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 D IS 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 LI NI C A L S T U D Y P R O T O C O L
P R O D U C T: G L A S SI A
S T U D Y TI T L E: A P h ase 3/ 4 St u d y t o E v al u ate t he S afet y, I m m u n o ge nicit y, a n d 
Effect s o n t he Al p h a 1-Pr otei n ase I n hi bit or ( A 1 PI) Le vels i n E pit heli al L i ni n g Fl ui d 
F oll o wi n g G L A S SI A T her a p y i n A 1 PI- Deficie nt S u bjects
S T U D Y S H O R T TI T L E: P h 3/ 4 G L A S SI A S afet y, I m m u n o ge nicit y, a n d 
Br o nc h o al ve ol ar L a v a ge St u d y
P R O T O C O L I D E N TI FI E R: 4 7 1 1 0 1
C LI NI C A L T RI A L P H A S E 3/ 4
A M E N D M E N T 2 : 2 0 1 5 M A Y 0 7
Re pl aces A me n d me nt 1: 2 0 1 5 J A N 1 9
A L L V E R SI O N S: 
A m e n d me nt 2 : 2 0 1 5 M A Y 0 7
A m e n d me nt 1: 2 0 1 5 J A N 1 9
Ori gi n al: 2 0 1 1 J U L 0 5
O T H E R I D(s)
N C T N u m ber: N ot A v ail a ble
I N D N U M B E R: 1 4 7 7 4
St u d y S p o ns or(s): 
B a x alt a U S I nc.
O ne B a xter W a y
Westl a ke Vill a ge, C A  9 1 3 6 2
U S A
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 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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
, Gl o bal Cl i nical De vel o p me nt
Ba xalta U S I nc.
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 onit or, s p o ns or’s 
re prese ntati ve(s), la b orat ories, steeri n g c o m 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 3 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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 ve sti gat or will c o m pl y wit h a p plica ble la ws/re q uire me nts f or re p 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 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.
See S A E Pr ot oc ol Secti o ns f or f urt her i nf or m ati o n a n d S A E R f or m f or co nt act 
i nf or mati o n.
F urt her det ails are als o a v ail a ble i n t he st u d y te a m r oster.
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

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

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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 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/ w ee k 
(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 wee 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. 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 be wai ve d 
fr o m u n der g oi n g t he 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. 
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 
(defi ne d as a t otal r ec o ver y of ≥2 0 % of t he i nstille d v ol u me of sali ne ) are 
o btai ne d at b ot h baseli ne a n d o n -treat me nt B A L visits.
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 pri or A 1 PI treat me nt 
wit h dra wal) d uri n g scree n i n g. Scree ni n g A 1 PI meas ure me nt ma y be re peate d 
d ue t o s us pecte d i na de q uate was h o ut. D uri n g t he was h o ut peri o d, s u bjects will 
be all o w e 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 la bele d 
d osa ge of 6 0 m g/ k g B W/ w ee k 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 o ne 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 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).
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
T a ble 3- 1
Tre at m e nt Assi g n me nts
Tre at m e nt 
A r 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 ow 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
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 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 1 3 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 ulatio 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.
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 o d y w ei g ht meas ure me nts, as well 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 T a 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 co n d ucte d bet w ee 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, as we ll as 
, 
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.
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 
disea se (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 
r e 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 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 we ver, t he o n -treat me nt B A L visit will be 
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 8 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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
Incl 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 6 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 (after 
a de q uate n u m ber of B A L e val ua ble s u bjects has bee n reac he d): 1 8 years of a ge or ol der at t he 
ti me of scree ni n g.
2.
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 ( e xcl u di n g M S, M Z, a n d S Z) .
3.
E n d o ge n o us plas ma (a nti ge nic ) A 1 PI le vel of < 1 1 µ M ( A 1 PI meas ure me nt ma y be re peate d f or 
s u bjects wit h a n i nitial scree ni n g A 1 PI le vel of 1 1 µ M or a b o ve t hat is s us pecte d t o be d ue t o 
i na de q uate was h o ut of pri or A 1 PI t hera p y).
4.
S u bject 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 mp h yse ma, e vi de nce of 
e mp h yse ma o n c o mp 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 b str 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 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 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 mo ki n g t hr o u g h o ut t he c o urse of t he st u d y.
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 illi 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.
9.
T he s u bject m ust ha ve p ul m o nar y f u ncti o ns 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 s ec o n d ( F E V 1) ≥5 0 % of pre dicte d
( b) If F E V1 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 # 9 is n ot a p plica ble t o s u bjects w h o are e nr olle d after t he tar get of 1 5 t o 1 8 
e val ua ble s u bjects has bee n reac he d a n d w h o are t heref ore 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 .
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 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 or p ul m o nale.
3.
T he s u bject r o uti nel y pr o d uce s m o re t ha n o ne 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 e e 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 re-
scree ne d 4 w ee 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 malitie s ( 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 -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 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 m alities 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 no m a 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 a n y 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 rec ei 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 s u p ple me ntati o n . (T he f oll o w i n g are 
all o we d: s h ort-ter m use of o x y ge n 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 x y ge n 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 wi t 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.
Se r 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.
H e 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 us 
( 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 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 safet y, or c o nf o u n d t he i nter pretati o n of st u d y res ults.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 n vesti gati o nal pr o d uct ( ot her 
t ha n A 1 PI) 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 n vesti gati o nal pr o d uct 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.
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 d e, 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 pti o n is l o w -d ose 
as piri n al o ne w hic h is all o we d.
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 e nr olle d after 
t he tar get of 1 5 t o 1 8 e val ua ble s u bjects has bee n reac he d a n d w h o are t heref ore 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 .
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 LF . 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 o ne-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 w ee 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

