c o h ort will be c o nsiste nt wit h 
sta n dar d of car e a n d i ncl u de t he ma xi m u ml y t olerate d d ose of R A S- bl oc ki n g a ge nts, s uc h as 
A C Eis or A R Bs.  
T he all o we d c o n c o mita nt treat me nt s h o ul d be hel d sta ble t hr o u g h o ut t he first 5 0 wee ks of t he 
Treat me nt Peri o d of t h e st u d y. 
6. 5. 4.  
A d diti o n al St a n d ar d of C are T her a p y f or L N C o h ort 
I n t he L N c o h ort, partici pa nts w h o meet criteria f or pr ot oc ol-defi ne d Re nal Flare ( Secti o n  8. 1. 6 ) 
will recei ve a d diti o nal sta n dar d of car e t hera p y.  
Partici pa nts i n t he L N c o h ort w h o meet t he criteri a f or E xtrare n al S L E Flare ( Secti o n  8. 1. 7 ) ma y 
recei v e a d diti o nal sta n dar d of care t hera p y, if c o nsi dere d cli nicall y a p pr o priate b y t he 
I n v esti gat or. If a d diti o nal sta n dar d of care t hera p y is a d mi nistere d f or a n E xtrare n al S L E Flare, 
t he e ve nt is c o nsi der e d a se vere E xtrare nal S L E Fl are. 
After Wee k  2 6, a d diti o nal sta n dar d of care t h era p y f or partici pa nts wit h S u b o pti mal Res p o nse 
( Secti o n 8. 1. 8 ) is all o we d at t he cli nical discreti o n of t he I n vesti gat or i n c o n versati o n wit h t he 
Me dical M o nit or. 
A d diti o nal sta n dar d of care t her a p y, all flares, a n d S u b o pti mal Res p o nse will be d oc u me nte d i n 
t he e C R F. 
A d diti o nal sta n dar d of care t her a p y is defi ne d as i nte nsificati o n of c urre nt sta n dar d of care or 
i ntr o d ucti o n of ne w i m m u n os u p pressi ve t hera pies. T he s pecific c h oice of a d diti o nal sta n dar d of 
care t h era p y is ge n er all y at t he discreti o n of t he I n vesti gat or a n d ma y i ncl u de a p pr o ve d 
me dicati o ns f or L N ( e g, v ocl os p ori n, beli m u ma b). H o we ver, if a C NI is us e d as a d diti o nal 
sta n dar d of car e t hera p y, A L X N 2 0 5 0 will nee d t o be disc o nti n ue d 3 da ys pri or t o C NI 
a d mi nistrati o n ( Secti o n  6. 5. 2 ). 
T he f oll o wi n g g ui deli nes f or c ortic oster oi d d osi n g f or pr ot oc ol- d efi ne d Re n al Flare a n d 
E xtrare n al S L E Flar e s h o ul d be c o nsi dere d t o mai ntai n treat me nt c o nsiste n c y:  
•  Partici pa nts wit h pr ot oc ol- defi ne d Re nal Flare ma y be treate d wit h oral pre d nis o ne u p 
t o 0. 5 m g/ k g/ da y ( n ot t o e xcee d 6 0 m g/ da y) f or u p t o 2 wee ks. Pre d nis o ne will t he n 
be ta per e d wee kl y t o 1 0 m g/ da y wit hi n 6 wee ks after t he i nitial pre d nis o ne i ncreas e. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 8 0  of 1 5 2  
Ale xi o n C o nfi de ntial  
Pre d nis o ne ma y f urt her b e ta pere d t o ≤ 7. 5 m g/ da y at t he discreti o n of t he 
I n v esti gat or. 
•  Partici pa nts wit h E xtrare nal S L E Flare m a y be treate d wit h oral pre d nis o ne u p t o 
1 m g/ k g/ da y ( n ot t o e xcee d 6 0 m g/ da y) f or u p t o 2 wee ks. Pre d nis o ne will t he n be 
ta pere d e ver y 2 wee ks t o ac hie ve 7. 5  m g/ da y wit hi n 1 2 wee ks after t he i nitial 
c ortic oster oi d i ncr ease.  
•  I ntr a ve n o us c ortic oster oi ds i n e q ui vale nt d oses ma y be all o we d if g astr oi ntesti nal 
i n v ol ve me nt te m p oralit y precl u des oral c ortic oster oi d use. 
Pre d nis o ne ≥ 1 0 m g f or ≤ 1 4 da ys will n ot be c o nsi dere d a d diti o nal sta n dar d of care t hera p y i n 
t he f oll o wi n g i nsta nces: 
•  Re nal Flar es n ot meeti n g t he pr ot oc ol defi ne d crit eria f or R e nal Fl are (see 
Secti o n  8. 1. 6 ). 
•  Ot her me dical c o n diti o ns or s ur ger y 
T he use of a d diti o nal sta n dar d of care t h era p y s h o ul d be disc usse d directl y bet wee n t he 
I n v esti gat or a n d Me di cal M o nit or. 
6. 5. 5.  
V acci n ati o n a n d A nti bi otic Pr o p h yl a xis 
T o miti gate t he p ote ntial ris k of me ni n g oc occal i nfecti o n, all partici pa nts m ust be vacci nat e d 
wit hi n 3  years pri or t o, or at t he ti me of, i nitiati n g t he st u d y i nter ve nti o n. Vacci nes a g ai nst 
ser ot y pes A, C, Y, W 1 3 5, a n d B, w here a vaila ble, are rec o m me n d e d t o pre v e nt c o m m o n 
pat h o ge nic me ni n g oc o ccal ser ot y pes. Partici pa nts w h o i nitiate st u d y i nter ve nti o n treat me nt less 
t ha n 2 wee ks after recei vi n g a me ni n g oc occal vacci ne m ust recei ve treat me nt wit h a p pr o priate 
pr o p h ylactic a nti bi otics u ntil at least 2  wee ks aft er vacci nati o n.  
Partici pa nts m ust be vacci nate d or re v acci nate d acc or di n g t o c urre nt nati o nal vacci n ati o n 
g ui deli nes or l ocal practice f or v acci nati o n use wit h c o m ple me nt i n hi bit ors. Vacci n ati o n ma y n ot 
be s ufficie nt t o pr e ve nt me ni n g oc occal i nfecti o n. All partici pa nts s h o ul d be m o nit ore d f or earl y 
si g ns of me ni n g oc occal i nfecti o n, e val u ate d i m me diatel y if i nfecti o n is s us pecte d, a n d treate d 
wit h a p pr o priate a nti bi otics, if necessar y. 
A n y partici pa nt wit h o ut s ufficie nt hist or y of t hese vacci nes ma y b e vacci nat e d or pr o vi de d 
b o osters per nati o nal or l ocal g ui deli nes. 
Gi ve n t he c hr o nic pr o gressi o n of I g A N, i n partici pa nts wit h I g A N, e ver y eff ort s h o ul d be ma de 
t o start t he me ni n g oc occal vacci n ati o n series at least 1 4 da ys pri or t o ra n d o mizati o n. 
Partici pa nts s h o ul d be vacci nate d or re v acci nat e d a gai nst ot her pat h o ge ns acc or di n g t o c urre nt 
nati o nal vacci nati o n g ui d eli nes or l ocal practice f or vacci n ati o n use as part of sta n dar d of care.  
6. 6.  
D ose M o dific ati o n  
D ose m o dificati o n of st u d y i nter ve nti o n f or a n i n di vi d ual partici pa nt is n ot per mitte d f or t his 
st u d y. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 8 1  of 1 5 2  
Ale xi o n C o nfi de ntial  
O nce t he o pti mal d ose of A L X N 2 0 5 0 is deter mi ne d, partici pa nts o n A L X N 2 0 5 0 w h o ha ve 
c o m plete d at least 5 0  w ee ks of treat me nt will be s witc he d t o t he o pti mal d ose as i n dicate d i n 
Fi g ure 1  (f or L N c o h ort) a n d Fi g ur e 2  (f or I g A N). 
6. 7.  
I nter ve nti o n After t he E n d of t he St u d y 
After a p artici pa nt c o m pl etes t he O L E Peri o d or wit h dra ws fr o m t he st u d y, st u d y i nter ve nti o n 
will n ot be a d mi nistere d.  
U p o n c o m pleti o n of t he last st u d y visit, partici pa nts will ret ur n t o t he care of t heir treati n g 
p h ysicia n. 
6. 8.  
Tre at me nt of O ver d ose  
F or t his st u d y, a n y bli n de d d ose of i n vesti gati o nal me dici nal pr o d uct (I M P) or Ale xi o n a u xiliar y 
me dici nal pr o d uct ( A x M P) greater t h a n t hat s pecifie d i n t he pr ot oc ol will be c o nsi dere d a n 
o ver d ose. 
Ale xi o n d oes n ot rec o m me n d s pecific treat me nt f or a n o ver d os e. Ge n eral s u p p orti ve meas ures 
are r ec o m me n d e d.  
O ver d oses are me di cati o n err ors t hat are n ot c o nsi dere d A Es u nl ess t here is a n u nt o war d me dical 
occ urr e nce res ulti n g fr o m t he o ver d ose. 
I n t he e ve nt of a n o ver d ose or s us pecte d o v er d ose, t he I n v esti gat or/treati n g p h ysicia n s h o ul d: 
1.  Ca pt ure a n d f or war d t he e ve nt, wit h or wit h o ut ass ociate d A Es, t o Ale xi o n Gl o bal Patie nt 
Safet y ( G P S) via e mail or facsi mile (cli nicalsae @ ale xi o n.c o m or + 1. 2 0 3. 4 3 9. 9 3 4 7) 
usi n g t he Ale xi o n Cli nical St u d y O ver d ose Re p ort F or m wit hi n 2 4 h o urs of a ware ness. 
2.  C o ntact t he Me dical M o nit or i m me diatel y.  
3.  E val uate t he partici pa nt t o deter mi ne, i n c o ns ultati o n wit h t he Me dical M o nit or, if 
p ossi ble, w het her st u d y i nter ve nti o n s h o ul d be i nterr u pte d or w het her t he d ose s h o ul d be 
re d uce d. 
4.  Cl osel y m o nit or t he partici pa nt f or a n y A E/ S A E a n d la b orat or y a b n or malities. 
5.  O btai n a plas ma sa m ple f or P K a nal ysis if re q u este d b y t he Me dical M o nit or ( deter mi ne d 
o n a case - b y-case b asis).  
6.  D oc u me nt t he q ua ntit y of t he e xcess d ose as w ell as t he d urati o n of t he o v er d ose. 
Decisi o ns re g ar di n g d ose i nterr u pti o ns or m o dificati o ns will be ma de b y t he I n vesti gat or i n 
c o ns ultati o n wit h t he Me dical M o nit or base d o n t he cli nical e val u ati o n of t he partici pa nt. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 8 2  of 1 5 2  
Ale xi o n C o nfi de ntial  
7.  
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D 
P A R TI CI P A N T DI S C O N TI N U A TI O N/ WI T H D R A W A L  
7. 1.  
Disc o nti n u ati o n of St u d y I nter ve nti o n  
Partici pa nts m ust be c o nsi dere d f or dis c o nti n uati o n fr o m st u d y i nter ve nti o n if a n y of t he 
f oll o wi n g occ ur d uri n g t he st u d y: 
•  Se vere h y perse nsiti vit y reacti o n. 
•  Se vere u nc o ntr olle d i nfecti o n. 
•  De vel o p me nt of sei z ures ( Secti o n  1 0. 1 4 ). 
•  Use of disall o we d me dicati o n (as defi ne d i n Secti o n  6. 5. 2 ) t o be c o nsi dere d o n a 
case- b y-cas e basis.  
•  Partici pa nts i n t he L N c o h ort recei vi n g h y dr o x yc hl or o q ui ne will be wit h dra w n if a 
Q T/ Q Tc i nter val > 5 0 0 msec or a n i ncreas e > 6 0 msec fr o m bas eli ne occ urs a n d is 
c o nfir me d o n r ec hec k. 
•  Pre g na nc y or pl a n ne d pr e g na nc y. A n y fe male p artici pa nt w h o bec o mes pre g na nt 
w hile partici pati n g i n t he st u d y will disc o nti n ue st u d y i nter ve nti o n a n d will be 
wit h dra w n fr o m t he st u d y.  
•  Ale xi o n or t he I n vesti gat or dee ms it is necessar y f or t he partici pa nt. 
•  A d verse e ve nt t hat w o ul d, i n t he o pi ni o n of t he I n vesti gat or, ma ke c o nti n u e d 
treat me nt wit h st u d y i nter ve nti o n a n u nacce pta bl e ris k. 
•  Partici pa nts i n t he L N c o h ort w h o ha ve 2 Treat me nt Fail ures. 
Data t o be c ollecte d at t h e ti me of st u d y i nter ve nti o n disc o nti n uati o n a n d f oll o w- u p a n d f or a n y 
f urt her e v al uati o ns t hat n ee d t o be c o m plet e d are pr o vi de d i n t he S o A ( Secti o n 1. 3 ). 
T he reas o n f or disc o nti n uati o n of st u d y i nter ve nti o n will be rec or d e d i n t he s o urce d o c u me nts 
a n d e C R F.  
If t he st u d y i nter ve nti o n is defi niti vel y disc o nti n ue d, e ver y eff ort s h o ul d be ma de t o ha ve t he 
partici pa nt re mai n i n t he st u d y a n d c o nti n ue t he st u d y visits as per t he S o A t hr o u g h Wee k 5 0 
( Secti o n 1. 3 ). 
Partici pa nts w h o disc o nti n ue st u d y i nter ve nti o n a n d re mai n i n t he st u d y ma y recei v e treat me nt 
c o nsiste nt wit h l ocal sta n dar d practice f or t heir dis ease per I n vesti gat or j u d g me nt, as a p plica ble. 
•  A Safet y F oll o w- u p Visit will be perf or me d 3 0 d a ys f oll o wi n g t he partici pa nt’s last 
d ose of st u d y i nter ve nti o n. 
If t he partici p a nt d oes n ot a gree t o c o nti n ue wit h t he st u d y visits after disc o nti n uati o n of st u d y 
i nter ve nti o n, t he f oll o wi n g acti vities s h o ul d be c o m plete d: 
•  E D Visit s h o ul d be perf or me d as o utli ne d i n t he S o A ( Secti o n  1. 3 ). 
•  A Safet y F oll o w- u p Visit will be perf or me d 3 0 d a ys f oll o wi n g t he partici pa nt’s last 
d ose of st u d y i nter ve nti o n 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 8 3  of 1 5 2  
Ale xi o n C o nfi de ntial  
If a partici pa nt disc o nti n ues st u d y i nter ve nti o n d ue t o a n A E, i ncl u di n g S A Es, t he e ve nt s h o ul d 
be f oll o we d as d escri be d i n Secti o n  1 0. 3. 3 . 
7. 2.  
P artici p a nt Disc o nti n u ati o n/ Wit h dr a w al fr o m t he St u d y  
•  All eff orts s h o ul d be ma d e t o e ns ure p artici pa nts are willi n g t o c o m pl y wit h st u d y 
partici pati o n pri or t o c o n d ucti n g t he scree ni n g pr o ce d ures. 
•  T he st u d y staff s h o ul d n otif y Ale xi o n a n d t heir site m o nit or of all st u d y wit h dra wals 
as s o o n as p ossi ble. T he r eas o n f or p artici pa nt disc o nti n uati o n m ust be rec or de d i n t he 
s o urce d oc u m e nts a n d e C R F. 
•  A partici pa nt ma y wit h dr a w fr o m t he st u d y at a n y ti me at his/ her o w n re q uest. 
− If t he partici p a nt wit h dra ws c o nse nt f or discl os ure of f ut ure i nf or mati o n, Ale xi o n 
ma y retai n a n d c o nti n ue t o use a n y data c ollecte d bef ore  s u c h a wit h dra wal of 
c o nse nt, if per mitte d b y l ocal re q uire me nts. 
− If a partici pa nt wit h dra ws fr o m t he st u d y, t he partici pa nt ma y re q uest d estr ucti o n 
of a n y sa m ples ta ke n a n d n ot teste d, a n d t he I n vesti gat or m ust d oc u me nt t his i n 
t he site st u d y rec or ds. 
•  A partici pa nt ca n be wit h dra w n at a n y ti me i n t he best j u d g me nt of t he I n vesti gat or 
f or saf et y, be ha vi or al, c o m plia nce, or a d mi nistrati ve reas o ns, s u c h as: 
− Pre g na nc y or pl a n ne d pre g na nc y 
− Lac k of efficac y  
− Partici pa nt n o nc o m plia nce 
− I nterc urre nt ill ness t hat w o ul d affect assess me nt of cli nical stat us t o a si g nifica nt 
de gree  
− U nacce pta ble t o xicit y (i n cl u di n g a cli nicall y si g nifica nt la b orat or y v al ue) t h at 
c o m pr o mises t he partici p a nt’s a bilit y t o c o nti n ue st u d y s pecific pr oce d ures 
− A n y ot her c o n diti o n or circ u msta nce t h at t hat w o ul d je o par dize t he welfare of 
partici pa nts wer e t he y t o c o nti n ue i n t he st u d y 
•  At t he ti me of disc o nti n ui n g fr o m t he st u d y, if p ossi ble, a n E D Visit s h o ul d be 
c o n d ucte d, as s h o w n i n t he S o A ( Secti o n  1. 3 ). Refer t o t he S o A f or d ata t o be 
c ollecte d at t he ti me of st u d y disc o nti n uati o n a n d f oll o w- u p a n d f or a n y f urt her 
e val uati o ns t hat nee d t o b e c o m plete d. 
7. 3.  
L ost t o F oll o w -u p  
A partici pa nt  will be c o nsi dere d l ost t o f oll o w - u p if t he partici pa nt re peat e dl y fails t o ret ur n f or 
sc he d ule d visits a n d is u na ble t o be c o ntacte d b y t he st u d y site. 
T he f oll o wi n g acti o ns m ust be ta ke n if a p artici pa nt fails t o ret ur n t o t he cli nic f or a re q uire d 
st u d y visit: 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 8 4  of 1 5 2  
Ale xi o n C o nfi de ntial  
•  T he site m ust atte m pt t o c o ntact t he partici pa nt t o resc he d ul e t he misse d visit as s o o n 
as p ossi ble, c o u nsel t he p artici pa nt o n t he i m p orta nce of mai ntai ni n g t he assi g ne d 
visit sc he d ule, a n d ascert ai n w het her or n ot t he partici pa nt wis hes t o a n d/ or s h o ul d 
c o nti n ue i n t he st u d y. 
•  Bef ore a p artici pa nt is dee me d l ost t o f oll o w - u p, t he I n vesti gat or or d esi g nee m ust 
ma ke e ver y eff ort t o re g ai n c o ntact wit h t he partici pa nt ( w here p ossi ble, 3 tele p h o ne 
calls a n d, if necessar y, a certifie d letter t o t he parti ci pa nt’s last k n o w n maili n g 
a d dress or l ocal e q ui vale nt met h o ds). T hese c o ntact atte m pts s h o ul d be d oc u me nte d 
i n t he partici pa nt’s me dical rec or d. 
•  S h o ul d t he partici pa nt c o nti n ue t o be u nreac ha ble, he/s he will be c o nsi dere d l ost t o 
f oll o w- u p. 
Disc o nti n uati o n of s pecific sites or of t he st u d y as a w h ole are ha n dle d as p art of Secti o n  1 0. 1. 9 . 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 8 5  of 1 5 2  
Ale xi o n C o nfi de ntial  
8.  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  
•  St u d y pr oce d ures a n d t heir ti mi n g are s u m marize d i n t he S o A ( Secti o n  1. 3 ). 
A d here n ce t o t he st u d y d esi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he S o A 
( Secti o n 1. 3 ), is esse ntial a n d re q uire d f or st u d y c o n d uct. 
•  I m me diat e saf et y c o ncer ns s h o ul d be disc usse d wit h Ale xi o n i m me diatel y u p o n 
occ urr e nce or a w ar e ness t o deter mi ne if t he partici pa nt s h o ul d c o nti n ue or 
disc o nti n ue st u d y i nter ve nti o n. 
•  All scree ni n g e v al uati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat p ote ntial 
partici pa nts meet all eli gi bilit y criteria. T he I n vesti gat or will mai ntai n a scree ni n g l o g 
t o rec or d d etails of all partici pa nts scree ne d a n d t o c o nfir m eli gi bilit y or rec ord 
reas o ns f or scr ee ni n g fail ure, as a p plica ble. Eli gi bilit y, st u d y a d mi nistrati ve, a n d 
scree ni n g assess me nts ar e f urt her dis c usse d i n Secti o n 8. 1 2 . 
•  Pr oce d ures c o n d ucte d as part of t he partici pa nt’s r o uti ne cli nical ma na ge m e nt (e g, 
bl o o d c o u nt) a n d o btai ne d bef ore si g ni n g of t he I C F ma y be utilize d f or s cree ni n g or 
baseli ne p ur p oses pr o vi de d t he pr oce d ures met t h e pr ot oc ol- s pecifie d criteria a n d 
were p erf or me d wit hi n t he ti me fra me d efi ne d i n t he S o A ( Secti o n  1. 3 ). 
•  
See Secti o n  1 0. 2  for t he list of cli nical la b orat or y t ests (t hat will be c o n d uct e d at a 
ce ntral/s pecialt y la b orat or y).  
8. 1.  
Effic ac y Assess me nts  
8. 1. 1.  
2 4- H o ur Uri ne C ollecti o n f or Pr otei n uri a  
F or t he d eter mi nati o n of pr otei n uria, 2 4- h o ur uri ne c ollecti o ns will be o btai ne d at t he ti me p oi nts 
s pecifie d i n t he S o A ( Secti o n 1. 3 ) an d will be a nal yze d b y a ce ntral la b orat or y. I n a d diti o n t o 
pr otei n, al b u mi n, s o di u m, a n d creati ni ne will be q ua ntifie d i n eac h 2 4- h o ur uri ne c ollecti o n. B ot h 
U P C R as well as uri ne al b u mi n t o creati ni ne rati o ( U A C R) will be calc ul ate d usi n g a n ali q u ot o f 
t he 2 4- h o ur uri ne c ollecti o ns. 
Ri g or o us e xercise a n d si g nifica nt c ha n g e i n diet (i n partic ular, salt i nta ke) s h o ul d be a v oi de d 
wit hi n 4 8 h o urs bef ore c ollecti o n of 2 4- h o ur uri n e sa m ples, w he n e ver p ossi ble. 
T he c ollecti o n s h o ul d be o btai ne d pri or t o a d mi nistrati o n of st u d y i nter ve nti o n o n d osi n g da ys. 
T he 2 4- h o ur uri n e c ollecti o ns c o ul d occ ur at t he p artici pa nt’s h o me b y a m o bile n urse if a gree d 
u p o n wit h t he I n v esti gat or a n d t he partici pa nt, acc or di n g t o l ocal re g ulati o ns. T he c ollecti o n will 
be rec or de d i n t he e C R F acc or di n g t o t he e C R F c o m pleti o n g ui deli nes.  
8. 1. 1. 1.  
L N C o h ort  
F or partici pa nts i n t he L N c o h ort, pr otei n uria will be meas ure d b y U P C R. A si n gle 2 4- h o ur uri ne 
c ollecti o n will be o btai ne d at Scree ni n g t o assess eli gi bilit y. T w o se parate 2 4 - h o ur uri ne 
c ollecti o ns will be o btai ne d wit hi n 2  wee ks pri or t o t he Wee k  2 6 Visit (t o assess t he pri mar y 
e n d p oi nt) a n d Wee k 5 0 Visit (t o assess a sec o n d ar y e n d p oi nt). A d diti o nal 2 4- h o ur uri ne 
c ollecti o n is als o sc he d ul e d f or Wee k  1 0 2 a n d Wee k 1 5 4. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 8 6  of 1 5 2  
Ale xi o n C o nfi de ntial  
C o nfir mati o n of a pr ot oc ol- defi ne d Re nal Flare or S u b o pti mal Res p o nse re q uires a si n gle 
2 4- h o ur uri ne c ollecti o n wit hi n 2 wee ks of t he s p ot uri ne sa m ple ( Secti o n  8. 1. 6  an d 
Secti o n  8. 1. 8 ). 
8. 1. 1. 2.  
I g A N C o h ort 
Partici pa nts i n t he I g A N  c o h ort will be re q uire d t o pr o vi de 2 se parate, c o m plete, a n d vali d 
2 4- h o ur uri ne c ollecti o ns d uri n g t he Scree ni n g Peri o d (t o assess eli gi bilit y). F or e v al uati o n of t he 
pri mar y a n d ke y s ec o n dar y e n d p oi nts, t he t w o 2 4- h o ur uri ne c ollecti o ns s h o ul d be o btai ne d 
wit hi n 2  wee ks bef ore t h e Wee k  2 6 a n d Wee k 5 0 Visits. A d diti o nal 2 4- h o ur uri ne c ollecti o n is 
als o sc he d ule d f or Wee k  1 0 2 a n d Wee k 1 5 4. 
He nce, a 2 4 - h o ur uri ne c ollecti o n is c o nsi dere d vali d if all t he f oll o wi n g criteria are met, 
ot her wise t he uri ne c ollecti o n is re q uire d t o be re peate d: 
•  T he c ollecti o n is bet wee n 2 2 t o 2 6 h o urs i n d urati o n (ie, ti me fr o m t he i nitial 
discar de d v oi d t o t he last v oi d/atte m pt t o v oi d). 
•  N o v oi ds are misse d bet wee n t he start a n d e n d ti me of t he c ollecti o n as i n dicate d b y 
t he partici pa nt’s uri n e c ollecti o n diar y. 
Uri ne c ollecti o ns will be re vie we d b y t h e Me dical M o nit ori n g tea m.  
I n a de q uat e c ollecti o ns m a y nee d t o be re peate d as s o o n as p ossi ble wit hi n t he ti me fra mes 
o utli ne d i n t he S o A ( Secti o n  1. 3 ) i n or der t o e ns ure t hat 2 vali d c ollecti o ns are o btai ne d f or eac h 
of t he st u d y ti me p oi nts. 
8. 1. 2.  
S p ot Uri ne S a m ple ( B ot h C o h orts)  
Uri nar y pr otei n, al b u mi n, a n d creati ni ne le vels fr o m m or ni n g s p ot uri ne sa m ples pri or t o d osi n g 
will be meas ure d at t he ti me p oi nts s pecifie d i n t he S o A ( Secti o n  1. 3 ) to assess t he effect of 
st u d y i nter ve nti o n o n U P C R a n d U A C R. 
T w o c o nsec uti ve s p ot uri ne sa m ples will be o btai n e d f or partici pa nts i n b ot h disease c o h orts at 
Wee k  1 6 f or t he L N c o h ort a n d at Wee k 1 8 f or t h e I g A N c o h ort. 
T he U P C R a n d U A C R res ults will be rec or de d i n t he partici pa nt’s e C R F. 
8. 1. 3.  
Esti m ate d Gl o m er ul ar Filtr ati o n R ate ( B ot h C o h orts)  
C ha n ges i n re nal f u n cti o n will be m o nit ore d usi n g meas ure me nts of e G F R ( m L/ mi n/ 1. 7 3 m 2) a n d 
creati ni ne clear a nce o n a 2 4 - h o ur uri ne c ollecti o n. Ser u m creati ni ne will be a nal yze d as part of 
t he cli nical c he mistr y ( Secti o n 1 0. 2 ) c ollecte d pre d ose. T he e G F R calc ulati o n will be base d o n 
t he C K D-E PI f or m ula.  
F or t he d eter mi nati o n of C R R a n d P R R i n t he L N C o h ort at Wee k 2 6 a n d Wee k  5 0, 2 ser u m 
creati ni ne s a m ples f or e G F R will be o btai ne d, t h e first wit hi n 2  wee ks pri or t o eac h of t hese 
st u d y visits a n d t he sec o n d o n t he st u d y visit da y. T he bl o o d sa m ple c ollecti o n c o ul d occ ur at t he 
partici pa nt’s h o me if a gr ee d u p o n wit h t he I n vesti gat or a n d t he partici pa nt. T he c ollecti o n will be 
rec or d e d i n t he e C R F acc or din g t o t he e C R F c o m pleti o n g ui deli nes. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 8 7  of 1 5 2  
Ale xi o n C o nfi de ntial  
8. 1. 4.  
He m at uri a ( B ot h C o h orts)  
F or partici pa nts i n b ot h disease c o h orts, h e mat uria fr o m s p ot uri ne sa m ples will be e val uate d t o 
assess t he effect of st u d y i nter ve nti o n o n disease c o urse. T he de gree of he m at uria will be 
assesse d b y e x a mi nati o n of t he s p u n uri ne se di me nt b y micr osc o p y ( R B C/ h pf).  
Si n gle v oi d c ollecti o ns f or ra n d o m s p ot uri ne sa m ple f or he mat uri a e val u ati o n s h o ul d be 
c ollecte d. If t he I n vesti gat or deter mi nes t hat t he he mat uria is tra nsie nt d ue t o me nses i n w o me n 
or e xer cise, t he sa m ple m a y nee d t o be re peate d.  
Ra n d o m s p ot uri ne sa m ples f or he mat uri a meas ure me nt will be c ollecte d t hr o u g h o ut t he st u d y as 
o utli ne d i n t he S o A ( Secti o n  1. 3 ) a n d will be a nal y ze d b y a ce ntral la b orat or y. Sa m ples s h o ul d be 
c ollecte d pri or t o st u d y i nter ve nti o n a d mi nistrati o n, if a p plica ble.  
T he l ocal he mat uri a e val uati o n b y micr osc o p y or uri nar y di pstic k ma y be use d t o deter mi ne 
eli gi bilit y f or t he st u d y at Scree ni n g f or partici pa nts wit h I g A N, if dia g n ostic bi o ps y is  >  1  year 
ol d.  
8. 1. 5.  
Al b u mi n ( L N C o h ort O nl y)  
F or r e nal f u ncti o n ass ess me nt, sa m ples f or ser u m al b u mi n will be c ollecte d as part of t he cli nical 
c he mistr y e val uati o ns descri be d i n Secti o n  1 0. 2 . 
8. 1. 6.  
Re n al Fl are ( L N C o h ort O nl y)  
Re nal Flar e is deter mi ne d i n t he o pi ni o n of t he I n vesti gat or i n a d diti o n t o t he criteri a o utli ne d 
bel o w:  
•  F or partici pa nts w h o ac hi e ve C R R ( Secti o n  8. 1. 1 0 ), a Re nal Flare is t he re pr o d uci ble 
rec urre nce of pr ot ei n uria  ≥ 1  g/ g  
•  F or all ot her p artici pa nts, a Re nal Flare is eit her of t he f oll o wi n g:  
− Re pr o d uci ble i ncr ease of ser u m creati ni ne  >  2 5 % hi g her t ha n baseli ne or a b o ve 
t he U L N, pl us a n y o ne of t he f oll o wi n g : 
o  Re pr o d uci ble pr otei n uri a  ≥ 7 5 % hi g her t ha n bas eli ne  
o  W orse ni n g acti ve uri nar y se di me nt c o m pare d t o b aseli ne as defi ne d b y a n 
i ncreas e of ≥ 5  R B Cs/ h pf or ne w R B C casts ( base d o n l ocal la b orat or y 
res ults fr o m at least 2 sa m ples) 
o  Ki d ne y bi o ps y de m o nstrati n g L N Class III or I V acti vit y w hic h was 
c o n d ucte d si nce t h e bi o ps y use d f or eli gi bilit y  
− Re pr o d uci ble d o u bli n g of t he U P C R fr o m a 2 4 -h o ur uri ne c ollecti o n c o m pare d 
wit h t he l o west pre vi o us val ue o btai ne d after t he first d ose of st u d y i nter ve nti o n.  
•  Re pr o d uci bilit y of pr otei n uri a  re q uires t hat U P C R fr o m t he m or ni n g s p ot uri ne 
c ollecti o n is c o nfir me d b y a ce ntral la b U P C R base d o n 2 4 -h o ur uri n e c ollecte d 
wit hi n 2 wee ks . 
•  Re pr o d uci bilit y of ser u m cre ati ni ne  re q uires 2 bl o o d tests wit hi n a 2  wee k peri o d.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 8 8  of 1 5 2  
Ale xi o n C o nfi de ntial  
Partici pa nts w h o meet criteria f or t he pr ot oc ol -defi ne d Re nal Flare will recei ve a d diti o nal 
sta n dar d of car e t hera p y ( Secti o n 6. 5. 4 ). T he Me di cal M o nit or s h o ul d be n otifie d of t he Re nal 
Flare b y t h e I n vesti gat or or S u b-i n vesti gat or. 
A n y Re nal Flare t hat d oes n ot meet t he pr ot oc ol- d efi ne d Re nal Flare criteria ma y be treate d wit h 
a li mite d d urati o n of i ncr ease d or al c ortic oster oi ds ( ≤ 1 4 da ys) after disc ussi o n wit h t he Me dical 
M o nit or. S uc h treat me nt will n ot be c o nsi dere d a d diti o nal sta n dar d of care t hera p y a n d will n ot 
be c o nsi der e d Treat me nt Fail ure.  
Re nal Flar e criteria will be rec or de d o n t he Re n al Flare e C R F. 
8. 1. 7.  
E xtr are n al S yste mic L u p us Er yt he m at os us Fl are ( L N C o h ort O nl y) 
T he S yste mic L u p us Er yt he mat os us Disease A cti vit y I n de x 2 0 0 0 ( S L E D AI- 2 K) is a n i nstr u me nt 
t hat assesses t he diseas e acti vit y of S L E. T his i nstr u me nt will be use d f or t he m o nit ori n g of 
E xtrare n al S L E Flar e i n t he L N C o h ort.  
E xtrare n al S L E Flar e is defi ne d as a n i ncrease i n S L E D AI -2 K Safet y of Estr o ge ns i n L u p us 
Er yt he mat os us Nati o nal Assess me nt ( S E L E N A) M o dificati o n ≥ 4 p oi nts (see Secti o n  8. 1 1. 2 ) 
t hat is n ot acc o u nte d f or b y pr otei n uria, he mat uri a, uri nar y cell ular casts, h y p oc o m ple me nte mia, 
or a n i ncr ease i n a nti - d o u ble-stra n de d D N A (a nti- ds D N A) a nti b o d y le vel. 
Partici pa nts i n t he L N c o h ort w h o meet t he criteri a f or E xtrare n al S L E Flare ma y recei ve 
a d diti o nal sta n dar d of car e t hera p y, if c o nsi dere d cli nicall y a p pr o priate b y t he I n vesti gat or. If 
a d diti o nal sta n dar d of car e t hera p y is a d mi nistere d, t he e ve nt is c o n si dere d a se vere E xtrare nal 
S L E Flare.  
Partici pa nts will be all o we d t o recei ve a li mite d n u m ber of c ortic ost er oi d treat me nts f or 
n o n- se ver e E xtrare nal S L E Flar e, if cli nicall y warra nte d as o utli ne d bel o w. S uc h treat me nt will 
n ot be c o nsi dere d a d diti o nal sta n dar d of care t hera p y a n d affecte d p ar tici pa nts will n ot be 
c o nsi dere d Treat me nt Fail ure.  
•  U p t o 2 c ortic oster oi d treat me nts will be all o we d f or a n o n -se v ere E xtrare n al S L E 
Flare.  
•  O ne c ortic oster oi d treat m e nt will be all o we d bet w ee n Wee k  1 2 (e n d of ster oi d ta per) 
a n d Wee k  2 2 ( 4 w ee ks pri or t o t he Wee k  2 6 pri mar y e n d p oi nt). 
•  O ne c ortic oster oi d treat m e nt will be all o we d bet w ee n Wee k  2 6 a n d Wee k 4 6 
( 4 wee ks pri or t o t he Wee k  5 0 a nal ysis). 
•  Eac h treat me nt c o urse s h o ul d be n o l o n ger t ha n 1 4 da ys i n d urati o n wit h t he ster oi d 
d ose ret ur ni n g t o 7. 5 m g/ da y b y Da y 1 4. 
•  U p t o a t otal of 2 0 m g/ da y ( pre d nis o ne or pre d nis o ne e q ui vale nt) is per mitte d. 
•  T here ca n be n o c o nc urre nt w orse ni n g of re n al disease (as defi n e d b y t he criteria f or a 
Re nal Flar e).  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 8 9  of 1 5 2  
Ale xi o n C o nfi de ntial  
8. 1. 8.  
S u b o pti m al Res p o nse ( L N C o h ort O nl y)  
A S u b o pti mal Res p o nse is deter mi ne d i n t he o pi ni o n of t he I n vesti gat or i n a d diti o n t o t he 
f oll o wi n g criteri o n aft er t he Wee k 2 6 Visit:  
•  Re pr o d uci ble pr otei n uri a ≤ 2 5 % decrease d c o m pare d t o baseli ne b ase d o n U P C R o n a 
2 4- h o ur uri ne c ollecti o n perf or me d b y ce ntral la b orat or y 
Re pr o d uci bilit y of pr otei n uri a  re q uires t hat t he pr otei n uria base d o n a U P C R fr o m a s p ot uri ne 
c ollecti o n is c o nfir me d b y a ce ntr al la b orat or y U P C R calc ulate d o n a 2 4 - h o ur uri ne c ollecti o n 
o btai ne d wit hi n a 2- wee k peri o d. 
Partici pa nts wit h S u b o pti mal Res p o nse m ust be disc usse d wit h t he I n vesti g at or a n d Me dical 
M o nit or. Partici pa nts wit h S u b o pti mal Res p o nse will sta y i n t he st u d y a n d c o nti n ue t o recei ve 
st u d y i nter ve nti o n. I nte nsificati o n of c urre nt sta n d ar d of care or i ntr o d ucti o n of ne w 
i m m u n os u p pressi ve t hera pies ar e all o we d p er t he cli nical discreti o n of t he I n v esti gat or i n 
c o n versati o n wit h t he Me dical M o nit or a n d will be c o nsi dere d a d diti o nal sta n dar d of care 
t hera p y. 
Partici pa nts wit h S u b o pti mal Res p o nse will be i ncl u de d as Treat me nt Fail ure.  
8. 1. 9.  
Tre at m e nt F ail ure ( L N C o h ort O nl y)  
Treat me nt Fail ure is defi ne d as t he r ecei pt of a d diti o nal sta n dar d of care t h era p y at a n y ti me 
d uri n g t he st u d y f or pr ot oc ol defi ne d Re n al Flare, se vere E xtrare nal S L E Flare, or S u b o pti mal 
Res p o nse. 
I n crease i n c ortic oster oi ds f or E xtrar e nal S L E Fl are n ot meeti n g t he pr ot oc ol defi niti o n of se vere 
E xtrare n al S L E Flar e, Re nal Flar e n ot meeti n g pr ot oc ol defi niti o n f or Re nal Flare, l ac k of 
res p o nse n ot meeti n g t he pr ot oc ol defi niti o n of S u b o pti mal Res p o nse, ot her me dical c o n diti o ns, 
or s ur ger y li mite d t o ≤ 1 4 da ys d urati o n are n ot  i ncl u de d i n Treat me nt Fail ure. 
Partici pa nts w h o meet t h e criteri a f or Treat me nt Fail ure ma y c o nti n ue t o recei ve t he st u d y 
i nter ve nti o n a n d sta y i n t he st u d y. If a p artici pa nt has 2 Treat me nt Fail ures, st u d y i nter ve nti o n 
disc o nti n uati o n s h o ul d be c o nsi der e d ( Secti o n  7. 1 ). If a C NI is use d f or a d diti o nal sta n dar d of 
care t h era p y, st u d y i nter v e nti o n will nee d t o be disc o nti n ue d 3 da ys pri or t o C NI a d mi nistrati o n. 
8. 1. 1 0.  
C o m plete a n d P arti al Re n al Res p o nse ( L N C o h ort O nl y) 
C o m plete Re nal Res p o nse a n d P R R will be assesse d at Wee k  2 6 a n d Wee k  5 0. 
T o ac hie ve C R R (R o vi n, 2 0 1 9 ), partici pa nts i n t he L N c o h ort m ust meet all 3 of t he f oll o wi n g 
criteria:  
•  A decr ease i n mea n U P C R t o ≤ 0. 5 g/ g base d o n t w o 2 4- h o ur uri ne c ollecti o ns 
o btai ne d wit hi n 2 wee ks pri or t o t he st u d y visit ( Wee k 2 6 or Wee k 5 0) 
•  Es ti mate d gl o mer ular filtrati o n rate > 6 0 m L/ mi n/ 1. 7 3 m2 or n o e G F R 
re d ucti o n ≥ 2 0 % fr o m t h e baseli ne val u e base d o n t he mea n of 2 val u es. T h e first 
e G F R val u e m ust be o btai ne d wit hi n 2 wee ks pri or t o t he st u d y visit ( Wee k 2 6 or 
Wee k  5 0) a n d t he sec o n d e G F R val u e will be o btai ne d o n t he st u d y visit ( Wee k 2 6 or 
Wee k  5 0). 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 9 0  of 1 5 2  
Ale xi o n C o nfi de ntial  
•  N o Treat me nt Fail ure (as defi ne d i n Secti o n 8. 1. 9 ) 
T o ac hie ve P R R (R o vi n, 2 0 1 9 ), partici pa nts w h o di d n ot ac hie ve C R R i n t he L N c o h ort m ust 
meet all 3 of t he f oll o wi n g criteria:  
•  A  decr ease i n U P C R ≥ 5 0 % c o m pare d t o t he baseli ne val ue base d o n mea n of t w o 
2 4- h o ur uri ne c ollecti o ns o btai ne d wit hi n 2 wee ks pri or t o t he st u d y visit ( Wee k 2 6 or 
Wee k  5 0) 
•  E sti mate d gl o mer ular filtrati o n rate > 6 0 m L/ mi n/ 1. 7 3  m2 or n o e G F R 
re d ucti o n ≥ 2 0 % fr o m t h e baseli ne val u e base d o n t he mea n of 2 val u es. T h e first 
e G F R val u e m ust be o btai ne d wit hi n 2 wee ks pri or t o t he st u d y visit ( Wee k 2 6 or 
Wee k  5 0) a n d t he sec o n d e G F R val u e will be o btai ne d o n t he st u d y visit ( Wee k 2 6 or 
Wee k  5 0) 
•  N o Treat me nt Fail ure (as defi ne d i n Secti o n 8. 1. 9 ) 
O verall Re nal Res p o nse is defi ne d as t he c o m p osite of C R R a n d P R R. 
8. 1. 1 1.  
P arti al Re missi o n (I g A N C o h ort O nl y) 
Partial Re missi o n will be defi ne d as mea n pr otei n uria  < 1 g/ 2 4 h o urs bas e d o n 2 vali d 2 4- h o ur 
uri ne c ollecti o ns o btai ne d wit hi n 2 wee ks pri or t o t he st u d y visit ( Wee k 2 6 or Wee k  5 0).  
8. 2.  
S afet y Assess me nts  
Pla n ne d ti me p oi nts f or all safet y assess me nts are pr o vi de d i n t he S o A ( Secti o n  1. 3 ). 
8. 2. 1.  
P h ysic al E x a mi n ati o ns 
•  A c o m plete p h ysical e x a mi nati o n will i ncl u de, at a mi ni m u m, assess me nts of t he 
f oll o wi n g or ga ns/ b o d y s yste ms: s ki n, hea d, ears, e yes, n ose, t hr oat, nec k, l y m p h 
n o des, c hest, heart, a b d o me n, e xtre mities, m usc ul os keletal, a n d ne ur ol o gical state 
( wit h e m p hasis o n prese n ce/ de gree of e de ma). Hei g ht ( Scree ni n g o nl y) a n d wei g ht 
will als o be meas ure d a n d rec or d e d.  
•  A n a b bre viat e d p h ysical e xa mi nati o n will i ncl u de, at a mi ni m u m, a b o d y s yste m 
rele va nt e x a mi nati o n bas e d u p o n t he I n vesti gat or’s cli nical j u d g me nt a n d 
partici pa nt’s healt h stat us.  
•  A s y m pt o m- base d ne ur ol o gic e xa mi nati o n s h o ul d be perf or me d if t he p artici pa nt has 
a n y c o m plai nts or cli nical fi n di n gs attri b uta ble t o t he ce ntral ner v o us s yste m, a n d if 
p ositi ve f or fi n di n gs, a f ull ne ur ol o gic e xa mi nati o n s h o ul d be perf or m e d as nee de d 
( deter mi ne d b y t he I n vesti gat or) at t hat assess me nt ti me p oi nt a n d at f ut ure ti me 
p oi nts. If a f ull ne ur ol o gi c e xa mi nati o n is re q uire d, t he I n v esti gat or s h o ul d perf or m 
t he f oll o wi n g e val uati o ns: 
− Me ntal stat us  
− Cra nial ner ve e xa mi nati o n  
− M ot or e xa mi nati o n 
− Gait e xa mi nati o n  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 9 1  of 1 5 2  
Ale xi o n C o nfi de ntial  
− C o or di nati o n e xa mi nati o n 
− Se ns or y e xa mi nati o n 
8. 2. 2.  
Vit al Si g ns  
•  B o d y te m perat ure (° C or ° F), p ulse rate, res pirat or y rate, s yst olic a n d diast olic bl o o d 
press ure ( m m H g), a n d p ulse o xi metr y will be assesse d. 
•  Bl o o d press ure a n d h eart rate meas ure me nts will b e assesse d wit h t he p artici pa nt i n a 
seate d or s u pi ne p ositi o n usi n g a c o m pletel y a ut o mate d de vice. M a n ual tec h ni q ues 
will be use d o nl y if a n a ut o mate d de vice is n ot a vaila ble. 
•  Bl o o d press ure a n d h eart rate meas ure me nts s h o ul d be prece de d b y at least 5  mi n utes 
of rest f or t he partici pa nt i n a q uiet setti n g wit h o ut distracti o ns (e g, tele visi o n, cell 
p h o nes). I deall y, t he sa m e ar m f or eac h partici pa nt s h o ul d be use d f or meas ure me nts. 
•  Vital si g ns will be ta ke n pre d ose at i n -cli nic d osi n g visits a n d bef ore bl o o d c ollecti o n 
f or la b orat or y visits a n d will c o nsist of a si n gle p ulse c hec k a n d a si n gle bl o o d 
press ure meas ure m e nt.  
8. 2. 3.  
Electr oc a r di o gr a ms  
•  Si n gle 1 2-lea d electr ocar di o gra ms ( E C Gs) will be c o n d ucte d l ocall y as o utli ne d i n t he 
S o A ( Secti o n  1. 3 ) t o o btai n heart rat e, P R i nter val (ti me fr o m t he o nset of t he P wa ve 
t o t he start of t he Q R S c o m ple x), c o m bi nati o n of t he Q wa v e, R  wa ve, a n d S  wa ve 
( Q R S) i nter val, Q T, a n d t he Q Tc i nter v al(s). Q T i nter val will be c orrect e d f or heart 
rate usi n g Fri dericia’s f or m ula. 
•  Partici pa nts m ust be s u pi ne f or a p pr o xi matel y 5 t o 1 0 mi n utes bef ore E C G c ollecti o n 
a n d re mai n s u pi ne b ut a wa ke d uri n g E C G c ollecti o n. 
•  T he I n vesti gat or will be r es p o nsi ble f or re vie wi n g t he E C G t o assess w het h er t he 
E C G is wit hi n n or mal li mits a n d deter mi ne t he cli nical si g nifica nce of t he res ults.  
•  Res ults will be rec or de d o n t he e C R F. Cli nicall y si g nifica nt fi n di n gs s h o ul d be 
rec or d e d o n t he A E f or m. 
8. 2. 4.  
Cli nic al S afet y L a b or at or y Assess me nts 
•  T he I n vesti gat or m ust re vie w t he la b orat or y re p ort, d oc u me nt t his re vie w, a n d rec or d 
a n y cli nicall y rele v a nt c h a n ges occ urri n g d uri n g t he st u d y i n t he A E secti o n of t he 
e C R F. T he la b or at or y r e p orts m ust be file d wit h t he s o urce d o c u me nts. Cli nicall y 
si g nifica nt a b n or mal la b orat or y fi n di n gs are t h ose w hic h are n ot ass ociate d wit h t he 
u n derl yi n g disease, u nless j u d ge d b y t he I n vesti gat or t o be m ore se vere t ha n e x pecte d 
f or t he partici p a nt’s c o n diti o n. 
•  All la b orat or y tests wit h val ues c o nsi dere d cli nicall y si g nifica ntl y a b n or mal d uri n g 
partici pati o n i n t he st u d y s h o ul d be re peate d u ntil t he val ues ret ur n t o n or mal or 
baseli ne or are n o l o n ger c o nsi dere d cli nicall y si g nifica nt b y t he I n vesti gat or or 
Me dical M o nit or. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 9 2  of 1 5 2  
Ale xi o n C o nfi de ntial  
− If s uc h val ues d o n ot ret ur n t o n or mal/ baseli ne wit hi n a peri o d of ti me j u d g e d 
reas o na bl e b y t he I n vesti gat or, t he eti ol o g y s h o ul d be i de ntifie d, a n d Ale xi o n 
n otifie d. 
− All pr ot oc ol-re q uir e d la b orat or y assess me nts, as defi ne d i n Secti o n 1 0. 2 , m ust be 
c ollecte d i n acc or d a nce wit h t he La b orat or y M a n ual a n d t he S o A ( Secti o n  1. 3 ). 
− La b orat or y assess me nts perf or me d at t he i nstit uti o n’s l ocal la b orat or y t hat re q uire 
a c ha n g e i n partici pa nt m a na ge me nt or are c o nsi dere d cli nicall y si g nifica nt b y t he 
I n v esti gat or m ust be rec or de d i n t he A E or S A E e C R F. W he n p ossi ble, para meter 
val ue o utsi de of t he r efere nce ra n ge s h o ul d be e nt ere d i n a free- te xt fiel d. 
•  Re peat la b or at or y tests ma y be o btai ne d f or safet y reas o ns or f or tec h ni cal iss ues wit h 
t he sa m ples 
8. 2. 4. 1.  
Vir us Ser ol o g y  
Testi n g f or HI V- 1 a n d HI V- 2 is re q uir e d f or all partici pa nts pri or t o e nr oll me nt. Partici pa nts w h o 
are HI V a nti b o d y p ositi ve will n ot be e nr olle d. 
Si milarl y, partici pa nts w h o are p ositi ve at t he Scree ni n g Visit f or H Bs A g, a nti -H Bc wit h 
ne gati ve a nti - H Bs, or H C V a nti b o d y p ositi ve (e xce pt f or partici p a nts wit h d oc u me nte d 
s uccessf ul treat me nt a n d d oc u me nte d s ustai ne d viral res p o nse) will n ot be e nr olle d. 
8. 2. 4. 2.  
C he mistr y, He m at ol o g y a n d C o a g ul ati o n 
Bl o o d sa m ples will be c ollecte d pre d os e a n d a n al y ze d f or t h e para meters liste d i n Secti o n  1 0. 2 . 
8. 2. 4. 3.  
R o uti ne Uri n al ysis a n d Uri ne Se di me nt  
Uri ne sa m ples will be c ollecte d at ti mes s pecifi e d i n t he S o A a n d a nal yze d f or t he para meters 
liste d i n Secti o n 1 0. 2 . A micr osc o pic e x a mi nati o n of uri ne sa m ples will be perf or me d if t he 
res ults of t he macr os c o pi c a nal ysis ar e a b n or m al. Sa m ples will be o btai ne d fr o m a m or ni n g v oi d 
pri or t o d osi n g. 
8. 2. 4. 4.  
F ollicle Sti m ul ati n g H or m o ne  
F ollicle sti m ulati n g h or m o ne ( F S H) m a y be o btai n e d t o c o nfir m p ost me n o p a usal stat us i n fe male 
partici pa nts w h o ar e c o nsi dere d p ost me n o pa usal. A hi g h F S H le vel i n t he p ost me n o pa usal ra n ge 
ma y be use d t o c o nfir m p ost me n o pa usal state i n w o me n n ot usi n g h or m o nal c o ntrace pti o n or 
h or m o ne re place me nt t hera p y ( H R T). 
T his test is n ot nee de d f or me n or f or w o me n of c hil d beari n g p ote ntial ( W O C B P). 
8. 2. 5.  
Pri or a n d C o nc o mit a nt Me dic ati o ns a n d Pr oce d ures  
Pri or a n d c o nc o mita nt m e dicati o ns, i ncl u di n g all o we d c o nc o mita nt t hera p y, will be re vie we d as 
s pecifie d i n t he S o A ( Secti o n 1. 3 ). 
Pri or me dicati o ns a n d/ or vacci nes (i ncl u di n g vita mi ns, her bal pre parati o ns, a n d t h ose disc usse d 
i n t he eli gi bilit y criteria [ Secti o n 5 ]) a n d pr o ce d ures (e g, s ur g er y, bi o ps y, p h ysical t hera p y) t h at 
t he partici pa nt recei ves or u n der g oes ≤ 3 0 d a ys pri or t o Scree ni n g or d uri n g t he Scree ni n g 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 9 3  of 1 5 2  
Ale xi o n C o nfi de ntial  
Peri o d, as well as a n y me ni n g oc occal v acci ne a d mi nistere d wit hi n t he last 3  years, will be 
rec or d e d i n t he partici p a nt’s e C R F. 
C o nc o mita nt me dicati o ns (i ncl u di n g a n y me dicati o n, vita mi n, her bal pre p arati o n or s u p ple me nt) 
a n d pr oce d ures ( d efi ne d i n Secti o n  6. 5 ) are t h ose recei ve d o n or aft er t he first st u d y i nter ve nti o n 
date ( Da y 1), i ncl u di n g t h ose starte d bef ore Da y 1 a n d c o nti n ue d aft er D a y 1. 
At eac h st u d y visit, partici pa nts s h o ul d be q uesti o ne d a b o ut a n y ne w me dicati o n or 
n o n p har mac ol o gic t hera pies or c ha n g es t o c o nc o mita nt me dicati o ns a n d n o n p har mac ol o gic 
t hera pies si nce t h e last visit. C o nc o mita nt me dicati o ns a n d n o n p har mac ol o gic t hera pies s h o ul d 
be rec or de d i n t he s o ur ce d oc u me nts a n d t he partici pa nt’s e C R F, i ncl u di n g: 
•  Reas o n f or use 
•  Dates of a d mi nistrati o n i ncl u di n g start a n d e n d dates 
•  D osa ge i nf or m ati o n i ncl u di n g d ose a n d fre q ue nc y 
A n y c o nc o mita nt me dicati o n dee me d necessar y f or t he partici pa nt’s care d uri n g t he st u d y, or f or 
t he treat me nt of a n y A E, al o n g wit h a n y ot her me dicati o ns, ot her t ha n t h ose liste d as disall o we d 
me dicati o ns i n Secti o n  6. 5. 2 , ma y be gi ve n at t he discreti o n of t he I n v esti gat or. H o we v er, it is 
t he res p o nsi bilit y of t he I n vesti gat or t o e ns ure t hat details re gar di n g all me dicati o ns are rec or de d 
i n f ull, i n t he partici pa nt’s s o urce d oc u m e nts a n d e C R F. 
Vacci n ati o n a n d a nti bi otics a d mi nistere d f or pr o p h yla xis of me ni n g oc occal i nfecti o n (if 
a p plica ble) d uri n g t he st u d y will als o be rec or d e d. 
T he Me dical M o nit or s h o ul d be c o ntacte d if t h ere are a n y q u esti o ns re gar di n g c o nc o mita nt 
me dicati o ns or pr oce d ures ( Secti o n  6. 5 ). 
I nf or mati o n o n pri or use of R A S i n hi bit ors or s yste mic i m m u n os u p pressi o n wit hi n 2 years of t he 
Scree ni n g Peri o d will be c ollecte d. C o nc o mita nt use of R A S i n hi bit ors ( A C Ei a n d A R B) will be 
rec or d e d as w ell. Use of t hese me dicati o ns will be rec or d e d i n t he s o urce d o c u me nts a n d t he 
partici pa nt’s e C R F, i ncl u di n g. 
•  Reas o n f or use 
•  Dates of a d mi nistrati o n i ncl u di n g start a n d e n d dates 
•  D osa ge i nf or m ati o n i ncl u di n g d ose a n d fre q ue nc y 
8. 2. 6.  
Pre g n a nc y  
A ser u m or uri ne pre g n a nc y test will be a d mi nistere d t o all fe male p artici p a nts of c hil d beari n g 
p ote ntial. A ne gati ve ser u m pre g na nc y test is re q uire d at t he Scree ni n g Visit a n d a ne gati ve uri n e 
pre g na nc y t est at Da y  1 i n or der t o be c o nsi dere d eli gi ble t o c o nti n ue i n t he st u d y. 
Pre g na nc y dat a fr o m f e m ale partici pa nts a n d fe male s p o uses/ part ners of male partici pa nts will be 
c ollecte d fr o m t he first d ose of st u d y i nter ve nti o n a n d at t he ti me p oi nts s pecifie d i n t he S o A. 
A n y fe male p artici pa nt w h o bec o mes pre g na nt w hile partici pati n g i n t he st u d y will be 
disc o nti n ue d fr o m st u d y i nter ve nti o n ( Secti o n  7 ). If a pre g na nc y is re p orte d, t he I n v esti gat or, or 
desi g nee, m ust i m me diatel y i nf or m Ale xi o n wit hi n 2 4  h o urs of a w are n ess of t he pre g n a nc y a n d 
f oll o w t he pr oce d ures o utli ne d i n Secti o n 1 0. 5. 3 . 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 9 4  of 1 5 2  
Ale xi o n C o nfi de ntial  
8. 2. 7.  
P artici p a nt S afet y C a r d  
Bef ore t he first d ose of t he st u d y i nter ve nti o n, a Partici pa nt Safet y Car d will be pr o vi de d t o 
partici pa nts t o carr y wit h t he m at all ti mes. T he car d is pr o vi de d t o i ncrease partici pa nt 
a war e ness of t he ris k of me ni n g oc occal i nfecti o n a n d pr o m ote q uic k rec o g niti o n a n d discl os ure 
of a n y p ote ntial si g ns or s y m pt o ms of me ni n g oc occal i nfecti o n e x peri e nce d d uri n g t he c o urse of 
t he st u d y a n d t o i nf or m partici pa nts o n w hat acti o ns m ust be ta ke n if t he y are e x perie nci n g si g ns 
or s y m pt o ms of i nfecti o n. 
At eac h visit t hr o u g h o ut t he st u d y, t he st u d y staff will e ns ure t hat t he partici pa nt has t he 
Partici pa nt Safet y Car d. Partici pa nts are re q uire d t o carr y t he s afet y car d u ntil 3 0 da ys after t he 
fi nal d ose of st u d y i nter v e nti o n. 
8. 3.  
A d verse E ve nts a n d Seri o us A d verse E ve nts  
T he defi niti o ns of A Es a n d S A Es ca n be f o u n d i n Secti o n  1 0. 3 . 
All A Es will be re p orte d t o t he I n v esti gat or or q ualifie d desi g nee b y t he p artici pa nt ( or, w he n 
a p pr o priate, b y a care gi v er, or s urr o gate). 
T he I n vesti gat or a n d a n y q ualifie d desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d 
rec or di n g e ve nts t hat meet t he defi niti o n of a n A E or S A E a n d re m ai n res p o nsi ble f or f oll o wi n g 
u p A Es t hat are s eri o us, c o nsi dere d rel ate d t o t he st u d y i nter ve nti o n or st u d y pr oce d ures, or t hat 
ca use d t he p artici pa nt t o disc o nti n ue t he st u d y i nter ve nti o n (see Secti o n  7 ). 
Pr oce d ures f or r ec or di n g, e val uati n g, f oll o w- u p, a n d re p orti n g of A Es a n d S A Es are o utli ne d i n 
Secti o n  1 0. 3 . 
8. 3. 1.  
Ti m e Peri o d a n d Fre q ue nc y f or C ollecti n g A E a n d S A E I nf or m ati o n  
All 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 C F u ntil t he Safet y F oll o w -u p Visit.  
All S A Es will be rec or de d a n d re p ort e d t o Ale xi o n i m me diatel y a n d u n der n o circ u msta nce 
s h o ul d t his e xcee d 2 4 h o urs, as i n dicate d i n Secti o n 1 0. 3 . T he I n vesti gat or will s u b mit a n y 
u p date d S A E data t o Ale xi o n wit hi n 2 4 h o urs of t he date t he i n vesti gati o nal site beca me a ware of 
t he e ve nt. 
I n v esti gat ors ar e n ot o bli gate d t o acti vel y see k A E or S A E data after c o n cl usi o n of t he st u d y 
partici pati o n. H o we v er, if t he I n vesti gat or lear ns of a n y S A E, i ncl u di n g a d eat h, at a n y ti me after 
a partici pa nt has b ee n dis c har ge d fr o m t he st u d y, a n d he/s he c o nsi ders t he e ve nt t o be reas o n a bl y 
relate d t o t he st u d y i nter v e nti o n or st u d y partici pati o n, t he I n v esti gat or m ust pr o m ptl y n otif y 
Ale xi o n. 
8. 3. 2.  
Met h o d of Detecti n g A Es a n d S A Es  
T he met h o d of rec or di n g, e val uati n g, a n d ass essi n g ca usalit y of A E a n d S A E a n d t he pr oce d ures 
f or c o m pleti n g a n d tra ns mitti n g S A E re p orts are pr o vi de d i n Secti o n 1 0. 3 . 
Care will be ta ke n n ot t o i ntr o d uce bias w he n d etecti n g A Es a n d/ or S A Es. O pe n-e n d e d a n d 
n o n-lea di n g ver b al q uesti o ni n g of t he partici pa nt is t he preferre d m et h o d t o i n q uire a b o ut A E 
occ urr e nces.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 9 5  of 1 5 2  
Ale xi o n C o nfi de ntial  
8. 3. 3.  
F oll o w- u p of A Es a n d S A Es  
After t he i nitial A E/ S A E re p ort, t he I n v esti gat or is re q uire d t o pr o acti vel y f oll o w - u p o n eac h 
partici pa nt at s u bse q ue nt visits/c o ntacts. All S A Es  will be f oll o we d u p u ntil res ol uti o n, 
sta bilizati o n, t he e ve nt is ot her wise e x plai n e d, or t he partici pa nt is l ost t o f oll o w- u p (as defi n e d 
i n Secti o n 7. 3 ). F urt her i nf or mati o n o n f oll o w- u p pr oce d ures is pr o vi de d i n Secti o n 1 0. 3 . 
8. 3. 4.  
Re g ul at or y Re p orti n g Re q uire me nts f or S A Es  
•  Pr o m pt n otificati o n of a n S A E b y t he I n v esti gat or t o Ale xi o n is esse ntial s o t hat le gal 
o bli gati o ns a n d et hical res p o nsi bilities t o war ds t he safet y of partici pa nts a n d t he 
safet y of a st u d y i nter v e nti o n u n der cli nical i n vesti gati o n are met. 
•  Ale xi o n has a le gal res p o nsi bilit y t o n otif y b ot h t he l ocal re g ul at or y a ut h orit y a n d 
ot her re g ulat or y a ge n cies a b o ut t he safet y of a st u d y i nter ve nti o n u n der cli nical 
i n vesti gati o n. Ale xi o n will c o m pl y wit h c o u ntr y-s pecific re g ulat or y re q uire me nts 
relati n g t o safet y r e p orti n g t o t he re g ulat or y a ut h orit y, I R Bs/I E Cs, a n d I n vesti gat ors. 
•  Ale xi o n is re q uire d t o s u b mit i n di vi d ual S U S A R re p orts ( defi n e d i n Secti o n 1 0. 3. 2 ) i n 
t he f or mat of Me d Watc h 3 5 0 0 or C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical 
Scie nces ( CI O M S) I F or m t o healt h a ut h orities a n d I n v esti gat ors as re q uire d. F or ms 
s u b mitte d t o I n vesti gat ors will be bli n de d t o treat me nt assi g n me nt. I n li mite d 
circ u msta nces, t he bli n d ma y be br o ke n i n t he cas e of ur ge nt safet y iss ues t hat c o ul d 
c o m pr o mise partici pa nt s afet y.  
•  A n I n vesti gat or w h o r ecei ves a n I n vesti gat or safet y re p ort descri bi n g a n S A E or ot her 
s pecific safet y i nf or mati o n (e g, s u m mar y or listi n g of S A Es) fr o m Ale xi o n will 
re vie w a n d t h e n file it al o n g wit h t he I B a n d will n otif y t he I R B/I E C, if a p pr o priate 
acc ordi n g t o l ocal re q uir e me nts. 
•  U n der t he E U C T R 5 3 6/ 2 0 1 4, e ve nts ot her t ha n S A Es (e g, u ne x p ecte d e ve nts) t hat 
ma y i m pact t he be nefit -ris k bala nce s h o ul d be re p orte d. See defi niti o ns i n 
Secti o n  1 0. 3. 5 . 
•  I n t he E ur o pea n U ni o n, t he S p o ns or will c o m pl y wit h safet y re p orti n g re q uire me nts 
a n d pr oce d ures as d escri be d i n t he E ur o pea n Cli nical Trials Re g ulati o n ( E U) N o 
5 3 6/ 2 0 1 4. All S U S A Rs t o i n vesti gati o nal me dici nal pr o d uct will be re p orte d t o t he 
E u dra Vi gila nce data bas e wit hi n t he re q uire d re g ulat or y ti meli nes. 
8. 3. 5.  
Me dic ati o n Err or, D r u g A b use, a n d Dr u g Mis use  
8. 3. 5. 1.  
Ti m eli nes  
If a n e v e nt of me dicati o n err or, dr u g a b use, or dr u g mis use occ urs d uri n g t he st u d y, t he n t he 
I n v esti gat or or ot her site pers o n nel will re p ort t o Ale xi o n or desi g nee i m m e diatel y b ut n o later 
t ha n 2 4 h o urs of w he n t h e y bec o me a ware of it. 
T he f ull defi niti o ns a n d e xa m ples of me dicati o n err or, dr u g a b us e, a n d dr u g mis use ca n be f o u n d 
i n Secti o n 1 0. 4 . 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 9 6  of 1 5 2  
Ale xi o n C o nfi de ntial  
8. 3. 5. 2.  
Me dic ati o n Err or  
F or t he p ur p os es of t his cli nical st u d y a me dicati o n err or is a n u ni nte n d e d fail ure or mista ke i n 
t he treat me nt pr ocess f or a n I M P or A x M P t hat eit her ca us es har m t o t he p artici pa nt or has t he 
p ote ntial t o ca use har m t o t he partici pa nt.  
8. 3. 5. 3.  
Dr u g A b use  
Dr u g a b use is t he p ersiste nt or s p ora dic i nte nti o nal, n o n- t hera pe utic e xcessi ve use of I M P or 
Ale xi o n A x M P f or a percei ve d re w ar d or d esire d n o n- t hera p e utic effect. 
8. 3. 5. 4.  
Dr u g Mis use  
Dr u g mis use is t he i nte nti o nal a n d i na p pr o priat e use of I M P or Ale xi o n A x M P f or me dici nal 
p ur p oses o utsi de of t he a ut h orize d pr o d uct i nf or mati o n, or f or u na ut h ori ze d I M Ps or Ale xi o n 
A x M P, o utsi de t he i nte n de d use as s pecifie d i n t h e pr ot oc ol, i ncl u di n g del i berate a d mi nistrati o n 
of t he pr o d uct b y t he wr o n g r o ute. 
8. 4.  
P h ar m ac o ki netics  
•  Bl o o d sa m ples will be c ollecte d f or meas ure me nt of c o nce ntrati o ns of A L X N 2 0 5 0 
bef ore a n d aft er a d mi nistrati o n of st u d y i nter ve nti o n at t he ti me p oi nts s pecifie d i n t he 
S o A ( Secti o n  1. 3 ). 
•  I nstr u cti o ns f or t he c ollecti o n a n d ha n dli n g of bi ol o gical sa m ples, i ncl u di n g bl o o d 
v ol u me re q uire me nts, will be pr o vi de d i n t he La b orat or y Ma n u al. T he act ual date a n d 
ti me ( 2 4- h o ur cl oc k ti me) of eac h sa m ple will be rec or de d. 
•  Sa m ples will be use d t o e val uate t he P K of A L X N 2 0 5 0. Sa m ples c ollecte d f or 
a nal yses of A L X N 2 0 5 0 c o nce ntrati o n ma y als o b e use d t o e val uate s afet y or efficac y 
as pects rel ate d t o c o ncer ns arisi n g d uri n g or after t he st u d y. 
•  Sa m ples ma y be use d f or researc h t o de v el o p met h o ds, assa ys f or pr o g n osis, 
dia g n ostics, a n d/ or treat me nt m o nit ori n g relate d t o L N a n d/ or I g A N, t he disease 
pr ocesses, p at h wa ys ass o ciate d wit h t he diseas e state, a n d/ or mec ha nis m of acti o n of 
A L X N 2 0 5 0. 
•  St u d y i nter ve nti o n c o nce ntrati o n i nf or mati o n t hat ma y u n bli n d t he st u d y will n ot be 
re p orte d t o i n vesti gati o nal sites or bli n de d pers o n nel u ntil t he st u d y has bee n 
u n bli n de d. 
8. 5.  
P h ar m ac o d y n a mics  
•  Bl o o d sa m ples f or deter mi nati o n of plas ma B b c o nce ntrati o n a n d s er u m A P acti vit y 
will be c ollecte d bef ore a n d after a d mi nistrati o n of st u d y i nter ve nti o n at t he ti me 
p oi nts s pecifie d i n t he S o A ( Secti o n  1. 3 ). 
•  I nstr u cti o ns f or t he c ollecti o n a n d ha n dli n g of bi ol o gical sa m ples i ncl u di n g bl o o d 
v ol u me re q uire me nts, are pr o vi de d i n t he La b orat or y Ma n ual. T he act ual date a n d 
ti me ( 2 4- h o ur cl oc k ti me) of eac h sa m ple will be rec or de d. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 9 7  of 1 5 2  
Ale xi o n C o nfi de ntial  
•  Sa m ples will be use d t o e val uate t he P D of A L X N 2 0 5 0. Sa m ples c ollecte d f or 
a nal yses of A L X N 2 0 5 0 c o nce ntrati o n ma y als o b e use d t o e val uate s afet y or efficac y 
as pects rel ate d t o c o ncer ns arisi n g d uri n g or after t he st u d y. 
•  Bi o mar ker i nf or mati o n t hat ma y u n bli n d t he st u d y will n ot be re p orte d t o 
i n vesti gati o nal sites or bli n de d pers o n nel u ntil t he st u d y has bee n u n bli n de d. 
8. 6.  
Ge netics  
Ge netics are n ot e v al uate d i n t his st u d y. 
8. 7.  
Bi o m ar kers  
C ollecti o n of bl o o d a n d uri ne sa m ples f or e x pl orat or y bi o mar ker researc h is als o part of t his 
st u d y ( details pr o vi de d i n Secti o n 1 0. 6 ). S pecific bl o o d a n d uri ne bi o mar kers t o be meas ure d are 
prese nte d i n  Ta bl e  1 3. 
8. 7. 1.  
Bl o o d Bi o m ar kers  
Bl o o d (ser u m a n d plas ma) sa m ples f or bi o mar ker researc h will be c ollecte d fr o m all partici pa nts 
at t he ti me p oi nts s pecifie d i n t he S o A ( Secti o n  1. 3 ). 
Bi o mar kers t o be meas ur e d ma y i ncl u de, b ut are n ot li mite d t o, assess me nts of t he f oll o wi n g: 
•  C o m ple me nt pat h wa y d ysre g ulati o n (e g, s ol u ble C 5 b 9 [s C 5 b- 9], Fact or Ba)  
See Secti o n  1 0. 2  for a list of la b orat or y tests.  
8. 7. 2.  
Uri ne Bi o m ar kers  
Uri ne sa m ples f or e x pl or at or y resear c h will be c ollecte d fr o m all partici pa nts d uri n g Scree ni n g 
a n d at t he ti me p oi nts s pecifie d i n t he S o A ( Secti o n  1. 3 ). 
Bi o mar kers t o be meas ur e d ma y i ncl u de, b ut are n ot li mite d t o, assess me nts of t he f oll o wi n g: 
•  C o m ple me nt pat h wa y d ysre g ulati o n (e g, s C 5 b- 9, Fact or  B a)  
•  Re nal i nj ur y bi o mar kers (e g, N- G A L, KI M -1, etc)  
•  Uri nar y creati ni ne 
See Secti o n  1 0. 2  for a list of la b orat or y tests.  
8. 7. 3.  
Ki d ne y Bi o ps y Bi o m ar kers  
Ki d ne y tiss ue bi o psies will be o btai ne d i n t he f or m of u nstai ne d tiss ue sli des a n d stai ne d f or t he 
prese nce of bi o mar k ers w hic h will pr o vi de cli nical e vi de nce of t he disease pat h o p h ysi ol o g y a n d 
res p o nse t o treat me nt (Ta ble  1 3). So me u nstai ne d sli des ma y als o be use d f or perf or mi n g 
pr ote o mic a nal ysis. 
8. 7. 4.  
A d diti o n al Bi o m ar ker Rese arc h  
Resi d ual bl o o d, uri ne, a n d bi o ps y sa m ples fr o m e x pl orat or y bi o mar kers, P K, a n d P D as well as 
resi d ual sa m ples fr o m 2 4- h o ur uri ne c ollecti o ns ma y be st ore d f or a d diti o nal met h o d 
de vel o p me nt of assa ys (e g, pr o g n ostic a n d/ or dia g n ostic tests relate d t o t he st u d y i nter ve nti o n 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 9 8  of 1 5 2  
Ale xi o n C o nfi de ntial  
tar get, disease pr ocess, pat h wa ys ass oci ate d wit h disease state, or ot h er c o m ple me nt-relate d 
diseases, a n d/ or mec ha nis m of acti o n of A L X N 2 0 5 0). 
Sa m ples ma y be retai n e d t o e na ble f urt h er a n al ysis o n A L X N 2 0 5 0 b ut f or n o l o n ger t ha n 
2 5 years after ter mi nati o n of t he st u d y or ot her peri o d as per l ocal re q uire me nts. 
8. 8.  
I m m u n o ge nicit y Assess me nts 
I m m u n o ge nicit y is n ot a p plica ble i n t his st u d y. 
8. 9.  
He alt h Ec o n o mics D at a a n d/ or Me dic al Res o urce Utiliz ati o n  
Healt h ec o n o mics d ata a n d/ or me dical res o urce utilizati o n para meters are n ot e val uate d i n t his 
st u d y. 
8. 1 0.  
P artici p a nt -re p orte d O utc o mes  
T he f oll o wi n g partici pa nt-re p orte d o ut c o me ( P R O) i nstr u me nts will be use d i n t his st u d y t o 
ca pt ure h ealt h -r elate d q u alit y of life ( Q o L):  
•  E ur o pea n Q o L Healt h 5- ite m q uesti o n naire di me nsi o ns 5 le vel ( E Q- 5 D- 5 L f or b ot h 
c o h orts) 
•  S h ort F or m ( S F) - 3 6 Healt h S ur ve y (f or b ot h c o h orts) 
•  F u ncti o nal Assess me nt of C hr o nic Ill ness T hera p y ( F A CI T)- Fati g ue scale (f or L N c o h ort 
o nl y) 
All i nstr u me nts will be self -re p orte d a n d a d mi nistere d at visits s pecifie d i n t he S o As. 
I nf or mati o n a b o ut t hese i nstr u me nts a n d q uesti o n naires, wit h t he c orrect versi o n a n d t he 
vali date d la n g ua g e versi o ns, if nee de d, will be pr o vi de d t o t he sites pri or t o t he start of t he st u d y. 
See Secti o n  1 0. 1 0 . 
8. 1 1.  
Ot her E x pl or at or y Assess me nts  
8. 1 1. 1.  
A ut o a nti b o dies ( L N C o h ort O nl y) 
Bl o o d sa m ples will be c ollecte d f or a ut oa nti b o dies (e g, a nti- ds D N A a n d a nti- C 1 q a ut oa nti b o dies, 
a m o n g ot hers) d uri n g Scr ee ni n g a n d acc or di n g t o t he S o A ( Secti o n  1. 3 ). 
See Secti o n  1 0. 2  for a list of la b orat or y tests.  
8. 1 1. 2.  
S L E D AI – 2 K ( L N C o h ort O nl y) 
T he S L E D AI – 2 K t o ol assesses disease acti vit y acr oss 2 4  disease des cri pt ors. T he t otal sc ore 
ra n ges fr o m 0 t o 1 0 5, wit h hi g her sc ores re prese nti n g m ore si g nifica nt de grees of diseas e acti vit y 
a n d c o vers a recall peri o d of ≤ 3 0 da ys. T he S L E D AI – 2 K ass ess me nt will be use d f or t h e 
deter mi nati o n of E xtrare nal S L E Flare ( Secti o n  8. 1. 7 ). F or t he p ur p ose of assess me nt f or 
prese nce of E xtr are n al S L E Flar e, t he f oll o wi n g 6 descri pt ors will n ot be acc o u nte d f or: 
pr otei n uria, he mat uri a, uri nar y casts, h y p oc o m ple me nte mia, p y uria, a n d i n creas e i n t he 
a nti- ds D N A a nti b o d y le v el. As a res ult, t he t otal n u m ber of diseas e acti vit y descri pt ors assess e d 
is 1 8 a n d t he t otal sc ore r a n ges fr o m 0 t o 8 5. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 9 9  of 1 5 2  
Ale xi o n C o nfi de ntial  
8. 1 2.  
Ge ner al Assess me nts a n d Pr oce d ures  
8. 1 2. 1.  
I nf or m e d C o nse nt 
Partici pa nts m ust be c o nse nte d per t he i nf or me d c o nse nt pr ocess o utli ne d i n Secti o n 1 0. 1. 3 . 
8. 1 2. 2.  
I ncl usi o n/ E xcl usi o n Criteri a 
All i ncl usi o n ( Secti o n  5. 1 ) a n d e xcl usi o n ( Secti o n 5. 2 ) criteria m ust be re vi e we d b y t he 
I n v esti gat or or q ualifie d desi g nee t o e ns ure t he partici pa nt q ualifies f or st u d y partici pati o n. 
8. 1 2. 3.  
De m o gr a p hics  
A re vie w of de m o gr a p hic para m eters, i ncl u di n g a ge, ge n der, race, a n d et h nicit y will be 
perf or me d at Scree ni n g, if all o we d per c o u ntr y-s p ecific re g ulati o ns, a n d d o c u me nte d i n t he 
e C R F. 
8. 1 2. 4.  
Me dic al Hist or y a n d L N a n d I g A N Hist or y 
T he partici pa nt’s rele v a nt me dical hist or y, i ncl u di n g pri or a n d c o n c o mita nt c o n diti o ns/ dis or ders 
(i ncl u di n g L N a n d I g A N dia g n osis), treat me nt hist or y, disease stat us ( n aï ve vers us rela ps e) if 
a vaila ble ( L N C o h ort o nl y), fa mil y hist or y of rele va nt diseases, s u bsta nce usa ge, a n d hist or y of 
me dical c o n diti o ns a n d s ur geries will be e v al uate d at Scree ni n g b y t he I n v esti gat or, or q ualifie d 
desi g nee, a n d d o c u me nte d i n t he s o urce d oc u m e nts a n d e C R F. A n y c h a n ges t o me dical hist or y 
occ urri n g d uri n g t he Scree ni n g Peri o d a n d pri or t o first d ose of st u d y i nter v e nti o n o n Da y 1 will 
be d oc u me nte d pri or t o st u d y i nter ve nti o n a d mi nistrati o n. 
8. 1 2. 5.  
Ki d ne y Bi o ps y  
Ki d ne y bi o psies ma y be perf or me d a n y ti me d uri n g t he st u d y at t he discreti o n of t he I n v esti gat or 
f or Re nal Flare or ot her i n dicati o ns. 
8. 1 2. 5. 1.  Scree ni n g Ki d ne y Bi o ps y  
F or partici pa nts i n t he L N c o h ort, t he dia g n osis of L N m ust ha ve bee n c o nfir me d b y bi o ps y 
o btai ne d ≤ 6 m o nt hs pri or t o Scree ni n g or d uri n g t he Scree ni n g Peri o d. 
T he dia g n osis of pri mar y I g A N m ust ha ve bee n esta blis he d base d o n ki d ne y bi o ps y o btai ne d a n y 
ti me pri or t o or d uri n g t he Scree ni n g Peri o d. 
Eli gi bilit y will be deter mi ne d usi n g t he l ocal pat h ol o g y re p ort acc or di n g t o sta n dar dize d gl o b all y 
rec o g nize d g ui deli nes. T he l ocal pat h ol o g y re p ort m ust be e ntere d i n t he e C R F d uri n g Scree ni n g 
acc or di n g t o t he C R F c o m pleti o n g ui deli nes. I n p artic ular, t he d e gree of I g G, I g A, 
i m m u n o gl o b uli n M (I g M), C 3, a n d C 1 q ( b ot h c o h orts); t he acti vit y sc ore/cl ass ( L N c o h ort o nl y); 
a n d t he mesa n gial, e n d o ca pillar y h y percell ularit y, se g me ntal scler osis, i nterstitial fi br osis/t u b ular 
atr o p h y-pres e nce of cres ce nts ( M E S T -C)  sc ore (I g A N c o h ort o nl y), will b e o btai ne d fr o m t he 
