A Randomized, Double-Blind, Placebo-Controlled, Dose-Titration, Safety, Tolerability, and Pharmacokinetics Study Followed by an Open-Label Safety and Efficacy Evaluation of SRP-4045 in Advanced-Stage Patients With Duchenne Muscular Dystrophy Amenable to Exon 45 Skipping
Phase: PHASE1
Conditions: Duchenne Muscular Dystrophy
Sponsor: Sarepta Therapeutics, Inc.

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 1  of 7 0  
 
 
 
C LI NI C A L S T U D Y P R O T O C O L  
 
D R U G ( C O D E N A M E):  
S R P -4 0 4 5  
P R O T O C O L N U M B E R:  
4 0 4 5 -1 0 1  
P R O T O C O L TI T L E:  
A Ra n d o mize d, D o u ble -Blin d, Pla c e b o -C o ntr olle d, 
D os e -Titratio n, Safet y, T olera bilit y, a n d 
P har ma c o kinetics St u d y F ollo w e d b y a n O pe n -La bel 
Safet y a n d Effic a c y E valuatio n of S R P -4 0 4 5 in 
A d va nc e d -Sta ge P atie nts wit h D uc he n ne M us c ular 
D ystr o p h y A me na ble t o E x o n 4 5 S kip pin g  
I N D N O. 
 
S T U D Y P H A S E:  
1  
S P O N S O R : 
Sare pta T hera pe utics, I nc.  
2 1 5 First Stre et  
Ca m brid ge, 
M A 0 2 1 4 2 U S A  
P h o ne:   + 1 -6 1 7 -2 7 4 -4 0 0 0  
C U R R E N T V E R SI O N ( D A T E):  
V ersio n 4. 0 ( A me n d me nt 3), 2 9  Marc h 2 0 1 8  
P RI O R V E R SI O N D A T E:  
V ersio n 3. 1 ( A me n d me nt 2), 0 2 Ma y 2 0 1 7        
V ersio n 2 ( A me n d me nt 1 ), 2 2 J uly 2 0 1 5 
V ersio n 1 , 1 2 J u ne 2 0 1 4  
 
 
 
 
 
 
 
 
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 2  of 7 0  
 
SI G N A T U R E P A G E F O R S P O N S O R  
Pr ot o c ol Title:  
A Ra n d o mize d, D o u ble -Blin d, Pla c e b o -C o ntr olle d, 
D os e -Titratio n, Safet y, T olera bilit y, a n d P har ma c o kinetics 
St u d y F ollo w e d b y a n O pe n -La bel Safet y a n d Effic a c y 
E valuatio n of S R P -4 0 4 5 in A d va nc e d -Sta ge P atie nts wit h 
D uc he n ne M us c ular D ystr o p h y A me na ble t o E x o n 4 5 S kip pin g  
St u d y N o:  
4 0 4 5 -1 0 1  ( A me n d me nt 3 ) 
C urre nt Ve rsi o n ( D ate):  
2 9  Marc h 2 0 1 8  
 
T his st u d y pr ot oc ol w as s u bje ct t o detaile d re vie w a n d has be e n a p pr o ve d b y t he a p pr o priate 
pers o n nel of t he S p o ns or ( Sare pta T hera pe utics, I nc). T he inf or matio n c o ntaine d in t his pr ot oc ol 
is c o nsiste nt wit h: 
 T he c urre nt ris k -be nefit e valuatio n of t he in vestigatio nal dr u g pr o d uct.  
 T he et hic al a n d s cie ntific principles g o ver nin g clinic al res e arc h as s et o ut in t he 
D e claratio n of H elsin ki, principles of I nter natio nal C o u ncil f or  H ar m o nizatio n (I C H), 
Go o d Clinic al Pra ctic e ( G C P) E 6, a n d/ or t he E ur o pe a n Clinic al Trial Dire ctive 
2 0 0 1/ 2 0/ E C.  
T he I n vestigat or will be s u p plie d wit h details of a n y sig nific a nt or ne w fin din gs, inclu din g 
a d vers e e ve nts, relatin g t o tre at me nt wit h t he in vestigatio nal dr u g pr o d uct.  
 
 
 
 
, M D , P h D 
  
 
  
  
 
D ate  
 
 
 
, 
M D 
  
 
  
  
 
D ate  
 
P P D

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 3  of 7 0  
 
I N V E S TI G A T O R’ S A G R E EM E N T  
 
I ha ve re a d Pr ot oc ol N o. 4 0 4 5-1 0 1 a n d a gre e t o c o n d uct t he st u d y as o utline d.  I a gre e t o 
maintain t he c o nfide ntialit y of all inf or matio n re c eive d or de velo pe d in c o n ne ctio n wit h t his 
pr ot oc ol.  
 
 
 
 
 
Printe d N a me of I n vestigat or  
 
 
 
Sig nat ure of I n vestigat or  
 
 
 
D ate  

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 4  of 7 0  
 
P R O C E D U R E S I N C A S E O F E M E R G E N C Y  
 
T a ble  1 : 
E me r g e nc y C o nt act I nfo r m ati o n 
R ol e i n St u dy  
Na m e  
A d dress a n d Tele p h o n e n u m be r  
Res p o nsible P h ysicia n  
, M D, P h D, 
 
 
 
 
T el ep h o ne:  
 
M o bile:  
 
 
 
P P D
P P D
P P D
P P D
P P D
P P D

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 5  of 7 0  
 
1.  
S Y N O P SI S  
N A M E O F C O M P A N Y  
S ar e pt a T her a pe utics, I nc.  
Ca m brid ge, M A 0 2 1 4 2 U S A  
P h o ne : + 1-6 1 7 -2 7 4 -4 0 0 0  
N A M E O F FI NI S H E D P R O D U C T  
S R P -4 0 4 5  I njectio n 
 
N A M E O F A C TI V E I N G R E DI E N T  
S R P -4 0 4 5  
TI T L E: A Ra n d o mize d, D o u ble -Blin d, Plac e b o -C o ntr olle d, D os e -Titr atio n, S af et y, T oler a bilit y, a n d 
P har m ac o kinetics St u d y F ollo w e d b y a n O pe n -La bel S af et y a n d Effic ac y  E valuatio n of S R P -4 0 4 5 in 
Ad va nc e d -Sta ge  P atie nts wit h D uc he n ne M us c ular D ystr o p h y A me na ble t o E x o n 4 5 S kip pin g  
P R O T O C O L N U M B E R:   4 0 4 5 -1 0 1  
P H A S E O F S T U D Y:  P has e 1  
I N V E S TI G A T O R S T U D Y SI T E S:  T his m ulti -c e nter st u d y will be c o n d ucte d  at a p pr o xi mately 4  sites 
in t he Unit e d States.  
O B J E C TI V E S:  
Pri m ar y o bjective:  
 T o e valuate t he s af et y a n d t oler a bilit y of 4  es c alatin g intr a ve n o us (I V) d os es ( 4, 1 0, 2 0, a n d 
3 0  m g/ k g) of S R P -4 0 4 5 a d minister e d o nc e w ee kly f or at least 2  w ee ks per d os e le vel  as c o m par e d to 
plac e b o  
S ec o n dar y o bjective:  
 T o det er mine t he p har mac o kinetic ( P K) pr ofile of 4  es c alatin g I V d os es of S R P -4 0 4 5  
M E T H O D O L O G Y:   
T his is a first -in-h u ma n, m ulti -c e nter, r a n d o mize d, d o u ble -blin d, plac e b o -c o ntr olle d, d os e -titr atio n st udy 
desig ne d t o ass ess t he s af ety, t oler a bilit y, a n d P K of  o nc e -w ee kly I V inf usio ns of S R P -4 0 4 5 in 
a d va nc e d -sta ge patie nts wit h ge n ot y pic ally  c o nfir me d D uc he n ne m us c ular d ystr o p h y (D M D ) 
c har act erize d b y deletio n s a me na ble t o e x o n  4 5 s kip pin g ( e g, e x o ns  1 2 -4 4, 1 8 -4 4, 4 4, 4 6 -4 7, 4 6 -4 8, 
4 6 -4 9, 4 6 -5 1, 4 6 -5 3, or 4 6 -5 5 ).  T his st u d y will e valuate 4  as c e n din g d os e le vels of S R P -4 0 4 5 ( 4, 1 0, 
2 0, a n d 3 0  m g/ k g  a d minister e d w ee kly  f or a mini m u m of 2 w ee ks per le vel) c o m par e d t o plac e b o o ver 
a p pr o xi m at ely 1 2  w ee ks  of a d o u ble -blin d d os e -titr atio n perio d .  T he d o u ble -blin d d os e -titr atio n perio d 
will be f ollo w e d b y an o pe n -la bel e xte nsio n perio d e valuat in g t he s af et y a n d effic ac y of S R P -4 0 4 5  at 
3 0  m g/ k g (or t he hig hest t oler ate d d os e as deter mine d d urin g t he d os e titr atio n) a d minister e d w ee kly  
t hr o u g h Wee k 1 4 4 .  After c o m pletin g  t he o pe n -la bel e xte nsio n perio d, eligible patie nts ma y e nter a 
pla n ne d lo n g-ter m e xte nsio n  ( L T E) st u d y f or e xte n de d tr eat me nt.  All activities f or t hes e s u bjects will 
be o utline d in a L T E  st u d y pr ot oc ol. 
S cr ee nin g  P erio d  
P atie nts will be e v aluate d f or inclusio n d urin g a S cr ee nin g perio d of u p t o a p pr o xi mately 4  w ee ks.  
Bas eline/ Wee k 1  
Eligible  patie nts w h o ha ve o ut -of -fr a me deletio ns t hat ma y be c orr ecte d b y s kip pin g e x o n 4 5 will be  
r a n d o mize d t o r ec eive o nc e-w ee kly I V inf usio ns of S R P -4 0 4 5 or  plac e b o.  
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 6  of 7 0  
 
N A M E O F C O M P A N Y  
S ar e pt a T her a pe utics, I nc.  
Ca m brid ge, M A 0 2 1 4 2 U S A  
P h o ne : + 1-6 1 7 -2 7 4 -4 0 0 0  
N A M E O F FI NI S H E D P R O D U C T  
S R P -4 0 4 5  I njectio n 
 
N A M E O F A C TI V E I N G R E DI E N T  
S R P -4 0 4 5  
D o u ble -Blin d D os e Titr atio n  wit h O pe n -La bel E xte nsio n (1 4 4  w ee ks)  
D osi n g  
T w elve patie nts will be r a n d o mize d ( 2:1)  in d o u ble-blin d f as hio n  t o r ec eive S R P-4 0 4 5 ( n = 8) or plac e b o 
( n = 4).  P atie nts will r ec eive a o nc e -w ee kly I V inf usio n of S R P -4 0 4 5  or plac e b o  at es c alatin g d os e 
le vels, eac h f or at least 2 w ee ks :  4  m g/ k g at  Wee ks  1 -2; 1 0  m g/ k g at  Wee ks  3 -4; 2 0  m g/ k g at  
Wee ks  5 -6; a n d  3 0  m g/ k g  be gin nin g at  Wee k  7 .  D urin g t he d os e titr atio n perio d of t he st u d y , d osin g 
will be int err u pte d or halte d if  s pecific pr e define d st o p pin g criteria ar e met , or if interr u ptio n is 
ot her wis e w arr a nte d at t he dis cr etio n of t he S p o ns or or I n vestigat or.  O nc e t he last patie nt has r ec eive d 
2  inf usio ns at 3 0 m g/ k g  ( Wee k 8), a n in de pe n de nt Data S af et y M o nit orin g Boar d ( D S M B) will r e vie w 
c u m ulative s af et y data.  Re vie w b y t he D S M B is nec ess ar y f or a d visin g t he S p o ns or a b o ut w het her t he 
s af et y dat a allo w f or lo n ger -ter m d osin g wit h S R P-4 0 4 5.  P atie nts will c o ntin ue t o r ec eive t h eir 
r a n d o mize d tr eat me nt ( S R P-4 0 4 5  or plac e b o) in a blin de d f as hio n u ntil t he D S M B r e vie w is c o m plete.  
Bas e d o n t he r es ults of t his r e vie w, t he S p o ns or will deter mine w het her t o r oll o ver t he patie nts int o t he 
o pe n -la bel e xte nsio n perio d.  D urin g t he o pe n -la bel e xte nsio n , patie nts will r ec eive S R P -4 0 4 5 at 
3 0  m g/ k g (or t he hig hest t oler ate d d os e as deter mine d d urin g t he d os e titr atio n) a d minister e d w ee kly.  
Assess me nts  
P atie nts will u n der g o r o utine s af et y e valuatio ns.   Ad vers e e ve nts ( A Es) a n d c o nc o mita nt me dic atio ns 
will be m o nit or e d a n d d oc u me nte d  c o ntin ually o ver t he c o urs e of t he st u d y.  
 