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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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
1. S T U D Y P E R S O N N E L ................................................................................................. 2
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 ..............................2
1. 2 St u d y Or g a niz ati o n ................................................................................................. 2
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 ........................................................... 3
3. S Y N O P SI S ..................................................................................................................... 4
4. T A B L E O F C O N T E N T S ........................................................................................... 1 2
5. LI S T O F A B B R E VI A T I O N S .................................................................................... 1 7
6. B A C K G R O U N D I N F O R M A TI O N .......................................................................... 2 0
6. 1 Descri pti o n of I n vesti g ati o n al Pr o d uct ............................................................... 2 3
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 3
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 3
6. 2 Cli nic al C o n diti o n/I n dic ati o n .............................................................................. 2 3
6. 3 P o p ul ati o n T o Be St u die d ..................................................................................... 2 4
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 4
6. 4. 1 S u m m ar y of N o ncli nic al D at a ....................................................................... 2 4
6. 4. 2 S u m m ar y of Cli nic al D at a ............................................................................. 2 4
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 5
6. 6 C o m pli a nce St ate me nt .......................................................................................... 2 5
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 6
7. 1 St u d y P ur p ose ....................................................................................................... 2 6
7. 2 Pri m ar y O bjecti ves ............................................................................................... 2 6
7. 3 Sec o n d ar y O bjecti ve ............................................................................................. 2 6
7. 4 E x pl or at or y O bjecti ve .......................................................................................... 2 6
8. S T U D Y D E SI G N ......................................................................................................... 2 6
8. 1 Brief S u m m ar y ...................................................................................................... 2 6
8. 2 St u d y Desi g n .......................................................................................................... 2 6
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 .................................... 2 8
8. 4 O utc o me Me as ures ............................................................................................... 2 9
8. 4. 1 Pri m ar y O utc o me Me as ures ......................................................................... 2 9
8. 4. 2 Sec o n d ar y O utc o me Me as ures ..................................................................... 2 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 1 3 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
8. 4. 3 E x pl or at or y O utc o me Me as ures .................................................................. 2 9
8. 5 R a n d o miz ati o n a n d Bli n di n g ............................................................................... 3 0
8. 5. 1 U n bli n di n g Pr oce d ures at St u d y Sites ......................................................... 3 0
8. 6 St u d y St o p pi n g R ules ............................................................................................ 3 0
8. 7 I n vesti g ati o n al Pr o d uct(s) .................................................................................... 3 1
8. 7. 1 P ac k a gi n g, L a beli n g, a n d St or a ge ................................................................ 3 1
8. 7. 2 Pre p ar ati o n of I nf usi o n S ol uti o n .................................................................. 3 1
8. 7. 3 A d mi nistr ati o n ............................................................................................... 3 1
8. 7. 4 Descri pti o n of Tre at me nt .............................................................................. 3 2
8. 7. 5 I n vesti g ati o n al Pr o d uct Acc o u nt a bilit y ....................................................... 3 2
8. 8 S o urce D at a ........................................................................................................... 3 2
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 3
9. 1 I ncl usi o n Crit eri a .................................................................................................. 3 3
9. 2 E xcl usi o n Criteri a ................................................................................................. 3 4
9. 3 Wit h dr a w al a n d Disc o nti n u ati o n ........................................................................ 3 6
1 0. S T U D Y P R O C E D U R E S .......................................................................................... 3 7
1 0. 1 I nf or me d C o nse nt a n d E nr oll me nt ................................................................... 3 7
1 0. 2 S u bject I de ntific ati o n C o de ................................................................................ 3 7
1 0. 3 Scree ni n g a n d St u d y Visits ................................................................................. 3 8
1 0. 3. 1 Scree ni n g Visit ............................................................................................. 3 8
1 0. 3. 1. 1 C o nfir m ati o n o f Se vere C o n ge nit al A 1 PI Deficie nc y ........................3 8
1 0. 3. 1. 2 P ul m o n ar y F u ncti o n Tests ................................................................... 3 9
1 0. 3. 1. 3 Rescree ni n g ........................................................................................... 3 9
1 0. 3. 2 I nf usi o n Visits ............................................................................................... 4 0
1 0. 3. 2. 1 I P A d mi nistr ati o n ................................................................................. 4 0
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 1
1 0. 3. 2. 3 Pre -Me dic ati o ns .................................................................................... 4 3
1 0. 3. 2. 4 P ost -I nf usi o n F oll o w-U p ...................................................................... 4 3
1 0. 3. 3 Cli nic al Assess me nt Visits ........................................................................... 4 3
1 0. 3. 4 B A L Visits ..................................................................................................... 4 3
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 nf ecti o n ( L R TI) ..........4 5
1 0. 5 Me dic ati o ns a n d N o n - Dr u g T her a pies.............................................................. 4 7
1 0. 6 S u bject C o m pleti o n/ Disc o nti n u ati o n ................................................................ 4 7
1 0. 7 Pr oce d ures f or M o nit ori n g S u bject C o m pli a nce ............................................. 4 8
1 1. A S S E S S M E N T O F E F FI C A C Y .............................................................................. 4 9
1 1. 1 E L F A nti ge nic a n d F u ncti o n al A 1 PI Le vels..................................................... 4 9
1 1. 2 
.................................................................................... 4 9
1 2. A S S E S S M E N T O F S A F E T Y ................................................................................... 5 0
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
1 2. 1 A d verse E ve nts .................................................................................................... 5 0
1 2. 1. 1 Defi niti o ns ..................................................................................................... 5 0
1 2. 1. 1. 1 Seri o us A d verse E ve nt .......................................................................... 5 0
1 2. 1. 1. 2 N o n -Seri o us A d verse E ve nt ................................................................. 5 1
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 1
1 2. 1. 1. 4 U ne x pecte d A d verse E ve nts ................................................................. 5 1
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 1
1 2. 1. 1. 6 Pree xisti n g Dise ases .............................................................................. 5 2
1 2. 1. 2 Assess me nt of A d verse E ve nts .................................................................... 5 2
1 2. 1. 2. 1 Se verit y .................................................................................................. 5 3
1 2. 1. 2. 2 C a us alit y ................................................................................................ 5 4
1 2. 2 Ur ge nt S afet y Me as ures ..................................................................................... 5 6
1 2. 3 U nt o w ar d Me dic al Occ urre nces ........................................................................ 5 6
1 2. 4 N o n -Me dic al C o m pl ai nts
................................................................................... 5 7
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 ................................... 5 7
1 2. 6 P h ysic al E x a mi n ati o ns ........................................................................................ 5 7
1 2. 7 Cli nic al L a b or at or y P ar a meters ........................................................................ 5 8
1 2. 7. 1 He m at ol o g y a n d Cli nic al C h e mistr y .......................................................... 5 8
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 .............................5 8
1 2. 7. 3 Vir al Ser ol o g y a n d N ucleic Aci d Tests ....................................................... 5 9
1 2. 7. 4 Uri ne Tests .................................................................................................... 5 9
1 2. 7. 5 Assess me nt of Cli nic al L a b or at or y V al ues ................................................ 6 0
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 0
1 2. 7. 6 Bi o b a n ki n g .................................................................................................... 6 0
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 1
1 2. 9 I m m u n o ge nicit y .................................................................................................. 6 2
1 2. 1 0 Vit al Si g ns .......................................................................................................... 6 2
1 3. S T A TI S TI C S ............................................................................................................. 6 3
1 3. 1 S a m ple Size a n d P o wer C alc ul ati o ns ................................................................ 6 3
1 3. 2 D at asets a n d A n al ysis C o h orts .......................................................................... 6 4
1 3. 2. 1 F ull A n al ysis Set ........................................................................................... 6 4
1 3. 2. 2 Per -Pr ot oc ol A n al ysis Set ............................................................................ 6 4
1 3. 2. 3 B A L A n al ysis Set ......................................................................................... 6 5
1 3. 2. 4 S afet y A n al ysis Set ....................................................................................... 6 5
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 ........................................... 6 5
1 3. 4 M et h o ds of A n al ysis ............................................................................................ 6 5
1 3. 4. 1 Effic ac y O utc o me Me as ures ....................................................................... 6 5
1 3. 4. 2 E x p os ure ....................................................................................................... 6 6
1 3. 4. 3 S afet y O utc o me Me as ures ........................................................................... 6 7
1 3. 5 Pl a n ne d I nteri m A n al ysis of t he St u d y ............................................................. 6 8
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 .................................... 6 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 1 5 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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...................................... 6 9
1 5. 1 I n vesti g at or’s Res p o nsi bilit y .............................................................................. 6 9
1 5. 1. 1 Fi n al Cli nic al St u d y Re p ort ........................................................................ 6 9
1 5. 2 Tr ai ni n g ............................................................................................................... 6 9
1 5. 3 M o nit ori n g ........................................................................................................... 6 9
1 5. 4 A u diti n g ............................................................................................................... 7 0
1 5. 5 N o n -C o m pli a nce wit h t he Pr ot oc ol ................................................................... 7 0
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 0
1 6. E T HI C S ..................................................................................................................... 7 0
1 6. 1 S u bject Pri v ac y ................................................................................................... 7 0
1 6. 2 Et hic s C o m mittee a n d Re g ul at or y A ut h orities ................................................ 7 0
1 6. 3 I nf or me d C o nse nt ............................................................................................... 7 1
1 6. 4 D at a M o nit ori n g C o m mittee .............................................................................. 7 1
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 2
1 7. 1 C o nfi de nti alit y P olic y ......................................................................................... 7 2
1 7. 2 St u d y D oc u me nts a n d C ase Re p ort F or ms ....................................................... 7 2
1 7. 3 D oc u me nt a n d D at a Rete nti o n ........................................................................... 7 2
1 8. FI N A N CI N G A N D I N S U R A N C E ........................................................................... 7 3
1 9. P U B LI C A TI O N P O LI C Y ........................................................................................ 7 3
2 0. S U P P L E M E N T S ....................................................................................................... 7 4
2 0. 1 St u d y Fl o w C h art ................................................................................................ 7 4
2 0. 2 Sc he d ule of St u d y Pr oce d ures a n d Assess me nts .............................................. 7 5
2 0. 3 Sc he d ule of Cli nic al L a b or at or y Assess me nts .................................................. 7 9
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 3
2 1. R E F E R E N C E LI S T.................................................................................................. 8 5
2 2. S U M M A R Y O F C H A N G E S .................................................................................... 8 8
T a bles
Ta ble 3- 1 Treat me nt Assi g n me nts ..................................................................................... 6
Ta ble 8 - 1 Treat me nt Assi g n me nts ................................................................................... 2 7
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........................................ 7 5
Ta ble 2 0. 3- 1 Cli nical La b orat or y  Assess me nts............................................................... 7 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 1 6 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
Fi g ur es
Fi g ure 1 0- 1 E xacer bati o n of C O P D ................................................................................. 4 6
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 ................................. 7 4
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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
˚ C
De gree Celsi us
˚ F
De gree Fa hre n heit
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 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
A T S
A merica n T h oracic S ociet y
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
CI s
C o nfi de nce i nter vals
c m
Ce nti meter(s)
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 F or m(s)
C T
C o m p uterize d t o m o gra p h y
d L
Deciliter(s)
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 g ra m
e C R F
Electr o nic case re p ort f or 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 1 8 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
A b bre vi ati o n
Defi niti o n
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 R S
E ur o pea n Res pirat or y  S ociet y
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 ni strati o n
F E V 1
F orce d e x pirat or y  v ol u me i n o ne 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 CF
I nf or me d c o nse nt f or m
I C H
I nter nati o nal C o nfere nce o n Har m o nizati o n
I g A
I m m u n o gl o b uli n A
i n
I nc h(es)
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
k D
Kil o dalt o n(s)
k g
Kil o gra m(s)
l b
P o u n d(s)
L D H
Lactic de h y d r o ge nase
L R T
L o wer res pirat or y  tract
L R TI
L o wer res pirat or y  tract i nfecti o n
μ M
Micr o m olar
M DI
Metere d d ose i n haler
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 5
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2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
A b bre vi ati o n
Defi niti o n
Me d D R A
Me dical Dicti o nar y f or Re g ul at or y Acti vities
m g
Milli gra m(s)
mi n
Mi n ute (s)
m L
Milliliter(s)
m m 3
C u bic milli meter
m m H g  
Milli meter(s) of merc ur y
N A T
N ucleic aci d test
N E
Ne utr o p hil elastase
n M
Na n o m olar(s)
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
p p m
Parts per milli o n
R B C
Re d bl o o d cell
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 0 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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 recessi ve 
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 % A frica 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, 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 p e, 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 yme rizati 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 ( LR 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 L R 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 cl i 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 1 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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, re a 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 n istrati o n ( F D A) i n 2 0 1 0, o n t he basis of safety 
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 t he A 1 PI. 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 acti ve 
c o m parat or use d i n t he P hase 2/ 3 trial, as well as 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 y o p hilize d p o w der. D uri n g t he P hase 2/ 3 cli nical 
trial, n o safety 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 nt s ( A Es) were c o nsiste nt wit h t h ose re p orte d f or t he 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 SIA (all s u bjects) fr o m Wee k 1 3
t o Wee k 2 4. 
I m m u no 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 o ne 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 de 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 [IB] ).
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. F o ur G L A S SI A l ots were 
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 SI A ma n ufact ure d. ( N ote t hat all G LA 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 
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
P har mac o peia [ U S P ] an 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 vel y 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 ( b y 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 ng t he n u m ber of particles t h at 
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 o tei 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 a b o ut pr otei n a g gre gates i n 
a t hera pe utic pr o d uct o n t he 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 safety pr ofile of G L A S SI A wit h 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 ys 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, 
h y perse nsiti vit y  or a na p h ylactic reacti o ns, a n d i m m u n o ge nicity i nci 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 nt ati 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 SIA 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 SIA 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 safet y 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 SIA 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. 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 SI A 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 yt e 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 py 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 
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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, as well as 
, i n t he E L F 
f oll o wi n g 1 3 wee ks of wee kly I V a d mi nistrati o n of G L A S SI A 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 preparati 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 pro vi de d i n t he certificate of a nal y sis). 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 ollecti o n ce nter s 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 pr eser 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 -deficie 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 tr 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 ntra ve n o us i nf usi o n), as well as t he i nf usi o n 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 pac ka ge 
i nsert.
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 ).
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 ema 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 t w o 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 o ne 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 o d y wei g ht, cli ni cal 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 b ute d t o G L A S SIA a d mi nistrati o n. 
I n t he 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 fi ve c o nsec uti ve da y s. A ni mals were m o nit ore d f or c ha n ges in cli nical 
si g ns, b o dy wei g ht, 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 
D a 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 me a 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 ver y was o b ser 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/ deter 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 ar e pr o vi de d i n t he G L A S SIA 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 5 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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 t w o 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 m a 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 cl eara 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 o deficie 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 ur i 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 vere 
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 ucted i n acc or da nce wit h t his pr ot oc ol, t he I nter nati o nal 
C o nfere nce o n Har m o nisati o n G ui deli ne f or G o o d Cli ni cal Practice E 6 (I C H G C P, 
A pril 1 9 9 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 ur o pea n 
Cli nical Trial Directi ve ( 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 6 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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 t w o-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 py 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 y se 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 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 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
 