l ocal pat h ol o g y re p orts, if a vaila ble, a n d d oc u me nte d i n t he e C R F. 
T he l ocal pat h ol o g y r e p ort a n d micr osc o p y sli des will be se nt t o t he Ce ntral Pat h ol o g y 
La b orat or y t o c o nfir m t he dia g n osis o n t he ki d ne y bi o ps y use d f or eli gi bilit y t o mi ni mize 
i nter pers o nal variati o n i n hist ol o gical sc ori n g. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 0 0  of 1 5 2  
Ale xi o n C o nfi de ntial  
8. 1 2. 5. 2.  Ki d ne y Bi o ps y D uri n g t he St u d y  
F or partici pa nts i n t he L N c o h ort, a r e peat bi o ps y at t he e n d of t he Bli n de d E xte n de d Treat me nt 
Peri o d ( Wee k  5 0) will be o pti o nal a n d ma y be perf or me d u p t o Wee k 5 4. 
8. 1 2. 5. 3.  Ce ntr al P at h ol o g y L a b or at or y 
A Ce ntral Pat h ol o g y La b orat or y will be use d t o c o nfir m t he dia g n osis o n t he ki d ne y bi o ps y use d 
f or eli gi bilit y t o mi ni mize i nter pers o n al variati o n i n hist ol o gical sc ori n g. T he Ce ntral Pat h ol o g y 
La b orat or y will be bli n de d t o treat me nt all ocati o n.  
T he Ce ntral Pat h ol o g y L a b orat or y will re vi e w: 
•  All ki d ne y bi o psies use d f or eli gi bilit y f or partici p a nts i n t he L N c o h ort 
•  Ki d ne y bi o psies perf or me d wit hi n 1 year of Scree ni n g or d uri n g Scree ni n g f or 
partici pa nts i n t he I g A N c o h ort 
•  All ki d ne y bi o psies perf or me d d uri n g t he st u d y a n y ti me pri or t o E D or c o m pleti o n of 
t he Bli n de d E xte n de d Tr eat me nt Peri o d ( Wee k 5 0) 
T he f oll o wi n g s h o ul d be se nt t o t he Ce ntral Pat h ol o g y La b orat or y as s o o n as feasi ble acc or di n g 
t o t he i nstr ucti o ns i n t he Ce ntral Pat h ol o g y La b orat or y Ma n ual: 
•  C o p y of t he l ocal pat h ol o g y re p ort 
•  All li g ht micr osc o p y sli des ( he mat o x yli n a n d e osi n stai n [ H/ E], peri o dic aci d – Sc hiff, 
J o nes & Tric hr o me stai ns) 
•  If a vaila bl e, u nstai ne d micr osc o p y sli des of t he ki d ne y bi o ps y s h o ul d als o be se nt t o 
t he Ce ntral Pat h ol o g y La b orat or y f or e x pl orat or y a nal yses of bi o mar k ers 
( Secti o n 8. 7. 4 ). T he site s h o ul d se n d all a vaila ble u nstai ne d sli des, u p t o a ma xi m u m 
of 8  sli des. 
E ver y eff ort s h o ul d be m a de t o o btai n t he micr osc o p y sli des fr o m t he site pat h ol o g y la b orat or y 
a n d s hi p t he m t o t he Ce ntral Pat h ol o g y La b orat or y. U p o n c o nfir mati o n wit h t he Ce ntral 
Pat h ol o g y La b orat or y, t h e ori gi nal bi o ps y sli des fr o m eac h partici pa nt will be ret ur n e d t o t he 
st u d y site as s o o n as p ossi ble. U nstai ne d sli des use d f or e x pl orat or y bi o mar ker a nal ys es will n ot 
be ret ur n e d. If t he s hi p m e nt of micr osc o p y sli des t o t he Ce ntral Pat h ol o g y La b orat or y is 
pr o hi bite d d ue t o l ocal re g ulati o ns, a sli de sca n ner ma y be use d t o se n d di gital i ma ges of t he 
sli des electr o nicall y, acc or di n g t o t he i nstr ucti o ns i n t he Ce ntral Pat h ol o g y La b orat or y M a n ual. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 0 1  of 1 5 2  
Ale xi o n C o nfi de ntial  
9.  
S T A TI S TI C A L C O N SI D E R A TI O N S  
9. 1.  
St atistic al H y p ot heses  
T he pri mar y h y p ot hesis f or t his st u d y is t hat A L X N 2 0 5 0 1 8 0 m g bi d is s u peri or t o place b o i n 
decreasi n g pr otei n uria. 
9. 2.  
S a m ple Size Deter mi n ati o n  
T his st u d y pla ns t o e nr oll a p pr o xi matel y 1 2 6 a d ult partici pa nts wit h eit her L N or I g A N i n t he 
st u d y (a p pr o xi matel y 7 0 partici pa nts i n t he L N c o h ort a n d a p pr o xi matel y 5 6 partici pa nts i n t he 
I g A N c o h ort) i n a 3: 1: 3 r ati o t o A L X N 2 0 5 0 1 8 0 m g bi d, A L X N 2 0 5 0 1 2 0 m g bi d, or place b o. All 
partici pa nts will recei ve sta n dar d - of-care treat me nt i n a d diti o n t o t heir ra n d o mize d treat me nt.  
T he pri mar y a n al ysis of t he pri mar y e n d p oi nt will test t he h y p ot hesis t hat A L X N 2 0 5 0 1 8 0 m g 
bi d is s u peri or t o place b o i n decreasi n g pr otei n uria. Data fr o m t he A L X N 2 0 5 0 1 2 0 m g bi d 
treat me nt gr o u p will be s u m marize d des cri pti vel y, wit h n o f or mal statistical testi n g pla n ne d. 
I n M arc h 2 0 1 8, a n N K F-s p o ns ore d w or ks h o p o n s urr o gate e n d p oi nts f or cli nical st u dies i n earl y 
sta ges of C K D was h el d. A 2 0 % t o 3 0 % re d u cti o n i n t he ge o metric mea n i n pr otei n uria was 
deci de d as a cli nicall y si g nifica nt treat me nt effect (Le ve y, 2 0 2 0 ). Sa m ple size cal c ulati o ns are 
base d o n a 1- si d e d 2-sa m ple t-test of l o g-tra nsf or me d pr otei n uria val u es. 
I n di vi d ual patie nt d ata fr o m rele va nt st u dies i n I g A N was pre vi o usl y use d t o esti mate varia bilit y 
a n d e x pecte d c h a n ges i n pr otei n uria f or p atie nts o n place b o wit h bac k gr o u n d sta n dar d- of- care 
treat me nt (Fellstr o m, 2 0 1 7 ). Base d o n t his data, t h e ge o metric mea n rati o ( G M R) of 2 6- wee k t o 
baseli ne pr otei n uria v al u es is ass u me d t o be 0. 8 5 (ie, a 1 5 % re d ucti o n fr o m baseli ne i n 
pr otei n uria) f or t he place b o gr o u p. I n or der t o tar g et at least a 3 0 % relati ve treat me nt effect, (i e 
1 mi n us G M R of A L X N 2 0 5 0 t o place b o at Wee k 2 6), t he G M R is ass u me d t o be 0. 5 5 (ie, a 4 5 % 
re d ucti o n fr o m bas eli ne i n pr otei n uria) f or t he A L X N 2 0 5 0 1 8 0 m g bi d gr o u p. T he l o g c ha n ge 
fr o m baseli ne i n pr otei n uria is calc ulate d as l o g ( 0. 8 5) a n d l o g ( 0. 5 5) f or t he place b o a n d 
A L X N 2 0 5 0 1 8 0 m g bi d treat me nt gr o u ps, res pecti vel y, f or t he I g A N c o h ort. A c o m m o n sta n dar d 
de viati o n ( S D) of l o g c ha n ge is ass u me d t o be 0. 6 0 (Fellstr o m, 2 0 1 7 ). Un d er t hese ass u m pti o ns 
a n d a n a ntici pate d 1 0 % dr o p o ut rate, a s a m ple size of 4 8 partici p a nts ( 2 4  p artici pa nts 
ra n d o mize d t o A L X N 2 0 5 0 1 8 0 m g bi d, 2 4 partici pa nts ra n d o mize d t o place b o) i n t he I g A N 
c o h ort will pr o vi de a p pr o xi matel y 8 0 % p o wer t o d etect a treat me nt differe n ce wit h a 1-si de d 
si g nifica nce le v el of 0. 0 5. A n a d diti o nal 8 partici p a nts will be e nr olle d i n t he A L X N 2 0 5 0 
1 2 0 m g bi d treat me nt gr o u p f or a t otal of 5 6 partici pa nts i n t he I g A N c o h ort. 
E x pecte d c h a n ges i n pr ot ei n uria a n d ass o ciate d varia bilit y were n ot a v aila ble o n t he l o g- scale f or 
L N; h o we ver, 2 st u dies of patie nts wit h L N w h o were treate d wit h M M F s h o we d mea n 
pr otei n uria val ues of a p pr o xi matel y 4 g/ da y at bas eli ne a n d a p pr o xi mat el y 2 g/ da y at Wee k  2 4 
(A p pel, 2 0 0 9 ; Gi nzler, 2 0 0 5 ). T he G M R of 2 6- w ee k t o baseli ne pr otei n uri a val ues is ass u me d t o 
be 0. 6 0 (ie, a 4 0 % re d u cti o n fr o m baseli ne i n pr ot ei n uria) f or t he place b o gr o u p. I n or der t o 
tar get at least a 3 0 % rel ati ve treat me nt effect, (ie, 1 mi n us G M R of A L X N 2 0 5 0 t o place b o at 
Wee k  2 6), t h e G M R is ass u me d t o be 0. 4 0 (ie, a 6 0 % re d ucti o n fr o m baseli ne i n pr otei n uria) f or 
t he A L X N 2 0 5 0 1 8 0 m g bi d gr o u p. T he l o g c ha n g e fr o m baseli ne i n pr otei n uria is calc ulate d as 
l o g ( 0. 6 0) a n d l o g ( 0. 4 0) f or t he place b o a n d A L X N 2 0 5 0 1 8 0 m g bi d treat me nt gr o u ps, 
res pecti vel y, f or t he L N c o h ort. A c o m m o n S D of l o g c ha n ge is ass u me d t o be 0. 6 0  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 0 2  of 1 5 2  
Ale xi o n C o nfi de ntial  
(Fellstr o m, 2 0 1 7 ). U n d er t hese ass u m pti o ns a n d a n a ntici pate d 1 0 % dr o p o ut rate, a sa m ple size 
of 6 0 partici pa nts ( 3 0 p artici pa nts ra n d o mize d t o A L X N 2 0 5 0 1 8 0 m g bi d, 3 0 partici pa nts 
ra n d o mize d t o place b o) i n t he L N c o h ort will pr o vi de a p pr o xi matel y 8 0 % p o wer t o detect a 
treat me nt differe nce wit h a 1-si de d si g nifica n ce le vel of 0. 0 5. A n a d diti o nal 1 0 partici pa nts will 
be e nr olle d i n t he A L X N 2 0 5 0 1 2 0 m g bi d treat me nt gr o u p f or a t otal of 7 0 partici pa nts i n t he L N 
c o h ort. 
9. 3.  
P o p ul ati o ns f or A n al yses  
T he p o p ulati o n sets use d f or a nal ysis are defi ne d b el o w. 
A n al ysis Set  
Descri pti o n  
E nr olle d Set 
All c o nse nte d partici pa nts e xcl u di n g scree n fail ures.  
Ra n d o mize d Set 
All ra n d o mize d partici pa nts. Partici pa nts will be a nal yze d as 
ra n d o mize d f or re p orti n g dis p ositi o n, de m o gra p hics, a n d baseli ne 
c haracteristics. 
F ull A nal ysis Set ( F A S)  
All ra n d o mize d partici pa nts w h o recei ve at least 1  d ose of st u d y 
i nter ve nti o n. Partici pa nts will be a nal yze d as ra n d o mize d f or 
re p orti n g efficac y data. 
Safet y Set  
All partici pa nts w h o recei ve at least 1  d ose of st u d y i nter ve nti o n. 
Partici pa nts will be a nal yze d acc or di n g t o t he st u d y i nter ve nti o n 
t he y act uall y recei ve d f or re p orti n g e x p os ure a n d safet y data. 
Per Pr ot oc ol Set  
All ra n d o mize d partici pa nts w h o recei ve at least 1  d ose of st u d y 
i nter ve nti o n a n d wit h o ut i m p orta nt pr ot oc ol de viati o ns. 
P har mac o ki netic ( P K) A nal ysis 
Set  
All ra n d o mize d partici pa nts w h o recei ve at least 1 d ose of st u d y 
i nter ve nti o n a n d w h o ha ve a baseli ne P K val ue a n d at least 
1 e val ua ble p ost d ose P K assess me nt.  
P har mac o d y na mic ( P D) A nal ysis 
Set  
All ra n d o mize d partici pa nts w h o recei ve at least 1 d ose of st u d y 
i nter ve nti o n a n d w h o ha ve a baseli ne P D val ue a n d at least 
1 e val ua ble p ost d ose P D assess me nt.  
9. 4.  
St atistic al A n al yses  
Statistical met h o ds descri be d i n t his secti o n will be f urt her ela b orate d i n a s e parat e Statistical 
A nal ysis Pla n ( S A P). T he a nal yses f or partici p a nts i n t he L N c o h ort a n d partici pa nts i n t he I g A N 
c o h ort will be c o n d ucte d a n d re p ort e d se paratel y. 
A nal yses will be perf or m e d usi n g t he S A S ®  s oft ware versi o n 9. 4 or hi g her. 
9. 4. 1.  
E nr oll m e nt a n d Dis p ositi o n 
T he n u m ber of p artici pa nts scree ne d, s cree n faile d, ra n d o mize d, a n d treat e d  will be prese nte d. 
T he n u m ber of p artici pa nts disc o nti n ue d (al o n g wit h reas o ns) will be s u m marize d. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 0 3  of 1 5 2  
Ale xi o n C o nfi de ntial  
9. 4. 2.  
De m o gr a p hics, B aseli ne C h ar acteristics, I ncl usi o n a n d E xcl usi o n Criteri a, a n d 
Pr ot oc ol D e vi ati o ns  
All de m o gra p hic i nf or mati o n a n d baseli ne c haracteristics will be re p orte d b y treat me nt gr o u p f or 
eac h disease c o h ort se par atel y . 
T he n u m ber a n d p erce nta ge of partici p a nts n ot meeti n g a s pecific i n cl usi o n or e xcl usi o n criteri o n 
will be s u m marize d b y tr eat me nt gr o u p f or eac h disease c o h ort s e paratel y . A si milar s u m mar y 
will be pr o vi de d f or i m p orta nt pr ot oc ol de viati o ns base d o n pres p ecifie d cate g ories.  
9. 4. 3.  
Me dic al Hist or y  
Me dical hist or y will be s u m marize d usi n g t he Me dical Dicti o nar y f or Re g ulat or y Acti vities 
( Me d D R A), V ersi o n 2 3 or later, S yste m Or ga n Class ( S O C) a n d Preferre d Ter m b y treat me nt 
gr o u p f or eac h disease c o h ort se parat el y . 
9. 4. 4.  
Pri or a n d C o nc o mit a nt Me dic ati o ns  
F or a n al ysis a n d re p orti n g p ur p oses, a n y me dicati o n starte d pri or t o first d ose of st u d y 
i nter ve nti o n will be c o nsi dere d pri or m e dicati o n, a n d me dicati o ns t hat starte d o n or aft er t he first 
d ose of st u d y i nter ve nti o n will be c o nsi dere d c o nc o mita nt me dicati o ns. All pri or a n d 
c o nc o mita nt me dicati o ns will be s u m marize d b y treat me nt gr o u p f or eac h disease c o h ort 
se parat el y. 
9. 4. 5.  
E xte nt of Dr u g E x p os ure  
T he c u m ulati ve a n d t otal dr u g e x p os ure a n d treat me nt d urati o n will be s u m marize d des cri pti vel y 
b y treat me nt gr o u p f or eac h disease c o h ort se parat el y.  
9. 4. 6.  
Effic ac y A n al yses  
9. 4. 6. 1.  
A n al yses of Pri m ar y Effic ac y E n d p oi nt  
T he pri mar y a n al ysis of t he pri mar y efficac y e n d p oi nt will be base d o n t he F ull A nal ysis Set 
( F A S). 
Pr otei n uria will be meas ure d a n d s u m marize d b y a bs ol ute pr otei n i n g/ da y as well as b y U P C R 
i n g/ g f or eac h disease c o h ort. 
F or t he L N c o h ort, t he pri mar y e n d p oi nt will be meas ure d b y U P C R i n g/ g deri ve d fr o m a si n gle 
2 4 -h o ur uri ne c ollecti o n at Scree ni n g a n d t h e mea n of 2  se parate 2 4-h o ur uri ne c ollecti o ns at 
Wee k  2 6.  
F or t he I g A N c o h ort, t he pri mar y e n d p oi nt will be meas ure d b y a bs ol ute pr otei n i n g/ da y deri ve d 
fr o m t he mea n of 2 v ali d 2 4 -h o ur uri ne c ollecti o ns.  
T o re d uce s ke w ness, t h e nat ural l o garit h m will be use d t o tra nsf or m pr otei n uria val ues bef ore 
a nal ysis. A n a nal ysis of c o varia nce ( A N C O V A) will be use d f or t he pri mar y efficac y e n d p oi nt t o 
c o m pare re d ucti o ns i n pr otei n uria bet wee n t he A L X N 2 0 5 0 1 8 0  m g bi d a n d place b o treat me nt 
gr o u ps. T he A N C O V A m o del will i ncl u de c ha n g e fr o m baseli ne i n l o g -tra nsf or me d pr otei n uria 
as t he res p o nse v aria ble a n d will a dj ust f or baseli ne l o g pr otei n uria. D ata fr o m t he A L X N 2 0 5 0 
1 2 0  m g bi d treat me nt gr o u p will be s u m marize d d escr i pti vel y, wit h n o f or mal statistical 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 0 4  of 1 5 2  
Ale xi o n C o nfi de ntial  
c o m paris o ns pla n ne d. T h e p oi nt esti mate a n d 2 -si de d 9 0 % c o nfi d e nce i nter val ( CI) f or t he mea n 
differe n ce of l o g -tra nsf or me d pr otei n uria will be b ac k-tra nsf or me d ( via e x p o ne ntiati o n) t o o btai n 
t he G M R a n d c orr es p o n di n g 2-si de d 9 0 % CI. T he val ues will t he n be e x presse d as perce nta g e 
c ha n ge i n a dj uste d g e o metric mea n of pr otei n uria at Wee k  2 6 relati ve t o baseli ne.  
F or t he L N c o h ort, data c ollecte d o n or after recei pt of a d diti o nal sta n dar d of care t hera p y will be 
i m p ute d usi n g t he pr otei n uria val ue fr o m t he 2 4-h o ur uri ne c ollecti o n perf or me d at t he ti me of 
Re nal Flar e f or t h e pri mar y efficac y a nal ysis. A d diti o nal se nsiti vit y a nal yses will be perf or me d 
t o assess t he i m pact of t h e missi n g data a n d ass u m pti o ns. 
T he pri mar y efficac y e n d p oi nt a nal ysis will als o be perf or me d o n t he Per Pr ot oc ol Set.  
F ull details of t hese a n al yses will be pr o vi de d i n t he S A P.  
9. 4. 6. 2.  
A n al yses of Sec o n d ar y Effic ac y E n d p oi nt(s)  
T he sec o n d ar y efficac y a nal yses will be descri pti v e i n nat ure a n d will be base d o n t he F A S.  
F or t he I g A N c o h ort, partici pa nts i nitiall y ra n d o mize d t o t he place b o gr o u p will recei ve 
A L X N 2 0 5 0 i n t he Bli n de d E xte n de d Treat me nt Peri o d. T heref ore, a nal ysis of t he sec o n d ar y 
e n d p oi nts d uri n g t he Bli n de d E xte n de d Treat me nt Peri o d will be s u m marize d se paratel y f or eac h 
treat me nt gr o u p a n d b aseli ne f or t he place b o gr o u p will be re defi n e d as t he last meas ure me nt 
ta ke n bef ore t he first d ose of A L X N 2 0 5 0 d uri n g t he O L E Peri o d (ie, t h e Wee k  2 6 meas ure me nt).  
9. 4. 6. 2. 1.  Sec o n d ar y Effic ac y A n al yses f or B ot h L N C o h ort a n d I g A N C o h ort  
T he per ce nt c h a n ge fr o m baseli ne i n pr otei n uria at Wee k  5 0 will be a nal yze d usi n g a mi xe d -
effect m o del f or r e peate d meas ures ( M M R M) i ncl u di n g c ha n ge fr o m baseli ne i n l o g -tra nsf or me d 
pr otei n uria as t he res p o nse varia ble a n d fi xe d, cat e g orical effects of treat me nt gr o u p, visit, a n d 
treat me nt gr o u p b y visit i nteracti o n as w ell as a fi x e d, c o nti n u o us effect of b aseli ne l o g 
pr otei n uria as a c o variate. A n u nstr uct ure d c o varia nce matri x will be use d t o m o del t he 
c orrel ati o ns a m o n g re peate d meas ure m e nts wit hi n eac h  p artici pa nt. If t his a nal ysis fails t o 
c o n ver ge, a first -or der a ut ore gressi ve c o varia n ce matri x will be use d. T he Ke n war d -R o ger 
a p pr o xi mati o n will be use d t o esti mate de n o mi nat or de grees of free d o m.  
•  F or t he I g A N c o h ort, partici pa nts i nitiall y ra n d o mize d t o t he place b o treat me nt gr o u p 
will s witc h t o recei ve A L X N 2 0 5 0 at Wee k  2 6. T h eref ore, t he p erce nta ge c ha n ge fr o m 
baseli ne i n pr otei n uria at Wee k  5 0 will be s u m marize d descri pti vel y f or eac h 
treat me nt gr o u p fr o m t he M M R M a nal ysis a n d n o f or mal treat me nt c o m paris o n will 
be ma de.  
•  F or t he L N c o h ort, t he tr eat me nt effect will be e v al uate d f or t h e A L X N 2 0 5 0 1 8 0  m g 
bi d a n d place b o tr eat me nt gr o u ps usi n g a c o ntrast f or treat me nt gr o u p -b y -visit ter m at 
Wee k  5 0. D ata fr o m t he A L X N 2 0 5 0 1 2 0  m g bi d treat me nt gr o u p will be s u m marize d 
descri pti vel y, wit h n o f or mal statistical c o m paris o ns pla n ne d. T he p oi nt esti mate a n d 
2si de d 9 0 % CI f or t he m ea n differe n ce of l o g -tra nsf or me d pr otei n uria will be 
bac k -tr a nsf or me d ( via e x p o ne ntiati o n) t o o btai n t he G M R a n d c orres p o n di n g 2 -si de d 
9 0 %  CI. T h e val ues w ill t he n be e x presse d as p erce nta ge c h a n ge i n a dj uste d 
ge o metric mea n of pr otei n uria at Wee k  5 0 relati ve t o baseli ne.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 0 5  of 1 5 2  
Ale xi o n C o nfi de ntial  
T he per ce nta g e of partici pa nts wit h  >  3 0 % a n d  >  5 0 % re d ucti o n i n pr otei n uria at Wee k  2 6 a n d 
Wee k  5 0 will be s u m marize d b y treat me nt gr o u p b y calc ulati n g t he p oi nt esti mate a n d 2 -si de d 
9 5 %  CI, b ase d o n e x act c o nfi de nce li mits usi n g t he Cl o p per -Pears o n met h o d.  
Esti mate d G F R will be s u m marize d at bas eli ne a n d eac h sc h e d ule d p ost bas eli ne ti me p oi nt b y 
treat me nt gr o u p usi n g descri pti ve statistics f or t he o bser ve d val u e as w ell as t he c ha n ge fr o m 
baseli ne.  
9. 4. 6. 2. 2.  Sec o n d ar y Effic ac y A n al yses f or L N C o h ort O nl y  
T he per ce nta g e of partici pa nts ac hie vi n g t he f oll o wi n g sec o n dar y e n d p oi nts will be s u m marize d 
b y treat me nt gr o u p b y calc ulati n g t he p oi nt esti mate a n d 2 -si de d 9 5 % CI, b ase d o n e xact 
c o nfi de nce li mits usi n g t he Cl o p per -Pears o n met h o d:  
− Meeti n g t he criteri a f or C R R as well as i n di vi d ual c o m p o ne nts of C R R at 
Wee k  2 6 a n d Wee k  5 0  
− Meeti n g t he criteri a f or P R R at Wee k  2 6 a n d Wee k  5 0  
− Ac hie vi n g c ortic oster oi d ta per t o 7. 5  m g/ da y at Wee k  1 2, Wee k  2 6, a n d Wee k  5 0  
− E x perie nce of pr ot o c ol -d efi ne d Re nal Flare t hr o u g h Wee k  5 0  
− E x perie nce of pr ot o c ol -d efi ne d E xtrare n al S L E Fl are t hr o u g h Wee k  5 0  
− Meeti n g t he criteri a f or Treat me nt Fail ure t hr o u g h Wee k  5 0  
− Meeti n g t he criteri a f or S u b o pti mal Res p o nse t hr o u g h Wee k  5 0  
Ti me t o t he first occ urre n ce of U P C R  ≤ 0. 5  g/ g will be s u m marize d bas e d o n s p ot uri ne sa m ples. 
A Ka pla n -M eier c u m ulati ve distri b uti o n c ur ve will be ge nerate d f or treat m e nt gr o u p, a n d a 
l o g-ra n k test c o m pari n g t he c ur ves f or A L X N 2 0 5 0 1 8 0 m g bi d a n d place b o treat me nt gr o u ps will 
be perf or me d. T he c orr es p o n di n g s u m mar y ta ble will prese nt b y treat me nt gr o u p t he c u m ulati ve 
distri b uti o n f u ncti o n ( C D F) esti mate, t he n u m b er of partici pa nts at ris k, t he n u m ber of 
partici pa nts res p o n di n g, a n d t he n u m ber of p artici pa n ts ce ns ore d at eac h p ost baseli ne ti me p oi nt. 
T he ta ble will als o pres e nt t he first q uartile, me dia n, a n d t hir d q uartile, al o n g wit h 2 -si de d 
9 5 % CI, of ti me t o U P C R  ≤ 0. 5  g/ g.  
Ser u m al b u mi n will be s u m marize d at bas eli ne a n d eac h sc h e d ule d p ost bas eli ne ti me p oi nt b y 
treat me nt gr o u p usi n g descri pti ve statistics f or t he o bser ve d val u e as w ell as t he c ha n ge fr o m 
baseli ne.  
9. 4. 6. 2. 3.  Sec o n d ar y Effic ac y A n al yses f or I g A N C o h ort O nl y  
T he per ce nta g e of partici pa nts meeti n g t he criteri a f or Partial Re missi o n ( defi ne d i n 
Secti o n  8. 1. 1 1 ) at Wee k 2 6 a n d Wee k  5 0 will be s u m marize d b y treat me nt gr o u p b y calc ulati n g 
t he p oi nt esti mate a n d 2-si de d 9 5 % CI, b ase d o n e xact c o nfi de n ce li mits usi n g t he 
Cl o p per -Pears o n met h o d.  
9. 4. 6. 3.  
M ulti plicit y A dj ust m e nt  
T he sec o n d ar y efficac y a nal yses will be descri pti v e i n nat ure a n d n o a dj ust me nt f or m ulti plicit y 
will be perf or me d.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 0 6  of 1 5 2  
Ale xi o n C o nfi de ntial  
9. 4. 6. 4.  
A n al yses of E x pl or at or y E n d p oi nt(s)  
E x pl orat or y a nal ys es will be descri pti ve i n nat ure a n d will be base d o n t he F A S. F ull details of 
t hese a nal yses will be pr o vi de d i n t he S A P. 
E x pl orat or y bi o mar kers will be a nal yze d if d ata is a vaila ble a n d ma y b e i n cl u de d i n t he cli nical 
st u d y re p ort ( C S R). A se parate S A P will be pr o vi de d f or t he e x pl orat or y bi o mar kers.  
9. 4. 7.  
S afet y A n al yses f or B ot h L N C o h ort a n d I g A N C o h ort  
T he safet y a n d t olera bilit y of A L X N 2 0 5 0 will be assesse d bas e d o n A Es, cli nical la b orat or y 
fi n di n gs, vital si g n fi n di n gs, E C G a b n or malities, a n d p h ysical e xa mi nati o n. All safet y a nal yses 
will be perf or me d o n t h e Safet y Set base d o n t he act ual treat me nt rec ei v e d.  
9. 4. 7. 1.  
A d verse E ve nts  
T he i nci de nce of treat me nt -e mer ge nt a d vers e e ve nts ( T E A Es), T E A Es lea di n g t o wit h dra wal 
fr o m t he st u d y, T E A Es lea di n g t o st u d y treat me nt disc o nti n uati o n, a n d S A Es will be s u m marize d 
b y treat me nt gr o u p f or eac h disease c o h ort se parat el y. All A Es will be c o d e d usi n g Me d D R A 
versi o n  2 3 or hi g her a n d will be s u m marize d b y S O C a n d Preferre d T er m o verall, b y se verit y, 
a n d b y relati o ns hi p t o treat me nt. Detaile d b y -p artici pa nt listi n gs of T E A Es, S A Es, relate d 
T E A Es, T E A Es lea di n g t o wit h dra wal fr o m t he st u d y, a n d T E A Es lea di n g t o st u d y treat me nt 
disc o nti n uati o n will be pr o vi de d.  
9. 4. 7. 2.  
P h ysic al E x a mi n ati o n a n d Vit al Si g ns  
A d verse c ha n ges fr o m baseli ne i n p h ysical e xa mi n ati o n fi n di n gs will be classifie d as A Es a n d 
a nal yze d acc or di n gl y.  
Vital si g ns will be s u m marize d d escri pti vel y b y treat me nt gr o u p at bas eli ne a n d eac h sc h e d ule d 
p ost baseli ne ti me p oi nt a n d f or c ha n g es fr o m b aseli ne se parat el y f or eac h disease c o h ort.  
9. 4. 7. 3.  
Cli nic al L a b or at or y Tests  
O bser ve d v al ues a n d c ha n ges fr o m baseli ne i n cli nical c he mistr y, he mat ol o g y, a n d uri nal ysis 
will be s u m marize d descri pti vel y b y treat me nt gr o u p at baseli ne a n d at eac h sc he d ule d 
p ost baseli ne ti me p oi nt se parat el y f or eac h diseas e c o h ort. F or la b orat or y res ults t hat ca n be 
classifie d as n or mal, l o w, or hi g h base d o n n or mal ra n ge val u es, s hifts fr o m baseli ne i n 
classificati o n will be s u m marize d f or all st u d y visits.  
9. 4. 7. 4.  
Electr oc a r di o gr a ms  
B y -partici pa nt data listi n gs of E C G para m eters will be pr o vi de d se paratel y f or eac h diseas e 
c o h ort. Electr o car di o gr a ms will be e val uate d a n d s u m marize d as n or m al, a b n or mal n ot cli nicall y 
si g nifica nt, or a b n or mal cli nicall y si g nifica nt. A s hift fr o m baseli ne t o w orst o n -st u d y E C G ta ble 
will be prese nte d f or E C G res ults. O bser v e d val u es a n d c ha n g e fr o m b aseli ne i n E C G i nter vals 
( P R, R R, Q T, a n d Q Tc) will be s u m marize d descri pti vel y at baseli ne a n d eac h sc h e d ule d 
p ost baseli ne ti me p oi nt. Q T i nter val will be c o rrecte d f or h eart rate usi n g Fri deri cia’s f or m ula 
( Q Tc F). 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 0 7  of 1 5 2  
Ale xi o n C o nfi de ntial  
9. 4. 8.  
P K/ P D A n al ysis f or B ot h L N C o h ort a n d I g A N C o h ort  
Descri pti ve statistics will be calc ul ate d f or plas m a c o nce ntrati o n data at eac h sa m pli n g ti me, as 
a p pr o priate. O bser v e d tr o u g h c o nce ntrati o ns ( C tr o u g h) a n d ser u m Cma x  will be s u m marize d.  
T he P D eff ects of A L X N 2 0 5 0 will be e val uate d b y assessi n g t he a bs ol ute val ues a n d c h a n ges 
a n d perce nta ge c ha n g es fr o m baseli ne i n ser u m A P acti vit y a n d plas ma B b c o nce ntrati o n o ver 
ti me, as a p pr o priate. Des cri pti ve statistics will be calc ulate d f or t he P D dat a at eac h sa m pli n g 
ti me, as a p pr o priate. 
P o p ulati o n P K m o deli n g will be c o n d ucte d t o c h aracterize t he P K of A L X N 2 0 5 0 i n partici pa nts 
w h o are o n t h e acti ve tr eat me nt. C o variates (s o urce of varia bilit y) t hat ha v e si g nifica nt i m pact o n 
t he P K will be i de ntifie d. Stea d y state e x p os ure p ara meters s u c h as t he area u n der t he 
c o nce ntr ati o n -ti me c ur ve ( A U C) a n d t he Cma x  will be deri ve d fr o m t he P o p ulati o n P K m o del. I n 
a d diti o n, a P K-P D m o del will be de vel o pe d. Fact ors c o ntri b uti n g t o t he P K -P D relati o ns hi p will 
als o be e x pl ore d. M a xi m u m P D res p o nse a n d t he  e x p os ure re q uire d t o ac hi e ve 5 0 % of t h e 
res p o nse will be pr ese nte d. Act ual d ose a d mi nistrati o n a n d sa m pli n g ti mes will be use d f or 
P o p ulati o n P K a n d P K -P D a nal yses.  
Details of P o p ulati o n P K m o deli n g, as well as P K -P D m o deli n g, will be prese nte d i n a 
P o p ulati o n P K/ P D A nal ysis Pla n. Res ults fr o m P o p ulati o n P K/ P D a nal yses will be prese nte d i n a 
se parat e P o p ulati o n P K/ P D A nal ysis Re p ort. 
9. 5.  
Pl a n ne d A n al yses  
T he pri mar y efficac y a n al ysis will be perf or me d f or eac h dis ease -s pecifi c c o h ort at t he e n d of t he 
2 6 -wee k Bli n de d I nitial E val uati o n Peri o d after all partici pa nts i n t he disease -s pecific c o h ort 
ha ve c o m plete d or wit h dra w n fr o m t he 2 6 -wee k Bli n de d I nitial E val uati o n Peri o d. T his a nal ysis 
will all o w f or i de ntificati o n of t he o pti mal d ose le vel, e val uati o n of t he pri mar y e n d p oi nt a n d 
P hase  3 pla n ni n g a n d will ha ve n o i m pact o n t he pr o gressi o n of t his st u d y.  
A n a d diti o nal a nal ysis will be perf or me d f or eac h disease -s pecific c o h ort at t he e n d of t he 
Bli n de d E xte n de d Treat me nt Peri o d after all partici pa nts i n t he disease -s p ecific c o h ort ha ve 
c o m plete d t he Wee k  5 0 Visit or wit h dra w n fr o m t he st u d y earl y.  
T he fi nal a n al ysis will be perf or me d at t he e n d of t he 2 -year O L E Peri o d aft er all partici pa nts 
ha ve c o m plete d t h e Safet y F oll o w -u p Visit.  
T he S A P will descri be t he pla n ne d a n al yses i n greater detail.  
9. 6.  
I nteri m A n al ysis 
A n earl y i nteri m a n al ysis ma y be c o n d uct e d at t he discreti o n of Ale xi o n ( b ase d o n feasi bilit y) 
w he n a p pr o xi matel y 5 0 % of partici pa nts i n t he I g A N a n d/ or L N disease -s pecific c o h orts ha ve 
bee n ra n d o ml y assi g ne d t o st u d y treat me nt a n d ha ve ha d t he o p p ort u nit y  t o c o m plete t he 
2 6 -wee k Pri mar y E val uati o n Peri o d or ha ve disc o nti n ue d fr o m t he st u d y treat me nt bef ore 
Wee k  2 6. T his earl y i nteri m a nal ysis, if perf or me d f or eit her t he I g A N c o h ort a n d/ or L N c o h ort, 
will be c o n d ucte d b y a s e parate u n bli n de d tea m a n d will be f or P hase 3 pla n ni n g p ur p oses o nl y 
wit h n o i m pact o n t he pr o gressi o n of t he st u d y.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 0 8  of 1 5 2  
Ale xi o n C o nfi de ntial  
9. 7.  
D at a M o nit ori n g C o m mittee  
A n i n de pe n de nt D M C, c o m prisi n g e x perts i n rele va nt fiel ds wit h n o direct relati o ns hi p t o t he 
st u d y, will be a p p oi nte d b y Ale xi o n or desi g nee. I n t his st u d y, t he i n de pe n de nt D M C will be 
res p o nsi ble f or r e vie w of efficac y a n d s afet y d ata. T he s pecific res p o nsi bilities of t he D M C a n d a 
sc he d ule of meeti n gs will be descri be d i n t he D M C C harter. 
9. 8.  
S afet y Re vie w C o m mittee  
A Safet y Re vie w C o m mittee will n ot be use d f or t his st u d y.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 0 9  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0.  
S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S  
1 0. 1.  
Re g ul at or y, Et hic al, a n d St u d y O versi g ht C o nsi der ati o ns  
1 0. 1. 1.  
Re g ul at or y a n d Et hic al C o nsi der ati o ns  
•  T his st u d y will be c o n d ucte d i n acc or da n ce wit h t he pr ot oc ol a n d t he f oll o wi n g:  
− C o nse ns us et hical pri nci ples deri ve d fr o m i nter nati o nal g ui deli nes i ncl u di n g t he 
Declar ati o n of Helsi n ki a n d CI O M S I nter nati o nal Et hical G ui deli nes  
− A p plica ble I C H G C P G ui deli nes  
− A p plica ble la ws a n d re g ulati o ns  
•  T he pr ot oc ol, pr ot oc ol a me n d me nts (ie, m o dificati o ns), I C F, I B, a n d ot her rele va nt 
d oc u me nts (e g, a d v ertise me nts) m ust be s u b mitte d t o a n I R B/I E C b y t he 
I n v esti gat or/ Ale xi o n, a n d re vie we d a n d a p pr o ve d b y t he I R B/I E C bef ore t h e st u d y is 
i nitiate d. 
− If a n y of t hes e d oc u me nts re q uire re g ulat or y/ healt h a ut h orit y a p pr o val per l ocal 
re g ulati o ns, Ale xi o n will als o o btai n s uc h a p pr o val bef ore t h e st u d y is i nitiate d. 
•  A n y s u bsta ntial a me n d me nts t o t he pr ot oc ol will re q uire I R B/I E C a n d 
re g ulat or y/ healt h a ut h orit y a p pr o val bef ore i m ple me ntati o n of c ha n ges m a de t o t he 
st u d y desi g n, e xce pt f or c ha n ges necessar y t o eli mi nate a n i m me diate hazar d t o st u d y 
partici pa nts.  
•  F or st u dies t o be a p pr o ve d b y t he Me dici nes a n d Healt hcare pr o d u cts Re g ulat or y 
A ge nc y: T he I n vesti gat or will n otif y t he I R B/I E C of de viati o ns fr o m t he st u d y 
pr ot oc ol or G C P as defi n e d b y a p plica ble l a w as a seri o us breac h or as re q uire d b y 
I R B/I E C pr oce d ures.  
•  T he I n vesti gat or will be r es p o nsi ble f or t he f oll o wi n g:  
− Pr o vi di n g writte n s u m maries of t he stat us of t he st u d y t o t he I R B/I E C a n n u all y or 
m ore fre q u e ntl y i n acc or da nce wit h t he re q uire m e nts, p olicies, a n d pr oce d ures 
esta blis he d b y t he I R B/I E C  
− N otif yi n g t he I R B/I E C of S A Es or ot her si g nifica nt safet y fi n di n gs as re q uire d b y 
I R B/I E C pr oce d ures 
− Pr o vi di n g o versi g ht of t he c o n d uct of t he st u d y at t he site a n d a d here nce t o 
re q uire me nts of 2 1 C F R, I C H g ui deli nes, t he I R B/I E C, E U C T R 5 3 6/ 2 0 1 4 f or 
cli nical st u dies, f or cli nical st u dies (if a p plica ble), a n d all ot her a p plica ble l ocal 
re g ulati o ns 
− Pr o m ptl y n otif yi n g Ale xi o n of a n y ( p ote ntial) s eri o us breac h of t he pr ot oc ol or 
re g ulati o ns (i ncl u di n g if a data breac h c o m pr o mises t he i nte grit y, c o nfi de ntialit y, 
or a vaila bilit y of t he pers o nal data of partici pa nts) s o t hat le gal a n d et hical 
o bli gati o ns are met. A ‘s eri o us breac h’ mea ns a breac h li kel y t o affect t o a 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 1 0  of 1 5 2  
Ale xi o n C o nfi de ntial  
si g nifica nt de gree t he safet y a n d ri g hts of a partici pa nt or t he relia bilit y a n d 
r o b ust ness of t he data g e nerate d i n t he cli nical st u d y. 
•  I n cert ai n re gi o ns/c o u ntri es, Ale xi o n has a le g al res p o nsi bilit y t o n otif y b ot h t he l ocal 
re g ulat or y a ut h orit y a n d ot her re g ulat or y a ge n cies a b o ut s uc h breac hes.  
− Ale xi o n will c o m pl y wit h c o u ntr y -s pecific re g ul at or y re q uire me nts relati n g t o 
seri o us breac h re p orti n g t o t he re g ulat or y a ut h orit y (i ncl u di n g data pr otecti o n 
a ut h orities a n d, if a p plica ble, affecte d p artici pa nts i n case of a pers o n al data 
breac h), I R B/I E C,  a n d I n vesti gat ors. U n der E U C T R 5 3 6/ 2 0 1 4, Ale xi o n is 
re q uire d t o e nt er details of seri o us breac hes i nt o t h e E M A C TI S. It is i m p orta nt t o 
n ote t hat re dacte d versi o ns of seri o us breac h re p orts will be a vaila ble t o t he p u blic 
via C TI S.  
− A “ pers o n al data br eac h ” mea ns a breac h of sec urit y lea di n g t o t he acci de nt al or 
u nla wf ul destr ucti o n, l oss, alterati o n, u na ut h orize d discl os ure of, or access t o, 
pers o nal data tr a ns mitte d, st ore d or ot her wis e pr ocesse d.  
•  T he I n vesti gat or s h o ul d ha ve a pr o cess i n place t o e ns ure t hat:  
− T he site staff or s er vice pr o vi ders dele g ate d b y t he I n v esti gat or/i nstit uti o n are a ble 
t o i de ntif y t he occ urr e nce of a ( p ot e ntial) seri o us breac h, i n cl u di n g pers o n al data 
breac h es.  
− A ( p ote ntial) seri o us br eac h is pr o m ptl y re p orte d t o Ale xi o n or dele gat e d p art y, 
t hr o u g h t he c o ntacts ( e mail a d dress or tel e p h o ne n u m ber) pr o vi de d b y Ale xi o n. 
•  T he C o or di nati n g I n vesti gat or will be i de ntifie d a m o n g t he e nr olli n g I n v esti gat ors 
d uri n g t he c o urse of t he st u d y a n d will be res p o nsi ble f or re vi e wi n g t he C S R a n d 
c o nfir mi n g t hat it acc ur at el y descri bes t he c o n d uct a n d res ults of t he st u d y.  
1 0. 1. 2.  
Fi n a nci al Discl os ure  
I n v esti gat ors a n d S u b-I n vesti gat ors will pr o vi de Ale xi o n wit h s ufficie nt, acc urat e fi na n cial 
i nf or mati o n as re q u este d t o all o w Ale xi o n t o s u b mit c o m plete a n d acc urat e fi na ncial certificati o n 
or discl os ure state me nts t o t he a p pr o priat e re g ulat or y a ut h oritie s. I n vesti gat ors are res p o nsi ble 
f or pr o vi di n g i nf or mati o n o n fi na ncial i nterests d uri n g t he c o urse of t he st u d y a n d f or 1 year after 
c o m pleti o n of t he st u d y.  
1 0. 1. 3.  
I nf or m e d C o nse nt Pr ocess 
•  It is t he r es p o nsi bilit y of t he I n v esti gat or or d esi g nee t o o btai n si g ne d ( writt e n or 
electr o nic si g nat ur e) i nf or me d c o nse nt fr o m all st u d y partici pa nts pri or t o p erf or mi n g 
a n y st u d y -relate d pr oce d ures i ncl u di n g scree ni n g assess me nts. 
•  T he I n vesti gat or or d esi g nee will e x plai n t he nat ure of t he st u d y (i ncl u di n g b ut n ot 
li mite d t o t he o bjecti ves, p ote ntial be nefits a n d ris ks, i nc o n ve nie nces, a n d t he 
partici pa nt’s ri g hts a n d r es p o nsi bilities) t o t he partici pa nt, defi ne d acc or di n g t o l ocal 
a n d c o u ntr y r e g ulati o ns w here t he st u d y is ta ki n g place, a n d a ns wer all q u esti o ns 
re gar di n g t he st u d y. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 1 1  of 1 5 2  
Ale xi o n C o nfi de ntial  
•  Partici pa nts m ust be i nf or me d t hat t heir partici p ati o n is v ol u ntar y. Partici pa nts will be 
re q uire d t o si g n a state m e nt of i nf or me d c o ns e nt or a certifie d tra nslati o n, if 
a p plica ble, t hat meets t he re q uire me nts of 2 1 C F R  5 0, l ocal re g ulati o ns, E U Ge neral 
Data Pr otecti o n Re g ulati o n ( G D P R), I C H G C P g ui deli nes, Healt h I ns ura n ce 
P orta bilit y a n d Acc o u nta bilit y Act ( HI P A A) re q uire me nts, w here a p plica ble, a n d t he 
I R B/I E C or st u d y ce nt er. 
•  T he partici pa nt’s m e dical rec or d m ust i ncl u de a state me nt t hat si g ne d ( writte n or 
electr o nic) i nf or me d c o nse nt was o btai ne d bef ore a n y scree ni n g pr oce d ures were 
perf or me d wit h a partici p a nt, a n d t he date t h e writte n c o nse nt was o bt ai ne d. T he 
a ut h orize d pers o n o btai ni n g t he i nf or me d c o nse nt  m ust als o si g n t he I C F(s). 
•  Partici pa nts m ust be rec o nse nte d  t o t he m ost c urre nt versi o n of t he I C F(s) d uri n g t heir 
partici pati o n i n t he st u d y, as a p plica ble. 
•  A c o p y of t he si g ne d ( writte n or electr o nic) i nf or me d c o nse nt d oc u me ntati o n (ie, a 
c o m plete set of partici pa nt i nf or mati o n s heets a n d f ull y e xec ute d si g nat ure pa ges) 
m ust be pr o vi de d t o t he partici pa nt. T his d oc u me nt ma y re q uire tra nslati o n i nt o t he 
l ocal la n g ua ge. Ori gi nal si g ne d ( writte n or el ectr o nic) c o nse nt f or ms m ust re mai n i n 
eac h p artici pa nt’s st u d y file a n d m ust be a vaila ble f or verifi cati o n at a n y ti me.  
Partici pa nts w h o are rescree ne d o utsi de of t he Scree ni n g wi n d o w ( T a ble  1) are re q uire d t o si g n a 
ne w I C F ( Secti o n  5. 4 ). 
1 0. 1. 4.  
Recr uit m e nt Str at e g y  
Partici pa nts will be i de ntifie d b y q ualifie d res earc h staff. T his ma y be d o ne t hr o u g h a re vie w of 
me dical rec or ds, e xter nal referrals, or usi n g d ata bases. Recr uit me nt strate gi es ma y i ncl u de st u d y 
p osters, ref err al letters, r ecr uit me nt br oc h ures, a d vertise me nts, s ocial me di a p osts, a n d we bsites, 
w here p er mitte d b y l ocal re g ulati o ns. All recr uit me nt materials will be s u b mitte d t o l ocal 
I R B/ E C as re q uir e d, f or r e vie w a n d a p pr o val f or use. 
1 0. 1. 5.  
D at a Pr ot ecti o n 
•  Partici pa nts will be assi g ne d a u ni q ue i de ntifier b y Ale xi o n or desi g nee. A n y 
partici pa nt rec or ds or d atasets t hat are tra nsferre d t o Ale xi o n will c o ntai n t he 
i de ntifier o nl y; partici pa nt na mes, i nitials, or a n y i nf or mati o n w hic h w o ul d ma ke t he 
partici pa nt  i de ntifia ble will n ot be tra nsferre d. 
•  Partici pa nts m ust be i nf or me d t hat t heir pers o n al st u d y -relate d a n d c o de d 
( pse u d o n y mize d) d ata will be use d i n acc or da nce wit h a p plica ble data pr otecti o n la w, 
a n d partici pa nts m ust als o be i nf or me d of a n y i n di vi d uals ri g hts t he y ma y ha ve wit h 
re gar d t o t heir p ers o nal d ata. Partici pa nts will be i nf or me d a b o ut h o w t heir pers o nal 
st u d y-relate d dat a will be discl ose d, a n d will be re q uire d t o a gree t o t he i nf or mati o n 
c o ntai ne d i n t he i nf or me d c o nse nt a n d pr o vi de c o nse nt t o t he pr ocessi n g of t heir 
pers o nal data, if re q uir e d b y a p plica ble dat a pr otecti o n la w. 
•  Partici pa nts m ust be i nf or me d t hat t heir me dical rec or ds ma y b e e xa mi ne d b y Cli nical 
Q ualit y Ass ura nce a u dit ors or ot her a ut h orize d pers o n nel a p p oi nte d b y Ale xi o n, 
a p pr o priate I R B/I E C me m bers, a n d i ns pect ors fr o m re g ulat or y a ut h orities. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 1 2  of 1 5 2  
Ale xi o n C o nfi de ntial  
•  Ale xi o n as a data c o ntr oller has i m ple me nte d pri v ac y a n d sec urit y c o ntr ols desi g ne d 
t o hel p pr otect partici pa nt pers o nal data, i ncl u di n g i nf or mati o n sec urit y c o ntr ols, 
fire walls, i nci de nt det ecti o n, a n d sec ure tra nsfer m eas ures. 
•  T he c o ntract bet wee n Al e xi o n a n d st u d y sites s pecifies res p o nsi bilities of t he parties 
relate d dat a pr otecti o n, i n cl u di n g ha n dli n g of data sec urit y breac hes a n d res pecti ve 
c o m m u nicati o n a n d c o o p erati o n of t he p arties.  
•  I nf or mati o n tec h n ol o g y s yste ms use d t o c ollect, pr ocess, a n d st ore st u d y-rel ate d data 
are sec ure d b y t ec h nical a n d or ga nizati o nal sec urit y meas ures desi g ne d t o pr otect 
s uc h data a g ai nst acci d e ntal or u nla wf ul l oss, alterati o n, or u na ut h orize d dis cl os ure or 
access. 
•  T he E U G D P R defi nes pse u d o n y mizati o n as t he pr ocessi n g of pers o nal dat a i n s uc h a 
wa y t hat t he pers o n al dat a ca n n o l o n ger be attri b ute d t o a s pecific i n di vi d u al wit h o ut 
t he use of a d diti o nal i nf or mati o n, pr o vi de d t hat s uc h a d diti o nal i nf or mati o n is ke pt 
se parat el y a n d pr otecte d b y tec h nical a n d or ga nizati o nal meas ures t o e ns ure t hat t he 
pers o nal data are n ot attri b ute d t o a n i de ntifie d or i de ntifia ble nat ural p ers o n.  
•  A p pr o priate s afe g u ar ds will be i m ple me nte d t o pr otect c o de d d ata d uri n g a n d after 
t he st u d y t hat i ncl u de: 
− Access t o t he c o de d dat a will be li mite d t o s pecific i n di vi d uals s u bject t o 
c o nfi de ntialit y o bli gati o ns (i ncl u di n g t he o bli gati o n t o n ot atte m pt t o re -i de ntif y 
i n di vi d uals/ dec o de t he cli nical data). 
− T he c o de d d ata will be pr otecte d wit h sec urit y meas ures t o a v oi d data alterati o n, 
l oss, a n d u na ut h orize d accesses a n d f urt her d e-i de ntificati o n tec h ni q ues ma y be 
a p plie d. 
− A data pr otecti o n i m pact assess me nt ( D PI A), w here re q uire d, will a p pl y t o 
i de ntif y a n d miti gate pri vac y ris ks, if a n y, ass ociat e d wit h eac h s cie ntific researc h. 
− T he c o de d d ata will n ot be s hare d f or direct mar k eti n g p ur p oses or ot her p ur p oses 
t hat are n ot le gal d uties or are n ot c o nsi dere d s cie ntific researc h acc or di n g t o t he 
a p plica ble data pr otecti o n le gislati o n. I n partic ular, it will n ot be use d t o ma ke 
decisi o ns a b o ut f ut ure ser vices a v aila ble t o t he partici pa nt, s uc h as i ns ura n ce.  
•  I n a d diti o n t o ha vi n g t he partici pa nts’ data a n d bi osa m ples c o de d, t he d ata is als o 
pr otecte d b y hi g h -sta n d ar d tec h nical sec urit y mea ns, s uc h as str o n g access c o ntr ol 
a n d e ncr y pti o n.  
•  Partici pa nts are als o pr otecte d le g all y b y t he f oll o wi n g mea ns if t he le vel of 
discl os ure of t he c o d e d d ata i ncl u des s hari n g of t he latter wit h ot her t hir d p arties, as 
t he partici pa nts will be e x plai ne d i n t he I C F: 
− T he partici pa nts’ c o de d d ata are pr otecte d b y c o ntract ual arra n g e me nts, C o des of 
C o n d uct, or certificati o ns t hat set t he r ules f or p ers o nal i nf or mati o n pr otecti o n t o 
t h ose a vaila ble i n E ur o p ea n c o u ntries or ot her alter nati ves set f ort h i n t he la w, as 
well as a n y s u p ple me ntar y tec h nical a n d or ga nizati o nal meas ures t hat ma y res ults 
o ut of c o n d ucte d tr a nsfer i m pact assess me nts.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 1 3  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 1. 6.  
Disse mi n ati o n of Cli nic al St u d y D at a 
St u d y-relate d i nf or mati o n a n d st u d y res ults ma y be p oste d o n p u blicl y accessi ble cli nical st u d y 
data bases ( e g, t he U S w e bsite  w w w.cli nicaltrials. g o v  o r t he E U we bsite 
w w w.cli nicaltrialsr e gister.e u ), as a p pr o priat e, a n d i n acc or d a nce wit h nati o nal, re gi o nal, a n d 
l ocal re g ulati o ns. H o w e v er, p osti n g of st u d y res ults per l ocal re g ulati o ns ma y be deferre d t o a 
later date f or o ne of t he f oll o wi n g reas o ns: 
•  St u d y is still o n g oi n g i n ot her c o u ntries or re gi o ns 
•  St u d y is part of a n o n g oi n g re vie w f or a p pr o v al b y Healt h A ut h orities; st u d y res ult data 
deferral r e q uest ca n b e s u b mitte d.  
1 0. 1. 7.  
D at a Q u alit y Ass ur a nce 
•  All partici pa nt data r elati n g t o t he st u d y will be rec or de d o n pri nte d C R F or e C R F 
u nless tra ns mitte d t o Ale xi o n or desi g nee el ectr o nicall y (e g, la b orat or y dat a). T he 
I n v esti gat or is res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y 
p h ysicall y or electr o ni call y si g ni n g t he C R F. 
•  T he I n vesti gat or m ust mai ntai n acc urate d o c u me ntati o n (s o urce dat a) t hat s u p p orts 
t he i nf or mati o n e nter e d i n t he e C R F. 
•  T he I n vesti gat or m ust per mit st u d y-relate d m o nit ori n g, a u dits, I R B/I E C re vie w, a n d 
re g ulat or y a g e nc y i ns pecti o ns a n d pr o vi de direct access t o s o urce data d o c u me nts. 
•  Ale xi o n or desi g nee is r es p o nsi ble f or t he data ma na ge me nt of t his st u d y i ncl u di n g 
q ualit y c hec ki n g of t he d ata. 
•  St u d y m o nit ors will perf or m o n g oi n g s o urce data verificati o n t o c o nfir m t hat data 
e ntere d i nt o t he e C R F b y a ut h orize d site pers o n nel are acc urate, c o m plete, a n d 
verifia ble fr o m s o urce d o c u me nts; t hat t he safet y a n d ri g hts of partici pa nts are bei n g 
pr otecte d; a n d t hat t he st u d y is bei n g c o n d ucte d i n acc o r d a nce wit h t he c urre ntl y 
a p pr o ve d pr ot o c ol a n d a n y ot her st u d y a gree me nts, I C H G C P, a n d all a p plica ble 
re g ulat or y r e q uire me nts. 
− Re m ote s o urce dat a verificati o n ma y be e m pl o ye d w here p er mitte d b y l ocal 
re g ulati o ns. 
− T he sc o pe of t h e s o urce data verifi cati o n will be descri be d i n det ail i n t he Cli nical 
M o nit ori n g Pla n. 
•  Rec or ds a n d d o c u me nts, i ncl u di n g si g ne d I C Fs, p ertai ni n g t o t he c o n d uct of t his 
st u d y m ust be retai ne d b y t he I n v esti gat or f or at least 2 5 years after st u d y c o m pleti o n 
( or per l ocal or i nstit uti o nal p olic y rec or d rete nti o n re q uire me nts). N o rec or ds ma y be 
destr o ye d wit h o ut t he writte n a p pr o val of Ale xi o n. N o rec or ds ma y be tra nsferre d t o 
a n ot her l ocati o n or p art y wit h o ut writte n n otificati o n t o Ale xi o n. Cli nical st u d y 
d oc u me nts a n d rec or ds r e q uire d as p art of t he T M F are arc hi ve d a n d st ore d b y 
Ale xi o n f or at least 3 0 years. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 1 4  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 1. 8.  
S o urce D oc u m e nts  
S o urce d oc u me nts pr o vi d e e vi de nce f or t h e e xiste n ce of t he p artici pa nt a n d s u bsta ntiate t he 
i nte grit y of t he data c ollecte d. T he I n v esti gat or or desi g nee will pre p are a n d mai ntai n a de q uate 
a n d acc urate s o urce d o c u me nts (e g, me dical rec or ds, E C Gs, A E a n d c o nc o mita nt me dicati o n 
re p orti n g, ra w data c ollecti o n f or ms) desi g ne d t o rec or d all o bser vati o ns a n d ot her perti ne nt dat a 
f or eac h partici p a nt. 
Data re p orte d o n t he e C R F t hat ar e tra nscri be d fr o m s o urce d oc u me nts m ust be c o nsiste nt wit h 
t he s o urce d o c u me nts or t he discre pa n cies m ust be e x plai ne d. T h ese e C R Fs m ust be c o m plete d 
b y t he I n vesti gat or or d esi g nee as i n dicate d i n t he site dele gati o n l o g.  T he I n vesti gat or ma y nee d 
t o re q uest pre vi o us me di cal rec or ds or tra nsfer rec or ds, de pe n di n g o n t he st u d y. Als o, c urre nt 
me dical rec or ds m ust be a vaila ble t o Ale xi o n, Ale xi o n dele gates, a n d h ealt h a ut h orities, as 
re q ueste d. S o ur ce d oc u m e nts are file d at the i n vesti gati o nal site.  
Per I C H E 6 ( R 2) g ui deli nes a n d g o o d d oc u me ntati o n practice re q uire m e nts, s o urce d oc u m e nts 
a n d st u d y rec or ds i n all me dia (e g, pa p er, electr o nic) m ust be Attri b uta ble, Le gi ble, 
C o nte m p ora ne o us, Ori gi nal, Acc ur ate, a n d C o m plete.  
1 0. 1. 9.  
St u d y a n d Site St art a n d Cl os ure  
St u d y St art  
T he st u d y start date is t he date o n w hic h t h e cli nical st u d y will be o pe n f or recr uit me nt of 
partici pa nts.  
T he first act of recr uit me nt is t he first site acti vati o n a n d will be t he st u d y start date.  
Ale xi o n reser ves t he ri g ht t o cl ose t he st u d y site or ter mi nate t he st u d y at a n y ti me f or a n y reas o n 
at its s ole discreti o n. St u d y sites will be cl ose d aft er t he st u d y is c o m plete d or f oll o wi n g t he 
decisi o n t o cl ose or ter mi nate t he st u d y. A st u d y site is c o nsi dere d cl os e d w he n all partici pa nts 
ha ve c o m plete d t h e E n d of St u d y or E D Visit, all data ha ve b ee n c ollecte d a n d e ntere d i nt o t he 
electr o nic d ata ca pt ure ( E D C) s yste m, all re q uire d d oc u me nts a n d st u d y s u p plies ha ve bee n 
c ollecte d a n d rec o n cile d, a n d a  st u d y site cl os ure visit has bee n perf or me d. 
T he I n vesti gat or m ust i nitiate st u d y site cl os ure if t here is reas o na ble ca use; s ufficie nt n otice 
m ust be gi ve n i n a d va nce of t he i nte n de d ter mi nati o n.  
Reas o ns f or t he earl y cl os ure of a st u d y site b y Al e xi o n or I n vesti gat or i ncl u de b ut are n ot 
li mite d t o: 
•  Fail ure of t he I n vesti gat or t o c o m pl y wit h t he pr ot oc ol, t he re q uire me nts of t he 
I R B/I E C or l ocal h ealt h a ut h orities, Ale xi o n’s pr oce d ures, or I C H G C P g ui deli nes 
•  I n a de q uat e recr uit me nt of partici pa nts b y t he I n v esti gat or 
•  Disc o nti n uati o n of f urt her st u d y i nter ve nti o n de vel o p me nt  
•  Wit h dra wal of t h e l ocal et hics c o m mittee/ healt h a ut h orit y fa v ora ble o pi ni o n or 
a p pr o val  
If t he st u d y is pre mat ur el y ter mi nate d or s us pe n d e d, Ale xi o n s hall pr o m ptl y i nf or m t he 
I n v esti gat ors, t he I E Cs/I R Bs, t he re g ulat or y a ut h orities, a n d a n y c o ntract researc h 
or ga nizati o n(s) us e d i n t he st u d y of t he reas o n f or t er mi nati o n or s us pe nsi o n, as s pe cifie d b y t he 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 1 5  of 1 5 2  
Ale xi o n C o nfi de ntial  
a p plica ble r e g ulat or y r e q uire me nts. T he I n v esti gat or s hall pr o m ptl y i nf or m t he partici pa nt a n d 
s h o ul d ass ure a p pr o priate partici pa nt t hera p y a n d/ or f oll o w-u p.  
1 0. 1. 1 0.  
P u blic ati o n P olic y  
•  W here p ossi ble, pri mar y ma n uscri pts re p orti n g res ults of t he pri mar y efficac y 
e n d p oi nt or t he fi nal res ults will be s u b mitte d f or p u blicati o n wit hi n 1 2 t o 1 8  m o nt hs 
of t he pri mar y e v al uati o n date or e n d of st u d y, w hic he ver is earlier.  
•  I n v esti gat ors w h o partici pate as a ut h ors i n ma n us cri pts deri ve d fr o m 
Ale xi o n -s p o ns ore d st u di es will a gree t o t he prere q uisites as o utli ne d i n t he Ale xi o n 
a ut h or e n ga g e me nt a gr ee me nt pri or t o e n ga gi n g i n ma n uscri pt de vel o p me nt.  
•  T he I n vesti gat or a grees t o s u b mit pr o p osals f or ne w ma n uscri pts ( w het h er or n ot t he 
pr o p ose d a nal ys es ar e deri ve d fr o m pr ot oc ol -s p ecifie d e n d p oi nts) t o Ale xi o n f or 
re vie w a n d c o nsi der ati o n. All ma n uscri pts or a bstracts e ma nati n g fr o m a p pr o ve d 
pr o p osals are  t o b e s u b mitte d t o Ale xi o n f or re vie w bef ore s u b missi o n t o t he 
j o ur nal/s ociet y. T his all o ws Ale xi o n t o pr otect pr o prietar y i nf or m ati o n a n d pr o vi de 
c o m me nts.  
− T he pr o prietar y nat ur e of s o me de vel o p me nt w or k ma y precl u de p u blicati o n. I n 
s o me cases, it ma y be n ecessar y t o del a y a p u blicati o n t o all o w Ale xi o n t o e ns ure 
pr otecti o n of i ntellect ual pr o pert y.  
•  Pri mar y p u blicati o ns, i ncl u di n g c o n gress a n d j o ur nal p u blicati o ns, c o ntai ni n g t he 
pr ot oc ol -s pecifi e d res ults of a st u d y s h o ul d occ ur pri or t o t he p u blicati o n of 
i n di vi d ual st u d y site res ults or case re p orts. Ale xi o n’s p olic y pr o hi bits d u plicate 
p u blicati o n , w here b y t he sa me res ults m ust n ot be p u blis he d i n m ulti ple 
peer -re vie w e d j o ur nal m a n uscri pts. 
− E nc ore c o n gress p u blicati o ns ma y be a p pr o priat e t o all o w c o m m u nicati o n of 
researc h fi n di n gs t o rel e v a nt a u die nce a n d ge o gra p hical re gi o ns. 
•  Ale xi o n will c o m pl y wit h t he re q uire m e nts f or p u blicati o n of st u d y res ults as defi ne d 
b y t he P har mace utical Researc h a n d Ma n ufact urers of A merica a n d t he I nter nati o nal 
C o m mittee of Me dical J o ur nal E dit ors a n d per t h e Ale xi o n P u blicati o n P olic y. I n 
acc or d a n ce wit h sta n dar d e dit orial a n d et hical practice, Ale xi o n will ge nerall y 
s u p p ort p u blicati o n of m ultice nter st u dies o nl y i n t heir e ntiret y a n d n ot as i n di vi d ual 
site data. I n t his case, a C o or di nati n g I n v esti gat or will be desi g nate d b y m ut ual 
a gree m e nt.  
•  A ut h ors hi p will be deter mi ne d b y m ut ual a gree m e nt a n d i n li ne wit h I nt er nati o nal 
C o m mittee of Me dical J o ur nal E dit ors a ut h ors hi p re q uire me nts a n d p er t he Ale xi o n 
P u blicati o n P olic y.  
•  Ale xi o n will p u blis h Patie nt La y S u m maries a n d i ncl u de partici pa nts a n d/ or 
care gi v ers as r e vie w ers f or rea d a bilit y a n d u n dersta n di n g of la y pers o n la n g ua ge.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 1 6  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 1. 1 1.  
G o o d Cli nic al Pr actice C o m pli a nce  
Ale xi o n a n d a n y t hir d part y t o w h o m as pects of t h e st u d y ma na ge me nt or m o nit ori n g ha ve bee n 
dele gate d will u n dert a ke t heir assi g ne d r oles f or t his st u d y i n c o m plia nce wit h all a p plica ble 
i n d ustr y re g ulati o ns, I C H G C P G ui deli ne E 6 R 2, E U Directi ve 2 0 0 1/ 2 0/ E C, as well as all 
a p plica ble nati o nal a n d l ocal la ws a n d re g ulati o ns.  
Visits t o sites are c o n d ucte d b y re pr ese ntati ves of Ale xi o n a n d/ or t he c o m p a n y 
or ga nizi n g/ ma na gi n g t he researc h o n be h alf of Ale xi o n t o i ns pect st u d y data, partici pa nts’ 
me dical rec or ds, a n d e C R Fs i n acc or da nce wit h c urre nt G C P a n d res p ecti v e l ocal a n d 
(i nter) nati o nal g o ver n me nt re g ulati o ns a n d g ui deli nes. Rec or ds a n d d ata ma y a d diti o nall y be 
re vie we d b y a u dit ors or b y re g ulat or y a ut h orities. 
Ale xi o n e ns ures t hat l ocal re g ulat or y a ut h orit y re q uire me nts are m et bef ore t he start of t he st u d y. 
Ale xi o n ( or desi g nee) is r es p o nsi ble f or t he pre parati o n, s u b missi o n, a n d c o nfir mati o n of recei pt 
of a n y re g ul at or y a ut h orit y a p pr o vals re q uire d pri or t o re leas e of st u d y i nter ve nti o n f or s hi p me nt 
t o t he site. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 1 7  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 2.  
Cli nic al L a b or at or y Tests  
•  T he tests detaile d i n  Ta bl e  1 3 will be perf or me d b y t he ce ntral la b orat or y or 
desi g nate d a ncillar y la b orat ories, u nless ot her wise n ote d. 
•  Pr ot oc ol-s pecific r e q uire me nts f or i ncl usi o n or e x cl usi o n of partici pa nts are detaile d 
i n Secti o n 5 . 
•  A d diti o nal tests ma y be perf or me d at a n y ti me d uri n g t he st u d y as deter mi ne d 
necessar y b y t he I n v esti gat or or re q uire d b y l ocal re g ulati o ns. 
•  Pre g na nc y testi n g: W O C B P s h o ul d o nl y be e nr olle d after a ne g ati ve ser u m pre g na nc y 
test res ult at Scree ni n g. S er u m pre g n a nc y tests s h o ul d als o be d o ne if t here is a n E D 
Visit a n d at t he Safet y F oll o w - u p Visit. A d diti o nal uri ne pre g n a nc y testi n g will be 
sta ndar d f or t h e pr ot oc ol u nless ser u m testi n g is re q uire d b y site p olicies, l ocal 
re g ulati o n, or I R B/I E C a n d s h o ul d be perf or m e d per t he ti me p oi nts s pecifie d i n t he 
S o A ( Secti o n  1. 3 ). 
•  I n v esti gat ors m ust d oc u me nt t heir re vie w of eac h la b orat or y safet y re p ort. Cli nicall y 
si g nifica nt fi n di n gs res ulti n g i n a n assess me nt of a T E A E s h o ul d be rec or de d o n t he 
A E e C R F.  
•  La b orat or y/a n al yte res ults t hat c o ul d u n bli n d t he st u d y will n ot be re p orte d t o 
i n vesti gati o nal sites or ot her bli n de d pers o n n el u ntil t he st u d y has bee n u n bli n de d. 
T a ble 1 3:  
Pr ot oc ol- re q uire d L a b or at or y Ass ess me nts  
L a b or at or y 
Assess me nts  
P ar a meters  
Cli nical c he mistr y  
•  Li ver f u ncti o n tests:  
o  A L T  
o  A S T  
o  A L P  
o  Al b u mi n 
o  T otal pr otei n  
o  Bilir u bi n (t otal, direct a n d i n direct) 
o  G G T  
o  Gl uc ose 
•  Re nal f u ncti o n tests:  
o  Bl o o d urea nitr o ge n 
o  Calci u m  
o  C hl ori de 
o  Creati ni ne a n d e G F R calc ulate d usi n g C K D -E PI f or m ula  
o  Ma g nesi u m  
o  P h os p hate 
o  P otassi u m  
o  S o di u m 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 1 8  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble  1 3 : 
Pr ot oc ol -re q uire d L a b or at or y Ass ess me nts  
L a b or at or y 
Assess me nts  
P ar a meters  
o  T otal car b o n di o xi de  
o  Creati ni ne ki nase  
o  Uric aci d  
•  Gl ycate d he m o gl o bi n ( H b A 1c)  
He mat ol o g y  
•  Re d bl o o d cell c o u nt  
•  He m o gl o bi n  
•  He mat ocrit  
•  Er yt hr oc ytes  
•  R B C i n dices 
o  Mea n c or p usc ular v ol u me  
o  Mea n c or p usc ular he m o gl o bi n  
o  Perce nta ge of retic ul oc ytes  
o  Mea n c or p usc ular he m o gl o bi n c o nce ntrati o n  
•  W hite bl o o d cell c o u nt wit h differe ntial (i ncl u di n g earl y pr o ge nit ors):  
o  Ne utr o p hils, se g me nte d  
o  L y m p h oc ytes  
o  M o n oc ytes  
o  E osi n o p hils  
o  Bas o p hils  
•  Platelet c o u nt  
•  Mea n platelet v ol u me  
C oa g ulati o n pa nel  
•  I N R 
•  P T  
•  A P T T  
•  D -Di mer  
•  Fi bri n o ge n  
Li pi d pr ofile  
•  C h olester ol/ H D L rati o  
•  Hi g h -de nsit y li p o pr otei n c h olester ol  
•  L o w -de nsit y li p o pr otei n c h olester ol  
•  N o n -H D L c h olester ol  
•  T otal c h olester ol 
•  Tri gl yceri des  
•  Ver y l o w -de nsit y li p o pr otei n c h olester ol  
2 4 -h uri ne  
•  T otal pr otei n, t otal creati ni ne, t otal al b u mi n, t otal s o di u m, creati ni ne 
cleara nce, pr otei n t o creati ni ne rati o, a n d al b u mi n t o creati ni ne rati o  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 1 9  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble  1 3 : 
Pr ot oc ol -re q uire d L a b or at or y Ass ess me nts  
L a b or at or y 
Assess me nts  
P ar a meters  
S p ot uri ne st u dies  
•  Pr otei n, al b u mi n, creati ni ne, a n d pr otei n t o creati ni ne a n d al b u mi n t o 
creati ni ne rati os 
R o uti ne uri nal ysis  
a n d uri ne se di me nt 
•  Al b u mi n  
•  Bilir u bi n  
•  Bl o o d  
•  Er yt hr oc ytes  
•  Gl uc ose  
•  Ket o nes  
•  Le u k oc yte esterase  
•  Nitrite  
•  p H  
•  Pr otei n  
•  S pecific gra vit y  
•  Ur o bili n o ge n  
•  Uri ne se di me nt: n u m ber of R B Cs/ hi g h-p o wer fiel d a n d n u m ber of R B C 
casts a 
Cli nical c o m ple me nt 
tests 
Ser u m sa m ples will i ncl u de, b ut are n ot li mite d t o, assess me nts of t he f oll o wi n g:  
C 3, C 4, F D, a n d C H 5 0  
P K/ P D  
•  Plas ma P K  
•  P D (ser u m A P acti vit y a n d plas ma B b c o nce ntrati o n)  
E x pl orat or y Bi o mar kers   E x pl orat or y bl o o d sa m ples ma y i ncl u de, b ut are n ot li mite d t o, assess me nts of 
t he f oll o wi n g: 
•  
C o m ple me nt pat h wa y d ysre g ulati o n (e g, s ol u ble C 5 b -9 [s C 5 b -9], 
Fact or Ba)  
E x pl orat or y uri ne bi o mar kers ma y i ncl u de, b ut are n ot li mite d t o, assess me nts 
of t he f oll o wi n g:  
•  
C o m ple me nt pat h wa y d ysre g ulati o n (e g, s C 5 b -9, Fact or  Ba)  
•  
Re nal i nj ur y bi o mar kers (e g, N -G A L, KI M -1)  
•  
Uri nar y creati ni ne  
Ki d ne y bi o ps y tiss ue e x pl orat or y bi o mar kers:  
•  
U nstai ne d ki d ne y tiss ue micr osc o p y sli des ( u p t o 8) will be stai ne d f or 
t he prese nce of bi o mar kers w hic h ma y i ncl u de, b ut are n ot li mite d t o, 
cli nical e vi de nce of t he disease pat h o p h ysi ol o g y a n d/ or res p o nse t o 
treat me nt (e g, C 5 b-9, C 3c, C 4 d, C D 6 8, pr o per di n). T he u nstai ne d 
sli de(s) ma y als o be use d f or pr ote o mic pr ofili n g. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 2 0  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble 1 3:  
Pr ot oc ol- re q uire d L a b or at or y Ass ess me nts  
L a b or at or y 
Assess me nts  
P ar a meters  
Ot her st u d y s pecific 
tests 
•  H C V P C R viral l oa d, H B V a nti ge n, a n d ser ol o g y pa nel 
•  HI V - 1 a n d HI V- 2 a nti b o d y 
•  Ser u m f ollicle sti m ulati n g h or m o ne (as nee de d i n w o me n of n o nc hil d beari n g 
p ote ntial o nl y)  
•  Ser u m or uri ne h u ma n c h ori o nic g o na d otr o pi n pre g na nc y test (as nee de d f or 
W O C B P)
b 
•  Ser u m a ut oa nti b o dies f or L N e g, A N A, a nti- ds D N A, a nti -S m, a nti -R N P, 
a nti- R o, a nti-La, a nti -C 1 q, a nti - p h os p h oli pi d a nti b o dies ( L N c o h ort o nl y) 
a F or partici pa nts i n t he I g A N c o h ort, eli gi bilit y f or he mat uria ca n be deter mi ne d via t he l ocal la b orat or y.  
b Ser u m pre g na nc y test re q uire d at Scree ni n g, E D a n d Safet y F oll o w -u p Visits; l ocal uri ne pre g na nc y test at all 
ot her ti mes as s pecifie d i n Sc he d ule of Acti vities ( Secti o n  1. 3 ). 
A b bre viati o ns: A L P  = al kali ne p h os p hatase; A L T  = ala ni ne a mi n otra nsferase; A N A  = a nti n uclear a nti b o dies; 
A P  = alter nati ve pat h wa y; 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 b  = B b fra g me nt of c o m ple me nt fact or  B; C 1 q, C 3, C 3c, C 4, C 4 d  = c o m ple me nt c o m p o ne nts  1 q, 3, 3c, 4, 4 d; 
C 5 b - 9 = ter mi nal c o m ple me nt c o m ple x; C D 6 8 = cl uster of differe ntiati o n  6 8; C H 5 0  = 5 0 % he m ol ytic c o m ple me nt 
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; ds D N A  = d o u ble -stra n de d D N A; 
E D  = earl y disc o nti n uati o n; e G F R = esti mate d gl o mer ular filtrati o n rate; F D  = c o m ple me nt fact or  D; 
G G T  = ga m ma -gl uta m yltra nsferase; H B V  = he patitis  B vir us ; H C V = he patitis  C vir us ; H D L = hi g h -de nsit y 
li p o pr otei n; 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; 
K 2 -E D T A  = di p otassi u m et h yle ne dia mi netetraacetic aci d; L N  = l u p us ne p hritis; P C R  = p ol y merase c hai n 
reacti o n; P D = p har mac o d y na mic(s); P K  = p har mac o ki netic(s); P T  = pr ot hr o m bi n ti me; R B C  = re d bl o o d cell; 
s C 5 b- 9 = s ol u ble C 5 b-9; W O C B P  = w o me n of c hil d beari n g p ote ntial  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 2 1  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 3.  
A d verse E ve nts: Defi niti o ns a n d Pr oce d ures f or Rec or di n g, 
E v al u ati n g, F oll o w -u p, a n d Re p orti n g  
1 0. 3. 1.  
Defi niti o n of A E  
A E Defi niti o n  
•  
A n A E is a n y u nt o war d me dical occ urre nce i n a partici pa nt or cli nical i n vesti gati o n partici pa nt 
a d mi nistere d a p har mace utical pr o d uct a n d w hic h d oes n ot necessaril y ha ve t o ha ve a ca usal 
relati o ns hi p wit h t his treat me nt (I C H E 2 A).  
•  
N ote : A n A E ca n t heref ore be a n y u nfa v ora ble a n d u ni nte n de d si g n (i ncl u di n g a n a b n or mal 
la b orat or y fi n di n g), s y m pt o m, or disease [ ne w or e xacer bate d] te m p orall y ass ociate d wit h t he use 
of t he st u d y i nter ve nti o n, w het her or n ot c o nsi dere d relate d t o t he st u d y i nter ve nti o n.  
 
