A Phase IIa Multi-Center, Randomized, Single-Blind Safety Study of Liposomal Cyclosporine A to Treat Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Stem Cell Transplantation
Phase: PHASE2
Conditions: Bronchiolitis Obliterans Syndrome (BOS), GVHD, Chronic, Stem Cell Transplant Complications
Sponsor: Zambon SpA

C O N FI D E N TI A L 
C LI NI C A L T RI A L P R O T O C O L 
B O S T O N- 4: A P h ase II a M ulti- Ce nter, R a n d o mize d, Si n gle- Bli n d S afet y a n d T ol er a bilit y 
St u d y of i n h ale d Li p os o m al C ycl os p o ri n e A i n B r o n c hi olitis O bliter a ns S y n dr o me 
F oll o wi n g All o g e neic He m at o p oietic Ste m Cell Tr a ns pl a nt ati o n  
Pr ot oc ol N o: B T – L- Cs A – 2 0 1 – S C T 
( B O S T O N- 4) 
E u dra C T N o.: 2 0 1 9- 0 0 0 7 1 8- 1 3 
Versi o n: 5. 0  
Date:  3 0 A pril 2 0 2 1 
Pr ot o c ol A me n d me nt N o 4 
S P O N S O R 
Z a m b o n S p A 
Via Lill o del D uca 1 0, 
2 0 0 9 1 Bress o ( MI) 
Ital y 
I N V E S TI G A TI O N A L M E DI CI N A L P R O D U C T 
Li p os o mal C y cl os p ori ne A f or i n halati o n ( L- Cs A) 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 4  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
Pr ot oc ol A c k n o wle d g me nt / C o nfi d e nti alit y 
B O S T O N- 4: A P h ase II a M ulti- Ce nter, R a n d o mize d, Si n gle- Bli n d S afet y a n d T ol er a bilit y 
St u d y of i n h ale d Li p os o m al C ycl os p o ri n e A i n B r o n c hi olitis O bliter a ns S y n dr o me 
F oll o wi n g All o g e neic He m at o p oietic Ste m Cell Tr a ns pl a nt ati o n  
( Pr ot oc ol N o.: B T – L- Cs A – 2 0 1 – S C T) 
B y si g ni n g t his Pr ot oc ol, t h e Pri nci pal I n v esti g at or ac k n o wle d ges a n d a grees: 
T he Pr ot oc ol c o ntai ns all necessar y details f or c o n d ucti n g t he cli nical trial. T he Pri nci pal 
I n v esti gat or will c o n d u ct t his cli ni cal trial as detail e d h erei n, i n c o m pli a nce wit h G o o d Cli nical 
Practice ( G C P) a n d t he a p plica ble re g ulat or y re q uire me nts, a n d will ma ke e ver y reas o n a ble eff ort 
t o c o m plete t h e cli nical trial wit hi n t he ti me desi g nate d. 
T he Pr ot o c ol a n d all rele v a nt i nf or mati o n o n t h e dr u g a n d de vi ce relati n g t o n o ncli nical a n d cli nical 
e x perie n ce, w hi c h was f ur nis he d b y t h e S p o ns or, Za m b o n S p A, will be m a de a v aila ble t o all 
p h ysicia ns, n urses a n d ot her p ers o n nel w h o parti ci pate i n t he c o n d u ct of t his cli nical trial. T he 
I n v esti gat or will disc uss t his materi al wit h t he m t o ass ure t h at t he y are f ull y i nf or me d re gar di n g 
t he I n v esti g ati o nal Me dici n al Pr o d u ct a n d t he c o n d uct of t h e cli nical trial. 
T his d o c u me nt c o ntai ns i nf or mati o n t hat is pri vile g e d or c o nfi de ntial. As s uc h, it ma y n ot be 
discl ose d u nless s pecific pri or p er missi o n is gra nt e d i n writi n g b y t h e S p o ns or or s uc h discl os ure 
is re q uire d b y fe d eral or ot h er la ws or re g ulati o ns. P ers o ns t o w h o m a n y of t his i nf or m ati o n is t o 
be discl ose d m ust first be i nf or me d t hat t he i nf or mati o n is c o nfi d e nti al. T h ese restricti o ns o n 
discl os ure will a p pl y e q uall y t o all f ut ure i nf or mati o n s u p plie d, w hic h is i n di cate d as pri vile ge d or 
c o nfi de ntial. 
Za m b o n S p A or its desi g nee will ha v e access t o a n y s o urce d oc u me nts fr o m w hi c h C ase R e p ort 
F or m i nf or mati o n ma y ha ve bee n ge nerate d. T he Case Re p ort F or ms a n d ot her data p erti n e nt t o 
t his cli nical tri al are t he s ole pr o p ert y of Za m b o n S p A w hic h ma y utilize t he data i n vari o us wa ys, 
s uc h as f or s u b missi o n t o g o ver n me nt re g ul at or y a ut h orities, or i n p u blicati o n of t h e res ults of t he 
cli nical trial. 
T he c o n d uct a n d res ults of t his cli nical trial will be ke pt c o nfi d e nti al. T he res ults of t his cli nical 
trial ma y be p u blis he d. U p o n c o m pleti o n of t he cli nical trial it is t he i nte nti o n of t he parties t o 
pre pare a j oi nt p u blicati o n re gar di n g or descri bi n g t he cli nical trial a n d all t h e res ults t here fr o m 
a n d b ot h parties s hall c o- o p erate i n t his re g ar d. 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 5  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
I h a ve rea d a n d a gree t o t he pr ot oc ol n u m bere d B T – L- Cs A – 2 0 1 – S C T. I a m a ware of m y 
res p o nsi bilities as a Pri nci p al I n vesti gat or a n d a gree t o c o n d uct t his cli nical trial acc or di n g t o 
i nter nati o nal sta n dar ds of G o o d Cli nical Practice (I nter n ati o nal C o u ncil o n Har m o nisati o n 
g ui deli nes), a p pli ca bl e g o ver n me nt re g ulati o ns, a n d I nstit uti o nal res earc h p olicies a n d pr oce d ures 
u n der t he g ui d eli n es of I nter nati o n al C o nfere nce o n Har m o nisati o n (I C H) G o o d Cli nical Practice 
( G C P), nati o n al re g ul ati o ns, a n d t h e pr ot oc ol. I a gree t o a p pr o pri atel y direct a n d assist t h e staff 
u n der m y c o ntr ol, w h o will be i n v ol ve d i n t he cli ni cal tri al. 
Pri n ci p al I n v esti g at or’s Si g n at u re 
Na me & Title _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
( Pri nt) 
Date   
Si g nat ure 
Ce nter Na m e _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
( Pri nt) 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 6  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
2  T A B L E O F C O N T E N T S 
1  SI G N A T O RI E S 
2  
2  T A BL E O F C O N T E N T S 
6  
3  A B B R E VI A TI O N S 
1 0  
4  P R O T O C OL S Y N O P SI S 
1 2  
5  I N T R O D U C TI O N 
2 0  
5. 1  B R O N C HI OLI TI S O BLI T E R A N S S Y N D R O M E  
2 0  
5. 1. 1 
B O S  I N H E M A T O P OI E TI C S T E M C ELL T R A N S PL A N T R E CI PI E N T S 
2 0 
6  B A C K G R O U N D I N F O R M A TI O N 
2 3  
6. 1  IN V E S TI G A TI O N AL M E DI CI N AL P R O D U C T  
2 3  
6. 1. 1 
D R U G C O M P O N E N T  
2 3 
6. 1. 2 
D E VI C E C O M P O N E N T  
2 3 
6. 1. 3 
N O N CLI NI C AL D A T A  
2 3 
6. 1. 4 
C LI NI C AL E X P E RI E N C E  
2 4 
6. 1. 5 
S U M M A R Y O F K N O W N A N D P O T E N TI AL R I S K S A N D B E N E FI T S  
2 5 
6. 1. 6 
J U S TIFI C A TI O N O F T H E R A P Y WI T H C Y CL O S P O RI N E A  A N D O F D O S E R E GI M E N 
2 7 
6. 1. 7 
S T A T E M E N T O F C O M PLI A N C E  
2 8 
6. 1. 8 
P O P UL A TI O N  
2 8 
7  T RI AL O BJ E C TI V E S A N D P U R P O S E 
2 8  
7. 1  T RI AL O BJ E C TI V E S  
2 8  
7. 2  P U R P O S E O F T H E T RI AL  
2 8  
8  T RI AL D E SI G N 
3 0  
8. 1  E N D P OI N T S  
3 0  
8. 1. 1 
P RI M A R Y A SS E SS M E N T 
3 0 
8. 1. 2 
S E C O N D A R Y A SS E SS M E N T S 
3 0 
8. 1. 3 
E X PL O R A T O R Y E FFI C A C Y A S S E SS M E N T 
3 0 
8. 1. 4 I M P  T OL E R A BILI T Y P A R A M E T E R S  
3 0 
8. 1. 5 
S A F E T Y P A R A M E T E R S  
3 0 
8. 1. 6 
P H A R M A C O KI N E TI C P A R A M E T E RS  
3 0 
8. 2  T RI AL D E SI G N 
3 1  
8. 3  S T R A TI FI C A TI O N A N D R A N D O MI Z A TI O N  
3 1  
8. 3. 1 
B LI N DI N G 
3 1 
8. 3. 2 I N V E S TI G A TI O N AL M E DI CI N AL P R O D U C T : T R E A T M E N T , D O S A G E A N D A D MI NI S T R A TI O N  
3 1 
8. 4  IN V E S TI G A TI O N AL M E DI CI N AL P R O D U C T P A C K A GI N G , L A B ELI N G A N D S T O R A G E  
3 5  
8. 4. 1 
P A C K A GI N G A N D L A B ELI N G O F I M P 
3 5 
8. 4. 2 
S T O R A G E 
3 5 
8. 4. 3 I N H AL A TI O N D E VI C E P A C K A GI N G  
3 5 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 7  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
8. 5  S T O P PI N G R UL E S A N D D I S C O N TI N U A TI O N C RI T E RI A  
3 6  
8. 5. 1 
P A TI E N T L E V EL 
3 6 
8. 5. 2 
C E N T E R L E V EL  
3 6 
8. 5. 3 
C LI NI C AL T RI AL L E V EL 
3 7 
8. 6  IN V E S TI G A TI O N AL M E DI CI N AL P R O D U C T : S U P PL Y A N D A C C O U N T A BILI T Y  
3 7  
9  S EL E C TI O N A N D WI T H D R A W AL O F P A TI E N T S 
3 8  
9. 1  P A TI E N T IN CL U SI O N C RI T E RI A  
3 8  
9. 2  P A TI E N T E X CL U SI O N C RI T E RI A  
3 8  
9. 3  P A TI E N T W I T H D R A W AL C RI T E RI A  
3 9  
9. 3. 1 
P R O C E D U R E S O F P A TI E N T W I T H D R A W AL A N D I M P DI S C O N TI N U A TI O N 
3 9 
9. 3. 2 
T Y P E A N D T I MI N G O F D A T A C OLL E C TI O N F O R P A TI E N T W I T H D R A W AL A N D I M P DI S C O N TI N U A TI O N  
4 0 
9. 3. 3 
R E PL A C E M E N T O F W I T H D R A W N P A TI E N T S  
4 0 
9. 3. 4 
F OLL O W -U P OF W I T H D R A W N P A TI E N T S  
4 0 
1 0  T R E A T M E N T O F P A TI E N T S 
4 1  
1 0. 1  C O N C U R R E N T T R E A T M E N T O R M E DI C A TI O N  
4 1  
1 0. 1. 1 
P R O P H YL A XI S A N D T H E R A P Y O F IN F E C TI O N S  
4 1 
1 0. 1. 2 I M M U N O S U P P R E SSI O N  
4 1 
1 0. 1. 3 
T R E A T M E N T F O R B O S 
4 1 
1 0. 1. 4 
O T H E R M E DI C A TI O N 
4 2 
1 0. 1. 5 
P R O HI BI T E D M E DI C A TI O N 
4 2 
1 1  A S S E S S M E N T O F E FFI C A C Y 
4 3  
1 1. 1  M E T H O D S A N D T I MI N G O F E FFI C A C Y A S S E S S M E N T S A N D A N AL Y S E S  
4 3  
1 1. 1. 1 
S PI R O M E T R Y  
4 3 
1 1. 1. 2 
S F- 3 6  Q U ALI T Y O F LI F E Q U E S TI O N N AI R E  
4 4 
1 2  A S S E S S M E N T O F S A F E T Y 
4 5  
1 2. 1  S A F E T Y P A R A M E T E R S  
4 5  
1 2. 1. 1 
D E FI NI TI O N S  
4 5 
1 2. 1. 2 
R EL A TI O N S HI P T O C LI NI C AL T RI AL T R E A T M E N T A SSI G N M E N T 
4 7 
1 2. 1. 3 
M A XI M U M IN T E NSI T Y  
4 7 
1 2. 1. 4 
S E RI O U S A D V E R S E E V E N T ( S A E) R E P O R TI N G  
4 7 
1 2. 1. 5 
T OL E R A BILI T Y O F I M P 
4 9 
1 2. 1. 6 
C LI NI C AL L A B O R A T O R Y  
5 0 
1 2. 1. 7 
V I T AL S I G N S 
5 1 
1 2. 1. 8 
P H Y SI C AL E X A MI N A TI O N S  
5 1 
1 2. 1. 9 
C LI NI C AL G L O B AL IM P R E SSI O N ( C GI) 
5 2 
1 2. 2  D A T A M O NI T O RI N G C O M MI T T E E ( D M C) 
5 2  
1 3  VI SI T S C H E D UL E 
5 3  
1 3. 1  C LI NI C AL T RI AL F L O W C H A R T  
5 6  
1 3. 2  V I SI T S 
5 7  
1 3. 2. 1 
S C R E E NI N G  
5 7 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 8  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 3. 2. 2 
V I SI T 1  / B A S ELI N E V I SI T / R A N D O MI Z A TI O N  
5 8 
1 3. 2. 3 
V I SI T 2  T H R O U G H V I SI T 5  / E O T 
5 9 
1 3. 2. 4 
V I SI T 3  A N D V I SI T 5 
5 9 
1 3. 2. 5 
V I SI T 6  / E N D O F S T U D Y ( EO S) 
5 9 
1 3. 2. 6 
U N S C H E D UL E D V I SI T S 
5 9 
1 3. 2. 7.     R E M O T E V I SI T S 
6 0 
1 4  S T A TI S TI C S 
6 1  
1 4. 1  A N AL Y SI S D A T A S E T S  
6 1  
1 4. 2  S T A TI S TI C AL A N D A N AL Y TI C AL M E T H O D S  
6 2  
1 4. 2. 1 
D E S C RI P TI V E S T A TIS TI C S 
6 2 
1 4. 2. 2 
C H A R A C T E RI Z A TI O N A N D B A S ELI N E C O M P A R A BILI T Y O F T R E A T M E N T G R O U P S  
6 2 
1 4. 2. 3 
A N AL Y SI S O F S A F E T Y  
6 3 
1 4. 2. 4 
A N AL Y S E S O F E FFI C A C Y 
6 4 
1 4. 2. 5 
P H A R M A C O KI N E TI C V A RI A BL E S  
6 4 
1 4. 3  IN T E RI M A N AL Y SI S  
6 5  
1 4. 4  M I S SI N G D A T A  
6 5  
1 4. 5  S A M PL E S I Z E C O N SI D E R A TI O N S  
6 5  
1 5  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 6  
1 6  Q U ALI T Y C O N T R OL A N D Q U ALI T Y A S S U R A N C E 
6 7  
1 7  E T HI C S C O M MI T T E E ( E C) 
6 8  
1 8  P A TI E N T I N F O R M E D C O N S E N T 
6 9  
1 9  H E AL T H A U T H O RI TI E S 
7 0  
2 0  D A T A H A N DLI N G A N D R E C O R D K E E PI N G 
7 1  
2 0. 1  C O NFI D E N TI ALI T Y  
7 1  
2 0. 2  C O M PL E TI O N O F E L E C T R O NI C C A S E R E P O R T F O R M S  
7 2  
2 0. 3  S O U R C E D A T A A N D P A TI E N T F IL E S 
7 3  
2 0. 4  IN V E S TI G A T O R F IL E A N D A R C HI VI N G  
7 4  
2 0. 5  M O NI T O RI N G , Q U ALI T Y A S S U R A N C E , A N D IN S P E C TI O N B Y A U T H O RI TI E S  
7 4  
2 0. 6  D A T A M A N A G E M E N T A N D D A T A C O N T R OL  
7 4  
2 1  FI N A N CI N G A N D I N S U R A N C E 
7 6  
2 2  P U BLI C A TI O N S 
7 7  
2 3  R E F E R E N C E S 
7 8  
2 4  A P P E N DI X I – C O R E I N F O R M E D C O N S E N T F O R M 
8 0  
2 5  A P P E N DI X II – A C C E P T A BL E M E T H O D S O F C O N T R A C E P TI O N 
8 2  

L- Cs A: 
Pr ot o c ol N u m b er: 
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Pa g e 9  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
 
LI S T O F T A B L E S 
T a bl e 1: Q u alit ati v e C o m p ositi o n of t h e I M P 
3 2  
 
LI S T O F FI G U R E S 
Fi g ur e 1:  K a pl a n- M ei er Esti m at es of S ur vi v al i n H e m at o p oi etic St e m C ell Tr a ns pl a nt R eci pi e nts 
2 1  
 
 
 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 1 0  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
3  A B B R E VI A TI O N S 
A D R  
A d verse Dr u g Reacti o n  
A E  
A d verse E ve nt  
all o-H S C T  
All o ge neic He mat o p oietic Ste m Cell Tra ns pla ntati o n  
A T S  
A m erica n T h oraci c S oci et y  
A U C  
Area U n der t h e C ur ve  
B i d 
Bis i n die , t wice dail y 
B O  
Br o n c hi olitis O blitera ns  
B O S  
Br o n c hi olitis O blitera ns S y n dr o me  
B D R M  
Bli n d Data Re vie w Meeti n g  
C GI  
Cli ni cal Gl o bal I m pressi o ns  
C G v H D  
C hr o nic Graft Vers us H ost Disease  
C ma x  
Ma xi m u m c o nce ntrati o n  
C R O  
C o ntract Researc h Or ga nizati o n  
Cs A  
C ycl os p ori ne A  
Cs A -P G  
C ycl os p ori ne A Pr o p yle n e Gl yc ol  
C S R  
Cli ni cal St u d y Re p ort  
Dl  
Deciliter  
D L T  
D o u ble L u n g Tra ns pla nt ati o n  
D M C  
Data M o nit ori n g C o m mittee  
E C  
Et hics C o m mittee  
e C R F  
Electr o n i c Case Re p ort F or m 
E o S  
E n d o f St u d y 
E o T  
E n d of Treat me nt  
E R S  
E ur o pea n Res pirat or y S ociet y  
E U  
E ur o pea n U ni o n  
E X P  
E x pirati o n dat e  
F A S  
F ull A nal ysis Set  
F E F 2 5 -7 5 
F orce d Mi d e x pirat or y Fl o w  
F E V 1 
F orce d E x pirat or y V ol u me i n O n e Sec o n d  
F V C  
F orce d Vital Ca p acit y  
G C P  
G o o d Cli ni cal Practice  
H S C T  
He mat o p oi etic Ste m Cell Tra ns pl a nt ati o n  
I B 
I n vesti gat or’s Br oc h ure 
I C F 
I nf or me d C o nse nt F or m 
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n of Tec h nical Re q uire me nts f or 
P har mace uticals f or H u ma n Us e  
I M P 
I n vesti gati o nal Me dici n al Pr o d uct (L -Cs A ) 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 1 2  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
4  P R O T O C O L S Y N O P SI S 
Pr ot oc ol Title: 
B O S T O N- 4: A P hase IIa M ulti- Ce nt er, R a n d o mi ze d, Si n gle- Bli n d 
Safet y a n d T olera bilit y St u d y of i n h ale d Li p os o mal C ycl os p ori ne A i n 
Br o nc hi olitis O blitera ns S y n dr o me F oll o wi n g All o ge neic 
He mat o p oietic Ste m C ell Tra ns pla ntati o n  
S p o ns or: 
Za m b o n S p A 
Via Lill o del D uca 1 0, 
2 0 0 9 1 Bress o ( MI) 
Ital y 
Pr ot oc ol N u m ber: 
B T – L- Cs A – 2 0 1 – S C T ( B O S T O N- 4) 
E U D R A C T 
N u m b er: 
2 0 1 9- 0 0 0 7 1 8- 1 3 
I N D N u m ber: 
7 8, 8 5 4 
I n vesti g ati o n al 
Me dici n al Pr o d u ct: 
Li p os o mal C y cl os p ori n e A ( L- Cs A) I n h alati o n S ol uti o n 
1 0 m g t wice d ail y ( bi d) 
or 
Li p os o mal C y cl os p ori n e A L- Cs A I n halati o n S ol uti o n 5 m g t wice 
dail y ( bi d) 
or 
Li p os o mal Pl ace b o ( 0 m g L- Cs A) I n h al ati o n S ol uti o n t wice d ail y 
( bi d) 
Pr ot oc ol P h as e: 
P h ase IIa 
Pr ot oc ol D ate: 
Versi o n 5. 0;  3 0 A pril 2 0 2 1 
Pr ot oc ol 
A me n d me nt 
4 
Cli nic al Tri al 
Ce nters/ C o u ntries: 
U p t o 2 0 ce nters i n E ur o pe. 
Pl a n ne d Cli nic al 
Tri al Peri o d:  
D urati o n of t hera p y: 1 2 wee ks  
T otal cli nical trial d urati o n per pati e nt: u p t o 1 8 wee ks 
Pl a n ne d N u m b er of 
P atie nts: 
2 4 pati e nts ra n d o mize d 
Ra n d o mizati o n: 1: 1: 1  
Patie nts will recei ve i n vesti gati o nal treat me nt or pl ace b o vi a t h e L-
Cs A s pecific 
 Ne b uli zer S yste m ( L- Cs A 
), i n a d diti o n t o sta n d ar d of care ( S o C) t hera p y. 
C CI
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 1 3  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
Treat me nt A: L- Cs A 1 0 m g bi d pl us S o C ( n = 8) 
Treat me nt B: L- Cs A 5 m g bi d pl us S o C ( n = 8) 
Treat me nt C: L -Cs A 0 m g  ( place b o) bi d  pl us S o C ( n = 8)  
O bjecti ve: 
T he o bjecti v es of t his st u d y are t o assess t h e t olera bilit y, safet y, 
p har mac o ki n etics ( P K), e x pl orat or y efficac y a n d q ualit y of life of t w o 
d oses of aer os olize d L- Cs A vs pl ace b o i n a d diti o n t o S o C t hera p y f or 
t he treat me nt of B O S i n a d ult all o ge n eic h e mat o p oietic st e m cell 
tra ns pl a ntati o n (all o- H S C T) reci pie nts. 
Cli nic al Tri al 
Desi g n: 
P h ase IIa pr os p ecti v e, m ulti-ce nter, si n gle- bli n d, ra n d o mize d cli nical 
trial assessi n g t w o d oses of i n h ale d L- Cs A a n d place b o.  
Eli gi bilit y Criteri a: 
I ncl usi o n Criteri a: 
1.
A ge  1 8 years
2.
Patie nts 
m ust 
ha ve 
u n der g o n e 
h e mat o p oi etic 
ste m 
cell
tra ns pla ntati o n a n d ha v e d oc u me nte d dia g n osis of c hr o nic Graft
vers us H ost Diseas e (c G v H D), g ui de d b y t he NI H c o ns e ns us
criteria.
3.
Patie nts m ust ha v e bee n di a g n ose d wit h B O S wit hi n > 6 m o nt hs a n d
≤3 y ears at Scree ni n g visit.
4.
S pir o metr y test carrie d o ut at Scree ni n g visit m ust s h o w:

A F E V 1 a b o v e 5 1 % of pre dicte d
A N D

A ≥ 1 0 % decli n e i n F E V 1 ( L) wit hi n 2 years
5.
P atie nt m ust be ca pa ble of u n derst a n di n g t h e p ur p oses a n d ris ks
of t he st u d y, has gi ve n writte n i nf or m e d c o nse nt, a n d a grees t o
c o m pl y wit h t h e st u d y re q uire me nts.
6.
W o me n of c hil d beari n g p ote ntial m ust ha ve a n e gati ve ser u m or
uri ne pre g na n c y test wit hi n 7 d a ys pri or t o ra n d o mizati o n a n d m ust
a gree t o use o ne of t he m et h o ds of c o ntrace pti o n list e d i n A p pe n di x
II t hr o u g h t heir E n d of St u d y Visit.
E xcl usi o n Cri teri a: 
1.
Ot her ac ute or c hr o ni c restri cti ve or o bstr ucti v e l u n g dis eases,
i ncl u di n g b ut n ot li mite d t o: acti v e ast h ma ( varia bl e a n d rec urri n g
s y m pt o ms of airfl o w o bstr u cti o n (re versi ble t o beta- 2 a g o nists) a n d
br o nc hial h y p er-res p o nsi ve ness), c hr o nic o bstr ucti ve p ul m o n ar y
disease, i nterstitial l u n g disease, or cr y pt o ge nic or ga nizi n g
p n e u m o ni a , ne ur o m usc ul ar wea k n ess or dia p hra g matic paral ysis.
2.
A n y ac ut e p ul m o nar y b acterial, viral (as c o nfir m e d b y m ulti ple x
P C R) or f u n g al i nfecti o n n ot s u ccessf ull y res ol v e d at least 4
wee ks pri or t o t he Scree ni n g Visit.