 
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 o o d a n d Dr u g A d mi nistrati o n [ 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 dy e nr oll me nt will 
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 pri or A 1 PI treat me nt wit h dra wal) d uri n g scree ni n g. Scree ni n g A 1 PI meas ure me nt ma y  
be re peate d d ue t o s us pecte d i na de q uate was h o ut. 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 ure s f or 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 be wai ve d fr o m 
u n der g oi n g t he 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. A s u bject will 
be c o nsi dere d e val ua ble o nl y  if acce pta ble B A L sa m ples (defi ne d as a t otal rec o ver y  of 
≥2 0 % of t he i nstille d v ol u me of sali ne) are o btai ne d at b ot h baseli ne a n d o n -treat me nt 
B A L.
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 bot 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.
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 attai ne 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 ac hie ve the B A L 
e nr oll me nt tar get.
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 o ne 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 m e nt Assi g n me nts
Tre at m e nt 
A r 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 part icle 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
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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/ m i 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 1 3 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 an 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 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, a s 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. 
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 o d y wei g ht 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 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 ure s/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, as well as 
 
, 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 kly 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.
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 verall d urati o n of t he st u d y  will be a p pr o xi matel y 2 years 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 1 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 urel y 
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.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 pr otei n 
a g gre gates 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 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 t o 
a n AE
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
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 nicall y si g nifica nt a b n or mal 
la b orat or y val ues 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 ucle ic 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
 