  Plas ma s a m ples f or s erial P K 
det er minatio n will be c ollecte d at Bas eline/ Wee k  1 a n d Wee ks  3, 5, 7 , a n d 6 0 .  U rine s a m ples f or s erial 
P K det er minatio n will be c ollecte d at Bas eline/ Wee k  1 a n d Wee ks  3, 5, 7 , a n d 1 2 .  
I n a d ditio n t o s erial P K, sta n dar d p o p ulatio n P K par a meters will be esti mate d fr o m a d ditio nal plas ma 
s a m ples t a ke n o ver t he c o urs e of  1 4 4  w ee ks.  
 
 
  An electr oc ar dio gr a m ( E C G ) will be perf or me d at Bas eline / Wee k 1 , Wee k 7 , Wee k 1 2, a n d 
t he n e ver y 1 2 w ee ks.  An ec h oc ar dio gr a m ( E C H O ) will be perf or me d at Wee k  1 2, a n d t he n e ver y 
2 4  w ee ks.  Clinic al la b or at or y ass ess me nts wil l be perf or me d at Bas eline/ Wee k 1, Wee ks  2 -9, a n d 
Wee k  1 2, t he n e v er y 4  w ee ks t o Wee k  3 6, a n d t he n e ver y 1 2  w ee ks.  Vital sig ns will be ass ess e d w ee kly 
pr e - a n d p ost -inf usio n.  H eig ht  will be ass ess e d e ver y 1 2  w ee ks.  Weig ht wi ll be ass ess e d at 
Bas eline/ Wee k  1, a n d t he n  e ver y 4  w ee ks.  A f ull p h ysic al e xa m inatio n will be c o n d ucte d at 
Bas eline/ Wee k  1, Wee k  4, Wee k  1 2, Wee k  2 4, a n d t he n e ver y 2 4  w ee ks.  A brief p h ysic al e xa m inatio n 
will be c o n d ucte d e ver y 4  w ee ks ( e xce pt at ti mes of a f ull p h ysic al e xa m inatio n) t o Wee k 3 6 , a n d t he n 
e ver y 2 4  w ee ks.   P atie nts will u n der g o a d ditio nal p h ysic al e xa minatio ns, E C Gs, clinic al la b or at or y 
ass ess m e nts a n d 
 d urin g t he first 8  w ee ks of o pe n -la bel tr eat me nt.  
D U R A TI O N O F S T U D Y:  
S cr ee nin g P erio d:  u p t o a p pr o xi mately 4  w ee ks  
D o u ble -B lin d D os e -Titr atio n wit h O pe n -La bel E xte nsio n :  u p t o 1 4 4  w ee ks  
P ost -tr eat me nt F ollo w -Up P erio d:  a p pr o xi mately 4  w ee ks  
T ot al d ur atio n of patie nt participatio n:  a p pr o xi mately 1 5 2  w ee ks  
C CI
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 7  of 7 0  
 
N A M E O F C O M P A N Y  
S ar e pt a T her a pe utics, I nc.  
Ca m brid ge, M A 0 2 1 4 2 U S A  
P h o ne : + 1-6 1 7 -2 7 4 -4 0 0 0  
N A M E O F FI NI S H E D P R O D U C T  
S R P -4 0 4 5  I njectio n 
 
N A M E O F A C TI V E I N G R E DI E N T  
S R P -4 0 4 5  
N U M B E R O F P A TI E N T S:  
1 2 patie nts ( 8  S R P -4 0 4 5 + 4  plac e b o)  
I N C L U SI O N C RI T E RI A:  
P atie nt s m ust meet all of t he f ollo win g inclusio n criteria t o be eligible f or t his st u d y.  
1.  Male a ge d  7 t o  2 1 , inclusive. 
2.  Est a blis he d clinic al dia g n osis of D M D wit h a deletio n  a me na ble t o e x o n  4 5 s kip pin g ( e g, deletio ns 
of e x o ns  1 2 -4 4, 1 8 -4 4, 4 4, 4 6 -4 7, 4 6 -4 8, 4 6 -4 9,  4 6 -5 1, 4 6 -5 3, or 4 6 -5 5) as d oc u me nte d b y a 
ge netic r e p ort fr o m a n ac cr e dite d la b or at or y c o nfir min g deletio n e n d p oints b y m ultiple x 
ligatio n-de pe n de nt pr o be a m plific atio n ( M L P A) or s e q ue ncin g.  
3.  S t a ble c ar diac a n d p ul m o nar y f u nctio n t hat, in t he I n vestigat or’s o pinio n, is u nlikely t o 
dec o m pe ns ate o ver t he d ur atio n of t he st u d y   
4.  N o n -a m b ulat or y, or inc a pa ble of w alkin g  ≥3 0 0  meters o n t he 6 -Min ute Walk T est ( 6 M W T).  
5.  O n a sta ble d os e of or al c ortic oster oids f or at least 2 4  w ee ks prior t o st u d y dr u g a d ministr atio n a n d 
t he d os e or d os e e q uivale nt is e x pecte d t o r e main c o nsta nt ( e xc e pt f or m o dific atio ns t o 
ac c o m m o date c ha n ges in w eig ht) t hr o u g h o ut t he st u d y, O R  has n ot r ec eive d c ortic oster oids f or at 
least 2 4 w ee ks prior t o st u d y dr u g a d ministr atio n a n d d oes n ot e x pect t o start c ortic oster oids 
t hr o ug h o ut t he st u d y.   
6.  P atie nts w h o ar e p ost -p u bertal a n d s e x ually active m ust a gr ee t o us e, f or t he e ntir e d ur atio n of t he 
st u d y a n d f or 9 0 da ys p ost last d os e, a male c o n d o m a n d t he f e male s e x ual part ner m ust als o us e a 
m e dic ally ac c e pta ble f or m of birt h c o nt r ol ( e g, or al c o ntrac e ptive). 
7.  Able t o u n dersta n d a n d c o m ply wit h all st u d y r e q uir e me nts, in t he I n vestigat or’s o pi nio n, or if 
u n der t he a ge of 1 8  years, m ust ha ve  (a) par e nt(s) or le gal g uar dia n(s) w h o is /ar e a ble t o 
u n dersta n d a n d c o m ply wit h all t he st u d y r e q uir e me nts.  
8.  Willin g t o pr o vide inf or me d c o ns e nt t o participate in t he s t u d y, or if u n der t he a ge of 1 8 years, 
willin g t o pr o vide inf or me d ass e nt, if a p plic a ble, a n d ha s (a) par e nt(s) or le gal g uar dia n(s) w h o 
is/ ar e willin g t o pr o vide writte n inf or me d c o ns e nt f or t he patie nt t o participate in t he st u d y.   
E X C L U SI O N C RI T E RI A:  
P atie nts w h o meet a n y of t he f ollo win g criteria will be e xclu de d fr o m t his st u d y.  
1.  Us e of a n y p har mac olo gic tr eat me nt  (ot her t ha n c ortic oster oids ) wit hin 1 2 w ee ks prior t o 
Bas eline/ Wee k  1 t hat mig ht in t he I n vestigat or’s ju d g me nt ha ve a n eff ect o n m us cle str e n gt h or 
f u nctio n ( e g, gr o wt h h or m o ne, a na b olic ster oids). ( C urr e nt gr o wt h h or m one tr eat me nt f or s h ort 
st at ur e will be allo w e d if me dic ally in dic ate d.)  
2.  C urr e nt or pr e vio us tr eat ment wit h t he e x peri me ntal a ge nts S M T C 1 1 0 0 ( B M N -1 9 5 ) or P R O 0 4 5  at 
a n y ti me.  

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 8  of 7 0  
 
N A M E O F C O M P A N Y  
S ar e pt a T her a pe utics, I nc.  
Ca m brid ge, M A 0 2 1 4 2 U S A  
P h o ne : + 1-6 1 7 -2 7 4 -4 0 0 0  
N A M E O F FI NI S H E D P R O D U C T  
S R P -4 0 4 5  I njectio n 
 
N A M E O F A C TI V E I N G R E DI E N T  
S R P -4 0 4 5  
3.  Us e of ot her R N A a ntis e ns e or ge ne t her a p y a ge nts.  
4.  C urr e nt or p r e vio us tr eat me nt wit h a n y ot her e x peri me ntal tr eat me nt ( ot her t ha n deflazac ort) wit hin 
1 2  w ee ks prior t o Bas eline/ Wee k  1  or participatio n in a n y ot her inter ve ntio nal clinic al trial wit hin 
1 2  w ee ks  prior t o Bas eline/ Wee k  1 .  
5.  Us e of a n y a min o glyc oside  a ntibiotic or statin wit hin 1 2  w ee ks prior t o Bas eline/ Wee k  1 or 
a nticipate d nee d f or a n a min o glyc oside a ntibiotic or statin d urin g t he st u d y.  
6.  I nitiatio n or c ha n ge of d osin g ( e xc e pt f or m o dific atio ns t o ac c o m mo date c ha n ges in w eig ht) wit hin 
1 2  w ee ks prior t o Bas eline/ Wee k  1 a n d/ or a nticipate d nee d f or a c ha n ge in d osin g ( e xc e pt f or 
m o dific atio ns t o ac c o m m o date c ha n ges in w eig ht) d urin g t he st u d y f or a n y of t he f ollo win g: 
a n giot e nsin -c o n vertin g e nz y me ( A C E) in hibit ors, a n giote nsin r ec e pt or bloc kin g a ge nts ( A R Bs), 
β -bloc kers, p otassiu m.  
7.  I nitiation or c ha n ge of d osin g wit hin 1 2  w ee ks prior t o Bas eline/ Wee k  1 a n d/ or a nticipate d nee d f or 
a c ha n ge in d osin g d urin g t he st u d y f or o ver -t he-c o u nter pr e par atio ns s uc h as her bal/ n o n -her bal 
s u p ple me nts, vita mins, miner als, a n d h o me o pat hic pr e par atio ns.  
8.  Left ve ntric ular ejectio n fr actio n ( L V E F) < 4 0 % o n t he S cr ee nin g E C H O, a n d/ or  Q T c F  ≥4 5 0  ms ec 
o n t he S cr ee nin g E C G.  
9.  F or c e d vital c a pacit y ( F V C) < 5 0 % of pr e dicte d value  at  S cr ee nin g a n d/ or Bas eline/ Wee k  1 , a n d/ or 
r e q uir e me nt f or n oct ur nal ve ntilatio n. 
1 0.  Major s ur ger y wit hin 3  m o nt hs prior t o Bas eline/ Wee k  1 or pla n ne d s ur ger y f or a n y ti me d urin g 
t his st u d y. 
1 1.  Pr es e nc e of ot her clinic ally sig nific a nt illness inclu din g c ar diac, p ul m o nar y, he patic, r e nal, 
he m at olo gic, i m m u n olo gic, or be ha vior al dis eas e, or malig na nc y.  
1 2.  An y ot her c o n ditio n t hat, in t he I n vestigat or’s o pinio n, c o uld interf er e wit h t he patie nt’s 
participatio n in t he st u d y.  
D O S E/ R O U T E/ R E GI M E N:  
S R P -4 0 4 5 (4, 1 0, 2 0, a n d 3 0  m g/ k g)  will be a d minister e d as a n I V inf usio n o ver a p pr o xi mately 
3 5 -6 0  min utes o nc e a w ee k . 
R E F E R E N C E T R E A T M E N T:  
P atie nts r a n d o mize d t o plac e b o will r ec eive n or mal s aline as a n I V inf usio n o ver a p pr o xi mately 
3 5 -6 0  min utes o nc e a w ee k u ntil t he o pe n -la bel e xte nsio n. 
C RI T E RI A F O R E V A L U A T I O N: 
T he pri m ar y st u d y e n d p oint is ass ess me nt of t he s af et y of S R P-4 0 4 5 d urin g t he d o u ble -b lin d 
d os e -titr atio n perio d  ac c or din g t o t he f ollo win g: 
 
I ncide nc e of A Es  
 
I ncide nc e of clinic al la b or at or y a b n or malities ( he mat olo g y, c he mistr y, c oa g ulatio n, urinalysis)  
 
I ncide nc e of a b n or malities in vit al sig ns a n d p h ysic al e xa minatio ns  ( P E)   
 
Clinic ally sig nific a nt w ors e nin g of E C Gs a n d E C H O  
T he s ec o n dar y st u d y e n d p oint is t o deter mine t he P K pr ofile of S R P -4 0 4 5 d urin g t he d o u ble -b lin d 
d os e -titr atio n perio d (s ee belo w). 