L- Cs A: 
Pr ot o c ol N u m b er: 
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Pa g e 1 5  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
S o C t h era p y 
Tre at me nt B ( L- Cs A 5 m g tre at me nt pl us S o C): 
L- Cs A 5 m g/ 1. 2 5 m L bi d f or a ma xi m u m of 1 2 wee ks 
pl us 
S o C t h era p y 
Tre at me nt C ( 0 m g L- Cs A ( pl ace b o) pl us S o C ): 
L- Cs A 0 m g/ 2. 5 m L bi d f or a ma xi m u m of 1 2 wee ks 
pl us 
S o C t h era p y  
E n d p oi nts: 
Pri m ary assess me nt:   
I M P t olera bilit y a n d safet y d uri n g t he first 4 wee ks of treat me nt 
Sec o n d ary assess me nts:   
 I M P t olera bilit y a n d safet y d uri n g t he first 1 2 wee ks of 
treat me nt; 
 Cs A P K 
E x pl or at ory effic acy assess me nts:   
 F E V 1 % pre dicte d at ra n d o mizati o n c o m pare d t o Wee k 2, 
Wee k 4, Wee k 8, a n d W ee k 1 2 
 F E V 1/ F V C at ra n d o mizati o n c o m p are d t o Wee k 2, Wee k 4, 
Wee k 8, a n d Wee k 1 2 
 
S F- 3 6 Q ualit y of Life Q u esti o n naire at Baseli n e, Wee k 2, 
Wee k 4, Wee k 8, a n d W ee k 1 2 visits  
 
C ha n ges i n t he d ose of c ortic oster oi ds a n d i m m u n os u p pressi v e 
t hera p y a d mi nistere d t hr o u g h o ut trial d urati o n 
I M P T oler a bilit y P ar a meters: 
 L oc al T oler a bilit y: 
o  C o u g h 
o  W h eezi n g 
o  Br o nc h os pas m 
o  T hr oat irritati o n 
o  C ha n ge i n F E V 1 
 Over all T oler a bilit y: 
o  Cli ni cal Gl o b al I m pressi o ns ( C GI) scale ( o n-site o nl y)  
o  I n v esti gat or’s t olera bilit y assess me nt at Visit 3 a n d 
Visit 5  
S afety P ar a meters: 
 A d verse e ve nts ( A Es) 
 Seri o us a d verse e v e nts ( S A Es) 
 Cli ni cal la b orat or y v al ues 
 Vit al si g ns 
 P h ysical E xa mi nati o n 
 
 
 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 1 6  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
P h ar m ac o ki n etic P ar a meters: 

P K: ( Wee k 0) at pre- d ose; directl y after e n d of i n h alati o n; 1 5,
3 0, a n d 4 5 mi n utes, a n d 1, 1. 5, 2, a n d 4 h o urs aft er e n d of
i n h al ati o n:
o
C ma x
o
tma x
o
A U C 0- 4 h

W h ole bl o o d tr o u g h le vels (at Wee ks 2, 4, 8, a n d 1 2)
Assess me nts 
Cli nic al Tri al Pl a n: 
At t otal of 7 visits ( S cree ni n g, Ra n d o mizati o n ( Wee k 0), Wee k 2, 
Wee k 4, Wee k 8, We e k 1 2 ( E n d of Treat me nt [ E o T]) a n d Wee k 1 4 
( E n d of St u d y [ E o S]) will be perf or m e d d uri n g t he cli nical trial. 
A Es a n d c o nc o mita nt me dicati o ns will b e rec or d e d at all visits. 
Scree ni n g:  Aft er i nf or m e d c o nse nt has b ee n o btai n e d. S cree ni n g Visit 
pr oce d ur es will be carrie d o ut t o c hec k g e n eral eli gi bilit y f or 
partici pati o n u p t o 4 wee ks pri or t o ra n d o mizati o n. 
Bl o o d will be dra w n f or safet y pr ofil es. 
Visit 1, W ee k 0 ( B aseli n e Visit, R a n d o miz ati o n):  Bl o o d f or baseli n e 
meas ures will be c olle cte d. S pir o metr y will be perf or me d. A 
pre g na nc y test will b e p erf or me d f or all fe m ales of c hil d beari n g 
p ote nti al pri or t o ra n d o mizati o n. A p h ysical e xa m, i ncl u di n g vital 
si g ns, will be perf or me d. T he C GI Q uesti o n n aire will b e a d mi nistere d. 
T he S F- 3 6 Q u alit y of Life Q uesti o n naire will b e a d mi nistere d.  
Patie nts will b e ra n d o mize d t o st u d y treat me nt a n d i nstr ucte d o n use 
of t h e L- Cs A  
. 
T he first d ose of I M P will be a d mi nistere d u n der o bser vati o n a n d 
safet y will be m o nit ore d. S pir o metr y will be re p eate d 1 h o ur  2 0 mi n 
after c o m pleti o n of t h e first d ose of I M P. 
Bl o o d will be dra w n f or safet y pr ofiles a n d P K d ata at pre- d os e. P K 
sa m ples will be o btai n e d directl y after e n d of first i n h alati o n, at 1 5, 
3 0, a n d 4 5 mi n utes, a n d 1, 1. 5, 2, a n d 4 h o urs aft er e n d of i n halati o n. 
If n o t olera bilit y iss u es are o bser ve d, p atie nts will be per mitte d t o 
lea ve t h e cli nic. 
Patie nts will recei ve t he f ull I M P s u p pl y f or t he 1 2 wee ks treat me nt 
peri o d. 
T he sec o n d d os e of I M P a n d all s u bse q u e nt d oses s h o ul d be i n hale d 
a p pr o xi m atel y 1 2 h o urs after t he first d ose.  
Visit 2, W ee k 2:  S pir o metr y will be o btai n e d. 
Bl o o d will be dra w n f or safet y pr ofil es a n d tr o u g h le vels of Cs A. A 
pre g na nc y test will b e p erf or me d f or all fe m ales of c hil d beari n g 
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 1 7  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
p ote nti al. A p h ysical e xa m, i n cl u di n g vit al si g ns, will be p erf or me d. 
T he C GI Q u esti o n n aire will be a d mi nistere d. T he S F- 3 6 Q u alit y of 
Life Q u esti o n n aire will be a d mi nistere d.  
A d ose of t he I M P will be a d mi nistere d u n der o bs er vati o n. 
Patie nts will bri n g use d a n d u n use d vials of t he I M P f or a vail a bilit y 
c hec k. 
Visit 3, W ee k 4:  D uri n g o n-site visits, s pir o metr y will b e o btai ne d. 
Bl o o d will be dra w n f or safet y pr ofil es a n d tr o u g h le vels of Cs A. A 
pre g na nc y test will b e p erf or me d f or all fe m ales of c hil d beari n g 
p ote nti al. A p h ysical e xa m, i n cl u di n g vit al si g ns, will be p erf or me d. 
T he C GI Q u esti o n n aire will be a d mi nistere d. T he S F- 3 6 Q u alit y of 
Life Q u esti o n n aire will be a d mi nistere d. A n I n v esti gat or’s T olera bilit y 
Assess me nt will b e perf or m e d. 
A d ose of t he I M P will be a d mi nistere d u n der o bs er vati o n d uri n g o n-
site visits. 
Patie nts will bri n g use d a n d u n use d vials of t he I M P f or a vail a bilit y 
c hec k at o n-site visits. 
Visit 4, W ee k 8:  D uri n g o n-site visits, s pir o metr y will b e o btai ne d. 
Bl o o d will be dra w n f or Cs A tr o u g h le vel a n d safet y para met ers. A 
pre g na nc y test will b e p erf or me d f or all fe m ales of c hil d beari n g 
p ote nti al. A p h ysical e xa m, i n cl u di n g vit al si g ns, will be p erf or me d. 
T he C GI Q u esti o n n aire will be a d mi nistere d. T he S F- 3 6 Q u alit y of 
Life Q u esti o n n aire will be a d mi nistere d. 
A d ose of t he I M P will be a d mi nistere d u n der o bs er vati o n d uri n g o n-
site visits. 
Patie nts will bri n g use d a n d u n use d vials of t he I M P f or a vail a bilit y 
c hec k at o n-site visits. 
Visit 5, W ee k 1 2 ( E o T):  S pir o metr y will be o btai ne d. 
Bl o o d will be dra w n f or Cs A tr o u g h le vel a n d safet y p ara met ers. A 
pre g na nc y test will b e p erf or me d f or all fe m ales of c hil d beari n g 
p ote nti al. A p h ysical e xa m, i n cl u di n g vit al si g ns, will be p erf or me d. 
T he C GI Q u esti o n n aire will be a d mi nistere d. T he S F- 3 6 Q u alit y of 
Life Q u esti o n n aire will be a d mi nistere d. A n I n v esti gat or´s t olera bilit y 
assess me nt will be p erf or me d. 
Patie nts will ret ur n all use d a n d u n use d vials of t h e I M P. Dr u g 
acc o u nt a bilit y will b e perf or me d. 
T he L- Cs A  
 will b e ret ur n e d. 
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 1 8  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
Visit 6, W ee k 1 4 ( E o S):   
Bl o o d will be dra w n f or safet y para meters. A pre g na nc y test will be 
perf or me d f or all fe males of c hil d b eari n g p ote ntial. A p h ysical e xa m, 
i ncl u di n g vital si g ns, will b e p erf or me d. 
Safet y a n d t olera bilit y will be m o nit ore d b y d o c u me ntati o n of A Es 
t hr o u g h o ut t h e st u d y.  
E ver y eff ort will be ma d e t o h a ve all pla n ne d a n d u nsc he d ule d visits at 
t he st u d y site. Ma n dat or y o n site visits are Scree ni n g a n d Visit 1, Visit 
2 a n d Visit 5.  
H o we ver, if o ne of t h e visits V 3, V 4 a n d V 6 ca n n ot be perf or me d at 
site d ue t o C O VI D- 1 9 , re m ote visits (e. g. b y tel e p h o ne) are p ossi ble. 
C O VI D -1 9 relat e d A d v erse E v e nts will b e re p ort e d as S A Es.  
D at a M o nit ori n g 
C o m mittee: 
A Dat a M o nit ori n g C o m mittee ( D M C) is esta blis he d t o m o nit or t he 
safet y of I M P. T h e D M C will m o nit or safet y b y e val uati n g t he safet y 
a nal yses ge nerate d b y t h e i n d e pe n de nt st atisticia n d uri n g t he c o urse of 
t he cli nical trial. Details of t he safet y a nal yses will b e i n cl u de d i n t he 
D M C C harter. 
T he D M C will e val uate treat me nt gr o u ps f or p ossi ble tre n ds i n A Es, 
det er mi ne w het h er t he b asic pr ot oc ol ass u m pti o ns re mai n v ali d, 
e val uate w het h er t he o v erall i nte grit y, scie ntific m erit a n d c o n d uct of 
t he cli nical trial re mai n acce pt a bl e, a n d ma ke rec o m m e n dati o ns t o t he 
S p o ns or. 
St atistic al 
C o nsi der ati o ns: 
E x pl orat or y statisti cal a nal yses will be p erf or me d usi n g met h o ds of 
des cri pti ve data a nal ysis. 
A n al ysis of s afet y:  Me d D R A c o de d, treat me nt e mer ge nt a d verse 
e ve nts ( T E A Es) will be ta b ulate d at t h e Preferre d Ter m ( P T) a n d t he 
S yste m Or ga n Cl ass ( S O C) le vels. Treat me nt gr o u p c o m p aris o ns of 
t he pr o p orti o n of patie nts wit h T E A Es will be b ase d o n Wils o n s c ore 
c o nfi de nce i nter vals. Pair wise gr o u p c o m paris o ns will be pr o vi de d at 
t he S O C le vel as w ell as f or t he e v e nts i d e ntifie d as l ocal t ol era bilit y 
meas ures ( c o u g h, w heezi n g, br o nc h os pas ms, t hr oat irritati o n, c ha n ge 
i n F E V1), wit h se parate a nal yses f or all e v e nts wit h o nset d uri n g t h e 
first 4 wee ks of treat me nt a n d f or e ve nts wit h o nset at a n y ti m e d uri n g 
ra n d o mize d treat me nt. C GI scales will be a nal yse d a n d c o m par e d 
bet wee n t he treat me nt gr o u ps. 
A n al ysis of effic ac y:  S pir o metric v ari a bles a n d S F- 3 6 sc ales will be 
a nal yze d a n d c o m pare d b et wee n t h e treat me nt gr o u ps usi n g mi xe d 
m o dels f or re p eate d meas ures ( M M R M). 
P h a r m ac o ki neti c m e as u res:  T h e statistical a n al ysis will be carrie d 
o ut b ase d o n a m ulti pli cati ve m o del f or A U C 0- 4 h a n d Cma x  val ues, 
w hile t ma x  a n d tr o u g h le vels will be e val u ate d o n t h e basis of a n 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 1 9  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
a d diti ve m o del. A nal yses of varia n ce will b e perf or m e d t o c o m pare 
t he treat me nt gr o u ps. 
S a m ple size d eter mi n ati o n:  T he sa m ple si ze f or t h e st u d y was 
esta blis he d base d o n c o nsi derati o ns of feasi bilit y rat her t ha n o n p o wer 
calc ul ati o ns. A t ot al of 2 4  p atie nts ( 3 ar ms x 8 p atie nts eac h) are 
pla n n e d t o b e ra n d o mize d. 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 2 2  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
T he first st u dies of a n i n hale d i m m u n os u p pressi ve f or B O S were c o n d ucte d i n p atie nts wit h l u n g 
tra ns pla nt ati o n. T h ese st u di es use d c ycl os p ori n e i n a f or m ulati o n t h at c o nt ai ne d pr o p yle n e gl yc ol 
( Cs A- pr o p yl e ne gl y c ol [ Cs A- P G]). I n t h ese st u di es, Cs A- P G s h o we d p o or t olera bilit y d ue t o t he 
h y per os m olalit y of t he P G f or m ulati o n a n d its pr o pe nsit y t o ca us e air wa y i nfla m mati o n. H o we v er, 
efficac y res ults fr o m cli nical trials e val uati n g pre ve nti o n of B O S were pr o misi n g [ Iac o n o 1 9 9 6; 
Iac o n o 2 0 0 6]. 
Wit h t he g oal of i n creasi n g t olera bilit y as w ell as i m pr o vi n g air wa y de p ositi o n, a li p os o mal 
f or m ulati o n of Cs A ( L- Cs A) was d e vel o pe d. L- Cs A als o was f or m ulate d s pecificall y f or use wit h 
t he 
 N e b ulizer S yste m ( L- Cs A  
) f or o pti mal aer os ol d y n a mics. 
T wi ce dail y ( bi d) i n h alati o n of L- Cs A was w ell t olerate d i n a 2- year pre ve nti o n st u d y a n d a 6-
m o nt h treat me nt st u d y of B O S after l u n g tra ns pla nt. T here are o ver 1 1 0 0 pati e nt m o nt hs of 
e x perie n ce wit h L- Cs A i n l u n g tra ns pl a nt reci pie nts wit h B O S. T his st u d y will be t h e first st u d y 
t o e val uat e safet y a n d t ol era bilit y of L- Cs A i n pati e nts wit h B O S f oll o wi n g all o- H S C T.   
C CI
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 2 3  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
6  B A C K G R O U N D I N F O R M A TI O N 
6. 1  I n v e sti g ati o n al M e di ci n al P r o d u ct 
T he I n vesti gati o nal Me di ci nal Pr o d uct (I M P) is a dr u g/ de vice c o m bi n ati o n c o nsisti n g of L- Cs A 
a n d t he L- Cs A  
. 
6. 1. 1  D r u g C o m p o n e nt 
L- Cs A c o nsists of t h e acti ve s u bsta nce Cs A a n d e xci pie nts as des cri b e d i n t h e I n vesti gat or’s
Br oc h ure (I B). L- Cs A is a l y o p hilisate f or rec o nstit uti o n wit h 0. 2 5 % sali ne. T he f or m ulati o n is
de vel o pe d f or i n halati o n use a n d is t h eref ore a dj uste d t o a p h ysi ol o gical t olera ble v al u e of p H 6. 5
± 0. 3 a n d a n os m olalit y of 4 3 0- 5 5 0 m Os m ol/ k g i n t h e rec o nstit ut e d f or m ulati o n.
T he li p os o me size i n t he rec o nstit ute d f or m ul ati o n is i n t he ra n ge of 4 0- 1 0 0 n m wit h a 
p ol y dis p ersit y i n de x ( PI) of n ot m ore t h a n 0. 5 0, w hic h i n dicates t he wi dt h of t h e size distri b uti o n. 
PI val ues a b o ve 0. 5 i n dicate a br o a d distri b uti o n. 
T he d oses of 0 m g a n d 1 0 m g L- Cs A are rec o nstit ute d i n a t otal v ol u me of 2. 5 m L. T he 5 m g L-
Cs A d ose is rec o nstit ut e d i n a t otal v ol u me of 1. 2 5 ml. T he e ntire v ol u m e of t h e rec o nstit ut e d 
s ol uti o n is use d per aer os ol a d mi nistrati o n.  
A d diti o n al i nf or mati o n ca n be f o u n d i n t he I B.  
6. 1. 2  D e vi c e C o m p o n e nt 
T he L- Cs A  
 (
) utilizes a ne w tec h n ol o g y of n e b uli zi n g 
li q ui d dr u gs wit h a perf orate d vi brati n g me m bra ne res ulti n g i n a n aer os ol wit h a l o w ballistic 
m o me nt u m a n d a hi g h perce nta g e of dr o plets i n a res pira ble size ra n g e of 3- 5 µ m.  
T he L- Cs A  
 t o be use d i n t his cli nical trial is a m o difi e d v ersi o n of t h e  
  
 
Ne b ulizer S yste m f or a n o pti mize d deli ver y of t he i n v esti g ati o n al dr u g f or t he desi g nate d p atie nt 
gr o u p. T he c o nfi g urati o n of t he o pti mize d L- Cs A  
h as a hi g h deli vere d d ose, s h ort 
ne b ulizati o n ti me a n d i n hi bits c o nta mi n ati o n of t he e n vir o n me nt b y usi n g a n e x hal ati o n filt er. T he 
de vice is C E- mar k e d i n E ur o pe. T he L- Cs A  
was use d i n t h e n o ncli nical a n d cli nical trials 
of L- Cs A.  
A d diti o n al i nf or mati o n ca n be f o u n d i n t he I B. 
6. 1. 3  N o n cli ni c al D at a 
F or s yste mic a d mi nistrati o n of Cs A, t he n o ncli ni cal p har m ac ol o gic, p har mac o ki neti c ( P K), a n d 
t o xicit y pr ofiles of s yste mic Cs A are w ell esta blis h e d [U K S m P C Cicl os p ori n A ( Ne oral ® )]. 
C CI
C CI
C CI
C CI
C CI
C CI
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 2 4  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
F or aer os olize d a d mi nistrati o n of L- Cs A, a d diti o n al n o ncli nical st u dies ha ve bee n c o n d ucte d wit h 
L- Cs A. I m p orta ntl y, L- Cs A i n hi bite d T-cell pr oliferati o n i n sti m ulate d h u ma n peri p h eral bl o o d
m o n o n uclear cells. Acr oss 3 n o ncli ni cal t o xic ol o g y st u dies i n rats, aer os olize d L- Cs A gi ve n as
4- da y, 6- wee k, a n d 2 6- wee k re peate d a p plicati o ns of u p t o 2. 6 m g/ k g/ da y, n o d ose-li miti n g
t o xicit y occ urre d. T he n o- o bser v e d-a d verse-effect-le vel is c o nsi dere d t o be 2. 0 m g/ k g/ da y via
i n h al ati o n f or c hr o nic a p plicati o n base d o n t he ma xi m u m d osa ge ac hie ve d i n t h e 2 6- wee k
i n h al ati o n st u d y i n rats.
N o ncli ni cal a n d cli nical data t o d ate wit h L- Cs A s h o w ne gli gi ble i n crease i n ser u m l e vels of 
calci n e uri n i n hi bit ors a n d d o n ot s h o w a n i n creas e d ris k of n e p hr ot o xicit y, res pirat or y i nfecti o ns, 
or mali g na ncies. 
A d diti o n al i nf or mati o n ca n be f o u n d i n t he I B. 
6. 1. 4  Cli ni c al E x p eri e n c e 
L- Cs A h as bee n e v al uate d i n 3 cli nical trials i n a d ult pati e nts w h o recei ve d a si n gle-l u n g
tra ns pla nt ati o n ( S L T) or d o u ble-l u n g tra ns pla ntati o n ( D L T): ( 1) a P hase 1 b st u d y of t h e d e p ositi o n
a n d P K of aer os olize d L- Cs A i n pati e nts wit h l u n g tra ns pla nt ati o n ( G 0 3 5. 0 1 1); ( 2) a P hase 3 st u d y
of t he efficac y, safet y, a n d P K of t h e a d diti o n of aer os oliz e d L- Cs A t o sta n dar d of care ( S o C)
s yste mic i m m u n os u p pressi o n t h era p y vs aer os olize d pl ace b o pl us S o C t h era p y i n t he pre v e nti o n
of B O S f oll o wi n g l u n g tra ns pla ntati o n ( 1 2 0 1 1. 2 0 1; st u d y was ter mi nate d earl y f or b usi ness
reas o ns); a n d ( 3) a n i n vesti g at or-i nitiate d st u d y of t he efficac y, safet y, a n d P K of t h e a d diti o n of
aer os oli ze d L- Cs A t o S o C s yste mic i m m u n os u p pressi o n t hera p y vs S o C t hera p y al o ne i n t he
treat me nt of B O S f oll o wi n g l u n g tra ns pla ntati o n ( AI 0 0 1). C oll ecti vel y, t hese st u dies pr o vi d e d
safet y, efficac y, a n d P K dat a t o s u p p ort f urt her e v al uati o n i n 2 P hase 3 st u dies of t he effic ac y a n d
safet y of t h e a d diti o n of aer os olize d L- Cs A t o S o C s yste mic i m m u n os u p pressi o n t hera p y vs S o C
t hera p y al o ne f or t h e treat me nt of B O S f oll o wi n g S L T ( B T – L- Cs A – 3 0 1 – S L T) or d o u bl e l u n g
tra ns pla nt ati o n ( B T – L- Cs A – 3 0 2 – D L T). I n partic ul ar:

T he P hase 1 b l u n g de p ositi o n st u d y ( G 0 3 5. 0 1 1) s h o we d t hat i n halati o n of 1 0 m g a n d 2 0 m g
L- Cs A via t he L- Cs A  
w o ul d res ult i n s ufficie nt peri p heral l u n g de p ositi o n of L- Cs A
( ≥1 5 m g L- Cs A/ wee k) i n l u n g tra ns pla nt reci pi e nts. Aer os ol a p pli cati o n of 1 0 m g L- Cs A was
ass ociate d wit h a n acce pt a bl e i n hal ati o n ti me of a p pr o xi matel y 9 mi n utes.