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 nl y 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 pt e 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 ) 
bei 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. 
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 mana 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 in 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 not 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 pr o 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.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 h e vali d re g ulat or y re q 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 ( 36 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 o d y wei g ht at scree ni n g. T he 
sa me d ose (i n m g) is t o be a d mi nistere d t o a n i n di vid ual s u bject t hr o u g h o ut t he c o urse of 
treat me nt. A dj ust me nts base d o n b o d y wei g ht c ha n ges d uri n g t he c o urse of t he st u d y are
n ot pla n ne d; h o we ver, d ose (i n m g) ma y  be a dj uste d if dee me d me dically necessar y  at t he 
discreti o n of t he i n vesti gat or (e g, b o d y we i ght c ha n ge b y > 1 0 %). O nl y  b o d y wei g ht 
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.
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 
fu 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 ntra ve n o us 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: 0. 2 m L / k g B W/ mi n
( T he rate of i nf usi o n will be reg ulate d b y a n a m b ulat or y i nf usi o n p u m 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 3 2 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
8. 7. 4 Descri pti o n of Tre at me nt
Tre at me nt : G L A S SI A [ Al p ha1-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 ollo we d b y 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 partiall y  use d a n d/ or u n use d I P(s) w ill 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 oye 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.
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 bser 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 h e 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.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 case re p ort f or ms ( C R Fs) , see 
Secti o n 1 7. 2.
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 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 py / B A L pr oce d ures: 1 8 t o 6 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 (after a de q uate n u m ber of B A L e val ua ble s u bjects has bee n 
reac he d): 1 8 y ears of a ge or ol der at t he ti me of s cree ni n g.
2.
A 1 PI  ge n ot ype 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 (e xcl u di n g M S, M Z, a n d S Z)
3.
E n d o ge n o us plas ma (a nti ge nic) A 1 PI le vel of < 1 1 µ M ( A 1 PI  meas ure me nt ma y be 
re peate d f or s u bjects wit h a n i nitial scree ni n g A 1 PI le vel of 1 1 µ M or a b o ve t hat is 
s us pecte d t o be d ue t o i na de q uate was h o ut of pri or A 1 PI t hera p y).
4.
S u bject 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 .
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 4 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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 ns 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 ncl usi o n criteri o n # 9 is n ot a p plica b le t o s u bjects w h o are e nr olle d after t he tar get 
of 1 5 t o 1 8 e val ua ble s u bjects has bee n reac he d a n d w h o are t heref ore 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.
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 g i 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 or p ul mo nale.
3.
T he s u bject r o uti nely pr o d uces m ore t ha n o ne 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 re-scree 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 h as 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 -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 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 h e 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 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 n t 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 sy 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 nt.
1 0. T he s u bject has a hist or y  of l u n g or a n y 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 .
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 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 x y ge n 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 x y ge n 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 O2 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 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 o tei 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 he patitis A vir us ( H A V), he patitis B vir us ( H B V), 
he pa titis C vir us ( 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 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 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 part ici pate d i n a n ot her cli nical st u d y i n v ol vi n g a n i n vesti gati o nal 
pr o d uct ( ot her t ha n A 1 PI) 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 n vesti gati o nal 
pr o d uct 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.
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 hy 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 .
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 ofe til, 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 h i 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 we d.
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 
e nr olle d after t he tar get of 1 5 t o 1 8 e val ua ble s u bjects has bee n reac he d a n d w h o are 
t heref ore 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. 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 will 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 nt i 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 u l d p ose a n u nacce pta ble ris k f or t he s u bject.
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.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
3.
T he s u bject de vel o ps a seri 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 bj ect 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 ut i ve wee kly 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 d y a n d/ or recei ves a n 
i n vesti gati o nal pr o d uct/ de vice ot her t ha n I P.
5.
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 s u bject will n ot be 
ra n d o mize d a n d will be disc o nti n ue d fr o m t he st u d y. T hese s u bje cts ma y be re-scree ne d 
after 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 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 .
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 dures 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 s u bject i de ntificati o n c o de (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, 2 - or 3 -di git n u m ber st u d y  
site n u m ber (e g, 0 2) t o be pr o vi de d by t he s p o ns or, a n d 3- or 4- di git s u bject n u m ber 
(e g, 0 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 C F). 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 2 will be i de ntifie d as S u bject 4 7 1 1 0 1 - 0 2 0 0 0 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 3 8 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
All st u d y d oc u me nts (e g, C R Fs, cli nical d oc u me ntati 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 
SI C(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 ows pers o nal i de ntificati o n of a s u bject (e g, c ollecti o n of a s u bject’s i nitials a n d birt h 
date w o ul d n ot be per mitte d), i n c o m plia 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 Incl 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. 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 ull y 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 e nr olle d. 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.
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 t hat i ncl u des 2 tests:

A 1 PI  ge n ot y p e

Meas ure m e nt of e n d o ge n o us plas ma A 1 PI  le vel
S u bjects m ust ha ve A 1 PI ge n ot y p e 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 (e xcl u di n g M S, M Z, a n d S Z) 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 bili t y criteria. A s u bject’s past ( pre-
st u d y) rec or ds, if a vaila ble, ma y be use d as a n i nitial assess me nt (e g, a s u bject will be 
c o nsi dere d i neli gi ble base d o n past rec or d of Pi * S Z ge n ot y p e). H o we ver, f or 
c o nfir mati o n of c o n ge nital A 1 PI deficie nc y, all ot her wise p ote ntiall y eli gi ble s u bjects 
will be re q uire d t o u n der g o A 1 PI ge n ot y pe a n d plas ma A 1 PI tests d uri n g scree ni n g. 
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.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
F or t h ose s u bjects w h o a re 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, 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 vel s. 
T heref ore, t hese s u bjects will be r e q uire d t o ha ve t hei r pre-st u d y A 1 PI t hera p y wit h dra w n 
f or a mi ni m u m of 4 wee ks t o all o w A 1 PI t o ret ur n t o t he s u bject’s u na u g me nte d le vels. 
T he 4 - wee k was h o ut peri o d s h o ul d be a de q uate, base d o n a n a vera ge A 1 PI half -life of 
4. 6 da y s a n d t hat t ypicall y  4 to 5 half -li ves w o ul d be re q uire d (ie, 1 8 t o 2 3 da ys). 
H o we ver, i n li g ht of i nter-s u bject varia bilit y i n A 1 PI  half-life, s o me s u bjects ma y re q uire 
a l o n ger was h o ut peri o d. T heref ore, 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.
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 mi nistrati 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 x 2 0 0 µ g or 4 x 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 plica te, 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 nal ys 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 or 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.
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
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 re -
scree ne d 4 we e ks after t he cli nical res 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 #7 a n d 8, a n d e xcl usi o n criteria # 7 a n d 1 5)
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 y iel d a de q uate 
baseli ne B A L sa m ples will be all o we d t o rescree n after 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 re-scree ne d, t he st u d y 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 gally 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 ures. 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. All scree ni n g pr oce d ures, wit h t he e xce pti o n of A 1 PI  
ge n ot y p e ( u nless re peat is necessar y, e g, t he test was n ot perf or me d or err o ne o us res ult 
was o btai ne d d uri n g i nitial scree ni n g), will be perf or me d d uri n g rescree ni n g.
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 will 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).
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 
pr o vi de d i n Secti o n 8. 7.
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 1 3 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 f acilitate 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) b y  a q ualifie d healthcare 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 sys 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 
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 1 ºF) 
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)
1 0. 3. 2. 2 M a n a ge m e 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 m a 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 o nti 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 
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 in 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 by 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 Me 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 m a 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 oster 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.

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 quire s ys te mic c ortic oster oi d treat me nt. T hese s h o ul d be treate d a p pr o priatel y 
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 r e-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 re-c 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.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 pr o 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 nvesti 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.
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 ma y ta ke place at 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. 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 y s 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 bj ect 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 acce pta ble B A L sa m ple ( defi ne d as a t otal rec o ver y of ≥2 0 % of t he i nstille d v ol u me 
of sali ne) c o llecte d fr o m eac h visit.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 tr eat 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 ( bel o w 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 ple te 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 IP a d mi nistrati 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 (t otal rec o ver y of ≥2 0 % of t he t otal ori gi nal i nstille d v ol u me of sali ne ). If n o 
acce pta ble B A L sa m ples ca n 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 
baseli ne B A L visit, t he s u bject will u n der g o earl y ter mi nati o n visit a n d be disc o nti n ue d 
fr o m t he st u d y.
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 oce 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 o ssi ble, it 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. V ital 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 accor da nce wit h sta n dar d practice at t he l ocal i nstit uti o n. 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 5 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 nd 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 we e 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. 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 same 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 ( L R TI)
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 i s be yo n d n or mal da y -t o-d a y  variati o ns a n d lea d 
t o a c ha n ge i n me dicati o 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 dy s 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 ntra ve n o us) 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 sy m 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 ger 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 ny 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
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
Fi g ure 1 0 - 1
E x acer b ati o n of C O P D
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 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 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 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.
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 xacerbati 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.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 hos 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 ntich 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)
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).
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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, 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 ysicia 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 b y 
s p o ns or, or ot her (reas o n t o be s pecifie d by 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 mpleti 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 ue d 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 y s.
If t he c o m pleti o n/ter mi nati o n visit is d o ne as a n a d 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 nt i 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.
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 de r 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 pli a nce.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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.
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.
Ure a 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)/ UB 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 
mea s 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 0 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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 ny 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 seri o us a d verse e ve nt ( 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 o ne 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 ncl 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 pit alizati 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 vent 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 n t 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 par v o vir us B 1 9 ( 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 1 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 d verse e ve nt w hic h met a n y of t he f oll o wi n g criteria: 
(a) a n a d verse e ve nt t hat be ga n d uri n g i nf usi o n or wit h i 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 d verse e ve nt 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 bly relate d t o IP a d mi nistrati o n, or 
(c) a n a d verse e ve nt 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 Rs 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 d verse e ve nt 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 d verse e ve nt 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 bly relate d t o IP a d mi nistrati o n, or 
(c) a n a d verse e ve nt 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 ur e, se verit y, s pecificity, 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 (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 Refere nce Safet y I nf or matio n 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.
A n y  A Es (e x pecte d a n d u ne x pecte d) will be rec or de d o n t he A E C R F.
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 m a 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.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 verity, 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 v e 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 nes s 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 hi c 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).
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 dosa 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 
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 sc 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 h orities.
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 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.
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 oced 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.