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 9  of 7 0  
 
N A M E O F C O M P A N Y  
S ar e pt a T her a pe utics, I nc.  
Ca m brid ge, M A 0 2 1 4 2 U S A  
P h o ne : + 1-6 1 7 -2 7 4 -4 0 0 0  
N A M E O F FI NI S H E D P R O D U C T  
S R P -4 0 4 5  I njectio n 
 
N A M E O F A C TI V E I N G R E DI E N T  
S R P -4 0 4 5  
P h ar m ac o ki n etics:  
S erial plas ma P K s a m plin g will be perf or me d  at Bas eline/ Wee k  1 a n d Wee ks  3, 5, 7 , a n d 6 0  at t he 
f ollo win g ti me p oints: i m me diately pr e -inf usio n, at a p pr o xi mately 5  t o 1 0 min utes after c o m pletio n of 
inf usio n, a n d at  1, 1. 5, 2, 4, 6, 8 1 2, 1 6, a n d  2 4  h o urs after c o m pletio n of inf usio n.  
 
 
 
 
 
 
 
  T he f ollo win g P K 
par a m et ers will be deter mine d:  
 
Ma xi m u m plas ma c o nc e ntr atio n ( C
ma x ) 
 
Ti me t o ma xi m u m plas ma c o nc e ntr atio n ( T ma x ) 
 
Ar ea u n der t he plas ma c o nc e ntr atio n -c ur ve ( A U C)  
 
Ap par e nt v olu me of distrib utio n at stea d y state ( V ss) 
 
Eli minatio n half -lif e (t½ ) 
 
T ot al clear a nc e ( C L)  
 
Mea n r eside nc e ti me ( M R T)  
 
Urinar y clear a nc e ( C L R ) 
 
 
S A M P L E SI Z E:   
T he s a m ple size f or t his st u d y is bas e d u p o n q ualitative c o nsider atio ns; n o f or mal s a m ple size 
c alc ulatio ns w er e perf or me d.  T he s elect e d s a m ple size is c o nsider e d s ufficie nt t o pr o vide initial s af et y 
e valuatio n of S R P -4 0 4 5 a n d t o pr o vide a de q uate data t o allo w f or esti matio n of P K par a meters.  
S T A TI S TI C A L M E T H O D S:  
Bas eline c har acteristics, s afet y, a n d t oler a bilit y will be bas e d u p o n t he r evie w of in divid ual values a n d 
s u m m ar y statistics.  I ncide nc e of treat me nt-e mer ge nt a d verse e ve nts  ( T E A Es) will be ta b ulate d b y 
C CI
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 1 0  of 7 0  
 
N A M E O F C O M P A N Y  
S ar e pt a T her a pe utics, I nc.  
Ca m brid ge, M A 0 2 1 4 2 U S A  
P h o ne : + 1-6 1 7 -2 7 4 -4 0 0 0  
N A M E O F FI NI S H E D P R O D U C T  
S R P -4 0 4 5  I njectio n 
 
N A M E O F A C TI V E I N G R E DI E N T  
S R P -4 0 4 5  
c o u nts a n d per c e nta ges.  Ab n or malities in clinic al la b or at or y, vital sig ns, a n d E C G will be bas e d o n 
pr e -define d n or mal r a n ges a n d will be ta b ulate d b y d os e a n d tr eat me nt gr o u p ( S R P -4 0 4 5 or plac e b o) 
s h o win g s u bject c o u nts a n d per c e nta ges.   
S af et y A n al ys es:  
T E A Es will be s u m marize d b y s yste m or ga n class ( S O C) a n d pr ef err e d ter m ( P T).  N o n -e mer ge nt 
e ve nts will be r ec or de d in t he data listin gs.  F or all A E ta bles, t he n u m ber a n d per c e nta ge of patie nts 
r e p ortin g A Es will be gr o u pe d usin g t he Me dic al Dictio nar y f or Re g ulat or y Activities ( Me d D R A) b o d y 
s yst e m a n d P T.  M ultiple oc c urr e nces of t he s a me A E ( at t he P T le vel) in t he s a me patie nt will be 
c o u nt e d o nly o nc e in t he fr e q ue nc y ta bles.  If a patie nt e x perie nc es m ultiple e pis o des of t he s a me e ve nt 
wit h diff er e nt r elatio ns hip/s e verit y, t he e ve nt wit h t he str o n gest r elatio ns hip or ma xi m u m s e veri t y t o 
in vestigatio nal dr u g pr o d uct will be us e d t o s u m marize A Es b y r elatio ns hip a n d s e verit y.  
Des criptive statistics f or E C G, E C H O, vital sig ns, bio mar kers, a n d s af et y la b or at or y par a meters will be 
dis pla ye d.   All s af et y data will be pr es e nte d in data li stin gs. 
P h ar m ac o ki n etic A n al yses:  
P har m ac o kinetic par a meters of S R P -40 4 5 will be deter mine d fr o m a nalys es of m ultiple plas ma a n d 
urine s a m ples c ollecte d f or eac h d os e le vel.  I n divid ual plas ma le vels of S R P-4 0 4 5 will be liste d wit h 
t he c orr es p o n din g ti me relate d t o in vestigatio nal dr u g pr o d uct a d ministr atio n a n d s u m mar y statistics will 
be ge ner at e d b y per -pr ot oc ol ti me of c ollectio n.   P K par a meters f or S R P -4 0 4 5 will be c alc ulate d usin g 
n o n -c o m part me ntal a nalysis.  Act ual s a m plin g ti mes will be us e d in all f inal P K a nalys es; per pr ot oc ol 
ti m es will be us e d t o c alc ulate mea n plas ma c o nc e ntr atio ns f or gr a p hical dis pla ys.  T he f ollo win g P K 
par a m et ers will be deter mine d:  
 
C ma x  
 
T ma x  
 
A U C  
 
V ss 
 
t½  
 
C L  
 
M R T  
 
C L R  
 
  Availa ble patie nt c har acteristics ( de m o gr a p hics, la b or at or y 
varia bles, ge n ot y pes, c o nc o mita nt me dic atio ns, etc) will be teste d as p ote ntial c o variates aff ectin g P K 
par a m et ers.  
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 1 1  of 7 0  
 
2.  
S C H E D U L E O F E V E N T S  
T he s c he d ule of st u d y e ve nts is pr o vide d in Ta ble  2 .  
 

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 1 2  of 7 0  
 
T a ble  2 : 
Sc he d ule of E v e nts : D o u ble-Bli n d  D os e Titr ati o n  w it h O pe n-L a bel E xte nsi o n  
We e k  
S C R N  
-4 T O 0  
B L/ 1  
2  
3  
4  
5  
6  
7  
8  
9  
1 0  
1 1  
1 2  
Visit Wi n do w  
≤4 We e ks  
± 1 da y  
I nf or me d c o ns ent/assent 
X  
 
 
 
 
 
 
 
 
 
 
 
 
I n cl usi o n/e xcl usi o n Crit eria 
X  
 
 
 
 
 
 
 
 
 
 
 
 
M e dic al Hist or y  a 
X  
 
 
 
 
 
 
 
 
 
 
 
 
D o c u me nt D M D Dia g n osis  
X  
 
 
 
 
 
 
 
 
 
 
 
 
W h ole Bl o o d ( Ge n ot y pe/ S N P)
 b 
X  
 
 
 
 
 
 
 
 
 
 
 
 
6 M W T  
X  
 
 
 
 
 
 
 
 
 
 
 
 
F ull P h ysic al Exa mi n ati o n  c 
X  
X  
 
 
X  
 
 
 
 
 
 
 
X  
Brief P h ysic al Exa mi n ati o n  d 
 
 
 
 
 
 
 
 
X  
 
 
 
 
Vit al si g ns
e  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Hei g ht  f 
X  
 
 
 
 
 
 
 
 
 
 
 
X  
W ei g ht  
X  
X  
 
 
X  
 
 
 
X  
 
 
 
X  
Co nfir m eli gi bilit y  
 
X  
 
 
 
 
 
 
 
 
 
 
 
Ra n d o mizati o n  g  
 
X  
 
 
 
 
 
 
 
 
 
 
 
1 2 -le a d E C G h 
X  
X  
 
 
 
 
 
X  
 
 
 
 
X  
E C H O  h 
X  
 
 
 
 
 
 
 
 
 
 
 
X  
Cli nic al la b orat or y  
X i 
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
 
X  
Plas ma/ uri n e f or P K k 
 
X  
 
X  
 
X  
 
X  
 
 
 
 
X  
D osi n g  l 
 
4  l 
mg/ k g  
4  
mg/ k g  
1 0  
mg/ k g  
1 0  
mg/ k g  
2 0  
mg/ k g  
2 0  
mg/ k g  
3 0  
mg/ k g  
3 0  
mg/ k g  
3 0  
mg/ k g  
3 0  
mg/ k g  
3 0  
mg/ k g  
3 0  
mg/ k g  
 
 
W e e kl y i nf usi o ns of t h e a b o ve d oses or pla c e b o b e gi n ni n g at Bas eli n e/ Wee k 1  
D S M B  m  
 
 
 
 
 
 
 
 
 
---------X --------- 
Co n c o mit a nt me dic ati o ns  
Co nti n u o us  
A E mo nit ori n g  
Co nti n u o us  
C CI
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 1 3  of 7 0  
 
6 M W T = 6 -mi n ute wal k t est; A E =a d verse e ve nt; B L = Baseli ne; D M D = D uc he n n e m usc ular d ystr o p h y; D S M B = Data Saf et y M o nit ori n g B o ard; E C G =ele c tr oc ardi o gr a m; 
E C H O =e c h o c ar di o gra m; 
 
 
a I n cl u des m e dic ati o n a n d p h ysi ot hera pe utic i nterve nti o n hist or y.  
b  P atie nts m ay start d osi n g base d o n l o c al ge n ot y pi n g r es ult s pro vi de d t hat t h ese r es ult s f ulfil t h e r e q uir e d i n cl usi o n criteri a ; h o we v er, all p atie nts  m ust u n der g o ge n e tic testi n g t o c o nfir m t h e 
e x o n  4 5 s ki p p able m utati o n a n d t o assess ge n etic 
 of dise ase se v erit y.  
c C o m plet e p h ysic al e x a mi nati o n t o i n cl u de r e vie w of ge n er al a p pe ara nc e, h e a d, e y es, e ars, n ose, a n d t hr oat ( H E E N T), h e art, l u n gs, a b d o m e n, s ki n, l y mp h n o des, m usc ul os keletal, a n d 
n e ur ol o gic al s yste ms.  
d  Brief p h ysic al e x a mi nati o ns will i n cl u de e x a mi nati o n of ge n eral a p pe ar a nc e, H E E N T, h e art, c hest, a b d o me n, a n d s ki n.  
e Vit al si g ns i n cl u de bl o o d pr ess ur e, p ulse, r es pir atio n r ate , a n d t e mperat ur e. F or i nfusi o n visits, vital si g ns ar e t o be c olle cte d wit hi n a p pr o xi matel y 3 0 mi n utes pri or t o i nfusi o n a n d 
a p pr o xi m atel y 5, 3 0, a n d 6 0 mi n ut es after t h e e n d of t h e i nf usi o n.  
f Hei g ht a n d ul n ar le n gt h ta ke n at Scr e e ni n g a n d W e e k  1 2.   If p atie nt is u n a ble t o sta n d, t he n h ei g ht c a n be c alc ulate d usi n g ul n ar le n gt h as descri be d i n Se cti o n  1 0. 3. 1 .  
g  Ra n d o miz ati o n ( 8  S R P -4 0 4 5 + 4  pla c eb o) will o c c ur at Baseli n e/ Wee k  1 after c o nfir mi n g all eli gi bilit y criteria pri or t o first d ose.  
h  1 2 -le a d E C Gs a n d E C H Os will be p erf or me d at a c o nsiste nt ti me of da y t hr o u g h o ut t he st u d y.  
i S af et y la b or at ory assess m e nts m ust be p erfor me d wit hi n 2  w e e ks pri or t o t h e Baseli n e/ We e k 1 visit, a n d r es ult s m ust be r e vie we d pri or t o d osi n g.  If Scr e e ni n g saf et y la b or at ory sa mples 
wer e c olle ct e d m ore t ha n 2  we e ks pri or t o t he Baseli n e/ We e k  1 visit, sa mples m ust be c olle cted a gai n a n d r es ults m ust be r e vie we d bef ore p atient s m ay be d ose d at Baseli n e/ We e k 1.  
 