I n t he P h ase 3 st u d y i n v esti gati n g pre v e nti o n of B O S ( 1 2 0 1 1. 2 0 1), t h e pri mar y e n d p oi nt f or
pre ve nti o n of B O S ( B O S-fre e s ur vi v al) was n ot met, alt h o u g h efficac y res ults ma y ha ve bee n
c o nf o u n de d b y earl y t er mi nati o n of t he trial d u e t o b usi ness reas o ns.

I n t h e i n v esti g at or-i nitiate d st u d y i n vesti gati n g treat me nt of B O S ( AI 0 0 1), t h e res p o n d er
a nal ysis of B O S pr o gressi o n-free s ur vi v al base d o n Ka pla n- Meier esti mates re veale d a
treat me nt s uccess rat e of 8 1. 8 % i n t he L- Cs A + S o C gr o u p ( 9 of 1 1 p atie nts) a n d 5 0 % i n t he
c o ntr ol gr o u p ( 5 of 1 0 patie nts). F E V 1 sl o pe a nal yses o v er ti me res ulte d i n m o nt hl y d ecre me nts
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
of - 0. 0 0 8 L i n t h e L- Cs A + S o C gr o u p a n d - 0. 0 4 5 L i n t he c o ntr ol gr o u p. T his differe nce 
tra nslate d i nt o a n a n n ual preser vati o n of F E V1 of m ore t ha n 4 0 0 m L i n t he L- Cs A + S o C 
gr o u p, c o nsiste nt wit h a mea ni n gf ul sl o wi n g of t h e pr o gressi o n of t he dise ase. T h e be n eficial 
effect of L- Cs A w as als o refle cte d i n c o nsiste ntl y p ositi ve tre n ds fa v ori n g t h e L- Cs A + S o C 
gr o u p i n ot h er l u n g f u ncti o n para meters, i ncl u di n g f orce d mi de x pirat or y fl o w ( F E F 2 5- 7 5), F V C, 
a n d F E V 1 % pre dicte d. Fi ve years after t he st art of St u d y AI 0 0 1 (as of Se pte m ber 2 0 1 7), 5 of 
1 1 pati e nts treate d wit h L- Cs A + S o C were ali v e, c o m p are d wit h 0 of 1 0 c o ntr ol pati e nts w h o 
recei v e d S o C al o ne. 
Wit h res pect  t o s afet y, i n hale d L- Cs A  w as g e nerall y well t olerate d  acr oss  all cli nical tri als. T he 
o verall a nal ysis of a d verse e ve nts ( A Es), seri o us a d verse e ve nts ( S A Es), a n d deat hs s h o we d t hat 
t hese were m ostl y ass ociate d wit h p ul m o nar y a n d i m m u n ol o gical e ve nts, w hic h are e x pe cte d i n a 
p o p ulati o n of l u n g tra ns pla nt a n d i m m u n os u p presse d patie nts a n d di d n ot differ fr o m t he c o ntr ol 
ar ms. Neit her la b orat or y val ues n or vital si g ns assess me nts s h o we d a n y cli nicall y rele va nt c h a n ges 
o ver ti me. 
N o ncli ni ca l a nd cli ni cal dat a t o d ate wit h L- C s A d o n o t s h o w a n i ncrease d ris k of ne p hr ot o xi cit y, 
res pirat or y i nfecti o ns, or mali g na ncies. 
A d diti o n a l i nf or mati o n ca n be f o u n d i n the I B. 
6. 1. 5  S u m m a r y of K n o w n a n d P ot e nti a l Ri s k s a n d B e n efit s 
C hr o nic G v H D, w hic h 
ma nifests cli nicall y i n t he res pirat or y tract as B O S, is a c o m m o n 
c o m plicati o n of he mat o p oietic ste m cell tra ns pla ntati o n ( H S C T) ( A g uilar 2 0 1 6 ; Ber ger o n 2 0 1 3 ). 
De vel o p me nt of B O S after H S C T is a maj or ca use of m or bi dit y a n d m ortalit y; b e nefi ci al treat me nt 
o pti o ns are li mite d t hera pe utic i nter ve nti o ns w hic h ha ve n ot bee n vali date d b y well-c o n d ucte d 
cli nical trials ( A g uilar 2 0 1 6). Wit h t he dia g n osis of B O S p ost-tra ns pla ntati o n a 1. 6-f ol d i ncrease 
i n ris k f or m ortalit y is c o nferre d. 
Br o nc hi olitis  o blitera ns  (a di a g n osis  ma de  b y  hist o pat h ol o g y)   a n d B O S  (a dia g n osis  ma de 
cli nicall y i n hi g h  ris k p ati e nts)  is t h e sa me u n derl yi n g  disease  re gar dl ess of t he  i n citi n g i nj ur y. 
[Bar k er N EJ M 2 0 1 4 ].  Earl y efficac y st u dies h a ve d e m o nstrate d a b e nefi ci al effe ct of L- Cs A f or 
t he treat me nt of B O S i n p atie nts wit h B O S f oll o wi n g l u n g tra ns pla nt ati o n.   
T his trial is t he first t o e val u ate t h e safet y, t olera bilit y, e x pl orat or y effic ac y a n d p har mac o ki n etics 
of L- Cs A f or t he tre at me nt of B O S i n p atie nts wit h B O S f oll o wi n g all o ge neic he mat o p oi etic ste m 
cell tra ns pla ntati o n. T he p har mac o ki neti c pr ofile of L- Cs A has bee n e val u ate d i n 3 cli nical trials 
i n a d ult patie nts w h o recei ve d a si n gle-l u n g tra ns pla ntati o n ( S L T) or d o u ble-l u n g tra ns pl a ntati o n 
( D L T). I n t he c urre nt trial f or t h e first ti me t h e p h ar ma c o ki neti c  pr ofile  will be e v al uate d i n  p atie nts 
wit h  B O S  f oll o wi n g all o ge neic  H S C T  t o g et  i nf or mati o n of  t he P K  pr ofile  i n t his p atie nt 
p o p ulati o n a n d t o s u p p ort f urt h er e v al uati o n i n t his i n dic ati o n.  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 2 5  of 8 2  
Cli nica l Tr ial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0 ; 3 0 A pri l 2 0 2 1 
 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 2 6  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
P atie nts i n cli nical trials g e nerall y ca n n ot e x pect t o recei ve direct b e nefit fr o m treat me nt d uri n g 
partici pati o n, as cli ni cal tri als are desi g ne d t o pr o vi de i nf or mati o n a b o ut t he safet y a n d 
effecti v e ness of a n i n v esti g ati o n al me di ci ne.  
T here are p ossi ble ris ks a n d dis c o mf orts ass o ciate d wit h t h e bl o o d dra w f or P K a nal ysis. T he 
ge neral k n o w n ris ks i n cl u di n g disc o mf ort at t h e p u ncti o n site of t he bl o o d dra w ca n be br uisi n g, 
blee di n g, i nfecti o n, a n d rarel y, fai nti n g or ner ve d a ma ge. 
L- Cs A is c o ntrai n dicate d i n pers o ns wit h a hist or y of aller g y t o c ycl os p ori n e or t o a n y of t he
i n gre die nts i n t h e f or m ul ati o n.
S yste mic f or m ulati o ns of c ycl os p ori ne are k n o w n t o ha ve c o ntrai n dicati o ns relate d t o St. J o h n’s 
W ort a n d me dici nes t h at are s u bstrates of P- g p or or g a ni c a ni o n-tra ns p orti n g p ol y pe pti de ( O A T P). 
Pri or st u dies of L- Cs A ha ve de m o nstrate d ne gli ble ser u m le vels a n d n o acc u m ulati o n o ver ti me of 
c ycl os p ori n e.  N o p ote nti al dr u g i nt eracti o ns d uri n g cli nical st u dies ha ve bee n re p orte d. Dr u g- dr u g 
i nteracti o ns are u nli kel y beca use t h e s yste mic c ycl os p ori ne e x p os ure wit h L- Cs A is m uc h l o wer 
t ha n f or a p pr o ve d t hera p e uti c d oses of oral a n d I V c y cl os p ori ne.  
Base d o n cli ni cal e x p erie nce t o dat e 
wit h L- Cs A, t h ere ar e n o s pecial preca uti o ns f or 
a d mi nistrati o n of L- Cs A i n cli nical st u dies usi n g t he dr u g pr o d uct a n d de vice c o m p o n e nt. 
P har m ac o ki netic st u dies ha ve s h o w n t hat t h e s yst e mic c ycl os p ori n e e x p os ure wit h L- Cs A is m u c h 
l o wer t h a n f or a p pr o ve d t hera p e uti c d oses of oral a n d I V c ycl os p ori ne. C o ns ult oral or I V 
c ycl os p ori n e prescri bi n g i nf or mati o n f or vari o us preca uti o ns ass oci at e d wit h t h e hi g her s yste mic 
e x p os ures t hat ma y occ ur after oral or I V d osi n g of c ycl os p ori ne. 
P atie nts w h o are gi v e n L- Cs A ma y als o recei v e ot her i n hale d me dicati o ns. 
W he n L- Cs A is 
a d mi nistere d c o nc o mit a ntl y wit h ot h er i n h al e d me dici n al pr o d ucts, t he or d er of i n halati o n s h o ul d 
be as f oll o ws: i n hale d br o nc h o dilat ors, i n hale d c orti c oster oi ds, i n h ale d a ntif u n g als/ a nti bi otics, 
a n d t he n i n hale d L- Cs A. L- Cs A i n h alati o n s h o ul d o cc ur at l east 1 h o ur after a d mi nistrati o n of a n y 
ot h er i n hal e d me dicati o ns. 
N o e ve nt ass ociate d wit h o ver d ose has bee n re p orte d i n a n y L- Cs A cli nical trial t o d ate. As has 
bee n de m o nstrate d t hr o u g h P K st u dies, s yste mic e x p os ure is si g nifica ntl y l o w c o m pare d wit h t he 
a p pr o v e d t hera pe utic d os es of oral or I V c y cl os p ori ne.  
C O VI D- 1 9 c o nsi derati o ns: At t his ti m e, it is u n k n o w n if s p ecific patie nt p o p ulati o ns are at hi g h er 
ris k of S A R S- C o V- 2 i nfecti o n. F urt her m ore, t he me dical s ur v eilla nce of tra ns pla nte d p atie nts is 
alrea d y bas e d o n s pecifi c preca uti o ns t y pical t o all patie nts t a ki n g i m m u n os u p pressi v e a ge nts. T he 
me di cal val ue of t his trial re mai ns u nc ha n g e d.  

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 2 8  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
T h us, L- Cs A 5 m g bi d is b ei n g e x pl ore d i n t his s p ecific p o p ulati o n.  A nal o u g o usl y, c hil dre n a ge 
6- 9 y ears ha ve s uffi ci e ntl y l o wer br o nc hial air wa y s urface area c o m pare d t o a d ults wit h t w o
f u ncti o ni n g l u n gs a n d t h us L- Cs A 5 m g bi d will be e x pl ore d i n f ut ure pe diatric st u dies t hat i ncl u de
t his a ge gr o u p.
T o date, t here is 1 1 0 0 patie nts- m o nt hs of t olera bilit y d ata f or L- Cs A deli vere d t o patie nts w h o are 
l u n g tra ns pla nt reci pie nts.  It is a ntici pate d t h at L- Cs A 1 0 m g bi d will be well t olerate d i n p atie nts 
wit h nati ve l u n gs affecte d b y B O S as well.  H o we ver, t he c urre nt st u d y will c o m pare t he 
t olera bilit y of L- Cs A 1 0 m g vs 5 m g bi d i n t he tar get patie nt p o p ulati o n.    
6. 1. 7  St at e m e nt of C o m pli a n c e 
T his st u d y will be c o n d ucte d i n c o m plia nce wit h t he pr ot oc ol a p pr o v e d b y t he a p pr o priate Et hics 
C o m mitt ees ( E C) a n d healt h a ut h orities, acc or di n g t o I nter n ati o nal C o m mittee o n Har m o nisati o n 
(I C H) a n d a p plic a ble G o o d Cli ni cal Practi ce ( G C P) sta n dar ds, a n d i n acc or da nce wit h t h e et hical 
pri nci pl es t h at ha ve t heir ori gi n i n t h e Declarati o n of Helsi n ki ( F ort aleza, 2 0 1 3). 
6. 1. 8  P o p ul ati o n 
Reci pie nts of a n all o g e neic st e m cell tra ns pla nt, ≥ 1 8 years of a ge, wit h d oc u me nt e d dia g n osis of 
c G v H D i n a n y or ga n ot h er t ha n t he l u n g a n d c o nfir me d dia g n osis of B O S.  
7  T RI A L O BJ E C TI V E S A N D P U R P O S E 
7. 1  T ri al O bj e cti v e s 
7. 1. 1  P ri m a r y O bj e cti v e: 
T he pri mar y o bjecti v e of t his st u d y is t o assess t he t olera bilit y a n d safet y of t w o d ose l e vels of 
aer os oli ze d L- Cs A vs place b o i n a d diti o n t o S o C t hera p y f or B O S i n a d ult all o- H S C T reci pi e nts. 
7. 1. 2  S e c o n d a r y O bj e cti v e s: 
T he sec o n d ar y o bjecti ves of t his st u d y are t o assess P K a n d e x pl orat or y efficac y a n d q ualit y of life 
of t w o d ose le vels of aer os olize d L- Cs A vs place b o i n a d diti o n t o S o C t h era p y f or B O S i n a d ult 
all o- H S C T reci pi e nts. 
7. 2  P u r p o s e of t h e T ri al 
C urre ntl y, t here is n o a p pr o ve d me di ci nal pr o d uct f or t h e pre ve nti o n or treat me nt of B O S after 
all o ge neic ste m cell tra ns pl a nt. All atte m pts f or t h era pe utic i nt er ve nti o n t o alter t he i nci de nce or 
t he pr o gressi o n of B O S are e m pirical a n d i n vesti gati o nal. T his circ u msta nce e x plai ns t h e di v ersit y 
a n d dis har m o n y of t hera pe utic c o nce pts i n t he H S C T c o m m u nit y. T here are S o C practices 
esta blis he d t o ma na ge B O S t h at d e vel o ps after all o- H S C T, b ut n o t h era pe utic re gi me ns h a ve 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 2 9  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
c o ncl usi vel y de m o nstrate d e vi d e nce of si g nifica nt be nefit i n t he pr e v e nti o n or treat me nt of B O S. 
A de q uatel y d esi g ne d a n d e xec ute d, ra n d o mi ze d, c o ntr olle d trials t o assess efficac y a n d safet y are 
nee de d t o i d e ntif y o pti mal t hera pies f or esta blis he d B O S.  
T he h y p ot h esis t hat l o cal d eli ver y of Cs A b y aer os ol i n halati o n will ac hie ve hi g her i ntra p ul m o nar y 
c o nce ntrati o n t ha n b y s yste mic a d mi nistrati o n al o ne, wit h li mit e d t o xicit y c o m pare d t o si milar 
s yste mic d oses d ue t o mi ni m al a bs or pti o n of dr u g i nt o t h e bl o o d circ ul ati o n has bee n s u bsta ntiat e d 
b y t h e st u di es descri be d i n S ecti o n 6. 1. 4 . 
I n p artic ular, t h e i n v esti g at or-i nitiate d trial AI 0 0 1 pr o vi d e d e vi de n ce of L- Cs A’s p ote ntial t o dela y 
pr o gressi o n of B O S w he n a d mi nistere d as a d d- o n i n h alati o n t h era p y as c o m p are d t o S o C f or 
s yste mic B O S t h era p y. I n c o m bi nati o n wit h t h e acce pta bl e safet y pr ofile of L- Cs A, o bser ve d i n 
cli nical trial 1 2 0 1 1. 2 0 1 w he n patie nts were treat e d f or u p t o 2 years, L- Cs A has t he p ote ntial t o 
pr o vi d e s u peri or efficac y o ver c urre nt b est practic e B O S t h era p y.  
T he p ur p ose of t his trial is t o assess t he safet y a n d t olera bilit y of L- Cs A i n patie nts wit h all o- H S C T 
as c urre nt u n d ersta n di n g ass u mes i de ntical pat h o p h ysi ol o g y of B O S after l u n g tr a ns pla nt a n d 
H S C T.  

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 3 0  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
8  T RI A L D E SI G N 
8. 1  E n d p oi nts 
8. 1. 1  P ri m a r y A ss e ss m e nt 
I M P t olera bilit y a n d safet y d uri n g t h e first 4 wee ks of treat me nt. 
8. 1. 2  S e c o n d a r y A s s e s s m e nt s 
I M P t olera bilit y a n d safet y d uri n g t he first 1 2 wee ks of treat me nt; Cs A P K. 
8. 1. 3  E x pl o r at o r y Effi c a c y A s s es s m e nt 

F E V 1 % pre dicte d at ra n d o mizati o n c o m pare d t o Wee k 2, Wee k 4, Wee k 8, a n d Wee k 1 2

F E V 1/ F V C at ra n d o mizati o n c o m p are d t o Wee k 2, Wee k 4, Wee k 8, a n d Wee k 1 2

S F- 3 6 Q ualit y of Life Q u esti o n naire at Wee k 2, W ee k 4, Wee k 8, a n d We e k 1 2

C ha n ges i n t he d ose of c ortic oster oi ds a n d i m m u n os u p pressi v e t hera p y a d mi nistere d
t hr o u g h o ut trial d urati o n
8. 1. 4  I M P T ol e r a bilit y P a r a m et e r s 

L ocal T olera bilit y :
o
C o u g h
o
W heezi n g
o
Br o nc h os pas m
o
T hr oat irritati o n
o
C ha n ge i n F E V 1

O verall T ol era bilit y :
o
Cli ni cal Gl o b al I m pressi o ns ( C GI) scale
o
I n v esti gat or’s t olera bilit y assess me nt at Visit 3 a n d Visit 5
8. 1. 5  S af et y P a r a m et er s 

A Es

S A Es

Cli ni cal la b orat or y val u es

Vit al si g ns

P h ysical E xa mi nati o n
8. 1. 6  P h a r m a c o ki n eti c P a r a m et e r s

P K: ( Wee k 0) at pre- d ose; directl y after e n d of i n h alati o n; 1 5, 3 0, a n d 4 5 mi n utes, a n d 1,
1. 5, 2, a n d 4 h o urs aft er e n d of i n halati o n:
o
C ma x

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 3 1  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
o
tma x
o
A U C 0- 4 h

W h ole bl o o d tr o u g h le vels (at Wee ks 2, 4, 8, a n d 1 2)
8. 2  T ri al D e si g n 
T his is a P hase II pr os pecti ve, m ulti-ce nt er, si n gl e- bli n d, ra n d o mize d cli nical trial e v al uati n g 
safet y a n d t ol era bilit y i n i n a d ult reci pie nts of a n all o- H S C T wit h B O S. T we nt y-f o ur patie nts are 
pla n n e d f or e nr oll me nt. T he cli nical trial will be c o n d uct e d i n u p t o 2 0 ce nters i n E ur o p e. Patie nts 
will be ra n d o ml y all oc at e d 1: 1: 1 t o recei ve eit h er L- Cs A ( 1 0 m g bi d or 5 m g bi d) pl us S o C or 0 
m g L- Cs A ( place b o) pl us S o C. I M P will be a d mi nist ere d f or u p t o 1 2 wee ks. 
8. 3  St r atifi c ati o n a n d R a n d o mi z ati o n 
At t he baseli ne visit (see  S ecti o n 1 3. 2. 2), aft er all i ncl usi o n a n d e xcl usi o n criteria ha v e bee n f ull y 
e val uate d, eli gi bl e patie nts will be assi g ne d t o o ne of t h e t hree treat me nt gr o u ps at a rati o of 1: 1: 1 
b y mea ns of bl oc k ra n d o mizati o n. Ra n d o mizati o n will be perf or me d b y a statisti cia n ot h er wise 
n ot i n v ol ve d wit h t he trial, usi n g v ali d ate d ra n d o m n u m ber ge nerat or s oft w are. T he r a n d o mi zati o n 
c o de of eac h p atie nt will be pr o vi d e d t o t he I n vesti gat or after c o m plia nce wit h all eli gi bilit y criteria 
has bee n c o nfir me d, t hr o u g h t h e electr o ni c C ase Re p ort F or m (e C R F) i nt o w hic h t he ge nerat e d 
ra n d o m c o d e list will b e u pl o a de d. Eac h p atie nt will be assi g ne d a n u m b er as part of t he 
ra n d o mizati o n pr o cess. T he n u m b er assi g ne d t o a patie nt will bec o me t h at pati e nt’s u ni q ue 
treat me nt n u m ber t hr o u g h o ut t he cli nical trial a n d ca n n ot be re-assi g ne d t o a n ot her p atie nt. 
N o stratificati o n will b e p erf or m e d. 
8. 3. 1  Bli n di n g 
T his is a si n gle- bli n d trial. D ue t o t he differe nt a p peara n ce of t he t hree teste d stre n gt hs of I M P, a 
f ull bli n di n g of t he st u d y was n ot p ossi ble. O nl y t he ra n d o mize d st u d y p atie nts will be bli n d e d t o 
st u d y treat me nt assi g n me nt.  F or details of t he bli n di n g of t he Data M o nit ori n g C o m mitt ee 
me m bers, see  Se cti o n 1 2. 2.  
8. 3. 2  I n v e sti g ati o n al M e di ci n al P r o d u ct: T r e at m e nt, D os a g e a n d A d mi ni st r ati o n 
8. 3. 2. 1  F o r m ul ati o n of L- Cs A 
T he c o m p ositi o n of t h e L- Cs A f or m ul ati o n is s h o w n i n Ta ble 1 . It is a l y o p hilis ate i nte n de d f or 
rec o nstit uti o n wit h 0. 2 5 % N a Cl. T he f or m ulati o n is de vel o pe d f or i n h al ati o n use a n d a dj uste d t o 
p h ysi ol o gi cal t olera ble v al ues of p H ( 6. 5 ±  0. 3) a n d os m olalit y 4 3 0- 5 5 0 m Os m ol/ k g). 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 3 2  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
T a bl e 1: Q u alit ati ve C o m p ositi o n of t he I M P 
I n gre die nt 
F u ncti o n 
Q u alit y 
C ycl os p ori ne A 
Acti ve i n gre die nt  
P h E ur 1 
Li p oi d S 1 0 0 
Carrier  
n o n c o m p e n dial 
P ol ys or bate 8 0 
S urfacta nt 
P h E ur 
Dis o di u m h y dr o g e n p h os p hate d o deca h y drate  
B uffer 
P h E ur 
S o di u m di h y dr o ge n p h os p hate di h y drat e 
B uffer 
P h E ur 
Dis o di u m e d etate di h y drate 
Sta bili zer 
P h E ur 
S u cr ose 
L y o pr otecta nt  
P h E ur 
Water 
Dis persi o n me di u m  
P h E ur/ U S P 2 
1: E ur o p ea n P h ar mac o peia 
2: U nite d States P h ar mac o peia 
T he p article si ze of t he li p os o mes is i n t h e ra n ge of 4 0- 1 0 0 n m wit h a PI of n ot m ore t h a n 0. 5 0, 
w hic h i n dicat es t he wi dt h of t h e size distri b uti o n. Val ues of p ol y dis persit y i n de x a b o ve 0. 5 i n dicate 
a br oa d distri b uti o n. F or c oll oi d al dis p erse s yste ms a PI of 0. 2 0 t o 0. 5 0 is a p pr o priate. 
T he I M P ( L- Cs A) a n d 0. 2 5 % Na Cl f or rec o nstit uti o n will be s u p plie d b y t he I M P d e p ot o n 
be half of t h e s p o ns or: 
 
 
 
