A Phase 3/4 Study to Evaluate the Safety, Immunogenicity, and Effects on the Alpha1-Proteinase Inhibitor (A1PI) Levels in Epithelial Lining Fluid Following Glassia Therapy in A1PI-Deficient Subjects
Phase: PHASE3
Conditions: Alpha1-antitrypsin Deficiency
Sponsor: Baxalta now part of Shire

B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E W I T H O U T P RI O R A P P R O V AL
P R O T O C O L: 4 7 1 1 0 1
TI T L E:
A P hase 3/ 4 St u d y  t o E val uate t he Safet y, Im m u n o ge nicit y , 
a n d Effects o n t he Al p ha 1 -Pr otei nase I n hi bit or ( A 1 PI ) Le vels 
i n E pit helial L i ni n g Fl ui d F oll o wi n g G L A S SI A T hera p y i n 
A 1 PI -Deficie nt S u bjects
S H O R T TI T L E:
P h 3/ 4 G L A S SI A Safet y,  Im m u n o ge nicit y, a n d Br o nc h oal ve olar 
La va ge St u d y
S T U D Y P H A S E:
P hase 3/ 4
D R U G:
G L A S SI A
N C T N U M B E R:
N C T 0 2 5 2 5 8 6 1
I N D N U M B E R:
1 4 7 7 4
S P O N S O R:
B a x alt a U S I nc. *, 
3 0 0 S hire Wa y , Le xi n gt o n, M A 0 2 4 2 1 , U S A
A N D
B a x alt a I n n o v ati o ns G m b H *, 
I n d ustriestrasse 6 7, A-1 2 2 1 Vie n na , A ustria
* Ba xalta is n o w part of S hire
P R O T O C O L 
HI S T O R Y:
A M E N D M E N T 7 : 2 0 2 0 M A Y 2 6
Re pl aces: A me n d me nt 6 : 2 0 1 8 A U G 2 7
A L L V E R SI O N S: 
A me n d me nt 7: 2 0 2 0 M A Y 2 6
A me n d me nt 6: 2 0 1 8 A U G 2 7
A me n d me nt 5: 2 0 1 7 N O V 2 1
A me n d me nt 4: 2 0 1 6 J A N 1 5
A me n d me nt 3: 2 0 1 5 A U G 2 6
A me n d me nt 2: 2 0 1 5 M A Y 0 7
A me n d me nt 1: 2 0 1 5 J A N 1 9
Ori gi nal: 2 0 1 1 J U L  0 5
F or n o n- c o m m er ci al u s e o nl y

F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 3 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1. S T U D Y P E R S O N N E L
1. 1 A ut h orize d Re prese nt ati ve ( Si g n at or y)/ Res p o nsi ble P art y
, M D
1. 2 St u d y Or g a niz ati o n
T he na me a n d c o ntact i nf or mati o n of t he res p o nsi ble part y a n d i n di vi d uals i n v ol ve d wit h 
t he st u d y (e g, i n vesti gat or(s), s p o ns or’s me dical e x pert a n d st u d y m o nit or, s p o ns or’s 
re prese ntati ve(s), la b orat ories, steeri n g c om mittees, a n d o versi g ht c o m mittees [i ncl u di n g 
et hics c o m mittees ( E Cs)], as a p plica ble) will be mai ntai ne d b y t he s p o ns or a n d pr o vi de d 
t o t he i n vesti gat or.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 4 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
2. S E RI O U S A D V E R S E E V E N T R E P O R TI N G
T he i n vesti gat or will c o m pl y  wit h a p plica ble la ws/re q uire me nts f or rep orti n g seri o us 
a d verse e ve nts ( S A Es) t o t he E Cs.
A L L S A Es , I N C L U DI N G S U S A Rs, A R E T O B E R E P O R T E D O N T H E A D V E R S E 
E V E N T E L E C T R O NI C C A S E R E P O R T F O R M ( E C R F) WI T HI N 2 4 H O U R S 
A F T E R B E C O MI N G A W A R E O F T H E E V E N T. I F T H E E C R F I S N O T 
A V AI L A B L E T H E N T H E S A E M U S T B E R E P O R T E D O N T H E S E RI O U S 
A D V E R S E E V E N T R E P O R T ( S A E R) F O R M A N D T R A N S MI T T E D T O T H E 
S P O N S O R T O M E E T T H E 2 4 H O U R TI M E LI N E R E Q UI R E M E N T.
Dr u g S afet y c o nt act i nf or m ati o n: see S A E Re p ort F or m.
Refer t o S A E Pr ot oc ol Secti o ns a n d t he st u d y te a m r oster f or f urt her i nf or m ati o n.
F or defi niti o ns a n d i nf or mati o n o n t he assess me nt of t hese e ve nts , refer t o t he f oll o wi n g:
  
A E, Secti o n 1 2. 1
  
S A E, Secti o n 1 2. 1. 1. 1
  
S U S A Rs, Secti o n 1 2. 1. 1. 2
  
Assess me nt of A Es , Secti o n 1 2. 1. 2
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 5 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
3. S Y N O P SI S
I N V E S TI G A TI O N A L P R O D U C T
N a m e of I n vesti g ati o n al Pr o d uct 
(I P)
G L A S SI A 
N a m e of Acti ve I n gre die nt
Al p ha 1-Pr otei nase I n hi bit or ( H u ma n)
C LI NI C A L C O N DI TI O N( S)/I N DI C A TI O N( S)
G L A S SI A is i n dicate d f or c hr o nic a u g me ntati o n a n d mai nte na nce t hera p y i n a d ults wit h cli nicall y 
e vi de nt e m p h yse ma d ue t o se vere c o n ge nital deficie nc y of al p ha 1-pr otei nase i n hi bit or ( A 1 PI) (als o 
k n o w n as al p ha 1-a ntitr y psi n [A A T ] deficie nc y ).
P R O T O C O L I D
4 7 1 1 0 1
P R O T O C O L TI T L E
A P hase 3/ 4 St u d y t o E val uate t he Safet y, I m m u n o ge nicit y, a n d 
Effects o n t he Al p ha 1-Pr otei nase I n hi bit or ( A 1 PI) Le vels i n 
E pit helial Li ni n g Fl ui d F oll o wi n g G L A S SI A T hera p y i n 
A 1 PI -Deficie nt S u bjects
S h ort Title
P h 3/ 4 G L A S SI A Safet y, I m m u n o ge nicit y, a n d 
Br o nc h oal ve olar La va ge St u d y
S T U D Y P H A S E
P h 3/ 4
P L A N N E D S T U D Y P E RI O D
I niti ati o n
Q 4 2 0 1 5
Pri m ar y C o m pleti o n
Q 3 2 0 2 0
St u d y C o m pleti o n
Q 1 2 0 2 1
D ur ati o n
A p pr o xi matel y 5 years
S T U D Y O B J E C TI V E S A N D P U R P O S E
St u d y P ur p ose
T he p ur p ose of t he st u d y is 2- f ol d: ( 1) t o f urt her e val uate t he safet y a n d p ote ntial i m m u n o ge nicit y of 
G L A S SI A f oll o wi n g i ntra ve n o us (I V) a d mi nistrati o n via i n -li ne filtrati o n; a n d, ( 2) t o assess t he effects 
of G L A S SI A a u g me ntati o n t hera p y o n t he le vels of A 1 PI a n d 
 i n t he e pit helial li ni n g 
fl ui d ( E L F) f oll o wi n g I V a d mi nistrati o n at a d osa ge of 6 0 m g/ k g b o d y  wei g ht ( B W )/ wee k acti ve A 1 PI 
pr otei n f or 2 5 we e ks i n s u bjects wit h e m p h yse ma d ue t o c o n ge nital A 1 PI deficie nc y.
Pri m ar y O bjecti ves
1.  T o e val uate t he effecti ve ness of t he use of 5 -micr o n i n -li ne filter o n t he safet y a n d p ote ntial 
i m m u n o ge nicit y o f G L A S SI A.
2.  T o deter mi ne t he effects of wee kl y I V a u g me ntati o n t hera p y wit h G L A S SI A at a d osa ge of 
6 0 m g/ k g B W o n a nti ge nic a n d f u ncti o nal A 1 PI le vels i n E L F i n s u bjects wit h c o n ge nital A 1 PI 
deficie nc y .
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 6 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
Sec o n d ar y O bjecti ve
1.  T o c ollect a d diti o nal safet y i nf or mati o n for G L A S SI A.
E x pl or at or y O bjecti ve
 
 
S T U D Y D E SI G N
St u d y T y pe/
Cl assific ati o n/
Disci pli ne
Safet y, I m m u n o ge nicit y , Efficac y
C o ntr ol T y pe
C o nc urre nt (acti ve)
St u d y I n dic ati o n T y pe
Treat me nt
I nter ve nti o n M o del
Parallel
Bli n di n g/ M as ki n g
D o u ble -bli n d
St u d y Desi g n
T his is a P hase 3/ 4, pr os pecti ve, 2 -ar m, d o u ble-bli n d, ra n d o mize d, 
c o ntr olle d, m ultice nter st u d y will assess t he safet y, i m m u n o ge nicit y, a n d 
effects o n t he a nti ge nic a n d f u ncti o nal A 1 PI le vels i n t he E L F f oll o wi n g 
G L A S SI A a d mi nistrati o n via a 5 -micr o n i n -li ne filter at a d o sa ge of 
6 0 m g/ k g B W/ wee k acti ve A 1 PI pr otei n (t he d osi n g re gi me n t hat is 
c urre ntl y a p pr o ve d b y t he F o o d a n d Dr u g A d mi nistrati o n [ F D A]) f or 
2 5 we e ks i n a p pr o xi matel y 3 6 A 1 PI -deficie nt s u bjects. S u bjects will be 
re q uire d t o u n der g o br o nc h osc o p y/ br o nc h oal ve olar la va ge ( B A L) 
pr oce d ures at baseli ne a n d d uri n g a u g me ntati o n t hera p y f or t he e val uati o n 
of t he effects of G L A S SI A a u g me ntati o n t hera p y o n t he le vels of A 1 PI a n d 
 i n t he E L F. A s u bject w ill be c o nsi dere d e val ua ble o nl y 
if acce pta ble B A L sa m ples (see Secti o n 1 0. 3. 4 f or defi niti o ns) are o btai ne d 
at b ot h baseli ne a n d o n-treat me nt B A L visits.
O nce t he tar get o f 1 5 t o 1 8 e val ua ble s u bjects has bee n reac he d, t he 
r e mai ni n g s u bjects t o be e nr olle d will n ot be re q uire d t o u n der g o baseli ne 
a n d o n-treat me nt br o nc h osc o p y/ B A L pr oce d ures. S u bjects wit h c o nfir me d 
me dical hist or y (I C # 1a, # 9 a, # 9 b, E x C # 2 0, # 2 1, # 2 2, # 2 3, a n d # 2 4) 
k n o w n n ot t o meet eli gi bilit y criteria t o u n der g o br o nc h osc o p y/ B A L 
pr oce d ures, ma y be scree ne d a n d ra n d o mize d wit h s p o ns or a p pr o val bef ore 
t he tar get e nr oll me nt of B A L e val ua ble s u bjects is reac he d. 
A 1 PI -deficie nt s u bjects, w h o are A 1 PI treat me nt -naï ve or ha ve bee n treate d 
wit h A 1 PI a u g me ntati o n t hera p y pri or t o st u d y e ntr y, will be e nr olle d. 
S u bjects w h o are recei vi n g or ha ve rece ntl y bee n e x p ose d t o A 1 PI 
a u g me ntati o n t hera p y at t he ti me of st u d y e nr oll me nt will be re q uire d t o 
u n der g o a n a de q uate was h o ut peri o d ( mi ni m u m of 4 w ee ks fr o m t he ti me 
of last A 1 PI treat me nt) d uri n g scree ni n g. Scree ni n g A 1 PI meas ure me nt 
ma y be ta ke n at a n y ti me d uri n g t he scree ni n g peri o d f or treat me nt -naï ve 
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 7 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
s u bjects. F or s u bjects w h o ha ve pre vi o usl y recei ve d al p ha -1 a u g m e ntati o n 
t hera p y h o we ver, scree ni n g A 1 PI meas ure me nt s h o ul d be ta ke n after t he 
wa s h o ut peri o d. D uri n g t he was h o ut peri o d, s u bjects will be all o we d t o 
u n der g o ot her scree ni n g pr oce d ures f or eli gi bilit y deter mi nati o n.
S u bjects meeti n g eli gi bilit y criteria w ill be re q uire d t o u n der g o 
br o nc h osc o p y/ B A L pr oce d ures at baseli ne t o c ollect B A L sa m ples f or t he 
e val uati o n of t he effects of G L A S SI A a u g me ntati o n t hera p y at t he 
a p pr o ve d la bele d d osa ge of 6 0 m g/ k g B W/ wee k acti ve A 1 PI pr otei n o n t he
le vels of A 1 PI a n d 
 i n t he E L F. S u bjects w h o ha ve 
c o m plete d t he baseli ne br o nc h osc o p y/ B A L visit a n d ha ve acce pta ble B A L 
sa m ples will be ra n d o mize d i n a 1: 1 rati o t o 1 of t he 2 treat me nt ar ms as 
s h o w n i n Ta ble 3- 1 . S u bjects w h o are wai ve d fr o m t he br o nc h osc o p y/ B A L 
pr oce d ures w ill be ra n d o mize d after c o m pleti n g scree ni n g pr oce d ures a n d 
c o nfir mati o n of eli gi bilit y ( n ote t hat B A L -relate d eli gi bilit y criteria are n ot 
a p plica ble f or t hese s u bjects).
T a ble 3- 1
Tre at me nt Assi g n me nts
Tre at m e nt 
Ar m
N o. of S u bjects 
P er A r m
Tre at m e nt
1
1 8
G L A S SI A l ot wit h particle l oa ds
re prese nti n g t he hi g h e n d wit hi n t he 
n or m al r a n ge o bser ve d i n G L A S SI A l ots 
ma n ufact ure d
2
1 8
G L A S SI A l ot wit h particle l oa ds
re prese nti n g t he l o w e n d wit hi n t he n or mal 
r a n ge o bser ve d i n G L A S SI A l ots 
ma n ufact ure d
D uri n g t he treat me nt peri o d, all s u bjects will recei ve wee kl y I V i nf usi o ns 
of G L A S SI A at 6 0 m g/ k g B W acti ve A 1 PI pr otei n a d mi nistere d at a rate of 
0. 2 m L/ k g/ mi n f or 2 5 w ee ks (ie, 2 5 pla n ne d i nf usi o ns) via a n I V 
a d mi nistrati o n set t hat i ncl u des a 5 -micr o n i n- li ne filter. T he first i nf usi o n 
( Wee k 1), as well as i nf usi o ns d uri n g Wee k 7, Wee k 1 3 , Wee k 1 9, a n d 
Wee k 2 5, m ust be a d mi nistere d at t he st u d y site t o facilitate m o nit ori n g a n d 
re p orti n g of p ote ntial a d verse e ve nts ( AEs) ass ociate d wit h G L A S SI A 
i nf usi o ns. At t he i n vesti gat or’s discreti o n, s u bse q ue nt i nf usi o ns ma y be 
a d mi nistere d at t he st u d y site or at a n ot her s uita ble l ocati o n (e g, t he 
s u bject’s h o me) b y a q ualifie d healt hcare pr ofessi o nal, as acce pta ble per 
l ocal re g ulati o ns a n d sta n dar d practices of t he st u d y site. T he i nf usi o n rate 
ma y be decrease d or t he i nf usi o n ma y be i nterr u pte d or disc o nti n ue d i n a n 
i n di vi d ual s u bject i n t he e ve nt of i nt olera ble m o derate t o se vere 
i nf usi o n-relate d A Es a n d/ or at t he discreti o n of t he i n vesti gat or.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 8 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
S u bjects will be as ke d t o ret ur n t o t he st u d y site e ver y 6 w ee ks (ie, d uri n g 
Wee ks 1, 7, 1 3, 1 9, a n d 2 5) f or B W meas ure me nts, as we ll as p h ysical 
e xa mi nati o n, vital si g n meas ure me nts, a n d bl o o d dra w f or plas ma A 1 PI 
a n d safet y la b orat or y sa m ple c ollecti o n , as a p plica ble (see Ta ble 2 0. 2 - 1 a n d 
Ta ble 2 0. 3 - 1 f or detaile d list of st u d y pr oce d ures/la b orat or y assess me nts). 
T he o n -treat me nt B A L visit will be c o n d ucte d bet wee n Wee k 1 2 a n d Wee k 
1 4 f oll o wi n g i nitiati o n of G L A S SI A a u g me ntati o n t hera p y f or t he 
deter mi nati o n of a nti ge nic a n d f u ncti o nal A 1 PI le vels i n E L F. 
Af ter c o mpleti n g t he o n -treat me nt B A L visit, s u bjects will c o nti n ue t o 
recei ve wee kl y G L A S SI A i nf usi o ns u ntil Wee k 2 5 (t he last i nf usi o n visit), 
f oll o we d b y t he st u d y c o m pleti o n visit ( Wee k 2 6) at 7 ( ± 3) da ys p ost -last 
i nf usi o n.
If a s u bject e x perie nces a m o derate or se vere c hr o nic o bstr ucti ve 
p ul m o nar y disease ( C O P D ) e xacer bati o n a n d/ or l o wer res pirat or y tract 
i nfecti o n (L R TI ) d uri n g t he scree ni n g peri o d, baseli ne B A L visit will be 
p ost p o ne d o nce i n or der f or t he s u bject t o rec o ver fr o m t he e xacer bati o n 
(ie, a n y si g ns a n d s y m pt o ms of t he C O P D e xacer bati o n a n d/ or L R TI are n o 
l o n ger cli nicall y e vi de nt) a n d re mai n sta ble f or at least 4 wee ks after t he 
e n d of e xacer bati o n. If a m o derate or se vere e pis o de of C O P D e xacer bati o n 
a n d/ or L R TI occ urs d uri n g t he treat me nt p hase, t he s u bject s h o ul d c o nti n ue 
wit h t he pla n ne d st u d y visits a n d t o recei ve w ee kl y i nf usi o ns of G L A S SI A 
as pla n ne d, u nless dee me d me dicall y i na p pr o priate b y t he i n vesti gat or. 
H o w e ver, t he o n -treat me nt B A L visit will be p ost p o ne d u ntil cli nical 
res ol uti o n of t he e xacer bati o n (ie, a n y si g ns a n d s y m pt o ms of t he C O P D 
e xacer bati o n a n d/ or L R TI are n o l o n ger cli nicall y e vi de nt ) pl us a n 
a d diti o nal mi ni m u m peri o d of 4 wee ks after t he e n d of e xacer bati o n.
Pl a n ne d D ur ati o n of 
S u bject P artici p ati o n
T he d urati o n of eac h s u bject’s partici pati o n w ill be a p pr o xi matel y 
8 m o nt hs, i ncl u di n g :
 
a scree ni n g peri o d of u p t o 6 wee ks, 
 
a baseli ne peri o d of u p t o 2 wee ks (f or s u bjects u n der g oi n g baseli ne 
B A L pr oce d ure), 
 
a treat me nt peri o d of 2 5 w ee ks, a n d 
 
a p ost-treat me nt safet y f oll o w- u p peri o d of 7 ( ± 3) da ys after t he last 
i nf usi o n.
Pri m ar y O utc o me Me as ures
S afet y
1.  
N u m ber ( pr o p orti o n) of A Es c o nsi dere d p ote ntiall y relate d t o t he prese nce of pr otei n 
a g gre gates ( particle l oa d) i n t he G L A S SI A s ol uti o n
2.  
I nci de nce of treat me nt-e mer ge nt a d verse reacti o ns ( A Rs) pl us s us pecte d A R s
3.  
N u m ber ( pr o p orti o n) of i nf usi o ns t hat are disc o nti n ue d, sl o we d, or i nterr u pte d d ue t o a n A E
4.  
N u m ber ( pr o p orti o n) of s u bjects w h o de vel o p bi n di n g a n d/ or ne utralizi n g a nti -A 1 PI a nti b o dies
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 9 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
Effic ac y
1.  
A nti ge nic A 1 PI le vels i n E L F
2.  
F u ncti o nal A 1 PI (als o k n o w n as a nti -ne utr o p hil elastase ca pacit y [ A N E C]) le vels i n E L F
Sec o n d ar y O utc o m e Me as ures
S afet y
1.  
I nci de nce of treat me nt-e mer ge nt A Es
2.  
N u m ber ( pr o p orti o n) of s u bjects w h o e x perie nce d a s hift fr o m n or mal or cli nicall y i nsi g nifica nt 
a b n or mal la b orat or y val ues at baseli ne t o cli nicall y si g nifica nt a b n or mal la b orat or y val ues
(t hres h ol ds as o utli ne d i n Secti o n 2 0. 4 ) f oll o wi n g G L A S SI A a d mi nistrati o n
3.  
N u m ber ( pr o p orti o n) of s u bjects wit h treat me nt -e mer ge nt ser oc o n versi o n or p ositi ve n ucleic 
aci d test ( N A T) f or par v o vir us B 1 9 ( B 1 9 V)
E x pl or at or y O utc o m e Me as ures
 
I N V E S TI G A TI O N A L P R O D U C T( S), D O S E A N D M O D E O F A D MI NI S T R A TI O N
Acti ve Pr o d uct
G L A S SI A
D ose: 6 0 m g/ k g B W acti ve A 1 PI pr otei n 
D os a ge f or m : I njecti o n, sol uti o n
D os a ge fre q ue nc y : Wee kl y
M o de of A d m i nistr ati o n: I ntra ve n o us
S U B J E C T S E L E C TI O N
T ar gete d Accr u al
E nr oll me nt will be cl ose d w he n b ot h c o n diti o ns are met: 
(a) 1 5 t o 1 8 e val ua ble s u bjects wit h acce pta ble B A L sa m ples 
c ollecte d fr o m b ot h t he baseli ne a n d o n -treat me nt B A L visits
( b) A mi ni m u m of 3 6 ra n d o mize d s u bjects.
N u m ber of 
Gr o u ps/ Ar ms/ C o h orts
2
I ncl usi o n Criteri a
A s u bject m ust meet A L L of t he f oll o wi n g criteria t o be eli gi ble f or i ncl usi o n i n t his st u d y:
1.  
Male or fe male s u bjects meeti n g t he f oll o wi n g a ge criteria:
(a) F or s u bjects w h o will u n der g o br o nc h osc o p y/ B A L pr oce d ures: 1 8 t o 7 5 years of a ge at t he 
ti me of scree ni n g. 
( b) F or s u bjects w h o will be wai ve d fr o m u n der g oi n g br o nc h osc o p y / B A L pr oce d ures -: 
1 8 years of a ge or ol der at t he ti me of scree ni n g.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 1 0 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
2.  
D oc u me nte d A 1 PI g e n ot y pe of Pi * Z/ Z, Pi * Z/ N ull, Pi * Malt o n/ Z, Pi * N ull/ N ull , or ot her “at -
ris k” allelic c o m bi nati o ns s uc h as S Z (e xcl u di n g M S
a n d M Z
wit h o ut t he prese nce of a n ot her 
all o wa ble at -ris k ge n ot y pe ) a n d a n e n d o ge n o us A 1 PI plas ma le vels of 
≤1 1 µ M ( ≤0. 5 7 2 m g/ m L) .
3.  
Scree ni n g le vels of e n d o ge n o us plas ma (a nti ge nic) A 1 PI of ≤1 1 µ M at a n y ti me d uri n g t he 
scree ni n g peri o d f or treat me nt -naï ve s u bjects, or f oll o w i n g a 4- we e k mi ni m u m was h o ut fr o m 
pre vi o us a u g me ntati o n t hera p y i n treat me nt -e x perie nce d s u bjects.
4.  
S u bject s m ust ha ve at least o ne of t he f oll o wi n g: cli nical dia g n osis of e m p h yse ma, e vi de nce of 
e mp h yse ma o n c hest X -r a y or c o m p uterize d t o m o gra p h y ( C T) sca n of t he c hest, a n d/ or 
e vi de nce of air wa y o bstr ucti o n w hic h is n ot c o m pletel y re verse d w it h br o nc h o dilat or treat me nt 
at t he ti me of scree ni n g.
5.  
If t he s u bject is bei n g treate d wit h a n y res pirat or y me dicati o ns i ncl u di n g i n hale d 
br o nc h o dilat ors, i n hale d a ntic h oli ner gics, i n hale d c ortic oster oi ds, or lo w -d ose s yste mic 
c ortic oster oi ds ( pre d nis o ne ≤1 0 m g/ da y or its e q ui vale nt), t he d oses of t he s u bject’s 
me dicati o ns ha ve re mai ne d u nc ha n ge d f or at least 1 4 da ys pri or t o scree ni n g.
6.  
T he s u bject is a n o ns m o ker or has cease d s m o ki n g f or a mi ni m u m of 1 3 w ee ks pri or t o 
scree ni n g (ser u m c oti ni ne le vel at scree ni n g wit hi n n or mal ra n ge of a n o ns m o ker) a n d a grees t o 
refrai n fr o m s m o ki n g t hr o u g h o ut t he c o urse of t he st u d y. S u bjects wit h a p ositi ve c oti ni ne test 
d ue t o nic oti ne re place me nt t hera p y (e g , patc hes, c he wi n g g u m), va p or ci garettes , or s n uff are 
eli gi ble.
7.  
If fe male of c hil d beari n g p ote ntial, t he s u bject prese nts wit h a ne gati ve pre g na nc y test at 
scree ni n g a n d a grees t o e m pl o y a de q uate birt h c o ntr ol meas ures f or t he d urati o n of t he st u d y.
8.  
T he s u bject is w illin g a n d a ble t o c o m pl y wit h t he re q uire me nts of t he pr ot oc ol.
9.  
T he s u bject m ust ha ve p ul m o nar y f u ncti o n at t he ti me of scree ni n g w hic h meet s b ot h of t he 
f oll o wi n g:
(a) P ost-br o nc h o dilat or f orce d e x pirat or y v ol u me i n 1 s ec o n d ( F E V 1) ≥5 0 % of pre dicte d
( b) If FE V 1 is > 8 0 % pre dicte d, t he n F E V 1/f orce d vital ca pacit y ( F V C) m ust be < 0. 7 .
N ote: I ncl usi o n criteri o n # 1a , # 9a, a n d # 9 b are n ot a p plica ble t o s u bjects w h o are n ot re q uire d t o 
u n der g o t he br o nc h osc o p y/ B A L pr oce d ures.
E xcl usi o n Criteri a
A s u bject w h o meets A N Y of t he f oll o wi n g criteria is N O T eli gi ble f or t his st u d y:
1.  
T he s u bject is e x perie nci n g or has a hist or y of cli nicall y si g nifica nt p ul m o nar y disease (ot her 
t ha n C O P D, e mp h yse m a, c hr o nic br o nc hitis, mil d br o nc hiectasis, a n d sta ble ast hma) .
2.  
T he s u bject is e x perie nci n g or has a hist or y of c hr o nic se vere c or p ul m o nale (resti n g mea n 
p ul m o nar y arter y press ure ≥4 0 m m H g) .
3.  
T he s u bject r o uti nel y pr o d uces m ore t ha n 1 ta bles p o o n of s p ut u m per da y.
4.  
T he s u bject has a hist or y of fre q ue nt p ul m o nar y e xacer bati o ns ( greater t ha n 2 m o derate or 
se vere e xacer bati o ns wit hi n 5 2 w ee ks pri or t o scree ni n g ; see Secti o n 1 0. 4 f or t he defi niti o n of 
m o derate a n d se vere e xacer bati o ns ).
5.  
T he s u bject is e x perie nci n g a p ul m o nar y e xacer bati o n at t he ti me of scree ni n g (s u bject ma y be 
rescree ne d 4 w ee ks after t he cli nical res ol uti o n of a n e xacer bati o n).
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 1 1 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
6.  
T he s u bject has cli nicall y si g nifica nt a b n or malities ( ot her t ha n e m p h yse ma, c hr o nic br o nc hitis, 
or mil d br o nc hiectasis) detecte d o n c hest X -ra y or C T sca n at t he ti me of scree ni n g . (Past 
rec or ds o btai ne d w it hi n 5 2 wee ks pri or t o scree ni n g ma y be use d, if a vaila ble ).
7.  
T he s u bject has cli nicall y si g nifica nt a b n or malities detecte d o n a 1 2 -lea d electr ocar di o gra m 
( E C G) perf or me d at t he ti me of scree ni n g (Past rec or ds o btai ne d wit hi n 2 6 w ee ks pri or t o 
scree ni n g ma y be use d, if a vaila ble) .
8.  
T he s u bject has cli nicall y si g nifica nt c o n gesti ve heart fail ure w it h Ne w Y or k Heart Ass ociati o n 
( N Y H A) Class III/I V s y m pt o ms.
9.  
T he s u bject is e x perie nci n g a n acti ve mali g na nc y or has a 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 t he f oll o wi n g: a de q uatel y treate d basal cell or 
s q ua m o us cell carci n o ma of t he s ki n, carci n o ma i n sit u of t he cer vi x, or sta ble pr ostate ca ncer 
n ot re q uiri n g treat me nt.
1 0. 
T he s u bject has a hist or y of l u n g or ot her or ga n tra ns pla nt, is c urre ntl y o n a tra ns pla nt list, or 
has u n der g o ne maj or l u n g s ur ger y.
1 1. 
T he s u bject is recei vi n g l o n g-t er m ar o u n d-t he-cl oc k o x y ge n ( O 2) s u p ple me ntati o n. (the 
f oll o wi n g are all o we d: s h ort-t er m use of O 2 s u p ple me ntati o n [e g, f or t he ma na ge me nt of ac ute 
C O P D e xacer bati o n ], O 2 s u p ple me ntati o n re q uire d d uri n g ni g ht ti me o nl y , a n d s u p ple me ntal O 2
wit h c o nti n u o us p ositi ve air wa y press ure [ C P A P] or bi -le vel p ositi ve air wa y press ure 
[ Bi P A P]).
1 2. 
K n o w n hist or y of h y perse nsiti vit y f oll o wi n g i nf usi o ns of h u ma n bl o o d or bl o o d c o m p o ne nts.
1 3. 
I m m u n o gl o b uli n A (I g A) deficie nc y ( < 8 m g/ d L at scree ni n g).
1 4. 
A b n or m al cli nical la b orat or y res ults o btai ne d at t he ti me of scree ni n g meeti n g a n y of t he 
f oll o wi n g criteria:
a.  Ser u m ala ni ne a mi n otra nsferase ( A L T) > 3. 0 ti mes u p per li mit of n or mal ( U L N)
b.  Ser u m t otal bilir u bi n > 2. 0 ti mes U L N
c.  > 2 + pr otei n uria o n uri ne di pstic k a nal ysis
d.  Ser u m creati ni ne > 2. 0 ti mes U L N
e.  A bs ol ute ne utr o p hil c o u nt ( A N C) < 1 5 0 0 cells/ m m
3
f.  He m o gl o bi n ( H g b) < 9. 0 g/ d L
g.  Platelet c o u nt < 1 0 0, 0 0 0/ m m 3
1 5. 
O n g oi n g acti ve i nfecti o n wit h he patitis A vir us ( H A V), he patitis B vir us ( H B V), he patitis C 
vir u s ( H C V), or h u ma n i m m u n o deficie nc y vir us ( HI V) T y pe 1/ 2 at t he ti me of scree ni n g.
1 6. 
T he s u bject has a n y cli nicall y si g nifica nt me dical, ps yc hiatric, or c o g niti ve ill ness, or a n y ot her 
u nc o ntr olle d me dical c o n diti o n (e g , u nsta ble a n gi na, tra nsie nt isc he mic attac k) t hat, i n t he 
o pi ni o n of t he i n vesti gat or, w o ul d i m pe de t he s u bject’s a bilit y t o c o m pl y wit h t he st u d y 
pr oce d ures, p ose i ncrease d ris k t o t he s u bject’s safet y, or c o nf o u n d t he i nter pretati o n of st u d y 
res ults.
1 7. 
T he s u bject has partici pate d i n a n ot her cli nical st u d y i n v ol vi n g a n I P or i n vesti gati o nal de vice
wit hi n 3 0 da ys pri or t o e nr oll me nt or is sc he d ule d t o partici pate i n a n ot her cli nical st u d y 
i n v ol vi n g a n I P or de vice d uri n g t he c o urse of t his st u d y.
1 8. 
T he s u bject is a fa mil y me m ber or e m pl o yee of t he i n vesti gat or.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 1 2 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 9. 
If fe male, t he s u bject is n ursi n g at t he ti me of scree ni n g.
N ote: E xcl usi o n criteria # 2 0, # 2 1, # 2 2, # 2 3, a n d # 2 4 are n ot a p plica ble t o s u bjects w h o are n ot re q uire d 
t o u n der g o t he br o nc h osc o p y/ B A L pr oce dures.
2 0. 
T he s u bject has c o ntrai n dicati o n(s) t o br o nc h osc o p y s uc h as rece nt m y ocar dial i nfarcti o n, 
u nsta ble a n gi na , ot her car di o p ul m o nar y i nsta bilit y, trac heal o bstr ucti o n or ste n osis, m o derate t o 
se vere h y p o xe mia or a n y de gree of h y perca p nia, u nsta ble ast h ma , Sta ge 4 or 5 c hr o nic ki d ne y 
disease , p ul m o nar y h y perte nsi o n, se vere he m orr ha gic diat hesis, a n d cer vical C 1/ C 2 art hritis.
2 1. 
T he s u bject has ha d l u n g s ur ger y w hic h ma y i nterfere w it h br o nc h osc o p y.
2 2. 
K n o w n hist or y of aller gic/ h y perse nsiti vit y reacti o ns t o me dicati o ns use d d uri n g a n d f or 
peri o perati ve care ass ociate d wit h t he br o nc h osc o p y/ B A L pr oce d ures, s uc h as l ocal a nest hetics, 
se dati ves, pai n c o ntr ol me dicati o ns.
2 3. 
T he s u bject is recei vi n g a n d re q uires l o n g -ter m ( > 4 wee ks) i m m u n os u p pressi ve t hera p y, s uc h 
as s yste mic c ortic oster oi ds at d oses greater t ha n 1 0 m g/ da y of pre d nis o ne ( or its e q ui vale nt), 
m yc o p he n olate m ofetil, azat hi o pri ne, c ycl o p h os p ha mi de, a n d rit u xi ma b.
2 4. 
If a s u bject is recei vi n g a ntic oa g ula nt or a nti-platelet t hera p y (s uc h as warfari n a n d 
cl o pid o grel), t he s u bject is u n willi n g t o or u na ble t o safel y disc o nti n ue a ntic oa g ula nt or a nti -
platelet t hera p y wit hi n 7 da ys pri or t o u ntil at least 2 4 h o urs after t he B A L pr oce d ures. A n 
e xce pti o n is l o w-d ose as piri n al o ne w hic h is all o w e d.
S T A TI S TI C A L A N A L Y SI S
S a m ple Size C alc ul ati o n
T he sa m ple size calc ulati o n f or t he B A L c o m p o ne nt of t he st u d y was base d o n t he nat ural l o g 
tra nsf or me d pri mar y e n d p oi nt data, E L F a nti ge nic A 1 PI le vel ( n M), ge nerate d d uri n g a pre vi o us cli nical 
st u d y (Cli nical Pr ot oc ol 4 6 0 5 0 2 ; Ba xter Healt hcare C or p orati o n) f or t he e val uati o n of t he effects of 
A 1 PI a u g me ntati o n t hera p y wit h A R A L A S T N P o n t he le vels of A 1 PI a n d ot her a nal ytes i n t he E L F . I n 
Cli nical St u d y 4 6 0 5 0 2, a mea n differe nce fr o m pre - t o p ost-treat me nt i n E L F a nti ge nic A 1 PI of 1. 3 2 
wit h sta n dar d de viati o n of 0. 9 6 o n nat ural l o g scale was o bser ve d. Usi n g t his varia nce esti mate, a sa m ple 
size of 1 5 e val ua ble s u bjects s h o ul d be s ufficie nt t o detect a mea n differe nce i n t he nat ural l o g 
tra nsf or me d E L F a nti ge nic A 1 PI of a p pr o xi matel y 0. 8 7 wit h 9 0 % p o wer, usi n g a paire d t -test a n d a 
1- si de d si g nifica nce le vel of 0. 0 2 5. 
A sa m ple size of 1 5 e val ua ble s u bjects will als o be s ufficie nt t o detect a mea n differe nce i n t he nat ural 
l o g tra nsf or me d E L F f u ncti o nal A 1 PI ( A N E C) of a p pr o xi matel y 1. 0 4, wit h 9 0 % p o wer, ass u mi n g a 
sta n dar d de viati o n i n t he differe nces bet wee n pre- a n d p ost-treat me nt A N E C val ues t o be 2 0 % hi g her 
t ha n t hat f or a nti ge nic A 1 PI.
Base d o n t he e x perie nce fr o m Cli nical St u d y 4 6 0 5 0 2 , it is esti mate d t hat a p pr o xi matel y 2 6 t o 3 2 s u bjects 
will be nee de d i n or der t o ac hie ve 1 5 t o 1 8 B A L eval ua ble s u bjects , res pecti vel y. T h us, a n o verall st u d y 
e nr oll me nt tar get of 3 6 s u bjects s h o ul d be a de q uate t o meet t he tar get sa m ple size f or t he B A L 
c o m p o ne nt of t he st u d y.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 1 3 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
Pl a n ne d St atistic al A n al ysis
E L F a nti ge nic a n d f u ncti o nal A 1 PI le vels, as well as c ha n ges fr o m baseli ne, will be s u m marize d 
descri pti vel y a n d dis pla ye d gra p hicall y ( data per mitti n g) base d o n data p o ole d acr oss b ot h treat me nt 
ar ms. T he se c ha n ges will be a nal yze d i n 1- si de d paire d t -tests at a n al p ha le vel of 0. 0 2 5.
Plas ma tr o u g h a nti ge nic a n d f u ncti o nal A 1 PI le vels , as well as c ha n ges fr o m baseli ne , will be 
s u m marize d descri pti vel y a n d dis pla ye d gra p hicall y ( data per mitti n g) base d o n data p o ole d acr oss b ot h 
treat me nt ar ms. Plas ma a nti ge nic a n d f u ncti o nal A 1 PI le vels o btai ne d at t he baseli ne a n d o n -treat me nt 
B A L visits will be s u m marize d se paratel y a n d, data per mitti n g, t o be c orrelate d w it h t he c orres p o n di n g 
val ues i n t he E L F.
 