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.
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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 ossi bilit 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 u salit 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: 
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.
F or n o n- c o m m er ci al u s e o nl y

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Pa ge 5 5 of 9 5
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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 as outli 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 s e 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 n vesti gati o nal pr o d uct, 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) s ys te m b y c o m pleti n g t he rele va nt electr o nic Case Re p ort 
F or m (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 S p 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 eve 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 re 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 le ast 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 der, a ge at o nset of e ve nt 
a n d/ or date of birt h)

I n vesti gati o nal pr o d uct e x p os ure

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:
o
Date of o nset
o
( S) A E treat me nt ( dr u g, d ose, r o ute of a d mi nistrati o n)
o
Ca usal relati o ns hi p b y  t he I n vesti gat or
o
Meas ures ta ke n (i.e., acti o n ta ke n re gar di n g i n vesti gati o nal pr o d uct i n 
direct relati o ns hi p t o t he A E)

Seri o us ness criteria (i. e., deat h, life-threate 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 re p orti n g 
I n vesti gat or (f or pa per S A E Re p ort F or ms) 
F or n o n- c o m m er ci al u s e o nl y

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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 diat e 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 n d ma y 
i ncl u de a ny of t he f oll o wi n g: 

I mme 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 safety
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 d a y  after t he 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 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.
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 ). H o we ver, eac 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 udi n g t he first I P 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 IP 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 he 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.
F or n o n- c o m m er ci al u s e o nl y

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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.
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 incl 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 ocr i ne; he mat o p oietic/l ym 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 bse 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 n d nec k, e yes 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, 
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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 meter s
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 o rat 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 ( he m o gl o bi n [ 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 ym p h oc y tes, 
m o n oc y tes, 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.
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, 
bic ar 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. 
Bl 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 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 ples t o be c ollecte d o n t he d a y  of IP 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 assess me nts 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 IP.
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. 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 o m 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, a n d circ ulati n g i m m u ne c o m ple xes.
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Bl o o d will be c ollecte d t o o btai n ser u m sa m ples 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.
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
Viral ser ol o g y tests f or H A V a nti b o d y , he patitis B vir us s urface a nti ge n ( H Bs A g), H C V 
a nti b o d y, a n d HI V- 1/HI V- 2 a nti b o d y  will be perf or me d at scree ni n g f or s u bject 
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 hai 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 early 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 IP.
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 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. Uri nal y sis will be perf or me d at a ce ntral la b orat or 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 0 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 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.
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 for 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 ollecte 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 ( o ne 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
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 5
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2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L

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 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 m atel y e q ual v ol u me ( o ne 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 mat or y)
assa ys

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 o ne of 
t he ali q u ots will ser ve as bac k u p sa m ple; see la b orat or y ma 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. S a 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 
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 bject s w h o are disc o nti n ue d early 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 h e earl y ter mi nati o n a nti-A 1 PI  a nti b o d y assess me nt. 
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-relate d a d verse e ve nts. At a ny s c he d ule d or 
u nsc he d ule d ti me p o i 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 la 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 V it 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.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 ( breaths/ 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 pre ss 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)/earl y ter mi nati o n visit (see als o 
Secti o n 1 0. 3. 2. 1 a n d Ta ble 2 0. 3- 1) .
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 1 º F)
F or s u bjects u n der 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 nest hesia.
Vi tal 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 nor 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.
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 o n) f 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 4 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 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 o ne-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 n t 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 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 ho 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 o ne I P i nf usi o n 
a n d ha ve at least o ne 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. 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 , miss i n g t w o 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 6 5 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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 i ncl usi o n a n d e xcl usi o n criteria, 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 o ne 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 k s i m me diately prece di n g t he o n- treat me nt B A L 
pr oce d ure

S u bjects m ust ha ve a vaila ble E L F data 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 y t e 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 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 
o ne 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 wil l 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 urea 
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 a gi ve n s u bject, if B A L  
meas ure me nts are o btai ne d fr o m m ore t ha n 1 l u n g l o be, t he n t he urea-c orrecte d val ues 
will be a vera ge d at t he c orres p o n di n g ti me p oi nt pri or t o bei n g s u m marize 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 6 6 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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 
o ne-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 o: 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 o: μ d ≤ 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 will be greater t ha n zer o.
H 1: μ d > 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.
 
 
 