Ger ma n y 
P P D

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 3 3  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
8. 3. 2. 2  T r e at m e nt a n d D os a g e 
After Scree ni n g, patie nts c o m pl yi n g wit h all i n cl usi o n a n d e xcl usi o n crit eri a (see Secti o ns 9. 1  
a n d 9. 2 ) will be ra n d o mi ze d t o o ne of t he f oll o wi n g treat me nts: 
Tre at me nt A ( L- Cs A 1 0 m g tr e at me nt pl us S o C): 
L- Cs A 1 0 m g/ 2. 5 m L bi d f or a ma xi m u m of 1 2 wee ks
pl us
S o C t h era p y
Tre at me nt B ( L- Cs A 5 m g tre at me nt pl us S o C): 
L- Cs A 5 m g/ 1. 2 5 m L bi d f or a ma xi m u m of 1 2 wee ks
pl us
S o C t h era p y
Tre at me nt C ( L- Cs A 0 m g ( Pl ace b o) pl us S o C ): 
L- Cs A 0 m g/ 2. 5 m L bi d f or a ma xi m u m of 1 2 we e ks
pl us
S o C t h era p y
8. 3. 2. 3  A d mi nist r ati o n of I M P 
I n cli nical trials 1 2 0 1 1. 2 0 1 a n d cli nical trial AI 0 0 1 t otali n g > 1 1 0 0 patie nt m o nt hs of e x p os ure, 
L- Cs A was w ell t olerat e d. Patie nts will be e d ucate d r e g ar di n g us e of t he L- Cs A  
 a n d
a d mi nistrati o n of t h e first d ose will be o bser v e d. At s u bse q ue nt st u d y visits, it will be re q uest e d
t hat t he p atie nt self-a d mi nist er a d ose of I M P w hil e o bser ve d b y st u d y p ers o n n el.
Eac h patie nt will recei v e t w o I M P a d mi nistrati o ns per d a y, o ne i n t h e m or ni n g a n d o ne i n t he 
e ve ni n g. T h e i n halati o ns are sc he d ul e d t o be ta ke n a p pr o xi matel y 1 2 h o urs ( b ut n ot less t ha n 
6 h o urs) a part, e. g., at 8: 0 0 a. m. a n d 8: 0 0 p. m. eac h da y. I nstr ucti o ns f or a d mi nistrati o n s h o ul d be 
f oll o we d as d escri be d i n t he I nstr ucti o ns F or Use. 
Ha n dli n g of I M P I n hal ati o n: 
Eac h p atie nt will o p e n a gl ass vial b y lifti n g u p t he plastic dis k/ca p, lifti n g u p t he metal fla p t o 
re m o ve t he metal ri n g, m etal ca p, a n d t he r u b ber st o p per. T he pl astic a m p o ule c o ntai ni n g 1. 2 ml 
or 2. 4 m L of t he 0. 2 5 % Na Cl as s ol ve nt will be o pe ne d b y t wisti n g t he hea d part se veral ti mes i n 
o ne directi o n. T h e N a Cl s ol uti o n will be s q ueeze d i nt o t h e glass vial c o ntai ni n g t he w hitis h 
l y o p hilisate ca ke. T he gl ass vial will be re-cl os e d wit h t he r u b b er st o p p er a n d s wirle d ge ntl y 
wit h o ut s pilli n g a n y li q ui d f or a mi ni m u m of 1 mi n ute a n d u p t o 5 mi n utes, u ntil t he visi ble 
particles are c o m pl etel y diss ol ve d. S h a ki n g of t h e vial m ust b e a v oi de d t o pre ve nt f o a mi n g of t he 
rec o nstit ute d s ol uti o n.  
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 3 4  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
Ne xt, t h e rec o nstit ute d I M P s h o ul d be p o ure d i nt o t he L- Cs A  
 c ha m b er. T he ne b ulizer 
s h o ul d be k e pt h oriz o ntal d uri n g o perati o n. D uri n g i n halati o n, t he pati e nt s h o ul d sit i n a n u pri g ht 
p ositi o n a n d i n hale a n d e x hale de e pl y t hr o u g h t he m o ut h piece of t he ne b uli zer wit h o ut i nterr u pti o n 
u ntil n e b uli zati o n s h uts off a ut o mati call y. T h e s ol uti o n is f or si n gl e use o nl y, a n d n o re mai ni n g 
s ol uti o n s h o ul d be l eft i n t h e glass vi al. All ot h er cli nical tri al materials, i n cl u di n g u n use d I M P, 
m ust be br o u g ht b ac k t o t he cli nical trial ce nter at eac h sc he d ul e d visit f or dr u g a n d d e vice 
acc o u nta bilit y. After c o m pleti o n of t h e i n h alati o n, t he patie nt s h o ul d re m o v e all e xcess I M P i n t he 
m o ut h a n d p har y n x b y ri nsi n g a n d gar gli n g wit h water a n d s u bse q u e ntl y dis c har gi n g t h e s ol uti o n. 
I nterr u pti o n of I M P I n h alati o n: 
If a patie nt n ee ds t o te m p oraril y i nterr u pt I M P i n halati o n (e. g., d ue t o c o u g hi n g), t h e p atie nt s h o ul d 
t ur n off t he de vice a n d t ur n it bac k o n w he n rea d y t o res u me i n hal ati o n.  
I M P ma y be te m p oraril y disc o nti n ue d as dee me d necessar y b y t he i n vesti gat or (see Secti o n 9. 3. 1 ) 
a n d will be d oc u me nte d i n t h e e C R F.  
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 3 5  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
8. 4  I n v e sti g ati o n al M e di ci n al P r o d u ct P a c k a gi n g, L a b eli n g a n d St o r a g e 
8. 4. 1  P a c k a gi n g a n d L a b eli n g of I M P 
P ac ka gi n g 
T he I M P will be pr o vi de d as 0 m g a n d 1 0 m g L- Cs A l y o p hilis ate i n glass vials t y p e I wit h gre y 
r u b b er st o p p ers a n d a n al u mi n u m ca p wit h a yell o w pl astic dis k a n d st ore d i n a n o uter pac ka gi n g 
b o x c o nsisti n g of 6 0 vi als wit h t h e L- Cs A/ place b o a n d 7 0 plastic a m p o ules c o nt ai ni n g 2. 4 m L 
0. 2 5 % N a Cl f or r ec o nstit uti o n. T he 5 m g L- Cs A l y o p hilisate will be s u p plie d i n glass vi als t y p e I 
wit h gre y r u b ber st o p pers a n d a n al u mi n u m ca p wit h a gree n plastic dis k a n d st ore d i n a n o uter 
pac ka gi n g b o x c o nsisti n g of 6 0 vi als wit h t he L- Cs A a n d 7 0 plasti c a m p o ules c o ntai ni n g 1. 2 m L 
0. 2 5 % N a Cl f or r ec o nstit uti o n. 
T he I M P will be la belle d i n c o m pli a n ce wit h G o o d M a n ufact uri n g Practice ( G M P) s p ecificati o ns 
acc or di n g t o a p plic a ble re g ulati o ns.  
8. 4. 2  St o r a g e 
T he u n o p e ne d I M P m ust be k e pt i n a sec ure, l oc k e d, te m perat ure-c o ntr olle d l ocati o n wit h access 
t o a ut h orize d st aff o nl y. I M P s h o ul d be st ore d n ot a b o ve 2 5 ° C pr otect e d fr o m li g ht.  
8. 4. 3  I n h al ati o n D e vi c e P a c k a gi n g 
T he I n vesti g ati o nal  
 Ne b ulizer S yst e m c o nsists of t he f oll o wi n g t w o pac ka ges: 
1) C o ntr oll er Kit
T he c o ntr oller kit will be pr o vi d e d at ra n d o miz ati o n visit a n d i ncl u des 
•
1 x e Trac k C o ntr oll er
•
1 x Ne b ulizer H a n dset i n cl u di n g c o n n ecti o n c or d, a n A C p o w er s u p pl y a n d
4 “ A A” b atteries
•
1 x Eas ycare clea ni n g ai d
•
1 x Carr yi n g ba g
•
1 x I nstr ucti o ns F or Us e
•
2 x Aer os ol Hea ds
2) 
 
 i n c o m bi nati o n wit h L- Cs A Kit bel o w
M o nt hl y S u p pl y – At E ac h f oll o wi n g Cli nic Visit
•
 
C CI
C C
C CI C CI
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 3 6  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
8. 5  St o p pi n g R ul es a n d Di s c o nti n u ati o n C rit eri a 
8. 5. 1  P ati e nt L e v el 
Re g ular ter mi nati o n of cli nical trial parti ci pati o n: 
T he i n vesti gati o nal treat me nt will be ter mi n ate d after 1 2 w ee ks ( E n d of Treat me nt [ E o T]). T he 
treat me nt peri o d will b e f oll o we d b y a 2- wee k f oll o w- u p peri o d ( E n d of St u d y [ E o S]). A n y p atie nts 
wit h o n g oi n g A Es a n d S A Es will b e f oll o we d- u p u ntil rec o v er y or st a bilizati o n of t he A E/ S A E.  
Pre mat ure t er mi nati o n of cli nical tri al partici pati o n: 

P atie nts ma y disc o nti n ue partici pati o n i n t he cli nical tri al at a n y ti me b y re v o ki n g t heir
i nf or me d c o nse nt.

T he I n v esti gat or ma y wit h dra w a patie nt at a n y ti me if it is i n t h e b est i nterest of t he p atie nt
base d u p o n cli nical ass ess me nts.

P atie nt is l ost t o f oll o w- u p

Pre g na nc y (t h e pati e nt will be f oll o we d via  t h e s p o ns or’s safet y d e part me nt)

T er mi nati o n of t he cli nic al trial as a w h ole b y Z a m b o n S p A as d efi n e d i n secti o n 8. 5. 3.
If t he partici p a nt fails t o ret ur n f or cli nical f oll o w- u p, t he patie nt will be c o nt act e d b y t el e p h o ne or 
a letter will be se nt re q u esti n g a cli ni c visit ( E o S), a n d t he reas o n f or n o n-c o m pli a n ce will be 
d oc u me nt e d. T he fi n al visit will e nc o m pass t he ass ess m e nts liste d u n d er E o S Visit ( Visit 6; 
S ecti o n 1 3. 2. 5 ). A d diti o nall y, use d a n d u n use d I M P a n d i n h alati o n de vice will be retrie ve d, if 
a p pli ca ble. Z a m b o n S p A will be n otifie d t h at t he p ati e nt has ter mi n at e d cli nical trial p artici p ati o n. 
8. 5. 2  C e nt e r L e v el 
Re g ular ter mi nati o n of cli nical trial ce nters: 
All ce nters will b e cl ose d after patie nts h a ve c o m plete d cli nical trial parti ci pati o n a n d t he data base 
has bee n l oc k e d. 
Pre mat ure t er mi nati o n of a cli nical trial ce nter: 
T he s p o ns or ma y cl os e a ce nt er f or t h e f oll o wi n g reas o ns: 

I n case of re p eate d a n d c o nti n u o us vi olati o ns of G C P a n d a p plica ble re g ul ati o ns

I n acc urate or i nc o m plete d ata c ollecti o n

Falsificati o n of rec or ds

Fail ure t o a d h ere t o t h e pr ot oc ol

Or ga nizati o nal or str uct ural c ha n g es i n t h e ce nter w hic h c halle n g e t he re q uire me nts or
q u alificati o n f or cli nical trial partici pati o n (e. g., c ha n ge of i n vesti gat or, s hift of ce nter
acti vities)

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 3 7  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
I n cas e a ce nter is cl ose d f or a n y of t he reas o ns a b o ve, eff orts will b e ma de t o e ns ure t he safet y 
a n d data r elia bilit y of o n g oi n g patie nts u ntil cli nical tri al c o m pleti o n. 
8. 5. 3  Cli ni c al T ri al L e v el 
Re g ular ter mi nati o n of t h e cli nical trial: 
T he cli nical trial will be c o nsi dere d c o m plete aft er t h e pre- defi ne d n u m b er of p atie nts h a ve b ee n 
ra n d o mize d a n d c o m plete d t h eir cli nical trial partici pati o n. T he last visit of t he l ast p atie nt is t h e 
defi n e d e n d of t h e st u d y. 
Pre mat ure t er mi nati o n of t he cli nical trial: 

S eri o us safet y c o ncer ns t hat i n dicate a p ote ntial healt h h azar d ca us e d b y treat me nt wit h t he
I M P (ter mi nati o n d ue t o s afet y iss ues)

T he cli nical trial ma y b e dis c o nti n ue d at a n y ti me f or reas o ns s u c h as b ut n ot li mite d t o me dical
f utilit y a n d a d mi nistrati ve reas o ns, u p o n t h e dis creti o n of Za m b o n S p A.
I n t his case, a n a b bre vi ate d cli ni cal st u d y re p ort will be re p orte d t o C o m p ete nt A ut h orities a n d 
Et hi cs C o m mittees acc or di n g t o a p plica ble re g ulat or y re q uire m e nts. T he I n v esti g at or m ust n otif y 
his/ h er E C of cli nical trial cl os ure. 
8. 6  I n v e sti g ati o n al M e di ci n al P r o d u ct: S u p pl y a n d A c c o u nt a bilit y 
Eac h I n vesti g at or is res p o nsi ble f or e ns uri n g t hat d eli veries of I M P vi als a n d b o x es, L- Cs A  
 
a n d ot h er cli nical trial m aterials are c orrectl y recei ve d a n d rec or d e d, t hat t h ese are h a n dle d a n d 
st ore d safel y i n a l oc ke d a n d t e m perat ure c o ntr oll e d st ora ge place wit h access f or a ut h orise d st u d y 
staff o nl y a n d t h at t he y are use d i n acc or da nce wit h t his pr ot o c ol. I n a d diti o n, t he I n v esti gat or will 
m o nit or eac h p atie nt’s treat me nt c o m plia nce b y c o u nti n g t he use d/ u n use d dr u g vials at eac h visit. 
F or t he p ur p ose of t his trial patie nts will be re gar d e d as c o m plia nt if n o m ore t h a n 4 5 vials of I M P 
o ver t h e e ntire treat me nt peri o d of 1 2 wee ks are ret ur ne d as u n use d – t his c orres p o n ds t o 
a p pr o xi m atel y 7 5 % treat m e nt c o m pli a nce. T he reas o n f or n o n-c o m plia nce s h all be d oc u me nt e d 
acc or di n g o n t he res pecti v e e C R F. 
U n use d I M P vials, a m p o ules, b o xes, a n d L- Cs A  
 m ust be ret ur n e d  or destr o y e d o n-site 
after a cc o u nta bilit y has bee n c o m plete d a n d d estr ucti o n is a p pr o ve d b y Za m b o n S p A. A list of 
I M P, L- Cs A  
, a n d ot h er materials recei ve d, use d, ret ur ne d, or d estr o ye d m ust be pre pare d, 
c o m plete d a n d si g ne d b y t he I n vesti gat or; a n y discre p a nci es m ust be acc o u nte d f or. 
C O VI D- 1 9 s pecifi c c o nsi derati o n: t he pati e nts will be s u p plie d d uri n g V 1 wit h t h e f ull a m o u nt of 
st u d y me dicati o n nee de d, t o c o ver t h e t otal treat m e nt peri o d of 1 2 w ee ks. Patie nt has t o bri n g all 
st u d y me dicati o n bac k t o t h e site at E o T Visit V 5 f or Dr u g Acc o u nta bilit y. 
C CI
C CI
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 3 9  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 4. Ps yc hiatric dis or ders or alt ere d me ntal stat us precl u di n g u n dersta n di n g of t h e i nf or me d
c o nse nt pr ocess a n d/ or c o m pl eti o n of t h e necessar y pr oce d ures.
1 5. A n y c o-e xisti n g m e dical c o n diti o n t h at i n t h e I n vesti gat or’s j u d g me nt will s u bsta ntiall y
i ncrease t he ris k ass o ci ate d wit h t h e patie nt’s parti ci pati o n i n t he cli nical trial.
1 6. Pre-sc he d ul e d h os pitalizati o ns, s ur g eries or i nter v e nti o ns pl a n n e d t o be perf or me d aft er
o btai ni n g I nf or me d C o nse nt f or t his st u d y.
9. 3  P ati e nt Wit h d r a w al C rit e ri a 
I n t he e ve nt of p atie nt wit h dra wal, t he I n vesti gat or m ust c o m plete t h e a p pr o pri at e e n d of st u d y 
f or m i n t he e C R F as s o o n as p ossi ble aft er wit h dra wal, stati n g t h e reas o n a n d date of wit h dra wal. 
A n a ut o mate d e- m ail al ert will be g e nerate d b y t he e C R F s yste m a n d will be s e nt t o t he Cli nical 
Researc h Or ga nizati o n ( C R O). 
9. 3. 1  P r o c e d u r e s of P ati e nt Wit h d r a w al a n d I M P di s c o nti n u ati o n 
Wit h dra wal: 
T he p atie nt is free t o wit h dra w fr o m t h e cli ni cal tri al f or a n y reas o n a n d at a n y ti me wit h o ut gi vi n g 
a reas o n f or d oi n g s o a n d wit h o ut pe nalt y or prej u di ce. T he I n vesti g at or is als o free t o ter mi nate a 
patie nt’s i n v ol ve me nt i n t he cli nical tri al at a n y ti me if t h e patie nt’s cli ni cal c o n diti o n warra nts it. 
I n cas e of earl y wit h dra w al, t he pati e nt will be e n c o ura ge d t o perf or m a fi n al visit. T h e fi nal visit 
will e nc o m p ass t h e assess me nts liste d u n d er E o S Visit ( S ecti o n 1 3. 2. 5 ).  
A d diti o n all y, use d a n d u n use d I M P a n d i n hal ati o n de vice will be retrie ve d, if a p plica ble. Za m b o n 
S p A will be n otifie d b y t h e I n v esti g at or via e ntr y i n a n d n otificati o n b y t he e C R F t h at t he patie nt 
has ter mi nate d cli nical tri al partici pati o n. 
I M P disc o nti n uati o n 
T he I n vesti g at or or p atie nt is free t o disc o nti n u e re g ular i nta ke of I M P, if t he cli nical c o n diti o n 
of t h e patie nt or ot her s eri o us reas o ns warra nt it. Reas o ns f or disc o nti n uati o n of I M P ma y 
i ncl u de ( b ut are n ot li mite d t o) t h e f oll o wi n g: 

Si g nifica nt res pirat or y i nfecti o n re q uiri n g t hera p y

Res pirat or y fail ure fr o m a n y ca use

Mec h a ni cal v e ntilati o n
If 1 0 or m ore c o ns ec uti ve d oses of I M P are miss e d, re gar dless of reas o n, t he n I M P will be 
c o nsi d ere d as disc o nti n u e d a n d s h o ul d n ot be res u me d.  If I M P i n hal ati o n is disc o nti n ue d, t he 
patie nt will be as ke d t o ret ur n f or cli nical trial visits acc or di n g t o t he visit sc he d ule defi ne d i n t he 
pr ot oc ol b ut s h all n ot recei v e I M P. 
St o p pi n g criteria are o utli ne d i n detail i n S ecti o n 8. 5. 1 . 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 4 1  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 0  T R E A T M E N T O F P A TI E N T S 
P atie nts will recei ve L- Cs A (eit h er 1 0 m g, 5 m g or 0 m g bi d) i n a d diti o n t o S o C as prescri b e d b y 
t he treati n g p h ysicia n a n d as descri be d i n S ecti o n 8. 3. 2 . L- Cs A will b e a d mi nistere d as 1 0 m g/ 2. 5 
m L, 5 m g/ 1. 2 5 m L, or 0 m g/ 2. 5 m L i n h alati o n vi a t he L- Cs A  
 f or u p t o 1 2 wee ks. 
A n y c ha n ges i n S o C treat me nt will be d o c u me nte d i n t he e C R F. 
1 0. 1  C o n c u r r e nt T r e at m e nt o r M e di c ati o n  
All partici pa nts will mai ntai n t h eir us ual care t hr o u g h o ut t he c o urse of t h e st u d y. S o C i n cl u des 
pr o p h yla xis a gai nst c o m m o n o p p ort u nisti c i nfecti o ns, i m m u n os u p pressi o n, a n d a n y ot h er c hr o nic 
me di cati o n. All c o nc urre nt treat me nt or me dicati o ns gi ve n wit hi n 3 0 d a ys pri or t o R a n d o mi zati o n 
u ntil E o S ( Visit 6) will be rec or de d i n t h e e C R F,  t his als o i ncl u des vacci nati o n f or S A R S- C o V- 
2. 
1 0. 1. 1  P r o p h yl a xi s a n d T h e r a p y of I nf e cti o n s 
All patie nts will recei ve sta n d ar d i nfecti o us disease pr o p h yla xis a n d t h era p y c o nsisti n g of 
a p pr o priatel y t ar gete d a nti bi otics, a nti virals a n d/ or a ntif u n gals acc or di n g t o i nstit uti o nal sta n dar ds. 
Dates of st art a n d st o p or c ha n ge i n d osa ge will be rec or d e d o n t he res pecti ve e C R F. 
1 0. 1. 2  I m m u n o s u p p r e s si o n 
I m m u n os u p pressi v e t hera p y is per mitte d a n d will be perf or me d t o ce nt ers’ sta n dar d re gi me n. 
T he use of differe nt f or m ulati o ns of aer os olize d C y cl os p ori ne A ot h er t ha n L- Cs A is strictl y 
pr o hi bit e d d uri n g t h e c o m plete cli nical trial peri o d. S yst e mi c a d mi nistrati o n of Cs A is per missi ble 
if me dicall y necessar y at t he decreti o n of t he i n vesti g at or. 
1 0. 1. 3  T r e at m e nt f o r B O S 
T he f oll o wi n g me dicati o ns will be per mitte d: 

I n h ale d c ortic oster oi ds are all o we d a n d p atie nts s h o ul d be o n a sta bl e d ose f or 4 wee ks
pri or t o ra n d o mizati o n a n d t hr o u g h o ut t he st u d y.

F or all ot h er i n h ale d me dicati o ns please refer t o S ecti o n 1 0. 1. 4 .

S yste mic c ortic oster oi d treat me nt f or B O S ( or c G V H D) will be p er mitt e d, b ut a p ulse d ose
has t o b e c o m plete d pri or t o scree ni n g.

E xtrac or p oreal p h ot o p h oresis ( E C P) f or treat me nt of B O S is per mitte d wit hi n 4 wee ks
pri or t o ra n d o mizati o n.