 
C ha n ges fr o m baseli ne i n E L F a n d plas ma a nti ge nic a n d f u ncti o nal A 1 PI le ve ls will be s u m marize d i n 
t he f oll o wi n g s u b gr o u ps: b y se x, a ge ( ≤6 5; > 6 5 ), race, a n d et h nicit y.
T he safet y o utc o me meas ures , i ncl u di n g A Es of i nterest t hat ma y be i m m u ne-me diate d, treat me nt -
e mer ge nt A Rs pl us s us pecte d A Rs (see Secti o n 1 2. 1. 1. 3 f or defi niti o ns), a n d treat me nt-e mer ge nt 
i nci de nce of i m m u n o ge nicit y a n d ser oc o n versi o n, will be s u m marize d descri pti vel y wit h 9 5 % 
c o nfi de nce i nter vals ( CIs) as a p pr o priate. I n t he e ve nt of treat me nt-e mer ge nt i m m u n o ge nicit y, a n y 
p ote ntial te m p oral relati o ns hi p of a nti -A 1 PI a nti b o d y f or mati o n wit h t he occ urre nce of p ote ntiall y 
i m m u ne-me diate d A Es will be e xa mi ne d.
S u m mar y ta bles of la b orat or y data as well as s hift ta bles of n or mal vers us a b n or mal l o w  / hi g h 
la b orat or y val ues will be create d b y eac h treat me nt ar m as well as p o ole d t o get her. I n a d diti o n, s hift 
ta bles of n or mal vers us a b n or mal cli nicall y si g nifica nt / n ot-cli nicall y si g nifica nt la b orat or y val ues 
( usi n g t hres h ol ds i n secti o n 2 0. 4 ) will be create d se paratel y b y eac h treat me nt ar m as well as p o ole d 
t o get her. T he cli nical si g nifica nce of a b n or mal la b orat or y val ues as assesse d b y t he i n vesti gat or is t o be 
ca pt ure d i n t he s o urce d oc u me nts. A b n or mal la b orat or y val ues c o nsi dere d cli nicall y si g nifica nt b y t he 
i n vesti gat or are t o be re p orte d i n t he C R F as a n A E or as Me dical Hist or y ( de pe n di n g o n w het her t he y 
occ urre d d uri n g or after t he first i nf usi o n or pri or t o t he first i nf usi o n).
Safet y para meters will be s u m marize d descri pti vel y b y se x, a ge (≤6 5; > 6 5) , race, a n d et h nicit y. N o 
h y p ot hesis tests are pla n ne d ; h o w e ver, 
 
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 1 4 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
4. T A B L E O F C O N T E N T S
P R O T O C O L SI G N A T U R E P A G E ................................................................................. 2
1. S T U D Y P E R S O N N E L .................................................................................................. 3
1. 1 A ut h orize d Re prese nt ati ve ( Si g n at or y)/ Res p o nsi ble P art y ................................ 3
1. 2 St u d y Or g a niz ati o n ................................................................................................. 3
2. S E RI O U S A D V E R S E E V E N T R E P O R TI N G ........................................................... 4
3. S Y N O P SI S ..................................................................................................................... 5
4. T A B L E O F C O N T E N T S ........................................................................................... 1 4
5. LI S T O F A B B R E VI A T I O N S .................................................................................... 1 9
6. B A C K G R O U N D I N F O R M A TI O N .......................................................................... 2 2
6. 1 Descri pti o n of I n vesti g ati o n al Pr o d uct ............................................................... 2 5
6. 1. 1 R ati o n ale f or t he Selecti o n of D osi n g Re gi me n ........................................... 2 5
6. 1. 2 R ati o n ale f or t he Selecti o n of R o ute of A d mi nistr ati o n a n d I nf usi o n R ate
......................................................................................................................... 2 5
6. 2 Cli nic al C o n diti o n/I n dic ati o n .............................................................................. 2 6
6. 3 P o p ul ati o n T o Be St u die d ..................................................................................... 2 6
6. 4 Fi n di n gs Fr o m N o ncli nic al a n d Cli nic al St u dies ............................................... 2 6
6. 4. 1 S u m m ar y of N o ncli nic al D at a ....................................................................... 2 6
6. 4. 2 S u m m ar y of Cli nic al D at a ............................................................................. 2 6
6. 5 E v al u ati o n of A ntici p ate d Ris ks a n d Be nefits of t he I n vesti g ati o n al Pr o d uct(s) 
t o H u m a n S u bjects................................................................................................ 2 7
6. 6 C o m pli a nce St ate me nt .......................................................................................... 2 7
7. S T U D Y P U R P O S E A N D O B J E C TI V E S ................................................................. 2 8
7. 1 St u d y P ur p ose ....................................................................................................... 2 8
7. 2 Pri m ar y O bjecti ves ............................................................................................... 2 8
7. 3 Sec o n d ar y O bjecti ve ............................................................................................. 2 8
7. 4 E x pl or at or y O bjecti ve .......................................................................................... 2 8
8. S T U D Y D E SI G N ......................................................................................................... 2 9
8. 1 Brief S u m m ar y ...................................................................................................... 2 9
8. 2 St u d y Desi g n .......................................................................................................... 2 9
8. 3 D ur ati o n of St u d y Peri o d(s) a n d S u bject P artici p ati o n .................................... 3 1
8. 4 O utc o me Me as ures ............................................................................................... 3 1
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 1 5 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
8. 4. 1 Pri m ar y O utc o me Me as ures ......................................................................... 3 1
8. 4. 2 Sec o n d ar y O utc o me Me as ures ..................................................................... 3 2
8. 4. 3 E x pl or at or y O utc o me Me as ures ................................................................... 3 2
8. 5 R a n d o miz ati o n a n d Bli n di n g ............................................................................... 3 2
8. 5. 1 U n bli n di n g Pr oce d ures at St u d y Sites ......................................................... 3 3
8. 6 St u d y St o p pi n g R ules ............................................................................................ 3 3
8. 7 I n vesti g ati o n al Pr o d uct(s) .................................................................................... 3 3
8. 7. 1 P ac k a gi n g, L a beli n g, a n d St or a ge................................................................ 3 3
8. 7. 2 Pre p ar ati o n of I nf usi o n S ol uti o n .................................................................. 3 3
8. 7. 3 A d mi nistr ati o n ............................................................................................... 3 4
8. 7. 4 Descri pti o n of Tre at me nt .............................................................................. 3 4
8. 7. 5 I n vesti g ati o n al Pr o d uct Acc o u nt a bilit y ....................................................... 3 4
8. 8 S o urce D at a ........................................................................................................... 3 5
9. S U B J E C T S E L E C TI O N , WI T H D R A W A L, A N D DIS C O N TI N U A TI O N ..........3 6
9. 1 I ncl usi o n Criteri a.................................................................................................. 3 6
9. 2 E xcl us i o n Criteri a................................................................................................. 3 7
9. 3 Wit h dr a w al a n d Disc o nti n u ati o n ........................................................................ 3 9
1 0. S T U D Y P R O C E D U R E S .......................................................................................... 4 1
1 0. 1 I nf or me d C o nse nt a n d E nr oll me nt ................................................................... 4 1
1 0. 2 S u bject I de ntific ati o n C o de ................................................................................ 4 1
1 0. 3 Scree ni n g a n d St u d y Visits ................................................................................. 4 1
1 0. 3. 1 Scree ni n g Visit .............................................................................................. 4 1
1 0. 3. 1. 1 C o nfir m ati o n of Se vere C o n ge nit al A 1 PI Deficie nc y ........................4 2
1 0. 3. 1. 2 P ul m o n ar y F u ncti o n Tests ................................................................... 4 2
1 0. 3. 1. 3 Rescree ni n g ........................................................................................... 4 3
1 0. 3. 2 I nf usi o n Visits ............................................................................................... 4 3
1 0. 3. 2. 1 I P A d mi nistr ati o n ................................................................................. 4 3
1 0. 3. 2. 2 M a n a ge me nt of Tre at me nt -E m er ge nt ( S) A Es ................................... 4 5
1 0. 3. 2. 3 Pre -Me dic ati o ns .................................................................................... 4 6
1 0. 3. 2. 4 P ost -I nf usi o n F oll o w-U p ...................................................................... 4 6
1 0. 3. 3 Cli nic al Assess me nt Visits ........................................................................... 4 7
1 0. 3. 4 B A L Visits ..................................................................................................... 4 7
1 0. 4 C O P D E x acer b ati o n a n d L o wer Res pir at or y Tr act I nfecti o n .......................4 9
1 0. 5 Me dic ati o ns a n d N o n - Dr u g T her a pies.............................................................. 5 0
1 0. 6 S u bject C o m pleti o n/ Disc o nti n u ati o n ................................................................ 5 1
1 0. 7 Pr oce d ures f or M o nit ori n g S u bject C o m pli a nce ............................................. 5 2
1 1. A S S E S S M E N T O F E F FI C A C Y .............................................................................. 5 3
1 1. 1 E L F A nti ge nic a n d F u ncti o n al A 1 PI Le vels................................ ..................... 5 3
1 1. 2 
.................................................................................... 5 3
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 1 6 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 2. A S S E S S M E N T O F S A F E T Y ................................................................................... 5 4
1 2. 1 A d verse E ve nts .................................................................................................... 5 4
1 2. 1. 1 Defi nit i o ns..................................................................................................... 5 4
1 2. 1. 1. 1 Seri o us A d verse E ve nt .......................................................................... 5 4
1 2. 1. 1. 2 N o n -Seri o us A d verse E ve nt ................................................................. 5 5
1 2. 1. 1. 3 A d verse Re acti o ns Pl us S us pecte d A d verse Re acti o ns ...................... 5 5
1 2. 1. 1. 4 U ne x pecte d A d verse E ve nts ................................................................. 5 5
1 2. 1. 1. 5 A d verse E ve nts P ote nti all y Ass oci ate d wit h Pr otei n A g gre g ates .....5 6
1 2. 1. 1. 6 Pree xisti n g Dise ases .............................................................................. 5 6
1 2. 1. 2 Assess me nt of A d verse E ve nts .................................................................... 5 6
1 2. 1. 2. 1 Se verit y .................................................................................................. 5 7
1 2. 1. 2. 2 C a us alit y ................................................................................................ 5 8
1 2. 1. 2. 3 S afet y Re p orti n g ................................................................................... 5 9
1 2. 2 Ur ge nt S afet y Me as ures ..................................................................................... 6 0
1 2. 3 U nt o w ar d Me dic al Occ urre nces ........................................................................ 6 1
1 2. 4 N o n -Me dic al C o m pl ai nts
................................................................................... 6 1
1 2. 5 Me dic al, Me dic ati o n, a n d N o n -Dr u g T her a p y Hist or y ................................... 6 2
1 2. 6 P h ysic al E x a mi n ati o ns ........................................................................................ 6 2
1 2. 7 Cli nic al L a b or at or y P ar a meters ........................................................................ 6 2
1 2. 7. 1 He m at ol o g y a n d Cli nic al C he mistr y .......................................................... 6 2
1 2. 7. 1. 1 Ot her A n al ysis ....................................................................................... 6 3
1 2. 7. 2 C o m ple me nt Acti v ati o n a n d I m m u ne C o m ple x P a nel ............................. 6 3
1 2. 7. 3 Vir al Ser ol o g y a n d N ucleic Aci d Tests ....................................................... 6 4
1 2. 7. 4 Uri ne Tests .................................................................................................... 6 4
1 2. 7. 5 Assess m e nt of Cli nic al L a b or at or y V al ues ................................................ 6 5
1 2. 7. 5. 1 Assess me nt of A b n or m al L a b or at or y V al ues ..................................... 6 5
1 2. 7. 6 Bi o b a n ki n g .................................................................................................... 6 5
1 2. 8 Pl as m a A nti ge nic a n d F u ncti o n al A 1 PI Le vels ................................................ 6 6
1 2. 9 I m m u n o ge nicit y .................................................................................................. 6 7
1 2. 1 0 Vit al Si g ns .......................................................................................................... 6 7
1 3. S T A TI S TI C S ............................................................................................................. 6 9
1 3. 1 S a m ple Size a n d P o wer C alc ul ati o ns ................................................................ 6 9
1 3. 2 D at asets a n d A n al ysis C o h orts .......................................................................... 6 9
1 3. 2. 1 F ull A n al ysis Set ........................................................................................... 6 9
1 3. 2. 2 Per -Pr ot oc ol A n al ysis Set ............................................................................ 6 9
1 3. 2. 3 B A L A n al ysis Set ......................................................................................... 7 0
1 3. 2. 4 Per -Pr ot oc ol B A L A n al ysis Set ................................................................... 7 0
1 3. 2. 5 S afet y A n al ysis Set ....................................................................................... 7 0
1 3. 3 H a n dli n g of Missi n g, U n use d, a n d S p uri o us D at a ........................................... 7 0
1 3. 4 Met h o ds of A n al ysis................................ ............................................................ 7 0
1 3. 4. 1 Effic ac y O utc o me Me as ures ....................................................................... 7 0
1 3. 4. 2 E x p os ure ....................................................................................................... 7 1
1 3. 4. 3 S afet y O utc o me Me as ures ........................................................................... 7 2
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 1 7 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 3. 5 Pl a n ne d I nteri m A n al ysis of t he St u d y ............................................................. 7 4
1 4. DI R E C T A C C E S S T O S O U R C E D A T A/ D O C U M E N T S .................................... 7 4
1 5. Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E...................................... 7 5
1 5. 1 I n vesti g at or’s Res p o nsi bilit y .............................................................................. 7 5
1 5. 1. 1 Fi n al Cli nic al St u d y Re p ort ........................................................................ 7 5
1 5. 2 Tr ai ni n g ............................................................................................................... 7 5
1 5. 3 M o nit ori n g ........................................................................................................... 7 5
1 5. 3. 1 S afet y M o nit ori n g ........................................................................................ 7 5
1 5. 4 A u diti n g ............................................................................................................... 7 6
1 5. 5 N o n -C o m pli a nce wit h t he Pr ot oc ol ................................................................... 7 6
1 5. 6 L a b or at or y a n d Re a der St a n d ar diz ati o n ......................................................... 7 6
1 6. E T HI C S ..................................................................................................................... 7 7
1 6. 1 S u bject Pri v ac y ................................................................................................... 7 7
1 6. 2 Et hics C o m mittee a n d Re g ul at or y A ut h orities ................................................ 7 7
1 6. 3 I nf or me d C o nse nt ............................................................................................... 7 7
1 6. 4 D at a M o nit ori n g C o m mittee .............................................................................. 7 8
1 7. D A T A H A N D LI N G A N D R E C O R D K E E PI N G................................................... 7 9
1 7. 1 C o nfi de nti alit y P olic y ......................................................................................... 7 9
1 7. 2 S t u d y D oc u me nts a n d C ase Re p ort F or ms....................................................... 7 9
1 7. 3 D oc u me nt a n d D at a Rete nti o n ........................................................................... 7 9
1 8. FI N A N CI N G A N D I N S U R A N C E ........................................................................... 8 0
1 9. P U B LI C A TI O N P O LI C Y ........................................................................................ 8 0
2 0. S U P P L E M E N T S ....................................................................................................... 8 1
2 0. 1 St u d y Fl o w C h art ................................................................................................ 8 1
2 0. 2 Sc he d ule of St u d y Pr oce d ures a n d Assess me nts .............................................. 8 2
2 0. 3 Sc he d ule of Cli nic al L a b or at or y Assess me nts .................................................. 8 5
2 0. 4 T hres h ol ds f or Cli nic all y Si g nific a nt L a b or at or y A b n or m alities .................. 8 8
2 1. R E F E R E N C E LI S T................................ .................................................................. 9 0
2 2. S U M M A R Y O F C H A N G E S .................................................................................... 9 3
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 1 8 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
T a bles
Ta ble 3- 1 Treat me nt Assi g n me nts ...................................................................................... 7
Ta ble 8- 1 Treat me nt Assi g n me nts .................................................................................... 3 0
Ta ble 2 0. 2- 1 Sc he d ule of St u d y  Pr oce d ures a n d Assess me nts......................................... 8 2
Ta ble 2 0. 3- 1 Cli nical La b orat or y  Assess me nts................................................................ 8 5
Fi g ures
Fi g ure 1 0- 1 E xacer bati o n of C O P D .................................................................................. 4 9
Fi g ure 2 0- 1 St u d y  Fl o w C hart f or Ba xalta Cli nical St u d y  4 7 1 1 0 1 .................................. 8 1
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 1 9 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
5. LI S T O F A B B R E VI A TI O N S
A b bre vi ati o n  
Defi niti o n
A 1 PI
Al p ha 1-Pr otei nase I n hi bit or
A A T
Al p ha 1-a ntitr ypsi n
A E/ A Es  
A d verse e ve nt/a d verse e ve nts
A L P
Al kali ne p h os p hatase
A L T
Ala ni ne a mi n otra nsferase
A N C
A bs ol ute ne utr o p hil c o u nt
A N E C  
A nti- ne utr o p hil elastase ca pacit y
A N O V A  
A nal y sis of Varia nce
A P E
Ac ute p ul m o nar y  e xacer bati o n
A R/ A Rs  
A d verse reacti o n/a d verse reacti o ns
A S T
As partate a mi n otra nsferase
B A L
Br o nc h oal ve olar la va ge
B 1 9 V  
Par v o vir us B 1 9
Bi P A P  
Bi -le vel p ositi ve air wa y press ure
B U N
Bl o o d urea nitr o ge n
B W
B o d y wei g ht
C 3
C o m ple me nt c o m p o ne nt 3
C 4
C o m ple me nt c o m p o ne nt 4
C F R
C o de of Fe deral Re g ulati o ns
C H 5 0  
5 0 % he m ol ytic c o m ple me nt acti vit y  of ser u m
Cis
C o nfi de nce i nter vals
C O P D  
C hr o nic o bstr ucti ve p ul m o nar y  disease
C P A P  
C o nti n u o us p ositi ve air wa y  press ure
C P K
Creati ne p h os p h o ki nase
C R F(s)  
Case re p ort for m(s)
C T
C o m p uterize d t o m o gra p h y
D M C
Data M o nit ori n g C o m mittee
E C
Et hics C o m mittee
E C G
Electr ocar di o gra m
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 2 0 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
A b bre vi ati o n  
Defi niti o n
e C R F  
Electr o nic case re p ort f or m
E D C
Electr o nic data ca pt ure
E D T A  
Et h y le ne dia mi netetraacetic aci d
E L F
E pit helial li ni n g fl ui d
E P
E ur o pea n P har mac o peia
E x C
E xcl usi o n criteri o n
F A S
F ull a nal ys is set
F D A
U nite d States F o o d a n d Dr u g A d mi nistrati o n
F E V 1
F orce d e x pirat or y  v ol u me i n 1 sec o n d
F V C
F orce d vital ca pacit y
G C P
G o o d Cli nical Practice
G G T
Ga m ma -gl uta m yl -tra nsferase
H A V
He patitis A vir us
H B V
He patitis B vir us
Hct
He mat ocrit
H C V
He patitis C vir us
H E V
He patitis E vir us
H g b
He m o gl o bi n
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
I C
I ncl usi o n criteri o n
I CF
I nf or me d c o nse nt f or m
I C H
I nter nati o nal C ou n cil for Har m o ni sati o n
I g A
I m m u n o gl o b uli n A
I P
I n vesti gati o nal pr o d uct
I R T
I nteracti ve res p o nse tec h n ol o g y
I V
I ntra ve n o us
I W R S  
I nteracti ve We b Res p o nse S yste m
L D H
Lactic de h y d r o ge nase
L R T
L o wer res pirat or y  tract
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 2 1 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
A b bre vi ati o n  
Defi niti o n
L R TI
L o wer res pirat or y  tract i nfecti o n
M DI
Metere d d ose i n haler
Me d D R A  
Me dical Dicti o nar y  f or Re g ulat or y Acti vities
N A T
N ucleic aci d test
N E
Ne utr o p hil elastase
N M C
N o n -me dical c o m plai nt
N Y H A  
Ne w Y or k Heart Ass ociati o n 
O 2
O x y ge n
P C R
P ol y merase c hai n reacti o n
P P
Per- pr ot oc ol
R B C
Re d bl o o d cell
R SI
Refere nce safet y i nf or mati o n
S A E
Seri o us a d verse e ve nt
S A E R  
Seri o us a d verse e ve nt re p ort
S/ D
S ol ve nt/ deter ge nt
SI C
S u bject i de ntificati o n c o de
U L N
U p per li mit of n or mal
U S
U nite d States
U S P
U nite d States P har mac o peia
W B C
W hite bl o o d cell
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 2 2 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
6. B A C K G R O U N D I N F O R M A TI O N
Al p ha 1 -Pr otei nase I n hi bit or ( A 1 PI), als o k n o w n as al p ha 1-a ntitr ypsi n ( A A T), is a 
ser u m gl yc o pr otei n of m olec ular mass 5 2 k D. T he pr otei n is s y nt hesize d i n t he li ver 
a n d is re p orte d t o be prese nt i n t he ser u m at le vels bet wee n 2 0 a n d 5 3 μ M ( 1 0 4 t o 
2 7 5. 6 m g/ d L) .1
Se vere A 1 PI deficie nc y  (als o k n o w n as A A T deficie nc y ) is a n a ut os o mal recessive 
here ditar y  dis or der affecti n g a n esti mate d 3 4, 3 9 5 t o 4 8, 9 0 4 i n di vi d uals i n t he U nite d 
States ( U S), wit h 9 1. 6 % bei n g Ca ucasia n A merica ns, 7. 8 % His pa nic A merica ns, a n d 
0. 5 % Africa n A merica ns .2, 3 I ndi vi d uals wit h a se vere deficie nc y  are defi ne d as t h ose wit h 
ser u m A 1 PI le vels less t ha n 3 5 % of t he a vera ge n or mal le vel 4 , 5, or les s t ha n 1 1 μ M .6, 7, 8
Se verel y affecte d i n di vi d uals ma y ha ve n o detecta ble A 1 PI  pr otei n i n t heir ser u m. I n 
a d diti o n, ge netic varia nts ass ociate d wit h re d uce d A 1 PI  le vels als o pr o d uce an altere d
f or m of A 1 PI, t he ca pacit y of w hic h t o i n hi bit ne utr o p hil elastase ( N E) is re d uce d.9 I n 
cli nical practice, t he maj orit y  ( 9 6 %) of A 1 PI deficie nc y relate d diseases are li n ke d t o 
Pi * Z Z ge n ot y pe , wit h t he re mai ni n g 4 % t o Pi * S Z a n d ot her rare or n ull ge n o t ypes.
I n di vi d uals wit h Pi * Z Z s h o w a si g nifica nt i ntracell ular p ol ymerizati o n of t heir A 1 PI i n 
t he li ver, ofte n res ulti n g i n li ver da ma ge wit h a varia ble cli nical prese ntati o n. I n a d diti o n, 
t he pr of o u n d s u p pressi o n of A 1 PI secreti o n i nt o t he s yste mic circ ulati o n si g nifica ntl y 
i ncreases t he ris k of de vel o p i n g pa naci nar e m p h y se ma.1 0 T he t hres h ol d le vel of A 1 PI 
i n t he l o wer res pirat or y tract ( L R T) nee de d t o pr o vi de cli nical be nefit is n ot k n o w n;
h o we ver, e m p h ys e ma i n A 1 PI -deficie nt s u bjects has bee n t h o u g ht t o de vel o p beca use 
t he le vel of A 1 PI i n t he L R T is i ns ufficie nt t o i n hi bit seri ne pr oteases. Seri ne pr oteases, 
s uc h as N E, are prese nt i n t he LR T i n hi g her t ha n n or mal c o nce ntrati o ns as a res ult of 
i nfla m mati o n or i nfecti o n.1 1 If left unc hec ke d, d ue t o i ns ufficie nt A 1 PI, t he pr ote ol yt ic 
acti vit y of t hese pr oteases ca n destr o y t he c o n necti ve tiss ue fra me w or k of t he l u n g 
pare nc h y m a.1 2 ,1 3
T hera p y f or A 1 PI -deficie nt s u bjects is directe d t o war ds re place me nt or a u g me ntati o n 
of ser u m A 1 PI le vels.6 , 8,1 1 ,1 3 ,1 4 ,1 5 ,1 6 ,1 7 ,1 8 T his t hera p y is base d o n t he c o nce pt t hat a n 
i ncrease i n t he ser u m le vel of A 1 PI will lea d t o hi g her A 1 PI c o nce ntrati o ns i n t he
l u n g pare nc h y m a, w hic h i n t ur n, ma y miti gate t he A 1 PI pr otease i m bala nce, t here b y 
pre ve nti n g or sl o wi n g t he destr ucti o n of l u n g tiss ue a n d t h us t he cli nical c o urse of t he 
disease .6 ,1 1 We wers et al. s h o we d t hat, at stea d y- state, a u g me ntati o n t hera p y wit h o nce a 
wee k d osi n g of A 1 PI (6 0 m g/ k g b o d y  wei g ht [B W ]/ wee k) res ulte d i n tr o u g h circ ulati n g 
A 1 PI  le vels t o > 1 1 µ M i n s u bjects wit h A 1 PI deficie nc y of Pi * Z/ Z ge n oty pe .1 1
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 2 3 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
H ist oricall y, it was belie ve d t hat 1 1 µ M is t he pr otecti ve t hres h ol d le vel, base d o n t he 
ass u m pti o n t hat s u bjects wit h Pi * Z/ Z, Pi * N ull/ N ull , or Pi * Z/ N ull ge n ot y p es ha d se vere 
A 1 PI  deficie nc y (circ ulati n g A 1 PI le vels bel o w 1 1 µ M ) a n d e m p h yse ma; w h ereas
s u bjects wit h Pi * S/ Z ge n ot y pe , w h o at t hat ti me were c o nsi dere d t o ha ve a n a vera ge A 1 PI 
le vel of 1 1 µ M, were pr otecte d fr o m e m p h yse ma. 
G L A S SI A is t he o nly sterile, rea d y- t o-use, li q ui d pre parati o n of p urifie d h u ma n A 1 PI  
i n dicate d f or c hr o nic a u g me ntati o n a n d mai nte na nce t hera py i n a d ults wit h cli nicall y 
e vi de nt e m p h ys e ma d ue t o se vere c o n ge nital deficie nc y of A 1 PI. T he pr o d uct was 
a p pr o ve d b y t he U S F o o d a n d Dr u g A d mi nistrati o n ( F D A) i n 2 0 1 0, o n t he basis of safet y 
a n d bi oc he mical de m o nstrati o n i n a P hase 1 d ose -escalati o n a n d a P hase 2/ 3 pi v otal 
cli nical trial i n a t otal of 6 5 i n di vi d ual s u bjects wit h se vere A 1 PI deficie nc y .
T he cli nical l ots use d i n t he G L A S SI A P hase 2/ 3 trial c o ntai ne d s mall a m o u nts of visi ble 
pr otei n partic ulates w hic h were a g gre gates of A 1 PI . G L A S SI A A 1 PI f u ncti o nal acti vit y  
is i n de pe n de nt of t he partic ulate l oa d of t he s ol uti o n f or i nf usi o n. Pr otei n a g gre gati o n is a 
k n o w n p he n o me n o n wit h pr otei n t hera pe utics a n d has bee n s h o w n t o be prese nt i n t he 
acti ve c o m parat or use d i n t he P hase 2/ 3 trial, as well as i n ot her c o m merciall y a vaila ble 
A 1 PI  pr o d ucts u p o n rec o nstit uti o n of t he l yo p hilize d p o w der. D uri n g t he P hase 2/ 3 
cli nical trial, n o safet y si g nals of c o ncer n were re p orte d . T he m ost c o m m o n a d verse 
reacti o ns ( A Rs) (> 0. 5 % of i nf usi o ns ) re p orte d were hea dac he a n d u p per res pirat or y tract 
i nfecti o n. T hese a d verse e ve nts ( A Es) were c o nsiste nt wit h t h ose re p orte d f or ot her 
lice nse d A 1 PI pr o d ucts. P ote ntial i m m u n o ge nicit y f oll o wi n g re peate d a d mi nistrati o n of 
G L A S SI A was e val uate d i n t he P hase 2/ 3 trial, w here 5 0 s u bjects recei ve d wee kly 
i nf usi o ns of eit her G L A S SIA or P R O L A S TI N (acti ve c o m parat or) fr o m Wee k 1 t o 
Wee k
1 2 a n d t he n wee kl y i nf usi o ns of G L A S SI A (all s u bjects) fr o m Wee k 1 3
t o
Wee k
2 4. I mm u n o ge nicit y  was m o nit ore d at baseli ne, Wee k 1 2, a n d Wee k 2 4. All 
sa m ples were ne gati ve f or t he prese nce of a nti-A 1 PI  a nti b o dies, wit h t he e xce pti o n of a 
si n gle sa m ple ( Wee k 1 2) wit h a l o w titer of 2 i n 1 s u bject. T he Wee k 2 4 sa m ple fr o m t his 
s u bject was ne gati ve, s u g gesti n g a l o w le vel, tra nsie nt i m m u n o ge nic res p o nse. 
Ne vert heless, as a n a d d e d preca uti o nar y meas ure, it is rec o m me n de d t hat G L A S SIA be 
filtere d t wice bef ore pr o d uct a d mi nistrati o n: t hr o u g h a 5-micr o n filter nee dle d uri n g 
pr o d uct p o oli n g a n d t he n t hr o u g h a 5- micr o n i n- li ne filter d uri n g pr o d uct a d mi nistrati o n 
(see G L A S SI A pac ka ge i nsert a n d/ or i n vesti gat or's br oc h ure [I B ]).
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 2 4 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
T he effecti ve ness of t he i n -li ne filtrati o n pr oce d ure i n re m o vi n g visi ble a n d s u b visi ble 
particles i n G L A S SI A was e xa mi n e d i n a rece nt i n vitr o st u d y. G L A S SI A l ots wit h at 
least a fact or of 2- f ol d differe ntial w ere c h ose n t o re prese nt t he hi g h a n d l o w e n ds of 
t he ra n ge of particle c o u nts n or mall y o bser ve d f or G L A S SIA ma n ufact ure d. 
( N ote t hat all G L A S SI A l ots m ust meet t he re q uire me nts f or visi ble a n d s u b visi ble 
partic ulates set f ort h b y  t he U nite d States P har maco peia [ U S P ] a n d t he E ur o pea n 
P har mac o peia [ E P ] pri or t o release f or use i n h u ma ns). T he use of a 5 -micr o n i n -li ne 
filter has bee n s h o w n t o effecti vely re m o ve visi ble particles (fr o m se veral t o > 1 0 particles 
i n u nfiltere d s ol uti o n t o n o m ore t ha n 2 particles per 5 0 -m L  vial after filtrati o n) a n d 
s u b visi ble particles ( by 1 2 - t o 7 6-f ol d f or particles acr oss all particle size cate g ories 
ra n gi n g fr o m 2 t o > 1 0 0 micr o n) ( data o n file). I n fact, t he 5-micr o n i n -li ne filter is 
als o effecti ve i n re d uci n g t he nu m ber of particles t hat are s maller ( 2 t o 5- micr o n i n 
dia meter) t ha n t he n o mi nal 5 -micr o n p ore -size of t he filter fr o m a n a vera ge of 2 3 2 2 7 t o 
4 8 9 particles per 5 0 -m L  vial, re prese nti n g a 4 9-f ol d re d ucti o n. T he filtrati o n pr ocess di d 
n ot alter t he A 1 PI p ote nc y , as de m o nstrate d b y a lac k of differe nce i n t he elastase 
i n hi bit or y acti vit y meas ure me nts i n u nfiltere d a n d filtere d G L A S SI A s ol uti o n.
Ne vert heless, gi ve n a lac k of clear u n dersta n di n g a n d t he pa ucit y of direct cli nical 
e vi de nce c orrelati n g pare nteral a d mi nistrati o n of pr otei n a g gre gates t o cli nical A Es a n d 
ris k of i m m u n o ge nicity, t here ha ve bee n t he oretical c o ncer ns raise d a b o ut pr otei n 
a g gre gates i n a t hera pe utic pr o d uc t re gar di n g t he p ote ntial safety ris ks t o h u ma ns. T o 
a d dress t hese c o ncer ns, a ke y g oal of t his st u d y  is t o e val uate t he cli nical safet y pr ofile of 
G L A S SI A wit h a f oc us o n A Es of i nterest t hat ha ve bee n s u g geste d t o be p ote ntiall y  
ass ociate d wit h pr otei n a g gre gates a n d visi ble/s u b visi ble particles, s uc h as p ul m o nar y  
e m b olis m partic ularl y of n o n -t hr o m b otic or micr o vasc ular ori gi n, u ne x plai ne d c hest pai n, 
d y s p nea, or car di o p ul m o nar y arrest of n o n-car diac eti ol o g y, i nterstitial p ne u m o nitis, 
i njecti o n site reacti o ns, gra n ul o ma, hy perse nsiti vit y or a na p h yl actic reacti o ns, a n d 
i m m u n o ge nicity i n ci de nce. G L A S SI A l ots c o ntai ni n g particles of ≥2 micr o n i n dia meter 
re prese ntati ve of t he hi g h a n d l o w e n ds of t he ra n ge n or mall y o bser ve d i n G L A S SI A 
ma n ufact uri n g will be selecte d f or e val uati o n i n t his st u d y . All G L A S SI A a d mi nistrati o ns 
will f oll o w t he 2 -ste p filtrati o n pr ocess (t hr o u g h a 5- micr o n filter nee dle d uri n g pr o d uct 
p o oli n g a n d t he n t hr o u g h a 5 micr o n i n -li ne filter d uri n g pr o d uct a d mi nistrati o n) as 
o utli ne d i n t he G L A S SI A pac ka ge i nsert a n d/ or I B.
T he sec o n d g oal of t his st u d y  is t o o btai n a d diti o nal safety data , a n d t o e val uate 
t he effects of G L A S SI A a u g me ntati o n t hera p y o n t he le vels of A 1 PI a n d   
 