E ve nts Meeti n g  t he A E Defi niti o n  
•  
A n y a b n or mal la b orat or y test res ults ( he mat ol o g y, cli nical c he mistr y, or uri nal ysis) or ot her safet y 
assess me nts (e g, E C G, ra di ol o gical sca ns, vital si g ns meas ure me nts), i ncl u di n g t h ose t hat w orse n 
fr o m baseli ne, c o nsi dere d cli nicall y si g nifica nt i n t he medical a n d scie ntific j u d g me nt of t he 
I n vesti gat or (ie, n ot relate d t o pr o gressi o n of u n derl yi n g disease). 
•  
E xacer bati o n of a c hr o nic or i nter mitte nt pre -e xisti n g c o n diti o n i ncl u di n g eit her a n i ncrease i n 
fre q ue nc y a n d/ or i nte nsit y of t he c o n diti o n. 
•  
Ne w c o n diti o ns detecte d or dia g n ose d after st u d y i nter ve nti o n a d mi nistrati o n e ve n t h o u g h it ma y 
ha ve bee n prese nt bef ore t he start of t he st u d y.  
•  
Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d dr u g -dr u g i nteracti o n.  
•  
Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d o ver d ose of eit her st u d y i nter ve nti o n or a 
c o nc o mita nt me dicati o n. O ver d ose per se will n ot be re p orte d as a n A E/ S A E u nless it is a n 
i nte nti o nal o ver d ose ta ke n wit h p ossi ble s uici dal/self-har mi n g i nt e nt. S uc h o ver d oses s h o ul d be 
re p orte d re gar dless of se q uelae. 
 