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 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 parately 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. 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 earl y ter mi nati o n visit will n ot be 
part of t his a nal ys is. 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.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
I n t he e ve nt of 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 a s ures
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 or 
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 v als ( 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 . In 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 y sis i ncl u di n g p ote ntial correlati 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.
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 ul ate d 
se paratel y a n d prese nte d acc or di n g t o seri o us ness, se verity, 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 us 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 nfusi 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 vely) 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) 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 o f 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 6 8 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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  a nti 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-relate d A Es, if a ny, will be 
e xa mi ne 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 mat es 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 b y 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 nal yze d a n d re p orte d, i ncl u di n g s hift ta bles.
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 % CIs.
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 nici t 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.
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.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 vie w 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 ons 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.
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 of t he st u d y 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 o nsi ble f or e ns uri n g a n d verif yi 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. 
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
T he i n vesti gat or will per mit t h e 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. 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 ntat i 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 g ui deli nes/re q uire me nts. 
T he i n vesti gat or will per mit a u dit ors t o v isit 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 vesti 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 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 d a 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 et hics c o m mittee 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 or at or y a n d Re a der St a n d ar diz ati o n
N ot a p plica ble ; ea c 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.
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 be 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 
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 n ts 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 otifica ti 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 xercise 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 C F 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 gulat 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 b y 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.
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 n d/ 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
A Data M o nit ori n g C o m mittee ( D M C) will n ot be use d f or t his st u d y , si nce t he IP is 
alrea d y a lice nse d pr o d uct a n d t he d osi n g re gi me n bei n g e val uate d is alrea d y a p pr o ve d 
f or c hr o nic treat me nt i n t he patie nt p o p ulati o n t o be e nr olle d i n 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 2 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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 a n 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 clarificati 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 oc u me ntati o n m ust be perfor 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 ns i 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 (electro 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 h e 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 7 3 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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 wil l 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 7 4 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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 xalt 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 7 5 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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
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
D e 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
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
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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
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
X g
X g
X g
X g
X g
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
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
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 .
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 7 7 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
C o nti n ue d
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 i f 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 o re 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). The 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 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 ore 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 p ri or t o recei vi n g a n y 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 dard practice b ut n ot t o e xcee d 
3 0 da ys .
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/re -scree 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). F or t h ose u n der g oi n g br o nc h osc o p y/ B A L pr oce d ures, ra n d o mizati o n is t o ta ke plac e o nl y 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 e val ua ble B A L sa m ples c ollecte d.
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. A dj ust me nt base d o n b o d y wei g ht c ha n ges d uri n g t he c o urse of t he st u d y is n ot pla n ne d; h o we ver, d ose ( i n m g) ma y be a dj uste d if 
dee me d me dicall y necessar y at t he discreti o n of t he i n vesti gat or (e g, cli nicall y si g nifica nt b o d y wei g ht c ha n ges).
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. M eas ure me nts ta ke n pri or t o t he first I P i nf usi o n ( Wee k 1) will ser ve as t he 
baseli ne val ues .
h
D uri n g treat me nt peri o d, v ital si g ns ( b o d y te m perat ure, res pirat or y rate, p ulse rate, a n d s yst olic 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 e e ks pri or t o scre e 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 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 .
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] an d f orce d vital ca pacit y [ F V C]), w hic h is t o be ta ke n 
3 0 ± 1 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 pl es 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 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.
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 7 8 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
C o nti n ue d
n
I n t he e ve nt of s us pecte d i m m u ne-relate d a d verse e ve nts, 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 mpa nie d b y  
plas ma sa m pl e 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 1 3 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 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.
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 d verse e ve nts t hat occ ur a n d/ or c o nc o m ita 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 7 9 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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
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
H e 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 A nti b o d y, 
H Bs A g, H C V 
A nti b o d y, a n d HI V -
1/ HI V -2 A nti b o d y
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
A 1 PI Ge n ot y pe
S
Scree ni n g 
( A nti ge nic) A 1 PIk,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
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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
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
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
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
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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
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
L
L
L
L
A b bre viati o ns: B A L = B r o nc h oalve olar la va ge; W =
W h ole bl o o d; S = S er u m; H A V = He patitis A Vir us; H Bs A g = He patitis B vir us s urface a nti ge n; 
H C V = He patitis C vir us; HI V = H u ma n i m m u n o deficie nc y vir us; N A T = N ucleic aci d test; B 1 9 V = Par v o vir us B 1 9; U = U ri ne; 
I g A = I m m u n o 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; 
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 ver e 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 o re 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 nces a m o derate or se vere C O P D e xacer bati o n a n d/ or L R TI (se e 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 s ite 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 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.
d
H e 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 ( he m o gl o bi n [ 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 pr i 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 otassi 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 d r 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.
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 2 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
C o nti n ue d
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 wi ll c o nsist of ser u m C 3, C 4, t otal c o m ple me nt ( C H 5 0), C 1 q bi n di n g, a n d 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 par v o vir us B 1 9 ( 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.
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, 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, ca sts).
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 ulati 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 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.
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 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 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 3 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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. I n de 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 e m o gl o bi n ( 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
Bi lir 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
Ser u m al b u mi n
< 3. 0 g/ d L
----
M a y  i n dicate pr otei n l oss, 
i nfla m mati o n or mal n utriti 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 8 4 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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
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
< 1 2 m g/ d L
Uri n al ysis
Pr otei n
---
> 3 +
M ust be i nte r 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 ol 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 8 5 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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. 
Al p ha 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 
Healt h Or ga n. 1 9 9 7; 7 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 d v. Res pir. Dis. 2 0 1 2; 6: 2 7 7 - 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 d v. Res pir. Dis. 
2 0 1 0; 4: 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 
deficie nc y . A m.J. Me d. 1 9 8 8; 8 4: 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: 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: 5 2-6 2.
7. O g us hi F, Fells G A, H u b bar d R C et al. Z-t ype al p ha 1- a ntitr ypsi n is less c o m pete nt 
t ha n M 1-t ype al p ha 1- a ntitr ypsi n as a n i n hi bit or of ne utr o p hil elastase. 
J. Cli n.In vest. 1 9 8 7; 8 0: 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. Re v. Res pir. Dis. 1 9 8 9; 1 4 0: 1 4 9 4 - 1 4 9 7.
9. St oller J K . Cli nical feat ures a n d nat ural hist or y of se vere al p ha 1 - a ntitr ypsi n 
deficie nc y . R o ger S. Mitc hell Lect ure. C hest. 1 9 9 7; 1 1 1: 1 23 S- 1 2 8 S.
1 0. Cr y stal R G, Bra ntly M L,  H u b bar d R C et al. 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 p y. C hest. 1 9 8 9; 9 5: 1 9 6 -
2 0 8.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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 h a 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 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 al p ha- 1-a ntitr ypsi n. J. A p pl. P h y si ol. 
1 9 8 7; 6 3: 2 0 1 5- 2 0 2 3.
1 3. Cr y stal R G. Al p ha 1 -a ntitr ypsi n deficie nc y : pat h o ge nesis a n d treat me nt. 
H os p. Pract.( Off. E d.) 1 9 9 1; 2 6: 8 1 - 8 9, 9 3.
1 4. Cr y stal R G. Al p ha 1 -a ntitr ypsi n deficie nc y, e m p h y se ma, a n d li ver disease. Ge netic 
basis a n d strate gies f or t hera p y. J. Cl i n.In vest. 1 9 9 0; 8 5: 1 3 4 3 - 1 3 5 2.
1 5. H u b bar d R C, Sellers S, Czers ki D et al . Bi oc he mical 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 al p ha-1- a ntitr ypsi n deficie nc y . J A M A. 1 9 8 8; 2 6 0: 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 o f al p ha 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 . Al p ha 1 -a ntitr 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. 
Cle ve. Cli n.J. Me d. 1 9 8 9; 5 6: 6 8 3 - 6 8 9.
1 8. We wers M D, Cas olar o M A, Cr y stal 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. Re v. Res pir. Dis. 1 9 8 7; 1 3 5: 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: 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 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; 3 5 9: 1 5 4 3- 1 5 5 4.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
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. Li n k t o P u blis her' s Site: 
htt p:// w w w. nc bi. nl m. ni h. g o v/ p mc/articles/ P M C 3 5 1 4 0 0 9/ p df/c o p d - 7-7 8 9. p df .
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT 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 2 : 2 0 1 5 M A Y 0 7
Re pl aces: Pr ot oc ol A me n d me nt 1: 2 0 1 5 J A N 1 9
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 1 , date d 