 i n t he E L F f oll o wi n g wee kl y i ntra ve n o us (I V) a u g me ntati o n t hera p y 
wit h G L A S SI A i n s u bjects wit h e m p h y se ma d ue t o c o n ge nital A 1 PI deficie nc y.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 2 5 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
I n t he pi v otal P hase 2/ 3 st u d y, t here were fe wer s u bjects ( 7 s u bjects i n t he G L A S SIA 
gr o u p a n d 2 s u bjects i n t he acti ve c o m parat or gr o u p) t ha n pla n ne d ( 1 5 s u bjects) ha vi n g 
E L F a nal y te res ults a vaila ble f or e val uati o n. A d diti o nall y, effect of G L A S SI A 
a u g me ntati o n t hera p y o n E L F f u ncti o nal A 1 PI (ie, a nti -ne utr o p hil elastase ca pacit y  
[ A N E C]) c o ul d n ot be e xa mi ne d d ue t o missi n g data. T h us, t his st u d y is desi g ne d t o 
i ncl u de br o nc h osc o py/ br o nc h oal ve olar la va ge ( B A L) visits t o c ollect data f or t he 
assess me nts of c ha n ge fr o m baseli ne i n t he a nti ge nic a n d f u ncti o nal A 1 PI le vels i n t he 
E L F f oll o wi n g 1 3 wee ks of wee kl y I V a d mi nistrati o n of G L A S SIA at t he a p pr o ve d d ose 
of 6 0 m g/ k g B W.
6. 1 Descri pti o n of I n vesti g ati o n al Pr o d uct
G L A S SI A is a sterile, rea d y -t o- use, li q ui d pre parati o n of p urifie d h u ma n A 1 PI . T he 
s ol uti o n c o ntai ns 2 % acti ve A 1 PI i n a p h os p hate-b uffere d sali ne s ol uti o n. T he s pecific 
acti vit y of G L A S SI A is at least 0. 7 m g f u ncti o nal A 1 PI per m g of t otal pr otei n (t he 
s pecific acti vit y of a partic ular l ot will be pr o vi de d i n t he certificate of a nal ysis). T he 
pr o d uct i s clear a n d c ol orless t o yell o w-gree n a n d ma y  c o ntai n a fe w particles (ie, pr otei n 
fila me nts).
G L A S SI A s u p plie d i n t he U S is pre pare d fr o m h u ma n plas ma o btai ne d fr o m U S-lice nse d 
plas ma c oll ecti o n ce nters b y a m o difie d versi o n of t he c ol d et ha n ol fracti o nati o n pr ocess 
a n d t he A 1 PI is t he n p urifie d usi n g c hr o mat o gra p hic met h o ds. G L A S SI A d oes n ot 
c o ntai n sta bilizers or a n y ot her a d de d s u bsta nces (s uc h as s ucr ose, al b u mi n or ma n nit ol). 
G L A S SI A c o ntai ns n o preser vati ves a n d n o late x.
F urt her i nf or mati o n ca n be f o u n d i n t he G L A S SI A p ac ka ge i nsert a n d/ or I B.
6. 1. 1 R ati o n ale f or t he Selecti o n of D osi n g Re gi me n
T he d osi n g re gi me n of G L A S SI A c h ose n f or t his st u d y, 6 0 m g/ k g gi ve n i ntra ve n o usly 
o nce per wee k, is t he sta n dar d F D A -a p pr o ve d d osi n g re gi me n f or G L A S SI A , as well as 
all ot her plas ma -deri ve d A 1 PI  pr o d ucts i n t he s a me class. At t his d osa ge, G L A S SI A has 
bee n de m o nstrate d t o be safe a n d well t olerate d i n a t otal of 6 5 s u bjects wit h c o n ge nital 
A 1 PI -d eficie nc y, a n d was s h o w n t o i ncrease a n d mai ntai n circ ulati n g thr o u g h a nti ge nic 
a n d f u ncti o nal A 1 PI le vels t o 1 4. 7 µ M ( me dia n; ra n ge: 1 1. 6 -1 8. 5 µ M) a n d 1 1. 9 µ M
( me dia n; ra n ge: 8. 2- 1 6. 9 µM) , res pecti vely (see G L A S SI A pac ka ge i nsert a n d/ or I B).
6. 1. 2 R ati o n ale f or t he Selecti o n of R o ute of A d mi nistr at io n a n d I nf usi o n R ate
T he r o ute of a d mi nistrati o n ( I V i nf usi o n), as well as t he i nf usi o n rate 
(ma xi m u m rate 0. 2 m L / k g B W/ mi n), selecte d f or t his st u d y are i n acc or da nce wit h t he 
F D A -a p pr o ve d p ac ka ge i nsert.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 2 6 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
6. 2 Cli nic al C o n diti o n/I n dic ati o n
G L A S SI A is i n dicate d f or c hr o nic a u g me ntati o n a n d mai nte na nce t hera p y  i n a d ults wit h 
cli nicall y e vi de nt e m p h yse ma d ue t o se vere c o n ge nital deficie nc y of A 1 PI ( A A T 
deficie nc y ).
6. 3 P o p ul ati o n T o Be St u die d
S u bjects wit h se vere c o n ge nital A 1 PI - deficie nc y a n d e m p h ys e ma are pla n ne d f or 
e nr oll me nt i nt o t his st u d y. 
6. 4 Fi n di n gs Fr o m N o ncli nic al a n d Cli nic al St u dies
6. 4. 1 S u m m ar y of N o ncli nic al D at a
G L A S SI A was e val uate d i n 2 si n gle d ose ge neral t o xic ol o g y st u dies i n S pra g ue-Da wle y  
rats a n d Ne w Zeala n d W hite ra b bits, a n d 2 re peate d d ose st u d y i n Ne w Zeala n d W hite 
ra b bits. 
I n si n gle d ose st u dies, a si n gle d ose of 0, 6 0 a n d 6 0 0 m g/ k g (ra b bits) or 6 4 0 m g/ k g (rats) 
was a d mi nistere d i ntra ve n o usl y a n d t he a ni mals were o bser ve d f or 1 4 da y s. T here were 
n o c ha n ges i n B W , cli nical c he mistr y, he mat ol o g y a n d gr oss pat h ol o g y t hat c o ul d be 
attri bute d t o G L A S SI A a d mi nistrati o n.
I n a re peate d d ose st u d y, Ne w Zeala n d W hite ra b bits recei ve d G L A S SI A ( 3 0 0 m g/ k g) 
o nce dail y f or 5 c o nsec uti ve da ys. A ni mals were m o nit ore d f or c han ges i n cli nical si g ns, 
B W , cli nical c he mistr y, he mat ol o g y, necr o ps y a n d hist o pat h ol o g y o n Da y 1 or 1 4 after 
t he last a d mi nistrati o n. A mi n or i ncrease i n gr o u p mea n ne utr o p hils was meas ure d o n 
D a y 1 after t he last G L A S SIA a d mi nistrati o n. Rec o v er y was o bser ve d after 1 4 da y s.
L o n g -ter m st u dies i n a ni mals t o e val uate carci n o ge nesis, m uta ge nesis or i m pair me nt of 
fertilit y ha ve n ot bee n c o n d ucte d.
A ni mal re pr o d ucti o n st u dies ha ve n ot bee n c o n d ucte d wit h G L A S SI A.
N o t o xic ol o gical effects d ue t o t he s ol ve nt/ d eter ge nt rea ge nts, tri -( n)-b ut yl  p h os p hate, 
a n d p ol ys or bate 8 0 ( T wee n 8 0), use d i n t he vir us i nacti vati o n pr oce d ure are e x pecte d 
si nce t he resi d ual le vels are less t ha n 5 a n d 2 0 p p m, res pecti vely.
6. 4. 2 S u m m ar y of Cli nic al D at a
Fi n di n gs fr o m cli nical st u dies are pr o vi de d i n t he G L A S SI A pac ka ge i nsert a n d/ or I B.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 2 7 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
6. 5 E v al u ati o n of A ntici p ate d Ris ks a n d Be nefits of t he I n vesti g ati o n al Pr o d uct(s) t o 
H u m a n S u bjects
Tra ns missi o n of bl o o d- b or ne diseases is a t he oretical ris k si nce G L A S SI A is deri ve d 
fr o m p o ole d h u ma n plas ma. T o decrease t he p ote ntial c o nta mi nati o n wit h bl o o d-b or ne 
vir uses, stri n ge nt pr oce d ures ha ve bee n e m pl o y e d i n t he ma n ufact ure of t his pr o d uct fr o m 
t he scree ni n g of plas ma d o n ors t hr o u g h plas ma c ollecti o n a n d pre parati o n. T o f urt her 
re d uce t he ris k of viral tra ns missi o n, t he ma n ufact uri n g pr ocess i ncl u des 2 ste ps of viral 
re m o val or i nacti vati o n: ( 1) treat me nt wit h a s ol ve nt/ deter ge nt ( S/ D) mi xt ure of
tri- n-b ut y l p h os p hate a n d p ol ys or bate 8 0 ( T wee n 8 0) w hic h i nacti vates e n vel o pe d viral 
a ge nts s uc h as h u ma n i m m u n o deficie nc y  vir us ( HI V), he patitis B vir us ( H B V), a n d 
he patitis C vir us ( H C V); a n d, ( 2) a na n ofiltrati o n ste p t hr o u g h a 1 5 n m filter w hic h ca n 
re m o ve b ot h e n vel o pe d a n d n o n-e n vel o pe d viral a ge nts (s uc h as he patitis A vir us 
[ H A V]). I n vitr o vir us cleara nce st u dies de m o nstrate d a vir us l o g re d ucti o n fact or of 4 or 
greater. T o date, n o ser oc o n versi o n f or he patitis B or C ( H B V or H C V) or h u ma n 
i m m u n odeficie nc y  vir us ( HI V) or a n y ot her k n o w n i nfecti o us a ge nt ha ve bee n re p orte d 
wit h t he use of G L A S SI A d uri n g t he cli nical st u dies.
G L A S SI A is c o ntrai n dicate d i n s u bjects wit h a hist or y of a na p h yl actic or se vere 
h y perse nsiti vit y  reacti o ns t o h u ma n A 1 PI  pre parati o ns.
G L A S SI A m a y  c o ntai n trace a m o u nts of i m m u n o gl o b uli n A (I g A). G L A S SI A is 
c o ntrai n dicate d i n s u bjects wit h k n o w n a nti b o dies t o I g A, a n d i n s u bjects wit h selecti ve 
or se vere I g A deficie nc y  w h o ma y de vel o p a nti-I gA a nti b o dies t hat ca n res ult i n se v ere 
h y perse nsiti vit y  a n d a na p h ylactic reacti o ns. I F A N A P H Y L A C TIC O R S E V E R E 
A N A P H Y L A C T OI D R E A C TI O N S O C C U R, T H E I N F U SI O N M U S T
B E 
DI S C O N TI N U E D I M M E DI A T E L Y. E pi ne p hri ne , a nti hista mi nes, a n d ot her a p pr o priate 
s u p p orti ve t hera py s h o ul d be a vaila ble f or t he treat me nt of a n y  ac ute a na p h ylactic or 
a na p h yl act oi d reacti o ns.
6. 6 C o m pli a nce St ate me nt
T his st u d y  will be c o n d ucte d i n acc or da nce wit h t his pr ot oc ol, t he Inter nati o nal C o u ncil
f or Har m o nisati o n G ui deli ne f or G o o d Cli nical Practice E 6 (I C H G C P E 6( R 2) ,
N o ve m ber 2 0 1 6 ), Title 2 1 of t he U S C o de of Fe deral Re g ulati o ns ( U S C F R), t he ( E U 
Directi ves 2 0 0 1/ 2 0/ E C a n d 2 0 0 5/ 2 8/ E C), a n d a p plica ble nati o nal a n d l ocal re g ulat or y  
re q uire me nts.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 2 8 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
7. S T U D Y P U R P O S E A N D O B J E C TI V E S
7. 1 St u d y P ur p ose
T he p ur p ose of t he st u d y  is 2- f ol d: ( 1) t o f urt her e val uate t he safet y a n d p ote ntial 
i m m u n o ge nicity of G L A S SI A f oll o wi n g I V a d mi nistrati o n via i n-li ne filtrati o n; a n d,
( 2) t o assess t he effects of G L A S SI A a u g me ntati o n t hera p y o n t he le vels of A 1 PI  a n d 
i n t he E L F f oll o wi n g I V a d mi nistrati o n at a d osa ge of 6 0 m g/ k g 
B W/ wee k f or 2 5 wee ks i n s u bjects wit h e m p h yse ma d ue t o c o n ge nital A 1 PI deficie nc y.
7. 2 Pri m ar y O bjecti ve s
1. 
T o e val uate t he effecti ve ness of t he use of 5 -micr o n i n -li ne filter o n t he safet y a n d 
p ote ntial i m m u n o ge nicit y of GL A S SI A .
2. 
T o deter mi ne t he effects of wee kl y I V a u g me ntati o n t hera py wit h G L A S SI A at a 
d osa ge of 6 0 m g/ k g B W o n a nti ge nic a n d f u ncti o nal A 1 PI  le vels i n E L F i n 
s u bjects wit h c o n ge nital A 1 PI deficie nc y.
7. 3 Sec o n d ar y O bjecti ve
  
T o c ollect a d diti o nal safet y  i nf or mati o n for G L A S SI A.
7. 4 E x pl or at or y O bjecti ve
 
 
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 2 9 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
8. S T U D Y D E SI G N
8. 1 Brief S u m m ar y
T his P hase 3/ 4, pr os pecti ve, 2 -ar m, d o u ble -bli n d, ra n d o mize d, c o ntr olle d, m ultice nter 
st u d y will assess t he safet y, i m m u n o ge nicit y, a n d effects o n t he a nti ge nic a n d f u ncti o nal 
A 1 PI  le vels i n t he E L F f oll o wi n g G L A S SI A a d mi nistrati o n via a 5 -micr o n i n -li ne filter at 
a d osa ge of 6 0 m g/ k g B W/ wee k (t he d osi n g re gi me n t hat is c urre ntly a p pr o ve d b y t he 
F D A) f or 2 5 wee ks i n A 1 PI -deficie nt s u bjects w h o are A 1 PI -treat me nt-naï ve , w h o are 
c urre ntl y recei vi n g A 1 PI treat me nt at t he ti me of e nr oll me nt, or w h o ha ve pre vi o usl y  
recei ve d A 1 PI treat me nt.
8. 2 St u d y Desi g n
A 1 PI -deficie nt s u bjects, w h o are A 1 PI -treat me nt-naï ve or ha ve pre vi o usl y bee n treate d 
wit h A 1 PI  a u g me ntati o n t hera py, will be e nr olle d. S u bjects w h o are recei vi n g or ha ve 
rece ntly bee n e x p ose d t o A 1 PI  a u g me ntati o n t hera p y at t he ti me of st u d y e nr oll me nt will 
be re q uire d t o u n der g o a n a de q uate was h o ut peri o d ( mi ni m u m of 4 wee ks fr o m t he ti me 
of last A 1 PI  treat me nt) d uri n g scree ni n g. Scree ni n g A 1 PI meas ure me nt ma y  be ta ke n at 
a n y ti me d uri n g t he s cree ni n g peri o d f or treat me nt- naï ve s u bjects. F or s u bjects w h o ha ve 
pre vi o usl y  recei ve d al p ha- 1 a u g me ntati o n t hera py, scree ni n g A 1 PI meas ure me nt s h o ul d 
be ta ke n at t he e n d of t he was h o ut peri o d. D uri n g t he was h o ut peri o d, s u bjects will be 
all o we d t o u n der g o ot her scree ni n g pr oce d ures f o r eli gi bilit y deter mi nati o n.
S u bjects meeti n g eli gi bilit y  criteria will be re q uire d t o u n der g o br o nc h osc o p y/ B A L 
pr oce d ures at baseli ne a n d f oll o wi n g I P treat me nt f or t he e val uati o n of t he effects of 
G L A S SI A a u g me ntati o n t hera p y  at t he la bele d d osa ge of 6 0 m g / k g B W/ wee k o n t he 
le vels of A 1 PI a n d 
 i n t he E L F. 
O nce t he tar get of 1 5 t o 1 8 e val ua ble s u bjects has bee n reac he d, t he re mai ni n g s u bjects t o 
be e nr olle d will n ot be re q uire d t o u n der g o baseli ne a n d o n- treat me nt br o nc h osc o p y/ B A L 
pr oce d ures. S u bjects wit h c o nfir me d me dical hist or y  (IC # 1a, # 9a, # 9 b, E x C # 2 0, # 2 1,
# 2 2, # 2 3, a n d #2 4) k n o w n n ot t o meet eli gi bilit y  criteria t o u n der g o br o nc h osc o p y/ B A L 
pr oce d ures, m a y be scree ne d a n d ra n d o mize d wit h s p o ns or a p pr o val bef ore t he tar get 
e nr oll me nt of B A L e val ua ble s u bjects is reac he d. 
E nr oll me nt will be cl ose d w he n b ot h c o n diti o ns are met: 
(a) 1 5 t o 1 8 e val ua ble s u bjects wit h acce pta ble B A L sa m ples c ollecte d fr o m b ot h t he 
baseli ne a n d o n -treat me nt B AL visits .
( b) A mi ni m u m of 3 6 ra n d o mize d s u bjects.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 3 0 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
If f or a ny reas o ns t he tar get of 1 5 t o 1 8 e val ua ble s u bjects ha ve n ot bee n ac hie ve d wit h 
i nitial 3 6 ra n d o mize d s u bjects, a d diti o nal s u bjects will be e nr olle d t o meet t he B A L 
e nr oll me nt tar get.
S u bjects w h o ha v e c o m plete d t he baseli ne br o nc h osc o p y / B A L visit a n d ha ve acce pta ble 
B A L sa m ples will be ra n d o mize d i n a 1: 1 rati o t o 1 of t he 2 treat me nt ar ms as s h o w n i n 
Ta ble 8 - 1. S u bjects w h o are wai ve d fr o m t he br o nc h osc o p y/ B AL pr oce d ures will be 
ra n d o mize d after c o m pleti n g scree ni n g pr oce d ures a n d c o nfir mati o n of eli gi bilit y ( n ote 
t hat B A L-relate d eli gi bilit y criteria are n ot a p plica ble f or t hese s u bjects).
T a ble 8- 1
Tre at me nt Assi g n me nts
Tre at m e nt 
Ar m
N o. of S u bjects P er 
A r m
Tre at m e nt
1
1 8
G L A S SI A l ot wit h particle l oa ds re prese nti n g t he hi g h e n d wit hi n 
t he n or m al r a n ge o bser ve d i n G L A S SI A l ots ma n ufact ure d
2
1 8
G L A S SI A l ot wit h particle l oa ds re prese nti n g t he l o w e n d wit hi n 
t he n or mal r a n ge o bser ve d i n G L A S SI A l ots ma n ufact ure d
D uri n g t he treat me nt peri o d, s u bjects i n b ot h treat me nt ar ms will recei ve wee kl y I V 
i nf usi o ns of G L A S SIA at 6 0 m g/ k g B W a d mi nistere d at a rate of 0. 2 m L/ k g/ mi n f or 
2 5 wee ks (ie, 2 5 pla n ne d i nf usi o ns) via a n I V a d mi nistrati o n set t hat i ncl u des a 5 -micr o n 
i n-li ne filter. T he first i nf usi o n ( Wee k 1), as well as i nf usi o ns d uri n g Wee k 7, Wee k
1 3, 
Wee k 1 9,
a n d Wee k 2 5, m ust be a d mi nistere d at t he st u d y  site t o facilitate m o nit ori n g 
a n d re p orti n g of p ote ntial A Es ass ociate d wit h G L A S SIA i nf usi o ns . At t he i n vesti gat or’s 
discreti o n, s u bse q ue nt i nf usi o ns ma y be a d mi nistere d at t he st u d y site or at a n ot her 
s uitable l ocati o n (e g, t he s u bject’s h o me) b y a q ualifie d healt hcare pr ofessi o nal, as 
acce pta ble per l ocal re g ulati o ns a n d sta n da r d practices of t he st u d y site.
S u bjects will be as ke d t o ret ur n t o t he st u d y  site e ver y 6 wee ks (ie, d uri n g Wee ks 1, 7, 1 3, 
1 9, a n d 2 5) f or B W meas ure me nts, as well as p h y sical e xa mi nati o n, vital si g n 
meas ure me nts, a n d bl o o d dra w s f or plas ma A 1 PI a n d safet y la b orat or y  sa m ple c ollecti o n, 
as a p plica ble (see Ta ble 2 0. 2- 1 a n d Ta ble 2 0. 3- 1 f or detaile d list of st u d y 
pr oce d ures/la b orat or y  assess me nts). T he o n -treat me nt B A L visit will be c o n d ucte d 
bet wee n Wee k 1 2 a n d Wee k 1 4 f oll o wi n g i nitiati o n of G L A S SI A a u g me ntati o n t hera p y 
f or t he deter mi nati o n of a nti ge nic a n d f u ncti o nal A 1 PI le vels a n d 
i n 
E L F. After c o m pleti n g t he o n -treat me nt B A L visit, s u bjects will c o nti n ue t o recei ve 
wee kl y G L A S SI A i nf usi o ns u ntil Wee k 2 5 (t he last i nf usi o n visit), f oll o we d b y  t he st u d y 
c o m pleti o n visit ( Wee k 2 6) at 7 ( ± 3) da ys p ost -last i nf usi o n.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 3 1 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
T he o verall st u d y  desi g n is ill ustrate d i n Fi g ure 2 0- 1 ( S u p ple me nt 2 0. 1 ).
8. 3 D ur ati o n of St u d y Peri o d(s) a n d S u bject P artici p ati o n
T he o ve rall d urati o n of t he st u d y  will be a p pr o xi matel y 5 ye ars fr o m st u d y i nitiati o n 
(ie, first s u bject e nr olle d) t o st u d y c o m pleti o n (ie, last s u bject last visit).
T he recr uit me nt peri o d is e x pecte d t o be a p pr o xi matel y 4 6 m o nt hs . T he d urati o n of eac h 
s u bject’s partici pati o n fr o m e nr oll me nt t o s u bject c o m pleti o n (ie, last st u d y visit) is 
a ntici pate d t o be a p pr o xi matel y 8 m o nt hs ( u nless t he s u bject wit h dra ws or is pre mat urely 
disc o nti n ue d fr o m t he st u d y ), i ncl u di n g:
  
a scree ni n g peri o d of u p t o 6 wee ks .
  
a baseli ne peri o d of u p t o 2 wee ks (f or s u bjects u n der g oi n g baseli ne B A L 
pr oce d ure ).
  