E ve nts N ot  Meeti n g t he A E Defi niti o n  
•  
Me dical or s ur gical pr oce d ure (e g, e n d osc o p y, a p pe n dect o m y): T he c o n diti o n t hat lea ds t o t he 
pr oce d ure is t he A E. Sit uati o ns i n w hic h a n u nt o war d me dical occ urre nce di d n ot occ ur (e g, 
h os pitalizati o n f or electi ve s ur ger y if pla n ne d bef ore si g ni n g t he I C F, a d missi o ns f or s ocial reas o ns 
or f or c o n ve nie nce).  
•  
A ntici pate d da y -t o-da y fl uct uati o ns of pre -e xisti n g disease(s) or c o n diti o n(s) prese nt or detecte d at 
t he start of t he st u d y t hat d o n ot w orse n. 
•  
A me dicati o n err or (i ncl u di n g i nte nti o nal mis use, a b use, a n d o ver d ose of t he pr o d uct) or use ot her 
t ha n w hat is defi ne d i n t he pr ot oc ol is n ot c o nsi dere d a n A E u nless t here is a n u nt o war d me dical 
occ urre nce as a res ult of a me dicati o n err or.  
•  
Cases of pre g na nc y t hat occ ur d uri n g mater nal or pater nal e x p os ure t o st u d y i nter ve nti o n are t o be 
re p orte d wit hi n 2 4 h o urs of I n vesti gat or/site a ware ness. Data o n fetal o utc o me a n d breastfee di n g 
will be c ollecte d f or re g ulat or y re p orti n g a n d safet y e val uati o n.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 2 2  of 1 5 2  
Ale xi o n C o nfi de ntial  
E ve nts N ot  Meeti n g t he A E Defi niti o n  
•  
A n y cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs or ot her a b n or mal safet y assess me nts w hic h 
are ass ociate d wit h t he u n derl yi n g disease, u nless j u d ge d b y t he I n vesti gat or t o be m ore se vere t ha n 
e x pecte d f or t he partici pa nt’s c o n diti o n.  
•  
T he disease/ dis or der bei n g st u die d or e x pecte d pr o gressi o n, si g ns, or s y m pt o ms of t he 
disease/ dis or der bei n g st u die d, u nless m ore se vere t ha n e x pecte d f or t he partici pa nt’s c o n diti o n.  
•  
Sit uati o ns i n w hic h a n u nt o war d me dical occ urre nce di d n ot occ ur (s ocial a n d/ or c o n ve nie nce 
a d missi o n t o a h os pital). 
•  
“ Lac k of efficac y” or “fail ure of e x pecte d p har mac ol o gical acti o n” per se will n ot be re p orte d as a n 
A E or S A E. S uc h i nsta nces will be ca pt ure d i n t he efficac y assess me nts. H o we ver, t he si g ns, 
s y m pt o ms, a n d/ or cli nical se q uelae res ulti n g fr o m lac k of efficac y will be re p orte d as A E or S A E if 
t he y f ulfill t he defi niti o n of a n A E or S A E. 
1 0. 3. 2.  
Defi niti o n of S A E  
If a n e v e nt is n ot a n A E per defi niti o n a b o ve, t h e n it ca n n ot be a n S A E e v e n if seri o us c o n diti o ns 
are met ( e g, h os pitalizati o n f or si g ns/s y m pt o ms of t he disease u n der st u d y, deat h d ue t o 
pr o gressi o n of diseas e).  
A n S A E is defi ne d as a n y u nt o w ar d me dic al occ urre nce t h at, at a n y d ose:  
1.  Res ults i n de at h  
2.  Is life-t hre ate ni n g 
T he ter m “life -t hreate ni n g” i n t he defi niti o n of “seri o us” refers t o a n e ve nt i n w hic h t he partici pa nt was 
at ris k of deat h at t he ti me of t he e ve nt. It d oes n ot refer t o a n e ve nt, w hic h h y p ot heticall y mi g ht ha ve 
ca use d deat h, if it was m ore se vere.  
3.  Re q uires i n p atie nt h os pit aliz ati o n or pr ol o n g ati o n of e xisti n g h os pit aliz ati o n  
I n ge neral, h os pitalizati o n si g nifies t hat t he partici pa nt has bee n detai ne d ( us uall y i n v ol vi n g at least a n 
o ver ni g ht sta y) at t he h os pital or e mer ge nc y war d f or o bser vati o n a n d/ or treat me nt t hat w o ul d n ot ha ve 
bee n a p pr o priate i n t he p h ysicia n’s office or  o ut patie nt setti n g. C o m plicati o ns t hat occ ur d uri n g 
h os pitalizati o n are A Es. If a c o m plicati o n pr ol o n gs h os pitalizati o n or f ulfills a n y ot her seri o us criteria, 
t he e ve nt is seri o us. W he n i n d o u bt as t o w het her “ h os pitalizati o n” occ urre d or was necessar y, t he A E 
s h o ul d be c o nsi dere d seri o us. 
H os pitalizati o n f or electi ve treat me nt of a pre -e xisti n g c o n diti o n t hat di d n ot w orse n fr o m baseli ne is 
n ot c o nsi dere d a n A E.  
4.  Res ults i n persiste nt dis a bilit y/i nc a p acit y  
•  
T he ter m disa bilit y mea ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit y t o c o n d uct n or mal life 
f u ncti o ns. 
•  
T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie nces of relati vel y mi n or me dical si g nifica nce s uc h 
as u nc o m plicate d hea dac he, na usea, v o miti n g, diarr hea, i nfl ue nza, a n d acci de ntal tra u ma (e g, 
s prai ne d a n kle) w hic h ma y i nterfere wit h or pre ve nt e ver y da y life f u ncti o ns b ut d o n ot c o nstit ute a 
s u bsta ntial disr u pti o n. 
5.  Is a c o n ge nit al a n o m al y/ birt h defect 
6.  Ot her sit u ati o ns:  
•  
Me dical or scie ntific j u d g me nt s h o ul d be e xercise d i n deci di n g w het her S A E re p orti n g is 
a p pr o priate i n ot her sit uati o ns s uc h as i m p orta nt me dical e ve nts t hat ma y n ot be i m me diatel y 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 2 3  of 1 5 2  
Ale xi o n C o nfi de ntial  
A n S A E is defi ne d as a n y u nt o w ar d me dic al occ urre nce t h at, at a n y d ose:  
life-t hreate ni n g or res ult i n deat h or h os pitalizati o n b ut ma y je o par dize t he partici pa nt or ma y 
re q uire me dical or s ur gical i nter ve nti o n t o pre ve nt o ne of t he ot her o utc o mes liste d i n t he a b o ve 
defi niti o n. T hese e ve nts s h o ul d us uall y be c o nsi dere d seri o us . 
•  
E xa m ples of s uc h e ve nts i ncl u de i n vasi ve or mali g na nt ca ncers, i nte nsi ve treat me nt i n a n 
e mer ge nc y r o o m or at h o me f or aller gic br o nc h os pas m, bl o o d d yscrasias or c o n v ulsi o ns t hat d o 
n ot res ult i n h os pitalizati o n, or de vel o p me nt of dr u g de pe n de nc y or dr u g a b use.  
 