k  Serial plas m a P K sa m pli n g will be p erf or me d d uri n g t he d o u ble -bli n d d ose -titrati o n p eri o d at Baseli ne/ We ek 1 a n d W e e ks  3, 5, a n d  7 at t h e f oll o wi n g ti me p oi nts at t h e first we e kl y d ose 
f or e a c h d ose le v el: i m me diatel y pre-i nfusi o n, a p pro xi matel y 5  t o 1 0 mi n ut es after c o mpleti o n of i nf usi o n, a n d at a p pro xi matel y 1, 1.5, 2, 4, 6, 8 , 1 2, 1 6, a n d 2 4  h o urs after c o mpleti o n of 
i nf usi o n.  At W e e ks 1, 3, 5, 7, a n d 1 2, u ri n e f or P K sa m pli n g will be c olle ct e d, o n a c u m ulati ve basis, d uri n g t h e f oll o wi n g ti me i ntervals  base d o n st art of i nfusi o n : 0 t o 4, 4  t o 8, 8  t o 1 2, 
a n d 1 2  t o 2 4  h o urs.  I n a d diti o n, at W e ek 7, uri n e will als o be c olle ct ed 2 4  t o 3 6  h o urs after t he st art of i nf usi o n.  P atie nts will be as k e d t o v oi d  t h eir bla d ders pri or t o t h e st art i nf usi o n.  
l Ra n d o miz e d p atie nts will be d ose -esc alat e d e v er y 2  we e ks t o r e c ei ve we e kl y i nfusi o ns of S R P -4 0 4 5 or pla ce b o at:  4  m g/ k g/ we e k ( We eks  1 -2), 1 0  m g/ k g/ we e k ( We e ks  3 -4), 
2 0  m g/ k g/ we e k ( W e eks  5 -6), a n d 3 0  m g/ k g  ( We e k 7 t o D S M B saf et y r e vie w).  T h e i nitial 4  p atie nts will b e st a g ger e d wit h a mi ni m u m of 3  da ys bet we e n a d mi nistr ati o ns of t h e i nitial 
d oses t o e a c h of t hese p atie nts. I nfusi o ns ar e t o be gi v e n a c c ordi n g t o i nstr ucti o ns i n t he P har ma c y M a n ual. Patie nts ar e t o be cl osel y m o nit ore d f or at le ast 1 h o ur f ollo wi n g t he c o m pleti o n 
of all i nf usi o ns.  
m  D S M B saf et y dat a e v al uati o n be gi ns o n c e t he last p atie nt h as r e c ei v ed 2  i nf usi o ns at 3 0  m g/ k g  ( W e ek 8).  P atients s h all c o nti n ue t o r ec ei ve d o u ble -bli n d tr e at m ent ( S R P-4 0 4 5 3 0  m g/ k g or 
pla c e b o) u ntil t h e D S M B c o m pletes its r e vie w.  Base d o n t he r es ults of t his r e vie w, t he Sp o ns or will det er mi ne wh et her t o r oll o ver p atie nts i nt o t he o pe n-label e xte nsi o n p eri o d.   
 
 
C CI
C CI
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 1 4  of 7 0  
 
T a ble  2 : 
Sc he d ule of E v e nts : D o u ble-Bli n d  D os e Titr ati o n  w it h O pe n-L a bel E xte nsi o n , c o nti nu e d 
We e k  
1 3 - 
1 5  
1 6  1 7 - 
1 9  
2 0  2 1 - 
2 3  
2 4  2 5 - 
2 7  
2 8  2 9 - 
3 1  
3 2  3 3 - 
3 5  
3 6  3 7 - 
4 7  
4 8  4 9 - 
5 9  
6 0  6 1 - 
7 1  
7 2  7 3 - 
8 3  
8 4  8 5 - 
9 5  
9 6  9 7 - 
1 0 7  
1 0 8  1 0 9 - 
1 1 9  
1 2 0  
Visit Wi n do w  
Afte r tr a nsiti o n t o o pe n -l a bel S R P-4 0 4 5:  ± 3 da ys s uc h t h at n o 2  i nf usi o ns ar e l ess t h a n 6 0 h o urs a part 
1 2 -le a d E C G 
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
E C H O  
 
 
 
 
 
 
 
 
 
 
 
X  
 
 
 
X  
 
 
 
X  
 
 
 
X  
 
 
F ull P h ysic al 
Exa m  c 
 
 
 
 
 
X  
 
 
 
 
 
 
 
X  
 
 
 
X  
 
 
 
X  
 
 
 
X  
Brief P h ysic al 
Exa mi n ati o n  d 
 
X  
 
X  
 
 
 
X  
 
X  
 
X  
 
 
 
X  
 
 
 
X  
 
 
 
X  
 
 
Hei g ht a n d ul n ar 
le n gt h e 
 
 
 
 
 
X  
 
 
 
 
 
X  
 
X  
 
X  
 
X  
 
X  
 
X  
 
X  
 
X  
W ei g ht  
 
X  
 
X  
 
X  
 
X  
 
X  
 
X  
O n c e e v er y 4 we e ks  
Vit al si g ns
 f 
W e e kl y Pre - a n d P ost -I nf usi o n 
Safet y La b 
As s ess me nts  g 
 
X  
 
X  
 
X  
 
X  
 
X  
 
X  
 
X  
 
X  
 
X  
 
X  
 
X  
 
X  
 
X  
P K h 
 
 
 
 
 
X  
 
 
 
 
 
X  
 
X  
 
X  
 
X  
 
X  
 
X  
 
X  
 
X  
D osi n g  i,j 
W e e kl y I nf usi o ns: Patie nts t o re c ei v e pla c eb o or S R P -4 0 4 5 as ra n d o mize d u ntil D S M B re vie w a n d S p o ns or d et er mi n ati o n of  
we e kl y o p e n -la b el d ose le v el 
Co n c o mit a nt 
me dic ati o ns  
Co nti n u o us  
A E mo nit ori n g  
Co nti n u o us  
A E =a d v erse e v e nt; D S M B = Data Saf et y M o nit ori n g B o ard; E C G =ele ctr oc ardi o gr a m; E C H O =e c h oc ardi o gr a m; 
 
 
 
a  A saf et y f oll o w -u p  visit will o c c ur a p pro xi matel y 4  we e ks after t he last st u d y i nfusi o n at t he E n d of St u d y  ( E o S) or f or E arl y T er mi nati o n ( E T).   
C CI
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 1 5  of 7 0  
 
c  F ull p h ysic al e x a mi nati o n t o i n cl u de r e vie w of ge n er al a p pe ara nc e, h e a d, e yes, e ars, n ose, a n d t hr oat ( H E E N T), h eart, l u n gs, a b d o m e n, s ki n, l y mp h n o des, m usc ul os k eletal, a n d 
n e ur ol o gic al s yste ms.  
d  Brief p h ysic al e x a mi nati o n t o i n cl u de e x a mi natio n of ge n er al a p p eara n ce, H E E N T, h eart, c h est, a b d o m e n, a n d s ki n. 
e  Hei g ht a n d ul n ar le n gt h t o be c olle cte d.   If p atie nt is u n a ble t o st a n d, t he n h ei g ht c a n be c alc ulate d usi n g ul n ar le n gt h as descri be d i n Se cti o n  1 0. 3. 1 .  
f Vit al si g ns i n cl u de bl o o d pr ess ur e, h e art r ate, r es pirati o n r ate, a n d or al te mp er at ur e.  F or i nfusi o n visits, vital si g ns ar e  t o be c olle cte d wit hi n a p pr o xi m atel y 3 0 min utes pri or t o i nf u si o n an d 
a p pr o xi m atel y 5, 3 0, a n d 6 0 mi n ut es after t h e e n d of t h e i nf usi o n.  If t he p atie nt h as n ot e x perie nc e d a n i nfusi o n r e a cti o n after 4 8 we e ks of o p en-la bel tr e at m ent, t he I n v estigat or h as 
discr eti o n t o c olle ct p ost -i nf usi o n vital si g ns at 5 a n d 3 0 mi n ut es .  
g  Bef or e p atie nts m a y be gi n d osi n g i n t h e o p en -la bel e xtensi o n p eri o d, saf et y la b orat or y assess me nts m ust be p erf or me d wit hin 2  we e ks pri or t o first d ose.  If saf et y la b or at ory sa mples wer e 
c olle ct e d m ore t h an 2  we e ks pri or t o t he first o pe n -la bel e xtensi o n visit, sa m ples m ust be c olle cte d a gai n a n d r es ult s m ust be r e vie we d bef or e d osi n g.  
h  At W e e ks  2 4, 3 6, 4 8, 7 2, 8 4, 9 6, 1 0 8, a n d 1 2 0, 
  A d diti o n al sa m ples will als o be t a k e n at W ee ks 2 4, 4 8, 7 2, 9 6, a n d  1 2 0 a p pro xi matel y 2 -4  h o urs after c o mpleti o n of t he i nfusi o n.  At We e k  6 0, plas ma sa m ples f or 
serial P K will be o bt ai n e d i m me diatel y pr e-i nf usi o n, a p pr o xi m atel y 5  t o 1 0 mi n utes after c o mpleti o n of t he i nfusi o n, a n d a p pro xi matel y 1, 1. 5, 2, 4, 6, 8, 1 2, 1 6, a n d 2 4  h o urs after 
c o m pleti o n of t he i nfusi o n.  
i All p atie nts will r e c ei v e o pe n -label tre at me nt wit h S R P-4 0 4 5 at 3 0  mg/ k g ( or t he hi gh est t oler ate d d ose  as det er mi ne d d uri n g t h e d ose titr ati o n) a d mi nist er e d we e kl y.  I nf usi o ns ar e t o be 
gi v e n a c c or di n g t o i nstr ucti o ns i n t he P h ar ma c y M a n ual. N ote t hat a n i m pla nte d v e n o us a c c ess p ort m ay be i nserted f or tr e at m ent a d ministrati o n at t he dis cr etio n of t h e I n vesti gat or. 
P atie nts ar e t o be cl osel y m o nit or e d f or at le ast 1  h o ur f oll o wi n g t he c o mpleti o n of all i nf usi o ns.  If t he p atie nt h as n ot e x perien ced a n i nfusi o n r e a cti o n after 4 8  we e ks of o p en -la bel 
tr e at me nt, t h e I n vesti gat or h as discr eti o n t o r e d uc e t he p ost -i nfusi o n o bser vati o n p eri o d t o 3 0 mi n utes.  
j H o m e i nf usi o ns m a y ta ke pla ce 3  o ut of e ver y 4  we e ks, wit h t he f o urt h we e k c o n d ucte d at t he st u d y site.  T his sc h ed ule is i nt e n de d t o r ed uc e st u d y b ur de n while m ai ntai ni n g o n g oi n g 
in -p ers o n s ur v eillan ce b y t he st u d y site.  Detaile d i nstr ucti o ns f or i n -h o m e d osi n g will be pr o vi de d i n a se p ar ate m a n ual t o t he visiti n g n urse.  
 