a treat me nt peri o d of 2 5 wee ks a n d 
  
a p ost-treat me nt safety f oll o w -u p peri o d of 7 ( ± 3 ) da y s after t he last i nf usi o n.
8. 4 O utc o me Me as ure s
8. 4. 1 Pri m ar y O utc o me Me as ure s
S afet y
1.  
N u m ber ( pr o p orti o n) of A Es c o nsi dere d p ote ntiall y  relate d t o t he prese nce of
particle l oa d i n t he G L A S SIA s ol uti o n .
2. 
I nci de nce of treat me nt -e mer ge nt A Rs pl us s us pecte d A Rs .
3. 
N u m ber ( pr o p orti o n) of i nf usi o ns t hat are disc o nti n ue d, sl o we d, or i nterr u pte d d ue 
to a n A E.
4. 
N u m ber ( pr o p orti o n) of s u bjects w h o de vel o p bi n di n g a n d/ or ne utralizi n g a nti-
A 1 PI  a nti b o dies.
Effic ac y
1. 
A nti ge nic A 1 PI le vels i n E L F .
2. 
F u ncti o nal A 1 PI (als o k n o w n as A N E C) le vels i n E L F .
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 3 2 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
8. 4. 2 Sec o n d ar y O utc o me Me as ure s
S afet y
1. 
I nci de nce of treat me nt-e mer ge nt A Es.
2. 
N u m ber ( pr o p orti o n) of s u bjects w h o e x perie nce d a s hift fr o m n or mal or 
cli nicall y i nsi g nifica nt a b n or mal la b orat or y val ues at baseli ne t o cli nically 
si g nifica nt a b n or mal la b orat or y val ues (t hres h ol ds as o utli ne d i n Secti o n 2 0. 4 ) 
f oll o wi n g G L A S SI A a d mi nistrati o n.
3. 
N u m ber ( pr o p orti o n) of s u bjects wit h treat me nt -e mer ge nt ser oc o n versi o n or 
p ositi ve viral n ucleic aci d test ( N A T ) f or par v o vir us B 1 9 ( B 1 9 V).
8. 4. 3 E x pl or at or y O utc o me Me as ures
8. 5 R a n d o miz ati o n a n d Bli n di n g
T his is a 2- ar m, d o u ble -bli n d, ra n d o mize d, c o ntr olle d cli nical st u d y. I n or der t o 
mi ni mize/a v oi d bias, s u bjects meeti n g all eli gi bilit y criteria ( Secti o n 9. 1 a n d Secti o n 9. 2 ) 
will be ra n d o ml y  assi g ne d t o 1 of 2 treat me nt ar ms at a rati o of 1: 1. N ote t hat 
ra n d o mizati o n is t o ta ke place o nly after t he s u bject has s uccessf ull y c o m plete d t he 
baseli ne B A L visit wit h verificati o n of ha vi n g e val ua ble B A L sa m ples c ollecte d. F or 
t h ose s u bjects t o be e nr olle d after t he tar get of 1 5 t o 1 8 e val ua ble B A L s u bjects ha ve 
bee n ac hie ve d a n d t h us e xe m pte d fr o m B A L pr oce d ures, ra n d o mizati o n will ta ke place 
u p o n c o nfir mati o n of t he mai n st u d y eli gi bilit y criteria ( Secti o n 9. 1 a n d Secti o n 9. 2 ) 
b ei n g met.
Ra n d o mizati o n c o des will be ge nerate d a n d mai ntai ne d b y a n I nteracti ve Res p o nse 
Tec h n ol o g y  (I R T) via a n I nteracti ve We b Res p o nse S y ste m (IW R S) . Treat me nt 
assi g n me nt will n ot be re veale d t o t he s u bject, i n vesti gat ors, st u d y  site pers o n nel or t he 
s p o ns or, e xce pt f or u n bli n de d st u d y pers o n nel s uc h as t he u n bli n de d bi ostatisticia n.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 3 3 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
8. 5. 1 U n bli n di n g Pr oce d ures at St u d y Sites
T he ra n d o mizati o n assi g n me nt is n ot t o be re veale d bef ore t he st u d y is ter mi nate d, e xce pt 
i n e mer ge nc y cases w he n u n bli n di n g is necessar y  f or t he cli nical ma na ge me nt of a n S A E. 
I n s uc h e ve nts, e ver y atte m pt m ust be ma de t o i nf or m t he s p o ns or bef ore brea ki n g t he 
bli n d or i m me diatel y  w he n u n bli n di n g has bee n perf or me d. T he i n vesti gat or ma y re q uest 
f or t he treat me nt assi g n me nt of t he s pecific i n di vi d ual s u bject i n v ol ve d i n t he e mer ge nc y 
e ve nt via t he ce ntr alize d ra n d o mizati o n ser vice or t he u n bli n de d bi ostatisticia n.
8. 6 St u d y St o p pi n g R ules
T he st u d y  ma y be ter mi nate d b y t he s p o ns or i n t he e ve nt of u ne x pecte d safet y or me dical 
c o ncer ns. S pecific s t o p pi n g r ules will n ot be esta blis he d f or t his st u d y, as G L A S SI A is a n 
a p pr o ve d pr o d uct (i n t he U S) wit h a de m o nstrate d rec or d of safet y at t he a p pro ve d
d osa ge of 6 0 m g / k g B W / wee k w hic h is t o be e m pl o ye d i n t his st u d y. T his st u d y  will 
i ncl u de a Data M o nit ori n g C o m mittee ( D M C) t o m o nit or t he st u d y f or a n y safet y or me dical 
c o ncer ns, a n d ma y rec o m me n d st o p pi n g t he st u d y base d o n t he criteria defi ne d i n t he D M C 
c harter (see Secti o n 1 6. 4 ).
8. 7 I n vesti g ati o n al Pr o d uct(s)
8. 7. 1 P ac k a gi n g, L a beli n g, a n d St or a ge
P ac k a gi n g : G L A S SI A will be s u p plie d as a sterile, n o n -p y r o ge nic, rea d y-t o-use s ol uti o n 
i n si n gle use vials c o ntai ni n g 1 gra m of f u ncti o nal A 1 PI  i n 5 0 m L of s ol uti o n.
D os a ge F or m : I njecti o n, sol uti o n
L a beli n g : T he pr o d uct will be la bele d acc or di n g t o t he vali d re g ulat or y  req uire me nts f or 
cli nical st u dies.
St or a ge : G L A S SI A m ust be st ore d at 2 - 8° C ( 3 6 t o 4 6°F ). D o n ot freeze t he pr o d uct. 
D o n ot use past t he e x pirati o n date.
8. 7. 2 Pre p ar ati o n of I nf usi o n S ol uti o n
T he d ose (i n m g) will be calc ulate d base d o n t he s u bject’s B W at screeni n g a n d at eac h 
s u bse q ue nt st u d y visit. D ose a dj ust me nt s base d o n B W c ha n ges fr o m scree ni n g or 
pre vi o us visit will be ma de if t he s u bject’s B W c ha n ges b y > 5 %. O nl y  B W
meas ure me nts ta ke n usi n g sta n dar dize d pr oce d ures d uri n g st u d y visits ( Wee ks 1, 7, 1 3, 
1 9, or 2 5) will be use d f or d ose calc ulati o ns.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 3 4 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
T he v ol u me of i nf usi o n s ol uti o n (i n m L) will be calc ulate d base d o n t he c o nte nt of 
f u ncti o nal A 1 PI ( p ote nc y) i n G L A S SIA vials, as s pecifie d i n t he certificate of a nal ys is t o 
be pr o vi de d wit h a partic ular G L A S SI A l ot a n d as pri nte d o n t he pr o d uct cart o n a n d vial .
F or i nstr ucti o ns f or t he pre parati o n a n d a d mi nistrati o n of G L A S SI A i nf usi o n s ol uti o n, 
please refer t o t he G L A S SI A pac ka ge i nsert a n d/ or I B.
8. 7. 3 A d mi nistr ati o n
G L A S SI A is f or I V use o nl y .
R o ute of a d mi nistr ati o n: I V i nf usi o n via a 5 - micr o n i n-li ne filter
R ate of a d mi nistr ati o n: ma xi m u m rate of 0. 2 m L/ k g B W/ mi n
( T he rate of i nf usi o n m a y be re g ulate d b y a n a m b ulat or y i nf usi o n p u m p, if a vaila ble, n ot 
e xcee di n g a n i nf usi o n rate of 0. 2 m L/ k g B W/ mi n .)
8. 7. 4 Descri pti o n of Tre at me nt
Tre at me nt : G L A S SI A ( Al p ha 1-Pr otei nase I n hi bit or [H u ma n] )
D ose : 6 0 m g/ k g B W/ wee k
D os a ge fre q ue nc y : O nce e ver y  wee k ( ±2 d a y s)
Tre at me nt peri o d : 2 5 wee ks (ie, 2 5 pla n ne d i nf usi o ns), t o be f oll o we d by a 7 ( ± 3 da y s)
p ost -treat me nt safet y f oll o w-u p peri o d
8. 7. 5 I n vesti g ati o n al Pr o d uct Acc o u nt a bilit y
T he i n vesti gat or will e ns ure t hat t he I P (s) is st ore d as s pecifie d i n t he pr ot oc ol a n d t hat 
t he st ora ge area is sec ure d, wit h access li mite d t o a ut h orize d st u d y  pers o n nel. T he 
i n vesti gat or will mai ntai n rec or ds t hat t he I P(s) was recei ve d, i ncl u di n g t he date recei ve d,
dr u g i de ntit y c o de, date of ma n ufact ure or e x pirati o n date, a m o u nt recei ve d a n d 
dis p ositi o n. I P(s) m ust be dis pe nse d o nl y at t he st u d y site or ot her s uita ble l ocati o n 
(e g, i nf usi o n ce nter; h o me , as a p plica ble per st u dy desi g n ). Rec or ds will be mai ntai ne d 
t hat i ncl u de t he s u bject i de ntificati o n c o de ( SIC), dis pe nsati o n date, a n d a m o u nt 
dis pe nse d. All re mai ni n g pa rtiall y use d a n d/ or u n use d I P(s) will be ret ur ne d t o t he 
s p o ns or or s p o ns or’s re prese ntati ve after st u dy c o m pleti o n/ter mi nati o n, or destr o ye d wit h 
t he per missi o n of t he s p o ns or i n acc or da nce wit h a p plica ble la ws a n d st u d y site 
pr oce d ures. If I P(s) is t o be destr o ye d, t he i n vesti gat or will pr o vi de d oc u me ntati o n i n 
acc or da nce wit h s p o ns or’s s pecificati o ns.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 3 5 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
8. 8 S o urce D at a
Per I C H G C P, s o urce data are defi ne d as all i nf or mati o n i n ori gi nal rec or ds a n d certifie d 
c o pies of ori gi nal rec or ds of cli nical fi n di n gs, o bse r vati o ns, or ot her acti vities i n a cli nical 
trial t hat are necessar y f or t he rec o nstr ucti o n a n d e val uati o n of t he trial. S o urce data are 
c o ntai ne d i n s o urce d oc u me nts ( ori gi nal rec or ds or certifie d c o pies), w hic h ma y  be i n 
pa per a n d/ or electr o nic f or mat. S o urce data f or t his st u d y  c o m prise t he f oll o wi n g: 
h os pital rec or ds, me dical rec or ds, cli nical a n d office c harts, la b orat or y  n otes, me m ora n da, 
e val uati o n c hec klists, o utc o mes re p orte d b y s u bjects, p har mac y  dis pe nsi n g rec or ds, 
rec or de d data fr o m a ut o mate d i nstr u me nts, c o pies or tra nscri pti o ns certifie d after 
verificati o n as bei n g acc urate c o pies, micr ofic hes, p h ot o gra p hic ne gati ves, micr ofil m or 
ma g netic me dia, X- ra ys, s u bject files, rec or ds e ntere d i nt o we b a n d / or p h o ne I R T s ys te m
a n d/ or a n y direct data ca pt ure s y ste m, a n d rec or ds ke pt at t he p har mac y , at t he 
la b orat ories a n d at me dic o-tec h nical de part me nts i n v ol ve d i n t he cli nical st u d y.
N o data will be e ntere d directl y  o nt o t he case re p ort f or m ( C R F).
F or a d diti o nal i nf or mati o n o n st u d y  d oc u me ntati o n a n d C R Fs, see Secti o n 1 7. 2 .
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 3 6 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
9. S U B J E C T S E L E C TI O N, WI T H D R A W A L, A N D DI S C O N TI N U A TI O N
9. 1 I ncl usi o n Criteri a
A s u bject m ust meet A L L of t he f oll o wi n g criteria t o b e eli gi ble f or i ncl usi o n i n t his 
st u d y:
1.  
Male or fe male s u bjects meeti n g t he f oll o wi n g a ge criteria:
(a) F or s u bjects w h o will u n der g o br o nc h osc o p y / B A L pr oce d ures: 1 8 t o 7 5 years 
o f a ge at t he ti me of scree ni n g.
( b) F or s u bjects w h o will be wai ve d fr o m u n der g oi n g b r o nc h osc o py / B A L 
pr oce d ures : 1 8 years of a ge or ol der at t he ti me of scree ni n g.
2. 
D oc u me nte d A 1 PI g e n ot y pe of Pi * Z/ Z, Pi * Z/ N ull, Pi * Malt o n/ Z, Pi * N ull/ N ull , or 
ot her “at-ris k” allelic c o m bi nati o ns s uc h as S Z (e xcl u di n g M S
a n d M Z
wit h o ut 
t he prese nce of a n ot her all o wa ble at-ris k ge n oty pe ) a n d a n e n d o ge n o us A 1 PI 
plas ma le vels of ≤1 1 µ M ( ≤0. 5 7 2 m g/ m L ).
3. 
Scree ni n g le vels of e n d o ge n o us plas ma (a nti ge nic) A 1 PI  of ≤1 1 µ M ma y  be 
c ollecte d at a n y ti me d uri n g t he scree ni n g peri o d f or treatme nt -naï ve s u bjects, or 
f oll o wi n g a 4 wee k mi ni m u m was h o ut fr o m pre vi o us a u g me ntati o n t hera p y  i n 
treat me nt-e x perie nce d s u bjects .
4. 
S u bject s m ust ha ve at least o ne of t he f oll o wi n g: cli nical dia g n osis of e m p h yse ma, 
e vi de nce of e m p h ys e ma o n c o m p uterize d t o m o gra p h y ( C T) sca n of t he c hest, 
a n d/ or e vi de nce of air wa y o bstr ucti o n w hic h is n ot c o m pletel y  re verse d wit h 
br o nc h o dilat or treat me nt at t he ti me of scree ni n g.
5. 
If t he s u bject is bei n g treate d wit h a ny res pirat or y me dicati o ns i ncl u di n g i n hale d 
br o nc h o dilat ors, i n hale d a ntic h oli ner gics, i n hale d c ortic oster oi ds, or l o w-d ose 
s yste mic c ortic oster oi ds ( pre d nis o ne ≤1 0 m g/ da y  or its e q ui vale nt), t he d oses of 
t he s u bject’s me dicati o ns ha ve re mai ne d u nc ha n ge d f or at least 1 4 da ys pri or t o 
scree ni n g.
6. 
T he s u bject is a n o ns m o ker or has cease d s m o ki n g f or a mi ni m u m of 1 3 wee ks
pri or t o scree ni n g (ser u m c oti ni ne le vel at scree ni n g wit hi n n or mal ra n ge of a 
n o ns m o ker) a n d a grees t o refrai n fr o m s m o ki n g t hr o u g h o ut t he c o urse of t he 
st u d y. S u bjects wit h a p ositi ve c oti ni ne test d ue t o nic oti ne re place me nt t hera p y  
(e g, patc hes, c he wi n g g u m), va p or ci garettes , or s n uff are eli gi ble.
7. 
If fe male of c hil d beari n g p ote ntial, t he s u bject prese nts wit h a ne gati ve pre g na nc y 
test at scree ni n g a n d a grees t o e m pl o y a de q uate birt h c o ntr ol meas ures f or t he 
d urati o n of t he st u d y .
8. 
T he s u bject is willi n g a n d a ble t o c o m pl y  wit h t he re q uire me nts of t he pr ot oc ol.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 3 7 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
9. 
T he s u bject m ust ha ve p ul m o nar y  f u ncti o n at t he ti me of scree ni n g meeti n g b ot h 
of t he f oll o wi n g:
(a) P ost-br o nc h o dilat or f orce d e x pirat or y  v ol u me i n 1 sec o n d ( F E V1) ≥5 0 % of 
pre dicte d .
( b) If F E V1 is > 8 0 % pre dicte d, t he n F E V1/f orce d vital ca pacity ( F V C) m ust 
be < 0. 7.
N ote: I n c l usi o n criteri o n #1a, # 9a , a n d # 9 b are n ot a p plica ble t o s u bjects w h o are n ot 
re q uire d t o un der g o t he br o nc h osc o p y / B A L pr oce d ures.
9. 2 E xcl usi o n Criteri a
A s u bject w h o meets A N Y of t he f oll o wi n g criteria is N O T eli gi ble f or t his st u d y :
1. 
T he s u bject is e x perie nci n g or has a hist or y  of cli nicall y si g nifica nt p ul m o nar y 
disease (ot her t ha n C O P D , e m p h yse ma, c hr o nic br o nc hitis, mil d br o nc hiectasis, 
a n d sta ble ast h ma) .
2. 
T he s u bject is e x perie nci n g or has a hist or y  of c hr o nic se vere c or p ul m o nale
(resti n g mea n p ul m o nar y arter y press ure ≥4 0 m m H g) .
3. 
T he s u bject r o uti nely pr o d uces m ore t ha n 1 ta bles p o o n of s p ut u m per da y.
4. 
T he s u bject has a hist or y  of fre q ue nt p ul m o nar y e xacer bati o ns ( greater t ha n 
2 m o derate or se vere e xacer bati o ns wit hi n 5 2 wee ks pri or t o scree ni n g ; see 
Secti o n 1 0. 4 f or t he defi niti o n of m o derate a n d se vere e xacer bati o ns).
5. 
T he s u bject is e x perie nci n g a p ul m o nar y  e xacer bati o n at t he ti me of scree ni n g 
(s u bject ma y be rescree ne d 4 wee ks after t he cli nical res ol uti o n of a n 
e xacer bati o n).
6. 
T he s u bject has cli nicall y si g nifica nt a b n or malities ( ot her t ha n e m p h ys e ma, 
c hr o nic br o nc hitis, or mil d br o nc hiectasis) detecte d o n c hest X- r a y or C T sca n at 
t he ti me of scree ni n g (Past rec or ds o btai ne d wit hi n 5 2 wee ks pri or t o scree ni n g 
ma y  be use d, if a vaila ble).
7. 
T he s u bject has cli nicall y si g nifica nt a b n or malities detecte d o n a 1 2 -lea d 
electr ocar di o gra m ( E C G) perf or me d at t he ti me of scree ni n g ( Pa st rec or ds
o btai ne d wit hi n 2 6 wee ks pri or t o scree ni n g ma y be use d, if a vaila ble) .
8. 
T he s u bject has cli nicall y si g nifica nt c o n gesti ve heart fail ure wit h Ne w Y or k 
Heart Ass ociati o n ( N Y H A) Class III/I V s y m pt o ms.
9. 
T he s u bject is e x perie nci n g a n acti ve mali g na nc y or has a hist or y  of mali g na nc y 
wit hi n 5 y ears pri or t o scree ni n g, wit h t he e xce pti o n of t he f oll o wi n g: a de q uatel y  
treate d basal cell or s q ua m o us cell carci n o ma of t he s ki n, carci n o ma i n sit u of t he 
cer vi x, or sta ble pr ostate ca ncer n ot re q uiri n g treat me n t.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 3 8 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 0. T he s u bject has a hist or y  of l u n g or ot her or ga n tra ns pla nt, is c urre ntly o n a 
tra ns pla nt list, or has u n der g o ne maj or l u n g s ur ger y.
1 1. T he s u bject is recei vi n g l o n g -ter m ar o u n d -t he-cl oc k o x y ge n ( O 2) 
s u p ple me ntati o n. (T he f oll o wi n g are all o we d: s h ort-ter m use of O 2
s u p ple me ntati o n [e g, f or t he ma na ge me nt of ac ute C O P D e xacer bati o n ], O 2
s u p ple me ntati o n re q uire d d uri n g ni g ht ti me o nl y, a n d s u p ple me ntal O 2 wit h 
c o nti n u o us p ositi ve air wa y press ure [ C P A P] or bi-le vel p ositi ve air wa y press ure 
[ Bi P A P]).
1 2. K n o w n hist or y  of h yperse nsiti vit y  f oll o wi n g i nf usi o ns of h u ma n bl o o d or bl o o d 
c o m p o ne nts.
1 3. I m m u n o gl o b uli n A (I g A) deficie nc y ( < 8 m g/ d L at scree ni n g).
1 4. A b n or mal cli nical la b orat or y  res ults o btai ne d at t he ti me of scree ni n g meeti n g a n y 
of t he f oll o wi n g criteria:
a. 
Ser u m a la ni ne a mi n otra nsferase ( A L T) > 3. 0 ti mes u p per li mit of n or mal 
( U L N)
b. 
Ser u m t otal bilir u bi n > 2. 0 ti mes U L N
c. 
> 2 + pr otei n uria o n uri ne di pstic k a nal y sis
d. 
Ser u m creati ni ne > 2. 0 ti mes U L N
e. 
A bs ol ute ne utr o p hil c o u nt ( A N C) < 1 5 0 0 cells/ m m
3
f. 
He m o gl o bi n ( H g b) < 9. 0 g/ d L
g. 
Platelet c o u nt < 1 0 0, 0 0 0/ m m 3
1 5.
O n g oi n g acti ve i nfecti o n wit h H A V, H B V, he patitis C vir us ( H C V), or HI V T y pe 
1/ 2 i nfecti o n at t he ti me of scree ni n g.
1 6. T he s u bject has a n y cli nicall y si g nifica nt me dical, ps yc hiatric, or c o g niti ve ill ness, 
or a n y ot her u nc o ntr olle d me dical c o n diti o n ( e g, u nsta ble a n gi na, tra nsie nt 
isc he mic attac k) t hat, i n t he o pi ni o n of t he i n vesti gat or, w o ul d i m pe de t he 
s u bject’s a bilit y t o c o m pl y wit h t he st u d y pr oce d ures, p ose i ncrease d ris k t o t he 
s u bject’s safety, or c o nf o u n d t he i nter pretati o n of st u d y  res ults.
1 7. T he s u bject has partici pate d i n a n ot her cli nical st u d y i n v ol vi n g a n I P or 
i n vesti gati o nal de vice wit hi n 3 0 da ys pri or t o e nr oll me nt or is sc he d ule d t o 
partici pate i n a n ot her cli nical st u d y  i n v ol vi n g a n I P or de vice d uri n g t he c o urse of
t his st u d y.
1 8. T he s u bject is a fa mil y  me m ber or e m pl o yee of t he i n vesti gat or.
1 9. If fe male, t he s u bject is n ursi n g at t he ti me of scree ni n g.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 3 9 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
N ote: E xcl usi o n criteria # 2 0, # 2 1, # 2 2, # 2 3, a n d # 2 4 are n ot a p plica ble t o s u bjects 
w h o are n ot re q uire d t o u n der g o t he br o nc h osc o p y/ B A L pr oce d ures.
2 0. T he s u bject has c o ntrai n dicati o n(s) t o br o nc h osc o p y  s uc h as rece nt my ocar dial 
i nfarcti o n, u nsta ble a n gi na , ot her car di o p ul m o nar y i nsta bilit y, trac heal o bstr ucti o n 
or ste n osis, m o derate t o se vere h y p o xe mia or a n y de gree of h y p erca p nia, u nsta ble 
ast h ma, Sta ge 4 or 5 c hr o nic ki d ne y disease, p ul m o nar y h yperte nsi o n, se vere 
he m orr ha gic diat hesis, a n d cer vical C 1/ C 2 art hritis .
2 1. T he s u bject has ha d l u n g s ur ger y  w hic h ma y i nterfere wit h br o nc h osc o py.
2 2. K n o w n hist or y  of aller gic/ h yperse nsiti vit y  reacti o ns t o me dicati o ns use d d uri n g 
a n d f or peri o perati ve care ass ociate d wit h t he br o nc h osc o p y /B A L pr oce d ures, 
s uc h as l ocal a nest hetics, se dati ves, pai n c o ntr ol me dicati o ns.
2 3.
T he s u bject is recei vi n g or re q uires l o n g-ter m ( > 4 wee ks) i m m u n os u p pressi ve 
t hera py, s uc h as s yste mic c ortic oster oi ds at d oses greater t ha n 1 0 m g/ da y of 
pre d nis o ne (or its e q ui vale nt ), m yc o p he n olate m ofetil, azat hi o pri ne, 
c ycl o p h os p ha mi de, a n d rit u xi ma b.
2 4. If a s u bject is recei vi n g a ntic oa g ula nt or a nti- platelet t hera p y (s uc h as warfari n 
a n d cl o pi d o grel), t he s u bject is u n willi n g t o or u na ble t o safel y disc o nti n ue 
a ntic oa g ula nt or a nti -platelet t hera p y wit hi n 7 da ys pri or t o u ntil at least 2 4 h o urs 
after t he B A L pr oce d ures. A n e xce pt i o n is l o w-d ose as piri n al o ne w hic h is 
all o we d.
9. 3 Wit h dr a w al a n d Disc o nti n u ati o n
A n y  s u bject ma y v ol u ntaril y wit h dra w (ie, re d uce t he de gree of partici pati o n i n t he st u d y) 
c o nse nt f or c o nti n ue d partici pati o n a n d data c ollecti o n. T he reas o n f or wit h dra wal wil l be 
rec or de d o n t he a p pr o priate C R F. Assess me nts t o be perf or me d at t he ter mi nati o n visit 
(i ncl u di n g i n cases of wit h dra w or disc o nti n uati o n) are descri be d i n Secti o n 1 0. 6 , 
Secti o n 2 0. 2 , a n d Secti o n 2 0. 3 .
Disc o nti n uati o n (ie, c o m plete wit h dra wal fr o m st u d y  partici pati o n) ma y be d ue t o 
dr o p o ut (ie, acti ve disc o nti n uati o n b y s u bject) or l oss t o f oll o w -u p (ie, disc o nti n uati o n b y  
s u bject wit h o ut n otice or acti o n). A d diti o nall y, t he i n vesti gat or a n d s p o ns or ha ve t he 
discreti o n t o disc o nti n ue a n y  s u bject fr o m t he st u d y if, i n t heir j u d g me nt, c o nti n ue d 
partici pati o n w o ul d p ose a n u nacce pta ble ris k f or t he s u bject.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 4 0 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
S u bjects als o will be wit h dra w n fr o m treat me nt or disc o nti n ue d fr o m f urt her st u d y  
partici pati o n f or t he f oll o wi n g reas o ns:
1. 
T he s u bject bec o mes pre g na nt . I P e x p os ure will be disc o nti n ue d. Atte m pts will be 
ma de t o f oll o w t he s u bject t hr o u g h c o m pleti o n of t he pre g na nc y  a n d u p t o 1 year 
p ost -deli ver y , if feasi ble. T he i n vesti gat or will rec or d a narrati ve descri pti o n of 
t he c o urse of t he pre g na nc y a n d its o utc o me.
2. 
T he s u bject be gi ns n ursi n g . I P e x p os ure will be disc o nti n ue d. T he i n vesti gat or 
will rec or d a narrati ve descri pti o n of t he c o urse of t he ba b y’s de vel o p me nt.
3. 
T he s u bject de vel o ps a se ri o us A E, w hic h, base d o n t he me dical j u d g me nt of t he 
i n vesti gat or, pre ve nts c o m pleti o n of partici pati o n i n t he st u d y.
4. 
T he s u bject fails t o c o m pl y  wit h pr ot oc ol re q uire me nts or pr oce d ures t hat ma y 
i ncl u de, b ut are n ot li mite d t o:
•
T he s u bject fre q ue ntl y m isses sc he d ule d a d mi nistrati o n of t he I P, defi ne d as 
missi n g a t otal of > 2 0 % (ie, > 5) of pla n ne d i nf usi o ns, or 4 or m ore 
c o nsec uti ve wee kl y i nf usi o ns .
•
T he s u bject is treate d wit h a n y  A 1 PI pr o d uct (i ncl u di n g c o m mercially 
a vaila ble G L A S SI A) ot her t ha n I P.
•
T he s u bject partici pates i n a n ot her cli nical st u dy a n d/ or recei ves a n I P/ de vice 
ot her t ha n I P.
5. 
If a s u bject e x perie nces > 1 m o derate or se vere C O P D e xacer bati o n a n d/ or l o wer 
res pirat or y tract i nfecti o n ( LR TI) d uri n g t he scree ni n g peri o d ( Rescree ni n g ma y 
be per m itte d as defi ne d i n Secti o n 1 0. 3. 1. 3 ).
6. 
T he s p o ns or ter mi nates t he st u d y .
F or s u bjects u n der g oi n g B A L pr oce d ures, if n o acce pta ble B A L sa m ple s ca n be o btai ne d 
fr o m an y  of t he 3 l o bes atte m pte d d uri n g t he baseli ne B A L visit, t he su bject will n ot be 
scree n faile d a n d t he n rescree ne d base d s olel y o n t his reas o n. T he s u bject ma y be 
ra n d o mize d t o t he i m m u n o ge nicit y p orti o n of t he st u d y wit h o ut t he nee d t o rescree n, wit h 
s p o ns or a p pr o val, pr o vi de d t he y are wit hi n t he scree ni n g wi n d o w a nd meet all a p plica ble 
criteria. If acce pta ble B A L sa m ples ca n be o btai ne d d uri n g t he baseli ne B A L visit b ut n ot 
fr o m t he o n-treat me nt B A L visit ( bet wee n Wee k 1 2 t o Wee k 1 4), t he s u bject will 
c o nti n ue t o c o m plete t he re mai ni n g i nf usi o n visits a n d t he st u d y  c o m pleti o n visit. T he se
s u bjects w o ul d n ot be c o nsi dere d as a B A L e val ua ble s u bject .
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 4 1 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 0. S T U D Y P R O C E D U R E S
T he o verall st u d y  fl o w c hart is ill ustrate d i n Fi g ure 2 0 - 1 ( S u p ple me nt 2 0. 1 ). Details o n 
t he pr oce d ures t o be perf or me d at eac h st u dy visit, i ncl u di n g scree ni n g, ca n be f o u n d i n 
S u p ple me nt 2 0. 2 Sc he d ule of St u d y  Pr oce d ures a n d Assess me nts a n d S u p ple me nt 2 0. 3
Sc he d ule of Cli nical La b orat or y  Assess me nts.
1 0. 1 I nf or me d C o nse nt a n d E nr oll me nt
A n y  patie nt w h o pr o vi des i nf or me d c o nse nt (ie, si g ns a n d dates t he i nf or me d c o nse nt 
f or m [IC F] ) is c o nsi dere d e nr olle d i n t he st u d y .
1 0. 2 S u bject I de ntific ati o n C o de
T he f oll o wi n g series of n u m bers will c o m prise t he SI C: pr ot oc ol i de ntifier (e g, 4 7 1 1 0 1 ) 
t o be pr o vi de d by t he s p o ns or, 3- di git n u m ber st u d y  site n u m ber (e g, 0 0 2) t o be pr o vi de d 
b y  t he s p o ns or, an d 3- di git s u bject n u m ber (e g, 0 0 3) reflecti n g t he or der of e nr oll me nt 
(ie, si g ni n g t he I CF) . F or e xa m ple, t he t hir d s u bject w h o si g ne d a n I CF at st u d y site 0 0 2
will be i de ntifie d as S u bject 4 7 1 1 0 1- 0 0 2 0 0 3. All st u d y  d oc u me nts (e g, C R Fs, cli nical 
d oc u me ntat i o n, sa m ple c o ntai ners, dr u g acc o u nta bilit y l o gs, etc.) will be i de ntifie d wit h 
t he SIC. A d diti o nall y , a u ni q uel y c o de d SIC(s) is per mitte d as l o n g as it d oes n ot c o ntai n 
a c o m bi nati o n of i nf or mati o n t hat all o ws pers o nal i de ntificati o n of a s u bject, i n 
c o mplia nce wit h la ws g o ver ni n g data pri vac y .
1 0. 3 Scree ni n g a n d St u d y Visits
1 0. 3. 1 Scree ni n g Visit
After i nf or me d c o nse nt has bee n o btai ne d fr o m t he s u bject a n d/ or t heir le gall y  a ut h orize d 
re prese ntati ve, s u bjects will be scree ne d o n-site f or eli gi bilit y base d o n t he In cl usi o n a n d 
E xcl usi o n Criteria (defi ne d i n Secti o n 9. 1 a n d Secti o n 9. 2 , res pecti vely ) a n d scree ni n g 
assess me nts (see Secti o n 2 0. 2 a n d Secti o n 2 0. 3 f or detaile d list of st u d y 
pr oce d ures/la b orat or y  assess me nts i ncl u di n g ser u m I g A, E C G, a n d C hest X-ra y/ C T).
R a n d o mizati o n is t o ta ke place after t he s u bject has met all eli gi bilit y  criteria a n d, as
a p plica ble, t he s u bject has s uccessf ully u n der g o ne t he baseli ne B A L visit wit h e val ua ble 
B A L sa m ples c ollecte d.
T he st u d y  site is res p o nsi ble f or mai ntai ni n g a n e nr oll me nt/scree ni n g l o g t hat i ncl u des all 
s u bjects w h o pr o vi de d i nf or me d c o nse nt. T he l o g als o will ser ve t o d oc u me nt t he reas o n 
f or scree ni n g fail ure. All scree ni n g data will be c ollecte d a n d re p orte d i n C R Fs, 
re gar dless of scree ni n g o utc o me. If a s u bject is rescree ne d, t he E n d of St u d y C R F s h o ul d 
be c o m plete d, a n d a ne w I C F, ne w SI C a n d ne w C R F are re q uire d f or t hat s u bject.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 4 2 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 0. 3. 1. 1 C o nfir m ati o n of Se vere C o n ge nit al A 1 PI Deficie nc y
T o esta blis h eli gi bilit y  f or partici pati o n i n t he st u d y, t he s u bject’s dia g n osis of se vere 
c o n ge nital A 1 PI deficie nc y m ust be c o nfir me d d uri n g scree ni n g b y m eas ureme nt of 
e n d o ge n o us plas ma A 1 PI le vel s. T he plas ma le vel m ust be ≤1 1 µ M, a n d t he plas ma 
sa m ple ca n be c ollecte d a n y ti me d uri n g scree ni n g f or treat me nt-naï ve A 1 PI deficie nt 
s u bjects, b ut o nl y f oll o wi n g a was h o ut fr o m pre vi o us A 1 PI  a u g me ntati o n t hera py i n 
treat me nt-e x perie nce d s u bjects. T he prese nce of e x o ge n o usl y -a d mi nistere d A 1 PI ma y 
i nterfere wit h t he verificati o n of e n d o ge n o us plas ma A 1 PI le vels i n treat me nt-
e x perie nce d s u bjects ; t heref ore, t he y will be re q uire d t o ha ve t heir pre-st u d y A 1 PI 
t hera py wit h dr a w n f or a mi ni m u m of 4 wee ks t o all o w A 1 PI le vels t o ret ur n t o t he 
s u bject’s pre -a u g me ntati o n le vels. Scree ni n g A 1 PI meas ure me nt ma y  be re peate d i n t he 
e ve nt of s us pecte d i na de q uate was h o ut res ulti n g i n i nitial scree ni n g A 1 PI le vel of 
> 1 1 µ M.
S u bjects m ust ha ve a dia g n osis of A 1 PI deficie nc y  (ie, ge n ot y pe of Pi * Z/ Z, Pi * Z/ N ull, 
Pi * Malt o n/ Z, or Pi * N ull/ N ull, or ot her “at -ris k” allelic c o m bi nati o ns s uc h as S Z 
[e xcl u di n g M S a n d M Z
wit h o ut t he prese nce of a n ot her all o wa ble at -ris k ge n oty p e])
A N D plas ma a nti ge nic A 1 PI le vel of ≤1 1 µ M i n or der t o meet eli gi bilit y  criteria. Res ults 
of t hese scree ni n g tests will be use d t o esta blis h t he s u bject’s eli gi bilit y  f or partici pati o n 
i n t he st u d y.
D uri n g t he was h o ut peri o d, t hese s u bjects will be all o we d t o u n der g o ot her scree ni n g 
pr oce d ures ( S u p ple me nt 2 0. 2 a n d S u p ple me nt 2 0. 3 ).
1 0. 3. 1. 2 P ul m o n ar y F u ncti o n Tests
1 0. 3. 1. 2. 1 S pir o metr y
S pir o metr y  tests are t o be c o n d ucte d acc or di n g t o sta n dar d g ui deli nes p u blis he d b y t he 
A merica n T h oracic S ociet y  a n d E ur o pea n Res pirat or y S ociety .1 9 ,2 0 W he ne ver p ossi ble, 
all meas ure me nts s h o ul d be perf or me d wit h t he sa me e q ui p me nt ar o u n d t he sa me ti me of 
t he da y ( ± 2 h o urs) d uri n g site visits t o mi ni mize e q ui p me nt a n d di ur nal varia bilit y. All 
s pir o metric meas ure me nts ( F E V 1 a n d F V C) are t o be meas ure d 3 0 ± 5 mi n utes f oll o wi n g 
a d ministrati o n of a s h ort -acti n g β - 2 a g o nist br o nc h o dilat or (e g, a t otal of 4 0 0 µ g of 
sal b uta m ol [ 2 × 2 0 0 µ g or 4 × 1 0 0 µ g] or its e q ui vale nt). S pir o metric meas ure me nts 
( F E V1 a n d F V C) are t o be perf or me d i n tri plicate, a n d t he hi g hest val ue at eac h ti me 
p oi nt f or eac h varia ble is t o be use d f or a nalys es. T he s pir o metr y e q ui p me nt is t o be 
cali brate d acc or di n g t o t he ma n ufact urer’s rec o m me n dati o n a n d d oc u me nte d i n a 
mai nte na nce l o g. T he sa me met h o d f or t he calc ulati o n of pre dicte d n or mal val ues will be 
a p plie d f o r all s u bjects a n d assess me nt ti me p oi nts t o mai ntai n sta n dar dizati o n.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 4 3 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 0. 3. 1. 3 Rescree ni n g
S u bjects ma y be rescree ne d o nce f or st u d y eli gi bilit y. S u bjects w h o ha ve faile d scree ni n g 
f or a ny of t he f oll o wi n g reas o ns ma y be rescree ne d:
1. 
Circ ulati n g a nti ge nic A 1 PI le vel of ≥1 1 µ M t hat is s us pecte d t o be d ue t o 
i na de q uate was h o ut of t he pri or A 1 PI t hera p y.
2. 
Err o ne o us scree ni n g res ults .
3. 
P ul m o nar y  e xacer bati o n at t he ti me of i nitial scree ni n g (N ote: s u bjects ma y be 
rescree ne d 4 wee ks after t he cli nical r es ol uti o n of a n e xacer bati o n) .
4. 
I neli gi bilit y d ue t o fail ure t o meet pr ot oc ol pre-s pecifie d ti me i nter vals 
(e g, i ncl usi o n criteria #5 a n d # 6 , a n d e xcl usi o n criteria #5 a n d # 1 7).
5. 
F or a d diti o nal reas o ns after disc ussi o n wit h t he me dical m o nit or a n d s p o ns or 
a ppr o val .
S u bjects w h o w ere disc o nti n ue d earl y fr o m t he st u d y d ue t o fail ure t o yi el d a de q uate 
baseli ne B A L sa m ples or fail ure t o meet t he eli gi bilit y  criteria re q uire d t o u n der g o t he 
br o nc h osc o p y/ B A L pr oce d ure will be all o we d t o be rescree ne d bef ore t he tar get 
e nr oll me nt of B A L e val ua ble s u bjects is c o m plete d.
If a s u bject is t o be rescree ne d, t he st u dy c o m pleti o n/ter mi nati o n C R F s h o ul d be 
c o m plete d . T he s u bject or his/ her le gall y a ut h orize d re prese ntati ve m ust si g n a ne w I C F
pri or t o rescree ni n g pr oce d ur es. A ne w SI C will be assi g ne d, a n d ne w C R Fs will be use d 
f or t he s u bject u p o n re-e nr oll me nt.
1 0. 3. 2 I nf usi o n Visits
G L A S SI A will be a d mi nistere d as I V i nf usi o ns at 6 0 m g/ k g B W e ver y  wee k ( ± 2 da ys) 
f or a t otal of 2 5 i nf usi o ns. Sc he d uli n g of a ll i nf usi o n or st u d y visits wi ll be base d o n t he 
date of t he first I P i nf usi o n visit ( Wee k 1, Da y 1). If a wee kly i nf usi o n is m ore t ha n 
+ 5 da y s fr o m t he e x pecte d date, t he i nf usi o n s h o ul d be s ki p pe d a n d t he ne xt re g ularl y 
sc he d ule d i nf usi o n s h o ul d ta ke place.
1 0. 3. 2. 1 IP A d mi nistr ati o n
Descri pti o n of G L A S SI A treat me nt i ncl u di n g treat me nt peri o d, d ose a n d d osi n g 
fre q ue nc y, m o de of a d mi nistrati o n, as well as pre parati o n of i nf usi o n s ol uti o n are detaile d 
i n Secti o n 8. 7 .
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 4 4 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
T he first i nf usi o n ( Wee k 1), as well as i nf usi o ns d uri n g Wee k 7, Wee k
1 3 , Wee k 1 9, a n d 
Wee k
2 5, m ust be a d mi nistere d at t he st u d y site t o facilitate m o nit ori n g a n d re p orti n g of 
p ote ntial A Es ass ociate d wit h G L A S SI A i nf usi o ns. At t he i n vesti gat or’s discreti o n, all 
ot her i nf usi o ns ma y  be a d mi nistere d at t he st u d y site or at a n ot her s uita ble l ocati o n (e g,
t he s u bject’s h o me) by a q ualifie d healt hcare pr ofessi o nal, as acce pta ble per l ocal 
re g ulati o ns a n d sta n dar d practices of t he st u d y site.
D uri n g Wee ks 1, 7, 1 3, 1 9, a n d 2 5 i nf usi o n visits , vital si g ns (ie, b o dy te m perat ure, 
res pirat or y rate, p ulse rate, a n d s ys t olic a n d diast olic bl o o d press ure; see Secti o n 1 2. 1 0
a n d Ta ble 2 0. 3- 1 f or a d diti o nal details) are t o be ta ke n o n t he da y of i nf usi o n at a n y ti me 
pri or t o t he start of a n i nf usi o n, at eac h rate re d ucti o n d ue t o A E(s) a n d/ or i nf usi o n 
i nterr u pti o n/ disc o nti n uati o n d ue t o A E(s), a n d at 3 0 ( ± 1 5) mi n utes after t he c o m pleti o n of 
a n i nf usi o n. T he i n vesti gat or s h o ul d be c o ntacte d t o deter mi ne a p pr o priate acti o n t o be 
ta ke n, as necessar y , if vital si g ns meet a ny of t he f oll o wi n g criteria:
  
S y st olic bl o o d press ure ≤8 0 m m H g or ≥1 8 0 m m H g a n d/ or diast olic bl o o d 
press ure: ≤5 0 m m H g or ≥1 1 0 m m H g
  
P ulse rate ≤4 8 beats/ mi n or ≥1 1 0 beats/ mi n
  
Res pirat or y  rate ≤8 breat hs/ mi n or ≥2 4 breat hs/ mi n
  
B o d y te m perat ure ≥3 8. 2 ° C ( 1 0 1°F) 
F or eac h i nf usi o n, t he f oll o wi n g I P a d mi nistrati o n i nf or mati o n will be rec or de d i n t he 
a p pr o priate C R F(s):
  
Date, start a n d e n d ti me of t he i nf usi o n
  
Pla n ne d i nf usi o n v ol u me
  
Act ual v ol u me i nf use d
  
I nf usi o n rate, i ncl u di n g eac h i nf usi o n rate c ha n ge (if a n y) a n d reas o n
  
I nf usi o n i nterr u pti o ns or earl y disc o nti n uati o n (if a n y), i ncl u di n g t he ti me of 
i nf usi o n i nterr u pti o n ( or early st o p) a n d restart 
  
A E(s)
  
C o nc o mita nt use of a n y me dicati o ns a n d a n y n o n -dr u g t hera pies, i ncl u di n g t h ose 
use d t o treat A E(s)
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 4 5 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 0. 3. 2. 2 M a n a ge me nt of Tre at me nt - Emer g e nt ( S) A Es
M il d-t o-m o derate n o n -seri o us A Es or ot her c o nstit uti o nal s ym pt o ms t hat de vel o pe d 
d uri n g a n i nf usi o n ma y  be treate d by sta n dar d of care me dical i nter ve nti o ns a p pr o priate 
f or t he A E at t he i n vesti gat or’s discreti o n. I n t he e ve nt t hat t he A E c o nti n ues or i ncrease 
i n se verit y des pite i nter ve nti o ns, t he i nf usi o n rate ma y be decrease d b y 0. 0 4 m L/ k g 
B W/ mi n or t he i nf usi o n ma y  be te m p oraril y i nterr u pte d at t he i n vesti gat or’s discreti o n. If 
t he A E is n ot res ol vi n g, t he i nf usi o n rate ma y be f urt her decrease d i n a ste p wise ma n ner 
b y  0. 0 4 m L/ k g B W/ mi n or disc onti n ue d. O nce a n A E res ol ves, t he i nf usi o n ma y  be 
res u me d or c o nti n ue d at a n i nf usi o n rate as t olerate d b y t he s u bject ( b ut n ot t o e xcee d 
0. 2 m L / k g B W/ mi n) at t he discreti o n of t he i n vesti gat or.
If a se vere, n o n- seri o us A E or S A E occ urs d uri n g a n i nf usi o n, t he i nf usi o n s h o ul d be 
i nterr u pte d pe n di n g assess me nt b y  t he i n vesti gat or, a n d a p pr o priate acti o n is t o be ta ke n 
t o treat t he A E. T he i nf usi o n ma y  be restarte d if t he A E res ol ves i n res p o nse t o 
i nter ve nti o ns a n d/ or re d ucti o n i n i nf usi o n rate a n d if it’s dee me d safe b y t he i n vesti gat or.
I n t he e ve nt of a life-t hreate ni n g S A E, st u d y pers o n nel s h o ul d ta ke i m me diate ste ps t o 
preser ve t he s u bject’s well -bei n g a n d call f or e mer ge nc y assista nce, as well as c o ntact t he 
i n vesti gat or a n d re p ort t he S A E as descri be d i n Secti o n 2 .
F or m o derate t o se vere h yperse nsiti vit y  reacti o ns (ie, urticaria, l o w bl o o d press ure,
a n gi oe de ma, or w heezi n g), t he i nf usi o n s h o ul d be st o p pe d i m me diatel y  a n d t he s u bject
s h o ul d be treate d acc or di n g t o t he sta n dar d of care at t he discreti o n of t he i n vesti gat or. 
Pri or t o f urt her I P a d mi nistrati o ns, t he i n vesti gat or s h o ul d c o ns ult t he s p o ns or’s m e dical 
m o nit or.
I n t he e ve nt a s u bject de vel o ps a ras h at a n y ti me d uri n g t he st u d y, t he nat ure , se verity, 
e xte nt of t he er u pti o n, its te m p oral relati o ns hi p t o t he last I P a d mi nistrati o n, a n d t he 
li kel y ca use(s) s h o ul d be e xa mi ne d pri or t o t he ne xt sc he d ule d i nf usi o n . Ma na ge me nt of 
ras hes i ncl u des, b ut is n ot li mite d t o, t he f oll o wi n g:
  
Mi n or ras hes are t h ose i n v ol vi n g 1 0 % of b o d y s urface or less wit h o ut blee di n g or
si g ns of sec o n dar y i nfecti o n. Mi n or ras hes ma y  be treate d as i n dicate d wit h 
t o pical me dicati o ns, i ncl u di n g a nti -pr uritic a n d c ortic oste r oi d crea ms. I nf usi o ns 
ca n be c o nti n ue d if t he ras h is c o nfir me d t o be mi n or a n d/ or dee me d u nrelate d t o 
I P.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 4 6 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
  
M aj or ras hes are t h ose t hat i n v ol ve m ore t ha n 1 0 % of t he b o dy s urface, are 
pr o gressi ve, are ass ociate d wit h he m orr ha ge a n d/ or sec o n dar y i nfecti o n, or re q uire 
s yste mic c ortic oster oi d treat me nt. T hese s h o ul d be treate d a p pr o priately a n d 
i nf usi o ns s h o ul d be disc o nti n ue d i m me diatel y u ntil t he c o n diti o n has res ol ve d 
c o m pletel y or is j u d ge d t o be n ot cli nicall y si g nifica nt. Pr oce d ures ( e g, bi o ps y  of 
t he lesi o n) m a y  be perf or me d t o i n vesti gate t he pat h o p h ysi ol o g y of t he ras h. At 
t he discreti o n of t he i n vesti gat or, IP treat me nt ma y  be res u me d o nly after t he ras h 
has res ol ve d a n d t he s u bject’s c o n diti o n is dee me d me dicall y  safe a n d a p pr o priate.
P re-me dicat i o ns s uc h as oral or t o pical c ortic oster oi d treat me nt ma y  be 
a d mi nistere d f or t he s u bse q ue nt 2 i nf usi o ns, as a p plica ble, at t he discreti o n of t he 
i n vesti gat or i n acc or da nce wit h t he sta n dar d of care at t he i n vesti gati ve site. 
S u bjects wit h rec urre nt maj or ras hes, ras hes t hat rec ur u p o n rec halle n ge of I P 
des pite (pre -)me dicati o n (s), or ras hes t hat d o n ot res ol ve wit hi n 6 wee ks will be 
disc o nti n ue d fr o m f urt her I P a d mi nistrati o n a n d will be f oll o we d as o utli ne d i n 
Secti o n 9. 3 .
A n y  rate re d ucti o ns, i nterr u pti o ns or disc o nti n uati o n of a n i nf usi o n a n d, if a p plica ble, a n y
me dicati o ns a n d/ or n o n -dr u g t hera pies use d t o treat A E(s), m ust be rec or de d i n t he
a p pro priate C R F(s).
1 0. 3. 2. 3 Pre -Me dic ati o n s
If t he sa me t y pe of mil d-t o-m o derate, n o n -seri o us A E e x pecte d t o be relate d t o IP 
i nf usi o n (e g, hea dac he, c hills, fe ver, fl us hi n g, a n d malaise) or ot her c o nstit uti o nal 
s ym pt o ms rec urs f or 2 or m ore i nf usi o ns, t he s u bject ma y be pre -me dicate d f or 
s u bse q ue nt i nf usi o n(s) at t he discreti o n of t he i n vesti gat or i n acc or da nce wit h t he 
sta n dar d of care at t he i n vesti gati ve site. T he use of a ny pre -me dicati o ns m ust be 
rec or de d i n t he a p pr o priate C R F(s).
1 0. 3. 2. 4 P ost -I nf usi o n F oll o w-U p
F oll o wi n g eac h i nf usi o n visit, tele p h o ne f oll o w-u p will be c o n d ucte d b y t he 
i n vesti gat or/ desi g nee at 7 2 h o urs ( + 1 b usi ness da y) t o d oc u me nt A Es, a n d/ or 
a d mi nistrati o n of c o nc o mita nt me dicati o ns or n o n- dr u g t hera pies, w hic h ma y  ha ve 
occ urre d wit hi n 7 2 h o urs after t he c o m pleti o n of a n i nf usi o n.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 4 7 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 0. 3. 3 Cli nic al Assess me nt Visits
F oll o wi n g Wee k 1 visit , s u bjects will be as ke d t o ret ur n t o t he st u d y site d uri n g Wee k 1 3 
a n d Wee k 2 5 f or o n- treat me nt cli nical a n d safet y la b orat or y assess me nts, as well as 
plas ma A 1 PI  meas ure me nts. A d diti o nal bl o o d sa m ples will be dra w n f or t he m o nit ori n g 
of plas ma A 1 PI le vels d uri n g Wee k 7 a n d Wee k 1 9 , w hic h will ta ke place at st u d y site b y 
a q ualifie d healt hcare pr ofessi o nal. F oll o wi n g t he last i nf usi o n ( Wee k 2 5), s u bjects will 
ret ur n t o t he st u d y site 7 ± 3 da ys p ost-i nf usi o n f or st u d y c o m pleti o n assess me nts.
A d etaile d list of assess me nts t o be perf or me d at eac h cli nical assess me nt visit is 
pr o vi de d i n S u p ple me nt 2 0. 2 a n d S u p ple me nt 2 0. 3 .
1 0. 3. 4 B A L V isits
T his secti o n a p plies t o s u bjects w h o are t o u n der g o br o nc h osc o p y/ B A L pr oce d ures. 
Br o nc h osc o p y/ B A L pr oce d ure will be wai ve d f or s u bjects w h o are e nr olle d after 1 5 t o 
1 8 B A L e val ua ble s u bjects ha ve bee n o btai ne d. A n e val ua ble s u bject is defi ne d as a 
s u bject w h o:
  
has s uccessf ull y c o m plete d b ot h t he baseli ne a n d t he o n-treat me nt B A L visits, a n d 
  
has at least 1 acce pta ble B A L sa m ple o btai ne d fr o m a n y  of t he 3 l o bes fr o m eac h 
visit a n d meeti n g t he f oll o wi n g criteria:
 
t otal rec o ver y of ≥2 0 % of t he i nstille d v ol u me of sali ne per l o be , a n d
 