A s us pecte d u ne x pecte d seri o us a d verse re acti o n ( S U S A R) is defi ne d as: 
A n e ve nt t hat is assesse d as seri o us b y t he I n vesti gat or a n d/ or Ale xi o n t hat is n ot liste d i n t he 
a p pr o priate Refere nce Safet y I nf or mati o n (I B) a n d has bee n assesse d t hat t here is at least a reas o na ble 
p ossi bilit y t hat t he e ve nt is relate d t o t he i n vesti ga ti o nal me dici nal pr o d uct b y t he I n vesti gat or a n d/ or 
Ale xi o n.  
Ale xi o n has pr oce d ures t hat will be f oll o we d f or t he rec or di n g, me dical assess me nt, a n d e x pe dite d 
re p orti n g of S U S A Rs t hat are c o nsiste nt wit h gl o bal re g ulati o ns, le gislati o n, a n d g ui da nce d oc u me nts. 
 
S us pecte d u ne x pecte d seri o us a d verse reacti o ns will u n der g o e x pe dite d re p orti n g t o t he nati o nal 
re g ulat or y a ut h orities, I R Bs/I E Cs, a n d I n vesti gat ors f oll o wi n g l ocal re g ulat or y re p orti n g re q uire me nts 
w here a p plica ble.  
1 0. 3. 3.  
Rec or di n g a n d F oll o w -U p of A E a n d/ or S A E  
Rec or di n g of A E a n d/ or S A E  
•  
W he n a n A E/ S A E occ urs, it is t he res p o nsi bilit y of t he I n vesti gat or t o re vie w all d oc u me ntati o n 
(e g, h os pital pr o gress n otes, la b orat or y re p orts, a n d dia g n ostics re p orts) relate d t o t he e ve nt. 
•  
T he I n vesti gat or will t he n rec or d all rele va nt A E/ S A E i nf or mati o n i n t he e C R F.  
•  
It is n ot acce pta ble f or t he I n vesti gat or t o se n d p h ot oc o pies of t he partici pa nt’s me dical rec or ds t o 
Ale xi o n i n lie u of c o m pleti o n of t he Ale xi o n A E/ S A E e C R F pa ge.  
•  
T here ma y be i nsta nces w he n c o pies of me dical rec or ds f or certai n cases are re q ueste d b y 
Ale xi o n. I n t his case, all partici pa nt i de ntifiers, wit h t he e xce pti o n of t he partici pa nt n u m ber, will 
be re dacte d o n t he c o pies of t he me dical rec or ds bef ore s u b missi o n t o Ale xi o n.  
•  
T he I n vesti gat or will atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, s y m pt o ms, 
a n d/ or ot her cli nical i nf or mati o n. W he ne ver p ossi ble, t he dia g n osis ( n ot t he i n di vi d ual 
si g ns/s y m pt o ms) will be d oc u me nte d as t he A E/ S A E. 
Assess me nt of I nte nsit y 
T he I n vesti gat or will ma ke a n assess me nt of i nte nsit y f or eac h A E a n d S A E re p orte d d uri n g t he st u d y 
a n d assi g n it t o o ne of t he f oll o wi n g cate g ories fr o m Nati o nal Ca ncer I nstit ute C T C A E v 5. 0, p u blis he d 
2 7  N o v  2 0 1 7:  
•  
Gra de  1: Mil d (a ware ness of si g n or s y m pt o m, b ut easil y t olerate d)  
•  
Gra de  2: M o derate ( disc o mf ort s ufficie nt t o ca use i nterfere nce wit h n or mal acti vities)  
•  
Gra de  3: Se vere (i nca pacitati n g, wit h i na bilit y t o perf or m n or mal acti vities)  
•  
Gra de  4: Life -t hreate ni n g 
•  
Gra de  5: Fatal  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 2 4  of 1 5 2  
Ale xi o n C o nfi de ntial  
Rec or di n g of A E a n d/ or S A E  
 