 
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 1 6  of 7 0  
 
T a ble  2 : 
Sc he d ule of E v e nts : D o u ble-Bli n d  D os e Titr ati o n  w it h O pe n-L a bel E xte nsi o n , c o nti nu e d 
We e k  
1 2 1 -1 3 1  
1 3 2  
1 3 3 -1 4 3  
1 4 4  
F/ U Eo S/ E T  a 
Visit Wi n do w  
Afte r tr a nsiti o n t o o pe n -l a bel S R P-4 0 4 5:  ± 3 da ys s uc h t h at 
n o 2  i nf usi o ns ar e l ess t h a n 6 0 h o urs a part 
 
1 2 -le a d E C G 
X  
X  
E C H O  
 
X  
 
 
 
F ull P h ysic al Exa m  c 
 
 
 
X  
X  
Brief P h ysic al Exa mi n ati o n  d 
 
X  
 
 
 
Hei g ht a n d ul n ar le n gt h  e 
 
X  
 
X  
X  
W ei g ht  
O n c e e v er y 4 we e ks  
X  
Vit al si g ns  f 
W e e kl y Pre - a n d P ost -I nf usi o n 
X  
Safet y La b As sess me nts  g 
 
X  
 
X  
X  
D osi n g  i,j 
W e e kl y I nf usi o ns: Patie nts t o re c ei v e pla c eb o or S R P -4 0 4 5 as 
ra n d o mize d u ntil D S M B re vie w a n d S p o ns or d eter mi n ati o n of 
we e kl y o p e n -la b el d ose le v el 
 
Co n c o mit a nt me dic ati o ns  
Co nti n u o us  
A E mo nit ori n g  
Co nti n u o us  
A E =a d v erse e v e nt; D S M B = Data Saf et y M o nit ori n g B o ard; E C G =ele ctr oc ardi o gr a m; E C H O =e c h oc ardi o gr a m; E o S =e n d of st u d y; E T =e arl y t er mi n ati o n; F/ U =f oll o w -u p; 
 
 
 
a F oll o w -u p ( F/ U ) f or E n d of St u d y (E o S ) is a p plic a ble f or p atie nts wh o c o mplete St u d y 4 0 4 5 -1 0 1 , b ut wh o d o n ot c h o ose t o p artici p ate i n t h e l o n g-ter m e xtensi o n (L T E ) st u d y. A saf et y 
f oll o w-u p visit will o c c ur a p pr o x i m atel y 4 we e ks after t h e last st u d y i nf usi o n at t he E o S or f or E arl y T er mi nati o n ( E T).   F/ U E T is r e q uir e d f or p atie nts wh o disc o nti n ue pre mat ur el y fro m 
St u d y 4 0 4 5 -1 0 1. P atie nts wh o c o mplete St u d y 4 0 4 5 -1 0 1 per prot oc ol a n d wh o r oll o ver t o t h e L T E st u d y will n ot r e q uir e a F/ U visit f or St u d y 4 0 4 5 -1 0 1 . 
c F ull p h ysic al e x a mi nati o n t o i n cl u de r e vie w of ge n er al a p pe ara nc e, h e a d, e yes, e ars, n ose, a n d t hr oat ( H E E N T), h eart, l u n gs, a b d o m e n, s ki n, l y mp h n o des, m usc ul os k eletal, a n d 
n e ur ol o gic al s yste ms.  
d  Brief p h ysic al e x a mi nati o n t o i n cl u de e x a mi natio n of ge n er al a p p eara n ce, H E E N T, h eart,  c h est, a b d o m e n, a n d s ki n.  
e Hei g ht a n d ul n ar le n gt h t o be c olle cte d.  If p atie nt is u n a ble t o st a n d, t he n h ei g ht c a n be c alc ulate d usi n g ul n ar le n gt h as descri be d i n Se cti o n  1 0. 3. 1 .  
f Vit al si g ns i n cl u de bl o o d pr ess ur e, h e art r ate, r es pirati o n r ate, a n d or al te mp er at ur e.  F or i nfusi o n visits, vital si g ns ar e  t o be c olle cte d wit hi n a p pr o xi m atel y 3 0 min utes pri or t o i nf usi o n an d 
a p pr o xi m atel y 5, 3 0, a n d 6 0 mi n ut es after t h e e n d of t h e i nf usi o n.  If t he p atie nt h as n ot e x perie nc ed a n i nfusi o n r e a cti o n after 4 8  we e ks of o p en -la bel tr e at m ent, t he I n v estigat or h as 
discr eti o n t o c olle ct p ost -inf usi o n vital si g ns at 5  a n d 3 0 mi n ut es.  
C CI
C CI
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 1 7  of 7 0  
 
g  Bef or e p atie nts m a y be gi n d osi n g i n t h e o p en -la bel e xtensi o n p eri o d, saf et y la b orat or y assess me nts m ust be p erf or me d wit hin 2  we e ks pri or t o first d ose.   If saf et y la b or at ory sa mples wer e 
c olle ct e d m ore t h an 2  we e ks pri or t o t he first o pe n -la bel e xtensi o n visit, sa m ples m ust be c olle cte d a gai n a n d r es ult s m ust be r e vie we d bef or e d osi n g.  
i All p atie nts will r e c ei v e o pe n -label tre at me nt wit h S R P-4 0 4 5 at 3 0  mg/ k g ( or t he hi g h est t oler ate d d ose as det er mi ne d d uri n g t h e d ose titr ati o n) a d mi nist er e d we e kl y.  I nf usi o ns ar e t o be 
gi v e n a c c or di n g t o i nstr ucti o ns i n t he P h ar ma c y M a n ual.  N ote t h at a n i m pla nte d v e n o us a c c ess p ort m a y be i nserte d f or tr eat me nt a d mi nistr ati o n at t h e discr eti o n of t he I n v estigat or.   
P atie nts ar e t o be cl osel y m o nit or e d f or at le ast 1  h o ur f oll o wi n g t he c o mpleti o n of all i nf usi o ns.  If t he p atie nt h as n ot e x perien ce d a n i nfusi o n r e a cti o n after 4 8  we e ks of o p en -la bel 
tr e at me nt, t h e I n vesti gat or h as discr eti o n t o r e d uc e t he p ost-i nfusi o n o bser vati o n p eri o d t o 3 0 mi n utes.  
j H o m e i nf usi o ns m a y ta ke pla ce 3  o ut of e ver y 4  we e ks, wit h t he f o urt h we e k c o n d ucte d at t he st u d y site.   T his sc h ed ule is i nt e n de d t o r ed uc e st u d y b ur de n while m ai ntai ni n g o n g oi n g 
i n-p ers o n s ur v eillan ce b y t he st u d y site.   Detaile d i nstr ucti o ns f or i n -h o m e d osi n g will be pr o vi de d i n a se p ar ate m a n ual t o t he visiti n g n urse.  
 
 
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 1 8  of 7 0  
 
T a ble  3 : 
Sc he d ule of E v e nts:  I ntr o d ucti o n of O pe n -L a bel Tre at me nt  
N ote :  O pe n -la bel tre at me nt ma y  c o m me nc e o nc e t he D S M B has re vie w e d d o u ble -bli n d d os e -titratio n s afet y data a n d t he S p o ns or’s 
de cisio n has be e n ma de t o pr oc e e d .  T he ass ess me nts in Ta ble  3  will oc c ur d urin g t he first 8  w e e ks of t he o pe n -la bel st u d y perio d a n d 
are in a d ditio n t o t he ass ess me nts in Ta ble  2 .  D u plic ate ass ess me nts at t he s a me st u d y visit s h o uld n ot be perf or me d.   
 
O P E N L A B E L I N T R O D U C TI O N  
St u dy we e k will var y f or e ac h pati e nt s uc h t h at t he O pe n La bel We e k  1 will be t he pati e nt ’s ne xt s c he d ul e d visit 
afte r t he D S M B r e vi e w a n d S po ns or dete r mi n ati o n of we e kl y o pe n -l a bel dos e l e vel 
O pe n La bel We e k  
O L W 1  
O L W 2  
O L W 3  
O L W 4  
O L W 5  
O L W 6  
O L W 7  
O L W 8  
F ull P h ysic al Exa mi n ati o n  a 
X  
 
 
X  
 
 
 
 
Brief P h ysic al Exa mi n ati o n  b 
 
 
 
 
 
 
 
X  
1 2 -le a d E C G  
X  
 
X  
 
 
 
 
 
Cli nic al La b orat or y  Assess me nts  
X  c 
X  
X  
X  
X  
X  
X  
X  
D S M B = Dat a Safet y M o nit ori n g Bo ar d; E C G =ele ctr o c ar di o gra m; O L = o p e n la b el; W = wee k.  
a F ull p h ysic al e x a mi nati o n t o i n cl u de r e vie w of ge n er al a p pe ara nc e, h e a d,  e yes, e ars, n ose, a n d t hr oat ( H E E N T), h eart, l u n gs, a b d o m e n, s ki n, l y mp h n o des, m usc ul os k eletal, a n d 
n e ur ol o gic al s yste ms.  
b Brief p h ysic al e x a mi nati o n will i n cl u de e x a mi nati o n of ge n eral a p p ear an ce, H E E N T, h e art, c hest, a b d o me n, a n d s ki n.  
c Bef or e p atie nts m a y be gi n o pe n -label tre at me nt, saf et y la b orat or y assess m e nts m ust be p erf or me d wit hi n 2 we e ks prior t o first d ose .  If saf et y la b or at ory sa mples wer e c olle cted m ore t ha n 
2  we e ks pri or t o t h e first o pe n -la bel e xte nsi o n visit, sa mples m ust be c olle cted a gai n a n d r es ults m ust be r e vie we d bef or e d osi n g.  
 
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 1 9  of 7 0  
 
3.  
T A B L E O F C O N T E N T S, L I S T O F T A B L E S, A N D LI S T O F 
FI G U R E S  
T A B L E O F C O N T E N T S  
1.  
S Y N O P SI S  ............................................................................................................5  
2.  
S C H E D U L E O F E V E N T S  ................................................................................... 1 1  
3.  
T A B L E O F C O N T E N T S, L I S T O F T A B L E S, A N D LI S T O F FI G U R E S .............. 1 9  
4.  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F  T E R M S  ........................... 2 4  
5.  
I N T R O D U C TI O N ................................................................................................ 2 7  
5. 4.  
Ratio nale f or t he C urre nt St u d y  ............................................................................. 2 8  
6.  
S T U D Y O BJ E C TI V E S ......................................................................................... 2 9  
6. 1.  
Pri mar y O bje cti ve ................................................................................................. 2 9  
6. 2.  
Se c o n dar y O bje cti ve  ............................................................................................. 2 9  
7.  
I N V E S TI G A TI O N A L P L A N ............................................................................... 3 0  
7. 1.  
O verall St u d y D esig n ............................................................................................ 3 0  
7. 2.  
D os e Sele cti o n Rati o nale  ...................................................................................... 3 3  
7. 3.  
St u d y E n d p oi nts  ................................................................................................... 3 4  
7. 4.  
Dis c ussio n of St u d y D esi g n  .................................................................................. 3 5  
7. 4. 3.  
C h oic e of E n d p oints  ............................................................................................. 3 6  
8.  
P A TI E N T P O P U L A TI O N A N D S E L E C TI O N ...................................................... 3 7  
8. 1.  
I ncl usio n Criteria .................................................................................................. 3 7  
8. 2.  
E xcl usio n Criteria ................................................................................................. 3 7  
C CI
C CI
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 2 0  of 7 0  
 
8. 3.  
C o m pletio n of a P atie nt’s P articipati o n a n d O verall St u d y C o m pleti o n ................... 3 8  
8. 4.  
P atie nt Wit h dra w al Criteria ................................................................................... 3 9  
9.  
T R E A T M E N T O F P A TI E N T S  ............................................................................. 4 0  
9. 6.  
A d mi nistratio n of I n vestigati o nal Dr u g Pr o d uct  ..................................................... 4 1  
9. 7.  
D os e M o dific atio n, Re d ucti o n, or D ela y ................................................................ 4 2  
9. 8.  
Safet y C o nsi derati o ns  ........................................................................................... 4 2  
9. 8. 1.  
Ge neral Safet y Pre c a utio ns  ................................................................................... 4 2  
9. 8. 2.  
Safet y M o nit ori n g D uri n g D os e Titrati o n  .............................................................. 4 3  
9. 8. 3.  
St o p pi n g R ules  ..................................................................................................... 4 3  
9. 8. 4.  
D ata Safet y M o nit ori n g B oar d  .............................................................................. 4 4  
9. 9.  
Ra n d o mizatio n a n d Bli n di n g  ................................................................................. 4 4  
9. 9. 1.  
Ra n d o mizatio n  ..................................................................................................... 4 4  
9. 9. 2.  
Bli n di n g f or D os e A d mi nistratio n  ......................................................................... 4 4  
9. 9. 3.  
U n bli n di n g Pr oc e d ures  ......................................................................................... 4 5  
9. 1 0.  
Prior a n d C o nc o mita nt Me dic atio ns a n d T hera pe utic Pr oc e d ures ............................ 4 5  
9. 1 1.  
Tre at me nt C o m plia nc e .......................................................................................... 4 6  
1 0.  
S T U D Y A S S E S S M E N T S ..................................................................................... 4 7  
1 0. 1.  
Scre e nin g Ass ess me nts  ......................................................................................... 4 7  
1 0. 2.  
Bas eli ne/ We e k 1 Ass ess me nts ............................................................................... 4 7  
1 0. 3.  
Safet y Ass ess me nts  .............................................................................................. 4 8  
1 0. 3. 1.  
Vital Si g ns i ncl u di n g Wei g ht a n d H ei g ht  ............................................................... 4 8  
1 0. 3. 2.  
P h ysic al E xa minati o n  ........................................................................................... 4 9  
1 0. 3. 3.  
Cli nic al La b orat or y Ass ess me nts ........................................................................... 4 9  
1 0. 3. 3. 1.  
H e mat olo g y .......................................................................................................... 5 0  
1 0. 3. 3. 2 . 
C oa g ulati o n  .......................................................................................................... 5 0  
1 0. 3. 3. 3.  
Ser u m C he mistr y  .................................................................................................. 5 0  
1 0. 3. 3. 4.  
Urinal ysis ............................................................................................................. 5 0  
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 2 1  of 7 0  
 