M o ntel u k ast will be p er mitte d, b ut p atie nts s h o ul d be o n a st a ble d ose f or 4 wee ks pri or t o
ra n d o mizati o n a n d t hr o u g h o ut t h e st u d y.
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 4 2  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 0. 1. 4  Ot h er M e di c ati o n 
All i n hale d me di cati o ns, e xce pt i n v esti g ati o n al i n hale d m e dicati o ns, are p er missi ble d uri n g t he 
trial.  
P atie nts o n br o n c h o dilat ors s h o ul d be o n a sta ble d ose 4 wee ks pri or t o ra n d o mizati o n a n d 
t hr o u g h o ut t h e st u d y.  All ot h er i n hale d m e dicati o n s h o ul d b e a d mi nistere d after s pir o metr y i n t he 
f oll o wi n g or der: i n h ale d c ortic ost er oi ds, i n hale d a ntif u n gals/a nti bi otics, a n d t h e n i n hal e d I M P. F or 
details wit h re gar d t o s pir o metr y meas ure m e nts, please refer t o S ecti o n 1 1. 1. 1 . 
1 0. 1. 5  P r o hi bit e d M e di c ati o n 
Azit hr o m yci n will n ot be p er mitte d. I n t h e e v e nt a patie nt has use d c hr o ni c azit hr o m y ci n, it m ust 
be disc o nti n u e d f or at l east 4 wee ks pri or t o ra n d o mizati o n.  
Zafirl u kast will n ot be per mitte d. 
Treat me nts wit h ot h er I n vesti gati o n al Me di ci nal Pr o d ucts (I M Ps) or pr e vi o us t hera pies wit hi n 
f o ur wee ks or fi ve ti mes h alf-life of t he dr u g, w hi c he ver is l o n ger, is pr o hi bite d pri or t o st u d y 
scree ni n g a n d d uri n g t h e st u d y. 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 4 4  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 

T he t w o lar g est v al ues of F E V 1 m ust be wit hi n 0. 1 5 0 L of eac h ot her
If b ot h of t hese crit eria are met, t he test sessi o n ma y be c o ncl u de d. 
If b ot h of t hese crit eria are n ot m et, c o nti n ue testi n g u ntil: 

B ot h of t he criteria are met wit h a nal ysis of a d diti o nal acce pta ble s pir o gra ms
or

A t otal of ei g ht t ests ha v e b ee n p erf or m e d ( o pti o n al)
or

T he p atie nt ca n n ot or s h o ul d n ot c o nti n u e
T he t hree b est v al u es o ut of t he p erf or me d ma n e u vers will be rec ore d i n t h e e C R F. 
Ti mi n g of s pir o metr y meas ures is pr o vi de d i n Secti o n 1 0. 1. 4 . Ti mi n g of s pir o metr y meas ures i n 
relati o n t o a d mi nistrati o n of I M P is pr o vi d e d i n Secti o n 1 3. 2 . 
1 1. 1. 2  S F- 3 6 Q u alit y of Lif e Q u e sti o n n ai r e 
T he S F- 3 6 Versi o n 1. 0 is a sta n dar dize d, s h ort f or m m eas ure of ge neric healt h stat us, d esi g ne d f or 
self-a d mi nistrati o n. It ta kes 5- 1 0 mi n ut es f or t h e pati e nt t o c o m plete t h e q uesti o ns. Patie nts will 
be as ke d t o c o m plete t h e q u esti o n n aire at Visits 1 ( Baseli ne), 2, 3, 4, 5, a n d res ults will be e nt ere d 
i nt o t h e e C R Fs b y t h e sit e staff. 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 4 5  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 2  A S S E S S M E N T O F S A F E T Y 
1 2. 1  S af et y P a r a m et e r s 
S afet y assess me nts at e ver y visit i ncl u d e A E re p orti n g, p h ysical e xa mi nati o n, C GI assess me nt, 
vital si g ns a n d cli nical l a b orat or y p ara meters ( perf or me d at t he l ocal l a bs i n eac h st u d y site). 
L- Cs A p har mac o ki neti c meas ure m e nts at Visits 1 t o 5 are a n al y ze d at t h e Ce ntral La b or at or y A C C
G m b H i n Ger ma n y, a n d als o liste d i n t his secti o n, alt h o u g h t h e y will n ot be a vaila bl e f or i m me diate
safet y assess me nt b y t h e D M C or I n v esti gat or.
C O VI D- 1 9 s p ecific c o nsi d erati o n: I n case t he pla n ne d o n-site visit ca n n ot be perf or me d d u e t o
C O VI D- 1 9 restricti o ns, t h e PI or t he S u b-I n v esti g at or a n d/ or a n a p pr o priat el y q ualifie d sit e st u d y
tea m me m ber m ust call t he pati e nt. A re m ot e visit m ust be perf or me d t o assess a n y p ote ntial
a d verse e ve nts ( A Es) a n d t o c o nfir m t he p atie nt’s stat us a n d well- bei n g (see als o S ecti o n 1 3. 2. 7 ).
1 2. 1. 1  D efi niti o n s 
A d verse E v e nt ( A E) 
A n A E is a n y u nt o war d me dical occ urre n ce i n a patie nt after a d mi nistrati o n of a p har mace utical 
pr o d uct a n d w hi c h d oes n ot necessaril y h a ve a ca usal relati o ns hi p wit h t his treat me nt. A n A E ca n 
t heref ore be a n y u nfa v ora ble a n d u ni nte n de d si g n (i n cl u di n g a n a b n or m al la b orat or y fi n di n g), 
s y m pt o m, or disease te m p orall y ass ociate d wit h t h e use of a me dici nal (i n v esti g ati o nal) pr o d uct, 
w het her or n ot relate d t o t he me dici n al (i n vesti gati o nal) pr o d u ct (I C H G ui d eli nes f or G o o d Cli nical 
Practice E 6( R 2), 9 N o v e m ber 2 0 1 6). 
T his i ncl u des w orse ni n g of a pr e-e xisti n g c o n diti o n or i n crease i n fre q ue nc y of a pr e-e xisti n g 
c o n diti o n. A n A E is c o nsi dere d seri o us if it meets a n y of t he seri o us criteria liste d b el o w. T o e ns ure 
n o c o nf usi o n or mis u n d ersta n di n g of t he differe nce b et wee n t he t er ms “seri o us” a n d “se vere”, 
w hic h are n ot s y n o n y m o us, t h e f oll o wi n g clarific ati o n is pr o vi d e d: 
T he ter m “s e vere” is ofte n use d t o descri be t he i nte nsit y (se verit y) of a s pecific e ve nt (as i n mil d, 
m o derate, or se vere m y o car dial i nfarcti o n); t he e v e nt itself, h o we ver, ma y be of relati vel y mi n or 
me di cal si g nifica nce (s uc h as se vere h ea dac h e). T his is n ot t he sa me as “seri o us”, w hic h is b ase d 
o n pati e nt/ e v e nt o ut c o me or acti o n criteria us uall y ass ociate d wit h e ve nts t h at p ose a t hreat t o a 
patie nt’s life or f u n cti o ni n g. Seri o us ness ( n ot se verit y) ser v es a g ui de f or d efi ni n g re g ul at or y 
re p orti n g o bli g ati o ns. 
T he official d efi niti o n als o e xte n ds t o A Es occ urri n g d uri n g t he off-treat me nt f oll o w- u p peri o d. 
Eac h p atie nt will be cl osel y o bser ve d a n d q u esti o ne d f or A Es t hr o u g h o ut t he cli nical tri al p eri o d 
wit h n o n-lea di n g q uesti o ns (e. g., h o w d o y o u feel ?). T he pati e nts will be i nstr uct e d t o re p ort t o t he 
cli nical trial staff i m me diatel y a n y s y m pt o ms a n d/ or si g ns w hic h occ ur bet w ee n t h e sc he d ul e d 
o bser v ati o n ti mes. 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 4 6  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
All A Es re p orte d b y t he patie nt or o bs er ve d b y t h e I n vesti gat or or h os pital p ers o n nel will be 
d oc u me nt e d i n t he res pecti ve e C R F. T h e f oll o wi n g i nf or mati o n re gar di n g eac h A E will be 
o btai ne d: date a n d ti me of o nset a n d res ol uti o n ( d urati o n), s eri o us or n o n-seri o us (as d efi n e d 
bel o w), se v erit y, treat me nt re q uire d, o ut c o me, relati o ns hi p t o certai n m e dicati o n, a n d if t h e A E 
ca use d wit h dra wal fr o m t h e cli nical trial. 
I n a d diti o n t o t h e I n vesti gat or’s o w n descri pti o n of t he A E, eac h A E e ve nt will be c o de d b y data 
ma na ge me nt acc or di n g t o t h e Me dical Di cti o nar y f or Re g ulat or y Acti viti es ( Me d D R A) c o d e list. 
T he v er b ati m ter m will be rec or de d i n t h e e C R F. 
A b n or mal la b orat or y test res ults will be re p orte d as A Es if t h e y are i n dicati v e of a cli nical 
c o n diti o n t hat meets t he criteria f or a n A E. 
A d verse Dr u g R eacti o n ( A D R) 
A d verse dr u g reacti o ns ( A D Rs) are all n o xi o us a n d u ni nte n d e d res p o nses t o a me dici nal pr o d u ct 
relate d t o a n y d ose t h at a ca usal relati o ns hi p bet wee n t he me dici nal pr o d u ct a n d a n A E is at least 
a reas o na bl e p ossi bilit y, i.e., t he rel ati o ns hi p ca n n ot be r ule d o ut. A n u n e x pecte d A D R is a n y 
a d verse reacti o n n ot i de ntifie d i n nat ure, fre q u e nc y, or i nt e nsit y list e d i n t h e referre nt safet y secti o n 
of t h e c urre nt I B. 
S eri o us A d verse E v e nt ( S A E) 
Eac h A E is t o be cl assifie d b y t he I n v esti g at or as S E RI O U S or N O N- S E RI O U S. 
T he I nter n ati o nal C o nfere nce o n Har m o nisati o n (I C H) of Tec h nical Re q uir e me nts f or Re gistrati o n 
of P har mace uticals f or H u ma n Use d efi n es a n S A E as a n y A E occ urri n g at a n y d os e t hat res ults i n 
a n y of t h e f oll o wi n g o utc o mes: 

Deat h

A life-t hre ate ni n g e ve nt (i m me diate ris k of deat h at t he ti me of t he e ve nt)

I n p atie nt h os pit alizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n

A persist e nt or si g nifica nt disa bilit y/i nca pacit y

A c o n g e nit al a n o mal y/ birt h d efect

Ot her i m p orta nt me dical e ve nt ( Me dical a n d scie ntific j u d g me nt s h o ul d be e xercise d i n
deci di n g w het her e x p e dit e d re p orti n g is a p pr o priate i n ot her sit uati o ns, s uc h as i m p orta nt
me dical e v e nts t hat 
m a y n ot be i m m e di atel y life-t hreate ni n g or res ult i n deat h or
h os pit alizati o n b ut ma y j e o par dize t h e patie nt or m a y re q uire i nter ve nti o n t o pre v e nt o ne of
t he ot her o ut c o mes liste d i n t he defi niti o n a b o v e. T hese s h o ul d als o us uall y be c o nsi d er e d
seri o us.)

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 4 7  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 2. 1. 2  R el ati o n s hi p t o Cli ni c al T ri al T r e at m e nt A s si g n m e nt 
All A Es will be e val uate d b y t he I n v esti g at or f or p ote ntial relati o ns hi p t o t h e cli ni cal trial treat me nt 
assi g n me nt ( L- Cs A or pl ace b o) i n t h e f oll o wi n g c ate g ori es: 

U nrel ate d : A n A E wit h a k n o w n ca use ot h er t ha n t h e use of I M P ( n o reas o na ble relati o ns hi p).

P ossi ble : A n A E t hat mi g ht be d u e t o t h e use of t h e I M P. A n alter nati ve e x pla nati o n, e. g.,
c o nc o mita nt dr u g(s), c o nc o mita nt disease(s), is i nc o ncl usi ve. T he relati o ns hi p i n ti me is
reas o na bl e; t heref ore t he ca usal relati o ns hi p ca n n ot b e e xcl u de d (reas o na ble rel ati o ns hi p).

Defi nite : A n A E t h at f oll o ws a reas o na ble te m p oral se q ue nce fr o m a d mi nistrati o n of t he I M P;
t hat f oll o ws a k n o w n or e x pecte d res p o nse p atter n t o t h e s us p ecte d cli nical trial treat me nt
assi g n me nt (reas o n a bl e relati o ns hi p).
I n t h e a bse nce of i nf or mati o n o n ca usalit y pr o vi de d b y t he re p orti n g i n v esti gat or, t he s p o ns or will 
c o ns ult t he i n vesti gat or a n d e nc o ur a ge hi m/ h er t o gi ve a n o pi ni o n o n t his e ve nt. T he ca usalit y 
assess me nt gi v e n b y t h e i n vesti gat or will n ot b e d o w n gra de d b y t he s p o ns or. If t h e s p o ns or 
disa grees wit h t he i n vesti gat or's ca usalit y assess m e nt, t he o pi ni o n of b ot h t h e i n v esti g at or a n d t he 
s p o ns or will be pr o vi d e d. 
1 2. 1. 3  M a xi m u m I nt e n sit y 
All A Es will be gra d e d a cc or di n g t o t he f oll o wi n g: 

Mil d : E ve nt re q uiri n g n o s pecial treat me nt a n d ge nerall y d oes n ot i nterfere wit h us u al
acti vities.

M o der ate : E v e nt t h at i m p airs us ual acti vities b ut ma y be a meli orate d b y si m pl e t h era pe utic
ma ne u vers.

S e vere *: E v e nt w hi c h i m p airs us ual acti viti es a n d re q uires i nter v e nti o n.
* T here is a disti ncti o n bet wee n a se ver e A E a n d a n S A E; a se ver e reacti o n is n ot a n S A E u nless
it meets o ne of t h e criteria f or seri o us e ve nts (see S ecti o n 1 2. 1. 1 ).
1 2. 1. 4  S e ri o us A d v e r s e E v e nt ( S A E) R e p o rti n g 
A n y S A E occ urri n g 

bet wee n t h e first cli nical trial pr oce d ure aft er o bt ai ni n g i nf or me d c o nse nt a n d wit hi n 2 wee ks
after t he c o m pleti o n of t he E o T Visit, w het h er or n ot c o nsi d ere d relate d t o t he cli nical trial
treat me nt assi g n me nt.
or

at a n y ti me aft er c o m pleti o n of t h e last f oll o w- u p a n d c o mi n g t o t he atte nti o n of t he
I n v esti g at or, if it is j u d ge d as rel ate d t o t h e p atie nt’s partici p ati o n i n t h e cli ni cal trial
m ust be re p orte d t o t he S p o ns o r’s Dr u g S afet y ( 
) I M M E DI A T E L Y, b ut wit hi n 2 4 h o urs 
u p o n k n o wl e d g e, as f oll o ws: 
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 4 8  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 

D oc u me nt t he e v e nt i n t he e C R F wit hi n 2 4 h o urs of disc o ver y

S u b mit t he S A E re p ort b y Fa x or e- mail t o a list of pre defi n e d reci pie nts

F oll o w- u p t he S A E u ntil t he o utc o me is deter mi ne d, pr o vi di n g peri o dic u p d ates i n t h e e C R F

Pr o vi de a n y a d diti o nal i nf or mati o n if re q ueste d
C o ntacts of t he S p o ns or’s Dr u g Safet y are as f oll o ws: 
 
 
 
 
 
Bel gi u m 
F a x: 
P h o n e: 
E- M ail:
 
1 2. 1. 4. 1  T i m eli n es f o r S us p e ct e d U n e x p ect e d S e ri o us A d v ers e R e a cti o n ( S U S A R) r e p o rti n g t o 
C o m p et e nt A ut h o riti e s a n d E Cs 
All s us pecte d u ne x pecte d seri o us a d verse reacti o ns ( S U S A Rs) will be re p orte d b y t he S p o ns or t o 
t he C o m pete nt A ut h orities a n d t o t he E Cs c o ncer ne d as s o o n as p ossi ble, b ut wit hi n a ma xi m u m 
of 1 5 da ys (fatal or life-t hreat e ni n g S U S A Rs wit hi n a ma xi m u m of 7 d a ys) of first k n o wle d ge. 
Rele va nt f oll o w- u p i nf or mati o n of fatal or life-t hreate ni n g S U S A Rs will be c o m m u ni cat e d 
s u bse q ue ntl y wit hi n a n a d diti o n al 8 da ys. 
1 2. 1. 4. 2  Ot h e r E v e nts t o b e t r e at e d as S e ri o us A d v e rs e E v e nt s 
E x p os ure t o dr u g d uri n g pre g na nc y/lact ati o n: 
I n pri nci ple, pre g na nc y a n d t he lactati o n p eri o d are e xcl usi o n criteri a. I n t h e e ve nt of a pre g n a n c y 
occ urri n g d uri n g t h e c o urse of t h e cli nical trial, t h e patie nt m ust be wit h dra w n fr o m all I M P 
treat me nt i m me diatel y a n d per ma n e ntl y. T he S p o ns or 
m ust be n otifie d wit h o ut d ela y b y 
c o m pleti n g t he Pre ga nc y F or m A a n d t he patie nt f oll o we d d uri n g t h e e ntire c o urse of t he 
pre g na nc y a n d p ost p art u m peri o d. Pre natal a n d n e o nat al o utc o mes m ust b e rec or de d e ve n if t h e y 
are c o m pletel y n or mal a n d wit h o ut A Es. T he pre g na nc y re p orti n g ti m eli nes are t he sa me as 
descri be d f or S A E re p orti n g pr oce d ure i n secti o n 1 2. 1. 4.  
If a n y cli nical trial pati e nt bec o mes pre g n a nt d uri n g t h e cli nical trial peri o d, t he I n v esti g at or m ust 
c o ntact Za m b o n S p A as t he S p o ns or of t he cli nical trial or its desi g nee t o dis c uss t he ma n a ge me nt 
of t h e patie nt. 
A d verse D e vice Effect 
I n pri nci ple, seri o us a d vers e ve nts ca us e d b y a de vice iss ue s h o ul d be re p orte d as S A Es as 
descri be d a b o ve.  
C CI
C CI
C CI
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 4 9  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
Ot h er de vice defici e ncies a n d malf u ncti o ns n ot ass ociate d wit h t h e a d v erse e ve nt s h o ul d be 
re p orte d via t h e  
 C o m plai nt F or m, pr o vi de d i n t he I M P ma n ual.  
C O VI D- 1 9 s pecific c o nsi derati o ns: 
All c o nfir me d c ases of C O VI D- 1 9, occ urri n g after t he p atie nt has pr o vi de d i nf or m e d c o nse nt a n d 
u ntil 4 wee ks after t h e E o T visit, m ust be re p orte d as S A E a n d re p orte d t o  
 wit hi n 2 4 h o urs 
u p o n k n o wle d ge. 
T he s eri o us ness crit eri o n f or C O VI D- 1 9 h os pitali ze d patie nts s h o ul d be “ h os pit alizati o n”; if t he 
patie nt was n ot a d mitt e d t o a h os pital or t he e v e nt is n ot res ulti n g i n pr ol o n ge d h os pit alizati o n, t he 
seri o us ness crit eri o n “ me dicall y si g nifica nt” s h o ul d b e use d. 
I n all cas es, details of t h e pati e nt's s y m pt o ms, treat me nt a n d a n y cli ni call y rele va nt i nf or mati o n, 
s h o ul d be e ntere d i n t h e S A E f or ms, as a p pr o pri at e. 
1 2. 1. 4. 3  I n v esti g ati o n al M e di ci n al Pr o d u ct (I M P) O v e r d o si n g 
A n o v er d ose is a deli berate or i na d vert e nt a d mi nistrati o n of a treat me nt at a d ose hi g h er t h a n 
s pecifie d i n t h e pr ot oc ol. F or t he p ur p oses of t his cli nical trial, a n y d ose of aer os olize d I M P 
a d mi nistere d t o a p atie nt t hat e xcee ds t he d ose f oresee n i n t h e pr ot oc ol b y m ore t h a n 5 0 % o v er 
4 wee ks s h o ul d b e re p ort e d as a n o ver d ose. A n y o cc urre n ce of o ver d ose are t o be re p orte d t hr o u g ht 
t he S A E pr oce d ures descri be d a b o ve. 
1 2. 1. 4. 4  E v e nts n ot r e g ar d e d as A d v e rs e E v e nts / S e ri o us A d v e rs e E v e nts 
T he f oll o wi n g e ve nts will be n ot re gar d e d as A Es/ S A Es: 

N ot a p plica ble
1 2. 1. 4. 5  D u r ati o n of F oll o w- u p aft er A d v e rs e E v e nts 
All A Es s h o ul d b e f oll o we d u ntil t h e y are res ol v e d or u ntil a sta ble cli ni cal e n d p oi nt is reac he d. 
T he o cc urre n ce of A Es a n d S A Es will be m o nit ore d u ntil 2 wee ks aft er t he E o T visit.  
1 2. 1. 5   T ol e r a bilit y of I M P 
L ocal t olera bilit y fi n di n gs will be rec or d e d as A Es i n t h e a p pr o pri ate e C R F. 
T he p atie nt will be o bs er ve d f or l o cal t olera bilit y fi n di n gs f or 1 h o ur after i n halati o n at eac h o n-
site st u d y visit.  
L ocal t olera bilit y e ve nts are: 

C o u g h

W heezi n g

Br o nc h os pas m
C CI
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 5 0  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 

T hr oat irritati o n

C ha n ge i n F E V 1
I n a d diti o n, t hese e ve nts will be s oli cite d acti v el y bef ore I M P i n halati o n at eac h st u d y visit 
(e xce pt E o S) b y q u esti o ni n g t h e patie nt w h et her h e/s he has e x perie nce d a n y of t he e ve nts i n-
bet wee n t he st u d y visits. If a p plica bl e, a n A E re p ort f or m will be c o m plet e d.  
O verall t ol era bilit y ass ess me nt b y t he i n vesti gat or i n cl u des: 

C GI q u esti o n naire ( G u y 1 9 7 6 )

I n v esti gat or’s t olera bilit y ass ess m e nts at Visit 3 a n d Visit 5, ass esse d b y mea ns of a fi ve-
p oi nt ver bal rati n g scale wit h t h e res p o ns e o pti o ns ‘ ver y g o o d’, ‘ g o o d’, ‘satisfact or y’,
‘ m o derate’, a n d ‘ p o or’
1 2. 1. 6  Cli ni c al L a b or at o r y 
La b orat or y assess me nts will be perf or me d f oll o wi n g t h e r o uti ne pr ot o c ols at eac h o n-site visit b y 
t he l o cal l a b orat or y at eac h site.  
T he f oll o wi n g cli nical la b orat or y p ara meters ha ve t o b e d oc u me nt e d: 

W hite bl o o d cell c o u nt wit h differe ntial

Re d bl o o d cell c o u nt

Platelet c o u nt

Al kali ne p h os p hatase

Ala ni ne a mi n otra nsferas e

As partate a mi n otra nsferase

Ga m ma gl uta m yl tra nsferase

Bl o o d urea nitr o ge n

S er u m bilir u bi n

S er u m creati ni ne
La b orat or y assess me nts liste d a b o ve will be p erf or me d at a l oc al facilit y, c hec ke d a n d i nt er prete d 
b y t h e i n vesti gat or a n d e ntere d i nt o t he a p pr o priate secti o n of t he e C R F. T h e N or mal La b or at or y 
Ra n ges of eac h l ocal la b orat or y will be use d f or t he t he assess me nt of cli nical si g nifica nce. 
1 2. 1. 6. 1  P r e g n a nc y T est 
S er u m or uri ne sa m ples fr o m w o me n of c hil d beari n g p ote ntial will b e c ollecte d f or pre g na nc y 
tests at S cree ni n g, a n d o n-site Visits 1, 2, 3, 4, 5, a n d 6. P ositi v e res ults will be rec or de d i n t h e 
e C R F a n d a p pr o pri at e acti o ns will be ta ke n. 
1 2. 1. 6. 2  P h ar m a c o ki n eti c P ar a m et e rs 
W h ole bl o o d sa m ples f or deter mi nati o n of c ycl os p ori ne A will be c ollecte d at Visit 1 pre- d ose, 
directl y after e n d of i n halati o n; a n d 1 5, 3 0, a n d 4 5 mi n utes ( +/- 5 mi n ut es), a n d 1, 1. 5, 2, a n d 4 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 5 1  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
h o urs ( +/- 1 5 mi n utes) after e n d of i n hal ati o n f or deter mi n ati o n of C ma x , tma x , a n d A U C0- 4 h. P K 
a nal ysis will b e perf or me d i n a ce ntral la b orat or y (
).  
All sites will be pr o vi d e d wit h s p ecific La b orat or y Kits f or c oll ecti n g t he P K bl o o d sa m ples. 
Bl o o d s h o ul d be c ollecte d i nt o t h e res pecti ve pre-l a belle d K 2- E D T A T u b es a n d s h o ul d be st ore d 
at - 2 0° C i m me diatel y aft er c ollecti o n u ntil s hi p me nt t o t he ce ntral la b orat or y.  
I nstr u cti o n o n ha n dli n g, pr ocessi n g, st ora ge a n d s hi p me nt are i n detaile d d escri b e d i n t he 
La b orat or y M a n ual f or P har mac o ki netic Bl o o d Sa m pli n g.  
1 2. 1. 6. 3  C y cl os p o ri n e A W h ol e Bl o o d T r o u g h L e v els 
A w h ole bl o o d sa m pl e f or t he deter mi n ati o n of c ycl os p ori ne A tr o u g h le vel will be c ollecte d at 
Visit 2 t o Visit 5 at eac h o n-site visit. T he sa m ple s h o ul d be c oll ect e d 1 5 mi n utes b ef ore i n halati o n 
T he tr o u g h l e vels of Cs A at visit 2 t o 5 will be a nal ysis will be perf or me d i n a ce ntral la b orat or y 
(
).  
All sites will be pr o vi d e d wit h s p ecific La b orat or y Kits f or c oll ecti n g t he P K bl o o d sa m ples. 
Bl o o d s h o ul d be c ollecte d i nt o t h e res pecti ve pre-l a belle d K 2- E D T A T u b es a n d s h o ul d be st ore d 
at - 2 0° C i m me diatel y aft er c ollecti o n u ntil s hi p me nt t o t he ce ntral la b orat or y.  
I nstr u cti o n o n ha n dli n g, pr ocessi n g, st ora ge a n d s hi p me nt are i n detaile d d escri b e d i n t he 
La b orat or y M a n ual f or P har mac o ki netic Bl o o d Sa m pli n g.  
1 2. 1. 7  Vit al Si g n s 
Vit al si g ns will b e assess e d at eac h o n-site visit. 
T he f oll o wi n g vital si g ns will be rec or d e d: 