B A L sa m ple s h o ws n o bl o o d b y  vis ual i ns pecti o n.
S u bjects will be as ke d t o u n der g o t he br o nc h osc o p y / B A L pr oce d ures o n 2 occasi o ns: at 
baseli ne ( pri or t o ra n d o mizati o n) a n d f oll o wi n g i nitiati o n of G L A S SI A treat me nt f or 
1 2 t o 1 4 wee ks.
T he baseli ne B A L visit m ust be c o n d ucte d after verificati o n of deficie nt plas ma 
(a nti ge nic) A 1 PI le vels (≤1 1 M) has bee n o btai ne d. S u bjects w h o ha ve bee n 
recei vi n g A 1 PI a u g me ntati o n t hera p y  pri or t o st u d y e ntr y m ust ha ve p las ma sa m ples
c ollecte d wit hi n 1 0 da y s pri or t o t he baseli ne B A L visit f or t he meas ure me nt of 
plas ma (a nti ge nic) A 1 PI le vels t o verif y t he a de q uac y of t he was h o ut fr o m A 1 PI 
t hera py pri or t o perf or mi n g B A L. T he baseli ne br o nc h osc o p y/ B A L visit m ust be 
c o m plete d pri or t o ra n d o mizati o n a n d wit hi n 4 8 h o urs pri or t o t he first I P 
a d mi nistr ati o n . I n or der f or a s u bject t o be ra n d o mize d a n d re mai n i n t he st u d y , t he 
s u bject m ust ha ve acce pta ble B A L sa m ple ( as per criteria a b o ve). If n o acce pta ble B A L 
sa m ples ca n be o btai ne d fr o m a ny of t he 3 l o bes atte m pte d d uri n g t he baseli ne B A L visit, 
t he s u bject will n ot be scree n faile d a n d t he n rescree ne d base d s olely o n t his reas o n. 
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 4 8 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
T he s u bject ma y  be ra n d o mize d t o t he i m m u n o ge nicit y p orti o n of t he st u d y wit h o ut t he 
nee d t o rescree n, wit h s p o ns or a p p r o val, pr o vi de d t he y are wit hi n t he scree ni n g wi n d o w 
a n d meet all a p plica ble criteria .
D uri n g G L A S SI A a u g me ntati o n t hera p y, t he s u bject will be as ke d t o u n der g o t he 
o n-treat me nt B A L visit bet wee n Wee k 1 2 a n d Wee k 1 4. T he o n -treat me nt 
br o nc h osc o p y/ B A L pr oc e d ure will be c o n d ucte d at 7 ( ± 1) da ys f oll o wi n g t he last IP 
i nf usi o n, b ut m ust be c o m plete d pri or t o t he ne xt I P i nf usi o n. W he ne ver p ossi ble, i t is 
rec o m me n de d t hat s ufficie nt ti me (t ypicall y  2 4 t o 4 8 h o urs) is all o we d f or t he s u bject t o 
rec o ver fr o m t he br o nc h osc o p y/ B A L pr oce d ures pri or t o I P a d mi nistrati o n. 
S u bjects w h o ha ve s uccessf ull y c o m pleted t he o n-treat me nt B A L visit a n d ha ve
acce pta ble B A L sa m ples will be c o nsi dere d as a n e val ua ble s u bject. If acce pta ble B A L 
sa m ples ca nn ot be o btai ne d fr o m a n y of t he 3 l o bes atte m pte d d uri n g t he o n -treat me nt 
B A L visit , t he s u bject will c o nti n ue t o c o m plete t he re mai ni n g i nf usi o n visits t hr o u g h 
Wee k 2 5 a n d t he st u d y c o m pleti o n visit ( Wee k 2 6). T hese s u bjects, h o we ver, w o ul d n ot 
be c o nsi dere d as a B A L e val ua ble s u bject. Ne w s u bjects ma y  be e nr olle d t o ac hie ve t he 
tar get of 1 5 t o 1 8 e val ua ble s u bjects , as necessar y.
D uri n g t he B A L visit s, plas ma sa m ple s will be c ollecte d wit hi n 2 h o urs pri or t o t he 
B A L pr oce d ure f or t he meas ure me nt of plas ma urea , as well as plas ma a nti ge nic a n d 
f u ncti o nal A 1 PI le vels. Vital si g ns will be meas ure d wit hi n 2 h o urs pri or t o eac h B A L 
pr oce d ure a n d wit hi n 1 h o ur after t he c o m pleti o n of t he B A L pr oce d ure. Pre-B A L vital 
si g ns are t o be assesse d pri or t o br o nc h o dilat or a n d l ocal a nest hesia a d mi nistrati o n.
T he s u bject s h o ul d be m o nit ore d f or E C G, bl o o d press ure, res pirat or y rate, a n d p ulse 
o xi metr y  d uri n g t he pr oce d ure i n acc or da nce wit h sta n dar d practice at t he l ocal 
i nstit uti o n. T he s u bject will re mai n i n t he h os pital/cli nic u ntil, i n t he i n vesti gat or’s 
me dical j u d g me nt , it is safe t o disc har ge t he s u bject. S u bjects will be f oll o we d f or p ost-
B A L safet y m o nit ori n g (ie , A Es a n d c o nc o mita nt me dicati o ns/ n o n-dr u g t hera pies) at t he 
st u d y site or by tele p h o ne wit hi n 2 wee ks after eac h B A L pr oce d ure .
I n or der t o assess t he effects of G L A S SI A mai nte na nce treat me nt o n t he E L F A 1 PI 
le vels, it is i m p orta nt f or t he o n-treat me nt B A L pr oce d ure be perf or me d after sta ble 
d osi n g of G L A S SI A has bee n mai ntai ne d f or at least 4 half-li ves of A 1 PI (ie, a vera ge 
half -life ~ 4. 6 da ys, see G L A S SI A pac ka ge i nsert a n d/ or I B). T h us, sh o ul d a s u bject miss 
1 or m ore c o nsec uti ve G L A S SI A i nf usi o n(s) wit h i n 4 wee k(s) i m me diatel y pri or t o t he 
sc he d ule d o n- treat me nt B A L visit , t he B A L pr oce d ure will be resc he d ule d t o occ ur after 
t he s u bject has recei ve d at least 4 c o nsec uti ve wee kl y G L A S SI A a d mi nistrati o ns.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 4 9 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
T he ti mi n g of t he resc he d ule d B A L visit will f oll o w t he sa me re q uire me nts as descri be d 
a b o ve f or t he o n-treat me nt B A L visit.
1 0. 4 C O P D E x acer b ati o n a n d L o wer Res pir at or y Tr act I nfecti o n
A n e xacer bati o n of C O P D is defi ne d as a n ac ute e ve nt c haracterize d b y  a w orse ni n g of 
t he patie nt’s res pirat or y s ym pt o ms t hat is be y o n d n or mal da y -t o-da y  variati o ns a n d lea d 
t o a c ha n ge i n me dicatio n. T he o nset of a n e xacer bati o n is defi ne d as t he first da y of a n 
i ncrease i n or ne w o nset of m ore t ha n o ne of t he res pirat or y sy m pt o ms (c o u g h, s p ut u m, 
s p ut u m p ur ule nce, w heezi n g, or dys p nea), c o m pare d t o t he s u bject’s us ual cli nical state, 
f or at least 2 c o nsec uti ve da ys a n d re q uiri n g treat me nt wit h a nti bi otics a n d/ or s yste mic 
( oral, i ntra m usc ular or I V) c ortic oster oi ds. T he e n d of a n e xacer bati o n is defi ne d as t he 
first da y t hat a n y si g ns a n d s ym pt o ms of C O P D e xacer bati o n a n d/ or L R TI s ym pt o ms are 
n o l o n g er cli nicall y e vi de nt (ie, t he first da y t hat a s u bject ret ur ns t o his/ her us ual cli nical 
state) f or at least 2 c o nsec uti ve da ys. As de picte d i n Fi g ure 1 0- 1 , t he t otal le n gt h of t he 
e pis o de i ncl u des a n y dela y i n treat me nt (ti me ta ke n f or treat me nt t o be i nitiate d after t he 
o nset of e xacer bati o n) a n d ti me t o res ol uti o n of si g ns a n d s ym pt o ms .2 1 ,2 2
Fi g ure 1 0- 1
E x acer b ati o n of C O P D
O ns et of 
E x ac er b ati o n
I niti ati o n of 
Tr e at m e nt
E n d of 
E x ac er b ati o n
D el a y i n 
Tr e at m e nt
R es ol uti o n of E x ac er b ati o n Si g ns a n d 
S y m pt o ms Si nc e C o m m e nc e m e nt of 
Tr e at m e nt
A d diti o n al 4 w e e ks d uri n g 
w hic h s u bj ects r e m ai n 
cli nic all y st a bl e 
Br o nc h osc o p y /B AL Visit
(As A p plic a bl e f or S u bj ects U n d er g oi n g 
Br o nc h osc o p y /B AL Pr oc e d ur e ) 
If a s u bject e x perie nces a m o derate or se vere C O P D e xacer bati o n a n d/ or L R TI  d uri n g t he 
scree ni n g peri o d, t he baseli ne B A L visit will be p ost p o ne d o nce i n or der f or t he s u bject t o 
rec o ver fr o m t he e xacer bati o n (ie, a n y si g ns a n d s y m pt o ms of t he C O P D e xacer bati o n 
a n d/ or LR TI  are n o l o n ger cli nicall y e vi de nt) a n d re mai n sta ble f or at least 4 wee ks after 
t he e n d of e xacer bati o n. If a m o derate or se vere e pis o de of C O P D e xacer bati o n a n d/ or 
L R TI occ urs d uri n g t he treat me nt p hase, t he s u bject s h o ul d c o nti n ue wit h t he pla n ne d 
st u d y visits a n d t o recei ve wee kly i nf usi o ns of G L A S SIA as pla n ne d, u nless dee me d 
me dicall y  i na p pr o priate b y t he i n vesti gat or. H o we ver, t he o n-treat me nt B A L visit will be 
p ost p o ne d u ntil cli nical res ol uti o n of t he e xacer bati o n (ie, a n y si g ns a n d s y m pt o ms of t he 
C O P D e xacer bati o n a n d/ or L R T I are n o l o n ger cli nicall y e vi de nt) pl us a n a d diti o nal 
mi ni m u m peri o d of 4 wee ks after t he e n d of e xacer bati o n.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 5 0 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
T he s e verit y of a C O P D e xacer bati o n a n d/ or L R TI will be cate g orize d as mil d, m o derate,
or se vere acc or di n g t o t he f oll o wi n g defi niti o ns:
  
Mil d – treate d at h o me wit h o ut seei n g a healt h care pr o vi der.
  
M o derate – visit wit h healt h care pr o vi der ( e g, h o me visit, visit t o a n o ut patie nt 
facilit y or a n e mer ge nc y de part me nt, b ut n ot re q uiri n g a d missi o n t o h os pital) .
  
Se vere – h os pitalizati o n (a n e mer ge nc y  de part me nt sta y  > 2 4 h o urs is c o nsi dere d a 
h os pitalizati o n) .
A n y  occ urre nces of C O P D e xacer bati o n a n d/or L R TI  are t o be rec or de d o n t he A E C R F.
1 0. 5 Me dic ati o ns a n d N o n - Dr u g T her a pies
T he f oll o wi n g me dicati o ns are n ot per mitte d at a n y ti me d uri n g t he c o urse of t he st u d y :
  
A n y  A 1 PI a u g me ntati o n t hera p y ot her t ha n IP i n t his st u d y; c o m mercially 
a vaila ble G L A S SI A is als o n ot per mitte d.
  
A n y  i n vesti gati o nal dr u g, bi ol o gic, or de vice ot her t ha n IP i n t his st u d y .
A s u bject w h o has ta ke n a n y  of t he a b o ve me dicati o ns will be disc o nti n ue d fr o m f urt her 
treat me nt a n d/ or fr o m t he st u d y. 
T he f oll o wi n g me dicati o ns are n ot per mitte d wit hi n a pre -s pecifie d ti me i nter val pri or t o 
eac h B A L pr oce d ure :
  
Im m u n os u p pressi ve t hera p ies (s uc h as sys te mic c ortic oster oi ds at d oses greater 
t ha n 1 0 m g/ da y of pre d nis o ne or its e q ui vale nt, m yc o p he n olate m ofetil, 
azat hi o pri ne, a n d c ycl o p h os p ha mi de) wit hi n 4 wee ks pri or t o a n d d uri n g t he 
B A L pr oce d ures

Rit u xi ma b at a n y  ti me d uri n g t he st u d y.
  
A ntic oa g ula nt or a nti -platelet t hera p y ( s uc h as warfari n a n d cl o pi d o grel) wit hi n 
7 da y s pri or t o a n d d uri n g t he B A L pr oce d ures, wit h t he e xce pti o n of l o w -d ose 
as piri n w hic h is all o we d.
T he f oll o wi n g me dicati o ns are per mitte d d uri n g t he c o urse of t he st u d y pr o vi de d t hat t he 
d osa ge re mai n s sta ble t hr o u g h o ut t he c o urse of t he st u d y:
1. 
A n y  res pirat or y me dicati o ns i ncl u di n g i n hale d br o nc h o dilat ors, i n hale d 
a ntic h oli ner gics, i n hale d c ortic oster oi ds, or l o w-d ose s y ste mic c ortic oster oi ds 
( pre d nis o ne ≤1 0 m g/ da y  or its e q ui vale nt)
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 5 1 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
2. 
T he o p h y lli ne.
3. 
Ot her me dicati o ns t hat a s u bject is ta ki n g f or a pre -e xisti n g me dical c o n diti o n
e xce pt f or t h ose liste d u n der pr o hi bite d me dicati o ns a b o ve .
D osa ge s of per mitte d c o nc o mita nt me dicati o ns are t o re mai n sta ble t hr o u g h o ut t he c o urse 
of t he st u d y , u nless ot her wise me dicall y i n dicate d.
1 0. 6 S u bject C o m pleti o n/ Disc o nti n u ati o n
A s u bject is c o nsi dere d t o ha ve c o m plete d t he st u d y  w he n he/s he ceases acti ve 
partici pati o n i n t he st u d y  beca use t he s u bject has, or is pres u me d t o ha ve, c o m plete d all 
st u d y pr oce d ures acc or di n g wit h t he pr ot oc ol ( wit h or wit h o ut pr ot oc ol de viati o ns) .
Reas o ns f or c o m pleti o n/ disc o nti n uati o n will be re p orte d o n t he 
C o m pleti o n/ Disc o nti n uati o n C R F, i ncl u di n g: c o m plete d, scree n fail ure, ( S)A E (e g, 
deat h), disc o nti n uati o n b y  s u bject (e g, l ost t o f oll o w- u p [ defi ne d as 3 d oc u me nte d 
u ns uccessf ul atte m pts t o c o ntact t he s u bject], dr o p o ut), p h y sicia n decisi o n (e g, 
pre g na nc y , pr o gressi ve disease, n o n-c o m plia nce wit h IP/ pr ot oc ol vi olati o n(s), rec o ver y ), 
st u d y ter mi nate d by s p o ns or, or ot her (reas o n t o be s pecifie d b y t he i n vesti gat or, e g, 
tec h nical pr o ble ms). Re gar dless of t he reas o n, all data a vaila ble f or t he s u bject u p t o t he 
ti me of c o m pleti o n/ disc o nti n uati o n s h o ul d be rec or de d o n t he a p pr o priate C R F. 
E ver y  eff ort will be ma de t o ha ve disc o nti n ued s u bjects c o m plete t he st u d y 
c o m pleti o n/ter mi nati o n visit. S u bjects w h o are disc o nti n ue d earl y fr o m t he st u d y pri or t o 
recei vi n g a ny I P a d mi nistrati o n will n ot nee d t o u n der g o earl y ter mi nati o n pr oce d ures , 
e xce pt f or t h ose s u bjects w h o ha ve u n der g o ne t he baseli ne B A L pr oce d ure i n w hic h case 
s u bjects will be f oll o we d f or p ote ntial p ost-B A L c o m plicati o ns f or a peri o d of ti me i n 
acc or da nce wit h l ocal i nstit uti o nal sta n dar d practice b ut n ot t o e xcee d 3 0 da ys.
If t he c o m pleti o n/ter mi nati o n visit is d o ne as a n ad diti o nal, u nsc he d ule d visit, t he 
assess me nt res ults s hall be rec or de d wit h t he c o m pleti o n/ter mi nati o n visit. If a s u bject 
ter mi nates partici pati o n i n t he st u d y a n d d oes n ot ret ur n f or t he c o m pleti o n/ter mi nati o n 
visit, t heir last rec or de d assess me nts s hall re mai n rec or de d wit h t heir last visit. T he 
reas o n f or disc o nti n uati o n will be rec or de d, a n d t he data c ollecte d u p t o t he ti me of 
disc o nti n uati o n will be use d i n t he a nal ys is a n d i ncl u de d i n t he cli nical st u d y re p ort. If 
a d diti o nal assess me nts are re q uire d , t he assess me nts s hall be rec or de d se paratel y. 
Assess me nts t o be perf or me d at t he ter mi nati o n visit (i ncl u di n g i n cases of wit h dra w or 
disc o nti n uati o n) ca n be f o u n d i n S u p ple me nt 2 0. 2 Sc he d ule of St u d y  Pr oce d ures a n d 
Assess me nts a n d S u p ple me nt 2 0. 3 Sc he d ule of Cli nical La b orat or y  Assess me nts.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 5 2 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
I n t he e ve nt of s u bject disc o nti n uati o n d ue t o a n ( S)A E, cli nical a n d/ or la b orat or y  
i n vesti gati o ns t hat are be y o n d t he sc o pe of t he re q uire d st u d y o bser vati o ns/assess me nts 
ma y  be perf or me d as part of t he e val uati o n of t he e ve nt. T hese i n vesti gati o ns will ta ke 
place u n der t he directi o n of t he i n vesti gat or i n c o ns ultati o n wit h t he s p o ns or, a n d t he 
details of t he o utc o me ma y  be re p orte d t o t he a p pr o priate re g ulator y  a ut h orities b y t he 
s p o ns or.
1 0. 7 Pr oce d ures f or M o nit ori n g S u bject C o m pli a nce
A ll st u d y pr oce d ures are t o be perf or me d u n der t he direct s u per visi o n of t he 
i n vesti gat or/a q ualifie d healt hcare pr ofessi o nal at t he st u d y  site or at a n ot her s uita ble 
l ocati o n (e g, t he s u bject’s h o me or i nf usi o n ce nter), a n d t h us, n o se parate pr oce d ures will 
be use d t o m o nit or s u bject c o m plia nce.
Tr o u g h a nti ge nic a n d f u ncti o nal A 1 PI  le vels i n plas ma w o ul d be deter mi ne d as a c hec k 
o n s u bject’s c o m plia nce/a d here nce t o treat me nt.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 5 3 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 1. A S S E S S M E N T O F E F FI C A C Y
1 1. 1 E L F A nti ge nic a n d F u ncti o n al A 1 PI Le vels
T his st u d y  will e val uate t he effects of G L A S SI A wee kl y a u g me ntati o n t hera p y o n t he 
A 1 PI  le vels i n t he E L F.
B A L sa m ples will be a nal y ze d f or t he deter mi nati o n of t he f oll o wi n g i n t he B A L fl ui d
usi n g vali date d bi oa nal yt ical assa ys at a q ualifie d la b orat or y:
1.
A nti ge nic A 1 PI le vel
2.
F u ncti o nal A 1 PI ( A N E C) le vel
3.
Urea le vel
E L F a nti ge nic a n d f u ncti o nal A 1 PI le vels will be esti mate d base d o n t he res pecti ve 
val ues meas ure d i n t he B A L  fl ui d usi n g t he plas ma-t o-B A L urea c orrecti o n met h o d. 
T his a p pr oac h is base d o n t he fact t hat urea is freel y  diff usi ble t hr o u g h m ost b o d y 
c o m part me nts, i ncl u di n g t he al ve olar wall. A dil uti o n fact or, k, will be deter mi ne d wit h 
t he f oll o wi n g f or m ula: dil uti o n fact or k = U P (c o nce ntrati o n of urea i n plas ma)/ U B A L
(c o nce ntrati o n of urea i n B A L fl ui d). Usi n g t his dil uti o n fact or, q ua ntitati ve 
meas ure me nts of E L F A 1 PI  a n d 
will be c orrecte d acc or di n gl y.
1 1. 2
 
 
 
 
 
 
 
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 5 4 of 9 8
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B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 2. A S S E S S M E N T O F S A F E T Y
1 2. 1 A d verse E ve nts
1 2. 1. 1 Defi niti o ns
A n A E is defi ne d as a n y u nt o war d me dical occ urre nce i n a s u bject a d mi nistere d a n I P 
t hat d oes n ot necessaril y ha ve a ca usal relati o ns hi p wit h t he treat me nt. A n A E ca n 
t heref ore be a ny u nfa v ora ble a n d u ni nte n de d si g n ( e g, a n a b n or mal la b orat or y fi n di n g), 
s ym pt o m (e g, ras h, pai n, disc o mf ort, fe ver, dizzi ness, etc.), disease (e g, perit o nitis, 
bactere mia, etc.) , or o utc o me of deat h te m p orall y ass ociate d wit h t he use of t he I P, 
w het her or n ot c o nsi dere d ca usall y relate d t o t he I P.
1 2. 1. 1. 1 Seri o us A d verse E ve nt 
A n S A E is defi ne d as a n u nt o war d me dical occ urre nce t hat at a n y d ose meets 1 or m ore 
of t he f oll o wi n g criteria:
  
O utc o me is fatal/res ults i n deat h (i nc l u di n g fetal deat h).
  
Is life-t hreate ni n g – defi ne d as a n e ve nt i n w hic h t he s u bject was, i n t he j u d g me nt 
of t he i n vesti gat or, 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 t hat h y p ot heticall y mi g ht ha ve ca use d deat h ha d it bee n m ore se vere.
  
Re q uires i n patie nt h os pitalizati o n or res ults i n pr ol o n gati o n of a n e xisti n g 
h os pitalizati o n – i n patie nt h os pitalizati o n refers t o a n y i n patie nt a d missi o n, 
re gar dless of le n gt h of sta y.
  
Res ults i n persiste nt or si g nifica nt disa bilit y /i nca pacit y (ie, 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).
  
Is a c o n ge nital a n o mal y/ birt h defect .
  
Is a me dically i m p orta nt e ve nt – a me dical e ve nt t hat ma y n ot be i m me diatel y life-
t hreate ni n g or res ult i n deat h or re q uire h os pitalizati o n b ut ma y je o par dize t he 
s u bject or ma y re q uire me dical or s ur gical i nter ve nti o n t o pre ve nt o ne of t he ot her 
o utc o mes liste d i n t he defi niti o ns a b o ve. E xa m ples of s uc h e ve nts are: 

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 ys crasias, 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 nce or dr u g a b use.

Re vie we d a n d c o nfir me d ser oc o n versi o n f or h u ma n i m m u n o deficie nc y  vir us 
( HI V), he patitis A vir us ( H A V), he patitis B vir us ( H B V), he patitis C vir us 
( H C V), he patitis E vir us ( H E V), or B 1 9 V.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 5 5 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
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B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 2. 1. 1. 1. 1 U nc o m plic ate d P re g n a ncies 
U nc o m plicate d pre g na ncies f oll o wi n g mater nal or pater nal e x p os ure t o t he I P are n ot 
c o nsi dere d a n ( S) A E; h o we ver, a n y pre g na nc y c o m plicati o n or pre g na nc y  ter mi nati o n b y 
t hera pe utic, electi ve, or s p o nta ne o us a b orti o n s hall be c o nsi dere d a n S A E.
1 2. 1. 1. 2 N o n -Seri o us A d verse E ve nt
A n o n -seri o us A E is a n A E t hat d oes n ot meet t he criteria of a n S A E.
1 2. 1. 1. 3 A d verse Re acti o ns Pl us S us pecte d A d verse Re acti o ns
A n A R pl us s us pecte d A R is a n y  A E w hic h met a n y  of t he f oll o wi n g criteria: 
(a) a n A E t hat be ga n d uri n g i nf usi o n or wit hi n 7 2 h o urs f oll o wi n g t he e n d of I P 
i nf usi o n, or
( b) a n A E c o nsi dere d b y eit her t he i n vesti gat or a n d/ or t he s p o ns or t o be p ossi bl y or 
pr o ba bl y  relate d t o IP a d mi nistrati o n, or 
(c) a n A E f or w hic h ca usalit y assess me nt was missi n g or i n deter mi nate.
I n a d diti o n, safety data will als o be a nal yze d f or a n y A R s pl us s us pecte d A Rs w hic h met 
a n y of t he f oll o wi n g criteria:
(a) a n A E t hat be ga n d uri n g i nf usi o n or wit hi n 2 4 h o urs f oll o wi n g t he e n d of I P 
i nf usi o n, or
( b) a n A E c o nsi dere d b y eit her t he i n vesti gat or a n d/ or t he s p o ns or t o be p ossi bl y or 
pr o ba bl y  relate d t o IP a d mi nistrati o n, or 
(c) a n A E f or w hic h ca usalit y assess me nt was missi n g or i n deter mi nate.
1 2. 1. 1. 4 U ne x pecte d A d verse E ve nts
A n u ne x pecte d a d verse e ve nt is a n A E w h ose nat ure, se verit y, s pecificit y, or o utc o me is 
n ot c o nsiste nt wit h t he ter m, re prese ntati o n, or descri pti o n use d i n t he Refere nce Safet y 
I nf or mati o n ( R SI) (e g, I B, pac ka ge i nsert). “ U ne x pecte d” als o refers t o t he A Es t hat are 
me nti o ne d i n t he R SI as occ urri n g wit h a class of dr u gs or as a ntici pate d fr o m t he 
p har mac ol o gical pr o perties of t he dr u g, b ut are n ot s pecificall y me nti o ne d as occ urri n g 
wit h t he partic ular dr u g u n der i n vesti gati o n. T he e x pecte d ness of A Es will be deter mi ne d 
b y  t he s p o ns or usi n g t he I B a n d/ or prescri bi n g i nf or mati o n as t he R SI. T his deter mi nati o n 
will i ncl u de c o nsi derati o ns s uc h as t he n u m ber of A Es pre vi o usl y  o bser ve d, b ut n ot o n 
t he basis of w hat mi g ht be a ntici pate d f or m t he p har mac ol o gical pr o perties of a pr o d uct.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 5 6 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 2. 1. 1. 5 A d verse E ve nts P ote nti all y Ass oci ate d wit h Pr otei n A g gre g ates
T he safet y data base will be re vie we d a n d assesse d f or A Es t hat ma y  p ote ntiall y be 
ass ociate d wit h pr otei n a g gre gates i n G L A S SI A s ol uti o n.
1 2. 1. 1. 6 Pree xisti n g Dise ases
Pree xisti n g diseases t hat are prese nt bef ore e ntr y  i nt o t he st u d y are descri be d i n t he 
me dical hist or y, a n d t h ose t hat ma nifest wit h t he sa me se verit y , fre q ue nc y, or d urati o n 
after I P e x p os ure, will n ot be rec or de d as A Es. H o we ver, w he n t here is a n i ncrease i n t he 
se verit y, d urati o n, or fre q ue nc y of a pree xisti n g disease, t he e ve nt m ust be descri be d o n 
t he A E C R F.
A n y  occ urre nces of C O P D e xacer bati o n a n d/or L R TI  are t o be rec or de d o n t he A E C R F 
(see Secti o n 1 0. 4 ).
1 2. 1. 2 Assess me nt of A d verse E ve nts
Eac h A E fr o m t he first I P e x p os ure u ntil st u d y  c o m pleti o n/earl y disc o nti n uati o n fr o m t he 
st u d y will be descri be d o n t he A E C R F usi n g t he me dical dia g n osis ( preferre d), or, if n o 
dia g n osis c o ul d be esta blis he d at t he ti me of re p orti n g t he A E, a s y m pt o m, or si g n, i n 
sta n dar d me dical ter mi n ol o g y i n or der t o a v oi d t he use of va g ue, a m bi g u o us, or 
c oll o q uial e x pressi o ns (see defi niti o n i n Secti o n 1 2. 1 ). Eac h A E will be e val uate d by t he 
i n vesti gat or f or:
  
Seri o us ness as defi ne d i n Secti o n 1 2. 1. 1. 1.
  
Se verit y  as defi ne d i n Secti o n 1 2. 1. 2. 1 .
  
Ca usal relati o ns hi p t o I P e x p os ure or st u d y  pr oce d ure as defi ne d i n 
Secti o n 1 2. 1. 2. 2 .
F or eac h A E, t he o utc o me (ie, rec o veri n g/res ol vi n g, rec o vere d/res ol ve d, 
rec o vere d/res ol ve d wit h se q uelae, n ot rec o vere d/ n ot res ol ve d, fatal, u n k n o w n) a n d if 
a p plica ble acti o n ta ke n (ie, d ose i ncrease d, d ose n ot c ha n ge d, d ose re d uce d, dr u g 
i nterr u pte d, dr u g wit h dra w n, n ot a p plica ble, or u n k n o w n) will als o be rec or de d o n t he A E 
C R F. Rec o veri n g/res ol vi n g A Es will be f oll o we d u ntil res ol uti o n, me dicall y  sta bilize d, or 
3 0 da y s after t he st u d y c o m pleti o n/ter mi nati o n visit, w hic he ver c o mes first. A E a n d ot her 
C R F(s), as a p plica ble, will be u p date d if a d diti o nal f oll o w-u p i nf or mati o n is 
c ollecte d/re p orte d pri or t o st u d y  c o m pleti o n ( n o a d diti o nal re p orti n g o n C R F(s) is 
necessar y  after st u d y c o m pleti o n).
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 5 7 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
If t he se verit y rati n g f or a n o n g oi n g A E c ha n ges bef ore t he e ve nt res ol ves, t he ori gi nal 
A E re p ort will be re vise d (ie, t he e ve nt will n ot be re p orte d as se parate A E). D uri n g t he 
c o urse of a n y A E, t he hi g hest se verit y rati n g will be re p orte d.
De viati o ns fr o m t he pr ot oc ol-s pecifie d d osa ge (i ncl u di n g o ver d osi n g [ b y > 5 0 %], 
u n der d osi n g [ b y >5 0 %] , a b use, a n d wit h dra wal), treat me nt err ors (i ncl u di n g i nc orrect 
r o ute of a d mi nistrati o n, use of a n i nc orrect pr o d uct, a n d de viati o ns fr o m t he pr ot oc ol-
defi ne d d osi n g s c he d ule), fail ures of e x pecte d p har mac ol o gical acti o ns, a n d u ne x pecte d 
t hera pe utic or cli nical be nefits will be f oll o we d wit h re gar d t o occ urre nce of A Es, lac k of 
efficac y, a n d/ or ot her o bser vati o ns beca use t hese e ve nts ma y be re p orta ble t o re g ulat or y 
a ut horities.
A n y  pre g na nc y t hat occ urs after a d mi nistrati o n of I P will be re p orte d o n a Pre g na nc y
Re p ort F or m wit hi n 2 4 h o urs of a ware ness a n d f oll o we d -u p at esti mate d date of deli ver y 
a n d 1 y ear p ost-deli ver y , if feasi ble. ( S) A Es ass ociate d wit h t hese e ve nts m ust be 
re p orte d o n t he a p pr o priate ( S) A E f or ms, a n d f oll o w t he g ui da nce o n ti mi n g of t he re p ort 
pr o vi de d i n Secti o n 1 2. 1. 2. 3 .
If a n i n vesti gat or bec o mes a ware of a n S A E occ urri n g i n a s u bject after st u d y c o m pleti o n, 
t he S A E m ust be re p orte d o n t he pr o vi de d S A E Re p ort F or m wit hi n 2 4 h o urs after 
a ware ness; n o a d diti o nal re p orti n g o n C R Fs is necessar y .
F or t he p ur p oses of t his st u d y , eac h A E (e x pecte d a n d u ne x pecte d) e x perie nce d b y a 
s u bject u n der g oi n g br o nc h osc o p y/ B A L pr oce d ure will be rec or de d o n t he A E C R F.
1 2. 1. 2. 1 Se verit y
T he i n vesti gat or will assess t he se verit y of eac h A E usi n g his/ her cli nical e x pertise a n d 
j u d g me nt base d o n t he m ost a p pr o priate descri pti o n bel o w:
  
Mil d
  
T he A E is a tra nsie nt disc o mf ort a n d d oes n ot i nterfere i n a si g nifica nt ma n ner 
wit h t he s u bject’s n or mal f u ncti o ni n g le vel.
  
T he A E res ol ves s p o nta ne o usl y  or ma y re q uire mi ni mal t hera pe utic 
i nter ve nti o n.
  
M o derate
  
T he A E pr o d uces li mite d i m pair me nt of f u ncti o n a n d ma y  re q uire t hera pe utic 
i nter ve nti o n.
  
T he A E pr o d uces n o se q uela/se q uelae.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 5 8 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
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B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
  
Se vere
  
T he A E res ults i n a mar ke d i m pair me nt of f u ncti o n a n d ma y  lea d t o te m p orar y 
i na bilit y t o res u me us ual life patter n.
  
T he A E pr o d uces se q uela/se q uelae, w hic h re q uire ( pr ol o n ge d) t hera pe utic 
i nter ve nti o n.
T hese se verit y  defi niti o ns will als o be use d t o assess t he se verity of a n A E wit h a 
st u d y-relate d pr oce d ure(s), if necessar y.
1 2. 1. 2. 2 C a us alit y
Ca usalit y  is a deter mi nati o n of w het her t here is a reas o na ble p ossibilit y  t hat t he IP is 
eti ol o gicall y relate d t o/ass ociate d wit h t he A E. Ca usalit y  assess me nt i ncl u des, e g, 
assess me nt of te m p oral relati o ns hi ps, dec halle n ge/rec halle n ge i nf or mati o n, ass ociati o n 
( or lac k of ass ociati o n) wit h u n derl yi n g disease, prese nce ( or a bse nce) of a m ore li kel y 
ca use, a n d p h ys i ol o gical pla usi bilit y. F or eac h A E, t he i n vesti gat or will assess t he ca usal 
relati o ns hi p bet wee n t he I P a n d t he A E usi n g his/ her cli nical e x pertise a n d j u d g me nt 
acc or di n g t o t he f oll o wi n g m ost a p pr o priate al g orit h m f or t he circ u msta nces of t he A E:
  
N ot relate d ( b ot h circ u msta nces m ust be met)

Is d ue t o u n derlyi 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 c o nc urre nt dr u gs.

Is n ot ass ociate d wit h t he IP (ie, d oes n ot f oll o w a reas o na ble te m p oral 
relati o ns hi p t o t he a d mi nistrati o n of IP or has a m uc h m ore li kel y alter nati ve 
eti ol o g y). 
  
U nli kel y  relate d (eit her 1 or b ot h circ u msta nces are met)

Has little or n o te m p oral relati o ns hi p t o t he I P .

A m ore li kel y alter nati ve eti ol o g y e xists.
  
P ossi bl y  relate d ( b ot h circ u msta nces m ust be met)

F oll o ws a reas o na ble te m p oral relati o ns hi p t o t he a d mi nistrati o n of IP.

A n alter nati ve eti ol o g y  is e q uall y or less li kel y c o m pare d t o t he p ote ntial 
relati o ns hi p t o t he IP.
 
Pr o ba bl y  relate d ( b ot h circ u msta nces m ust be met)

F oll o ws a str o n g te m p oral relati o ns hi p t o t he a d mi nistrati o n of IP, w hic h ma y  
i ncl u de b ut is n ot li mite d t o t he f oll o wi n g: 
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 5 9 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
o
Rea p peara nce of a si milar reacti o n u p o n re -a d mi nistrati o n ( p ositi ve 
rec halle n ge).
o
P ositi ve res ults i n a dr u g se nsiti vit y  test (s ki n test, etc.).
o
T o xic le vel of t he I P as e vi de nce d b y  meas ure me nt of t he IP 
c o nce ntrati o ns i n t he bl o o d or ot her b o dil y  fl ui d.

A n ot her eti ol o g y  is u nli kel y or si g nifica ntl y less li kel y.
F or e ve nts assesse d as n ot relate d or u nli kel y relate d a n d occ urri n g wit hi n 7 2 h o urs 
f oll o wi n g c o m pleti o n of eac h I P a d mi nistrati o n, t he i n vesti gat or s hall pr o vi de t he 
alter nati ve eti ol o g y. T hese ca usality defi niti o ns will als o be use d t o assess t he 
relati o ns hi p of a n A E wit h a st u d y-relate d pr oce d ure(s), if necessar y.
1 2. 1. 2. 3 S afet y Re p orti n g
A d verse e ve nts/ S A Es will be assesse d at all st u d y  visits (fr o m first I P e x p os ure) as 
o utli ne d i n t he Sc he d ule of St u d y  Pr oce d ures a n d Assess me nts (see Ta ble 2 0. 2- 1 ) a n d 
Secti o n 1 2. 1 a b o ve.
A d verse E ve nts/ S A Es are t o be rec or de d o n t he A E pa ge of t he e C R F. Eac h e ve nt s h o ul d 
be rec or de d se paratel y.
A n y  S A E, i ncl u di n g deat h d ue t o a n y ca use, w hic h occ urs d uri n g t his st u d y, w het her or 
n ot relate d t o t he I P, m ust be re p orte d i m me diatel y ( wit hi n 2 4 h o urs of t he st u d y ce nter’s 
first k n o wle d ge of t he e ve nt). All S A Es m ust be re p orte d via t he Electr o nic Data Ca pt ure 
( E D C) sys te m b y c o m pleti n g t he rele va nt electr o nic C R F (e C R F) pa ge(s) i n E n glis h.
O nce t he S A E has bee n rec or de d i n t he E D C s y ste m, t he sp o ns or a n d ot her desi g nate d 
reci pie nts will be i nf or me d of t he e ve nt a ut o maticall y. F or i nsta nces i n w hic h t he E D C 
ma y  bec o me u na vaila ble, S A Es m ust be re p orte d usi n g t he bac k u p pa per S A E Re p ort 
F or m t o meet t he 2 4 -h o ur ti meli ne re q uire me nt (c o ntacts a n d i nstr ucti o ns t o be pr o vi de d 
i n se parate d oc u me ntati o n). O nce t he E D C bec o mes a vaila ble, t he site m ust e nter all S A E 
data as re p orte d o n t he bac k u p pa per S A E R e p ort F or m o n t he a p plica ble e C R F pa ges.
T he i nitial S A E i nf or mati o n re p orte d o n t he a p plica ble e C R F pa ges ( or bac k u p S A E 
Re p ort F or m, if a p plica ble) m ust at least i ncl u de t he f oll o wi n g:
  
Pr ot oc ol N u m ber
  
S u bject i de ntificati o n n u m ber a n d de m o gra p hics ( ge n de r, a ge at o nset of e ve nt 
a n d/ or date of birt h)
  
I P e x p os ure
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 6 0 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
  
Me dical Ter m f or E ve nt ( Dia g n osis prefera bl y)  
  
Descri pti o n of t he ( S) A E, i ncl u di n g:
 
Date of o nset
 
( S) A E treat me nt ( dr u g, d ose, r o ute of a d mi nistrati o n)
 
Ca usal relati o ns hi p b y  t he i n vesti gat or
 
Meas u res ta ke n (ie, acti o n ta ke n re gar di n g I P i n direct relati o ns hi p t o t he A E)
  
Seri o us ness criteria (i e, deat h, life-t hreate ni n g, or ot her criteri o n)
  
Ca use of deat h
  
A ut o ps y  fi n di n gs (if a vaila ble)
  
Na me, a d dress, fa x n u m ber, e mail, a n d tele p h o ne n u m ber of t he r e p orti n g 
in vesti gat or (f or pa per S A E Re p ort F or ms) 
1 2. 2 Ur ge nt S afet y Me as ures
A n ur ge nt safet y meas ure is a n i m me diate acti o n ta ke n, w hic h is n ot defi ne d b y t he 
pr ot oc ol, i n or der t o pr otect s u bjects partici pati n g i n a cli nical trial fr o m i m me diate har m. 
Ur ge nt safet y  meas ures ma y be ta ke n b y t he s p o ns or or cli nical i n vesti gat or, a nd ma y  
i ncl u de a ny of t he f oll o wi n g: 
  
I m me diate c ha n ge i n st u d y desi g n or st u dy pr oce d ures .
  
Te m p orar y  or per ma ne nt halt of a gi ve n cli nical trial or trials.
  