A n e ve nt is defi ne d as “seri o us” w he n it meets at least o ne of t he pre defi ne d o utc o mes as descri be d i n 
t he defi niti o n of a n S A E, n ot w he n it is rate d as se vere. 
 
Assess me nt of C a us alit y  
•  
T he I n vesti gat or is o bli gate d t o assess t he relati o ns hi p bet wee n t he st u d y i nter ve nti o n a n d eac h 
occ urre nce of eac h A E or S A E. A n I n vesti gat or ca usalit y assess me nt m ust be pr o vi de d f or all A Es 
( b ot h n o nseri o us a n d seri o us). T his assess me nt m ust be rec or de d i n t he e C R F a n d o n a n y 
a d diti o nal f or ms, as a p pr o priate. T he defi niti o ns f or t he ca usalit y assess me nts are as f oll o ws:  
− N ot relate d: T here is n o reas o na ble p ossi bilit y t he st u d y i nter ve nti o n ca use d t he A E.  
− T he A E has a m ore li kel y alter nati ve eti ol o g y; it ma y be d ue t o u n derl yi n g or 
c o nc urre nt ill ness, c o m plicati o ns, c o nc urre nt treat me nts, or effects of a n ot her 
c o nc urre nt dr u g. 
− T he e ve nt d oes n ot f oll o w a reas o na ble te m p oral relati o ns hi p t o a d mi nistrati o n 
of t he st u d y i nter ve nti o n.  
− Relate d: T here is a reas o na ble p ossi bilit y t he st u d y i nter ve nti o n ca use d t he A E.  
− T he A E has a te m p oral relati o ns hi p t o t he a d mi nistrati o n of t he st u d y 
i nter ve nti o n. 
− T he e ve nt d oes n ot ha ve a li kel y alter nati ve eti ol o g y.  
− T he e ve nt c orres p o n ds wit h t he k n o w n p har mace utical pr ofile of t he st u d y 
i nter ve nti o n. 
− T here is i m pr o ve me nt o n disc o nti n uati o n a n d/ or rea p peara nce o n rec halle n ge.  
•  
T he I n vesti gat or will use cli nical j u d g me nt t o deter mi ne t he relati o ns hi p.  
•  
Alter nati ve ca uses, s uc h as u n derl yi n g disease(s), c o nc o mita nt t hera p y, a n d ot her ris k fact ors, as 
well as t he te m p oral relati o ns hi p of t he e ve nt t o st u d y i nter ve nti o n a d mi nistrati o n will be 
c o nsi dere d a n d i n vesti gate d.  
•  
T he I n vesti gat or will als o c o ns ult t he I B a n d/ or Pr o d uct I nf or mati o n, f or mar kete d pr o d ucts, i n 
his/ her assess me nt.  
•  
F or eac h A E/ S A E, t he I n vesti gat or m ust  d oc u me nt i n t he me dical n otes t hat he/s he has re vie we d 
t he A E/ S A E a n d has pr o vi de d a n assess me nt of ca usalit y. 
•  
T here ma y be sit uati o ns i n w hic h a n S A E has occ urre d, a n d t he I n vesti gat or has mi ni mal 
i nf or mati o n t o i ncl u de i n t he i nitial re p ort t o Ale xi o n. H o we ver, it is ver y i m p orta nt t hat t he 
I n vesti gat or al wa ys ma ke a n assess me nt of ca usalit y f or e ver y e ve nt bef ore t he i nitial tra ns missi o n 
of t he S A E data t o Ale xi o n.  
•  
T he I n vesti gat or ma y c ha n ge his/ her o pi ni o n of ca usalit y i n li g ht of f oll o w -u p i nf or mati o n a n d 
se n d a n S A E f oll o w-u p re p ort wit h t he u p date d ca usalit y assess me nt.  
•  
T he ca usalit y assess me nt is o ne of t he criteria use d w he n deter mi ni n g re g ulat or y re p orti n g 
re q uire me nts. 
 
F oll o w -u p of A Es a n d S A Es  
•  
T he I n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d uct of s u p ple me ntal 
meas ure me nts a n d/ or e val uati o ns as me dicall y i n dicate d or as re q ueste d b y Ale xi o n t o el uci date 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 2 5  of 1 5 2  
Ale xi o n C o nfi de ntial  
F oll o w -u p of A Es a n d S A Es  
t he nat ure a n d/ or ca usalit y of t he A E or S A E as f ull y as p ossi ble. T his ma y i ncl u de a d diti o nal 
la b orat or y tests or i n vesti gati o ns, hist o pat h ol o gical e xa mi nati o ns, or c o ns ultati o n wit h ot her 
healt h care pr ofessi o nals.  
•  
If a partici pa nt dies d uri n g partici pati o n i n t he st u d y or d uri n g a rec o g nize d f oll o w-u p peri o d, t he 
I n vesti gat or will pr o vi de Ale xi o n wit h a c o p y of a n y p ost m orte m fi n di n gs i ncl u di n g 
hist o pat h ol o g y.  
•  
Ne w or u p date d i nf or mati o n will be rec or de d i n t he ori gi nall y c o m plete d e C R F.  
•  
T he I n vesti gat or will s u b mit a n y u p date d S A E data t o Ale xi o n wit hi n 2 4  h o urs of recei pt of t he 
i nf or mati o n. 
1 0. 3. 4.  
Re p orti n g of S A Es  
S A E Re p orti n g t o Ale xi o n vi a a n Electr o nic D at a C ollecti o n T o ol  
•  
All S A Es will be rec or de d a n d re p orte d t o Ale xi o n i m me diatel y a n d wit hi n 2 4  h o urs of 
a ware ness. 
•  
T he pri mar y mec ha nis m f or re p orti n g a n S A E t o Ale xi o n will be t he E D C s yste m.  
•  
If t he electr o nic s yste m is u na vaila ble or site staff is u na ble t o pr ocess t he S A E via t he E D C 
s yste m at t he ti me t hat t he I n vesti gat or or site bec o mes a ware of a n S A E, t he site will use t he 
pa per C o nti n ge nc y F or m f or S A E Re p orti n g via facsi mile or e mail. Facsi mi le tra ns missi o n or 
e mail ma y als o be use d i n t he e ve nt of electr o nic s u b missi o n fail ure.  
− E mail: cli nicalsae @ale xi o n.c o m or Fa x: + 1. 2 0 3. 4 3 9. 9 3 4 7  
•  
T he site will e nter t he S A E data i nt o t he E D C s yste m as s o o n as it bec o mes a vaila ble.  
•  
W he n f urt her i nf or mati o n bec o mes a vaila ble, t he E D C s h o ul d be u p date d i m me diatel y wit h t he 
ne w i nf or mati o n a n d a n u p date d S A E re p ort s h o ul d be s u b mitte d t o Ale xi o n G P S wit hi n 2 4  h o urs 
of I n vesti gat or/site a ware ness.  
•  
After t he partici pa nt has c o m plete d t he st u d y, n o ne w data or c ha n ges t o e xisti n g data are 
e x pecte d t o be e ntere d i n t he E D C s yste m.  
o  If a site recei ves a re p ort of a ne w S A E fr o m a st u d y partici pa nt w hic h t he I n vesti gat or 
c o nsi ders t o be relate d t o t he st u d y i nter ve nti o n, or t he site recei ves u p date d data o n a 
pre vi o usl y re p orte d S A E after t he E D C s yste m has bee n ta ke n offli ne, t he n t he  site ca n 
re p ort t his i nf or mati o n o n a pa per C o nti n ge nc y F or m f or S A E Re p orti n g via facsi mile 
or e mail.  
1 0. 3. 5.  
U ne x pecte d E ve nts  
A part fr o m t he re p orti n g of S U S A Rs, t here ma y b e ot her e v e nts w hic h are rele va nt i n ter ms of 
be nefit -ris k bal a nce a n d w hic h s h o ul d be re p orte d i n a ti mel y ma n ner acc or di n g t o re gi o nal a n d 
nati o nal re q uire m e nts, e g, E U C T R 5 3 6/ 2 0 1 4 ( 4 8). It is i m p orta nt f or  p artici pa nt safet y t hat, i n 
a d diti o n t o S A Es a n d reacti o ns, all u ne x pecte d e v e nts t hat mi g ht materiall y i nfl ue nce t he 
be nefit -ris k ass ess me nt of t he st u d y i nter ve nti o n or t hat w o ul d lea d t o c ha n ges i n t he 
a d mi nistrati o n of t he st u d y i nter ve nti o n or i n o ve rall c o n d uct of a cli nical trial s h o ul d be 
re p orte d. E x a m ples of s u c h u ne x pecte d e v e nts i ncl u de a n i ncrease i n t he rate of occ urre n ce of 
e x pecte d s eri o us a d verse reacti o ns w hic h m a y be cli nicall y i m p orta nt, a si g nifica nt hazar d t o t he 
patie nt p o p ulati o n, s uc h as lac k of efficac y of a m e dici nal pr o d uct, or a maj or safet y fi n di n g fr o m 
a ne wl y c o m plete d a ni mal st u d y (s uc h as, carci n o ge nicit y).  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 2 6  of 1 5 2  
Ale xi o n C o nfi de ntial  
U n der t he E U C T R 5 3 6/ 2 0 1 4 ( 4 9), w here u ne x p ecte d e ve nts re q uire a n ur ge nt m o dificati o n of a 
cli nical trial, it s h o ul d be p ossi ble f or Ale xi o n a n d t he I n v esti gat or t o ta ke ur ge nt safet y meas ures 
wit h o ut a waiti n g pri or a ut h orizati o n. If s uc h meas ures c o nstit ute a te m p orar y halt of t he cli nical 
trial, Ale xi o n s h o ul d a p pl y f or a s u bsta ntial m o dificati o n bef ore rest arti n g t he cli nical trial. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 2 7  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 4.  
Me dic ati o n Err or, Dr u g A b use, a n d Dr u g Mis use  
Me dic ati o n Err or  
F or t he p ur p os es of t his cli nical st u d y a me dicati o n err or is a n u ni nte n d e d fail ure or mista ke i n 
t he treat me nt pr ocess f or a n I M P or Ale xi o n A x M P t hat eit her ca uses h ar m t o t he partici pa nt or 
has t he p ote ntial t o ca use har m t o t he partici pa nt.  
A n y e ve nts of me dicati o n err or, wit h or wit h o ut ass ociate d A Es, are t o be ca pt ure d a n d 
f or war de d t o Ale xi o n G P S via e mail or facsi mile (cli nicalsae @al e xi o n.c o m or 
+ 1. 2 0 3. 4 3 9. 9 3 4 7) usi n g t he Ale xi o n Cli nical St u d y Me dicati o n Err or R e p ort F or m. 
A me dicati o n err or is n ot lac k of efficac y of t he st u d y i nter ve nti o n, b ut rat h er a h u ma n or pr ocess 
relate d f ail ure w hile t he i nter ve nti o n is u n der c o ntr ol of t he st u d y site staff or partici pa nt. 
Me dicati o n err or i ncl u des sit uati o ns w here a n err or:  
•  Occ urre d  
•  Was i de ntifie d a n d i nterce pte d bef ore t he p artici pa nt recei ve d t h e dr u g  
•  Di d n ot occ ur, b ut cir c u msta nces were rec o g nize d t hat c o ul d ha ve le d t o a n err or 
E xa m ples of e ve nts t o be re p orte d i n cli nical st u dies as me dicati o n err ors:  
•  Dr u g na me c o nf usi o n 
•  Dis pe nsi n g err or, e g, me dicati o n pre pare d i nc orrectl y, e ve n if it was n ot act uall y 
gi ve n t o t he partici pa nt 
•  Dr u g n ot a d mi nistere d as i n dicate d, e g, wr o n g r o ute or wr o n g site of a d mi nistrati o n 
•  Dr u g n ot ta ke n as i n dicate d, e g, ta blet diss ol ve d i n water w h e n it s h o ul d be ta ke n as a 
s oli d ta blet  
•  Dr u g n ot st ore d as i nstr u cte d, e g, ke pt i n t he refri gerat or w h e n it s h o ul d be at r o o m 
te m perat ur e  
•  Wr o n g partici p a nt recei v e d t he me dicati o n (e xcl u di n g I nteracti ve Res p o ns e 
Tec h n ol o g y [I R T]/ Ra n d o mizati o n a n d Trial S u p pl y Ma na ge me nt [ R T S M] err ors) 
•  Wr o n g dr u g a d mi nister e d t o partici pa nt (e x cl u di n g I R T/ R T S M err ors) 
E xa m ples of e ve nts t hat d o n ot  re q uire re p orti n g as me dicati o n err ors i n cli nical st u dies: 
•  Err ors r elate d t o or r es ulti n g fr o m I R T/ R T S M - i ncl u di n g t h ose w hic h le d t o o ne of 
t he a b o ve liste d e ve nts t h at w o ul d ot her wise ha v e bee n a me di cati o n err or  
•  Partici pa nt acci d e ntall y misse d dr u g d ose(s), e g, f or g ot t o ta ke me dicati o n 
•  Acci de ntal o v er d ose ( will be ca pt ure d as a n o v er d ose [refer t o Secti o n  6. 8  for 
i nf or mati o n o n treat me nt of o ver d ose]) 
•  Partici pa nt faile d t o ret ur n u n use d me dicati o n or e m pt y pac ka gi n g  
Me dicati o n err ors ar e n ot re gar d e d as A Es b ut A Es ma y occ ur as a c o ns e q u e nce of t h e 
me dicati o n err or.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 2 8  of 1 5 2  
Ale xi o n C o nfi de ntial  
Dr u g A b use  
F or t he p ur p os e of t his st u d y, dr u g a b use is defi n e d as t he persiste nt or s p ora dic i nte nti o nal, 
n o n -t hera p e utic e xcessi ve use of I M P or Al e xi o n A x M P f or a percei ve d re war d or d esire d 
n o n -t hera p e utic effect. 
A n y e ve nts of dr u g a b use, wit h or wit h o ut ass ociate d A Es, are t o be ca pt ure d a n d f or w ar de d t o 
Ale xi o n G P S via e mail or facsi mile ( cli nicalsae @ ale xi o n.c o m or +  1. 2 0 3. 4 3 9. 9 3 4 7) usi n g t he 
Ale xi o n Cli nical St u d y Dr u g Mis use or Dr u g A b us e Re p ort F or m. T his f or m s h o ul d be use d b ot h 
if t he dr u g a b use h a p pe n e d i n a st u d y partici pa nt or if t he dr u g a b us e i n v ol ves a pers o n n ot 
e nr olle d i n t he st u d y (s uc h as a rel ati ve of t he st u d y partici pa nt). 
E xa m ples of dr u g a b us e i ncl u de b ut are n ot li mite d t o:  
•  T he dr u g is use d wit h t he i nte nt of getti n g a percei ve d re w ar d ( b y t h e st u d y 
partici pa nt or a p ers o n n ot e nr olle d i n t he st u d y)  
•  T he dr u g i n t he f or m of a ta blet is cr us he d a n d i njecte d or s n orte d wit h t he i nte nt of 
getti n g hi g h  
Dr u g Mis use  
Dr u g mis use is t he i nte nti o nal a n d i na p pr o priat e use ( b y a st u d y partici p a nt) of I M P or Ale xi o n 
A x M P  f or me dici nal p ur p oses o utsi de of t he a ut h orize d pr o d u ct i nf or mati o n, or f or u na ut h ori ze d 
I M Ps or Ale xi o n A x M Ps, o utsi de t he i nte n de d use as s pecifie d i n t he pr ot oc ol, i ncl u di n g 
deli berate a d mi nistrati o n of t he pr o d uct b y t he wr o n g r o ute.  
E ve nts of dr u g mis use, wit h or wit h o ut ass ociate d A Es, are t o be ca pt ure d a n d f or war de d t o 
Ale xi o n G P S via e mail or facsi mile ( cli nicalsae @ ale xi o n.c o m or +  1. 2 0 3. 4 3 9. 9 3 4 7) usi n g t he 
Ale xi o n Cli nical St u d y Dr u g Mis use or Dr u g A b us e Re p ort F or m. T his f or m s h o ul d be use d b ot h 
if t he dr u g mis use ha p pe ne d i n a st u d y partici pa nt or if t he dr u g mis use i n v ol ves a pers o n n ot 
e nr olle d i n t he st u d y (s uc h as a rel ati ve o f t he st u d y partici pa nt). 
E xa m ples of dr u g mis use i ncl u de b ut are n ot li mite d t o:  
•  T he dr u g is use d wit h t he i nte nti o n t o ca use a n effect i n a n ot her p ers o n 
•  T he dr u g is s ol d t o ot her pe o ple f or recreati o nal p ur p oses  
•  T he dr u g is use d t o facilitate assa ult i n a n ot her p ers o n  
•  T he dr u g is deli ber atel y a d mi nistere d b y t he wr o n g r o ute  
•  T he dr u g is s plit i n half beca use it is easier t o s wall o w, w he n it is state d i n t he 
pr ot oc ol t hat it m ust be s wall o we d w h ole  
•  O nl y half t he d ose is ta ke n beca use t h e st u d y parti ci pa nt feels t hat h e/s he is feeli n g 
better w he n n ot ta ki n g t h e w h ole d ose  
•  S o me o ne w h o is n ot e nr olle d i n t he st u d y i nte nti o nall y ta kes t he dr u g  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 2 9  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 5.  
C o ntr ace pti ve G ui d a nce a n d C ollecti o n of Pre g n a nc y I nf or m ati o n  
1 0. 5. 1.  
Defi niti o ns  
W o m a n of C hil d be ari n g P ote nti al ( W O C B P)  
A w o ma n is c o nsi der e d f ertile f oll o wi n g me narc h e a n d u ntil bec o mi n g p ost me n o pa usal u nless 
per ma ne ntl y sterile (see bel o w).  
If fertilit y is u nclear (e g, a me n orr h ea i n a d oles ce nts or at hletes) a n d a me nstr ual c ycle ca n n ot be 
c o nfir me d bef ore first d ose of st u d y i nter ve nti o n, a d diti o nal e val uati o n s h o ul d be c o nsi dere d.  
W o m e n i n t he F oll o wi n g C ate g ories Are N ot C o nsi dere d W O C B P  
1.  Pre me nar c hal  
2.  Pre me n o pa usal f e male wit h o ne of t he f oll o wi n g:  
•  D oc u me nte d h yster ect o m y  
•  D oc u me nte d bilater al t u bal li gati o n or bilateral sal pi n gect o m y  
•  D oc u me nte d bilater al o o p h orect o m y  
F or i n di vi d uals wit h per ma ne nt i nfertilit y d ue t o a n alter nat e me dical ca us e ot her t ha n t he a b o ve, 
(e g, M ulleria n a g e nesis, a n dr o ge n i nse nsiti vit y), I n vesti gat or discreti o n s h o ul d be a p plie d t o 
deter mi ni n g st u d y e ntr y.  
N ote : D oc u m e ntati o n ca n c o me fr o m t he site pers o n nel’s re vie w of t he partici pa nt’s me dical 
rec or ds, me di cal e x a mi nati o n, or me dical hist or y i nter vie w. 
3.  P ost me n o pa usal fe male  
•  A p ost me n o pa usal state is defi ne d as n o me ns es f or 1 2  m o nt hs wit h o ut a n alter nati ve 
me dical ca us e pri or t o t h e Da y  1 Visit.  
− A hi g h F S H le vel i n t he p ost me n o pa usal ra n ge m a y be use d t o c o nfir m a 
p ost me n o pa usal state i n w o me n n ot usi n g h or m o nal c o ntrace pti o n or H R T. 
H o we ver, i n t he a bse n ce of 1 2  m o nt hs of a me n orr hea, c o nfir mati o n wit h m ore 
t ha n o ne F S H meas ure m e nt ma y be re q uire d. I n t he a bse nce of 1 2 m o nt hs of 
a me n orr h ea t he r eas o n f or n ot o btai ni n g F S H le vels s h o ul d be d oc u me nte d b y t he 
I n v esti gat or at t he ti me of Scree ni n g. 
•  Fe males o n H R T a n d w h ose me n o pa usal stat us is i n d o u bt will be re q uire d t o use o ne 
of t he n o n -estr o g e n h or m o nal hi g hl y effecti ve or acce pta bl e c o ntrace pti o n met h o ds if 
t he y wis h t o c o nti n ue t heir H R T d uri n g t he st u d y. Ot her wise, t he y m ust disc o nti n ue 
H R T t o all o w c o nfir mati o n of p ost me n o pa usal stat us bef ore st u d y e nr oll me nt.  
4.  Per ma ne nt sterilizati o n at least 6  wee ks pri or t o t he Da y  1 Visit.  
1 0. 5. 2.  
C o ntr ace pti o n G ui d a nce  
C o ntrace pti ve use b y mal e or fe m ale partici p a nts s h o ul d be c o nsiste nt wit h l ocal re g ulati o ns 
re gar di n g t he m et h o ds of c o ntrace pti o n utilize d f or t h ose partici pati n g i n cli nical st u dies. If 
terat o ge nic eff ects ar e s us pecte d t o be tra nsferre d t o a fet us/e m br y o fr o m a fe male s p o use/ part ner 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 3 0  of 1 5 2  
Ale xi o n C o nfi de ntial  
of a male partici pa nt, pre g na nc y f oll o w -u p i nf or mati o n will be o btai ne d f or t he part ner w h o 
bec o mes pr e g na nt (r efer t o Secti o n  1 0. 5. 3. 1 ). I n t h ese cas es, f oll o w-u p will be c o n d ucte d o n t h e 
pre g na nt part ner i n t he sa me ma n ner as a fe m ale p artici pa nt w h o bec o mes pre g na nt d uri n g t he 
st u d y. 
1 0. 5. 2. 1.  G ui d a nce f or Fe m ale P artici p a nts  
Fe male p artici pa nts of c hil d beari n g p ote ntial m ust ha ve a n e gati ve ser u m pre g na nc y t est as 
re q uire d b y l ocal re g ulati o ns at Scree ni n g a n d a ne gati ve uri ne pre g na nc y t est bef ore t he first 
d ose of st u d y i nter ve nti o n o n Da y  1. A d diti o nal re q uire me nts f or pre g na nc y testi n g d uri n g a n d 
after d osi n g wit h st u d y i nter ve nti o n ar e i n dicate d i n t he S o A ( Secti o n  1. 3 ). 
T he I n vesti gat or is r es p o nsi ble f or t he re vi e w of me dical hist or y, me nstr u al hist or y, a n d rece nt 
se x ual acti vit y t o decr eas e t he ris k f or i ncl usi o n of a w o ma n wit h a n earl y u n detecte d pre g na n c y.  
T he I n vesti gat or s h o ul d e val uate t he p ote ntial f or c o ntrace pti ve met h o d i n relati o ns hi p t o t he first 
d ose of st u d y i nter ve nti o n.  
Fe male p artici pa nts of c hil d beari n g p ote ntial m ust use a hi g hl y effecti ve or acce pta ble met h o ds 
of c o ntrace pti o n, i ncl u di n g at least 1 of t he f oll o wi n g u ntil at least 3 0 da ys after t he fi nal d ose of 
st u d y i nter ve nti o n. Hi g hl y effecti ve met h o ds are: 
1.  I ntr a uteri ne d e vice i n place f or at least 6 wee ks pri or t o first d ose of st u d y i nter ve nti o n.  
2.  Pr o gest o ge n -o nl y h or m o nal c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n (eit her 
oral, i njecta ble, or i m pla nta ble) f or at least 6  wee ks pri or t o first d ose of st u d y 
i nter ve nti o n. 
3.  I ntr a uteri ne pr o gest o ge n releasi n g s yste m f or at least 6 wee ks pri or t o first d ose of st u d y 
i nter ve nti o n. 
4.  Bilateral t u bal occl usi o n f or at least 6  w ee ks pri or t o first d ose of st u d y i nter ve nti o n.  
5.  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 ntrace pti o n (eit her oral, 
i ntra va gi nal, or tra ns d er mal) f or at least 6 wee ks pri or t o first d ose of st u d y i nter ve nti o n.  
6.  S ur gical sterilizati o n of t he male part n er ( me di cal assess me nt of az o os per mia is re q uire d 
if vasect o m y was p erf or me d wit hi n t he pri or 6 m o nt hs pri or t o t he first d ose of st u d y 
i nter ve nti o n). Male part n er is still re q uire d t o use c o n d o m d uri n g se x ual i nterc o urs e. 
7.  Se x ual a bsti ne nce f or f e male partici pa nts:  
•  Se x ual a bsti ne nce is c o nsi dere d a hi g hl y effecti ve met h o d o nl y if defi ne d as 
refr ai ni n g fr o m heter ose x ual i nterc o urse. I n t his st u d y, a bsti ne nce is o nl y acce pta bl e 
if c o nsiste nt wit h t he partici pa nt’s preferre d a n d us ual lifest yle. A bsti ne nt fe male 
partici pa nts m ust refr ai n fr o m heter os e x ual i nterc o urse f or at least 3 0  da ys after t he 
fi nal d ose of st u d y i nter v e nti o n. 
Fe male p artici pa nts of c hil d beari n g p ote ntial ma y als o use t he f oll o wi n g acce pta ble met h o ds 
(c o nsi dere d eff ecti ve, b ut n ot hi g hl y effecti ve mea ns fail ure rate of ≥ 1 % p er year) of 
c o ntrace pti o n:  
1.  Pr o gest o ge n -o nl y oral h or m o nal c o ntrace pti o n w h ere i n hi biti o n of o v ulati o n is n ot t he 
pri mar y m o de of acti o n  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 3 1  of 1 5 2  
Ale xi o n C o nfi de ntial  
2.  Male or fe m ale c o n d o m wit h or wit h o ut s per mici de  
3.  Cer vical ca p, dia p hra g m, or s p o n ge wit h s per mici de  
4.  A c o m bi nati o n of male c o n d o m wit h eit her cer vi cal ca p, dia p hra g m, or s p o n ge wit h 
s per mici de ( d o u ble-barrier met h o ds). If l ocall y re q uire d, i n acc or da n ce wit h Cli nical Trial 
Facilitati o n Gr o u p ( C T F G) g ui deli nes, acce pta bl e c o ntrace pti ve met h o ds are li mite d t o t h ose 
w hic h i n hi bit o v ulati o n as t he pri mar y m o de of acti o n.  
T he f oll o wi n g met h o ds of c o ntrace pti o n are c o nsi dere d u nacce pta ble ( n ot all o we d) i n t his st u d y:  
•  Peri o dic a bsti ne nce (cal e n dar, s y m pt ot her mal, or p ost o v ulati o n met h o ds)  
•  Wit h dra wal ( c oit us i nterr u pt us)  
•  S per mici des o nl y  
•  Lactati o nal a me n orr hea met h o d  
•  Fe male c o n d o m a n d mal e c o n d o m s h o ul d n ot be use d t o get her.  
1 0. 5. 2. 2.  G ui d a nce f or M ale P artici p a nts  
C o ntrace pti o n is t he res p o nsi bilit y of t he heter ose x uall y acti ve male partici pa nts i n t he st u d y, 
re gar dl ess of his fe male part ner’s m et h o d of c o ntrace pti o n. 
Male partici pa nts w h o h a ve ha d a v asect o m y  >  6  m o nt hs pri or t o t he first d ose of st u d y 
i nter ve nti o n m ust use a c o n d o m d uri n g heter ose x u al i nterc o urse. M ale partici pa nts w h o ha ve h a d 
a vasect o m y  <  6  m o nt hs pri or t o t he first d ose of st u d y i nter ve nti o n  a n d t h ose w h o ha ve n ot h a d 
a vasect o m y m ust use a c o n d o m ( wit h or wit h o ut s per mici de) d uri n g h eter ose x ual i nterc o urs e f or 
at least 9 0 da ys (ie, 1 s p er mat o ge nesis c ycl e) after t heir fi nal d ose of st u d y i nter ve nti o n.  
1 0. 5. 2. 2. 1.  Se x u al A bsti ne nce f or M ale P arti ci p a nts  
Se x ual a bsti ne nce is c o nsi dere d a hi g hl y effecti ve met h o d o nl y if defi ne d as refrai ni n g fr o m 
heter ose x u al i nterc o urs e. I n t his st u d y, a bsti ne nce is o nl y acce pta ble if c o nsiste nt wit h t he 
partici pa nt’s pr eferre d a n d us ual lifest yle. A bsti ne nt male partici pa nts w h o bec o me 
heter ose x u all y acti ve m ust use a c o n d o m wit h or wit h o ut s per mici de d uri n g i nterc o urse.  
Peri o dic a bsti ne nce (e g, cale n dar, s y m pt ot her mal, or p ost o v ulati o n met h o ds f or a fe male 
part ner) is n ot c o nsi dere d a hi g hl y effecti ve or acce pta ble met h o d of c o ntrace pti o n f or male 
partici pa nts.  
1 0. 5. 3.  
C ollecti o n of Pre g n a nc y I nf or m ati o n  
Pre g na nc y dat a will be c ollecte d d uri n g t his st u d y f or all fe mal e partici pa nts a n d fe male 
s p o uses/ part ners of m ale partici pa nts fr o m t he first d ose of st u d y i nter ve nti o n u ntil t he Safet y 
F oll o w -u p Visit. A n y fe male partici pa nt w h o b ec o mes pre g na nt d uri n g t he st u d y will be 
disc o nti n ue d fr o m t he st u d y i nter ve nti o n  a n d wit h dra w n fr o m t he st u d y. E x p os ure d uri n g 
pre g na nc y (als o r eferre d t o as e x p os ure i n uter o) ca n be t he res ult of eit her mater nal e x p os ure or 
tra ns missi o n of st u d y i nter ve nti o n via se me n f oll o wi ng pater nal e x p os ure. If a fe m ale partici p a nt 
or a male partici pa nt’s f e male s p o use/ part ner bec o mes pre g na nt d uri n g t he c o n d uct of t his st u d y, 
t he I n v esti gat or m ust s u b mit t he “ Pre g na nc y/ Breastfee di n g Re p orti n g a n d O utc o me F or m” t o 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 3 2  of 1 5 2  
Ale xi o n C o nfi de ntial  
Ale xi o n G P S via facsi mile or e mail. W he n t h e o utc o me of t he pre g na n c y b ec o mes k n o w n, t he 
f or m s h o ul d be u p date d a n d s u b mitte d t o Ale xi o n G P S. If a d diti o nal f oll o w-u p is re q uire d, t he 
I n v esti gat or will be re q u este d t o pr o vi de t he i nf or mati o n. 
E x p os ure of a n i nfa nt t o st u d y i nter ve nti o n d uri n g breastfee di n g m ust als o be re p ort e d ( via t he 
“ Pre g na nc y/ Br eastfee di n g Re p orti n g a n d O utc o m e F or m”) a n d a n y A Es e x perie nce d b y t he 
i nfa nt m ust be re p orte d t o Ale xi o n G P S via e mail or facsi mile. 
Pre g na nc y is n ot re g ar de d as a n A E u nless t here is a s us pici o n t hat t he st u d y i nter ve nti o n ma y 
ha ve i nterf ere d wit h t he effecti ve n ess of a c o ntrace pti ve me dicati o n. H o we v er, c o m plicati o ns of 
pre g na nc y a n d a b n or mal o utc o mes of pre g n a nc y are A Es a n d m a y meet  t he criteria f or a n S A E 
(e g, ect o pic pre g n a nc y, s p o nta ne o us a b orti o n, i ntra uteri ne fetal de mise, ne o natal deat h, or 
c o n ge nital a n o mal y). Electi ve a b orti o ns wit h o ut c o m plicati o ns s h o ul d n ot be re p ort e d as A Es.  
1 0. 5. 3. 1.  M ale P arti ci p a nts wit h P art ners W h o Bec o me Pre g n a nt  
•  T he I n vesti gat or will atte m pt t o c ollect pre g na nc y i nf or mati o n o n a n y male 
partici pa nt’s f e male part ner w h o bec o mes pre g na nt w hile t he male partici p a nt is i n 
t his st u d y. T his a p plies o nl y t o male partici pa nts w h o recei ve st u d y i nter v e nti o n. 
•  After o btai ni n g t he necessar y si g ne d i nf or me d c o nse nt fr o m t he pre g n a nt fe male 
part ner dir ectl y, t he I n v esti gat or will rec or d pre g n a nc y i nf or mati o n o n t he a p pr o priate 
“ Pre g na nc y/ Br eastfee di n g Re p orti n g a n d O utc o m e F or m” a n d s u b mit it t o Ale xi o n 
wit hi n 2 4  h o urs of lear ni n g of t he part ner’s pre g n a nc y. T he fe male p art ner will als o 
be f oll o we d t o deter mi ne t he o utc o me of t he pre g na nc y. I nf or mati o n o n t he stat us of 
t he m ot her a n d c hil d will be f or w ar de d t o Al e xi o n. Ge nerall y, t he f oll o w-u p will be 
n o l o n ger t ha n  3  m o nt hs f oll o wi n g t he deli ver y date. A n y ter mi nati o n of t h e 
pre g na nc y will be re p ort e d re gar dless of fetal stat us ( prese n ce or a bse nce of 
a n o malies) or i n dicati o n f or t he pr oce d ure.  
1 0. 5. 3. 2.  Fe m ale P artici p a nts W h o Bec o me Pre g n a nt  
•  T he I n vesti gat or will c oll ect pre g n a nc y i nf or m ati o n o n a n y fe male p artici pa nt w h o 
bec o mes pr e g na nt w hile partici pati n g i n t his st u d y. T he i nitial i nf or mati o n will be 
rec or d e d o n t he a p pr o pri ate f or m a n d s u b mitte d t o Ale xi o n wit hi n 2 4  h o urs of 
lear ni n g of a p artici pa nt’s pre g na nc y. 
•  F or all Ale xi o n pr o d u cts, b ot h i n de vel o p me nt or p osta p pr o val, e x p os ure d uri n g 
pre g na nc y m ust be rec or de d a n d t he pre g na nc y f oll o we d, u ntil t he o utc o me of t he 
pre g na nc y is k n o w n (ie, s p o nta ne o us miscarria g e, electi ve ter mi nati o n, n or mal birt h, 
or c o n ge nita l a b n or malit y), e ve n if t he p artici pa nt disc o nti n ues t he st u d y i nter ve nti o n 
or wit h dra ws fr o m t he st u d y. T he I n vesti gat or will c ollect f oll o w -u p i nf or mati o n o n 
t he partici pa nt a n d t he n e o nate a n d t he i nf or mati o n will be f or war de d t o Al e xi o n. 
Ge ner all y, f ol l o w-u p will n ot be re q uire d f or l o n ger t ha n 3  m o nt hs be y o n d t he 
esti mate d deli ver y date. A n y ter mi nati o n of pre g n a nc y will be re p orte d, re gar dless of 
fetal stat us ( pres e nce or a bse nce of a n o malies) or i n dicati o n f or t he pr o ce d ure. 
•  Pre g na nc y is n ot c o nsi dere d as a n A E u nless t here is a s us pici o n t hat t he st u d y 
i nter ve nti o n ma y ha ve i nterfere d wit h t he effecti ve ness of a c o ntrace pti ve me dicati o n. 
W hile pre g na n c y itself is n ot c o nsi dere d t o be a n A E or S A E, a n y pre g na n c y 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 3 3  of 1 5 2  
Ale xi o n C o nfi de ntial  
c o m plicati o n or electi ve t er mi nati o n of a pre g na nc y f or me dical reas o ns will be 
re p orte d as a n A E or S A E. A s p o nta ne o us a b orti o n ( occ urri n g at <  2 2  w ee ks 
gestati o nal a ge) or still birt h ( occ urri n g at  >  2 2  w ee ks gestati o nal a ge) is al wa ys 
c o nsi dere d t o be a n S A E a n d will be re p ort e d as s uc h. A n y p ostst u d y 
pre g na nc y -rel ate d S A E c o nsi dere d reas o na bl y relate d t o t he st u d y i nter ve nti o n b y t he 
I n v esti gat or will be re p orte d t o Ale xi o n. W hile t he I n v esti gat or is n ot o bli gate d t o 
acti vel y see k t his i nf or m ati o n i n f o r mer st u d y partici pa nts, he or s he ma y lear n of a n 
S A E t hr o u g h s p o nta ne o us re p orti n g.  
•  A n y fe male p artici pa nt w h o bec o mes pre g na nt w hile partici pati n g i n t he st u d y  will 
disc o nti n ue st u d y i nter ve nti o n a n d be wit h dra w n fr o m t he st u d y.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 3 4  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 6.  
E x pl or at or y Bi o m ar kers  
•  Bl o o d a n d uri ne sa m ples will be c ollecte d f or bi o mar ker a nal yses, a n d t h e data will 
be use d f or researc h (e g, e x pl orat or y) relate d t o A L X N 2 0 5 0, L N, I g A N,  a n d relate d 
diseases. T he s a m ples ma y als o be use d t o de v el o p tests/assa ys i ncl u di n g dia g n ostic 
tests relate d t o A L X N 2 0 5 0, L N, a n d I g A N. 
•  T he sa m ples ma y be a nal yze d as part of a m ultist u d y assess me nt of bi o mar kers i n t he 
res p o nse t o A L X N 2 0 5 0 t o u n dersta n d st u d y disease or relat e d c o n diti o ns. 
•  T he res ults of bi o mar k er a nal yses ma y be re p ort e d i n t he C S R or i n a se parate st u d y 
s u m mar y. 
•  Ale xi o n or desi g nee will st ore t he sa m ples o btai ne d f or bi o mar ker a nal yses i n a 
sec ure st or a ge s pace wit h a de q uate m eas ures t o pr otect c o nfi de ntialit y. 
•  T he sa m ples will be ret ai ne d w hile res earc h o n A L X N 2 0 5 0 c o nti n ues b ut n o l o n ger 
t ha n 2 5  years after all dat a ha ve b ee n c ollecte d f or t he st u d y or ot her peri o d/ti me 
p oi nt per l ocal re q uir e me nts.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 3 5  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 7.  
S yste mic L u p us Er yt he m at os us Di a g n osis Cl assific ati o n  
T he 2 0 1 9 E U L A R/ A C R Classificati o n Criteria f or S L E (Ari n ger, 2 0 1 9 ) will be use d f or 
eli gi bilit y of t he L N  C o h ort. 
 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 3 6  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 8.  
Re vise d 2 0 1 8 I nter n ati o n al S ociet y of Ne p hr ol o g y/ Re n al P at h ol o g y 
S ociet y (I S N/ R P S) Cl assific ati o n  
C ate g or y  
Rec o m me n d ati o n  
Class II  
Defi niti o n f or mesa n gial h y percell ularit y a dj uste d: F o ur or m ore n uclei f ull y 
s urr o u n de d b y matri x i n t he mesa n gial area n ot i ncl u di n g t he hilar re gi o n  
Class III a n d I V  
T he ter m e n d oca pillar y pr oliferati o n is re place d b y e n d oca pillar y 
h y percell ularit y  
 