S yst oli c a n d diast olic bl o o d press ure (sitti n g, after mi ni m u m 5 mi n ut es of rest),

p uls e rate (sitti n g, after mi ni m u m 5 mi n utes of rest),

b o d y te m perat ure (t he sa me met h o d s h o ul d be use d f or ea c h patie nt a n d t hr o u g h o ut t he
cli nical trial),

res pirat or y rate.
1 2. 1. 8  P h y si c al E x a mi n ati o n s
A p h ysi cal e xa mi nati o n will b e carrie d o ut at t h e S cree ni n g Visit a n d at e ver y s u bse q ue nt o n-site 
visit. T h e f oll o wi n g b o d y s yste ms will b e e xa mi ne d: b o d y wei g ht a n d hei g ht (at S cree ni n g visit 
o nl y), car di o v asc ul ar, res pirat or y, n er v o us, gastr oi ntesti nal, he patic, r e n al, der mat ol o gical, 
m usc ul os kel etal, e xtre mities, e yes, ears, n ose, t hr o at, a n d l y m p h atic. 
A b n or mal fi n di n gs will be s u m m arize d f or eac h p atie nt a n d will be d oc u me nte d as A E. 
C CI
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 5 2  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 2. 1. 9  Cli ni c al Gl o b al I m p r e s si o n ( C GI) 
T he C GI is a 3-ite m o bser ver-rat e d scale t hat meas ures ill n ess se verit y, gl o bal i m pr o ve me nt or 
c ha n ge a n d t hera pe uti c res p o nse. A m o difie d v ersi o n of t he C GI will be use d i n t his trial t o assess 
“ill ness” i nstea d of “ m e ntal” ill ness. I n v esti g at ors will c o m pl ete t he q uesti o n naire at Visits 1 
( Baseli ne), 2, 3, 4, 5, a n d res ults will be e ntere d i nt o t he e C R Fs b y t h e site staff. A C GI ca n o nl y 
be assess e d d uri n g a n o n-site visit a n d n ot be assesse d re m otel y. 
1 2. 2  D at a M o nit o ri n g C o m mitt e e ( D M C) 
A n i n de pe n de nt Data M o nit ori n g C o m mittee ( D M C) will be esta blis he d t o m o nit or t he safet y of 
I M P t hr o u g h o ut st u d y B T – L- Cs A – 2 0 1 – S C T. T h e D M C, re prese nte d b y f o ur me m bers i n t ot al, 
t hree e x p ert p h ysici a ns i n t h e fiel d of B O S a n d o n e n o n- me di cal e x p ert, will m o nit or safet y b y 
e val uati n g t h e safet y a nal yses pre pare d b y t he i n d e pe n de nt D M C statiscia n d uri n g t h e c o urs e of 
t he cli nical trial. Details of t he c o m p ositi o n, meeti n g fre q u e nc e a n d safet y a n al yses will be 
i ncl u de d i n t he D M C’s C harter. 
T he D M C will e v al u ate treat me nt gr o u ps f or p ossi ble tre n ds i n A Es, deter mi n e w het her t he basic 
cli nical trial ass u m pti o ns re m ai n vali d, e val uate w het h er t he o verall i nte grit y, sci e ntific merit a n d 
c o n d uct of t h e cli nical trial re mai n acce pt a bl e, a n d ma ke re c o m me n dati o ns t o S p o ns or.  
Me m b ers of t he D M C will be u n bli n de d. 
T he D M C will pef or m a c o m paris o n b et wee n t he rat e of o bser ve d C O VI D- 1 9 cas es a n d rate of 
patie nts wit h dra wal a m o n g trial parti ci pa nts i n b ot h treat me nt ar ms. 
D M C rec o m me n dati o ns ma y i ncl u de a d vice re gar di n g c o nti n uati o n, m o difi cati o n, s us pe nsi o n or 
disc o nti n u ati o n of t he trial base d o n safet y ( b ut n ot o n efficac y) reas o ns. H o we ver, t he fi nal 
decisi o n f or trial c o nti n uati o n, m o dificati o n, s us p e nsi o n or disc o nti n uati o n rests s olel y wit h t he 
S p o ns or  

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 5 3  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 3  VI SI T S C H E D U L E 
All cli nical trial visits, i n v esti g ati o ns a n d acti vities are liste d i n t he Cli nical Trial Sc he d ul e of 
Acti vities bel o w. F urt h er details o n t he met h o d ol o g y of t h ese i n vesti gati o ns a n d acti viti es are 
descri be d i n detail i n S ecti o n 1 1  a n d S ecti o n 1 2 . T he i n vesti gat or will a d here t o t h e visit a n d 
pr oce d ur e sc he d ul e as cl osel y as p ossi ble. 
All patie nts assi g ne d t o a ra n d o mizati o n n u m ber will be f oll o we d acc or di n g t o t he pr ot oc ol u nless 
c o nse nt f or f oll o w- u p is wit h dra w n. T h e S p o ns or m ust be n otifie d of all de viati o ns fr o m t he 
pr ot oc ol visit sc he d ule or e val uati o ns, a n d t h ese visits/e val uati o ns, if a p plica bl e, m ust be 
resc he d ul e d or perf or me d at t he cl osest p ossi ble ti me t o t he ori gi nal sc he d ule. 
Pr o per patie nt u n dersta n di n g a n d c o m pet e nc y of t h e L- Cs A  
 us e will be e ns ure d i n a n 
i n di vi d ual trai ni n g b y t h e res p o nsi ble cli ni c pers o n nel. T he p atie nt will b e a d mi nisteri n g t h e dr u g 
i n d e pe n de ntl y u n der s u per visi o n t o verif y patie nt c o m pete nc y wit h t h e e q ui p me nt a n d dr u g 
t olera bilit y. 
F or e m er g e nc y a n d ot h er u nsc h e d ule d visits t o a me di cal facilit y ot h er t ha n t h e cli nical trial site, 
me di cal re c or ds of t he visit s h o ul d be o btai n e d b y t h e I n v esti g at or. 
If a patie nt pre mat urel y disc o nti n u es cli nical trial partici pati o n f or a n y reas o n, e. g., t he patie nt 
wit h dra ws c o nse nt f or f urt h er p artici p ati o n i n t h e cli nical trial, t h e e val uati o n liste d u n d er “ E n d of 
St u d y Visit ( E o S)” ( Visit 6) s h o ul d be c o m pl ete d pri or t o disc o nti n uati o n w he ne ver p ossi ble (t he 
reas o n f or pre mat ure wit h dra wal s h o ul d al w a ys be d oc u me nte d). 
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Z a m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 5 4  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
Sc he d ule of Acti viti es 
Cli nic al Tri al P eri o d  
Scree ni n g 
Tre at me nt 
F oll o w- U p 
Visit N u m ber 
-
V 1  
V 2 
V 3 
V 4  
V 5 / E O T 
Re m ote Visits 
V 6 / E o S 
Wee k & Wi n d o w 
W - 4 t o W 
0 
W 0 D a y 1 
W 2 
 3 D a ys 
W 4 
 3 D a ys 
W 8 
 7 D a ys 
W 1 2 
 7 D a ys 
V 3, V 4 a n d V 6 
ca n be perf or m e d 
r e m otel y 
W 1 4 
 3 D a ys 
I nf or m e d C o nse nt1  
X 
De m o gra p hi cs/ Me di cal 
Hist or y  
X 
- 
I n cl usi o n/ E xcl usi o n 
criteria 
X 
Ser u m/ Uri n e 
P re g n a nc y Test 
X 
X 
X 
X 
X 
X 
X 
P h ysical E xa mi n ati o n 2  
X 
X 
X 
X 
X 
X 
X 
Vital si g ns 3 
X 
X 
X 
X 
X 
X 
X 
Cli nical L a b orat or y 
Tests 4 
X 
X 
X 
X 
X 
X 
X 
P K Bl o o d Sa m pli n g 5 
X 
X 
X 
X 
X 
S pir o metr y 7 
X 
X 6  
X6 
X 6 
X 6 
X 6 
Ra n d o mi zati o n 
X 
S F- 3 6 
X 
X 
X 
X 
X 
X 8 
C GI Q uesti o n n aire 
X 
X 
X 
X 
X 
I n v esti g at or’s 
T ol era bilit y 
Assess me nt  
X 
X 
L ocal I M P T ol era bilit y 
X 
X 
X 
X 
X 
I M P A d mi nistrati o n 
T wice d ail y a d mi nistrati o n 
X 
C o n c o mita nt 
Me dicati o n  
X 
X 
X 
X 
X 
X 
X 
X 
A d v erse E v e nts 
Per ma ne nt assess m e nt t hr o u g h o ut t h e c o m plete cli nical trial peri o d 
Dr u g 
Acc o u nta bilit y/I M P 
a vaila bilt y c hec k 
X 
X 
X 
X 
X 
1
C o n d uct pri or t o a n y scree ni n g a cti vities. 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 5 6  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 3. 1  Cli ni c al T ri al Fl o w C h a rt 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 5 8  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 3. 2. 2  Visit 1 / B as eli n e Vi sit / R a n d o mi z ati o n 
B aseli n e Pri or t o St art of Tre at me nt 

Verif y I nf or me d C o nse nt was o btai ne d

Verif y D e m o gra p hics/ M e di cal Hist or y

Re peat Uri ne/ S er u m Pre g na nc y T est ( Uri ne sa m pl es ca n be c oll ecte d at t he Ra n d o mi zati o n
Visit i n or der t o o btai n res ults q ui c kl y w hile t he p atie nt is i n t he cli nic a n d n ot del a y
ra n d o mizati o n)

P h ysical e xa mi n ati o n

Vital si g ns

Cli nical la b orat or y tests

P K bl o o d sa m ple pre- d os e

S pir o metr y

Ra n d o mizati o n

C o n c o mit a nt me dicati o ns/t hera pies

A Es

C GI (Ite m 1 o nl y)

S F- 3 6 q uesti o n naire
St art of Tre at me nt 
F oll o wi n g acti vities will be p erf or me d: 

Trai n p atie nt o n L- Cs A 
 use, dr u g st ora g e, a n d i n h alati o n tec h ni q ue

I M P A d mi nistrati o n. S u p er vis e first i n halati o n f or pr o per us e of t he ne b ulizer a n d f or
t olera bilit y iss u es.

Verif y pati e nt is fa miliar wit h dr u g a d mi nistrati o n a n d use of ne b ulizer de vi ce

E m p h asize i m p orta nce of a d here n ce t o I M P

E m p h asize i m p orta nce of a d h ere n ce t o us u al me dicati o ns as ta ke n pri or t o p artici pati n g i n t he
trial

S pir o metr y: ( 1 h o ur ± 2 0 mi n utes after c o m pl eti o n of d osi n g wit h I M P)

P K bl o o d sa m ples directl y after e n d of i n halati o n, 1 5, 3 0, a n d 4 5 mi n ut es ( +/- 5 mi n), a n d 1,
1. 5, 2, a n d 4 h o urs ( +/- 1 5 mi n.) aft er e n d of i n hal ati o n

L ocal I M P t olera bilit y
Pri or t o rel eas e fr o m cli nic, st u d y dr u g a n d t h e n e b ulizer s yste m f or h o m e use will be dis pe nse d t o 
eac h p ati e nt. Pati e nt will recei ve f ull I M P s u p pl y f or t he 1 2 wee ks treat me nt peri o d.  
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 6 1  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 4  S T A TI S TI C S 
T his secti o n prese nts a n o ver vie w of t he pla n ne d a nal yses. Fi nal a nal yses are n ot li mit e d t o t he 
s u m mari es d escri be d h erei n. T he Statistical A nal ysis Pla n ( S A P) will pr o vi de a d etail e d 
descri pti o n of t h e pl a n ne d statisti cal a n al yses a n d dat a s u m maries, a n d will be fi nali ze d b ef ore 
data base l o c k or a n y u n bli n di n g f or t his st u d y. If circ u mst a nces aris e d uri n g t he cli nical tri al t hat 
ma ke t hese a nal yses i n a p pr o priate or if i m pr o ve d met h o ds bec o me a vail a ble, t h e S A P ma y be 
re vise d. If discre pa nci es e xist bet wee n t he te xt of t h e st atistical a nal ysis as pla n ne d i n t he pr ot oc ol 
a n d t h e fi n al S A P, t he fi nal S A P will defi n e t h e pla n n e d a nal ysis of rec or d. Reas o ns f or s uc h 
discre pa n cies will b e d escri be d i n t he fi nal Cli ni cal St u d y Re p ort ( C S R).  
T his is a P h ase IIa, pr os pecti ve, m ultice nt er, ra n d o mize d, pl ace b o-c o ntr olle d trial wit h a fi xe d 
sa m ple size d esi g n. 
All a nal yses will be e x pl orat or y, a n d he nce a n y p- val u es will b e i nter prete d descri pti v el y wit h o ut 
a dj ust me nt. 
Data will be liste d b y pati e nt a n d treat me nt gr o u p. 
1 4. 1  A n al y si s D at a S et s 
T he f oll o wi n g a nal ysis d at a sets will be a nal y ze d: 
S afet y A n al ysis Set ( S A F S et) 
T he S A F is defi ne d as all ra n d o mize d patie nts w h o h a ve recei v e d a parti al d ose of I M P at least 
o nce. All data c ollecte d after b aseli n e t o t h e e n d of cli nical trial parti ci pati o n will b e i n cl u de d i n 
t he safet y s u m mari es.  
F ull A n al ysis S et ( F A S) 
T he F A S is defi ne d as all ra n d o mize d patie nts f or w h o m at l east o ne p ost- baseli ne meas ure m e nt 
of a n effi cac y o utc o me meas ure is a v aila ble, i.e. f or s pir o metr y or q ualit y of life meas ures is 
a vaila bl e.  
A Bli n d Data Re vie w M eeti n g ( B D R M) will be use d t o deter mi n e if patie nts s h o ul d b e e xcl u d e d 
fr o m t he F A S i n cases of si g nifica nt, maj or pr ot oc ol d e viati o ns t hat precl u de a n assess me nt of 
treat me nt effi cac y (e. g., ra n d o mize d patie nts n ot s ufferi n g fr o m t he c o n diti o n u n der i n vesti g ati o n). 
Per Pr ot oc ol Set ( P P S) 
T he P P S is defi n e d as all patie nts i n cl u de d i n t h e F A S 

w h o c o m plete ra n d o mize d treat me nt as sc he d ule d or w h o are wit h dra w n pre mat urel y d ue t o
lac k of efficac y or lac k of t olera bilit y of t he cli nic al trial treat me nt, a n d

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 6 2  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 

f or w h o m n o maj or pr ot oc ol de viati o ns was i de ntifie d d uri n g t he dat a re vie w meeti n g. T he
maj or pr ot oc ol d e viati o n crit eria will be defi ne d i n t he pr ot o c ol de viati o n list a n d re vi e w e d
bef ore d ata base cl os ure. T he re vie w e d pr ot oc ol de vi ati o n list will be i n cl u de d i nt o i n t he
cli nical st u d y re p ort as a p pe n di x. .
Eli gi bilit y f or t h e a nal ysis data s ets will b e d eter mi ne d i n a B D R M h el d after cl osi n g t h e data base 
bef ore u n bli n di n g. Pr ot o c ol de viati o ns will be classifie d as ‘ maj or’ w he n a si g nifica nt i nfl u e nce 
o n t he assess me nt of treat me nt efficac y ca n n ot b e e xcl u de d. C o m pre he nsi v e j ustificati o n f or t he 
classificati o n of a pr ot oc ol de viati o n as ‘ maj or’ will be gi v e n i n t h e B D R M mi n utes as well as i n 
t he i nte grate d C S R. A n y e xcl usi o n of patie nts fr o m t he F A S will re q uire i n di vi d u al j ustificati o n. 
A n y dat a p ert ai ni n g t o safet y a n d t olera bilit y will b e a nal yze d i n t he S A F. T h e a nal ysis of treat me nt 
efficac y will b e perf or me d i n t he F A S. A n a d diti o nal effi cac y a n al ysis i n t he P P S will be pr o vi d e d 
as a s e nsiti vit y a nal ysis. F or s afet y o ut c o mes p atie nts will be a nal yse d acc or di n g t o t h e treat me nt 
act u all y recei ve d. F or efficac y meas ures p atie nts will be a nal yse d as ra n d o mi ze d. 
1 4. 2  St ati sti c al a n d A n al yti c al M et h o d s 
1 4. 2. 1  D e s c ri pti v e St ati sti c s 
T he d ata rec or de d i n t h e case re p ort f or ms will be s u m m arize d as a p pr o priate, p er treat me nt gr o u p 
a n d f or t h e t otal gr o u p, usi n g t he f oll o wi n g descri pti v e meas ures: 

All c o nti n u o us assess m e nts will be s u m marize d usi n g descri pti ve st atistics (i. e., N, mea n,
sta n dar d d e vi ati o n, 
me di a n, l o wer q u artile ( Q 1), u p per q uartile ( Q 3), 
mi ni m u m, a n d
ma xi m u m).

All cate g orical assess me nts will b e s u m mari ze d b y ti me p oi nt, as a p plica bl e, usi n g fre q ue n c y
c o u nts a n d perce nta g es.

Discrete or di nal or metric data will b e s u m mariz e d as c o nti n u o us d ata, b ut a ta b ul ati o n of
cate g ories m a y b e i ncl u de d a d diti o n all y d e pe n di n g o n t he n u m ber of cate g ori es.
F or all meas ures a nal y ze d d escri pti v el y (i. e., me as ures t o c haracterize t h e treat me nt gr o u ps a n d 
t heir b aseli n e stat us, effi cac y, a n d safet y o utc o mes), ta b ul ati o ns c o m pari n g t h e treat me nt gr o u ps 
will be pre pare d. F or o ut c o mes meas ure d m ore t h a n o nce, t he a nal yses will i n cl u de ta b ulati o ns of 
t he meas ure d val ues b y visit as well as a n a nal ysis of c ha n ge fr o m baseli n e. W here pr o vi d e d, all 
c o nfi de nce i nter vals will b e t w o-si de d 9 5 % c o nfi de nce i nter v als. 
1 4. 2. 2  C h a r a ct e ri z ati o n a n d B a s eli n e C o m p a r a bilit y of T r e at m e nt G r o u p s 
T he n u m ber a n d perce nt a ge of p ati e nts w h o c o m plet e a n d disc o nti n u e t he cli nical trial as w ell as 
reas o ns f or earl y disc o nti n uati o n will be prese nte d. 
Descri pti v e statistics will b e prese nt e d f or de m o gra p hic, a nt hr o p o metric, a n d me dical d ata. 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 6 4  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 4. 2. 3. 3  M e as u r es of O v e r all T ol er a bilit y 
F or t he meas ures of o ver-all t olera bilit y i de ntifi e d i n Secti o n 1 2. 1. 5 , d escri pti ve statistics will be 
prese nte d b y visit (see S ecti o n 1 4. 2. 1 ). P air wise treat m e nt gr o u p c o m p aris o ns will b e p erf or m e d 
f or a p plica bl e visits usi n g e xact Wil c o x o n- M a n n- W hit ne y U-t ests. 
1 4. 2. 3. 4  L a b o r at o r y a n d Ot h er S af et y E v al u ati o ns 
F or cli ni cal safet y l a b orat or y test res ults a n d vit al si g ns, t he n u meric val u es a n d c orres p o n di n g 
c ha n ges fr o m b aseli ne will be s u m marize d usi n g d escri pti v e statistics b y p ara meter a n d ti m e p oi nt. 
I n a d diti o n t o t he ta bl es s h o wi n g t he distri b uti o n para meters, la b orat or y me as ures will be prese nt e d 
i n ‘s hift ta bles’ t hat s h o w t h e p ositi o n of all p atie nts relati v e t o t h e a p plic a ble refere nce ra n ge at 
cli nical trial e ntr y, br o k e n d o w n b y t h e p ositi o n at cli nical trial e xit. 
1 4. 2. 4  A n al y s e s of Effi c a c y 
A nal yses of efficac y will be b ase d o n t he F A S a n d o n t h e P P S a nal ysts p o p ul ati o ns. 
S c ori n g of t h e ei g ht scal es a n d t w o s u m m ar y sc ores of t he S F- 3 6 will b e perf or me d acc or di n g t o 
t he i nstr ucti o ns pr o vi d e d f or t h e A ustrali a n L o n git u di n al St u d y o n W o ma n’s Healt h.). 
F or t he s pir o metr y meas ures i d e ntifie d i n S ecti o n 1 1. 1. 1  as well as f or t he scales a n d s u m mar y 
sc ores of t he S F- 3 6, t he n u meric val u es a n d c orres p o n di n g c ha n g es fr o m baseli ne will be 
s u m mari ze d usi n g descri pti ve st atisti cs b y p ara meter a n d ti me p oi nt. 
T he a nal ysis will be carrie d o ut wit h a mi xe d m o del f or re peat e d meas ur es ( M M R M), usi n g all 
a vaila bl e meas ure m e nts of t h e o utc o m e of i nt erest. T he de pe n de nt v aria bl es will be t h e a bs ol ute 
c ha n ge fr o m b aseli n e of t h e o ut c o me of i nterest at t he visits sc he d ule d f or Wee ks 2 t hr o u g h 1 2, 
usi n g fi xe d effects f or tre at me nt, visit, a n d t h e treat m e nt x visit i nteracti o n a n d t h e b aseli n e val ue 
as a fi xe d effect c o vari ate. Ttreat me nt gr o u p c o m p aris o ns at eac h visit will be esti m ate d b y 
differe n ces b et wee n t he mar gi nal (a dj uste d) mea ns fr o m t he treat me nt x visit i nteracti o n, weit h 
acc o m pa n yi n g p- valies a n d 9 5 % c o nfi d e nce i nt er vals. F urt her details of t h e a n al ysis will be 
descri be d i n detail i n t he S A P. 
Descri pti v e s u m mar y me as ures will be pr o vi d e d b ase d o n all o bser ve d v al u es as w ell as b ase d o n 
t he mar gi n al mea ns deter mi ne d vi a M M R M a nal yses. 
1 4. 2. 5  P h a r m a c o ki n eti c V a ri a bl es 
T he st atistical a nal ysis will be perf or m e d as a vali d case a nal ysis i ncl u di n g all p atie nts of t he F A S. 
N o s u b gr o u p a n al ysis is pl a n ne d. 
Descri pti v e statistics will b e use d b y t he 
 ( N, arit h meti c mea ns, 
sta n dar d d e vi ati o n, ge o metric mea ns, g e o metric c oefficie nt of v ari ati o n, me dia ns, mi ni m u m a n d 
ma xi m u m) a n d will be prese nte d f or all P K p ara meters i n dicate d i n S ecti o n 8. 1. 6 , s e paratel y f or 
eac h treat me nt b y usi n g t h e 
.  
C CI
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 6 5  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
T he plas ma c o nce ntrati o n le vels i n t he 
 are meas ure d usi n g a 
vali d ate d L C- M S / M S met h o d. T he pr oce d ure f or vali dati o n a n d t he acce pt a nce li mits are bas e d 
o n t h e re q uire me nts of t he E M A G ui d eli n e ( G ui deli n e o n bi oa nal ytical met h o d vali dati o n ( E M E A 
/ C H M P / E W P / 1 9 2 2 1 7/ 2 0 0 9 Re v. 1 C orr. 2 * *), J ul y 2 0 1 1). 
T he statistical a nal ysis will be carrie d o ut o n a l o g scale f or A U C 0- 4 h a n d Cma x - val u es, w hil e tma x  
a n d tr o u g h le vels will be e val uat e d o n a li n ear scal e. A nal yses of varia nce will b e p erf or me d t o 
c o m p are t h e treat me nt gr o u ps. 
1 4. 3  I nt e ri m A n al ysi s  
N ot a p plica bl e. 
1 4. 4  Mi s si n g D at a 
N o missi n g data i m p utati o n will b e perf or me d. F or efficac y o ut c o mes, ti me c o urses will be 
m o dele d via M M R M (see Secti o n 1 4. 2. 4 ). 
1 4. 5  S a m pl e Si z e C o n si d e r ati o n s 
T his is a P hase IIa st u d y i n a rare i n di cati o n wit h v er y li mite d a vaila bilit y of eli gi ble p atie nts a n d 
a p urel y descri pti ve st atistical c o nce pt. Acc or di n gl y, t he sa m ple si ze f or t he st u d y was esta blis he d 
base d o n c o nsi d erati o ns of feasi bilit y rat h er t h a n o n p o wer calc ul ati o ns. 
A t ot al of 2 4  p atie nts ( 3 ar ms x 8 p atie nts eac h) are pla n ne d t o be ra n d o mi ze d. 
C CI