A n y  ot her i m me diate acti o n ta ke n i n or der t o pr otect cli nical trial partici pa nts 
fr o m i m me diate hazar d t o t heir healt h a n d safet y.
T he i n vesti gat or ma y  ta ke a p pr o priate ur ge nt safet y meas ures i n or der t o pr otect s u bjects 
a gai nst a n y i m me diate hazar d t o t heir healt h or safet y. T he meas ures s h o ul d be ta ke n 
i m me diatel y a n d ma y be ta ke n wit h o ut pri or a ut h orizati o n fr o m t he s p o ns or. In t he 
e ve nt(s) of a n a p pare nt i m me diate hazar d t o t he s u bject, t he i n vesti gat or will n otif y  t he 
s p o ns or i m me diatel y b y p h o ne a n d c o nfir m n otificati o n t o t he s p o ns or i n writi n g as s o o n 
as p ossi ble, b ut wit hi n 1 cale n dar da y  after the c ha n ge is i m ple me nte d. T he s p o ns or will 
als o e ns ure t he res p o nsi ble et hics c o m mittee ( E C) a n d rele va nt c o m pete nt a ut h orit y (s) are 
n otifie d of t he ur ge nt safet y meas ures ta ke n i n s uc h cases acc or di n g t o l ocal re g ulati o ns.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 6 1 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 2. 3 U nt o w ar d Me dic al Occ urre nces
U nt o war d me dical occ urre nces occ urri n g bef ore t he first e x p os ure t o IP are n ot 
c o nsi dere d A Es (acc or di n g t o t he defi niti o n of A E, see Secti o n 1 2. 1 ). Ho we ver, e ac h 
seri o us u nt o war d me dical occ urre nce e x perie nce d bef ore t he first I P e x p os ure (ie, fr o m 
t he ti me of si g ne d i nf or me d c o nse nt u p t o b ut n ot i ncl u di n g t he first IP e x p os ure) will be 
descri be d o n t he A E C R F (a n d S A E Re p ort F or m if e C R F is n ot a vaila ble) . T hese e ve nts 
will n ot be c o nsi dere d as S A Es a n d will n ot be i ncl u de d i n t he a nalys is of S A Es.
F or t he p ur p oses of t his st u d y , eac h n o n-seri o us u nt o war d me dical occ urre nce 
e x perie nce d b y a s u bject u n der g oi n g st u d y-relate d pr oce d ure(s) (e g, was h o ut of a 
s u bject’s pre-st u d y A 1 PI a u g me ntati o n t hera py, br o nc h osc o p y / B AL pr oce d ures ) will be 
rec or de d o n t he A E C R F . T hese e ve nts, if occ urre d bef ore t he first I P e x p os ure, will n ot
be c o nsi dere d as A Es a n d will n ot be i ncl u de d i n t he a nal ys is of A Es. O n t h e ot her ha n d, 
t hese e ve nts, if occ urre d after i nitiati o n of I P treat me nt, will be c o nsi dere d as A Es a n d 
will be i ncl u de d i n t he a nal y sis of A Es.
1 2. 4 N o n - Me dic al C o m pl ai nts
A n o n -me dical c o m plai nt ( N M C) is a n y  alle ge d pr o d uct deficie nc y t hat relates t o 
i de ntit y, q ualit y, d ura bilit y, relia bilit y, safety a n d perf or ma nce of t he pr o d uct b ut di d n ot 
res ult i n a n A E. N M Cs i ncl u de b ut are n ot li mite d t o t he f oll o wi n g:
  
A fail ure of a pr o d uct t o e x hi bit its e x pecte d p har mac ol o gical acti vit y a n d/ or 
desi g n f u ncti o n, e g rec o nstit uti o n diffic ult y .
  
Missi n g c o m p o ne nts .
  
Da ma ge t o t he pr o d uct or u nit cart o n .
  
A misla bele d pr o d uct (e g, p ote ntial c o u nterfeiti n g/ta m peri n g).
  
A bacteri ol o gical, c he mical, or p h ys ical c ha n ge or deteri orati o n of t he pr o d uct 
ca usi n g it t o malf u ncti o n or t o prese nt a hazar d or fail t o meet la bel clai ms .
A n y  N M Cs of t he pr o d uct will be d oc u me nte d o n a n N M C f or m a n d re p orte d t o t he 
s p o ns or wit hi n 1 b usi ness da y. If re q ueste d, defecti ve pr o d uct(s) will be ret ur ne d t o t he 
s p o ns or f or i ns pecti o n a n d a nalys is acc or di n g t o pr oce d ures.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 6 2 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 2. 5 Me dic al, Me dic ati o n, a n d N o n -Dr u g T her a p y Hist or y
At scree ni n g, t he s u bject’s me dical hist or y  will be descri be d f or t he f oll o wi n g b o d y 
s yste ms i ncl u di n g se verit y (as defi ne d i n Secti o n 1 2. 1. 2. 1 ) or s ur ger y a n d start a n d e n d 
dates, if k n o w n: e y es, ears, n ose, a n d t hr oat; res pirat or y ; car di o vasc ular; gastr oi ntesti nal; 
m usc ul os keletal; ne ur ol o gical; e n d ocri ne; he mat o p oietic/l y m p hatic ; der mat ol o gical; a n d 
ge nit o uri nar y .
All me dicati o ns ta ke n a n d n o n- dr u g t hera pies recei ve d fr o m e nr oll me nt u ntil 
c o m pleti o n/ter mi nati o n will be rec or de d o n t he c o nc o mita nt me dicati o ns a n d n o n -dr u g 
t hera pies C R Fs.
1 2. 6 P h ysic al E x a mi n ati o ns
At scree ni n g a n d s u bs e q ue nt st u d y visits (as descri be d i n Ta ble 2 0. 2- 1 ), a p h ysical 
e xa mi nati o n will be perf or me d o n t he f oll o wi n g b o d y  sys te ms: ge neral a p peara nce, hea d 
a nd nec k, e y es a n d ears, n ose a n d t hr oat, c hest, l u n gs, heart, a b d o me n, e xtre mities a n d 
j oi nts, l ym p h n o des, s ki n, a n d ne ur ol o gical. At scree ni n g, if a n a b n or mal c o n diti o n is 
detecte d, t he c o n diti o n will be descri be d o n t he me dical hist or y  C R F. At st u d y visits, if a 
ne w a b n or mal or w orse ne d a b n or mal pre -e xisti n g c o n diti o n is detecte d, t he c o n diti o n will 
be descri be d o n t he A E C R F. If t he a b n or mal val ue was n ot dee me d a n A E beca use it 
was d ue t o a n err or, d ue t o a pree xisti n g disease ( descri be d i n Secti o n 1 2. 1. 1. 6 ), n ot 
cli nicall y si g nifica nt, a s ym pt o m of a ne w/ w orse ne d c o n diti o n alrea d y rec or de d as a n A E, 
or d ue t o a n ot her iss ue t hat will be s pecifie d, t he i n vesti gat or will rec or d t he j ustificati o n 
o n t he s o urce rec or d.
1 2. 7 Cli nic al L a b or at or y P ar a meters
T he sc he d ule of sa m ple c ollecti o n f or cli nical la b orat or y assess me nts is pr o vi de d i n 
Ta ble 2 0. 3- 1 Cli nical La b orat or y  Assess me nts. Detaile d re q uire me nts f or sa m ple 
c ollecti o n a n d ha n dli n g ca n be f o u n d i n t he La b orat or y  Ma n ual.
1 2. 7. 1 He m at ol o g y a n d Cli nic al C he mistr y
T he he mat ol o g y  pa nel will c o nsist of c o m plete bl o o d c o u nt : H g b , he mat ocrit (Hct ), 
er yt hr oc y tes (ie, re d bl o o d cell [R B C ]) c o u nt, le u k oc ytes (ie, w hite bl o o d cell [W B C ])
c o u nt wit h differe ntial (ie, bas o p hils, e osi n o p hils, l ym p h oc y tes, m o n oc ytes, a n d 
ne utr o p hils), a bs ol ute ne utr o p hil c o u nt ( A N C), a bs ol ute l y m p h oc y te c o u nt, retic ul oc yte 
c o u nt, a n d platelet c o u nt.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 6 3 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
T he cli nical c he mistr y  pa nel will c o nsist of s o di u m, p otassi u m, calci u m, c hl ori de, 
bicar b o nate, t otal pr otei n, a l b u mi n, ala ni ne a mi n otra nsferase ( A L T), as partate 
a mi n otra nsferase ( A S T), al kali ne p h os p hatase ( A L P), lactic de hy dr o ge nase ( L D H), 
ga m ma -gl uta m y l-tra nsferase ( G G T), bilir u bi n ( direct a n d t otal), bl o o d urea nitr o ge n 
(B U N ), uric aci d, creati ni ne, creati ne p h os p h o ki nase ( C P K), a n d gl uc ose. 
W h ole b l o o d will be c ollecte d f or t he assess me nt of he mat ol o g y  a n d ser u m f or cli nical 
c he mistr y para meters d uri n g eac h of t he f oll o wi n g visits: scree ni n g, Wee k 1 (pri or t o t he 
first IP i nf usi o n ; t his will ser ve as baseli ne val ue), Wee k 1 3, Wee k 2 5, a n d at st u d y 
c o m pleti o n ( Wee k 2 6 ) visit. Sa m p les t o be c ollecte d o n t he da y  of I P a d mi nistrati o n (ie, 
Wee k 1, Wee k 1 3, a n d Wee k 2 5) m ust be c ollecte d pri or t o t he start of I P i nf usi o n. 
S u bjects w h o are disc o nti n ue d earl y fr o m t he st u d y will be as ke d t o u n der g o he mat ol o g y  
a n d cli nical c he mistr y assessme nts at t he Earl y Ter mi nati o n visit , o nl y  if t hese s u bjects 
ha ve bee n e x p ose d t o I P.
He mat ol o g y  a n d cli nical c he mistr y assess me nts will be perf or me d o n 
et h yle ne dia mi netetraacetic aci d (E D T A )-a ntic oa g ulate d w h ole bl o o d a n d ser u m sa m ples, 
res pecti vely, at a ce ntral la b orat or y.
1 2. 7. 1. 1 Ot her A n al ysis
Ser u m sa m ples will be c ollecte d f or ser u m c oti ni ne c o nce ntrati o ns f or n o ns m o ki n g 
assess me nts (le vels wit hi n n or mal ra n ge of a n o ns m o ker).
1 2. 7. 2 C o m ple me nt Acti v ati o n a n d I m m u ne C o m ple x P a nel
C o m ple me nt acti vati o n a n d i m m u ne c om ple x pa nel will c o nsist of ser u m c o m ple me nt 
c o m p o ne nt 3 (C 3 ), c o m ple me nt c o m p o ne nt 4 ( C 4 ), total c o m ple me nt ( 5 0 % he m ol y tic 
c o m ple me nt acti vit y of ser u m; C H 5 0) , C 1 q bi n di n g assa y f or circ ulati n g i m m u ne 
c o m ple xes .
Bl o o d will be c ollecte d t o o btai n ser u m sa mples f or t he assess me nt of c o m ple me nt 
acti vati o n a n d circ ulati n g i m m u ne c o m ple xes d uri n g eac h of t he f oll o wi n g visit s: Wee k 1 
(pri or t o t he first I P i nf usi o n; t his will ser ve as baseli ne val ue), Wee k 1 3, Wee k 2 5, a n d at 
st u d y c o m pleti o n ( Wee k 2 6) visit. Sa m ples t o be c ollecte d o n t he da y  of I P a d mi nistrati o n 
(ie, Wee k 1, Wee k 1 3, a n d Wee k 2 5) m ust be c ollecte d pri or t o t he start of I P i nf usi o n. 
S u bjects w h o are disc o nti n ue d earl y fr o m t he st u d y will be as ke d t o u n der g o c o m ple me nt 
acti vati o n a n d i m m u ne c o m ple x e val uati o n at t he Earl y Ter mi nati o n visit, o nl y  if t hese 
s u bjects ha ve bee n e x p ose d t o IP.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 6 4 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
C o m ple me nt acti vati o n a n d i m m u ne c o m ple x assess me nts will be perf or me d at a ce ntral 
la b orat or y.
1 2. 7. 3 Vir al Ser ol o g y a n d N ucleic Aci d Tests
At scree ni n g, s u bjects w o ul d be teste d f or H A V, He p B, H C V a n d HI V 1/ HI V 2 b y  
ser ol o g y f or a nti ge ne mia or a nti b o dies or b y P C R base d N A T, t o war ds eli gi bilit y 
deter mi nati o n.
Viral testi n g f or B 1 9 V will c o nsist of B 1 9 V a nti b o d y ser ol o g y test a n d N A T , base d o n 
real-ti me p oly m erase c h ai n reacti o n ( P C R) detecti o n of B 1 9 V D N A . S er u m sa m ples will 
be c ollecte d pri or t o t he first I P i nf usi o n d uri n g Wee k 1 ( w hic h ser ves as t he baseli ne 
val ue) a n d at t he last i nf usi o n visit ( Wee k 2 5). I f a s u bject’s Wee k 1 pre-d ose sa m ple is 
teste d p ositi ve, t he n n o f urt her testi n g (e g, Wee k 2 5) is re q uire d. A n y e vi de nce of
ser oc o n versi o n (e g, c ha n ge fr o m a ne gati ve test res ult at baseli ne [ Wee k 1 pri or t o t he 
first IP i nf usi o n] t o a p ositi ve res ult at a p ost -baseli ne assess me nt) f or B 1 9 V s h o ul d be 
re-teste d. S u bjects w h o are disc o nti n ue d earl y fr o m t he st u d y will be as ke d t o u n der g o 
viral ser ol o g y  a n d N A T testi n g at t he Early Ter mi nati o n visit, o nl y  if t hese s u bjects ha ve 
bee n e x p ose d t o I P.
Ser ol o g y  testi n g a n d N A T will be perf or me d at a ce ntral la b orat or y .
1 2. 7. 4 Uri n e Tests
Uri nal y sis will c o nsist of c ol or, s pecific gra vity, p H, pr otei n, gl uc ose, ket o nes, bilir u bi n, 
ur o bili n o ge n, bl o o d, nitr ite, le u k oc yte esterase, a n d micr osc o pic e xa mi nati o n ( R B C, 
W B C, bacteria, casts). Uri nal y sis will be perf or me d d uri n g eac h of t he f oll o wi n g visits: 
scree ni n g, Wee k 1 ( pri or t o
t he first IP i nf usi o n; t his will ser ve as baseli ne val ue),
Wee k
1 3, Wee k 2 5 , a n d at st u d y c o m pleti o n ( Wee k 26 ) visit. Sa m ples t o be c ollecte d o n 
t he da y of I P a d mi nistrati o n (ie, Wee k 1, Wee k 1 3, a n d Wee k 2 5) m ust be c ollecte d pri or 
t o t he start of IP i nf usi o n. Uri nal y sis will be perf or me d at a ce ntral la b orat or y.
P re g na nc y test will be perf or me d f or fe males of c hil d beari n g p ote ntial at scree ni n g a n d at 
st u d y c o m pleti o n ( Wee k 26) visit. S u bjects w h o are disc o nti n ue d earl y fr o m t he st u d y  
will be as ke d t o u n der g o uri nal y sis a n d uri ne/ser u m pre g na nc y test (f or fe males of 
c hil d beari n g p ote ntial o nl y ) at t he Early Ter mi nati o n visit, o nl y  if t hese s u bjects ha ve 
bee n e x p ose d t o I P. Uri ne pre g na n c y test will be perf or me d , u nless ser u m pre g na nc y test 
is ma n dat or y as s pecifie d b y l ocal re g ulat or y/i nstit uti o nal re q uire me nts.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 6 5 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 2. 7. 5 Assess me nt of Cli nic al L a b or at or y V al ues
1 2. 7. 5. 1 Assess me nt of A b n or m al L a b or at or y V al ues
T he i n vesti gat or’s assess me nt of eac h safet y- relate d la b orat or y val ue will be rec or de d o n 
t he la b orat or y f or m. F or eac h a b n or mal la b orat or y val ue, t he i n vesti gat or will deter mi ne 
w het her t he val ue is c o nsi dere d cli nicall y si g nifica nt or n ot. F or cli nicall y si g nifica nt 
val ues, t he i n vesti gat or will i n dicate if t he val ue c o nstit utes a n ne w A E (see defi niti o n i n 
Secti o n 1 2. 1 , a n d rec or d t he si g n, sy m pt o m, or me dical dia g n osis o n t he A E C R F), is a 
s ym pt o m or relate d t o a pre vi o usl y  rec or de d A E, is d ue t o a pre-e xisti n g disease 
( descri be d i n Secti o n 1 2. 1. 1. 6 ), or is d ue t o a n ot her iss ue t hat will be s pecifie d. If t he 
a b n or mal val ue was n ot cli nicall y  si g nifica nt, t he i n vesti gat or will i n dicate t he reas o n, ie 
beca use it is d ue t o a pree xisti n g disease, d ue t o a la b err or, or d ue t o a n ot her iss ue t hat 
will be s pecifie d. A d diti o nal tests a n d ot her e val uati o ns re q uire d t o esta blis h t he 
si g nifica nce or eti ol o g y of a n a b n or mal val ue, or t o m o nit or t he c o urse of a n A E s h o ul d 
be o btai ne d w he n cli nicall y  i n dicate d. A n y s er oc o n versi o n res ult f or B 1 9 V s h o ul d be 
re-teste d. A n y a b n or mal val ue t hat persists s h o ul d be f oll o we d at t he discreti o n of t he 
i n vesti gat or.
I n a d diti o n t o i n vesti gat or’s assess me nt of t he cli nical si g nifica nce of la b orat or y 
a b n or malities, cli nical la b orat or y a b n or malities wit h val ues t hat meet t he criteria liste d i n 
Secti o n 2 0. 4 will be se parately a nal yz e d a n d re p orte d.
1 2. 7. 6 Bi o b a n ki n g
Bac k u p sa m ples s h o ul d be ta ke n a n d st ore d a p pr o priatel y f or a d diti o nal a nal ysis, if 
necessar y . T hese sa m ples ma y be use d f or re-testi n g, f urt her e val uati o n of a n A E, or 
f oll o w- u p of ot her test res ults. T he f oll o wi n g sa m ples are pla n ne d:
  
Plas ma sa m ples c oll ecte d f or t he deter mi nati o n of t he f oll o wi n g a nal yt es will eac h 
be s plit i nt o d u plicate ali q u ots of a p pr o xi matel y  e q ual v ol u me ( 1 of t he 2 ali q u ots 
will ser ve as t he bac k u p sa m ple) :
  
Plas ma a nti ge nic A 1 PI
  
Plas ma f u ncti o nal A 1 PI  (ie, A N E C)
  
Plas ma urea
 
Ser u m sa m ples c ollecte d f or t he deter mi nati o n of t he f oll o wi n g a nalyt es will eac h 
be s plit i nt o d u plicate ali q u ots of a p pr o xi matel y  e q ual v ol u me ( 1 of t he 2 ali q u ots 
will ser ve as bac k u p sa m ple) :
  
A nti- A 1 PI  a nti b o dies f or bi n di n g a nti b o d y ( scree ni n g a n d c o nfir mator y )
assa ys
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 6 6 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
  
A nti- A 1 PI  a nti b o dies f or ne utralizi n g a nti b o d y assa y
  
B A L sa m ples c ollecte d f or t he deter mi nati o n of t he f oll o wi n g a nalyt es will eac h 
be s plit i nt o 2 or m ore ali q u ots of a p pr o xi matel y e q ual v ol u me (at least 1 of t he 
ali q u ots will ser ve as bac k u p sa m ple; see L a b orat or y M a n ual f or f urt her details ):
  
B A L a nti ge nic A 1 PI
  
B A L f u ncti o nal A 1 PI (ie, A N E C)
  
B A L urea
Bac k u p sa m ples t hat re mai n after st u d y testi n g is d o ne ma y be st ore d a n d use d f or 
a d diti o nal testi n g (e g, f urt her e val uati o n of a n a b n or mal test or a n A E ). Sa m ples will be 
st ore d i n a c o de d f or m f or u p t o 2 y ears after t he fi nal st u d y re p ort has bee n c o m plete d, 
u nless ot her wise n otifie d b y  t he s p o ns or, a n d t he n the sa m ples will s u bse q ue ntl y be 
destr o y e d.
1 2. 8 Pl as m a A nti ge nic a n d F u ncti o n al A 1 PI Le vels
T hr o u g h o ut t he treat me nt peri o d, plas ma tr o u g h A 1 PI  le vels will be assesse d t o m o nit or 
t he i ncrease i n a n d mai nt e na nce of plas ma A 1 PI le vels at tar get of 1 1 µ M or greater . 
Plas ma sa m ples f or t he deter mi nati o n of tr o u g h a nti ge nic A 1 PI a n d f u ncti o nal A 1 PI  (als o 
k n o w n as A N E C) le vels will be c ollecte d pri or t o t he first I P i nf usi o n d uri n g Wee k 1 , o n 
t he da y of I P a d mi nistrati o n ( m ust be c ollecte d pri or t o t he start of I P i nf usi o n) d uri n g
Wee k 7, Wee k 1 3, Wee k 1 9, a n d Wee k 2 5, a n d at t he st u d y c o m pleti o n ( Wee k 2 6) visit.
F or s u bjects w h o are t o u n der g o B A L assess me nts , plas ma sa m ples f or baseli ne a nti ge nic 
A 1 PI  le vel will be c ollecte d wit hi n 1 0 da ys pri or t o t he baseli ne B A L visit t o verif y t he 
a de q uac y of t he was h o ut fr o m A 1 PI t hera py pri or t o perf or mi n g t he baseli ne B A L visit . 
T he n, o n t he da y  of t he baseli ne B A L visit, plas ma sa m ples f or t he meas ure me nt of 
a nti ge nic a n d f u ncti o nal A 1 PI le vels will be c ollecte d si m ulta ne o usl y wit h plas ma 
sa m ples f or urea meas ure me nts wit hi n 2 h o urs pri or t o t he B A L pr oce d ure. T hese val ues 
will be use d f or t he calc ulati o n of t he c orres p o n di n g A 1 PI le vels i n E L F usi n g plas ma -t o-
B A L urea c orrecti o n met h o d . Sa m ple c ollecti o n f or plas ma a nti ge nic a n d f u ncti o nal A 1 PI 
a n d urea will be re peate d o n t he da y  of t he o n-treat me nt B A L visit wit hi n 2 h o urs pri or t o 
t he B A L pr oce d ure (see Secti o n 1 0. 3. 4 ).
S u bjects w h o are disc o nti n ue d earl y fr o m t he st u d y after ha vi n g bee n e x p ose d t o IP 
a d mi nistrati o n will be as ke d t o ha ve a plas ma sa m ple c ollecte d f or A 1 PI deter mi nati o n. 
T he earl y  ter mi nati o n plas ma sa m ple will be a nalyze d t o s u p p ort a nal ysis/i nter pretati o n 
of t he earl y  ter mi nati o n a nti-A 1 PI  a nti b o d y assess me nt.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 6 7 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
Sa m ple a nal ys is f or t he deter mi nati o n of plas ma a nti ge nic a n d f u ncti o nal A 1 PI le vels will 
be perf or me d usi n g vali date d bi oa nal yt ical assa ys at a q ualifie d la b orat or y.
1 2. 9 I m m u n o ge nicit y
Bl o o d will be c ollecte d t o o btai n ser u m sa m ples f or m o nit ori n g t he a p peara nce/ prese nce 
of a nti -A 1 PI a nti b o dies pri or t o t he first IP i nf usi o n d uri n g Wee k 1, o n t he da y  of I P 
a d mi nistrati o n ( m ust be c ollecte d pri or t o t he start of I P i nf usi o n) d uri n g Wee k 1 3 a n d 
Wee k 2 5, a n d at st u d y  c o m pleti o n ( Wee k 2 6) visit. S u bjects w h o are disc o nti n ue d earl y 
fr o m t he st u d y after ha vi n g bee n e x p ose d t o IP a d mi nistrati o n will be as ke d t o ha ve a 
ser u m sa m ple c ollecte d f or i m m u n o ge nicity assess me nt at t he Earl y Ter mi nati o n visit.
U nsc he d ule d sa m ples f or t he detecti o n of circ ulati n g a nti -A 1 PI  a nti b o dies ma y be 
c ollecte d as necessar y a n d u p o n c o ns ultati o n wit h or n otificati o n b y t he s p o ns or, t o 
s u p p ort i n vesti gati o n of s us pecte d i m m u ne-me diate d A Es . At a ny sc he d ule d or 
u nsc he d ule d ti me p oi nts, plas ma sa m ples f or t he deter mi nati o n of circ ulati n g A 1 PI le vels 
will be c ollecte d c o nc urre ntl y  t o assess p ote ntial i nterfere nce wit h t he assa y. 
Eac h sa m ple is t o be st ore d as d u plicate ali q u ots eac h wit h s ufficie nt v ol u me nee de d f or 
sa m ple a nalys is. Detaile d sa m ple ha n dli n g a n d st ora ge i nstr ucti o ns will be pr o vi de d i n 
t he L a b orat or y Ma n ual.
A nti -A 1 PI  a nti b o dies will be detecte d usi n g vali date d bi n di n g a n d ne utralizi n g a nti-A 1 PI 
a nti b o d y assa ys at a q ualifie d i m m u n oassa y la b orat or y. T he prese nce of a nti-A 1 PI  
a nti b o dies i n a sa m ple will be detecte d usi n g a scree ni n g assa y a n d c o nfir me d usi n g a 
c o nfir mat or y assa y. O nl y t h ose sa m ples wit h c o nfir me d p ositi ve res ults will be f urt her 
a nal yz e d f or t he e xa mi nati o n f or t he prese nce of ne utralizi n g a nti b o dies.
1 2. 1 0 Vit al Si g ns
B o d y hei g ht (i n or c m) will be c ollecte d at scree ni n g o nl y. B o d y wei g ht (l b or k g) will be 
meas ure d at scree ni n g a n d at st u d y  visits d uri n g Wee ks 1, 7, 1 3, 1 9, a n d 2 5.
Vital si g ns will i ncl u de b o d y  te m perat ure (° C or ° F), res pirat or y rate ( breat hs/ mi n), p ulse 
rate ( beats/ mi n), a n d sys t olic a n d diast olic bl o o d press ure ( m m H g). Bl o o d press ure 
meas ure me nts will be ta ke n w he n s u bjects are i n eit her t he sitti n g or s u pi ne p ositi o n; t he 
sa me p ositi o n s h o ul d prefera bly be mai ntai ne d eac h ti me a bl o o d press ure is meas ure d.
T hese v ital si g ns will be meas ure d at scree ni n g, d uri n g treat me nt peri o d ( Wee ks 1, 7, 1 3, 
1 9, a n d 2 5 ), a n d at st u d y c o m pleti o n ( Wee k 2 6)/E arl y Ter mi nati o n V isit (see als o 
Secti o n 1 0. 3. 2. 1 a n d Ta ble 2 0. 3 - 1).
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 6 8 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
F or eac h of t he I P i nf usi o n visits w here vital si g ns are t o be ta ke n, vital si g ns will be 
rec or de d at a ny ti me pri or t o t he start of a n i nf usi o n, at eac h rate re d ucti o n d ue t o A E(s) 
a n d/ or i nf usi o n i nterr u pti o n/ disc o nti n uati o n d ue t o A E(s), a n d at 3 0 ( ± 1 5) mi n utes after 
t he c o m pleti o n of a n i nf usi o n. T he i n vesti gat or s h o ul d be c o ntacte d t o deter mi ne 
a p pr o priate acti o n t o be ta ke n, as necessar y , if vital si g ns meet a ny of t he f oll o wi n g 
criteria:
  
S y st olic bl o o d press ure ≤8 0 m m H g or ≥1 8 0 m m H g a n d/ or diast olic bl o o d 
press ure: ≤5 0 m m H g or ≥1 1 0 m m H g .
  
P ulse rate ≤4 8 beats/ mi n or ≥1 1 0 beats/ mi n .
  
Res pirat or y  rate ≤8 breat hs/ mi n or ≥2 4 breat hs/ mi n .
  
B o d y te m perat ure ≥3 8. 2 º C ( 1 0 1º F).
F or s u bjects u n d er g oi n g B A L pr oce d ures, vital si g ns will be meas ure d wit hi n 2 h o urs 
pri or t o eac h B A L pr oce d ure a n d wit hi n 1 h o ur after t he c o m pleti o n of t he B A L 
pr oce d ure. Pre -B A L v ital si g ns are t o be perf or me d pri or t o t he a d mi nistrati o n of 
br o nc h o dilat or a n d l ocal a ne st hesia.
Vital si g n val ues are t o be rec or de d o n t he C R F. F or eac h a b n or mal vital si g n val ue, t he 
i n vesti gat or will deter mi ne w het her or n ot t o re p ort a n A E (see defi niti o n i n Secti o n 1 2. 1
a n d rec or d t he me dical dia g n osis ( prefera bl y) , s ym pt o m, or si g n o n t he A E C R F) . 
A d diti o nal tests a n d ot her e val uati o ns re q uire d t o esta blis h t he si g nifica nce or eti ol o g y  of 
a n a b n or mal vital si g n val ue or t o m o nit or t he c o urse of a n A E s h o ul d be o btai ne d w he n 
cli nicall y i n dicate d. A n y a b n or mal val ue t hat persists s h o ul d be f oll o we d at t he discreti o n 
of t he i n vesti gat or.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 6 9 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 3. S T A TI S TI C S
1 3. 1 S a m ple Size a n d P o wer C alc ul ati o ns
T he sa m ple size calc ulati o n f or t he B A L c o m p o ne nt of t he st u d y  was base d o n t he nat ural 
l o g tra nsf or me d pri mar y e n d p oi nt data, E L F a nti ge nic A 1 PI le vel ( n M), ge nerate d d uri n g 
a pre vi o us cli nical st u d y (Cli nical Pr ot oc ol 4 6 0 5 0 2 ; Ba xter Healt hcare C or p orati on) f or 
t he e val uati o n of t he effects of A 1 PI a u g me ntati o n t hera py wit h A R A L A S T N P o n t he 
le vels of A 1 PI a n d ot her a nalyt es i n t he E L F. In Cli nical St u d y  4 6 0 5 0 2, a mea n 
differe nce fr o m pre - t o p ost-treat me nt i n E L F a nti ge nic A 1 PI of 1. 3 2 wit h sta n dar d 
de via ti o n of 0. 9 6 o n nat ural l o g scale was o bser ve d. Usi n g t his varia nce esti mate, a 
sa m ple size of 1 5 e val ua ble s u bjects s h o ul d be s ufficie nt t o detect a mea n differe nce i n 
t he nat ural l o g tra nsf or me d E L F a nti ge nic A 1 PI of a p pr o xi matel y 0. 8 7 wit h 9 0 % p o wer, 
us i n g a paire d t-test a n d a 1-si de d si g nifica nce le vel of 0. 0 2 5.
A sa m ple size of 1 5 e val ua ble s u bjects will als o be s ufficie nt t o detect a mea n differe nce 
i n t he nat ural l o g tra nsf or me d E L F f u ncti o nal A 1 PI ( A N E C) of a p pr o xi matel y 1. 0 4, wit h 
9 0 % p o wer, ass u m i n g a sta n dar d de viati o n i n t he differe nces bet wee n pre- a n d p ost-
treat me nt A N E C val ues t o be 2 0 % hi g her t ha n t hat f or a nti ge nic A 1 PI.
Base d o n t he e x perie nce fr o m Cli nical St u d y  4 6 0 5 0 2, it is esti mate d t hat a p pr o xi matel y 
2 6 t o 3 2 s u bjects will be nee de d i n or der t o ac hie ve 1 5 t o 1 8 B A L e val ua ble s u bjects, 
res pecti vely. T h us, a n o verall st u d y  e nr oll me nt tar get of 3 6 s u bjects s h o ul d be a de q uate 
t o meet t he tar get sa m ple size f or t he B A L c o m p o ne nt of t he st u d y.
1 3. 2 D at asets a n d A n al ysis C o h orts
1 3. 2. 1 F ull A n al ysis Set
T he f ull a nal ys is set ( F A S) will i ncl u de all s u bjects w h o recei ve d at least 1 I P i nf usi o n 
a n d ha ve at least 1 a vaila ble A 1 PI  meas ure me nt d uri n g t he treat me nt peri o d.
1 3. 2. 2 Per -Pr ot oc ol A n al ysis Set
T he per -pr ot oc ol ( P P) a nal ysis set will i ncl u de a s u bset of t he f ull a nalys is set, 
c o m prisi n g s u bjects wit h n o maj or pr ot oc ol de viati o ns w hic h ma y  i m pact t he efficac y 
assess me nt . F or t he p ur p ose of statistical a nal ys is, maj or de viati o ns i ncl u de, b ut are n ot
li mite d t o, t he f oll o wi n g: fail ure t o c o m ply wit h t he was h o ut peri o d f or pre -st u d y A 1 PI
a u g me ntati o n t hera p y , miss i n g 2 or m ore c o nsec uti ve wee kl y i nf usi o ns a n d/ or > 1 5 % of 
pla n ne d i nf usi o ns , a n d use of a n A 1 PI pr o d uct (i ncl u di n g c o m merciall y a vaila ble 
G L A S SI A) ot her t ha n I P d uri n g t he st u d y treat me nt peri o d.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 7 0 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 3. 2. 3 B A L A n al ysis Set
T he B A L a nal ys is set will i ncl u de a s u bset of t he F A S a nal ys is set, c o m prisi n g s u bjects 
w h o meet all of t he f oll o wi n g criteria:
  
S u bjects w h o ha ve m et all st u d y Incl usi o n a n d E xcl usi o n C riteria, i ncl u di n g 
a d diti o nal B A L-relate d eli gi bilit y criteria.
  
S u bjects ha ve s uccessf ull y c o m plete d b ot h t he baseli ne a n d t he o n-treat me nt B A L 
visits a n d ha ve a mi ni m u m of 1 e val ua ble sa m ple per B A L visit wit h n o missi n g
i nf usi o n(s) wit hi n 4 wee ks i m me diatel y prece di n g t he o n- treat me nt B A L 
pr oce d ure .
  
S u bjects m ust h a ve acce pta ble E L F data ( defi niti o n as per Secti o n 1 0. 3. 4 ) f or b ot h 
t he baseli ne a n d t he o n-treat me nt B A L visits i n or der t o be i ncl u de d i n t he 
efficac y a nalys es f or t he assess me nt of E L F a nalyte le vels f oll o wi n g G L A S SI A 
a u g me ntati o n t hera p y.
1 3. 2. 4 Per - Pr ot oc ol B A L A n al ysis Set
T he per -pr ot oc ol B A L ( P P B A L) a nal ys is set will be a s u bset of t he B A L a nal ysis set wit h 
n o maj or pr ot oc ol de viati o ns t hat ma y  im pact t he B A L assess me nt. F urt her details will be 
gi ve n i n t he statistical a nal y sis pla n.
1 3. 2. 5 S afet y A n al ysis Set
T he safet y a nal ys is set will i ncl u de all s u bjects e nr olle d i n t he st u d y w h o recei ve d at least 
1 I P i nf usi o n.
1 3. 3 H a n dli n g of Missi n g, U n use d, a n d S p uri o us D at a
N o missi n g data i m p utati o n will be perf or me d.
1 3. 4 Met h o ds of A n al ysis
1 3. 4. 1 Effic ac y O utc o me Me as ure s
A nti ge nic a n d f u ncti o nal A 1 PI  le vels i n t he E L F will be esti mate d base d o n t he 
c orres p o n di n g B A L meas ure me nts at eac h ti me p oi nt usi n g plas ma -t o-B A L u rea 
c orrecti o n met h o d . E L F a nti ge nic a n d f u ncti o nal A 1 PI le vels, as well as c ha n ges fr o m 
baseli ne, will be s u m marize d descri pti vel y  a n d dis pla ye d gra p hicall y (data per mitti n g )
base d o n data p o ole d acr oss b ot h treat me nt ar ms .
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 7 1 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
Si nce a n i ncrease fr o m baseli ne i n t he mea n E L F le vels of a nti ge nic A 1 PI is e x pecte d, 
a 1-si de d paire d t- test will be c o n d ucte d at a n α -le vel of 0. 0 2 5 wit h t he f oll o wi n g n ull a n d 
alter nati ve h y p ot heses w here t he mea n c ha n ge i n a nti ge nic A 1 PI fr o m baseli ne t o t he o n-
treat me nt B A L meas ure me nt is μ d: 
H 0: Mea n c ha n ge i n a nti ge nic A 1 PI i n t he E L F fr o m baseli ne t o t he o n- treat me nt 
meas ure me nt will be less t ha n or e q ual t o zer o.
H 0: μd ≤0
H 1: Mea n c ha n ge i n a nti ge nic A 1 PI i n t he E L F fr o m baseli ne t o t he o n- treat me nt
meas ure me nt wil l be greater t ha n zer o.
H 1: μd > 0
T he mea n c ha n ge i n f u ncti o nal A 1 PI  ( A N E C) fr o m baseli ne t o o n- treat me nt 
meas ure me nt will be a nal y ze d i n a si milar fas hi o n, if data per mit. T he nat ural l o garit h m 
tra nsf or mati o n ma y be a p plie d t o t he E L F a nti ge nic or f u ncti o nal A 1 PI val ues pri or t o 
a nal ys is if t he distri b uti o ns are hi g hly s ke we d. T his a nal ysis will be c o n d ucte d wit h t he 
B A L a nal ys is set. A se nsiti vit y  a nalys is will be perf or me d base d o n t he P P B A L anal y sis 
set.
 