T he ter m cresce nt is use d f or a lesi o n c o nsisti n g of e xtraca pillar y 
h y percell ularit y, c o m p ose d of a varia ble mi xt ure of cells. Fi bri n a n d fi br o us 
matri x ma y be prese nt; 1 0 % or m ore of t he circ u mfere nce of B o w ma n’s 
ca ps ule s h o ul d be i n v ol ve d. 
 
Cell ular cresce nt: m ore t ha n 7 5 % cells a n d fi bri n a n d less t ha n 2 5 % fi br o us 
matri x  
 
Fi br o us cresce nt: m ore t ha n 7 5 % fi br o us matri x a n d less t ha n 2 5 % cells a n d 
fi bri n  
 
Fi br ocell ular cresce nt: 2 5 % t o 7 5 % cells a n d fi bri n a n d t he re mai n der 
fi br o us matri x  
 
A d hesi o n: a n area of is olate d c o nti n uit y of e xtracell ular matri x material 
bet wee n t he t uft a n d ca ps ule e ve n w he n t he u n derl yi n g se g me nt d oes n ot 
ha ve o vert scler osis 
 
Fi bri n oi d necr osis: fi bri n ass ociate d wit h gl o mer ular base me nt me m bra ne 
disr u pti o n a n d/ or l ysis of t he mesa n gial matri x; t his lesi o n d oes n ot re q uire 
t he prese nce of kar y orr he xis 
 
Eli mi nati o n of se g me ntal a n d gl o bal s u b di visi o ns of Class I V  
 
M o dificati o n of t he Nati o nal I nstit utes of Healt h ( NI H) l u p us ne p hritis 
acti vit y a n d c hr o nicit y sc ori n g s yste m t o be use d i nstea d of t he c urre ntl y 
use d A, C, a n d A/ C para meters  
T u b ul oi nterstitial 
lesi o ns 
I n dicate w het her i nterstitial i nfla m mati o n occ urs i n prese nce or a bse nce of 
i nterstitial fi br osis 
S o urce: (Baje ma, 2 0 1 8 ) 
 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 3 7  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 9.  
I g A N Di a g n osis Cl assific ati o n Criteri a 
A partici pa nt m ust ha ve a bi o ps y pr o ve n dia g n osis of I g A N bas e d o n a n a p pr o priate sta n dar dize d 
classificati o n met h o d (e g, 2 0 1 6 O xf or d Classificati o n [( Tri marc hi, 2 0 1 7 )]; Haas classifi cati o n 
(Haas, 1 9 9 7 ); Lee’s gl o mer ular gr a di n g s yste m (L ee, 2 0 0 5 ). A d escri pti o n of t he 2 0 1 6 O xf or d 
Classificati o n criteria is pr o vi de d bel o w.  
2 0 1 6 O xf or d Cl assific ati o n fr o m t he I g A Ne p hr o p at h y Cl assific ati o n W or ki n g Gr o u p 
Detaile d descri pti o n of t he feat ures pr ese nt o n: 
•  Li g ht micr osc o p y 
•  I m m u n o hist oc he mistr y or i m m u n ofl u oresce n ce 
•  Electr o n micr osc o p y 
S u m mar y of 5 ke y pat h ol o gic feat ur es 
•  Mesa n gial sc or e  < 0. 5 ( M 0) or > 0. 5 ( M 1) 
•  E n d oca pillar y h y percell ularit y a bse nt ( E 0) or pres e nt ( E 1) 
•  Se g me ntal gl o mer ul oscler osis a bse nt ( S 0) or prese nt ( S 1); prese nce or a bs e nce of 
p o d oc yte h y pertr o p h y/ti p lesi o ns i n bi o ps y s peci me ns wit h S 1 
•  T u b ular atr o p h y/i nterstitial fi br osis  ≤ 2 5 % ( T 0), 2 6 % t o 5 0 % ( T 1), or > 5 0 % ( T 2)  
•  Cell ular/fi br ocell ular  cresce nts a bse nt ( C 0), prese nt i n at least 1 gl o mer ul us ( C 1), 
i n > 2 5 % of gl o mer uli ( C 2) 
Q ua ntitati ve data  
•  T otal n u m ber of gl o mer uli 
•  N u m ber of gl o mer uli wit h e n d oca pillar y h y p ercell ularit y, necr osis, e xtraca pillar y 
h y percell ularit y (cell ular/fi br ocell ular cres ce nts), gl o bal gl o mer ul oscler osis, a n d 
se g me ntal gl o mer ul oscler osis 
S o urce: (Tri mar c hi, 2 0 1 7 ) 
 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 3 8  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 1 0.  
P artici p a nt -re p orte d O utc o me I nstr u me nts  
All i nstr u me nts will be self -re p orte d a n d a d mi nistere d at visits s pecifie d i n t he S o As. 
I nf or mati o n a b o ut t hese i nstr u me nts a n d q uesti o n naires, wit h t he c orrect versi o n a n d t he 
vali date d la n g ua g e versi o ns, if nee de d, will be pr o vi de d t o t he sites pri or t o t he start of t he st u d y. 
1 0. 1 0. 1.  
E Q -5 D -5 L ( F or B ot h C o h orts)  
T he E Q -5 D -5 L is a self -r e p orte d sta n dar dize d i nstr u me nt t o meas ure h ealt h-relate d Q o L a n d has 
bee n use d i n a wi de ra n g e of healt h c o n diti o ns. T he E Q -5 D -5 L is defi ne d b y 5 di me nsi o ns: 
m o bilit y, us ual acti vities, self -care, p ai n/ disc o mf ort, a n d a n xiet y/ de pre ssi o n. A 0 t o 1 healt h state 
i n de x sc ore ( or utilit y sc ore), w h ere 0 i n dicates a h ealt h state e q ui vale nt t o d eat h a n d 1 i n dicat es 
perfect healt h, will be calc ulate d fr o m i n di vi d ual h ealt h pr ofiles usi n g a U S T T O val ue set.  
Ne gati ve val u es i n dicate healt h s tates c o nsi dere d w orse t ha n deat h. Eac h of t he E Q-5 D -5 L 
di me nsi o ns ma y be s u m marize d a n d a nal yze d as a cate g orical varia ble, pr o vi di n g data o n t he 
healt h pr ofile of t he st u d y patie nts. T he vis ual a nal o g scale ( V A S) a n d E Q -5 D -5 L i n de x sc ore 
ma y be s u m marize d a n d a nal yze d as c o nti n u o us v aria bles.  
1 0. 1 0. 2.  
S F -3 6 ( F or B ot h C o h orts)  
T he S h ort F or m ( 3 6) Healt h S ur ve y ( S F -3 6) is a set of ge neric, c o here nt, a n d easil y a d mi nistere d 
Q o L meas ures. It has 3 6 ite ms gr o u pe d i n 8 di me nsi o ns: It meas ures eac h of t he f oll o wi n g 8 
healt h d o mai ns: P h ysical F u ncti o ni n g, P h ysical, B o dil y Pai n, Vitalit y, Ge neral Healt h, E m oti o n, 
Me ntal Healt h, a n d S ocial F u ncti o ni n g.  
1 0. 1 0. 3.  
F A CI T -F A TI G U E ( F or L N C o h ort O nl y)  
T he F A CI T -Fati g ue scal e is a c ollecti o n of Q o L q uesti o ns pertai ni n g t o t he ma na ge me nt of 
fati g ue s y m pt o ms d ue t o a c hr o nic ill ness. T he F A CI T-Fati g ue s cale ( Versi o n  4) is a s h ort, 
1 3 -ite m, self-re p orte d, eas y t o a d mi nister t o ol t hat meas ures a n i n di vi d ual’s le vel of fati g ue 
d uri n g t heir us ual dail y acti vities o ver t he past wee k. T he le vel of fati g ue is meas ure d o n a 
fi ve-p oi nt Li kert -t y pe s cale ( 0 =  n ot at all fati g ue d; 1  =  a little bit fati g ue d, 2  =  s o me w hat 
fati g ue d, 3 =  q uite a bit f ati g ue d, a n d 4  =  v er y  m u c h fati g ue d). All ite ms c o ntri b ute t o t he s u m 
sc ore wit h e q u al wei g ht. T his i nstr u me nt will be use d i n t he L N c o h ort. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 3 9  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 1 1.  
C O VI D -1 9 Ris k Assess me nt  
L u p us ne p hritis a n d I g A N ca n ca use irre versi ble m or bi dit y a n d e ve n m ort alit y, if u ntreate d. As 
s uc h, a n d d ue t o t he li mite d n u m ber of a vaila ble treat me nt o pti o ns, t he be nefit a partici pa nt ma y 
recei v e fr o m j oi ni n g a n i n vesti gati o nal st u d y wit h a t hera p e utic treat me nt is p ote ntiall y 
si g nifica nt. Gi ve n t hat treat me nt f or L N a n d I g A N d oes i n v ol ve i m m u n os u p pressi o n, t here is a 
t he oretical c o n cer n t h at t he ris k f or i nfecti o n ma y be hi g her t ha n i n partici pa nts n ot recei vi n g 
i m m u n os u p pressa nts. H o we ver, t here is n o s pecific data t o f urt h er i nf or m t his ris k. T he site 
I n v esti gat or will t heref or e bala nce t he ris k/ be nefit c o nsi derati o ns i n t he st u d y partici pa nt ta ki n g 
t hese fact ors i nt o acc o u nt. 
T he p ote ntial ris ks i de ntifie d a n d miti gati o n meas ures p ut i n place i n li g ht of t he C O VI D - 1 9 
pa n de mic ar e pr o vi de d i n  Ta ble  1 4. 
T a ble 1 4:  
P ote nti al Ris ks a n d Miti g ati o n Me as ures d ue t o C O VI D- 1 9 
Ris ks c ate g or y  
S u m m ar y of D at a/  
R ati o n ale f or Ris k  
Miti g ati o n Str ate g y 
P ote nti al ris ks  
Healt hcare 
i nstit uti o n 
a vaila bilit y f or 
n o n- C O VI D - 1 9 
relate d acti vities  
C O VI D - 1 9 pa n de mic ma y i m pact t he w or kl oa d 
of healt hcare i nstit uti o ns gl o ball y a n d ma y 
re d uce staff a vaila bilit y t o perf or m n o n- ur ge nt 
acti vities a n d n o n-C O VI D - 1 9 relate d acti vities. 
D uri n g t he ti me t hat t he 
C O VI D -1 9 pa n de mic is 
acti ve, Ale xi o n will n ot o pe n 
st u d y sites or e nr oll ne w 
partici pa nts at sites u nless 
t he sites ha ve t he res o urci n g 
a n d ca pa bilities t o i m ple me nt 
t he st u d y per pr ot oc ol. 
Data q ualit y a n d 
i nte grit y 
Lac k of a vaila bilit y of site pers o n nel t o perf or m 
st u d y assess me nts a n d ca pt ure st u d y s pecific 
data i n a ti mel y ma n ner a n d t o mai ntai n 
a de q uate q ualit y sta n dar ds. 
Lac k of a vaila bilit y of site pers o n nel t o e ns ure 
a de q uate a n d c o nti n u o us c hai n of c ust o d y, 
st ora ge c o n diti o ns, a n d m o nit ori n g f or 
i n vesti gati o nal pr o d uct a n d bi ol o gical sa m ples. 
I na bilit y of st u d y m o nit ors a n d q ualit y 
pers o n nel t o c o n d uct i n -pers o n visits t o e xercise 
a de q uate o versi g ht of st u d y e xec uti o n at 
i n vesti gati o nal sites. 
Missi n g data ( C O VI D - 1 9 pa n de mic ma y i m pact 
st u d y visit sc he d ules a n d i ncrease misse d visits 
a n d/ or partici pa nt st u d y disc o nti n uati o ns 
i na d verte ntl y res ulti n g i n missi n g data [e g, f or 
pr ot oc ol- s pecifie d pr oce d ures]). 
D uri n g t he ti me t hat t he 
C O VI D -1 9 pa n de mic is 
acti ve, Ale xi o n will o nl y 
o pe n st u d y sites t hat re p ort 
e n o u g h pers o n nel ca pacit y t o 
s ufficie ntl y c o n d uct cli nical 
st u d y-relate d acti vities. 
D uri n g t his ti mefra me, site 
ca pacit y will be re vie we d b y 
t he site I n vesti gat or a n d t he 
st u d y Me dical M o nit or pri or 
t o Scree ni n g. Eac h site is 
als o e val uate d f or t he 
ca pacit y t o perf or m re m ote 
m o nit ori n g visits a n d re m ote 
s o urce data verificati o n. 
D uri n g t he ti me t hat t he 
C O VI D -1 9 pa n de mic is 
acti ve, it will be i m p orta nt t o 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 4 0  of 1 5 2  
Ale xi o n C o nfi de ntial  
T a ble  1 4 : 
P ote nti al Ris ks a n d Miti g ati o n Me as ures d ue t o C O VI D -1 9  
Ris ks c ate g or y  
S u m m ar y of D at a/  
R ati o n ale f or Ris k  
Miti g ati o n Str ate g y  
ca pt ure s pecific i nf or mati o n 
i n t he e C R F t hat e x plai ns t he 
reas o n t he data is missi n g 
(e g, misse d st u d y visits or 
partici pa nt st u d y 
disc o nti n uati o ns d ue t o 
C O VI D -1 9).  
A b bre viati o ns: C O VI D -1 9  =  c or o na vir us disease 2 0 1 9; e C R F =  electr o nic case re p ort f or m  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 4 1  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 1 2.  
C O VI D -1 9 V acci ne Ris k Assess me nt  
F oll o wi n g a re vie w of t h e a vaila ble C O VI D- 1 9 v acci ne d ata (e g, Pfizer/ Bi o N Tec h, M o der na, 
Astra Ze neca, J o h ns o n & J o h ns o n), it is u nli kel y t hat t he i m m u ne res p o nse t o a C O VI D- 1 9 
vacci ne (a n d t heref ore t h e effi cac y of t he vacci nati o n) w o ul d be di mi nis he d wit h c o nc o mita nt 
A L X N 2 0 5 0 a d mi nistrati o n, base d o n A L X N 2 0 5 0’s mec ha nis m of acti o n. T here is c urre ntl y n o 
i nf or mati o n a vaila ble e v al uati n g t he safet y a n d effi cac y of C O VI D- 1 9 v acci nes i n partici pa nts 
treate d wit h A L X N 2 0 5 0. T he sa me pr eca uti o ns s h o ul d be ta ke n as des cri be d i n Secti o n 6. 5. 5 . 
Vacci n ati o n ma y f urt her acti vate c o m ple me nt. As a res ult, patie nts wit h c o m ple me nt -me diate d 
diseases ma y e x p erie n ce i ncreas e d si g ns a n d s y m pt o ms of t heir u n derl yi n g disease. If p ossi ble, 
c o nsi der vacci nati o n w he n t he u n derl yi n g c o m ple me nt- me diate d diseas e is cli nicall y c o ntr olle d. 
Patie nts s h o ul d be cl osel y m o nit ore d f or disease s y m pt o ms after rec o m me n de d vacci nati o n. 
Beca use v acci n es ma y acti vate c o m ple me nt, if p ossi ble, c o nsi der vacci nati o n w he n t he 
u n derl yi n g c o m ple me nt- me diate d disease is cli nicall y c o ntr olle d a n d s u bse q ue nt c o m ple me nt 
bl oc ka de is rel ati vel y hi g h, s h ortl y after a d mi nistrati o n. 
L ocal a n d nati o nal g ui deli nes s h o ul d be c o ns ulte d f or rec o m me n dati o ns rel ate d t o C O VI D- 1 9 
vacci nati o n.  
T he p ote ntial ris ks i de ntifie d a n d miti gati o n meas ures p ut i n place i n li g ht of t he C O VI D - 1 9 
vacci nati o n r oll o ut ar e pr o vi de d i n  Ta ble  1 5. 
T a ble 1 5:  
P ote nti al Ris ks a n d Miti g ati o n Me as ures d ue t o C O VI D 1 9 V acci ne 
Ris ks c ate g or y 
S u m m ar y of D at a/ R ati o n ale f or Ris k 
Miti g ati o n Str ate g y 
P ote nti al ris ks  
Data q ualit y a n d 
i nte grit y 
Missi n g data d ue t o a p p oi nt me nts f or 
C O VI D -1 9 vacci nati o n or si de effects of 
C O VI D -1 9 vacci ne ma y i m pact st u d y visit 
sc he d ules a n d i ncrease misse d visits a n d/ or 
partici pa nt st u d y disc o nti n uati o ns, 
i na d verte ntl y res ulti n g i n missi n g data (e g, 
f or pr ot oc ol-s pecifie d pr oce d ures). 
 