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 6 6  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 5  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 
S o urce dat a is all i nf or mati o n, 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 necess ar y f or t h e rec o nstr ucti o n a n d e v al uati o n of t h e trial. S o urce dat a are 
c o ntai ne d i n s o urce d o c u me nts. E x a m pl es of t h ese ori gi n al d oc u m e nts a n d dat a rec or ds i ncl u de 
b ut are n ot li mite d t o: h os pital rec or ds, cli nical a n d office c harts, l a b orat or y n otes, me m ora n d a, 
patie nts’ diaries or q u esti o n naires or e val u ati o n c hec klists, p har mac y dis pe nsi n g rec or ds, rec or de d 
data fr o m a ut o mat e d i nstr u me nts, c o pies or tra nscri pti o ns certifie d after verificati o n as b ei n g 
acc urate a n d c o m plete, micr ofic hes, p h ot o gra p hic n e gati ves, mi cr ofil ms or ma g netic me di a, X-
ra ys, p atie nt fil es, a n d rec or ds ke pt at t he p har ma c y, at t h e 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 trial. T h e e C R F is n ot c o nsi dere d t o b e s o urce data. 
Case re p ort f or ms, all c o pies of test res ults, a n d cli ni cal trial-relate d re g ul at or y d oc u me nts (e. g., 
I nf or me d C o nse nts, E C fa v o ura bl e o pi ni o n / c orres p o n de nce) m ust be a vaila bl e al wa ys f or 
re g ul at or y a g e nc y i ns p ecti o n a n d re vie w b y t h e S p o ns or or its d esi g nee. D uri n g t he peri o di c site 
m o nit ori n g visits, t he s o urce d oc u me nts will b e v erifie d a gai nst d ata e nt ere d o nt o t he e C R F t o 
ass ure t hat all data is acc uratel y a n d c o m plet el y reflecte d o n t he p atie nt’s e C R F. 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 6 7  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 6  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 
T his cli nical trial will b e m o nit ore d b y t he S p o ns or or its desi g nee acc or di n g t o I C H G C P 
g ui deli nes. A sit e visit will be h el d pri or t o i nitiati o n of patie nt e nr oll me nt. T h e pr ot oc ol, e C R Fs, 
I M P s u p pli es, a n d rele va nt pr oce d ures will be e x plai ne d i n detail at t he Site I nitiati o n Visit. 
S u bse q u e nt t o p atie nt e nr oll me nt, a site m o nit or fr o m t he S p o ns or or its d esi g nee will re vie w t he 
e C R Fs a n d s o urce d o c u me nts t o e ns ure t h at t he cli nical trial is c o n d uct e d ac c or di n g t o t h e pr ot o c ol 
a n d I C H G C P g ui deli nes. 
T o e ns ure c o m plia nce wit h I C H G C P g ui d eli n es a n d all a p plica bl e re g ulat or y re q uire me nts, t he 
S p o ns or or its desi g n ee ma y c o n d uct q u alit y ass ura nce a u dits. A n y p ote ntial seri o us G C P n o n-
c o m pli a n ce will b e pr o m ptl y re p orte d t o s p o ns or b y t he C R O a n d Healt h A ut h orities a n d Et hics 
C o m mitees, as a p plica ble. 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 6 8  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 7  E T HI C S C O M MI T T E E ( E C) 
T he pr ot oc ol a n d I C F(s) f or t his cli nical trial m ust h a ve recei v e d a fa v o ura bl e o pi ni o n b y a n 
a p pr o priatel y c o nstit ute d Et hics C o m mittee ( E C) as defi ne d b y l ocal re q uire me nts. A list of t he 
E C v oti n g me m bers, t heir titl es or occ u pati o n, a n d t heir i nstit uti o nal affiliati o ns (if a vaila ble a n d 
all o wa ble u n der E U l a w) a n d/ or t h e E C ge neral ass ura nce n u m b er, if a p plica bl e, m ust be s u b mitt e d 
t o t he S p o ns or or its desi g nee t o be arc hi ve d i n t he Trial Master Fil e. 
A n y d o c u me nts t hat t h e E C ma y n ee d t o f ulfill its res p o nsi bilities, s u c h as pr ot oc ol a me n d me nts, 
a n d i nf or m ati o n c o n cer ni n g patie nt recr uit m e nt, pa y me nt or c o m p e ns ati o n pr oce d ures, or 
i nf or mati o n fr o m Za m b o n S p A will be s u b mitte d t o t he E C. T he E C’s writte n fa v o ura ble o pi ni o n 
of t h e pr ot o c ol a n d t he I C F/ pati e nt i nf or m ati o n l eaflet will be i n t he p oss essi o n of t h e I n vesti gat or 
bef ore t he cli nical tri al is i nitiate d. T he E C’s fa v o ura ble o pi ni o n state me nt will be tra ns mitte d b y 
t he I n vesti g at or t o Za m b o n S p A or its d esi g nee pri or t o s hi p me nt of I M P s u p plies t o t he site. T his 
fa v o ura bl e o pi ni o n m ust refer t o t he cli nical trial b y e xact pr ot oc ol title a n d n u m ber, a n d s h o ul d 
i de ntif y t h e d oc u me nts re vie we d a n d t he d ate of re vie w. 
Pr ot oc ol m o difi cati o ns or c h a n ges ma y n ot b e i nitiate d wit h o ut pri or writte n E C f a v o ura bl e 
o pi ni o n e xce pt w he n necessar y t o eli mi n at e i m me diate hazar ds t o t h e patie nts or w he n t he 
c ha n ge(s) i n v ol ves o nl y l o gisti cal or a d mi nistrati ve as pects of t he cli nical tri al. S uc h m o difi cati o ns 
will be s u b mitte d t o t he E C a n d writte n verificati o n t hat t he m o dificati o n was s u b mitte d s h o ul d be 
o btai ne d. 
T he E C m ust be i nf or me d b y t he I n v esti g at or of i nf or me d c o nse nt c ha n g es or re visi o ns of ot h er 
d oc u me nts ori gi nall y s u b mitte d f or re vie w; s eri o us a n d/ or u n e x pect e d A Es occ urri n g d uri n g t he 
cli nical trial; ne w i nf or mati o n t hat ma y a d versel y affect t he safet y of t he patie nts or t he c o n d u ct of 
t he cli nical trial; a n a n n u al u p d ate a n d/ or r e q u est f or re vi e w a n d o pi ni o n; a n d w he n t he cli nic al 
trial has bee n c o m pl et e d. 
T he I n vesti gat or will e ns ure t h at t h e c o n d uct of t he cli ni cal trial c o nf or ms t o t h e Declarati o n of 
Helsi n ki (c urre nt re visi o n) a n d wit h a p plica ble n ati o nal la ws a n d re g ul ati o ns f or cli nical rese arc h. 
Bef ore starti n g t his cli nical trial, t he pr ot oc ol will be s u b mitt e d t o eac h ce nter’s Et hics C o m mittee 
f or e val uati o n at eac h site. As re q uire d, t h e cli nic al trial will n ot start bef ore t h e E C has gi ve n 
fa v o ura bl e o pi ni o n. 
P eri o dic stat us re p orts a n d S A Es m ust be s u b mitt e d t o t h e E C acc or di n g t o t h e E C re p orti n g 
re q uire me nts. T he E C m ust als o b e n otifie d of c o m pleti o n of t h e cli nical trial a n d a fi nal re p ort 
m ust b e s u b mitte d t o t h e E C i n acc or da nce wit h t he E C re p orti n g re q uire m e nts. T he I n vesti gat or 
m ust mai ntai n a n acc urat e a n d c o m plete rec or d of all c o m m u nicati o n, re p orts a n d s u b missi o ns t o 
t he E C. 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 6 9  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 8  P A TI E N T I N F O R M E D C O N S E N T 
P atie nts will be re q uire d t o si g n a state me nt of i nf or me d c o ns e nt t h at meets t h e re q uire me nts of 
E ur o pea n a n d l ocal re g ulati o ns, I C H E 6 ( R 2) g ui deli nes, a n d t he E C of t he ce nter. T h e me di cal 
rec or d will i n cl u de a st at e me nt t hat writt e n i nf or me d c o nse nt was o btai ne d bef ore t h e patie nt was 
e nr olle d i n t h e cli nical trial a n d t he d ate writte n c o nse nt was o btai ne d. 
Me m b ers of t h e treati n g tea m will re vi e w t he n at ur e of t he cli nical trial, its p ur p ose, t he pr oc e d ures 
i n v ol ve d, t he e x pect e d d urati o n, t he p ote ntial ris ks a n d be nefits a n d alter n ati ve t hera pies i n cl u di n g 
best s u p p orti ve care. P atie nts m ust b e i nf or me d t hat p artici p ati o n i n t h e cli nical trial is v ol u ntar y, 
he/s he ma y wit h dra w fr o m t h e cli ni cal tri al at a n y ti me a n d wit h dra wal fr o m t he trial will n ot affect 
his/ h er s u bse q ue nt me dical treat me nt or relati o ns hi p wit h t h e treati n g p h ysicia n. Fi n a ncial c osts 
t hat will or ma y be i n c urre d as a res ult of partici p ati o n i n t he trial, as well as t he eff orts t o mai ntai n 
patie nt c o nfi de ntialit y will als o b e disc usse d. 
T his c o nse nt m ust be wit n esse d a n d d ate d a n d retai ne d b y t he I n vesti gat or as part of t h e cli nical 
trial rec or ds. A c o p y of t h e I C F m ust be gi v e n t o t he patie nt. If t h e p atie nt si g ne d t he i nf or m e d 
c o nse nt m ore t ha n 3 0 da ys pri or t o t h e d ate of ra n d o mi zati o n, it s h o ul d b e d o c u me nte d t h at c o nse nt 
has n ot bee n resci n de d. Alter nati v el y, t h e site s h o ul d f oll o w t he E C’s re q uire me nt f or re-
c o nse nti n g a p atie nt. 
A c o p y of t he E C a p pr o ve d c o nse nt f or m m ust be s u b mitte d t o Z a m b o n S p A or its desi g nee pri or 
t o s hi p me nt of I M P s u p pli es t o t h e I n v esti gat or. Eac h pati e nt’s si g ne d i nf or me d c o ns e nt m ust be 
ke pt o n file b y t h e I n vesti gat or f or re g ulat or y a ut h orit y a n d S p o ns or i ns pecti o n at a n y ti me. 
T he Decl arati o n of H elsi n ki, as a me n d e d ( v ersi o n of F ortaleza, Brazil, 2 0 1 3), rec o m me n dati o ns 
g ui di n g d o ct ors i n cli nical researc h s h o ul d b e f oll o we d b y t he I n v esti gat or.  

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 7 0  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 9  H E A L T H A U T H O RI TI E S 
T he pr ot o c ol a n d a n y rel at e d d o c u me ntati o n i ncl u di n g all s u bse q u e nt c ha n g es (s u bsta ntial 
a me n d me nts) of t h ese d oc u me nts will be s u b mitt e d f or a p pr o v al t o t he re g ul at or y a ut h orities i n 
c o m pli a n ce wit h a p plica ble E ur o pea n re g ul ati o ns. 
N o n-s u bsta ntial a me n d m e nts will be s u b mitt e d acc or di n g t o l ocal re g ul at or y re q uire me nts f or 
n otificati o n.  
A n y pre mat ure ter mi nati o n of t he cli nical trial will be s u b mitte d wit hi n 1 5 d a ys, a n d re g ul ar e n d 
of t h e st u d y will be n otifie d as well. 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 7 1  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
2 0  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 
2 0. 1  C o nfi d e nti alit y 
T o mai ntai n c o nfi de nti alit y, all la b orat or y s p eci m e ns, e val uati o n f or ms, re p orts a n d ot h er rec or ds 
will be i d e ntifie d b y a c o de d n u m ber a n d i nitials o nl y. All cli ni cal trial rec or ds will be ke pt at eac h 
ce nt er i n a l o c ke d fil e ca bi n et. Cli nical i nf or m ati o n will n ot be releas e d wit h o ut writte n per missi o n 
of t h e patie nt, e xce pt as n ecessar y f or m o nit ori n g or i ns pecti o ns b y t he a ut h oriti es or a d esi g nee of 
t he S p o ns or as d escri b e d i n t h e i nf or me d c o nse nt f or m.  
T he I n v esti gat or m ust ass ure t hat t he pri v ac y of t he p atie nts, i n cl u di n g t h eir pers o nal i de ntit y a n d 
all pers o nal me dical i nf or mati o n, will be mai ntai ne d at all ti mes. I n e C R Fs a n d ot her d o c u me nts 
patie nts will n ot b e i d e ntifie d b y t heir na mes, b ut b y a n i de ntificati o n c o de (e. g., b y a n ar bitrar y, 
u ni q ue patie nt n u m b er). 
T he I n vesti g at or a grees t hat all i nf or mati o n recei ve d fr o m Z a m b o n S p A i ncl u di n g b ut n ot li mit e d 
t o t his pr ot oc ol, e C R F, a n d a n y ot her cli ni cal trial i nf or mati o n, re mai n t he s ole a n d e x cl usi ve 
pr o pert y of Z a m b o n S p A d uri n g t he c o n d u ct of t he cli nical trial a n d t h ereafter. T his i nf or mati o n 
is n ot t o be discl ose d t o a n y t hir d p art y ( e x ce pt e m pl o yees or a ge nts directl y i n v ol v e d i n t he 
c o n d uct of t he trial or as re q uire d b y l a w) wit h o ut pri or writte n c o nse nt fr o m Za m b o n S p A. T he 
I n v esti gat or f urt her a gr ees t o ta k e all reas o n a bl e preca uti o ns t o pr e ve nt t h e discl os ure b y a n y 
e m pl o y ee or a g e nt of t h e i n vesti gati ve site t o a n y t hir d part y or ot her wise i nt o t he p u blic d o mai n. 
Wit h refere nce t o E U Re g ul ati o n n o. 6 7 9/ 2 0 1 6 of E ur o pea n P arlia me nt a n d of t h e C o u ncil of 2 7 
A pril 2 0 1 6, t he Ge neral Data Pr otecti o n Re g ulati o n ( G D P R), a n d ot her l o cal la w pr o visi o ns t he 
data pr ot ecti o n r ol es wit hi n t h e st u d y are t he f oll o wi n g: 

t he s p o ns or a n d t h e i n vesti gati o nal ce nter are a ut o n o m o us d ata c o ntr ollers, a n d will pr ocess
t he pers o n al a n d st u d y d at a of t h e partici pa nts e x cl usi vel y f or st u d y relate d p ur p oses a n d f or
p har mac o vi gil a n ce p ur p oses.

T he C R O will pr o cess t he parti ci p a nt’s data o n b e half of t h e s p o ns or a n d will be a p p oi nte d as
a dat a pr o cess or b y t he s p o ns or. T he C R O ma y a vail itself of s u b c o ntract ors, w h o will be
a p p oi nte d as s u b pr ocess ors as well, p urs ua nt t o art. 2 8 of G D P R.

T he pri n ci pal i n vesti gat ors will pr ocess t he data as a data pr ocess or, o n be half of t h e st u d y
ce nt er.
As c o ncer ns t he d ata pr ot ecti o n i nf or mati o n/ n otice, partici pa nts m ust be i nf or me d pr o perl y a b o ut 
all t he dat a pr otecti o n ele me nts pr o vi d e d b y art. 1 3 a n d 1 4 of G D P R. I n v esti g at or or his/ h er 
re pres e ntati ve will gi v e t o t he partici pa nt a pr o per data pr otecti o n i nf or mati o n n otice c o m plia nt 
wit h G D P R, a n d will c o nse q ue ntl y as k t o t h e parti ci pa nt a data pr otecti o n c o nse nt, t o get her wit h 
t he st u d y i nf or me d c o nse nt. Acc or di n g t o t he pr o visi o ns of t he G D P R, t he le vel of discl os ure i n 
t he i nf or me d c o nse nt m ust als o be e x plai ne d t o t he partici pa nt. T h e p artici pa nt m ust b e i nf or me d 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 7 2  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
t hat his/ her me dical rec or ds ma y b e e xa mi ne d b y A u dit ors or ot her a ut h ori ze d pers o n n el a p p oi nt e d 
b y t h e s p o ns or, b y a p pr o priate I R B/I E C me m bers, a n d b y i ns pect ors fr o m re g ulat or y a ut h orities. 
As re g ar ds t h e or ga nizati o nal a n d sec urit y meas ures a d o pte d, t he o p erati o ns of c ollecti o n, st ora ge, 
circ ulati o n of bi ol o gical sa m ples as well as all t he data pr ocessi n g o p erati o ns re gar di n g t he st u d y 
data are perf or me d i n c o m plia nce wit h G D P R. T he i n vesti g at or or his/ her re prese ntati ve will 
assi g n t o t h e p artici pa nts a u ni q ue i d e ntifier. I n v esti g at or will be t h e o nl y o ne w h o ca n matc h t he 
partici pa nt’s i de ntit y wit h t he dat a referre d t o t he st u d y. A n y p artici pa nt rec or ds or d atasets t h at 
are tra nsferre d t o t he s p o ns or will c o nt ai n t he i d e ntifier c o d e o nl y; parti ci pa nt na mes or a n y ot h er 
i nf or mati o n w hic h w o ul d ma ke t he partici p a nt i de ntifia ble will n ot be tra nsferre d t o t he s p o ns or. 
2 0. 2  C o m pl eti o n of El e ct r o ni c C a s e R e p o rt F o r m s 
A n e C R F will be use d i n t his cli nical trial. Staff a ut h orize d t o e nter or m o dif y dat a o n t he e C R F 
will be assi g ne d a n a p pr o priate user r ole: 

st u d y c o or di n at ors or n urses ma y e nter, m o dif y, or d elete d ata a n d ma y e nter, m o dif y, or delete
res p o nses t o q ueri es;