 
C ha n ges fr o m baseli ne i n E L F a n d plas ma a nti ge nic a n d f u ncti o nal A 1 PI le vels , as well 
as 
, will be s u m marize d i n t he f oll o wi n g s u b gr o u ps: b y  
se x, a ge (≤6 5; > 6 5) , race, a n d et h nicit y. 
1 3. 4. 2 E x p os ure
Plas ma tr o u g h a nti ge nic a n d f u ncti o nal A 1 PI le vels, as well as c ha n ges fr o m baseli ne, 
will be s u m marize d descr i pti vel y a n d dis pla ye d gra p hicall y ( data per mitti n g) base d o n 
data se parately b y treat me nt ar m as well as p o ole d acr oss b ot h treat me nt ar ms f or t he 
F A S a n d P P a nal ys is sets. Plas ma a nti ge nic a n d f u ncti o nal A 1 PI le vels o btai ne d at t he 
baseli ne a n d o n -treat me nt B A L visits will be s u m marize d se paratel y  a n d, data per mitti n g, 
t o be c orrelate d wit h t he c orres p o n di n g val ues i n t he E L F f or t he B A L a n d P P B A L 
anal ys is sets. 
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 7 2 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
I n t he e ve nt t hat a nti-A 1 PI  a nti b o d y f or mati o n is detecte d, t he i n di vi d ual a nti ge nic a n d 
f u ncti o nal A 1 PI le vels ma y be e val uate d i n c o nj u ncti o n wit h bi n di n g a n d ne utralizi n g 
a nti-A 1 PI  a nti b o d y titers, as a p plica ble.
1 3. 4. 3 S afet y O utc o me Me as ure s
T he safet y a nal ys is set will be use d f or t he f oll o wi n g a nalys es, u nless ot her wise state d:
A Es t hat are c o nsi dere d p ote ntiall y  relate d t o t he prese nce of pr otei n a g gre gates a n d
i m m u ne- me diate d will be s u m marize d descri pti vel y wit h 9 5 % c o nfi de nce i nter vals ( CIs) 
as a p pr o priate f or eac h A E of i nterest b y  eac h treat me nt ar m a n d, if a p pr o priate, p o ole d 
acr oss b ot h treat me nt ar ms . 
A Rs pl us s us pecte d A Rs , usi n g a ti me fra me f or A E o nset of (a) d uri n g a n d wit hi n 
2 4 h o urs a n d ( b) d uri n g a n d wit hi n 7 2 h o urs of c o m pleti o n of a n i nf usi o n, will be 
ta b ulate d se parately a n d prese nte d acc or di n g t o seri o us ness, se verit y, a n d ca usalit y , as 
well as b y Me d D R A preferre d ter m. Si milar ta b ulati o n of data will be c o n d ucte d f or A Es 
a n d S A Es.
T he n u m ber ( pr o p orti o n) of s u bjects e x perie nci n g S A Es, A Es, relate d A Es, a n d/ or A Rs 
pl us s u s pecte d A Rs will be s u m marize d b y  eac h treat me nt ar m a n d, if a p pr o priate, p o ole d 
acr oss b ot h treat me nt ar ms wit h t heir p oi nt esti mates a n d e xact 9 5 % CIs.
T he n u m ber ( pr o p orti o n) of i nf usi o ns ( defi ne d as perce nta ge of t he t otal n u m ber of 
i nf usi o ns a d mi nistere d) te m p orall y ass ociate d wit h A Es or S A Es ( defi ne d as d uri n g or 
wit hi n (a) 2 4 h o urs a n d ( b) 7 2 h o urs of c o m pleti o n of i nf usi o n) will be c o m p ute d f or eac h 
s u bject. T he me dia n ( 9 5 % CI), mi ni m u m, a n d ma xi m u m of t hese n u m bers ( or 
perce nta ges, res pecti vel y) w ill be ta b ulate d.
T he n u m ber ( pr o p orti o n) of i nf usi o ns ( defi ne d as perce nta ge of t he t otal n u m ber of 
i nf usi o ns a d mi nistere d) ca usall y ass ociate d wit h A Es or S A Es will be c o m p ute d f or eac h 
s u bject. T he me dia n ( 9 5 % CI), mi ni m u m, a n d ma xi m u m of t hese n u m bers ( or 
perce nta ges, res pecti vel y) will be ta b ulate d.
T he n u m ber ( pr o p orti o n) of i nf usi o ns ( defi ne d as perce nta ge of t he t otal n u m ber of 
i nf usi o ns a d mi nistere d) ass ociate d wit h A Rs will be c o m p ute d f or eac h s u bject. T he 
me dia n ( 9 5 % CI), mi ni m u m, a n d ma xi m u m of t hese n u m bers ( or perce nta ges, 
res pecti vely) will be ta b ulate d.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 7 3 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
T he n u m ber ( pr o p orti o n) of i nf usi o ns t hat are disc o nti n ue d, sl o we d, or i nterr u pte d d ue t o 
a n A E will be s u m marize d. T he rates of A Es a n d A Rs e x presse d as t he n u m ber of e ve nts 
t hat occ urre d i n t otal n u m ber of i nf usi o ns a d mi nistere d will be pr o vi de d b y Me d D R A 
ter m.
T he pr o p orti o n of s u bjects w h o de vel o p bi n di n g a n d/ or ne utralizi n g a nti -A 1 PI  a nti b o dies 
will be s u m marize d wit h t heir p oi nt esti mates a n d e xact 9 5 % CI s. Treat me nt-e mer ge nt 
a nti-A 1 PI  anti b o d y  data will be liste d al o n g wit h t he c orres p o n di n g plas ma a nti ge nic a n d 
f u ncti o nal A 1 PI le vels i n t he i n di vi d ual s u bject. A d diti o nall y, te m p oral relati o ns hi p of 
a nti-A 1 PI  a nti b o d y f or mati o n wit h p ote ntiall y i m m u ne-me diate d A Es, if a n y , will be 
e xa mi ne d.
S u m mar y  ta bles of la b orat or y data as well as s hift ta bles of n or mal vers us a b n or mal l o w / 
hi g h la b orat or y  val ues will be create d b y eac h treat me nt ar m as well as p o ole d t o get her. 
I n a d diti o n, s hift ta bles of n or mal vers us a b n or mal cli nicall y si g nifica nt / n ot-cli nicall y 
si g nifica nt la b orat or y val ues ( usi n g t hres h ol ds i n secti o n 2 0. 4 ) will be create d se parately 
b y  eac h treat me nt ar m as well as p o ole d t o get her. T he cli nical si g nifica nce of a b n or mal 
la b orat or y val ues as assesse d b y t he i n vesti gat or is t o be ca pt ure d i n t he s o urce 
d oc u me nts a n d is t o be re p orte d i n t he C R F as f oll o ws:
  
A b n or mal la b orat or y  val ues t hat are c o nsi dere d cli nicall y si g nifica nt b y t he 
i n vesti gat or a n d occ urre d pri or t o t he first i nf usi o n will be re p orte d as me dical 
hist or y . 
  
A b n or mal la b orat or y  val ues t hat are c o nsi dere d cli nicall y si g nifica nt by t he 
i n vesti gat or a n d occ urre d d uri n g or after t he first i nf usi o n will be re p orte d as a n 
A E. 
C ha n ges i n vital si g ns o btai ne d pre- a n d p ost-i nf usi o ns, as well as pre- a n d p ost-B A L
pr oce d ures as a p plica ble , will be pr o vi de d i n a listi n g.
T he pr o p orti o n of s u bjects wit h c o nfir me d treat me nt -e mer ge nt ser oc o n versi o n b y viral 
ser ol o g y or n ucleic aci d test f or B 1 9 V d uri n g or f oll o wi n g treat me nt wit h G L A S SI A will 
be s u m marize d wit h e xact 9 5 % CI s.
Safet y  para meters will be s u m marize d descri pti vel y b y se x, a ge ( ≤6 5; > 6 5), race, a n d 
et h nicit y. N o hy p ot hesis tests are pla n ne d ; h o we ver, 
 
A Es t hat occ ur bef ore treat me nt will be liste d se paratel y.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 7 4 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 3. 5 Pl a n ne d I nteri m A n al ysis of t he St u d y
N ot a p plica ble ; n o i nteri m a nal y ses are pla n ne d f or t his st u d y.
1 4. DI R E C T A C C E S S T O S O U R C E D A T A/ D O C U M E N T S
T he i n vesti gat or/st u d y  site will c o o perate a n d pr o vi de direct access t o st u d y d oc u me nts 
a n d data, i ncl u di n g s o urce d oc u me ntati o n f or m o nit ori n g b y t he st u d y m o nit or, a u dits b y 
t he s p o ns or or s p o ns or’s re prese ntati ves, re view b y  t he E C, a n d i ns pecti o ns b y a p plica ble 
re g ulat or y a ut h orities, as descri be d i n t he Cli nical St u d y A gree me nt. If c o ntacte d b y a n 
a p plica ble re g ulat or y a ut h orit y, t he i n vesti gat or will n otif y t he s p o ns or of c o ntact, 
c o o perate wit h t he a ut h orit y , pr o vi de t he s p o ns or wit h c o pies of all d oc u me nts recei ve d 
fr o m t he a ut h orit y, a n d all o w t he s p o ns or t o c o m me nt o n a ny res p o nses, as descri be d i n 
t he Cli nical St u d y A gree me nt.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 7 5 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 5. Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E
1 5. 1 I n vesti g at or’s Res p o nsi bilit y
T he i n vesti gat or will c o m pl y wit h t he pr ot oc ol ( w hic h has bee n a p pr o ve d/ gi ve n fa v ora ble 
o pi ni o n b y  t he E C), I C H G C P, a n d a p plica ble re g ulat or y re q uire me nts as descri be d i n t he 
Cli nical St u d y  A gree me nt. T he i n vesti gat or is ulti matel y res p o nsi ble f or t he c o n d uct of 
all as pects o f t he st u dy at  t he st u d y site a n d verifies b y si g nat ure t he i nte grit y of all data 
tra ns mitte d t o t he s p o ns or. T he ter m “i n vesti gat or” as use d i n t his pr ot oc ol as well as i n 
ot her st u d y d oc u me nts, refers t o t he i n vesti gat or or a ut h orize d st u d y pers o n nel t hat t he 
i n vesti gat or has desi g nate d t o perf or m certai n d uties. S u b-i n vesti gat ors or ot her 
a ut h orize d st u d y pers o n nel are eli gi ble t o si g n f or t he i n vesti gat or, e xce pt w here t he 
i n vesti gat or’s si g nat ure is s pecifically re q uire d.
1 5. 1. 1 Fi n al Cli nic al St u d y Re p ort 
T he i n vesti gat or, or c o or di nati n g i n vesti gat or(s) f or m ultice nter st u dies, will si g n t he 
cli nical st u d y re p ort. T he c o or di nati n g i n vesti gat or will be selecte d bef ore st u d y start.
1 5. 2 Tr ai ni n g
T he st u d y m o nit or will e ns ure t hat t he i n vesti gat or a n d st u d y  site pers o n nel u n dersta n d all 
re q uire me nts of t he pr ot oc ol, t he i n vesti gati o nal stat us of t he I P, a n d his/ her re g ulat or y 
res p o nsi bilities as a n i n vesti gat or. Trai ni n g ma y be pr o vi de d at a n i n vesti gat or’s meeti n g, 
at t he st u d y site, a n d/ or b y i nstr ucti o n ma n uals. I n a d diti o n, t he st u d y m o nit or will be 
a vaila ble f or c o ns ultati o n wit h t he i n vesti gat or a n d will ser ve as t he liais o n bet wee n t he 
st u d y site a n d t he s p o ns or.
1 5. 3 M o nit ori n g
T he st u d y  m o nit or is res p onsi ble f or e ns uri n g a n d verif y i n g t hat eac h st u d y site c o n d ucts 
t he st u d y acc or di n g t o t he pr ot oc ol, sta n dar d o perati n g pr oce d ures, ot her writte n 
i nstr ucti o ns/a gree me nts, I C H G C P, a n d a p plica ble re g ulat or y g ui deli nes/re q uire me nts. 
T he i n vesti gat or will per mit t he st u d y  m o nit or t o visit t he st u d y site at a p pr o priate 
i nter vals, as descri be d i n t he Cli nical St u d y A gree me nt. M o nit ori n g pr ocesses s pecific t o 
t he st u d y will be descri be d i n t he cli nical m o nit ori n g pla n. 
1 5. 3. 1 S afet y M o nit ori n g
T he safet y of t he s u bject s i n t his st u d y s hall be m o nit ore d b y  a n e xter nal Data 
M o nit ori n g
C o m mittee ( D M C). T he D M C is a gr o u p of i n di vi d uals wit h perti ne nt 
e x pertise t hat re vie ws o n a re g ular basis acc u m ulati n g data fr o m a n o n g oi n g cli nical 
st u d y. F or t his st u d y, t he D M C will be c o m p ose d of rec o g nize d e x perts i n t he fiel d of 
p ul m o nar y  cli nical care a n d researc h w h o are n ot recr uiti n g s u bjects f or t his st u d y . 
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 7 6 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
T he D M C will rec o m me n d t o t he s p o ns or w het her t o c o nti n ue or st o p t he trial or t o 
c o nti n ue t he st u d y after pr o per a me n d me nt t o t he pr ot oc ol.
1 5. 4 A u diti n g
T he s p o ns or a n d/ or s p o ns or’s re prese ntati ves ma y c o n d uct a u dits t o e val uate st u d y  
c o n d uct a n d c o m plia nce wit h t he pr ot oc ol, sta n dar d o perati n g pr oce d ures, ot her writte n 
i nstr ucti o ns/a gree me nts, I C H G C P, a n d a p plica ble re g ulat or y gui deli nes/re q uire me nts. 
T he i n vesti gat or will per mit a u dit ors t o visit t he st u d y site, as descri be d i n t he Cli nical 
St u d y  A gree me nt. A u diti n g pr ocesses s pecific t o t he st u d y will be descri be d i n t he 
a u diti n g pla n.
1 5. 5 N o n -C o m pli a nce wit h t he Pr ot oc ol
T he i n ves ti gat or ma y de viate fr o m t he pr ot oc ol o nl y t o eli mi nate a n a p pare nt i m me diate 
hazar d t o t he s u bject. I n t he e ve nt(s) of a n a p pare nt i m me diate hazar d t o t he s u bject, t he 
i n vesti gat or will n otif y t he s p o ns or i m me diatel y b y p h o ne a n d c o nfir m n otificati o n t o the 
s p o ns or i n writi n g as s o o n as p ossi ble, b ut wit hi n 1 cale n dar da y after t he c ha n ge is 
i m ple me nte d. T he s p o ns or ( Ba xalta) will als o e ns ure t he res p o nsi ble E C is n otifie d of t he 
ur ge nt meas ures ta ke n i n s uc h cases acc or di n g t o l ocal re g ulati o ns .
If m o nit ori n g a n d/ or a u diti n g i de ntif y seri o us a n d/ or persiste nt n o n-c o m plia nce wit h t he 
pr ot oc ol, t he s p o ns or ma y  ter mi nate t he i n vesti gat or’s partici pati o n. T he s p o ns or will 
n otif y  t he E C a n d a p plica ble re g ulat or y a ut h orities of a n y i n vesti gat or ter mi nati o n.
1 5. 6 L a b o r at or y a n d Re a der St a n d ar diz ati o n
N ot a p plica ble ; eac h t ype of assa y is pla n ne d t o be c o n d ucte d at a si n gle la b orat or y
facilit y f or c o nsiste nc y a n d sta n dar dizati o n.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 7 7 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 6. E T HI C S
1 6. 1 S u bject Pri v ac y
T he i n vesti gat or will c o m pl y  wit h a p plica ble s u bject pri vac y re g ulati o ns/ g ui da nce as 
descri be d i n t he Cli nical St u d y  A gree me nt.
1 6. 2 Et hics C o m mittee a n d Re g ul at or y A ut h orities
Bef ore e nr oll me nt of patie nts i nt o t his st u d y, t he pr ot oc ol, I CF , a ny pr o m oti o nal 
material/a d vertise me nts, a n d a n y ot her writte n i nf or mati o n t o b e pr o vi de d will be 
re vie we d a n d a p pr o ve d/ gi ve n fa v ora ble o pi ni o n b y t he E C a n d a p plica ble re g ulat or y 
a ut h orities. T he E C’s c o m p ositi o n or a state me nt t hat t he E C’s c o m p ositi o n meets 
a p plica ble re g ulat or y criteria will be d oc u me nte d. T he st u d y  will c o m me nce o nl y  u p o n 
t he s p o ns or’s recei pt of a p pr o val/fa v ora ble o pi ni o n fr o m t he E C a n d, if re q uire d, u p o n t he 
s p o ns or’s n otificati o n of a p plica ble re g ulat or y a ut h orit y(ies) a p pr o val, as descri be d i n t he 
Cli nical St u d y  A gree me nt.
If t he pr ot oc ol or a ny ot her i nf or mati o n gi ve n t o t he s u bject is a me n de d, t he re vise d 
d oc u me nts will be re vie we d a n d a p pr o ve d/ gi ve n fa v ora ble o pi ni o n b y  t he E C a n d 
a p plica ble re g ulat or y a ut h orities, w here a p plica ble. T he pr ot oc ol a me n d me nt will o nl y be 
i m ple me nte d u p o n t he s p o ns or’s recei pt of a p pr o val a n d, if re q uire d, u p o n t he s p o ns or’s 
n otificati o n of a p plica ble re g ulat or y  a ut h ority(i es) a p pr o val.
1 6. 3 I nf or me d C o nse nt
I n vesti gat ors will c h o ose patie nts f or e nr oll me nt c o nsi deri n g t he st u dy eli gi bilit y  criteria. 
T he i n vesti gat or will e xer cise n o selecti vit y s o t hat n o bias is i ntr o d uce d fr o m t his s o urce. 
All patie nts a n d/ or t heir le gall y a ut h orize d re prese ntati ve m ust si g n a n I C F bef ore 
e nteri n g i nt o t he st u d y acc or di n g t o a p plica ble re g ulat or y re q uire me nts a n d IC H G C P. 
Bef ore use, t he I CF will be re vie we d b y  t he s p o ns or a n d a p pr o ve d b y t he E C a n d 
re g ulat or y a ut h ority(i es), w here a p plica ble, (see Secti o n 1 6. 2 ). T he I CF will i ncl u de a 
c o m pre he nsi ve e x pla nati o n of t he pr o p ose d treat me nt wit h o ut a n y  e xc ul pat or y 
state me nts, i n acc or da nce wit h t he ele me nts re q uire d by I C H G C P a n d a p plica ble 
re g ulat or y re q uire me nts. Patie nts or t heir le gall y  a ut h orize d re prese ntati ve(s) will be 
all o we d s ufficie nt ti me t o c o nsi der partici pati o n i n t he st u d y. B y si g ni n g t he I CF, patie nts 
or t heir le gall y a ut h orize d re prese ntati ve(s) a gree t hat t he y will c o m plete all e val uati o ns 
re q uire d by t he st u d y, u nless t he y wit h dra w v ol u ntaril y  or are ter mi nate d fr o m t he st u d y 
f or a ny reas o n.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 7 8 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
T he s p o ns or will pr o vi de t o t he i n vesti gat or i n writte n f or m a n y ne w i nf or mati o n t hat 
si g nifica ntly bears o n t he s u bjects’ ris ks ass ociate d wit h I P e x p os ure. T he i nf or me d 
c o nse nt will be u p date d, if necessar y . T his ne w i nf or mati o n a nd/ or re vise d I CF t hat ha ve 
bee n a p pr o ve d b y t he a p plica ble E C a n d re g ulat or y a ut h orities, w here a p plica ble, will be 
pr o vi de d b y t he i n vesti gat or t o t he s u bjects w h o c o nse nte d t o partici pate i n t he st u d y (see 
Secti o n 1 6. 3 ).
1 6. 4 D at a M o nit ori n g C o m mittee
T his st u d y  will be m o nit ore d b y Data M o nit ori n g C o m mittee ( D M C). T he D M C is a 
gr o u p of i n di vi d uals wit h perti ne nt e x pertise t hat re vie ws o n a re g ular basis acc u m ulati n g 
data fr o m a n o n g oi n g cli nical st u d y . F or t his st u d y, t he D M C will be c o m p ose d of 
rec o g nize d e x perts i n t he fiel d of A 1 PI deficie nc y a n d C O P D cli nical care a n d researc h 
w h o are n ot recr uiti n g s u bjects f or t his st u d y . 
T he D M C will be res p o nsi b le f or m o nit ori n g t he safet y of t he st u d y partici pa nts i ncl u di n g 
peri o dic re vie w of S A Es, A Es, a n d a n y rele va nt i nf or mati o n t hat ma y ha ve a n i m pact o n t he 
safet y of t he partici pa nts or t he et hics of t he trial. Base d o n data re vie w, t he D M C ma y ma ke 
a rec o m me n dati o n t o c o nti n ue t he st u d y as is, te m p oraril y s us pe n d t he st u d y, or ter mi nate t he 
st u d y base d o n pre-defi ne d criteria s uc h as u nacce pta ble t o xicities or lac k of treat me nt 
be nefits. T he me m bers hi p, res p o nsi bilities, i nteracti o ns, a n d o perati o ns of t he D M C i n 
pr o vi di n g o versi g ht of t he st u d y, as well as criteria f or D M C rec o m me n da ti o ns, are detaile d 
i n t he D M C charter.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 7 9 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 7. D A T A H A N D LI N G A N D R E C O R D K E E PI N G
1 7. 1 C o nfi de nti alit y P olic y
T he i n vesti gat or will c o m pl y  wit h t he c o nfi de ntialit y p olic y as descri be d i n t he Cli nical 
St u d y  A gree me nt.
1 7. 2 St u d y D oc u me nts a n d C ase Re p ort F or ms
T he i n vesti gat or will mai ntai n c o m plete a n d acc urate pa per f or mat st u d y d oc u me ntati o n 
i n a se parate file. St u d y  d oc u me ntati o n ma y i ncl u de i nf or mati o n defi ne d as “s o urce data” 
(see Secti o n 8. 8 ), rec or ds detaili n g t he pr o gress of t he st u d y f or eac h s u bject, si g ne d 
I CFs , c orres p o n de nce wit h t he E C a n d t he st u d y m o nit or/s p o ns or, e nr oll me nt an d 
scree ni n g i nf or mati o n, C R Fs, S A E Re p orts ( S A E Rs), la b orat or y re p orts (if a p plica ble), 
a n d data clarifica ti o ns re q ueste d b y t he s p o ns or.
T he i n vesti gat or will c o m pl y  wit h t he pr oce d ures f or data rec or di n g a n d re p orti n g. A ny 
c orrecti o ns t o pa per st u d y d ocu me ntati o n m ust be perf or me d as f oll o ws: 1) t he first e ntr y  
will be cr osse d o ut e ntirel y , re mai ni n g le gi ble; a n d 2) eac h c orrecti o n m ust be date d a n d 
i nitiale d b y t he pers o n c orrecti n g t he e ntr y; t he use of c orrecti o n fl ui d a n d erasi n g are 
pr o hi bite d.
T he i n vesti gat or is res p o nsi ble f or t he pr oc ure me nt of data a n d f or t he q ualit y of data 
rec or de d o n t he C R Fs. C R Fs will be pr o vi de d i n electr o nic f or m.
If electr o nic f or mat C R Fs are pr o vi de d by t he s p o ns or, o nl y a ut h orize d st u d y  site 
pers o n nel will rec or d or c ha n ge data o n t he C R Fs. If data is n ot e ntere d o n t he C R Fs 
d uri n g t he st u d y visit, t he data will be rec or de d o n pa per, a n d t his d oc u me ntati o n will be 
c o nsi dere d s o urce d oc u me ntati o n. C ha n ges t o a C R F will re q uire d oc u me ntati o n of t he 
reas o n f or eac h c ha n ge. A n i de ntical (electr o nic/ pa per) versi o n of t he c o m plete set of 
C R Fs f or eac h s u bject will re mai n i n t he i n vesti gat or file at t he st u d y site i n acc or da nce 
wit h t he data rete nti o n p olic y  (see Secti o n 1 7. 3 ).
T he ha n dli n g of data b y t he s p o ns or, i ncl u di n g data q ualit y  ass ura nce, will c o m pl y wit h 
re g ulat or y g ui deli nes (e g, IC H G C P) a n d t he sta n dar d o perati n g pr oce d ures of t he 
s p o ns or. Data ma na ge me nt a n d c o ntr ol pr ocesses s pecific t o t he st u d y  will be descri be d 
i n t he data ma na ge me nt pla n.
1 7. 3 D oc u me nt a n d D at a Rete nti o n 
T he i n vesti gat or will retai n st u d y  d oc u me ntati o n a n d data ( pa per a n d electr o nic f or ms) i n 
acc or da nce wit h a p plica ble re g ulat or y  re q uire me nts a n d t he d oc u me nt a n d data rete nti o n 
p olic y , as descri be d i n t he Cli nical St u d y A gree me nt.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 8 0 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 8. FI N A N CI N G A N D I N S U R A N C E
T he i n vesti gat or will c o m pl y  wit h i n vesti gat or fi na nci n g, i n vesti gat or/s p o ns or i ns ura nce, 
a n d s u bject c o m pe nsati o n p olicies, if a p plica ble, as descri be d i n t he Cli nical St u d y  
A gree me nt.
1 9. P U B LI C A TI O N P O LI C Y
T he i n vesti gat or will c o m pl y  wit h t he p u blicati o n p olic y as descri be d i n t he Cli nical 
St u d y  A gree me nt. 
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 8 1 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
2 0. S U P P L E M E N T S
2 0. 1 St u d y Fl o w C h art
Fi g ure 2 0- 1
St u d y Fl o w C h art f or B a x alt a Cli nic al St u d y 4 7 1 1 0 1
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 8 2 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
2 0. 2 Sc he d ule of St u d y Pr oce d ures a n d Assess me nts
T a ble 2 0. 2- 1
Sc he d ule of St u d y Pr oce d ures a n d Assess me nts
Pr oce d ures/
Assess me nts
Scree ni n g
( Ma x 
6 Wee ks)
B aseli ne
B A L a ( Ma x 
2 W ee ks)
Wee k 1
(M a x 
4 8 h o urs after 
B aseli ne B A L)
Wee k 7
( ±2 D a ys)
O n -Tre at m e nt 
B A L ( Wee k 
1 2 - 1 4)b
Wee k 1 3
( ± 2 D a ys)
Wee k 1 9
( ± 2 D a ys)
Wee k 2 5
( ± 2 D a ys)
St u d y C o m pleti o n 
( Wee k 2 6± 3 D a ys )/
E arl y Ter mi n ati o n c
I nf or me d C o nse ntd
X
Eli gi bilit y Criteria  
X
Ra n d o mizati o n
X e
De m o gra p hics
X
Me dical a n d 
Me dicati o n Hist or y
X
Hei g ht
X
B o d y  Wei g htf
X
X
X
X    
X    
X
P h y sical E xa m
X
X g
X g
X g
X g
X g
Vital Si g ns
X
X h
X h
X h
X h
X h
E C G i
X
C hest X -r a y/ C Tj
X
P ul m o nar y F u ncti o n 
Tests k
X
Scree ni n g/ Safet y 
La b orat or y Tests l
X
X g
X g
X g
X
Scree ni n g/ O n -
Treat me nt Tr o u g h 
A 1 PI m
X
X g
X g
X g
X g
X g
X
X g
X g
X g
X g
X g
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 8 3 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
T a ble 2 0. 2- 1
Sc he d ule of St u d y Pr oce d ures a n d Assess me nts
Pr oce d ures/
Assess me nts
Scree ni n g
( Ma x 
6 Wee ks)
B aseli ne
B A L a ( Ma x 
2 W ee ks)
Wee k 1
(M a x 
4 8 h o urs after 
B aseli ne B A L)
Wee k 7
( ±2 D a ys)
O n -Tre at m e nt 
B A L ( Wee k 
1 2 - 1 4)b
Wee k 1 3
( ± 2 D a ys)
Wee k 1 9
( ± 2 D a ys)
Wee k 2 5
( ± 2 D a ys)
St u d y C o m pleti o n 
( Wee k 2 6± 3 D a ys )/
E arl y Ter mi n ati o n c
A nti -A 1 PI 
A nti b o dies m, n
X g
X g
X g
X
Wee kl y G L A S SI A 
I nf usi o nso
X
A d verse E ve nt
X    
X
X
C o nc o mita nt 
Me dicati o ns a n d N o n -
dr u g T hera pies
X    
X
X
X
Tele p h o ne F oll o w -u p p
X
A d diti o n al Pr oce d ures f or S u bjects U n der g oi n g B A L Pr oce d ures
B A L Pr oce d ure
X
X
Vital Si g ns
X q
X q
B A L a n d Plas ma 
Urea a n d A 1 PI m
X
X
A b bre viati o ns: B A L = Br o nc h oal ve olar la va ge; E C G = Electr ocar di o gra m; A 1 PI = Al p ha 1 -Pr otei nase I n hi bit or.
a
F or s u bjects w h o u n der g o br o nc h osc o p y/ B A L pr oce d ures (see Secti o n 1 0. 3. 4 f or m ore details). T he baseli ne br o nc h osc o p y/ B A L visit will be 
p ost p o ne d o nce if a s u bject e x perie nces a m o derate o r se vere C O P D e xacer bati o n a n d/ or L R TI d uri n g t he scree ni n g peri o d (see Secti o n 1 0. 4 f or m ore 
details).
b
T he o n -treat me nt B A L pr oce d ure will be perf or me d bet wee n Wee k 1 2 a n d Wee k 1 4 (see Secti o n 1 0. 3. 4 f or m ore details). T he o n-treat me nt 
br o nc h osc o p y/ B A L visit will be p ost p o ne d o nce if a s u bj ect e x perie nces a m o derate or se vere C O P D e xacer bati o n a n d/ or L R TI (see Secti o n 1 0. 4 f or 
m o re details).
c
S u bjects w h o are bei n g disc o nti n ue d fr o m t he st u d y earl y a n d ha vi n g bee n e x p ose d t o I P will be as ke d t o ret ur n t o t he st u d y site 7 ± 3 da ys after t he last 
i nf usi o n f or earl y ter mi nati o n assess me nts. S u bjects w h o are disc o nti n ue d earl y fr o m t he st u d y pri or t o recei vi n g a n y I P a d ministrati o n will n ot nee d t o 
u n der g o earl y ter mi nati o n pr oce d ures, e xce pt f or t h ose s u bjects w h o ha ve u n der g o ne t he baseli ne B A L pr oce d ure i n w hic h case s u bjects will be 
f oll o we d f or p ote ntial p ost-B A L c o m plicati o ns f or a peri o d of ti me i n acc or da nce wit h l ocal i nstit uti o nal sta n dar d practice b ut n ot t o e xcee d 3 0 da ys.
C o nti n ue d o n Next P a ge
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 8 4 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
C o nti n ue d
d
Writte n i nf or me d c o nse nt m ust be o btai ne d pri or t o perf or ma nce of a n y st u d y pr oce d ures i ncl u di n g scree ni n g/rescree ni n g pr oce d ures.
e
Ra n d o mizati o n is t o ta ke place after verificati o n of s u bject’s meeti n g all t he mai n eli gi bilit y criteria, as well as a d diti o nal br o nc h osc o p y/ B A L -relate d 
eli gi bilit y criteria (as a p plica ble). Br o nc h osc o p y/ B A L visit wit h e val ua ble B A L sa m ples c ollecte d m ust be c o m plete d pri or t o ra n d o mizati o n an d 
wit hi n 4 8 h o urs pri or t o t he first I P a d mi nistrati o n.
f
B o d y  wei g ht will be ta ke n at scree ni n g (f or t he calc ulati o n of t he i nitial I P i nf usi o n d ose [i n m g]/ v ol u me [i n m L]). B o d y wei g ht will be m o nit ore d at 
6- wee k i nter vals (ie, d uri n g Wee ks 1, 7, 1 3, 1 9, a n d 2 5) t hr o u g h o ut t he st u d y. All b o d y wei g ht meas ure me nts m ust be ta ke n usi n g sta n dar dize d 
pr oce d ures. D ose a dj ust me nt base d o n b o d y w ei g ht c ha n ges d uri n g t he c o urse of t he st u d y ma y be ma de if t he c ha n ges are cli nic all y si g nifica nt 
(e g, > 5 %).
g
T o be perf or me d pri or t o d osi n g o n t he da y of t he I P a d mi nistrati o n. Meas ure me nts ta ke n pri or t o t he first I P i nf usi o n ( Wee k 1) w ill ser ve as t he 
baseli ne val ues.
h
D uri n g treat me nt peri o d, vital si g ns ( b o d y te m perat ure, res pirat or y rate, p ulse rate, a n d s yst o lic a n d diast olic bl o o d press ure) are t o be ta ke n o n t he da y 
of I P i nf usi o n d uri n g Wee ks 1, 7, 1 3, 1 9, a n d 2 5 i nf usi o n visits at a n y ti me pri or t o t he i nf usi o n, at eac h rate re d ucti o n d ue t o A E(s) a n d/ or i nf usi o n 
i nterr u pti o n/ disc o nti n uati o n d ue t o A E(s), a n d at 3 0 ( ± 1 5) mi n utes after t he c o m pleti o n of a n i nf usi o n.
i
E C G o btai ne d wit hi n 2 6 w ee ks pri or t o scree ni n g ma y be use d, if a vaila ble.
j
C hest X -r a y or C T sca n o btai ne d wit hi n 5 2 wee ks pri or t o scree ni n g ma y be use d, if a vaila ble.
k
P ul m o nar y f u ncti o n tests i ncl u de s pir o metr y (f orce d e x pirat or y v ol u me i n 1 sec o n d [ F E V 1] a n d f orce d vital ca pacit y [ F V C]) t o be perf or me d i n 
tri plicate, w hic h is t o be ta ke n 3 0 ± 5 mi n utes after a d mi nistrati o n of a s h ort-acti n g i n hale d β 2 a g o nist br o nc h o dilat or (e g, 4 0 0 μ g of sal b uta m ol, or its 
e q ui vale nt).
l
F or la b orat or y assess me nts, see  T a ble 2 0. 3 - 1.
m
Sa m ples will eac h be s plit i nt o d u plicate ali q u ots of a p pr o xi ma te e q ual v ol u me. O ne of t he 2 ali q u ots will ser ve as t he bac k u p sa m ple a n d st ore d 
a p pr o priatel y u ntil n otifie d b y t he s p o ns or.
n
I n t he e ve nt of s us pecte d i m m u ne-relate d A Es, u nsc he d ule d a nti-A 1 PI a nti b o d y sa m ples ma y be c ollecte d as necessar y a n d u p o n c o ns ultati o n wit h or 
n otificati o n b y t he s p o ns or t o s u p p ort A E i n vesti gati o n. T he u nsc he d ule d a nti -A 1 PI a nti b o d y sa m ples m ust be acc o m pa nie d b y plas ma sa m ple 
c ollecti o n f or t he deter mi nati o n of a nti ge nic a n d f u ncti o nal A 1 PI le vels.
o
T he first i nf usi o n ( Wee k 1), as w ell as i nf usi o ns at Wee k 7, Wee k 1 3, Wee k 1 9, a n d Wee k 2 5, m ust be a d mi nistere d at t he st u d y site. Ot her wee kl y 
i nf usi o ns ma y be a d mi nistere d at t he st u d y site or at a n ot her s uita ble l ocati o n (e g, t he s u bject’s h o me) b y a q ualifie d healthcare pr o fessi o nal, as 
acce pta ble per l ocal re g ulati o ns a n d sta n dar d practices of t he st u d y site.
p
F oll o w i n g eac h i nf usi o n visit, tele p h o ne f oll o w-u p will be c o n d ucte d b y t he i n vesti gat or/ desi g nee at 7 2 h o urs ( + 1 b usi ness da y) t o d oc u me nt A Es, 
a n d/ or a d mi nistrati o n of c o nc o mita nt me dicati o ns or n o n -dr u g t hera pies, w hic h ma y ha ve occ urre d w it hi n 7 2 h o urs after t he c o m pleti o n of a n i nf usi o n. 
A n y A Es t hat occ ur a n d/ or c o nc o mita nt me dicati o ns/ n o n -dr u g t hera pies t hat t he s u bject ta kes after t he p ost -i nf usi o n tele p h o ne f oll o w-u p will be 
c ollecte d d uri n g t he s u bse q ue nt wee kl y i nf usi o n visit.
q
Vital si g ns will be meas ure d wit hi n 2 h o urs pri or t o eac h B A L pr oce d ure a n d w it hi n 1 h o ur after t he c o m pleti o n of t he B A L pr oce d ure. Pre -B A L vital 
si g ns are t o be perf or me d pri or t o t he a d mi nistrati o n of br o nc h o dilat or a n d l ocal a nest hesia.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 8 5 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
2 0. 3 Sc he d ule of Cli nic al L a b or at or y Assess me nts
T a ble 2 0. 3- 1
Cli nic al L a b or at or y Assess me nts
Assess me nts
Scree ni n g
( Ma x 6 
Wee ks)
B aseli ne 
B A L a
( Ma x 2 
W ee ks)
Wee k 1   
(M a x
4 8 h o urs 
after B aseli ne 
B A L)
Wee k 7
( ± 2 Da ys)
O n -Tre at m e nt 
B A L
( Wee k 1 2-1 4) b
Wee k 1 3
( ± 2 D a ys)
Wee k 1 9
( ± 2 Da ys)
Wee k 2 5
( ± 2 Da ys)
St u d y C o m pleti o n 
( Wee k 2 6 ± 3 Da ys)/
E arl y Ter mi n ati o n c
He m at ol o g y d
W
W
e
W
e
W
e
W
Cli nical C he mistr y f
S
S e
S e
S e
S
C o m ple me nt Acti vati o n 
a n d I m m u ne C o m ple x 
Pa nel g
S e
S e
S e
S
H A V , H BV , H C V, a n d 
HI V 1/ HI V 2 b y ser ol o g y 
f or a nti ge ne mia or 
a nti b o dies or b y P C R 
base d N A T
S
B 1 9 V Ser ol o g y a n d 
N A T h
S e
S e
S
Uri nal ysis i
U
U e
U e
U e
U
Pre g na nc y Test j
S/ U
S/ U
Ser u m I g A
S
Ser u m C oti ni ne
S
S e
S
S
Scree ni n g ( A nti ge nic) 
A 1 PI k,l
P
O n -Treat me nt Tr o u g h 
Plas ma A nti ge nic A 1 PI l
P e
P e
P e
P e
P e
P
O n -Treat me nt Tr o u g h 
Plas ma F u ncti o nal 
A 1 PI l
P e
P e
P e
P e
P e
P
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 8 6 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
T a ble 2 0. 3- 1
Cli nic al L a b or at or y Assess me nts
Assess me nts
Scree ni n g
( Ma x 6 
Wee ks)
B aseli ne 
B A L a
( Ma x 2 
W ee ks)
Wee k 1   
(M a x
4 8 h o urs 
after B aseli ne 
B A L)
Wee k 7
( ± 2 Da ys)
O n -Tre at m e nt 
B A L
( Wee k 1 2-1 4) b
Wee k 1 3
( ± 2 D a ys)
Wee k 1 9
( ± 2 Da ys)
Wee k 2 5
( ± 2 Da ys)
St u d y C o m pleti o n 
( Wee k 2 6 ± 3 Da ys)/
E arl y Ter mi n ati o n c
P e
P e
P e
P e
P e
Ser u m A nti -A 1 PI 
A nti b o dies l
S e
S e
S e
S
A d diti o n al Pr oce d ures f or S u bjects U n der g oi n g B A L Pr oce d ures
Plas ma Urea l
P m
P m
Plas ma A nti ge nic A 1 PI l
P m, n
P m
Plas ma F u ncti o nal 
A 1 PI l
P m
P m
P m
P m
B A L Urea l
L
L
B A L A nti ge nic A 1 PI l
L
L
B A L F u ncti o nal A 1 PI 
( A N E C)l
L
L
L
L
L
L
L
L
A b bre viati o ns: B A L = Br o nc h oal ve olar la va ge; W = W h ole bl o o d; S = Ser u m; H A V = He patitis A Vir us; H B V = He patitis 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; N A T = N ucleic aci d test; B 1 9 V = Par v o vir us B 1 9; U = Uri ne; 
I g A = I m m u no gl o b uli n A; A 1 PI = Al p ha 1 -Pr otei nase I n hi bit or; P = Plas ma; L = Br o nc h oal ve olar la va ge fl ui d; 
A N E C = A nti -ne utr o p hil elastase ca pacit y; 
C o nti n ue d o n Next P a ge
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 8 7 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
C o nti n ue d
a
F or s u bjects u n der g oi n g br o nc h osc o p y/ B A L pr oce d ures (see Secti o n 1 0. 3. 4 f or m ore details). T he baseli ne br o nc h osc o p y/ B A L visit will be p ost p o ne d 
o nce if a s u bject e x perie nces a m o derate or se vere C O P D e xacer bati o n a n d/ or L R TI d uri n g t he scree ni n g peri o d (see Secti o n 1 0. 4 f or m ore details).
b
T he o n -treat me nt B A L pr oce d ure will be perf or me d bet wee n Wee k 1 2 a n d Wee k 1 4 (see Secti o n 1 0. 3. 4 f or m ore details). T he o n-treat me nt 
br o nc h osc o p y/ B A L visit will be p ost p o ne d o nce if a s u bject e x perie n ces a m o derate or se vere C O P D e xacer bati o n a n d/ or L R TI (see Secti o n 1 0. 4 f or 
m o re details).
c
S u bjects w h o are bei n g disc o nti n ue d fr o m t he st u d y ea rl y a n d ha vi n g bee n e x p ose d t o I P will be as ke d t o ret ur n t o t he st u d y site 7 ± 3 da ys after t he last 
i nf usi o n f or earl y ter mi nati o n assess me nts. S u bjects w h o are disc o nti n ue d earl y fr o m t he st u d y pri or t o recei vi n g a n y I P a d ministrati o n will n ot nee d t o 
u n d er g o earl y ter mi nati o n pr oce d ures, e xce pt f or t h ose s u bjects w h o ha ve u n der g o ne t he baseli ne B A L pr oce d ure i n w hic h case s u bj ects will be 
f oll o we d f or p ote ntial p ost-B A L c o m plicati o ns f or a peri o d of ti me i n acc or da nce wit h l ocal i nstit uti o nal sta n dar d pra ctice b ut n ot t o e xcee d 3 0 da ys.
d
He m at ol o g y pa nel will c o nsist of c o m plete bl o o d c o u nt: H g b, he mat ocrit ( Hct), er yt hr oc ytes (ie, re d bl o o d cell [ R B C]) c o u nt, le u k oc ytes (ie, w hite 
bl o o d cell [ W B C]) c o u nt wit h differe ntial (ie, bas o p hils, e osi n o p hils, l y m p h oc ytes, m o n oc ytes, a n d ne utr o p hils), a bs ol ute ne utr o p hil c o u nt ( A N C), 
a bs ol ute l y m p h oc yte c o u nt, retic ul oc yte c o u nt, a n d platelet c o u nt.
e
Sa m ples m ust be c ollecte d pri or t o G L A S SI A a d mi nistrati o n.
f
Cli nical c he mistr y pa nel will c o nsist of s o di u m, p o tassi u m, calci u m, c hl ori de, bicar b o nate, t otal pr otei n, al b u mi n, ala ni ne a mi n otra nsferase ( A L T), 
as partate a mi n otra nsferase ( A S T), al kali ne p h os p hatase ( A L P), lactic de h y dr o ge nase ( L D H), ga m ma -gl uta m yl -tra nsferase ( G G T), bilir u bi n ( direct a n d 
t otal), bl o o d urea nitr o ge n ( B U N), uric aci d, creati ne, creati ne p h os p h o ki nase ( C P K), a n d gl uc ose.
g
C o m ple me nt acti vati o n a n d i m m u ne c o m ple x pa nel will c o nsist of ser u m C 3, C 4, 5 0 % he m ol ytic c o m ple me nt acti vit y of ser u m ( C H 5 0 ), C 1 q bi n di n g 
assa y (circ ulati n g i m m u ne c o m ple xes).
h
Viral testi n g will c o nsist of viral ser ol o g y f or P V B 1 9 a nti b o d y a n d N A T ( P V B 1 9 P C R). If a s u bject’s Wee k 1 pre -d ose sa m ple is teste d p ositi ve, t he n 
n o f urt her testi n g (e g, Wee k 2 5) is re q uire d. A n y e vi de nce of ser oc o n versi o n (e g, c ha n ge fr o m a ne gati ve test res ult at baseli ne [ Wee k 1 pri or t o t he 
first I P i nf usi o n] t o a p ositi ve res ult at a p ost-baseli ne assess me nt) f or B 1 9 V s h o ul d be re -teste d.
i
Uri nal ysis will c o nsist of c ol or, s pecific gra vit y, p H, pr otei n, gl uc ose, ket o nes, bilir u bi n, ur o bili n o ge n, bl o o d, nitrite, le u k oc yte esterase, a n d 
micr osc o pic e xa mi nati o n ( R B C, W B C, bacteria, casts).
j
F or fe males of c hil d beari n g p ote ntial o nl y. Uri ne pre g na nc y test will be perf or me d, u nless ser u m pre g na nc y test is ma n dat or y as s pecifie d b y l ocal 
re g ulat or y/i nstit uti o nal re q uire me nts.
k
F or t h ose s u bjects w h o are recei vi n g or ha ve rece ntl y bee n e x p ose d t o A 1 PI t hera p y at t he ti me of st u d y e nr oll me nt, pre -st u d y A 1 PI t hera p y m ust be 
disc o nti n ue d a n d sa m ple f or t he deter mi nati o n of e n d o ge n o us circ ulat i n g A 1 PI le vel is t o be ta ke n after c o m pleti o n of a n a de q uate was h o ut peri o d 
(a p pr o xi matel y 4 half-li ves; a vera ge half-life ~ 4. 6 da ys). T he scree ni n g A 1 PI meas ure me nt ma y be re peate d if a n e xcl usi o nar y le vel (≥1 1 µ M) is 
o btai ne d t hat is s us pecte d t o be d ue t o i na de q uate was h o ut of t he pri or A 1 PI t hera p y.
l
Sa m ples will eac h be s plit i nt o d u plicate ali q u ots of a p pr o xi mate e q ual v ol u me. O ne of t he 2 ali q u ots w ill ser ve as t he bac k up sa m ple a n d st ore d 
a p pr o priatel y u ntil n otifie d b y t he s p o ns or. 
m
Sa m ples m ust be c ollecte d wit hi n 2 h o urs pri or t o B A L pr oce d ure.
n
F or s u bjects w h o ha ve recei ve d A 1 PI a u g me ntati o n t hera p y pri or t o st u d y e ntr y, plas ma sa m ple f or baseli ne a nti ge nic A 1 PI le ve l will be c ollecte d 
wit hi n 1 0 da ys pri or t o t he baseli ne B A L vi sit t o verif y t he a de q uac y of t he was h o ut fr o m A 1 PI t hera p y pri or t o perf or mi n g B A L.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 8 8 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
2 0. 4 T hres h ol ds f or Cli nic all y Si g nific a nt L a b or at or y A b n or m alities
Eac h a b n or mal la b orat or y  test res ult will be assesse d f or cli nical si g nifica nce b y t he 
i n vesti gat or base d o n t he me dical j u d g me nt of t he i n vesti gat or. T he cl i nical si g nifica nce 
of a b n or mal la b orat or y  val ues is t o be ca pt ure d i n t he s o urce d oc u me nts. A b n or mal 
la b orat or y val ues c o nsi dere d cli nically si g nifica nt b y t he i n vesti gat or are t o be re p orte d i n 
t he C R F as a n A E or as Me dical Hist or y, de pe n di n g o n w het her t he y occ urre d d uri n g or 
after t he first i nf usi o n or pri or t o t he first i nf usi o n. I nde pe n de ntl y, a b n or mal cli nical 
la b orat or y val ues t hat meet t he f oll o wi n g criteria will be a nalyz e d a n d re p orte d.
L a b or at or y Test
L o west Alert 
L i mit
Hi g hest Alert 
L i mit
C o m me nt
H e m at ol o g y
H g b
( M) 1 0. 0 g/ d L
( F) 9. 0 g/ d L
----
----
Serial H g b val ues all o w  assess me nt 
of t he rate of decli ne o ver ti me
Le u k oc ytes
2 8 0 0/ m m 3
1 6, 0 0 0/ m m 3
T o be i nter prete d i n t he c o nte xt of 
cli nical s y m pt o ms
A bs ol ute ne utr o p hil c o u nt  
< 1 0 0 0/ m m 3
---
Retic ul oc yte c o u nt
< 0. 5 %
> 1 0 %  
T o be i nter prete d i n relati o n t o 
c ha n ges i n H g b a n d ot her e vi de nce 
of b o ne marr o w  s u p pressi o n or 
he m ol ysis 
Platelet c o u nt
< 5 0, 0 0 0/ m m 3
> 7 5 0, 0 0 0/ m m 3
Cli nic al C he mistr y
S o di u m 
< 1 2 5 m m ol/ L   
> 1 6 0 m m ol/ L  
Serial val ues all o w assess me nt of 
rate of c ha n ge
P otassi u m
< 3 m m ol/ L   
> 6 m m ol/ L  
T o be i nter prete d i n c o nj u ncti o n 
wit h p ossi ble c ha n ges i n E C G 
A L T
---
> 3 x U L N
A S T
---
> 3 x U L N
A L P
---
> 3 x U L N
L D H
---
> 3 x U L N
G G T
---
> 3 x U L N
Bilir u bi n (t otal a n d 
i n direct)
---
> 3 x U L N
Ser u m creati ni ne
---  
( M) > 2. 0 m g/ d L
( F) > 1. 6 m g/ d L
C P K
---
> 5 x U L N
Gl uc ose
< 3 0 m g/ d L  
> 2 0 0 m g/ d L  
H y per gl yce mia s h o ul d be 
i nter prete d i n t he c o nte xt of k n o w n 
dia betes as a c o m or bi dit y
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 8 9 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
L a b or at or y Test
L o west Alert 
L i mit
Hi g hest Alert 
L i mit
C o m me nt
Ser u m al b u mi n
< 3. 0 g/ d L
----  
Ma y  i n dicate pr otei n l oss, 
i nfla m mati o n or mal n utriti o n
C o m ple me nt Acti v ati o n a n d I m m u ne C o m ple x
Ser u m C 3
< 7 0 m g/ d L  
---
Ser u m C 4
< 1 4 m g/ d L  
---
T otal c o m ple me nt ( C H 5 0)  
< 3 0 U/ ml
---
C 1 q bi n di n g / CI Cs
< 1 2 m g/ d L
Uri n al ysis
Pr otei n
---
> 3 +  
M ust be i nter prete d i n relati o n t o 
uri nar y c o nce ntrati o n. O nl y vali d 
w he n uri ne s pecific gra vit y is 
≥1. 0 1 0
R B C
---  
> 1 5/ h pf or gr oss 
he mat uria
A b bre viati o ns: M = Male; F = Fe male; H g b = He m o gl o bi n; A L T = Ala ni ne a mi n otra nsferase; 
U L N = U p per li mit of n or mal; A S T = As partate a mi n otra nsferase; A L P = Al kali ne p h os p hatase; 
L D H = Lactic de h y dr o ge nase; G G T = Ga m ma - gl uta m yl-tra nsferase; C P K = creati ne p h os p h o ki nase; 
C 3 = C o m ple me nt c o m p o ne nt 3; C 4 = C o m ple me nt c o m p o ne nt 4; C H 5 0 = 5 0 % he m o l ytic c o m ple me nt 
acti vit y of ser u m; R B C = Re d bl o o d cell; h pf = Hi g h p o wer fiel d.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 9 0 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
2 1. R E F E R E N C E LI S T
1.   
a 1-a ntitr ypsi n deficie nc y : me m ora n d u m fr o m a W H O meeti n g. B ull W orl d He alt h 
Or g a n, . 1 9 9 7; 7 5( 5): 3 9 7- 4 1 5.
2.  
de Serres FJ, Bla nc o I. Pre vale nce of a 1 -a ntitr ypsi n deficie nc y  alleles PI * S a n d 
PI * Z  w orl d wi de a n d effecti ve scree ni n g f or eac h of t he fi ve p he n oty pic classes 
PI * M S, PI * M Z, PI * S S, PI * S Z, a n d PI * Z Z: A c o m pre he nsi ve re vie w. T her A dv 
Res pir Dis . 2 0 1 2; 6( 5): 2 77 - 2 9 5.
3.  
de Serres FJ, Bla nc o I, Fer ná n dez -B ustill o E. Et h nic differe nces i n al p ha- 1 
a ntitr ypsi n deficie nc y  i n t he U nite d States of A merica. T her A dv Res pir Dis . 
2 0 1 0; 4( 2): 6 3 - 7 0.
4.  
Bra ntl y M, N u ki wa T, Cr ystal R G. M olec ular basis of al p ha - 1-a ntitr ypsi n 
d eficie nc y. A m J Me d . 1 9 8 8; 8 4( 6 A): 1 3- 3 1.
5.  
H utc his o n D C. Nat ural hist or y  of al p ha- 1-pr otease i n hi bit or deficie nc y . A m J Me d . 
1 9 8 8; 8 4( 6 A): 3 -1 2.
6.  
H u b bar d R C, Cr y stal R G. Al p ha- 1-a ntitr ypsi n a u g me ntati o n t hera p y  f or al p ha-1-
a ntitr ypsi n deficie nc y . A m J Me d . 1 9 8 8; 8 4( 6 A): 5 2 - 6 2.
7.  
O g us hi F, Fells G A, H u b bar d R C, Stra us S D, Cr ystal R G. Z -t ype a 1 -a ntitr ypsi n is 
less c o m pete nt t ha n M 1-t ype a 1 - a ntitr ypsi n as a n i n hi bit or of ne utr o p hil elastase. J 
Cli n I nvest . 1 9 8 7; 8 0( 5): 1 3 6 6- 1 3 7 4.
8.  
B uist A S, B urr o ws B, C o he n A, et al. G ui deli nes f or t he a p pr oac h t o t he patie nt 
wit h se vere here ditar y  al p ha- 1-a ntitr ypsi n deficie nc y . A merica n T h oracic S ociet y. 
A m Rev Res pir Dis . 1 9 8 9; 1 4 0( 5): 1 4 9 4- 1 4 9 7.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 9 1 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
9.   
St oller J K. Cli nical feat ures a n d nat ural hist or y  of se vere a1- a ntitr ypsi n d eficie nc y. 
R o ger S. Mitc hell Lect ure. C hest . 1 9 9 7; 1 1 1( 6 S u p pl): 1 2 3 S-1 2 8 S.
1 0. 
Cr y stal R G, Bra ntly M L,  H u b bar d R C, C uriel D T, States DJ, H ol mes M D. T he 
al p ha 1-a ntitr ypsi n ge ne a n d its m utati o ns. Cli nical c o nse q ue nces a n d strate gies f or 
t hera py. C hest . 1 9 8 9; 9 5( 1): 1 9 6-2 0 8.
1 1. 
We wers M D, Cas olar o M A, Sellers S E, et al. Re place me nt t hera p y f or al p ha 1-
a ntitr ypsi n deficie nc y  ass ociate d wit h e m p h yse ma. N E n gl J Me d . 
1 9 8 7; 3 1 6( 1 7): 1 0 5 5 -1 0 6 2.
1 2.  
Cas olar o M A, Fells G, We wers M, et al. A u g me ntati o n of l u n g a nti ne utr o p hil 
elastase ca pacit y wit h rec o m bi na nt h u ma n a - 1-a ntitr ypsi n. J A p pl P hysi ol . 
1 9 8 7; 6 3( 5): 2 0 1 5 -2 0 2 3.
1 3. 
Cr y stal R G. a 1-a ntitr ypsi n deficie nc y : pat h o ge nesis a n d treat me nt. H os p Pr act ( Off 
E d) . 1 9 9 1; 2 6( 2): 8 1-8 9, 9 3 - 9 4.
1 4. 
Cr y stal R G. a 1-a ntitr ypsi n deficie nc y , e m p h yse ma, a n d li ver disease. Ge netic basis 
a n d strate gies f or t hera p y. J Cli n I nvest . 1 9 9 0; 8 5( 5): 1 3 4 3- 1 3 5 2.
1 5. 
H u b bar d R C, Sellers S, Czers ki D, Ste p he ns L , Cr ystal R G. Bi oc hemical efficac y  
a n d safet y of m o nt hl y a u g me ntati o n t hera p y f or a - 1-a ntitr ypsi n deficie nc y . J A M A. 
1 9 8 8; 2 6 0( 9): 1 2 5 9 -1 2 6 4.
1 6. 
H u b bar d R C, Cr y stal R G. A u g me ntati o n t hera p y of a 1-a ntitr ypsi n deficie nc y . E ur 
Res pir J S u p pl . 1 9 9 0; 9: 4 4s-5 2s.
1 7. 
St oller J K. a 1 -antitr y psi n deficie nc y  a n d a u g me ntati o n t hera p y i n e m p h yse ma. 
Cleve Cli n J Me d . 1 9 8 9; 5 6( 7): 6 8 3- 6 8 9.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 9 2 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 8. 
We wers M D, Cas olar o M A, Cr ystal R G. C o m paris o n of al p ha - 1-a ntitr ypsi n le vels 
a n d a nti ne utr o p hil elastase ca pacit y of bl o o d a n d l u n g i n a patie nt wit h t he al p ha- 1-
a ntitr ypsi n p he n ot y pe n ull -n ull bef ore a n d d uri n g al p ha -1- a ntitr ypsi n a u g me ntati o n 
t hera py. A m Rev Res pir Dis . 1 9 8 7; 1 3 5( 3): 5 3 9-5 4 3.
1 9. 
Miller M R, Ha n ki ns o n J, Br usasc o V, et al. Sta n dar disati o n of s pir o metr y . E ur 
Res pir J . 2 0 0 5; 2 6( 2): 3 1 9- 3 3 8.
2 0. 
Miller M R, Cra p o R, Ha n ki ns o n J, et al. Ge neral c o nsi derati o ns f or l u n g f u ncti o n 
testi n g. E ur Res pir J . 2 0 0 5; 2 6( 1): 1 5 3- 1 6 1.
2 1. 
Tas h ki n D P, Celli B, Se n n S, et al. A 4 -year trial of ti otr o pi u m i n c hr o nic 
o bstr ucti ve p ul m o nar y  disease. N E n gl J Me d . 2 0 0 8; 35 9( 1 5): 1 5 4 3 - 1 5 5 4.
2 2. 
Vija y asarat ha K, St oc kle y R A. Relati o ns hi p bet wee n fre q ue nc y, le n gt h, a n d 
treat me nt o utc o me of e xacer bati o ns t o baseli ne l u n g f u ncti o n a n d l u n g de nsit y i n 
al p ha-1 a ntitr y psi n -deficie nt C O P D. I nt J C hr o n O bstr uct P ul m o n Dis. 2 0 1 2; 7: 7 8 9-
7 9 6.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 9 3 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
2 2. S U M M A R Y O F C H A N G E S
Pr ot oc ol A me n d me nt 7 : 2 0 2 0 M A Y 2 6
Re pl aces: Pr ot oc ol A me n d me nt 6 : 2 0 1 8 A U G 2 7
I n t his secti o n, c ha n ges fr o m t he pre vi o us versi o n of t he P r ot oc ol A me n d me nt 6 , date d 
2 0 1 8 A U G 2 7 , are descri be d a n d t heir rati o nale is gi ve n.
1. 
T hr o u g h o ut t he d oc u me nt
Descri pti o n of C h a n ge : E dit orial/ gra m matical a n d/ or a d mi nistrati ve c ha n ges t hat 
d o n ot s u bsta nti vel y  affect t he st u d y c o n d uct or patie nt safety ha ve bee n ma de.
P ur p ose of C h a n ge : T o i m pr o ve t he rea da bilit y a n d/ or clarit y of t he pr ot oc ol , a n d 
t o reflect mi n or a d mi nistrati ve/ o perati o nal c ha n ges.
2. 
Secti o n 6. 1. 2 a n d Secti o n 8. 7. 3 ( Pr o d uct a d mi nistr ati o n)
Descri pti o n of C h a n ge : T he rate of a d mi nistrati o n was clarifie d as f oll o ws: 
“ m a xi m u m r ate of 0. 2 m L / k g B W/ mi n ( T he rate of i nf usi o n m a y be re g ulate d b y  
a n a m b ulat or y i nf usi o n p u m p, if a v ail a ble, n ot e xcee di n g a n i nf usi o n r ate of 
0. 2 m L/ k g B W/ mi n. )”
P ur p ose of C h a n ge : T o clarif y  t hat s u bjects ma y recei ve a sl o wer i nf usi o n rate. T he 
rate of a d mi nistrati o n s h o ul d be a ma xi m u m rate of 0. 2 m L/ k g B W/ mi n i n 
acc or da nce wit h t he Pac ka ge I nsert f or G L A S SI A. 
3. 
S y n o psis a n d Secti o n 8. 3 ( Pl a n ne d St u d y Peri o d)
Descri pti o n of C h a n ge : T he pri mar y  c o m pleti o n was u p date d t o Q 3 2 0 2 0 a n d st u d y 
c o m pleti o n u p date d t o Q 1 2 0 2 1. T he o verall d urati o n of t he st u d y  will be 
a p pr o xi matel y 5 years fr o m st u d y i nitiati o n. T he recr uit me nt peri o d is n o w 
e x pecte d t o be a p pr o xi matel y 4 6 m o nt hs. 
P ur p ose of C h a n ge : U p date of st u d y  d urati o n a n d ti meli nes.
4. 
S y n o psis a n d Secti o n 8. 4. 2 ( Sec o n d ar y O utc o me Me as ures)
Descri pti o n of C h a n ge : T he sec o n dar y  o utc o me meas ure descri pti o n was clarifie d 
as f oll o ws (see a d de d te xt i n b ol d): “ N u m ber ( pr o p orti o n) of s u bjects w h o 
e x perie nce d a s hift fr o m n or mal or cli nicall y i nsi g nifica nt a b n or mal la b orat or y 
val ues at baseli ne t o cli nicall y  si g nifica nt a b n or mal la b orat or y val ues (t hres h ol ds 
as o utli ne d i n Secti o n 2 0. 4) f oll o wi n g G L A S SI A a d mi nistrati o n.”
P ur p ose of C h a n ge : Clarifi cati o n t hat t hres h ol ds f or cli nicall y si g nifica nt 
la b orat or y a b n or malities as o utli ne d i n Secti o n 2 0. 4 will be use d f or t he s hift 
a nal ys is. 
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 9 4 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
5. 
Secti o n 8. 4. 3 ( E x pl or at or y O utc o me Me as ures)
Descri pti o n of C h a n ge:
 