1 0. 3. 4.  
C o nc o mita nt Me dic atio ns a n d P h ysiot hera pe utic I nter ve nti o n  ................................ 5 1  
1 0. 3. 5.  
Ot her Safet y Ass ess me nts  ..................................................................................... 5 1  
1 0. 3. 5. 1.  
Ele ctr oc ar di o gra m ( E C G)  ..................................................................................... 5 1  
1 0. 3. 5. 2.  
Ec h oc ar dio gra p h y ( E C H O)  ................................................................................... 5 1  
1 0. 3. 5. 3.  
A d vers e E ve nts  .................................................................................................... 5 1  
1 0. 5.  
P har ma c o kinetic Ass ess me nts  ............................................................................... 5 3  
1 0. 5. 1.  
Bl o o d Sa m ple C olle ctio n  ...................................................................................... 5 3  
1 0. 5. 2.  
Urine Sa m ple C olle cti o n  ....................................................................................... 5 3  
1 1.  
A D V E R S E E V E N T S ............................................................................................ 5 4  
1 1. 1.  
C oll e cti o n of A d vers e E ve nts  ................................................................................ 5 4  
1 1. 2.  
D efiniti o n of A d vers e E ve nts  ................................................................................ 5 4  
1 1. 2. 1.  
A d vers e E ve nt ( A E) .............................................................................................. 5 4  
1 1 . 2. 2. 
Seri o us A d vers e E ve nt ( S A E)  ............................................................................... 5 4  
1 1. 3.  
Classific ati o n of A d vers e E ve nts  ........................................................................... 5 5  
1 1. 3. 1.  
Relatio ns hi p t o I n vestigati o nal Dr u g Pr o d uct  ......................................................... 5 5  
1 1. 3. 2.  
Relatio ns hi p t o St u d y Pr oc e d ures  .......................................................................... 5 5  
1 1. 3. 3.  
Relatio ns hi p t o U n derlyi n g Dis e as e ....................................................................... 5 5  
1 1. 3. 4.  
Se verit y of A d vers e E ve nts  ................................................................................... 5 6  
1 1. 3. 5.  
O utc o me  .............................................................................................................. 5 6  
1 1. 3. 6.  
A cti o n Ta ke n Re gar di n g t he I n vestigati o nal Dr u g Pr o d uct  ..................................... 5 6  
1 1. 3. 8.  
S us pe cte d U ne x pe cte d Seri o us A d vers e Re actio ns ( S U S A R)  ................................. 5 6  
1 1. 4.  
Re c or di n g A d vers e E ve nts  .................................................................................... 5 6  
1 1. 5.  
Re p ortin g Serio us A d vers e E ve nts  ........................................................................ 5 7  
1 1. 6.  
S pe cial Sit uati o ns  ................................................................................................. 5 7  
1 1. 6. 1.  
O ver d os e  .............................................................................................................. 5 7  
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 2 2  of 7 0  
 
1 1. 6. 2.  
D e at h  ................................................................................................................... 5 7  
1 1. 6. 3.  
U n bli n di n g d ue t o a Me dic al E mer ge nc y  ............................................................... 5 7  
1 1. 6. 4.  
Res p o nsi bilities of t he I n vestigat or ........................................................................ 5 8  
1 1. 6. 5.  
Res p o nsi bilities of t he S p o ns or  ............................................................................. 5 8  
1 2.  
S T A TI S TI C S  ....................................................................................................... 5 9  
1 2. 1.  
Ge neral C o nsi derati o ns  ......................................................................................... 5 9  
1 2. 2.  
D eter mi natio n of Sa m ple Size  ............................................................................... 5 9  
1 2. 3.  
A nal ysis Sets  ........................................................................................................ 5 9  
1 2. 4.  
Statistic al A nal ysis  ............................................................................................... 5 9  
1 2. 4. 1.  
Pr ot oc ol D e viatio ns  .............................................................................................. 5 9  
1 2. 4. 2.  
Dis p ositi o n, D e m o gra p hics, a n d Bas eli ne C hara cteristics ....................................... 6 0  
1 2. 4. 3.  
Prior a n d C o nc o mita nt Me dic atio ns  ...................................................................... 6 0  
1 2. 4. 4.  
Me dic al Hist or y .................................................................................................... 6 0  
1 2. 4. 5.  
D osi n g  ................................................................................................................. 6 0  
1 2. 4. 6.  
Safet y V aria bles  ................................................................................................... 6 0  
1 2. 4 . 7. 
Safet y A nal ysis  .................................................................................................... 6 0  
1 2. 4. 8.  
P har ma c o kinetic A nalys es  .................................................................................... 6 1  
1 3.  
D A T A C O L L E C TI O N, Q U A LI T Y A S S U R A N C E, A N D M A N A G E M E N T  ......... 6 3  
1 3. 1.  
Re c or di n g of D ata  ................................................................................................ 6 3  
1 3. 2 . 
Q ualit y Ass ura nc e  ................................................................................................ 6 3  
1 3. 3.  
Rete nti o n of St u d y D oc u me nts  .............................................................................. 6 3  
1 3. 4.  
Ter minati o n of St u d y or St u d y Site  ....................................................................... 6 4  
1 4.  
S P E CI A L R E Q UI R E M E N T S  A N D P R O C E D U R E S ............................................. 6 5  
1 4. 1.  
C o m plia nc e wit h Et hic al a n d Re g ulat or y Gui delines .............................................. 6 5  
1 4. 2.  
Re g ulat or y a n d I n de pe n de nt Et hics C o m mitte e Re vie w  ......................................... 6 5  
1 4. 3.  
I nf or me d C o ns e nt/ Ass e nt...................................................................................... 6 5  
1 4. 4.  
C o m plia nc e wit h t he Pr ot oc ol  ............................................................................... 6 5  
1 4. 5.  
C o nfi de ntialit y  ..................................................................................................... 6 6  
1 4. 5. 1.  
D ata  ..................................................................................................................... 6 6  
1 4. 5. 2.  
P atie nt A n o n y mit y ................................................................................................ 6 6  
1 5.  
S T U D Y D O C U M E N T A TI O N A N D G E N E R A L I N F O R M A T I O N ....................... 6 7  
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 2 3  of 7 0  
 
1 5. 1.  
Ess e ntial St u d y D oc u me nts  ................................................................................... 6 7  
1 5. 2.  
Ge neral I nf or matio n  ............................................................................................. 6 7  
1 5. 3.  
Diss e mi natio n of St u d y Res ults ............................................................................. 6 7  
1 5. 4.  
Pr o d uct H a n dli n g a n d C o m plai nts Re p orti n g  ......................................................... 6 8  
1 6.  
LI S T O F R E F E R E N C E S  ...................................................................................... 6 9  
 
LI S T O F T A B L E S  
Ta ble  1: 
E mer ge nc y C o nta ct I nf or mati o n ..............................................................................4  
Ta ble  2: 
Sc he d ule of E ve nts: D o u bl e -Blin d D os e Titratio n wit h O pe n -La bel 
E xte nsio n  ............................................................................................................. 1 2  
Ta ble  3: 
Sc he d ule of E ve nts:  I ntr o d uctio n of O pe n -La bel Tre at me nt  .................................. 1 8  
Ta ble  4: 
List of A b bre viati o ns a n d D efi niti o ns  .................................................................... 2 4  
 
LI S T O F FI G U R E S  
Fig ure  1: 
St u d y D esi g n Sc he matic  ....................................................................................... 3 2  
 
 

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 2 4  of 7 0  
 
4.  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F  T E R M S  
T he f ollo win g a b bre viatio ns, a cr o n y ms, a n d ter ms are us e d in t his st u d y pr ot oc ol.  
T a ble  4 : 
List of A b bre vi ati o ns a n d D efi niti o ns  
A b bre vi ati o n or t e r m  Defi niti o n  
2 D  
2 -di me nsio nal  
6 M W T  
6 -Min ute Walk T est  
A C E  
a n giote nsin -c o n vertin g e nz y me  
A E(s)  
a d vers e e ve nt  
A L T  
ala nine a min otr a nsf er as e  
a P T T  
activate d partial t hr o m b o plastin ti me  
A R B  
a n giote nsin r ec e pt or bloc ker  
A S T  
as partate a min otr a nsf er as e  
A U C  
ar ea u n der t he plas ma c o nc e ntr atio n -ti me c ur ve 
B M D  
Bec ker m us c ular d ystr o p h y  
B MI  
b o d y mass in de x  
B U N  
blo o d ur ea nitr o ge n  
° C 
de gr ees Celsius  
C A P  
C olle ge of A meric a n P at h olo gist s 
C D  
c o m pact dis c  
C F R  
C o de of F e der al  Re g ulatio ns  
C K  
cr eatine kinas e 
C LI A  
Clinic al La b or at or y I m pr o ve me nt A me n d me nts  
C L  
t otal clear a nc e  
C L R  
urinar y clear a nc e  
C ma x  
ma xi m u m plas ma c o nc e ntr atio n  
C R F  
c as e r e p ort f or m  
C R O  
c o ntr act r es ear c h or ga nizatio n  
C R P  
C -r eactive pr otein 
C S R  
clinic al st u d y r e p ort 
D M D  
D uc he n ne m us c ular d ystr op h y  
D N A  
de o x yrib o n ucleic acid  
D S M B  
Data S af et y M o nit orin g Boar d  

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 2 5  of 7 0  
 
T a ble  4 : 
List of A b bre vi ati o ns a n d D efi niti o ns  
A b bre vi ati o n or t e r m  Defi niti o n  
E C G  
electr oc ar dio gr a m  
E C H O  
ec h oc ar dio gr a m/ec hocar dio gr a p h y  
e C R F  
electr o nic c as e r e p ort f or m  
E D C  
electr o nic data c a pt ur e  
E F  
ejectio n fr actio n  
E o S  
e n d of st u d y  
E T  
early ter minatio n  
F D A  
F o o d a n d Dr u g Ad ministr atio n  
F V C  
f or c e d vital c a pacit y 
G C P  
G o o d Clinic al Pr actic e  
G G T  
ga m ma gluta m yl tr a nsf er as e  
H E E N T  
hea d, e yes, ears, n os e, a n d t hr oat  
h G H 
h u ma n gr o wt h h or m o ne  
HI P A A  
Healt h I ns ur a nc e P orta bilit y a n d Ac c o u nta bilit y Act  
I C F 
inf or me d c o ns e nt f or m 
I C H 
I nter natio nal C o u ncil  o n Har m o ni satio n 
I E C 
I n de pe n de nt Et hics C o m mittee 
I N D 
I n vestigatio nal Ne w Dr u g 
I N R 
I nter natio nal N or malize d Ratio 
I P 
in vestigatio nal pr o d uct 
I R B 
I nstit utio nal Re vie w Boar d  
I V 
intr a ve n o us 
KI M -1  
k id ne y injur y m olec ule  1  
L D H  
lactas e de h y dr o ge nas e 
L T E  
lo n g-ter m e xte nsio n 
L V E F  
left ve ntric ular ejectio n fr actio n 
Me d D R A  
Me dic al Dictio nar y f or Re g ulat or y Activities  
M L P A  
m ultiple x ligatio n -de pe n de nt pr o be a m plific atio n  
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 2 6  of 7 0  
 
T a ble  4 : 
List of A b bre vi ati o ns a n d D efi niti o ns  
A b bre vi ati o n or t e r m  Defi niti o n  
M M W R  
M or bidit y a n d M ortalit y Wee kly Re p ort  
m R N A  
mess e n ger R N A  
M R T  
mea n r eside nc e ti me  
N O A E L  
n o o bs er va ble a d vers e eff ect le vel 
P B S  
p h os p hate -b uff er e d s aline  
P D E -5  
p h os p h o diester as e t y pe  5  
P E  
p h ysic al e xa minatio n  
PI  
Principal I n vestigat or  
P K  
p har mac o kinetic(s)  
P M O  
p h os p h or o dia midate m or p h olin o olig o mer  
P T  
pr ef err e d ter m  
R N A  
rib o n ucleic acid 
R B C  
r e d blo o d c ell 
S A E  
s erio us a d vers e e ve nt 
S A P  
statistic al a nalysis pla n 
S ar e pt a  
S ar e pta T her a pe utics, I nc.  
S N P  
sin gle n ucle otide p oly m or p his m 
S O C  
s yste m or ga n class or sta n dar d of car e 
S R P -4 0 4 5  
in vestigatio nal dr u g pr o d uct f or e x o n 4 5 s kip pin g 
S U S A R  
s us pecte d u ne x pecte d serio us a d verse r eactio n  
t½  
eli minatio n half -lif e 
T E A E  
tr eat me nt-e mer ge nt A E 
T ma x  
ti me t o ma xi m u m plas ma c o nc e ntr atio n  
V ss 
v olu me of distrib utio n at stea d y -state 
U L N  
u p per li mit of n or mal  
U S  
Unite d States  
W B C  
w hite blo o d c ell ( c o u nt)  
C CI
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 2 7  of 7 0  
 