i n v esti g at ors ma y perf or m t h e sa me acti vities as st u d y c o or di n at ors. M ore o ver, t he y ma y
a ut h orize d ata b y e nteri n g a n electr o ni c si g nat ure.
A n y dat a e ntries, m o dificati o ns, a n d deleti o ns will be re c or de d i n a n a ut o mat e d a u dit trail t o get her 
wit h a ti me sta m p a n d t he i de ntificati o n c o de of t he pers o n perf or mi n g t h e e ntr y / m o dificati o n / 
deleti o n. 
T o access t h e e C R F a ut h orize d users will recei v e a u ni q u e user na me a n d pass w or d t h at will als o 
be re q uire d f or d ata a ut h orizati o n (i n vesti g at ors o nl y). T hese cre de ntials are strictl y pers o n al a n d 
c o nfi de ntial a n d m ust n ot be s hare d wit h a n y o ne. 
I n v esti gat ors will be pr o vi d e d wit h d et aile d e C R F C o m pleti o n G ui d eli n es t hat will i de ntif y t he 
re q uire d d at a p oi nts t o be c oll ect e d, h o w t o d o c u me nt t he m a n d w he n t hese data s h o ul d be 
d oc u me nt e d. A p pr o priate trai ni n g i n electr o nic d ata ca pt ure a n d s u p p ort will be pr o vi de d. 
It is t he res p o nsi bilit y of t he I n vesti gat or t o mai ntai n a d e q uate a n d acc urate e C R Fs t o rec or d 
(acc or di n g t o t he e C R F C o m pleti o n G ui d eli n es) all o bser vati o ns a n d ot h er d ata perti ne nt t o t h e 
cli nical trial o btai n e d d uri n g sc he d ul e d or u nsc he d ule d visits. All e C R Fs s h o ul d be f ull y c o m plete d 
t o e ns ure acc urate data i nter pretati o n. 
All e C R F e ntries s h o ul d b e ma de wit hi n a ma xi m u m of 5 da ys of a visit b y a desi g nate d a n d trai n e d 
me m ber of t he site staff. T he I n vesti gat or m ust e ns ure t he acc urac y, c o m plete ness l e gi bilit y a n d 
ti meli ness of d ata re p ort e d i n t he e C R F a n d all re q uire d re p orts. A n y c ha n g e or c orrecti o n t o a n 
e C R F m ust be d oc u me nte d as i nstr uct e d a n d e x plai ne d (if n ecessar y) i n t h e cli nic n otes, t his 
a p pli es t o b ot h writte n a n d electr o nic c h a n ges. T he pati e nt’s me dical s o urce d oc u me nts m ust 
s u p p ort a n y c ha n ges ma d e. 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 7 3  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
Data re p orte d i n t h e e C R F t hat are d eri v e d fr o m s o urce d o c u me nts s h o ul d be c o nsiste nt wit h t he 
s o urce d o c u m e nts or t he discre p a ncies s h o ul d be e x plai n e d. 
T he i n vesti g at or m ust re vi e w a n d electr o ni call y si g n t he c o m pl et e d e C R F case b o o k t o verif y its 
acc urac y. 
T he mai n o bjecti v e is t o o bt ai n t h ose data re q uire d b y t he pr ot oc ol i n a c o m plete, acc urate, le gi ble, 
a n d ti m el y fas hi o n. T hese data i n t he e C R F s h o ul d b e c o nsiste nt wit h t he rele va nt s o urc e 
d oc u me nts. 
T he e C R Fs a n d t h e c orres p o n di n g electr o ni c dat a base s h all b e pr ocess e d, e v al u at e d, a n d st ore d i n 
a n o n y m o us f or m i n acc or da nce wit h t he data- pr otecti o n re g ulati o ns. 
T hese d at a rec or de d i n t h e c o urse of t his cli nical trial ma y peri o dicall y be r e m otel y re vie we d a n d 
c o m p are d t o t he el ectr o ni c dat a base. T he c o m p uteri ze d ha n dli n g of t h ese d at a after recei pt of t he 
e C R Fs ma y ge nerate a d diti o n al re q uests vi a electr o ni c q ueries t o w hi c h t he I n v esti g at or is o bli ge d 
t o res p o n d b y c o nfir mi n g or m o dif yi n g t h ese d ata q uesti o ne d. T hese re q u ests wit h t h eir res p o nses 
will be a p pe n de d t o t he e C R Fs hel d b y t h e I n vesti gat or a n d S p o ns or. 
I n t he case of missi n g data/re m ar ks, t he e ntr y s paces pr o vi de d f or i n t h e e C R F s h o ul d b e ca ncell e d 
o ut t o a v oi d u n necess ar y f oll o w- u p i n q uiries. T he e C R Fs are re g ul at or y d oc u me nts a n d m ust be 
s uita ble f or ele ctr o nic s u b missi o n t o a ut h oriti es. 
T he I n vesti gat or m ust k ee p a s e p arat e pati e nt i de ntifi cati o n list s h o wi n g c o de n u m bers, na m es, 
a n d dates of birt h t o all o w u na m bi g u o us i d e ntificati o n of eac h pati e nt i ncl u de d i n t he cli ni cal trial. 
A n ote will be ma de i n t h e h os pital me dical r ec or ds t h at t h e patie nt is partici p ati n g i n a cli nical 
trial. T he e C R F will be c o m plete d a p pr o priatel y. 
2 0. 3  S o u r c e D at a a n d P ati e nt Fil e s 
T he I n vesti g at or has t o k ee p a p a per or electr o ni c pati e nt file f or e ver y patie nt partici pati n g i n t he 
cli nical trial. I n t his p atie nt file, t h e a vail a ble d e m o gra p hi c a n d m e dical i nf or mati o n of a p atie nt 
has t o b e d oc u me nte d, i n partic ul ar t he f oll o wi n g: na me, d ate of birt h, se x, h ei g ht, wei g ht, p atie nt 
hist or y, c o nc o mita nt dise ases a n d c o nc o mita nt me dicati o n (i ncl u di n g c ha n ges d uri n g t h e cli nical 
trial), state me nt of e ntr y i nt o t h e cli nical trial, trial i de ntifi cati o n, p atie nt n u m b er, t he dat e of 
i nf or me d c o nse nt, all visit dat es, pre- d efi n e d perf or me d e xa mi nati o ns a n d cli nical fi n di n gs, 
o bser v e d A Es (if a p pli ca ble) a n d reas o n f or wit h dra wal fr o m cli nical trial treat me nt or fr o m t he 
trial (if a p plica ble). It s h o ul d be p ossi ble t o verif y t he i ncl usi o n a n d e x cl usi o n criteri a f or t he 
cli nical trial fr o m t h e a v aila ble d ata i n t his fil e. It m ust be p ossi ble t o i de ntif y eac h p atie nt b y usi n g 
t his pati e nt file. 
A d diti o n all y, a n y ot her d o c u me nts wit h s o urce data, es peciall y ori gi nal pri nt o uts of data t hat were 
ge nerat e d b y tec h ni cal e q ui p me nt ha ve t o be file d. T his m a y i n cl u de la b orat or y v al ue listi n gs, 
electr ocar di o gra m rec or di n gs, X-ra ys, c o m p ute d t o m o gra p h y sca ns, et c. (if a p pli ca ble). All t hese 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 7 4  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
d oc u me nts ha ve t o be ar at least t h e patie nt i d e ntificati o n a n d t h e pri nti n g date pri nt e d b y t he 
rec or di n g d e vice t o i n dic ate t o w hi c h patie nt a n d t o w hic h pr oce d ure t h e d oc u me nt bel o n gs. T he 
me di cal e val u ati o n of s uc h rec or ds s h o ul d be d oc u me nte d as necess ar y a n d si g n e d/ d ate d b y t he 
I n v esti gat or. 
Pri nt o uts of c o m p uterize d pati e nt files m ust be si g ne d a n d date d b y t he I n v esti gat or, a n d k e pt as a 
s o urce d o c u m e nt. 
2 0. 4  I n v e sti g at o r Fil e a n d Ar c hi vi n g 
T he S p o ns or will pr o vi de, a n d t he i n vesti gat or will mai ntai n a n I n v esti g at or Site File (I S F) 
c o ntai ni n g all esse ntial d oc u me nts f or t he cli nical trial. T h e I S F will c o nt ai n eac h p atie nt’s e C R F 
p df after t he data base has bee n l o c ke d. T h e i n v esti g at or s h o ul d mai ntai n a rec or d of t he l ocati o n(s) 
of t heir res pecti ve esse nti al d oc u me nts i n cl u di n g s o urce d oc u me nts. T he st ora ge s yste m use d 
d uri n g t he trial a n d f or arc hi vi n g (irres p ecti ve of t he t y p e of me di a use d) s h o ul d pr o vi de f or 
d oc u me nt i d e ntificati o n, versi o n hist or y, searc h a n d retri e val. 
Esse ntial d o c u me nts ar e s u bject t o a u dit a n d i ns pe cti o n at all ti mes a n d will be arc hi v e d acc or di n g 
t o a p plica bl e re g ul at or y re q uire me nts. 
2 0. 5  M o nit o ri n g, Q u alit y As s u r a n c e, a n d I n s p e cti o n b y A ut h o riti e s 
T his cli ni cal trial is t o be c o n d ucte d i n acc or da n ce wit h I C H E 6 ( R 2) a n d a p pli ca ble E ur o pea n 
re g ul ati o ns. M o nit ori n g a n d a u diti n g of t he trial will b e t he res p o nsi bilit y of t he S p o ns or or a 
desi g nee a ut h ori ze d b y t he S p o ns or. 
T o e ns ure c o m plia nce wit h I C H G C P g ui d eli n es a n d all a p plica bl e re g ulat or y re q uire me nts, t he 
S p o ns or or its desi g nee m a y c o n d uct q ualit y ass ura nce a u dits. R e g ulat or y a ge ncies ma y als o 
c o n d uct a re g ulat or y i ns p ecti o n of t his cli ni cal trial. S uc h a u dits or i ns pecti o ns ca n o cc ur at a n y 
ti me d uri n g or after c o m pleti o n of t he cli nical trial. If a u dits or i ns pecti o ns occ ur, t h e I n vesti gat or 
a n d t he i nstit uti o n a gree t o all o w t he a u dit or/i ns p ect or direct access t o all rel e va nt d oc u me nts a n d 
t o all ocate his/ her ti m e a n d t h e ti me of his/ her staff t o t h e a u dit or/i ns pect or t o disc uss fi n di n gs a n d 
a n y rel e va nt iss ues. 
2 0. 6  D at a M a n a g e m e nt a n d D at a C o nt r ol 
T he S p o ns or will be res p o nsi ble f or t h e pr oc essi n g a n d q ualit y c o ntr ol of t he data. Data 
ma na ge me nt a n d fili n g will b e carrie d o ut as descri b e d i n t he c o ntracte d C R O’s Sta n dar d 
O perati n g Pr oce d ures f or cli ni cal tri als. 
Pri or a n d c o nc urre nt me dicati o ns wit hi n 3 0 da ys of ra n d o mizati o n will be liste d. Pri or/c o n c urre nt 
me di cati o ns will be c o de d usi n g t h e W orl d Healt h Or ga nizati o n Dr u g Di cti o nar y classifi cati o n 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 7 5  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
s yste m a n d gr o u pe d b y dr u g class a n d pr eferre d ter m. A Es a n d c urre nt me dical c o n diti o ns f or 
c o nc o mita nt me dicati o ns will be c o de d usi n g M e d D R A.  
T he e C R F dat a a n d pati e nt data listi n gs will be arc hi ve d b y t he S p o ns or f or t h e lifeti me of t he 
pr o d uct. N o cli nical trial d oc u me nt s h o ul d be destr o ye d wit h o ut pri or writte n a gree me nt b et wee n 
t he S p o ns or a n d t he I n vesti gat or. S h o ul d t he I n vesti gat or wis h t o assi g n t h e cli nical trial rec or ds 
t o a n ot her part y or m o ve t h e m t o a n ot h er l ocati o n, a d va nce writte n n otice s h o ul d be gi ve n t o t he 
S p o ns or. 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 7 6  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
2 1  FI N A N CI N G A N D I N S U R A N C E 
A se parat e fi na ncial a gree me nt ( Cli nical I n vesti gat ors' A gr ee me nt) will be ma de bet w ee n eac h 
I n v esti gat or a n d t he S p o ns or bef ore t h e I M P is deli v ere d. T he S p o ns or will e ns ure fi n a nci n g of t he 
c o m plete cli nical tri al. 
T he cli nical trial is c o vere d u n der a S p o ns or gr o u p c o m bi n e d lia bilit y i ns ura nce p olic y. T he 
certifi cate of i ns ura nce a n d a n i nf or mati o n leaflet c o ntai ni n g ess e ntial i nf or mati o n a b o ut t he 
i ns ura nce c o vera ge will be pr o vi de d u p o n re q uest. 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 7 7  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
2 2  P U B LI C A TI O N S 
After c o ncl usi o n of t he cli nical trial, a n i nte grat e d cli nical a n d statistical st u d y re p ort will be 
pre pare d b y t h e S p o ns or or d esi g ne e. T he first p u blicati o n of t he cli nical trial will c o m prise of data 
fr o m t he e ntire cli ni cal tri al p o p ulati o n e nr oll e d at all sites. A n y p u blicati o ns of t he res ults, eit h er 
i n part or i n t otal (a bstracts i n j o ur nals or ne ws p a pers, oral prese ntati o ns, etc.) b y I n vesti g at ors or 
t heir re prese nt ati ves will re q uire pre-s u b missi o n re vie w b y t h e S p o ns or. T he S p o ns or is e ntitle d t o 
dela y p u blicati o n i n or der t o o bt ai n pate nt pr otecti o n. F or m ore details re g ar di n g p u blicati o ns, refer 
t o t he cli ni cal trial a gree me nt/I n v esti gat or trial a gree me nt. 
T he res ults of t h e cli nical trial will be p u blis h e d a n d/ or prese nt e d i n scie ntific meeti n gs i n a ti mel y 
ma n n er. A n y f or mal p u blicati o n of cli nical trial res ults will be a c olla b or ati ve eff ort b et wee n t he 
S p o ns or a n d t he I n vesti gat or(s). All ma n uscri pts a n d a bstracts will be re vi e we d a n d a p pr o ve d i n 
writi n g b y t he S p o ns or pri or t o s u b missi o n.  
P oli cies re gar di n g t h e p u blicati o n of t he cli nical trial res ults are defi n e d i n t he Cli nical 
I n v esti gat or’s A gr ee me nt. 

L- Cs A: 
Pr ot o c ol N u m b er: 
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Pa g e 7 8  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
2 3  R E F E R E N C E S 
1.  A g uilar 
P R, 
Mi c hels o n 
A P, Isa k o w 
W. 
O bliterati ve br o nc hi olitis. 
Tra ns pla ntati o n 
2 0 1 6; 1 0 0( 2): 2 7 2- 8 3.  
2.  A u B K, A u M A, C hie n J W. Br o n c hi olitis o blitera ns s y n dr o me e pi de mi ol o g y aft er all o ge n eic 
he mat o p oietic cell tra ns pl a ntati o n. Bi ol Bl o o d Marr o w Tra ns pla nt 2 0 1 1; 1 7( 7): 1 0 7 2- 8. 
3.  Bar ker A F, Ber ger o n, A R o m 
W N et al. O blit erati v e br o nc hi olitis. N E n gl J 
M e d 
2 0 1 4; 3 7 0: 1 8 2 0- 1 8 2 8. 
4.  Be hr J, Zi m m er ma n n G, Ba u m g art n er R et al. L u n g de p ositi o n of a li p os o mal c ycl os p ori n e A 
i n halati o n s ol uti o n i n patie nts after l u n g tra ns pl a ntati o n. J Aer os ol M e d P ul m Dr u g Deli v 
2 0 0 9; 2 2( 2): 1 2 1- 1 3 0. 
5.  Ber ger o n A, C he vret S, Gra nata A et al. Effect of azit hr o m yci n o n airfl o w decli ne-free s ur vi v al 
after all o g e neic he mat o p oietic st e m cell tra ns pla nt: t he A L L O ZI T H R O ra n d o mi ze d cli nical 
trial. J A M A 2 0 1 7; 3 1 8( 6): 5 5 7- 5 6 6. 
6.  C orc ora n T E, S mal d o ne G C, Da u ber J H et al. Preser vati o n of p ost-tra ns pl a nt l u n g f u ncti o n 
wit h aer os ol c ycl os p ori n. E ur Res pir J 2 0 0 4; 2 3( 3): 3 7 8- 3 8 3. 
7.  C orc ora n T E. I n h ale d deli ver y of aer os olize d c y cl os p ori ne. 
A d v 
Dr u g 
Deli v 
R e v 
2 0 0 6; 5 8: 1 1 1 9- 1 1 2 7. 
8.  Este n ne M, Ma urer J R, B o e hl er A et al. Br o nc hi olitis o blitera ns s y n dr o me 2 0 0 1: a n u p date of 
t he dia g n osti c criteria. J Heart L u n g Tra ns pla nt 2 0 0 2; 2 1( 3): 2 9 7- 3 1 0. 
9.  G u y W, e dit or. E C D E U Assess me nt M a n u al f or Ps y c h o p har mac ol o g y. 1 9 7 6. R oc k ville, M D, 
U. S. De part me nt of H ealt h, E d ucati o n, a n d Welfare. 
1 0.  Hall ora n P F. I m m u n os u p pressi ve a ge nts i n cli ni cal trials i n tra ns pla ntati o n. A m J M e d Sci 
1 9 9 7; 3 1 3( 5): 2 8 3- 2 8 8. 
1 1.  Iac o n o A T, Kee na n RJ, D u nca n S R et al. Aer os oli ze d c ycl os p ori n e i n l u n g reci pie nts wit h 
refract or y c hr o nic r ejecti o n. A m J R es pir Crit Care M e d 1 9 9 6; 1 5 3( 4 Pt 1): 1 4 5 1- 1 4 5 5. 
1 2.  Iac o n o A T, J o h ns o n B A, Gr g uric h W F et al. A ra n d o mize d trial of i n h ale d c ycl os p ori n e i n 
l u n g-tra ns pla nt reci pie nts. N E n gl J Me d 2 0 0 6; 3 5 4( 2): 1 4 1- 1 5 0. 
1 3.  Ja gasia M H, Grei ni x H T, Ar ora M et al. N ati o n al I nstit utes of Healt h C o nse ns us De vel o p me nt 
Pr oject o n Crit eria f or Cli nical Tri als i n C hr o nic Graft- vers us- H ost Disease: I. T h e 2 0 1 4 
Dia g n osis a n d 
Sta gi n g 
W or ki n g 
Gr o u p 
Re p ort. 
Bi ol 
Bl o o d 
Marr o w 
Tra ns pla nt 
2 0 1 5; 2 1( 3): 3 8 9- 4 0 1. 
1 4.  Mill er M R, Ha n ki ns o n J, Br usasc o V et al. St a n dar dis ati o n of s pir o metr y. E ur Res pir J 
2 0 0 5a; 2 6: 3 1 9- 3 3 8. 

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 7 9  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
1 5.
Mill er M R, Cra p o R, Ha n ki ns o n J et al. Ge n eral c o nsi derati o ns f or l u n g f u ncti o n t esti n g. E ur
Res pir J 2 0 0 5 b; 2 6: 1 5 3- 1 6 1.
1 6. P elle gri n o R, Vi e gi G, Br usasc o V et al. I nt er pretati v e strate gies f or l u n g f u ncti o n tests. E ur
Res pir J 2 0 0 5; 2 6( 5): 9 4 8- 9 6 8.
1 7. S o u b a ni 
A O, 
U berti J P. Br o n c hi olitis o blitera ns f oll o wi n g hae mat o p oieti c ste m cell
tra ns pla ntati o n. E ur Res pir J 2 0 0 7; 2 9( 5): 1 0 0 7- 1 0 1 9.
1 8.
U K S m P C Ci cl os p ori n A ( Ne oral ® ).
1 9.
Wa n ger J, Cla use n J L, C o ates A et al. Sta n dar disati o n of t he me as ure m e nt of l u n g v ol u mes.
E ur Res pir J 2 0 0 5; 2 6( 3): 5 1 1- 5 2 2.
2 0.
Wils o n E B. Pr o ba ble i nfere n ce, t he la w of s uccessi o n, a n d st atistical i nfere nce. J A S A
1 9 2 7; 2 2: 2 0 9- 2 1 2.

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
Pa g e 8 0  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
2 4  A P P E N DI X I – C O R E I N F O R M E D C O N S E N T F O R M 
T he i nf or me d c o nse nt f or m m ust be a da pte d t o l ocal re q uire m e nts b ut m ust c o ntai n at least t he 
f oll o wi n g p oi nts: 

T hat t he trial i n v ol v es res earc h.

T he p ur p ose of t he trial.

T he trial treat me nt(s) a n d t he pr o ba bilit y f or ra n d o m assi g n me nt t o eac h treat m e nt.

T he trial pr oc e d ures t o b e f oll o we d, i ncl u di n g all i n vasi v e pr oce d ures.

T he p atie nt’s res p o nsi biliti es.

T h ose as p ects of t he tri al t h at are e x p eri me ntal.

T he reas o n a bl y f oreseea ble ris ks or i n c o n ve nie nces t o t h e p atie nt a n d, w he n a p plica ble, t o a n
e m br y o, fet us, or n ursi n g i nfa nt.

T he re as o na bl y e x p ecte d be nefits. W h e n t here is n o i nte n de d cli nical b e nefit t o t h e p atie nt,
t he patie nt s h o ul d be ma de a ware of t his.

T he alter nati ve pr oce d ure(s) or c o urse(s) of treat m e nt t hat ma y be a vaila bl e t o t he p atie nt, a n d
t heir i m p orta nt p ote ntial be nefits a n d ris ks.

T he c o m pe ns ati o n a n d/ or treat me nt a vaila ble t o t he patie nt i n t he e v e nt of trial relate d patie nt
i nj ur y.

T he a ntici pate d pr orate d pa y me nt, if a n y, t o t he p atie nt f or partici p ati n g i n t he trial.

T he a ntici pate d e x pe nses, if a n y, t o t h e patie nt f or p artici pati n g i n t he trial.

T hat t he p atie nt‘s partici pati o n i n t he tri al is v ol u ntar y a n d t h at t he pati e nt ma y ref us e t o
partici pate or wit h dra w fr o m t he trial, at a n y ti me, wit h o ut p e nalt y or l oss of b e nefits t o w hi c h
t he patie nt is ot h er wise e ntitle d.

T hat t h e m o nit or(s), t h e a u dit or(s), t h e E C, a n d t he re g ulat or y a ut h orit y(ies) will be gra nt e d
direct access t o t he p atie nt‘s ori gi nal me dical rec or ds f or v erificati o n of cli nical trial
pr oce d ures a n d/ or d ata, wit h o ut vi ol ati n g t he c o nfi d e ntialit y of t h e patie nt, t o t h e e xte nt
per mitt e d b y t he a p pli ca ble la ws a n d re g ulati o ns a n d t h at, b y si g ni n g a writte n i nf or me d
c o nse nt f or m, t h e p atie nt or t he p atie nt‘s le gall y acce pta bl e re prese ntati ve is a ut h orizi n g s u c h
access.

T hat rec or ds i de ntif yi n g t he patie nt will be k e pt c o nfi d e ntial a n d, t o t he e xt e nt per mitte d b y
t he a p plica bl e l a ws a n d/ or re g ul ati o ns, will n ot b e ma de p u blicl y a vail a bl e. If t he res ults of
t he trial are p u blis he d, t h e patie nt’s i de ntit y will re mai n c o nfi d e nti al.

T hat t he patie nt or t he p atie nt‘s le gall y acce pta ble re pres e ntati v e will b e i nf or me d i n a ti mel y

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 8 1  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
ma n ner if i nf or mati o n bec o mes a vail a ble t hat ma y b e rele va nt t o t h e p atie nt‘s willi n g n ess t o 
c o nti n ue p arti ci pati o n i n t he trial. 

T he pers o n(s) t o c o nt act f or f urt her i nf or m ati o n re gar di n g t h e trial a n d t h e ri g hts of trial
patie nts, a n d w h o m t o c o ntact i n t he e ve nt of trial-rel at e d i nj ur y.

T he f oreseea ble cir c u msta nces a n d/ or reas o ns u n d er w hi c h t he pati e nt‘s parti ci pati o n i n t he
trial m a y b e ter mi nate d.

T he e x pect e d d urati o n of t h e p atie nt‘s partici p ati o n i n t h e trial.

T he a p pr o xi m ate n u m b er of patie nts i n v ol v e d i n t h e trial.

I nf or mati o n re gar di n g t h e trial ca n b e f o u n d o n cli ni caltrials. g o v.

L- Cs A: 
Pr ot o c ol N u m b er:
S p o ns or: 
Treat me nt of B O S after H S C T 
B T – L- Cs A – 2 0 1 – S C T 
Za m b o n S p A 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pa g e 8 2  of 8 2  
Cli nical Trial Pr ot o c ol B T – L- Cs A – 2 0 1 – S C T 
Versi o n 5. 0; 3 0 A pril 2 0 2 1 
 
2 5  A P P E N DI X II – A C C E P T A B L E M E T H O D S O F C O N T R A C E P TI O N 
A w o ma n is c o nsi dere d of c hil d beari n g p ote ntial, i.e. fertil e, f oll o wi n g me narc he a n d u ntil 
bec o mi n g p ost- me n o pa usal u nless per ma ne ntl y sterile. T he stat us of p ost- me n o pa usal is defi n e d 
as n o me nses f or 1 2 m o nt hs wit h o ut a n alter nati ve me dical ca us e a n d/ or t h e a g e of 6 0 ye ars. 
Acc or di n g t o t he Cli nical Trial Facilit ati o n Gr o u p ( C T F G) d at e d 2 1/ S e p/ 2 0 2 0, t he f oll o wi n g 
met h o ds are all o w e d f or c o ntrace pti o n d uri n g t h e cli nical trial wit h a fail ure rat e of less t h a n 1 %: 

c o m bi n e d (estr o ge n a n d pr o g est o ge n c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d wit h
i n hi biti o n of o v ulati o n 1:
o
oral
o
i ntra va gi nal
o
tra ns der mal

pr o g est o ge n- o nl y h or m o nal c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n 1:
o
oral
o
i njecta ble
o
i m pla nta bl e 2

i ntra uteri ne d e vice (I U D) 2

i ntra uteri ne h or m o ne-releasi n g s yste m (I U S) 2

bilateral t u bal occl usi o n 2

vas ect o mise d part ner 2, 3

se x u al a bsti ne nce 4
Fr o m res ults of pre vi o us cli nical trials wit h aer os olize d L- Cs A p ote ntial i nteracti o ns bet w ee n t h e 
I M P a n d h or m o n al c o ntrace pti ves ha ve n ot b ee n i n vesti gate d.  It is rec o g ni ze d t h at h or m o n al 
c o ntrac e pti v es ca n i n cre ase ser u m le vels of s yste micall y d ose d c ycl os p ori n e, b ut c ycl os p ori ne 
d oes n ot alt er t he effic ac y of h or m o n al c o ntrace pti ves.  S u bjects i n t h e trial will be m o nit ore d f or 
s yste mic c ycl os p ori n e le vels.   
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
1 H or m o nal c o ntrace pti o n ma y be s usce pti ble t o i nteracti o n wit h t he I M P, w hic h ma y re d u ce t he efficac y of t he c o ntrace pti o n 
met h o d 
2 C o ntrace pti o n met h o ds t h at i n t h e c o nt e xt of t his g ui d a nce are c o nsi d ere d t o h a ve l o w user d e pe n de nc y. 
3V asect o mise d part n er is a hi g hl y effecti ve birt h c o ntr ol met h o d pr o vi d e d t h at p art ner is t h e s ol e s e x ual p art ner of t h e W O C B P 
trial p arti ci pa nt a n d t h at t h e vasect o mis e d p art ner h as recei v e d me di cal assess me nt of t he s ur gical s uccess. 
4 I n t h e c o nte xt of t his g ui d a n ce se x u al a bsti n e nce is c o nsi d ere d a hi g hl y effecti v e met h o d o nl y if defi n e d as refrai ni n g fr o m 
h eter ose x ual i nterc o urse d uri n g t he e ntire p eri o d of ris k ass o ciat e d wit h t h e st u d y treat me nts. T h e relia bilit y of se x ual a bsti n e n ce 
n ee ds t o be e val u at e d i n relati o n t o t h e d urati o n of t he cli ni cal trial a n d t he pref erre d a n d us u al lifest yle of t h e s u bj ect.