2 0 1 5 J A N 1 9 , 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 ha 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.
Rearra n ge me nt/ m o dificati o ns of secti o ns a n d te xt ha ve bee n ma de t o ali g n wit h t he 
c urre nt versi o n of t he s p o ns or’s pr ot oc ol te m plate. C ha n ges i n t he n u m beri n g of 
secti o ns wit h o ut s u bsta ntial/ maj or c ha n ges i n t he c o nte nt will n ot be liste d 
i n di vi d uall y i n t he list of c ha n ges bel o w.
P ur p ose f or C ha n ge : T o c o m pl y  wit h c urre nt pr ot oc ol sta n dar ds a n d re g ulat or y 
re q uire me nts, to i m pr o ve t he rea da bilit y a n d/ or clarit y of t he pr ot oc ol, t o mi ni mize
re d u n da nc y, t o c orrect t yp os a n d i nc o nsiste ncies, a n d t o reflect mi n or 
a d mi nistrati ve/ o perati o nal c ha n ges .
2.
T hr o u g h o ut t he d oc u me nt
Descri pti o n of C ha n ge : T he st u d y was c ha n ge d fr o m P hase 4 t o P hase 3/ 4.
P ur p ose f or C ha n ge: As t he pr o d ucts d o n ot ha ve a mar ket a ut h orizati o n i n all of t he 
tar get st u d y c o u ntries, t he cli nical st u d y p hase was re vise d t o i ncl u de t he pre-mar ket 
a ut h orizati o n st u d y p hase (e. g. P hase 3/ 4).
3.
T hr o u g h o ut t he d oc u me nt
Descri pti o n of C ha n ge : ( 1) st u d y s p o ns or was c ha n ge d fr o m Ba xter Healt hcare 
C or p orati o n (“ Ba xter”) t o Ba xalta U S I nc. (“ Ba xalta”). ( 2) Ba xter I n n o vati o ns
G m b H was re m o ve d fr o m t he list of st u d y s p o ns ors.
P ur p ose f or C ha n ge : ( 1) As t he c o m pa n y Ba xalta m o ves t o war ds bec o mi n g a 
se parate e ntit y o n J ul y 1st, 2 0 1 5, t he na me of t he st u d y s p o ns or has bee n re vise d 
acc or di n gl y. ( 2) Si nce last versi o n of t he pr ot oc ol, t he t ar get c o u ntr y list has bee n 
fi nalize d t o U S, Ca na da, a n d A ustralia w hic h are all c o vere d u n der t he le gal e ntit y of 
Ba xa lta U S I nc.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
4.
T hr o u g h o ut t he d oc u me nt
Descri pti o n of C ha n ge : All refere nces t o t he n u m ber of e val ua ble B A L s u bjects was 
c ha n ge d fr o m “at least 1 5” t o “ 1 5 t o 1 8”.
P ur p ose f or C ha n ge : T his c ha n ge was ma de f or c o nsiste nc y  si nce b ot h were 
pre vi o usl y  writte n i nterc ha n gea bly t hr o u g h o ut t he pr ot oc ol.
5.
Secti o n 8. 5 R a n d o miz ati o n a n d Bli n di n g
Descri pti o n of C ha n ge : Re vise d t he la n g ua ge re gar di n g st u d y pers o n nel t o re m o ve 
refere nce t o a n u n bli n de d p har macist a n d st u dy m o nit or(s).
P ur p ose f or C ha n ge : T o reflect t he pla ns f or st u dy c o n d uct w here bli n di n g ( of t he 
G L A S SI A l ots) will be mai ntai ne d via c o de I Ds assi g ne d, t h us eli mi nati n g t he nee d 
f or u n bli n de d st u d y pers o n nel.
6.
Sect io n 3 S y n o psis, Secti o n 9. 1 I ncl usi o n Criteri a # 1
Descri pti o n of C ha n ge : T he a ge criteria were re v ise d t o i ncl u de a n u p per a ge li mit of 
6 5 y ears f or s u bjects w h o will be u n der g oi n g br o nc h osc o p y / B AL pr oce d ures. 
P ur p ose f or C ha n ge : Base d o n fee d bac k o btai ne d fr o m a cli nical e x pert, 
br o nc h osc o p y/ B A L pr oce d ures perf or me d o n i n di vi d uals ol der t ha n 6 5 years of a ge 
are ass ociate d wit h p o orer ret ur ns e ve n w he n t he s u bject’s F E V 1 is greater t ha n 5 0 %. 
T he pr ot oc ol was re vise d t o s pecif y s u bjects partici pati n g i n t he br o nc h osc o p y / B A L 
c o m p o ne nt of t he st u d y m ust n ot e xcee d 6 5 y ears of a ge. O nce t he tar get n u m ber o f 
B A L e val ua ble s u bjects has bee n reac he d, t he u p per a ge li mit will n o t a p pl y .
7.
Secti o n 3 S y n o psis, Secti o n 9. 1 I ncl usi o n Criteri a # 2, Secti o n 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
Descri pti o n of C ha n ge : T he eli gi bilit y  criteria was re vise d t o state: “ A 1 PI ge n ot ype 
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 n ati o ns (e xcl u di n g M S, M Z, a n d S Z). ”
P ur p ose f or C ha n ge : Base d o n fee d bac k o btai ne d fr o m m ulti ple cli nical e x perts, t he 
pr ot oc ol was re vise d t o e x pa n d t he list of eli gi ble A 1 PI  ge n ot ypes t hat are ass ociate d 
wit h se vere A 1 PI deficie nc y .
8.
Secti o n 3 S y n o psis, Secti o n 9. 1 I ncl usi o n Criteri a # 3
Descri pti o n of C ha n ge : T he scree ni n g A 1 PI t hres h ol d was re vise d t o be less t ha n 
1 1 µ M , as f oll o ws: “E n d o ge n o us plas ma (a nti ge nic) A 1 PI le vel of < 1 1 µ M ( A 1 PI  
meas ure me nt ma y  be re peate d f or s u bjects wit h a n i nitial scree ni n g A 1 PI le vel of 1 1 
µ M or a b o ve t hat is s us pecte d t o be d ue t o i na de q uate was h o ut of pri or A 1 PI  
t hera py). ”
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
P ur p ose f or C ha n ge : T he scree ni n g A 1 PI le vel was re vise d base d o n fee d bac k 
o btai ne d fr o m cli nical e x perts/i n vesti gat ors, a n d f or c o nsiste nc y wit h t hat use d i n t he 
Ka ma da’s pi v otal efficac y st u d y f or G L A S SI A as well as all ot her past a n d o n g oi n g 
cli nical trials e val uati n g t he effects of A 1 PI a u g me ntati o n t hera p y i n patie nts wit h 
A 1 PI  deficie nc y.
9.
Sect io n 3 S y n o psis, Secti o n 9. 1 I ncl usi o n Criteri a # 4
Descri pti o n of C ha n ge : T he eli gi bilit y criteria was re vise d as f oll o ws: “S u bject 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 y se ma, e vi de nce of 
e m p h yse 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 wit hi n 5 2 wee ks of 
scree ni n g, 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 .” 
P ur p ose f or C ha n ge : T o re m o ve t he p hrase “ wit hi n 5 2 wee ks of scree ni n g” as t his is 
n ot a p plica ble. 
1 0.
Secti o n 3 S y n o psis, Secti o n 9. 1 I ncl usi o n Criteri a # 9 ( b), Secti o n 1 0. 3. 1. 2. 2 
Si n gle -Bre at h Deter mi n ati o n of C ar b o n M o n o xi de U p d ate i n t he L u n g ( D L C O )
Descri pti o n of C ha n ge : La n g ua ge re gar di n g D Lc o was re m o ve d.
P ur p ose f or C ha n ge : T o si m plif y  scree ni n g pr oce d ures.
1 1.
Secti o n 3 S y n o psis, Secti o n 9. 2 E xcl usi o n Criteri a # 1
Descri pti o n of C ha n ge : T he eli gi bilit y  re q uire me nt was re w or de d t o state: “ 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).”
P ur p ose f or C ha n ge : T he la n g ua ge was re w or de d t o pr o vi de clarit y, a n d t o e x plicitl y  
state t hat s u bjects wit h sta ble ast h ma are n ot e xcl u de d fr o m t he st u d y.
1 2. Secti o n 3 S y n o psis, Secti o n 9. 2 E xcl usi o n Criteri a # 3
Descri pti o n of C ha n ge : T he eli gi bilit y  re q uire me nt was re vise d t o state: T he s u bject 
r o uti nel y pr o d uces m ore t ha n o ne ta bles p o o n of s p ut u m per da y. 
P ur p ose f or C ha n ge: Base d o n i n vesti gat or fee d bac k, t he eli gi bilit y  re q uire me nt was 
re vise d t o s pecif y t he a m o u nt i n ta bles p o o ns rat her t ha n milliliters as s u bjects ma y 
fi n d t his easier t o meas ure a n d pr o vi de i nf or mati o n t o assess t heir eli gi bilit 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 9 1 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
1 3.
Secti o n 3 S y n o psis, Secti o n 9. 2 E xcl usi o n Criteri a # 4
Descri pti o n of C ha n ge : T he eli gi bilit y  re q uire me nt was re vise d t o state: “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 scr ee ni n g; see Secti o n 1 0. 4 f or t he 
defi niti o n of m o der ate a n d se vere e x acer b ati o ns .)” 
P ur p ose f or C ha n ge : Base d o n i n vesti gat or fee d bac k, t he refere nce t o t he defi niti o n 
of e xacer bati o n se verit y was a d de d t o i m pr o ve clarit y . 
1 4.
Secti o n 3 S y n o psis, Secti o n 9. 2 E xcl usi o n Criteri a # 6
Descri pti o n of C ha n ge : T he eli gi bilit y  re q uire me nt was re vise d as f oll o ws: “ T he 
s u bject has cli nically 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 -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 wit hi n 5 2 wee ks pri or t o scree ni n g ma y be use d, if 
a vaila ble.)”
P ur p ose f or C ha n ge : Base d o n i n vesti gat or fee d bac k, t he eli gi bilit y  re q uire me nt was 
re vise d t o s pecif y t hat s u bjects wit h mil d br o nc hiectasis will n ot be e xcl u de d as 
br o nc hiectasis is c o m m o n i n t his patie nt p o p ulati o n.
1 5.
Secti o n 3 S y n o psis, S ecti o n 9. 2 E xcl usi o n Criteri a # 7
Descri pti o n of C ha n ge : T he eli gi bilit y  re q uire me nt was m o ve d fr o m i ncl usi o n 
criteria secti o n t o e xcl usi o n criteria secti o n: “ 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 wee ks pri or t o scre e ni n g ma y be use d, 
if a vaila ble.)”
P ur p ose f or C ha n ge : T o i m pr o ve rea da b ilit y.
1 6.
Secti o n 3 S y n o psis, Secti o n 9. 2 E xcl usi o n Criteri a # 1 1
Descri pti o n of C ha n ge : T he eli gi bilit y  re q uire me nt was re vise d as f oll o ws: “ 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 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 x y ge n s u p ple me nt ati o n [e g, f or t he 
m a n a ge me nt of ac ute C O P D e x acer b ati o n], o x y ge n s u p ple me nt ati 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 O2 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]).
P ur p o se f or C ha n ge: Base d o n i n vesti gat or fee d bac k, t he eli gi bilit y  re q uire me nt was 
re vise d t o clarif y t hat o nl y l o n g ter m ar o u n d-t he-cl oc k o x yge n s u p ple me ntati o n is 
n ot all o we d . This patie nt p o p ulati o n q uite c o m m o nl y  uses o xy ge n s u p ple me ntati o n 
at ni g ht ti me or o n a s h ort-ter m basis (e g, f or p ul m o nar y 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 9 2 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
1 7.
Secti o n 3 S y n o psis, Secti o n 9. 2 E xcl usi o n Criteri a # 1 5
Descri pti o n of C ha n ge : T he f oll o wi n g eli gi bilit y  re q uire me nt was re vise d as f oll o ws: 
“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 us ( H C V), or h u ma n i m m u n o deficie nc y  vir us ( HI V) T ype 1/ 2 
i nfecti o n at t he ti me of scree ni n g .”
P ur p ose f or C ha n ge : Base d o n i n vesti gat or fee d bac k, t he eli gi bilit y  re q uire me nt was 
re vise d t o s pecif y t hat s u bjects wit h o ng oi n g acti ve i nfecti o n of t hese vir uses at t he 
ti me of scree ni n g will be e xcl u de d fr o m t he st u d y. S u bjects wit h p ositi ve ser ol o g y  
res ults (e g, he patitis B) d ue t o past i nfecti o n or vacci nati o n will be all o we d.
1 8.
Secti o n 3 S y n o psis, Secti o n 9. 2 E xcl usi o n Crit eri a # 2 0
Descri pti o n of C ha n ge : T he eli gi bilit y  re q uire me nt was re vise d t o state: “ 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.”
P ur p ose f or C ha n ge : T o m ore acc uratel y  defi ne t he me dical ter ms t hat ma y 
pre dis p ose s u bjects t o ris ks ass ociate d wit h br o nc h osc o p y  pr oce d ures.
1 9.
Secti o n 9. 3 Wit h dr a w al a n d Disc o nti n u ati o n, Secti o n 1 0. 3. 1 Scree ni n g Visit
Descri pti o n of C ha n ge : T he f oll o wi n g te xt (i n b ol d f o nt) “ 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 ples ca n 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 baseli ne B A L visit, t he s u bject will n ot be ra n d o mize d 
a n d will be disc o nti n ue d fr o m t he st u d y. T hese s u bjects m a y be re -scree ne d after 
t he t ar get e nr oll me nt of B A L e v al u a ble s u bjects is c o m plete d .” a n d “S u bjects 
w h o were disc o nti n ue d e arl y fr o m t he st u d y d ue t o f ail ure t o yiel d a de q u ate 
b aseli ne B A L s a m ples will be all o we d t o rescree n after t he t ar get e nr oll me nt of 
B A L e v al u a ble s u bjects is c o m plete d .” were a d de d.
P ur p ose f or C ha n ge : T o clarif y  t hat s u bjects w h o faile d baseli ne B A L visit will be 
all o we d t o rescree n b ut o nl y  w he n t he B A L tar get has bee n reac he d a n d e nr oll me nt 
is still o pe n t o f ulfill a mi ni m u m of o verall 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 9 3 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
2 0.
Secti o n 1 0. 3. 2. 1 I P A d mi nistr ati o n, Secti o n 1 2. 1 0 Vit al Si g ns, 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
Descri pti o n of C ha n ge : T he wi n d o w f or o btai ni n g vital si g ns was c ha n ge d fr o m 
“wit hi n 9 0 mi n utes ” t o “at 3 0 ( ± 1 5) mi n utes ” after t he c o m pleti o n of a n i nf u si o n.
P ur p ose f or C ha n ge : T he p ost -i nf usi o n vital si g n c ollecti o n ti me p oi nt was re vise d t o 
all o w fle xi bilit y of 1 5 mi n utes, w hile sta n dar dizi n g wit hi n a ti g hter ti mefra me of 3 0 
mi n utes rat her t ha n 9 0 mi n utes.
2 1.
Secti o n 3 S y n o psis, Secti o n 1 0. 3. 4 B A L Visit, S u p ple me nt 2 0. 5
Br o nc h osc o p y/ Br o nc h o al ve ol ar L a v a ge Pr oce d ure (i n pre vi o us pr ot oc ol 
versi o ns)
Descri pti o n of C ha n ge : T he descri pti o n of a n acce pta ble B A L sa m ple fr o m t he 
baseli ne a n d o n -treat me nt B A L visit was defi ne d as t otal rec o ver y of ≥2 0 % of t he 
i nstille d v ol u me of sali ne.
P ur p ose f or C ha n ge : T he acce pta nce criteria f or B A L  was si m plifie d base d o n 
fee d bac k recei ve d fr o m cli nical e x pert. Details of t he br o nc h osc o p y/ B A L pr oce d ures 
( pre vi o usl y i n S u p ple me nt 2 0. 5) were delete d fr o m t he pr ot oc ol as 
g ui da nce /i nstr ucti o ns will be detaile d i n t he br o nc h osc o p y/ B A L ma n ual t o be 
pr o vi de d t o st u d y  sites.
2 2.
Secti o n 1 0. 3. 4 B A L Visit
Descri pti o n of C ha n ge : T he f oll o wi n g te xt were a d de d: “ T he b aseli 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 r a n d o miz ati o n a n d wi t hi n 
4 8 h o urs pri or t o t he first I P a d mi nistr ati o n .” a n d “T he o n -tre at me nt 
br o nc h osc o p y/ B A L pr oce d ure will be c o n d ucte d 7 ( ± 1) d a ys f oll o wi n g t he l ast 
I P 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, it is rec o m me n de d t h at s ufficie nt ti me (t y pic all 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 ure .”
P ur p ose f or C ha n ge : T o re vise a n d clarif y  t he ti mi n g of br o nc h osc o py/ B A L 
pr oce d ures relati ve t o ra n d o mizati o n a n d I P i nf usi o ns, base d o n fee d bac k fr o m 
cli nical e x pert.
2 3.
Secti o n 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 9 4 of 9 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
2 4.
Secti o n 1 2. 7. 4 Uri ne Tests, Secti o n 2 0. 3 Sc he d ule of Cli nic al L a b or at or y 
Assess me nts
Descri pti o n of C ha n ge : Uri n al ysis pa nel will i ncl u de nitrite, rat her t ha n nitrate.
P ur p ose f or C ha n ge : T o c orrect f or t he a p pr o priate a nalyt e.
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 5
Cli nical St u d y Pr ot oc ol I de ntifier: 4 7 1 1 0 1
2 0 1 5 M A Y 0 7
 