5.  
I N T R O D U C TI O N 
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Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 2 8  of 7 0  
 
5. 4.  
R ati o n ale f o r t he C urre nt St u d y  
T he ratio nale of t he c urre nt st u d y is t o ass ess t he s afet y a n d t olera bilit y of S R P -4 0 4 5 f or t he first 
ti me in a clinic al s ettin g. I n a d ditio n, t his st u d y will e valuate P K of S R P -4 0 4 5 , as w ell as ass ess 
 effic a c y e n d p oints in D M D patie nts a me na ble t o s kip pin g e x o n 4 5 
a n d will be us e d t o esta blis h t he d os e f or us e in f urt her clinic al trials wit h S R P -4 0 4 5.  
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 2 9  of 7 0  
 
6.  
S T U D Y O B J E C TI V E S  
6. 1.  
Pri m ary O bjecti ve  
 T o e valuate t he s afet y a n d t olera bilit y of 4  es c alatin g I V d os es ( 4, 1 0, 2 0, a n d 
3 0  m g/ k g) of S R P -4 0 4 5 a d minist ere d o nc e w e e kly f or at le ast 2  w e e ks per d os e le vel 
as c o m pare d t o pla c e b o.  
6. 2.  
Sec o n d ary O bjecti ve  
 T o deter mine t he P K pr ofile of 4  es c alatin g d os e s of S R P-4 0 4 5 . 
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 3 0  of 7 0  
 
7.  
I N V E S TI G A TI O N A L P L A N  
7. 1.  
O verall St u d y Desi g n  
T his is a first -in-h u ma n, 
m ultic e nter, m ultiple -d os e st u d y desig ne d t o ass ess t he s afety, 
t olera bilit y, a n d P K of o nc e-w e e kly I V in f usio ns of S R P-4 0 4 5 in a m b ulat or y patie nts wit h 
ge n ot y pic all y  c o nfir me d D M D c hara cterize d b y deletio n s a me na ble t o e x o n 4 5 s kip pin g (e g , 
deletio ns of e x o ns  1 2 -4 4, 1 8 -4 4, 4 4, 4 6 -4 7, 4 6 -4 8, 4 6 -4 9,4 6 -5 1, 4 6 -5 3, or 4 6 -5 5).  T his st u d y 
will be c o n d ucte d at a p pro xi mately 4  st u d y c e nters as a ra n d o mize d, d o u ble -blin d, 
pla c e b o -c o ntr olle d, d os e -titratio n e valuatio n of 4  d os e le vels of S R P -4 0 4 5 ( 4, 1 0, 2 0, a n d 
3 0  m g/ k g  a d ministere d w e e kly  f or a mini m u m of 2  w e e ks  per le vel) c o m pare d t o pla c e b o o ver 
a p pr o xi mately 1 2 w e e ks .  T he d o u ble -blin d d os e -titratio n perio d will be f ollo w e d b y a n 
o pe n -la bel e xte nsio n perio d e valuatin g t he s afet y a n d effic a c y of S R P -4 0 4 5 3 0  m g / k g ( or t he 
hig hest t olerate d d os e as deter mine d d urin g t he d os e titratio n)  a d ministere d w e e kly t hr o u g h 
We e k 1 4 4 .  After c o m pletin g t he o pe n-la bel e xte nsio n perio d, eligible patie nts ma y e nter a 
pla n ne d lo n g-ter m e xte nsio n (L T E ) st u d y f or e xte n de d tre at me nt.  All a ctivities f or t hes e s u bje cts 
will be o utline d in a L T E  st u d y pr ot oc ol.  
T he t otal st u d y d uratio n will be a p pr o xi mately 1 5 2  w e e ks, e nc o m passin g a Scre e nin g perio d ( u p 
t o a p pr o xi mately 4  w e e ks), a d o u ble -bli n d d os e -titratio n perio d f ollo w e d b y a n o pe n -la bel 
e xte nsio n ( u p t o 1 4 4  w e e ks) , a n d a 4-w e e k p ost -tre at me nt s afet y f ollo w-u p .  F ollo w -u p f or e n d 
of st u d y is a p plic a ble f or patie nts w h o c o m plete St u d y 4 0 4 5-1 0 1 , b ut w h o d o n ot c h o os e t o 
participate in t he L T E st u d y .  A s afet y f ollo w-u p visit will oc c ur a p pr o xi mately 4 w e e ks after t he 
last st u d y inf usio n at t he e n d of st u d y or f or e arly ter minatio n.  F ollo w -u p f or e arly ter minatio n is 
re q uire d f or patie nts w h o dis c o ntin ue pre mat urely fr o m St u d y 4 0 4 5-1 0 1.  P atie nts w h o c o m plete 
St u d y 4 0 4 5 -1 0 1 per pr ot oc ol a n d w h o r oll o ver t o t he L T E st u d y will n ot re q uire a f ollo w -u p 
visit f or St u d y 4 0 4 5 -1 0 1.  
N o n -a m b ulat or y D M D patie nts or D M D  patie nts u na ble t o w alk 3 0 0  m eters  or m ore  o n t he 
6 M W T will participate in a n u p t o a p pr o xi mately 4 -w e e k Scre e nin g perio d t o e ns ure eligibilit y 
prior t o ra n d o mizatio n t o S R P -4 0 4 5 or pla c e b o.   A n e c h oc ar dio gra m ( E C H O) a n d 
ele ctr oc ar dio gra m ( E C G) will als o oc c ur d urin g Scre e nin g.  A D N A s a m ple t o  c o nfir m t he 
ge netic deletio n a n d  
 
, a n d blo o d a n d urine s a m ples f or clinic al la b orat or y 
testin g will be ta ke n.  
 
 
 
  A f ull 
p h ysic al e xa minatio n will be c o n d ucte d d urin g Scre e nin g.   Eligible patie nts w h o ha ve 
o ut -of -fra me deletio ns t hat ma y be c orre cte d b y s kip pin g e x o n 4 5 will be ra n d o mize d t o re c eive 
o nc e -w e e kly I V inf usio ns of S R P -4 0 4 5 or pla c e b o.  T w elve patie nts will be ra n d o mize d ( 2:1) in 
d o u ble -blin de d fas hio n t o re c eive S R P -4 0 4 5 ( n = 8) or pla c e b o ( n = 4 ).  P atie nts will re c eive a  
o nc e -w e e kly I V inf usio n of S R P -4 0 4 5 or pla c e b o at es c alatin g d os e le vels, e a c h f or at le ast 
2  w e e ks:  4  m g/ k g at We e ks  1  t o 2; 1 0  m g/ k g at We e ks  3  t o 4; 2 0  m g/ k g at We e ks  5  t o 6; a n d 
3 0  m g/ k g be gin nin g at We e k  7.   Refer t o Se ctio n  7. 2. 3  f or s pe cific details re gar din g s pa cin g of 
initial d os es bet w e e n patie nts d urin g d os e titratio n.  D urin g t he d os e titratio n p erio d of t he st u d y, 
d osin g  will be interr u pte d or halte d if s pe cific pre define d st o p pin g criteria are met or if ot her wis e 
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 3 1  of 7 0  
 
w arra nte d at t he dis cretio n of t he S p o ns or or I n vestigat or.  O nc e t he last patie nt has re c eive d 
2  inf usio ns at 3 0 m g/ k g ( We e k 8), a n in de pe n de nt D ata Safet y M o nit orin g B oar d ( D S M B) will 
re vie w c u m ulative s afet y data.  Re vie w b y t he D S M B is ne c ess ar y  f or a d visin g t he S p o ns or 
a b o ut w het her t he s afet y data allo w f or lo n ger -ter m d osin g wit h S R P-4 0 4 5.  P atie nts will 
c o ntin ue t o re c eive t heir ra n d o mize d tre at me nt ( S R P -4 0 4 5 or pla c e b o) in a blin de d fas hio n u ntil 
t he D S M B re vie w is c o m plete.  Bas e d o n t he res ults of t his re vie w, t he S p o ns or will deter mine 
w het her t o r oll o ver patie nts int o t he o pe n -la bel e xte nsio n perio d.  D urin g t he o pe n -la bel 
e xte nsio n, patie nts will re c eive S R P -4 0 4 5 at 3 0  m g/ k g (or t he hig hest t olerate d d os e as 
deter mine d d urin g t he d os e titratio n)  w e e kly.  
P atie nts will u n der g o r o utine s afet y e valuatio ns.  A d vers e e ve nts ( A Es) a n d c o nc o mita nt 
me dic atio ns will be m o nit ore d a n d d oc u me nte d c o ntin uall y o ver t he c o urs e of t he st u d y.  
 
  Plas ma s a m ples f or 
s erial P K deter minatio n will be c olle cte d at Bas eline/ We e k 1 a n d We e ks  3, 5, 7 , a n d 6 0 .  Urine 
s a m ples f or s erial P K deter minatio n will be c olle cte d at Ba s eline/ We e k 1 a n d We e ks  3, 5, 7, 
a n d 1 2.  
 
 
 
  
A n E C G will be perf or me d at  Scre e nin g, Bas eline/ We e k  1, We e k  7, We e k  1 2, a n d, t he n e ver y 
1 2  w e e ks.  A n E C H O will be pe rf or me d at Scre e nin g, We e k 1 2, a n d, t he n e ver y 2 4  w e e ks.   
Clinic al la b orat or y ass ess me nts will be perf or me d at Scre e nin g, Bas eline/ We e k 1, We e ks  2 -9, 
We e k  1 2, t he n, e ver y 4  w e e ks t o We e k  3 6, a n d, t he n e ver y 1 2  w e e ks.  Vital sig ns will be 
ass ess e d w e e kly pre - a n d p ost-inf usio n.  H eig ht will be ass ess e d at Scre e nin g a n d, t he n, e ver y 
1 2  w e e ks.  Weig ht will be ass es s e d at Scre e nin g, Bas eline/ We e k 1, a n d, t he n, e ver y 4  w e e ks.  A 
f ull p h ysic al e xa m will be c o n d ucte d at Scre e nin g, Bas eline/ We e k 1, We e k  4, We e k  1 2, 
We e k  2 4, a n d, t he n, e ver y 2 4  w e e ks.  A brief p h ysic al  e xa m will be c o n d ucte d e ver y 4  w e e ks 
(e xc e pt at ti mes o f a f ull p h ysic al e xa m) t o We e k 3 6 a n d, t he n, e ver y 2 4  w e e ks.  
A d ditio nal s afet y ass ess me nts will be perf or me d d urin g  t he first 8 w e e ks of o pe n -la bel tre at me nt, 
as s pe cifie d in in t he Sc he d ule of E ve nts (Ta ble  3 ). 
All ass ess me nts are s pe cifie d in t he Sc he d ule of E ve nts ( Ta ble  2  a n d Ta ble  3 ).  Fig ure  1  is a 
s c he matic of t he st u d y desig n.  
 