Ca pt ure s pecific i nf or mati o n i n 
t he e C R F t hat e x plai ns t he 
reas o n t he data is missi n g (e g, 
misse d st u d y visits d ue t o 
a p p oi nt me nts f or C O VI D - 1 9 
vacci nati o n or si de effects of 
C O VI D -1 9 vacci ne)  
A b bre viati o ns: C O VI D -1 9  = c or o na vir us disease 2 0 1 9; e C R F  = electr o nic case re p ort f or m  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 4 2  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 1 3.  
Re m ote S o urce D at a Verific ati o n D uri n g C O VI D -1 9 P a n de mic  
T o e ns ure t he ri g hts, safet y, a n d well -bei n g of trial partici pa nts, as well as t he i nte grit y of t he 
st u d y a n d its data d uri n g t he C O VI D -1 9 p a n de mic,  w he n o nsite st u d y m o nit ori n g acti vities are 
restricte d, re m ote s o urce data verifi cati o n (r S D V) ma y be e m pl o ye d w h ere ver per mitte d b y l ocal 
re g ulati o ns. 
A L X N 2 0 5 0 -N E P H -2 0 1 is a P hase  2 st u d y i n partici pa nts wit h L N a n d I g A N. Ale xi o n has 
assesse d t hat t he i na bilit y t o c o m plete o n g oi n g s o urce dat a verifi cati o n ( S D V) c o ul d p ose a ris k 
t o t he r o b ust ness of t he st u d y data. Dela yi n g o n g oi n g verificati o n of k e y efficac y ( pri mar y a n d 
sec o n dar y) e n d p oi nts a n d i m p orta nt safet y e n d p oi nts c o ul d res ult i n late i de ntificati o n of 
i nc orrect or missi n g data, w hic h c o ul d i m pact t he i nte grit y of t he st u d y data. 
Re m ote S D V will be carrie d o ut i n writte n a gree me nt wit h t he I n v esti gat or a n d, if a p plica ble, t h e 
i nstit uti o n, u n der c o n diti o ns e ns uri n g a de q u ate data pr otecti o n a n d partici pa nts’ ri g hts. 
De pe n di n g o n l ocal r e g ul ati o n a n d a gree me nt wit h t he site I n v esti gat or a n d i nstit uti o n 
prefere nce, r S D V ma y b e c o n d ucte d t hr o u g h direct a n d c o ntr olle d rea d -o nl y m o nit or access t o 
i nstit uti o n electr o nic me dical rec or ds s yste ms, passi ve access t o s o urce d o c u me nts via li ve i ma ge 
tra ns missi o n, a n d/ or s hari n g of re dacte d c o pies of s o urce d oc u m e nts via a s ec ure, v ali date d, a n d 
access -restri cte d s yste m. Re gar di n g t he electr o nic s hari n g of re d acte d c o pies of s o urce 
d oc u me nts, t he f oll o wi n g re q uire me nts m ust be f oll o we d:  
•  Sca n ne d or el ectr o nic d o c u me nts t o be u pl oa de d (as P D F, j pe g, or ot her i ma ge 
f or mat) t hat are of s uffici e nt res ol uti o n t o e ns ure rea da bilit y, i n blac k a n d w hite or 
c ol or. 
•  T o e ns ure c o m plet e ness of t he s hare d c o nte nt, t he m o nit or will pre pare a writte n 
re q uest t o t he i n vesti gati ve site listi n g t he s o urce data nee d e d t o c o n d uct r S D V a n d 
will perf or m a q ualit y c h ec k o n t he list of d oc u me nts s hare d b y t he site a g ai nst t he list 
of re q ueste d s o urce data.  
•  Site staff m ust perf or m a q ualit y c hec k e ns uri n g s o urce d oc u m e nts are re d acte d 
bef ore m a ki n g t he m a vaila ble t o m o nit ors. A data breac h m a na ge m e nt p olic y a n d a 
sec urit y tea m will be i n place t o i de ntif y vi olati o ns a n d t o e ns ure c orrect a n d ti mel y 
acti o n. 
•  T o pre ve nt l oss of or u n a ut h orize d access t o s o urce data, i n vesti gati ve site pers o n nel 
will nee d t o acti vel y gra nt access t o t heir s p ecific m o nit or. T he m o nit or will o nl y 
ha ve vie wi n g ri g hts, t her e b y pre ve nti n g l oss, alterati o n, or d o w nl oa d of s o urce dat a.  
•  Tracea bilit y of pse u d o n y mize d d oc u me nts re vi e w e d re m otel y will be ke pt b y t he 
m o nit or f or verificati o n o nsite.  
T he detaile d sc o p e of r S D V will be o utli ne d i n s u p p orti n g st u d y pla ns (e g, Cli nical M o nit ori n g 
Pla n).  C o n d uct of r S D V will o nl y be perf or me d d uri n g t he C O VI D -1 9 p a n de mic.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 4 3  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 1 4.  
M a n a ge me nt of Seiz ures  
Seiz ure is c o nsi der e d a p ote ntial ris k t hat is t o be cl osel y m o nit ore d i n partici pa nts. Seiz ures are 
defi ne d as a tra nsie nt occ urre nce of cli nical si g ns a n d/ or s y m pt o ms t hat are d ue t o a b n or mal 
e xcessi ve or s y n c hr o n o us ne ur o nal acti vit y i n t he brai n.  
C o n v ulsi o ns a n d/ or electr oe nce p h al o gra m ( E E G) a b n or malities ha ve b ee n o bser ve d d uri n g d o g 
a n d m o use re p eat -d ose t o xic ol o g y st u dies. T he d o g is t he m ost se nsiti ve n o ncli nical s pecies 
st u die d, a n d t he N O A E L base d o n t he d o g 1 3-w ee k t o xic ol o g y st u d y is 6 2. 5  m g/ k g/ da y.  
S h o ul d a s us pecte d seiz ure occ ur d uri n g t he st u d y, t he f oll o wi n g pr oce d ures s h o ul d be 
perf or me d:  
•  Partici pa nts a n d/ or fa mil y me m bers s h o ul d be i nstr ucte d t o call a n a m b ula n ce or 
re p ort t o a me dical facilit y if t he partici pa nt e x p eri e nces a s eiz ure. I n ge n eral, m ost 
seiz ures are self-li miti n g a n d d o n ot re q uire ac ute p har mac ol o gic i nter ve nti o n. 
•  F or seiz ures t hat are n ot self -li miti n g, t he partici pa nt s h o ul d be treate d m e dicall y 
acc or di n g t o l ocal pr ot oc ols f or o n g oi n g seiz ure.  
•  Partici pa nts a n d fa mil y me m bers s h o ul d be i nstr ucte d t o call t he I n v esti gat or t o 
i nf or m t he m of t he seiz ur e. 
•  Treat me nt wit h st u d y i nter ve nti o n s h o ul d be s us p e n de d u ntil a c o m plete w or k u p is 
perf or me d.  
•  T he f oll o wi n g assess me nts are rec o m me n de d f or all partici pa nts wit h s us pecte d 
seiz ure: 
− Bl o o d sa m ples s h o ul d be ta ke n t o e val uate electr ol ytes (i ncl u di n g calci u m a n d 
ma g nesi u m), gl uc ose, c o m plete bl o o d c o u nt, re nal f u ncti o n tests, li ver f u ncti o n 
tests, creati ni ne ki nas e, t o xic ol o g y scree n, et ha n ol le vel, a n d ser u m lactate. A n y 
ot her tests or i n vesti gati o ns deter mi ne d t o be perti ne nt s h o ul d als o be perf or me d 
(e g, brai n i ma gi n g, bl o o d, a n d uri ne c ult ures). 
− Bl o o d sa m ples s h o ul d be ta ke n t o e val uate P K l e v els.  
− A n E E G s h o ul d be perf or me d.  
•  If t he eti ol o g y of t he sei z ure is assesse d as relat e d t o t he st u d y i nter ve nti o n, t he st u d y 
i nter ve nti o n will be disc o nti n ue d, a n d t he partici pa nt will be als o disc o nti n ue d fr o m 
t he st u d y. 
•  If a n alter nati ve ca use f or t he seiz ure is det er mi ne d, d osi n g wit h st u d y i nter ve nti o n 
ma y res u me as d ee me d a p pr o priate b y t he I n v esti gat or i n c o ns ultati o n wit h t he 
Me dical M o nit or.  
A n y e ve nt of sei z ure or s us pecte d seiz ure m ust be re p orte d t o Ale xi o n wit hi n 2 4  h o urs of t he 
I n v esti gat or’s a war e ness as a treat me nt-e mer g e nt seri o us a d vers e e v e nt ( T E S A E). T he f oll o wi n g 
cli nical i nf or mati o n i n a d diti o n t o t he a b o ve rec o m me n de d assess me nts s h o ul d als o be c ollecte d:  
•  Seiz ure start dat e a n d ti me  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 4 4  of 1 5 2  
Ale xi o n C o nfi de ntial  
•  Descri pti o n of t he sei z ur e  
− T he t y pe of seiz ure ( e g, g e neralize d t o nic -cl o nic s eiz ure, partial seiz ure)  
− A detaile d descri pti o n of w hat t he partici pa nt w as d oi n g bef ore, d uri n g, a n d after 
eac h sei z ure. If p ossi ble, descri be all as pects fr o m start t o e n d.  
− W hat was t he earliest si g n of seiz ure o nset?  
− D urati o n of seiz ure(s)  
− Was t he partici pa nt u nc o nsci o us, u na ware, or c o nf use d?  
− Was t her e e vi de n ce of b o wel or bla d der d ysf u ncti o n?  
− P ost -ictal peri o d d urati o n a n d si g ns 
− Ne ur ol o gic e x a mi nati o n fi n di n gs  
− E E G res ults  
− E vi de nce of i nj ur y fr o m t he seiz ure (e g, t o n g ue bit es, br uises, or ot her i nj uri es)  
− H o w di d t he partici pa nt rec o ver after t he seiz ure?  
•  D oc u me nt i de ntifia ble seiz ure tri g gers  
− Was t her e a n y r ec o g niza ble tri g ger t hat ma y ha v e pr o v o ke d t he seiz ures f or t he 
partici pa nt? Pleas e i ncl u de a n y rece nt me dicati o n c ha n ges, ill ness, or slee p 
de pri vati o n.  
− Was t her e a n y hist or y of alc o h ol or dr u g use, or rece nt disc o nti n uati o n of al c o h ol 
use?  
•  Past me dical a n d s ur gical hist or y re vie w  
− Is t here r ele va nt me dical hist or y? 
− D oc u me nt c o nc o mita nt me dicati o ns  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 4 5  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 1 5.  
Selecte d Me dic ati o ns K n o w n t o L o wer t he Seiz ure T hres h ol d a n d/ or 
C a use Seiz ure  
T he f oll o wi n g me dicati o ns are P R O HI BI T E D w hile o n t he st u d y:  
•  Me peri di ne/ pet hi di ne  
•  Tra ma d ol  
•  T y pical (first ge n erati o n) a nti ps yc h otics  
•  Cl oza pi ne  
•  Ola nza pi ne  
•  Lit hi u m  
•  Tric yclic a nti de pressa nts  
•  B u pr o pi o n  
•  A mi n o p h ylli ne/t he o p h ylli ne  
 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 4 6  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 1 6.  
List of I n hi bit ors, I n d ucers a n d S u bstr ates of C Y P 3 A  
T a ble  1 6: 
List of Pr o hi bite d I n d ucers, I n hi bit ors a n d S u bstr ates of C Y P 3 A 
Cl assific ati o n  
Me dic ati o n  
T a ble N u m ber a 
Str o n g C Y P 3 A 
i n hi bit ors 
b oce pre vir, c o bicistat, da n o pre vir  a n d rit o na vir, 
el vite gra vir a n d rit o na vir, gra pefr uit j uice, i n di na vir a n d 
rit o na vir, itrac o naz ole, ket oc o naz ole, l o pi na vir a n d 
rit o na vir, parita pre vir a n d rit o na vir a n d ( o m bitas vir 
a n d/ or dasa b u vir), p osac o naz ole, rit o na vir, sa q ui na vir 
a n d rit o na vir, tela pre vir, ti pra na vir a n d rit o na vir, 
telit hr o m yci n, tr olea n d o m yci n, v oric o naz ole, 
clarit hr o m yci n, i delalisi b, nefaz o d o ne, a n d nelfi na vir 
3- 2 
M o derate C Y P 3 A 
i n hi bit ors 
a pre pita nt, ci pr ofl o xaci n, c o ni va pta n, criz oti ni b, 
c ycl os p ori ne, diltiaze m, dr o ne dar o ne, er yt hr o m yci n, 
fl uc o naz ole, fl u v o xa mi ne, i mati ni b, t ofis o pa m, a n d 
vera pa mil  
3- 2 
Str o n g i n d ucers of 
C Y P 3 A  
a pal uta mi de, car ba maze pi ne, e nzal uta mi de, mit ota ne, 
p he n yt oi n, rifa m pi n, a n d St. J o h n’s w ort 
3- 3 
M o derate i n d ucers of 
C Y P 3 A  
b ose nta n, efa vire nz, etra viri ne, p he n o bar bital, a n d 
pri mi d o ne 
3- 3 
Se nsiti ve s u bstrates of 
C Y P 3 A  
alfe nta nil, a va nafil, b us pir o ne, c o ni va pta n, darife naci n, 
dar u na vir, e basti ne, e ver oli m us, i br uti ni b, l o mita pi de, 
l o vastati n, mi daz ola m, nal o xe g ol, nis ol di pi ne, 
sa q ui na vir, si m vastati n, sir oli m us, tacr oli m us, 
ti pra na vir, triaz ola m, var de nafil, b u des o ni de, dasati ni b, 
dr o ne dar o ne, eletri pta n, e plere n o ne, fel o di pi ne, 
i n di na vir, l urasi d o ne, mara vir oc, q uetia pi ne, sil de nafil, 
tica grel or, t ol va pta n 
3- 1 
a Ta ble n u m ber fr o m F D A Ta ble of Cli nical C Y P I n hi bit ors a n d I n d ucers  
A b bre viati o n: C Y P 3 A  = c yt oc hr o me P 4 5 0, fa mil y 3, s u bfa mil y A  
N ote: T his list is c o m plete as of 2 5  Ja n 2 0 2 1. Please visit t he li n k bel o w f or t he m ost u p -t o-date i nf or mati o n.  
S o urce: (F D A, 2 0 2 2 )  
 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 4 7  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 0. 1 7.  
Pr ot oc ol A me n d me nt Hist or y  
T he pr ot oc ol a me n d m e nt s u m mar y of c ha n g es ta ble f or t he c urre nt a me n d me nt is l ocate d 
directl y bef or e t he Ta bl e of C o nte nts.  
D O C U M E N T HI S T O R Y  
D oc u me nt/ T y pe of A me n d me nt 
( Gl o b al or C o u ntr y-s pecific)/ D ate 
S u m m ar y of Ke y C h a n ges i n t he A me n d me nt  
A me n d me nt 2. 0 ( Gl o bal)/ 3 1 Ma y 2 0 2 3  
Re vise d t o a d dress t he re q uire me nts f or c o n d ucti n g a 
cli nical st u d y u n der t he E U C T R.  
A me n d me nt 1. 2/ C hi na/ 3 1 A u g 2 0 2 2  
Re m o ve d e x pl orat or y bi o mar kers a n d refere nces t o se n di n g 
tiss ue sa m ple sli des t o t he Ce ntral Pat h ol o g y La b orat or y 
o utsi de C hi na as s hi p pi n g of bi ol o gical sa m ples o ut of 
C hi na is restricte d.  
A me n d me nt 1. 1/ U nite d Ki n g d o m/ 1 0 J u n 
2 0 2 3  
Re vise d t o i nc or p orate c o m me nts fr o m t he Me dici nes a n d 
Healt hcare pr o d ucts Re g ulat or y w hic h were ma de i n 
A me n d me nt 0. 1.  
A me n d me nt 1 ( Gl o bal)/ 1 7 Ma y 2 0 2 2  
Re vise d t o i nc or p orate i n t he gl o bal pr ot oc ol, w here 
a p pr o priate, t he c ha n ges ma de at t he re q uest of re g ulat or y 
a ut h orities, I R Bs, I E Cs, a n d I n vesti gat ors. T he eli gi bilit y 
criteria were clarifie d or m o difie d, a n d a sec o n dar y 
e n d p oi nt t o assess S u b o pti mal R es p o nse was a d de d f or t he 
L N c o h ort. Of n ote, t he ma xi m u m d ose of M M F a 
partici pa nt i n t he L N C o h ort ca n recei ve was i ncrease d, a n d 
a d diti o nal c ortic oster oi d ta per f oll o wi n g Wee k  2 6 was 
all o we d. Als o of n ote, a d diti o nal C O VI D -1 9 relate d 
miti gati o n a n d m o ni t ori n g g ui da nce were i ncl u de d. 
A me n d me nt 0. 2/ Ger ma n y/ 0 5  Ma y  2 0 2 2  
Re vise d t o a d dress c o m me nts fr o m t he Ger ma n E C  
A me n d me nt 0. 1/ U nite d Ki n g d o m/ 
2 4  N o v  2 0 2 1  
Re vise d t o a d dress c o m me nts fr o m t he Me dici nes a n d 
Healt hcare pr o d ucts Re g ulat or y A ge nc y  
Ori gi nal pr ot oc ol/ 0 3  J u n 2 0 2 1  
N ot a p plica ble  
 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 4 8  of 1 5 2  
Ale xi o n C o nfi de ntial  
1 1.  
R E F E R E N C E S  
Al maa ni S, Pari k h S V. Me m bra n o us l u p us ne p hritis: a cli nical re vie w. A d v C hr o nic Ki d ne y Dis. 
2 0 1 9; 2 6( 5): 3 9 3 -4 0 3.  
Al maa ni S, Meara A, R o vi n B H. U p date o n l u p us ne p hritis. Cli n J A m S oc Ne p hr ol. 
2 0 1 7; 1 2( 5): 8 2 5 -8 3 5.  
A p pel G B, C o ntreras G, D o ole y M A, et al. M yc o p he n olate m ofetil vers us c ycl o p h os p ha mi de f or 
i n d ucti o n treat me nt of l u p us ne p hritis. J A m S oc Ne p hr ol. 2 0 0 9; 2 0( 5): 1 1 0 3-1 1 1 2.  
Ari n ger M, C oste n ba d er K, Dai k h D, et al. 2 0 1 9 E ur o pea n L ea g ue A gai nst 
R he u matis m/ A merica n C olle ge of R he u mat ol o g y classificati o n criteria f or s yste mic l u p us 
er yt he mat os us. A n n R he u m Dis. 2 0 1 9; 7 8( 9): 1 1 5 1 -1 1 5 9.  
Arrie ns C, P ol ya k o va S, A dzeri k h o I, R a n d ha w a S, S ol o m o ns N. O P 0 2 7 7  A U R O R A p hase 3 
st u d y de m o nstrates v ocl os p ori n statistical s u peri orit y o ver sta n dar d of care i n l u p us ne p hritis 
( L N). A n n R he u m Dis. 2 0 2 0; 7 9( S u p pl 1): 1 7 2-1 7 3.  
Baje ma I M, Wil hel m us S, Al pers C E, et al. Re visi o n of t he I nter n ati o nal S ociet y of 
Ne p hr ol o g y/ Re nal Pat h ol o g y S ociet y classificati o n f or l u p us ne p hritis: clarificati o n of 
defi niti o ns, a n d m o difie d Nati o nal I nstit utes of Healt h acti vit y a n d c hr o nicit y i n dic es. Ki d ne y 
I nt. 2 0 1 8; 9 3( 4): 7 8 9-7 9 6.  
Ba o L, C u n ni n g ha m P N, Q ui g g RJ. C o m ple me nt i n l u p us ne p hritis: ne w pers pecti ves. Ki d ne y 
Dis ( Basel). 2 0 1 5; 1( 2): 9 1 -9 9.  
Bertsias G K, Te kt o ni d o u M, A m o ura Z, et al. J oi nt E ur o pea n Lea g ue A g ai nst R he u matis m a n d 
E ur o pea n Re n al Ass ociati o n -E ur o pea n Dial ysis a n d Tra ns pla nt Ass ociati o n ( E U L A R/ E R A -
E D T A) r ec o m me n dati o ns f or t he ma na g e me nt of a d ult a n d pae diatri c l u p us ne p hritis. A n n 
R he u m Dis. 2 0 1 2; 7 1( 1 1): 1 7 7 1 -1 7 8 2.  
Biesec ker G, Katz S, K offler D. Re nal l ocalizati o n of t he me m bra n e attac k c o m ple x i n s yste mic 
l u p us er yt he mat os us ne p hritis. J E x p Me d. 1 9 8 1; 1 5 4( 6): 1 7 7 9-1 7 9 4.  
Bir mi n g ha m DJ, Merc ha nt M, Wai kar S S, Na garaja H, Klei n J B, R o vi n B H. Bi o mar kers of 
l u p us ne p hritis hist ol o g y a n d flar e: deci p heri n g t he rele v a nt a mi dst t he n oise. Ne p hr ol Di al 
Tra ns pla nt. 2 0 1 7; 3 2( S u p pl 1):i 7 1 -i 7 9. 
Bir mi n g ha m DJ, Irs h ai d F, Na g araja H N, et al. T he c o m ple x nat ure of ser u m C 3 a n d C 4 as 
bi o mar kers of l u p us r e nal flare. L u p us. 2 0 1 0; 1 9( 1 1): 1 2 7 2 -1 2 8 0.  
C ores h J, Heers pi n k HJ L, Sa n g Y, et al. C ha n ge i n al b u mi n uria a n d s u bse q ue nt ris k of e n d -sta g e 
ki d ne y disease: a n i n di vi d ual partici pa nt -le v el c o ns orti u m meta-a nal ysis of o bser vati o nal st u dies. 
La ncet Dia b etes E n d ocri n ol. 2 0 1 9; 7( 2): 1 1 5 -1 2 7.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 4 9  of 1 5 2  
Ale xi o n C o nfi de ntial  
Dall' Era M, St o ne D, Le v es q ue V, Cister nas M, W ofs y D. I de ntificati o n of bi o mar kers t hat 
pre dict res p o ns e t o treat me nt of l u p us ne p hritis wit h m yc o p he n olate m ofetil or p ulse 
c ycl o p h os p ha mi de. Art hritis Care Res ( H o b o ke n). 2 0 1 1; 6 3( 3): 3 5 1- 3 5 7. 
Elli ott M K, Jar mi T, R uiz P, X u Y, H olers V M, Gil kes o n G S. Effects of c o m ple me nt fact or D 
deficie nc y o n t h e re n al disease of M R L/l pr mice. Ki d ne y I nt. 2 0 0 4; 6 5( 1): 1 2 9- 1 3 8. 
F D A. Dr u g De v el o p me nt a n d Dr u g I nteracti o ns | Ta ble of S u bstrates, I n hi bit ors a n d I n d ucers 
2 0 2 2 [ u p date d 0 8/ 2 4/ 2 0 2 2]. A vaila ble fr o m:  htt ps:// w w w.f da. g o v/ dr u gs/ dr u g- i nteracti o ns-
la beli n g/ dr u g- de vel o p me nt-a n d- dr u g-i nteracti o ns-ta ble-s u bstrates-i n hi bit ors-a n d-i n d ucers. 
Fellstr o m B C, Barratt J, C o o k H, et al. Tar get e d-release b u d es o ni de vers us place b o i n patie nts 
wit h I g A n e p hr o pat h y ( N E FI G A N): a d o u ble- bli n d, ra n d o mise d, place b o-c o ntr olle d p hase 2 b 
trial. La ncet. 2 0 1 7; 3 8 9( 1 0 0 8 4): 2 1 1 7- 2 1 2 7. 
F urie R, R o vi n B H, H o ussia u F, et al. T w o- year, ra n d o mize d, c o ntr olle d tri al of beli m u ma b i n 
l u p us ne p hritis. N E n gl J Me d. 2 0 2 0; 3 8 3( 1 2): 1 1 1 7- 1 1 2 8. 
Gali n d o-Iz q uier d o M, Pa bl os Al varez J L. C o m ple me nt as a t hera pe utic tar get i n s yste mic 
a ut oi m m u ne diseases. Cells. 2 0 2 1; 1 0( 1). 
Gas par ott o M, Gatt o M, Bi n da V, D oria A, M or o ni G. L u p us ne p hritis: cli nical prese nt ati o ns a n d 
o utc o mes i n t he 2 1st ce nt ur y. R he u mat ol o g y ( O xf or d, E n gla n d). 2 0 2 0; 5 9( S u p pl 5): v 3 9- v 5 1. 
Gi nzler E M, D o ole y M A, Ara n o w C, et al. M y c o p he n olate m ofetil or i ntra v e n o us 
c ycl o p h os p ha mi de f or l u p us ne p hritis. N E n gl J Me d. 2 0 0 5; 3 5 3( 2 1): 2 2 1 9- 2 2 2 8. 
Gr oss ma n T R, Hettric k L A, J o h ns o n R B, et al. I n hi biti o n of t he alter nati ve c o m ple me nt pat h wa y 
b y a ntise nse oli g o n ucle oti des tar geti n g c o m ple me nt fact or B i m pr o ves l u p us ne p hritis i n mice. 
I m m u n o bi ol o g y. 2 0 1 6; 2 2 1( 6): 7 0 1- 7 0 8. 
Haas M. Hist ol o gic s u bcl assificati o n of I g A n e p hr o pat h y: a cli nic o pat h ol o gic st u d y of 2 4 4 cases. 
A m J Ki d ne y Dis. 1 9 9 7; 2 9( 6): 8 2 9- 8 4 2. 
Har b oe M, Ul v u n d G, Vie n L, F u n g M, M oll nes T E. T he q ua ntitati ve r ole of alter nati ve p at h wa y 
a m plificati o n i n classical pat h wa y i n d uce d t er mi nal c o m ple me nt acti vati o n. Cli n E x p I m m u n ol. 
2 0 0 4; 1 3 8( 3): 4 3 9- 4 4 6. 
Has hi m ot o A, S uz u ki Y, S uz u ki H, et al. Deter mi n ati o n of se verit y of m uri n e I g A ne p hr o pat h y 
b y gl o mer ular c o m ple me nt acti vati o n b y a berra ntl y gl yc os ylate d I g A a n d i m m u ne c o m ple xes. 
A m J Pat h ol. 2 0 1 2; 1 8 1( 4): 1 3 3 8- 1 3 4 7. 
He bert L A, Wil mer W A, Fal ke n h ai n M E, La ds o n - W off or d S E, N a h ma n N S, Jr., R o vi n B H. 
Re n o pr otecti o n: o ne or ma n y t hera pies ? Ki d ne y I nt. 2 0 0 1; 5 9( 4): 1 2 1 1- 1 2 2 6. 
K DI G O. Cli nical Practice G ui deli ne f or Gl o mer ul o ne p hritis. Ki d ne y Disease I m pr o vi n g Gl o bal 
O utc o mes. 2 0 1 2; 2( 2): 2 0 9- 2 1 7. 

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 5 0  of 1 5 2  
Ale xi o n C o nfi de ntial  
K DI G O. Cli nical pr actice g ui deli ne u p date f or t he dia g n osis, e val uati o n, pre ve nti o n, a n d 
treat me nt of C hr o nic Ki d ne y Disease-Mi neral a n d B o ne  Dis or der ( C K D -M B D). Ki d ne y I nt 
S u p pl ( 2 0 1 1). 2 0 1 7; 7( 1): 1 -5 9.  
K DI G O. K DI G O cli nical practice g ui d eli ne o n gl o mer ular diseas es ( D R A F T). J u ne 2 0 2 0. 2 0 2 0.  
Ki m A HJ, Stra n d V, Se n D P, et al. Ass ociati o n of bl o o d c o nce ntrati o ns of c o m ple me nt s plit 
pr o d uct i C 3 b a n d ser u m C 3 wit h s yste mic l u p us er yt he mat os us disease acti vit y. Art hritis 
R he u mat ol. 2 0 1 9; 7 1( 3): 4 2 0 -4 3 0.  
Ki m H, Ki m T, Ki m M, et al. Acti vati o n of t he alt er nati ve c o m ple m e nt pat h wa y pre dicts re nal 
o utc o me i n patie nts wit h l u p us ne p hritis. L u p us. 2 0 2 0; 2 9( 8): 8 6 2 -8 7 1.  
Lai K N, Le u n g J C, Ta n g S C. Rece nt a d va nces i n t he u n dersta n di n g a n d m a na ge me nt of I g A 
ne p hr o pat h y. F 1 0 0 0 Res. 2 0 1 6; 5: 1 6 1.  
Lee H S, Lee M S, Lee S M, et al. Hist ol o gical gra di n g of I g A ne p hr o p at h y pre dicti n g re n al 
o utc o me: re visiti n g H. S. Lee's gl o mer ular gra di n g s yste m. Ne p hr ol Dial Tra ns pla nt. 
2 0 0 5; 2 0( 2): 3 4 2 -3 4 8.  
Le ve y A S, Ga ns e v o ort R T, C ores h J, et al. C ha n g e i n al b u mi n uria a n d G F R as e n d p oi nts f or 
cli nical trials i n earl y sta ges of C K D: A scie ntific w or ks h o p s p o ns ore d b y t he Nati o nal Ki d ne y 
F o u n dati o n i n c olla b orati o n wit h t he U S F o o d a n d Dr u g A d mi nistrati o n a n d E ur o pea n M e dici nes 
A ge nc y. A m J Ki d ne y Dis. 2 0 2 0; 7 5( 1): 8 4 -1 0 4.  
L u ka ws ka E, P olc y n -A d a mcza k M, Ni e mir ZI. T he r ole of t he alter nati ve pat h wa y of 
c o m ple me nt acti vati o n i n gl o mer ular diseas es. Cli n E x p Me d. 2 0 1 8; 1 8( 3): 2 9 7 -3 1 8.  
L v J C, Z ha n g L X. Pre val e nce a n d disease b ur de n of c hr o nic ki d ne y disease. A d v E x p Me d Bi ol. 
2 0 1 9; 1 1 6 5: 3 -1 5.  
Maillar d N, W yatt RJ, J ulia n B A, et al. C urre nt u n dersta n di n g of t he r ol e of c o m ple me nt i n I g A 
ne p hr o pat h y. J A m S oc Ne p hr ol. 2 0 1 5; 2 6( 7): 1 5 0 3 -1 5 1 2.  
Mar k o witz G S, D' A g ati V D. T he I S N/ R P S 2 0 0 3 classificati o n of l u p us ne p hritis: a n assess me nt 
at 3 years. Ki d n e y I nt. 2 0 0 7; 7 1( 6): 4 9 1 -4 9 5.  
Me djeral -T h o m as 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 ur es 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.  
Merle N S, C h urc h S E, Fr e mea u x -Bacc hi V, R o u m e ni na L T. C o m ple me nt s yste m part I - 
m olec ular mec h a nis ms of acti vati o n a n d re g ulati o n. Fr o nt I m m u n ol. 2 0 1 5a; 6: 2 6 2.  
Merle N S, N oe R, H al b w ac hs -Mecar elli L, Fre mea u x -Bacc hi V, R o u me ni na L T. C o m ple me nt 
s yste m part II: r ole i n i m m u nit y. Fr o nt I m m u n ol. 2 0 1 5 b; 6: 2 5 7. 
M orales E, Gali n d o M, Tr ujill o H, Pra ga M. U p date o n l u p us ne p hritis: l o o ki n g f or a ne w visi o n. 
Ne p hr o n. 2 0 2 1; 1 4 5( 1): 1 -1 3.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 5 1  of 1 5 2  
Ale xi o n C o nfi de ntial  
O ort wij n B D, Eij ge nraa m J W, Rastal di M P, R o os A, Da ha M R, va n K o ot e n C. T he r ole of 
secret or y I g A a n d c o m ple me nt i n I g A ne p hr o p at h y. Se mi n Ne p hr ol. 2 0 0 8; 2 8( 1): 5 8-6 5.  
Pari k h S V, R o vi n B H. C urre nt a n d e mer gi n g t hera pies f or l u p us ne p hritis. J A m S oc Ne p hr ol. 
2 0 1 6; 2 7( 1 0): 2 9 2 9 -2 9 3 9.  
Pari k h S V, Al maa ni S, Br o ds k y S, R o vi n B H. U p date o n l u p us ne p hritis: c ore c urric ul u m 2 0 2 0. 
A m J Ki d ne y Dis. 2 0 2 0; 7 6( 2): 2 6 5 -2 8 1.  
Pic keri n g M C, Wal p ort MJ. Li n ks bet wee n c o m ple me nt a b n or malities a n d s yste mic l u p us 
er yt he mat os us. R he u mat ol o g y ( O xf or d). 2 0 0 0; 3 9( 2): 1 3 3 -1 4 1.  
P u g h D, Gallac her PJ, D ha u n N. Ma na g e me nt of h y perte nsi o n i n c hr o nic ki d ne y disease. Dr u gs. 
2 0 1 9; 7 9( 4): 3 6 5 -3 7 9.  
Ra ue n T, Eit ner F, Fitz n er C, et al. I nte nsi ve s u p p orti ve care pl us i m m u n os u p pressi o n i n I g A 
ne p hr o pat h y. N E n gl J M e d. 2 0 1 5; 3 7 3( 2 3): 2 2 2 5 -2 2 3 6.  
Reic h H N, Tr o y a n o v S, Sc h ole y J W, Cattra n D C. Re missi o n of pr otei n uria i m pr o ves pr o g n osis 
i n I g A n e p hr o pat h y. J A m S oc Ne p hr ol. 2 0 0 7; 1 8( 1 2): 3 1 7 7-3 1 8 3.  
Riz k D V, Maillar d N, J ulia n B A, et al. T he e m er gi n g r ole of c o m ple me nt pr otei ns as a tar get f or 
t hera p y of I g A ne p hr o p at h y. Fr o nt I m m u n ol. 2 0 1 9; 1 0: 5 0 4. 
R o vi n B H, S ol o m o ns N, Pe n der graft W F, 3r d, et al. A ra n d o mize d, c o ntr olle d d o u ble -bli n d 
st u d y c o m pari n g t he efficac y a n d saf et y of d ose-ra n gi n g v ocl os p ori n wit h place b o i n ac hie vi n g 
re missi o n i n patie nts wit h acti ve l u p us ne p hritis. Ki d ne y I nt. 2 0 1 9; 9 5( 1):2 1 9 -2 3 1.  
S o n g D, Z h o u W, S heeri n S H, Sac ks S H. C o m part me ntal l ocalizati o n of c o m ple me nt c o m p o ne nt 
tra nscri pts i n t he n or mal h u ma n ki d ne y. Ne p hr o n. 1 9 9 8; 7 8( 1): 1 5-2 2.  
S o n g D, G u o W Y, Wa n g F M, et al. C o m ple me nt alter nati ve pat h w a ys acti vati o n i n patie nts wit h 
l u p us ne p hritis. A m J Me d Sci. 2 0 1 7; 3 5 3( 3): 2 4 7-2 5 7.  
Te kt o ni d o u M G, Das g u pta A, War d M M. Ris k of e n d -sta ge re nal disease i n patie nts wit h l u p us 
ne p hritis, 1 9 7 1 -2 0 1 5: a s yste matic re vie w a n d ba y esia n meta -a nal ysis. Art hritis R he u mat ol. 
2 0 1 6; 6 8( 6): 1 4 3 2 -1 4 4 1.  
T h ur ma n J M. C o m ple me nt i n ki d ne y disease: c ore c urric ul u m 2 0 1 5. A m J Ki d ne y Dis. 
2 0 1 5; 6 5( 1): 1 5 6 -1 6 8.  
T h ur ma n J M. C o m ple me nt a n d t he ki d ne y: a n o ver vie w. A d v C hr o nic Ki d n e y Dis. 
2 0 2 0; 2 7( 2): 8 6 -9 4.  
T h ur ma n J M, H olers V M. T he ce ntr al r ole of t h e alter nati ve c o m ple me nt pat h wa y i n h u ma n 
disease. J I m m u n ol. 2 0 0 6; 1 7 6( 3): 1 3 0 5 -1 3 1 0.  

Pr ot oc ol A me n d me nt 3. 0  
A L X N 2 0 5 0 -N E P H -2 0 1  
2 1  Fe b  2 0 2 4  
D 7 8 4 5 C 0 0 0 0 1  
Pa ge 1 5 2  of 1 5 2  
Ale xi o n C o nfi de ntial  
T ortaja da A, G utierr ez E, Pic keri n g M C, Pra ga Tere nte M, Me djeral -T h o m as N. T he r ole of 
c o m ple me nt i n I g A ne p hr o pat h y. M ol I m m u n ol. 2 0 1 9; 1 1 4: 1 2 3 -1 3 2.  
Tri marc hi H, Barratt J, Cattra n D C, et al. O xf or d classificati o n of I g A ne p hr o pat h y 2 0 1 6: 
a n u p date fr o m t he I g A n e p hr o pat h y classifi cati o n w or ki n g gr o u p. Ki d ne y I nt. 2 0 1 7; 9 1( 5): 1 0 1 4 -
1 0 2 1.  
Wata na b e H, G ar nier G, Circ ol o A, et al. M o d ulati o n of re nal diseas e i n M R L/l pr mice 
ge neticall y defi cie nt i n t he alter nati ve c o m ple me nt pat h wa y fact or B. J I m m u n ol. 
2 0 0 0; 1 6 4( 2): 7 8 6 -7 9 4.  
Wil mer W A, R o vi n B H, He bert CJ, Ra o S V, K u m or K, He b ert L A. Ma n a g e me nt of gl o mer ular 
pr otei n uria: a c o m me ntar y. J A m S oc Ne p hr ol. 2 0 0 3; 1 4( 1 2): 3 2 1 7 -3 2 3 2.  
Wils o n H R, Me djeral -T h o mas N R, Gil m ore A C, et al. Gl o mer ular me m bra ne attac k c o m ple x is 
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