  
 
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 D I S T RI B U T E WI T H O UT P RI O R A P P R O V A L
I N V E S TI G A T O R A C K N O W LE D G E M E N T
P R O D U C T: G L A S SI A
S T U D Y TI T L E: A P h ase 3/ 4 St u d y t o E v al u ate t he S afet y, I m m u n o ge nicit y, a n d 
Effect s o n t he Al p h a 1-Pr otei n ase I n hi bit or ( A 1 PI) Le vels i n E pit heli al Li ni n g Fl ui d 
F oll o wi n g G L A S SI A T her a p y i n A 1 PI - Deficie nt S u bjects
P R O T O C O L I D E N TI FI E R: 4 7 1 1 0 1
C LI NI C A L T RI A L P H A S E 3/ 4
A M E N D M E N T 2 : 2 0 1 5 M A Y 0 7
Re pl aces A me n d me nt 1: 2 0 1 5 J A N 1 9
A L L V E R SI O N S: 
A m e n d me nt 2: 2 0 1 5 M A Y 0 7
A m e n d me nt 1: 2 0 1 5 J A N 1 9
Ori gi n al: 2 0 1 1 J U L 0 5
O T H E R I D(s)
N C T N u m ber: N ot A v ail a ble
I N D N U M B E R: 1 4 7 7 4
B y  si g ni n g bel o w, t he i n vesti gat or ac k n o wle d ges t hat he/s he has rea d a n d u n dersta n ds 
t his pr ot oc ol, a n d will c o m pl y wit h t he re q uire me nts f or o btai ni n g i nf or me d c o nse nt fr o m 
all st u d y s u bjects pri or t o i nitiati n g a n y pr ot oc ol-s pecific pr oce d ures, o btai ni n g writte n 
i nitial a n d o n g oi n g E C(s) pr ot oc ol re vie w a n d a p pr o val, u n dersta n ds a n d a bi des b y  t he 
re q uire me nts f or mai nte na nce of s o urce d oc ume ntati o n, a n d pr o vi des ass ura nce t hat t his 
st u d y will be c o n d ucte d acc or di n g t o all re q uire me nts as defi ne d i n t his pr ot oc ol, cli nical 
st u d y a gree me nt, I C H G C P g ui deli nes, a n d all a p plica ble re g ulat or y re q uire me nts.
Si g nat ure of Pri nci pal I n vesti gat or
Date
Pri nt N a me of Pri nci pal I n vesti gat or
F or n o n- c o m m er ci al u s e o nl y