 
P ur p ose of C h a n ge: Secti o n 8. 4. 3 re vise d as it ha d n ot bee n a me n de d i n li ne wit h 
pr o p ose d c ha n ges i n t he St u d y  Sy n o psis d uri n g Pr ot oc ol A me n d me nt 3, date d 
2 6 A u g ust 2 0 1 6. 
6. 
Secti o n 1 0. 3. 4 ( B A L Visits)
Descri pti o n of C h a n ge: T he te xt f or acce pta ble B A L  sa m ple criteria was m o difie d 
t o rea d as f oll o ws:
“A n e val ua ble s u bject is defi ne d as a s u bject w h o:

has s uccessf ull y  c o m plete d b ot h t he baseli ne a n d t he o n-treat me nt B A L 
visits, a n d

has at least 1 acce pta ble B A L sa m ple o btai ne d fr o m a n y  of t he 3 l o bes fr o m 
eac h visit a n d meeti n g t he f oll o wi n g criteria:

t otal rec o ver y of ≥2 0 % of t he i nstille d v ol u me of sali ne per l o be , a n d

B A L sa m ple s h o ws n o bl o o d b y  vis ual i ns pecti o n 
T he f oll o wi n g te xt was delete d “ …, o verall n u m ber of acce pta ble ali q u ots n o less 
t ha n 3 per l o be”.
P ur p ose of C h a n ge: T he te xt was m o difie d f or clarit y  a n d t o be c o nsiste nt wit h t he 
st u d y pr oce d ures. T he delete d te xt was a d de d i n err or i n Pr ot oc ol A me n d me nt 4 
a n d s u bse q ue nt a me n d me nts. Sta n dar d pr oce d ures f or o btai ni n g B A L sa m ple 
ali q u ots var y fr o m site t o site a n d n o s pecific i nstr ucti o ns o n obtai ni n g B A L sa m ple 
ali q u ots were pr o vi de d t o t he st u d y sites; all re mai ni n g sa m ple criteria were 
c o nfir me d t o be vali d.
7. 
Secti o n 1 2. 9, Secti o n 1 3. 4. 3 a n d T a ble 2 0. 2. 1 (I m m u n o ge nicit y)
Descri pti o n of C h a n ge: C ha n ge of w or di n g fr o m “i m m u ne -relate d” t o “i m m u ne-
me diate d” treat me nt -e mer ge nt A Rs i n se veral secti o ns.
P ur p ose of C h a n ge : W or di n g u p date d f or c o nsiste nc y  t hr o u g h o ut t he pr ot oc ol.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 9 5 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
8. 
Secti o n 1 3. 2. 2 ( Per -Pr ot oc ol A n al ysis Set)
Descri pti o n of C h a n ge : T he te xt f or s u bjects u n der g oi n g B A L pr oce d ures was 
m o difie d as f oll o ws (see a d de d te xt i n b ol d): “ T he per - pr ot oc ol ( P P) a nalys is set 
will i ncl u de a s u bset of t he f ull a nal ys is set, c o m prisi n g s u bjects wit h n o maj or 
pr ot oc ol de viati o ns w hic h m a y i m p act t h e effic ac y assess me nt . F or t he p ur p ose 
of statistical a nal ys is, maj or de viati o ns i ncl u de, b ut are n ot li mite d t o, t he 
f oll o wi n g: fail ure t o c o m pl y wit h t he was h o ut peri o d f or pre-st u d y A 1 PI
a u g me ntati o n t hera p y, missi n g 2 or m ore c o nsec uti ve wee kl y i nf usi o ns a n d/ or 
> 1 5 % of pla n ne d i nf usi o ns, a n d use of a n A 1 PI  pr o d uct (i ncl u di n g c o m merciall y 
a vaila ble G L A S SI A) ot her t ha n I P d uri n g t he st u d y treat me nt peri o d.” 
P ur p ose of C h a n ge : T he te xt was m o difie d t o clarif y  t hat all maj or pr ot oc ol 
de viati o ns will be re vie we d f or t heir p ote ntial i m pact o n efficac y  assess me nts.
9. 
Secti o n 1 3. 2. 3 ( B A L A n al ysis Set)
Descri pti o n of C h a n ge: T he f oll o wi n g te xt was u p date d t o rea d: “ S u bjects m ust 
ha ve acce pt a ble E L F data ( defi niti o n as per Secti o n 1 0. 3. 4) f or b ot h t he baseli ne 
a n d t he o n -treat me nt B A L visits i n or der t o be i ncl u de d i n t he efficac y a nal yses f or 
t he assess me nt of E L F a nal yte le vels f oll o wi n g G L A S SI A a u g me ntati o n t hera p y.”
P ur p ose of C h a n ge: T o clarif y  t hat a defi niti o n f or acce pta ble E L F data ca n be 
f o u n d i n Secti o n 1 0. 3. 4 w hic h defi nes t he criteria f or acce pta ble B A L sa m ples.
1 0. Secti o n 1 3. 2. 4 ( Per-Pr ot oc ol B A L A n al ysis Set)
Descri pti o n of C h a n ge: T his is a ne wl y  a d de d s u bsecti o n. T he f oll o wi n g te xt was 
a dde d: T he per- pr ot oc ol B A L a nal ys is set will be a s u bset of t he B A L a nal ysis set 
wit h n o maj or pr ot oc ol de viati o ns t hat ma y  i m pact t he B A L assess me nt. F urt her 
details will be gi ve n i n t he statistical a nal ys is pla n.”
P ur p ose of C h a n ge: T his a nal ys is set was a d de d t o assess t he i m pact of maj or 
pr ot oc ol de viati o ns o n t he B A L assess me nts. 
1 1. Secti o n 1 3. 4. 1 ( Effic ac y O utc o me Me as ures)
Descri pti o n of C h a n ge: T he f oll o wi n g te xt was a d de d: “ A se nsiti vit y  a nal ysis will 
be perf or me d base d o n t he P P B A L anal ys is set.“
P ur p ose of C h a n ge: A d diti o n of a se nsiti vit y  a nal ysis f or t he a d diti o nal a nal ysis set 
descri be d i n Secti o n 1 3. 2. 4 ( Per-Pr ot oc ol B A L A nal y sis Set).
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 9 6 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 2. S y n o psis ( Pl a n ne d St atistic al A n al ysis) a n d 
Secti o n 1 3. 4. 1 ( Effic ac y O utc o me Me as ures)
Descri pti o n of C h a n ge: T he f oll o wi n g se nte nce was delete d:   
 
 
 
P ur p ose of C h a n ge:
 
 
.
1 3. Secti o n 1 3. 4. 2 ( E x p os ure A n al ysis)
Descri pti o n of C h a n ge: T he te xt was re vise d as f oll o ws (see a d de d te xt i n b ol d a n d 
delet e d te xt): 
“ Plas ma tr o u g h a nti ge nic a n d f u ncti o nal A 1 PI le vels, as well as c ha n ges fr o m 
baseli ne, will be s u m marize d descri pti vel y  a n d dis pla ye d gra p hicall y ( data 
per mitti n g) base d o n data se p ar atel y b y tre at me nt ar m as well as p o ole d acr oss 
b ot h treat me nt ar ms f or t he F A S a n d P P a n al ysis sets. Plas ma a nti ge nic a n d 
f u ncti o nal A 1 PI le vels o btai ne d at t he baseli ne a n d o n-treat me nt B A L visits will be 
s u m marize d se parately a n d, data per mitti n g, to be c orrelate d wit h t he 
c orres p o n di n g val ues i n t he E L F f or t he B A L a n d P P B A L a n al ysis sets. Plas ma 
A 1 PI  le vels o btai ne d at t he st u d y c o m pleti o n ( Wee k 2 6) or Early Ter mi nati o n Visit 
will n ot be part of t his a nal y sis. T hese a nalys es will be c o n d ucte d wit h b ot h t he 
F A S a n d t he P P a nal ys is sets.”
P ur p ose of C h a n ge: T he Earl y Ter mi nati o n a n d C o m pleti o n visits will n o w be 
i ncl u de d i n t he s u m mar y ta bles. A d diti o nall y, it was clarifie d o n w hic h datasets t he 
a nal ys es will be d o ne (i n acc or da nce wit h t he Statistical A nal y sis Pla n). 
1 4. Secti o n 1 3. 4. 3 ( S afet y O utc o me Me as ures)
D escri pti o n of C h a n ge : I n t he f oll o wi n g te xt “ or” was re place d by “a n d” t o rea d : 
“A Es t hat are c o nsi dere d p ote ntiall y  relate d t o t he prese nce of pr otei n a g gre gates 
a n d i m m u ne-me diate d will be s u m m arize d descri pti vel y wit h 9 5 % c o nfi de nce 
i nter vals ( CIs) as a p pr o priate f or eac h A E of i nterest b y eac h treat me nt ar m a n d, if 
a p pr o priate, p o ole d acr oss b ot h treat me nt ar ms.”
P ur p ose of C h a n ge: T he te xt was c ha n ge d f or clarit y  as t he a nalys is will f oc us o n 
t he pri mar y o utc o me meas ure f or t he st u d y, ie, t he “N u m ber ( pr o p orti o n) of A Es 
c o nsi dere d p ote ntiall y relate d t o t he prese nce of pr otei n a g gre gates ( particle l oa d) 
i n t he G L A S SIA s ol uti o n ”.
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 9 7 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 5. S y n o psis a n d Secti o n 1 3. 4. 3 ( S afet y O utc o me Me as ures)
Descri pti o n of C h a n ge : T he f oll o wi n g te xt relate d t o safety o utc o me meas ures was 
delete d: “I n t he e ve nt of a n y  cli nicall y si g nifica nt tre n ds i n treat me nt-e mer ge nt 
A E(s) of i nterest, f urt her a nal ys is i ncl udi n g p ote ntial c orrelati o n wit h t he prese nce 
of partic ulates i n t he G L A S SI A s ol uti o n will be perf or me d.”
P ur p ose of C h a n ge : T he a nal ys is was deter mi ne d n ot t o be re q uire d f or t he st u d y  
d ue t o t he s mall sa m ple size.
1 6. S y n o psis ( Pl a n ne d St atistic al A n al ysis) a n d 
Secti o n 1 3. 4. 3 ( S afet y O utc o me Me as ures)
Descri pti o n of C h a n ge: T he secti o n was u p date d t o clarif y  t he f oll o wi n g sc he d ule d 
a nal ys is of la b orat or y data: 
“ S u m mar y ta bles of la b orat or y data as well as s hift ta bles of n or mal vers us 
a b n or mal l o w / hi g h la b orat or y  val ues will be create d b y eac h treat me nt ar m as well 
as p o ole d t o get her. I n a d diti o n, s hift ta bles of n or mal vers us a b n or mal cli nicall y  
si g nifica nt / n ot-cli nicall y si g nifica nt la b orat or y val ues ( usi n g t hres h ol ds i n 
Secti o n 2 0. 4) will be create d se paratel y b y eac h treat me nt ar m as well as p o ole d 
t o get her. T he cli nical si g nifica nce of a b n or mal la b orat or y val ues as assesse d b y t he 
i n vesti gat or is t o be ca pt ure d i n t he s o urce d oc u me nts a n d is t o be re p orte d i n t he 
C R F as f oll o ws: 

A b n or mal la b orat or y  val ues t hat are c o nsi dere d cli nicall y si g nifica nt by t he 
i n vesti gat or a n d occ urre d pri or t o t he first i nf usi o n will be re p orte d as me dical 
hist or y . 

A b n or mal la b orat or y  val ues t hat are c o nsi dere d cli nicall y si g nifica nt by t he 
i n vesti gator a n d occ urre d d uri n g or after t he first i nf usi o n will be re p orte d as 
a n A E. 
T he f oll o wi n g te xt was delete d: “ T he n u m ber ( pr o p orti o n) of s u bjects w h o 
e x perie nce d a s hift fr o m n or mal or cli nicall y n o n -si g nifica nt a b n or mal la b orat or y 
val ues at baseli ne t o cli nicall y si g nifica nt a b n or mal la b orat or y val ues will be 
s u m marize d wit h t heir p oi nt esti mates a n d e xact 9 5 % CIs. A ny cli nicall y 
si g nifica nt la b orat or y val ues t hat are c o nsi dere d as cli nicall y si g nifica nt by t he 
i n vesti gat or (ie, re p orte d as A Es), as well as i n acc or da nce wit h t he t hres h ol ds 
pr o vi de d i n Secti o n 2 0. 4 , will be a nalyz e d a n d re p orte d, i ncl u di n g s hift ta bles.”
P ur p ose of C h a n ge: D ue t o t he sa m ple size, it was deter mi ne d t hat 9 5 % CI w o ul d 
n ot be nee de d f or t he s hift ta bles. T he sc he d ule d a nal y sis of la b orat or y data was 
f urt her clarifie d i ncl u di n g h o w a b n or mal la b orat or y val ues are t o be assesse d a n d 
re p orte d by t he i n vesti gat or. 
F or n o n- c o m m er ci al u s e o nl y

G L A S SI A
Pa ge 9 8 of 9 8
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 2 0 M A Y 2 6
B A X A L T A C O N FI D E N TI A L – R E S T RI C T E D: D O N O T DI S T RI B U T E WI T H O U T P RI O R A P P R O V A L
1 7. Secti o n 2 0. 4 ( T hres h ol ds f or Cli nic all y Si g nific a nt L a b or at or y A b n or m alities)
Descri pti o n of C h a n ge: T he f oll o wi n g te x t was a d de d:
“ T he cli nical si g nifica nce of a b n or mal la b orat or y  val ues is t o be ca pt ure d i n t he 
s o urce d oc u me nts. A b n or mal la b orat or y val ues c o nsi dere d cli nically si g nifica nt b y 
t he i n vesti gat or are t o be re p orte d i n t he C R F as a n A E or as Me dical Hist or y , 
de pe n di n g o n w het her t he y  occ urre d d uri n g or after t he first i nf usi o n or pri or t o t he 
first i nf usi o n.”
P ur p ose of C h a n ge: Clarificati o n t hat a b n or mal la b orat or y  val ues are t o be 
ca pt ure d i n t he s o urce d oc u me nts a n d are t o be re p orte d i n t he C R F as A Es or as
Me dical Hist or y .
F or n o n- c o m m er ci al u s e o nl y