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol N o. 4 0 4 5 -1 0 1, V ersio n 4. 0  
 
P a ge 3 2  of 7 0  
 
Fi g ure  1 : 
St u d y D e si g n Sc he m atic  
 
 

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 3 3  of 7 0  
  
7. 2.  
D ose Selecti o n R ati o nale  
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 3 4  of 7 0  
  
7. 3.  
St u d y E n d p oi nts  
T he f ollo win g st u d y e n d p oints will be e valuate d in t his st u d y.   D es criptio ns of all st u d y 
ass ess me nts a n d pr oc e d ures are pr o vide d in Se ctio n  1 0 . 
T he pri mar y e n d p oint is ass ess me nt of  t he s afet y of S R P -4 0 4 5  d urin g t he d o u ble -blin d 
d os e -titratio n perio d a c c or din g t o t he f ollo win g:  
 I ncide nc e of A Es  
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 3 5  of 7 0  
  
 I ncide nc e of clinic al la b orat or y a b n or malities ( he mat olo g y, c he mistr y, c oa g ulatio n, 
urinalysis)  
 I ncide nc e of a b n or malities in vital sig ns a n d p h ysic al e xa minatio ns   
 Cli nic ally sig nific a nt w ors e nin g of E C Gs a n d E C H O  
T he s e c o n dar y e n d p oint is t o deter mine t he P K pr ofile of S R P -4 0 4 5 d urin g t he d o u ble -blin d 
d os e -titratio n perio d: 
 Ma xi m u m plas ma c o nc e ntratio n ( C
m a x ) 
 Ti me t o ma xi m u m plas ma c o nc e ntratio n ( T m a x ) 
 Are a u n der t he plas ma c o nc e ntratio n -c ur ve ( A U C)  
 A p pare nt v olu me of distrib utio n at ste a d y state ( V ss) 
 Eli minatio n half -life (t½ ) 
 T otal cle ara nc e ( C L)  
 Me a n reside nc e ti me ( M R T)  
 Urinar y cle ara nc e ( C L R ) 
7. 4.  
Disc ussi o n of St u d y Desi g n  
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 3 6  of 7 0  
  
7. 4.3.  
C h oic e of E n d p oi nts  
T his is a P has e  1 clinic al st u d y t o e valuate t he s afet y, t olera bilit y, a n d P K of S R P -4 0 4 5.   
 
w ere c h os e n f or t h eir rele va nc e t o D M D.   
 w ere c h os e n bas e d o n 
t he dis a bilit y le vel e x pe cte d in t he st u d y p o p ulatio n.  
C CI
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 3 7  of 7 0  
  
8.  
P A TI E N T P O P U L A TI O N A N D S E L E C TI O N  
8. 1.  
I ncl usi o n Criteria  
P atie nts m ust me et all of t he f ollo win g inclusio n criteria t o be eligible f or t his st u d y.  
1.  Male s a ge d 7 t o  2 1, inclusive.  
2.  Esta blis he d clinic al dia g n osis of D M D w it h a deletio n a me na ble t o e x o n 4 5 s kip pin g (e g , 
d eletio ns of e x o ns  1 2 -4 4, 1 8 -4 4, 4 4, 4 6 -4 7, 4 6 -4 8, 4 6 -4 9,  4 6 -5 1, 4 6 -5 3, or 4 6 -5 5) as 
d oc u me nte d b y a ge netic re p ort fr o m a n a c cre dite d la b orat or y c o nfir min g deletio n 
e n d p oints b y m ultiple x ligatio n-de pe n de nt pr o be a m plific ati o n ( M L P A) or s e q ue ncin g.  
3.  Sta ble  c ar dia c a n d p ul m o nar y f u nctio n t hat, in t he I n vestigat or’s o pinio n, is u nlikely t o 
de c o m pe ns ate o ver t he d uratio n of t he st u d y . 
4.  N o n -a m b ulat or y, or inc a pa ble of w alkin g ≥3 0 0  meters o n t he 6 -Min ute 
Walk Test 
( 6 M W T). 
5.  O n a sta ble d os e of oral c ortic oster oids f or at le ast 2 4 w e e ks prior t o st u d y dr u g 
a d ministratio n a n d t he d os e  or d os e e q uivale nt  is e x pe cte d t o re main c o nsta nt (e xc e pt f or 
m o dific atio ns t o a c c o m m o date c ha n ges in w eig ht) t hr o u g h o ut t he st u d y, O R  has n ot 
re c eive d c ortic oster oids f or at le ast 2 4  w e e ks prior t o st u d y dr u g a d ministrati o n a n d  d oes 
n ot e x pe ct t o start c ortic oster oids t hr o u g h o ut t he st u d y.   
6.  P atie nts w h o are p ost -p u bertal a n d s e x ually a ctive m ust a gre e t o us e, f or t he e ntire 
d uratio n of t he st u d y a n d f or 9 0  da ys p ost last d os e, a male c o n d o m, a n d t he fe male 
s e x ual part ner m ust als o us e a me dic ally a c c e pta ble f or m of birt h c o ntr ol (e g, oral 
c o ntra c e ptive).  
7.  A ble t o u n dersta n d a n d c o m ply wit h all st u d y re q uire me nts, in t he I n vestigat or’s o pi nio n, 
or if u n der t he a ge of 1 8  ye ars, m ust ha ve (a) pare nt(s) or le gal g uar dia n(s) w h o is/are  
a ble t o u n dersta n d a n d c o m ply wit h all t he st u d y re q uire me nts.  
8.  Willin g t o pr o vide inf or me d c o ns e nt t o participate in t he st u d y, or if u n der t he a ge of 
1 8  ye ars , willin g t o pr o vide inf or me d ass e nt, if a p plic a ble, a n d has (a) pare nt(s) or le gal 
g uar dia n(s) w h o is/are willin g t o pr o vide writte n inf or me d c o ns e nt f or t he patie nt t o 
participate in t he st u d y.   
8. 2.  
Excl usi o n Criteri a  
P atie nts w h o me et a n y of t he f ollo win g criteria will be e xclu de d fr o m t his st u d y.  
1.  Us e of a n y p har ma c olo gic tre at me nt  ( ot her t ha n c ortic oster oids) wit hin 1 2 w e e ks prior t o 
Bas eline/ We e k  1 t hat mig ht in t he I n vestigat or’s ju d g me nt ha ve a n effe ct o n m us cle 
stre n gt h or f u nctio n (e g, gr o wt h h or m o ne, a na b olic ster oids).   ( C urr e nt gr o wt h h or m o ne 
tr eat me nt f or s h ort stat ure will be allo w e d if me dic ally in dic ate d.)  
2.  C urre nt  or p re vio us tre at me nt wit h t he e x peri me ntal a ge nts S M T C 1 1 0 0 ( B M N-1 9 5) or 
P R O 0 4 5 at a n y ti me.  
3.  Us e of ot her R N A a ntis e ns e or ge ne t hera p y a ge nts.  

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 3 8  of 7 0  
  
4.  C urre nt or pre vio us tre at me nt wit h a n y ot her e x peri me ntal tre at me nt ( ot her t ha n 
defla za c ort ) wit hin 1 2 w e e ks prior t o Bas eline/ We e k  1 or participatio n in a n y ot her 
inter ve ntio nal clinic al trial wit hin 1 2  w e e ks  prior t o Bas eline/ We e k  1.  
5.  Us e of a n y a min o glyc oside  a ntibiotic or statin wit hin 1 2 w e e ks prior t o Bas eline/ We e k  1 
or a nticipate d ne e d f or a n a min o glyc oside a ntibiotic or statin d urin g t he st u d y.  
6.  I nitiatio n or c ha n ge of d osin g (e xc e pt f or m o dific atio ns t o a c c o m m o date c ha n ges in 
w eig ht ) wit hin 1 2 w e e ks prior t o Bas eline/ We e k  1 a n d/ or a nticipate d ne e d f or a c ha n ge in 
d osin g  (e xc e pt f or m o dific atio ns t o a c c o m m o date c ha n ges in w eig ht) d urin g t he st u d y f or 
a n y of t he f ollo win g: a n giote nsin -c o n verti n g e nz y me ( A C E) in hibit ors, a n giote nsin 
re c e pt or bloc kin g a ge nts ( A R Bs), β-bloc kers, p otassiu m.  
7.  I nitiation or c ha n ge of d osin g wit hi n 1 2  w e e ks prior t o Bas eline/ We e k  1 a n d/ or 
a nticipate d ne e d f or a c ha n ge in d osin g d urin g t he st u d y f or o ver -t he-c o u nter pre paratio ns 
s uc h as her bal/ n o n-her bal s u p ple me nts, vita mins, 
minerals, a n d h o me o pat hic 
pre paratio ns.  
8.  Left ve ntric ular eje ctio n fra ctio n ( L V E F) < 4 0 % o n t he S cre e nin g E C H O, a n d/ or Q Tc F  
≥4 5 0  ms e c o n t he Scre e nin g  E C G.  
9.  F orc e d  vital c a pa cit y ( F V C) < 5 0 % of pre dicte d value  at Scre e nin g a n d/ or 
Bas eline/ We e k  1, a n d/ or  re q uire me nt f or n oct ur nal ve ntilatio n. 
1 0.  Major  s ur ger y wit hin 3 m o nt hs prior t o Bas eline/ We e k  1 or pla n ne d s ur ger y f or a n y ti me 
d urin g t his st u d y.  
1 1.  Pres e nc e  of ot her clinic all y sig nific a nt illness inclu din g c ar dia c, p ul m o nar y, he patic, 
re nal, he mat olo gic, i m m u n ol o gic, or be ha vioral dis e as e, or malig na nc y. 
1 2.  A n y ot her c o n ditio n t hat, in t he I n vestigat or’s o pinio n, c o uld interfere wit h t he patie nt’s 
participatio n  in t he st u d y. 
8. 3.  
C o m pleti o n of a P atie nt’s P artici p ati o n a n d O verall St u d y 
C o m pleti o n  
T he le n gt h of a patie nt’s participatio n in t he d o u ble -bli n d d os e -titratio n perio d of t he st u d y wi ll 
be fr o m t he ti me t hat t he inf or me d ass e nt/c o ns e nt f or ms are sig ne d u ntil a p pr o xi mately 4 w e e ks 
after t he last patie nt e nr olle d in t he st u d y re c eive d 1 2 w e e kly d os es of d o u ble -bli n d tre at me nt.   
Bas e d u p o n t he fin din gs of t he D S M B in its re vie w of d os e-titratio n s afet y data, t he S p o ns or will 
deter mine w het her t o r oll o ver p atie nts o nt o o pe n -la bel tre at me nt wit h S R P -4 0 4 5 at 3 0  m g/ k g  ( or 
t he hig hest t olerate d d os e as deter mine d d urin g t he d os e titratio n).  Tre at me nt will c o ntin ue  u ntil 
S t u d y W e e k 1 4 4 , s uc h t hat t he last patie nt e nr olle d will ha ve re c eive d a p pr o xi mately 1 2 8  w e e ks 
of o pe n -la bel S R P-4 0 4 5.  
A fter c o m pletio n of tre at me nt, patie nts will ret ur n f or a p ost-tre at me nt s afet y visit a p pr o xi mately 
4  w e e ks after t heir last st u d y inf usio n.   T he st u d y will e n d o nc e t he last patie nt has c o m plete d his 
last st u d y visit.  
F ollo w -u p f or e n d of st u d y is a p plic a ble f or patie nts w h o c o m plete St u d y 4 0 4 5-1 0 1 , b ut w h o d o 
n ot c h o os e t o participate in t he L T E st u d y .  A s afet y f ollo w-u p visit will oc c ur a p pr o xi mately 4 
w e e ks after t he last st u d y inf usio n at t he e n d of st u d y or f or e arly ter minatio n .  F ollo w-u p f or 

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 3 9  of 7 0  
  
e arly ter minatio n is re q uire d f or patie nts w h o dis c o ntin ue pre mat urely fr o m St u d y 4 0 4 5-1 0 1.  
P atie nts w h o c o m plete St u d y 4 0 4 5 -1 0 1 per pr ot oc ol a n d w h o r oll o ver t o t he L T E st u d y will n ot 
re q uire a f ollo w-u p visit f or St u d y 4 0 4 5 -1 0 1.  
8. 4.  
P atie nt Wit h dra wal Criteri a  
A n y patie nt c a n de cide t o wit h dra w fr o m st u d y participatio n at a n y ti me f or a n y re as o n.  I n 
a d ditio n, t he st u d y S p o ns or ma y de cide t o st o p t he st u d y participatio n of a n y patie nt as de e me d 
ne c ess ar y.  T he Principal I n vestigat or ( PI) ma y als o st o p t he st u d y participatio n of a n y patie nt at 
a n y ti me.  Re as o ns f or st u d y wit h dra w al inclu de b ut are n ot li mite d t o:  
 T he patie nt w as err o ne o usly inclu de d in t he st u d y (i e, w as f o u n d t o n ot ha ve met t he 
eligibilit y criteria s pe cific ally as it relate d t o ha vin g a c o nfir me d m utatio n a me na ble 
t o e x o n 4 5 s kip pin g.  
 T he patie nt e x perie nc es a n int olera ble A E.  
 T he patie nt is u na ble t o c o m ply wit h t he re q uire me nts of t he pr ot oc ol.  
T he I n vestigat or or st u d y staff will d oc u me nt t he re as o n(s) f or tre at me nt dis c o ntin uati o n in 
s o urc e d oc u me nts.  P atie nts w h o re c eive at le ast o ne ( 1)  d os e of in vestigatio nal dr u g pr o d uct 
w h o are wit h dra w n fr o m tre at me nt will be as ke d t o c o m plete all e arly ter minatio n ass ess me nts 
wit hin 3 0  da ys of wit h dra w al.  T hes e ass ess me nts will inclu de t h os e liste d f or We e k  1 4 4  a n d f or 
t he 4-w e e k s afet y f ollo w -u p /clos e-o ut  ass ess me nts  (Ta ble  2 ).  I n t he c as e of d u plic ate 
ass ess me nts at We e k 1 4 4  a n d t he F ollo w -u p visit, o nly F ollo w -u p visit ass ess me nts s h o uld be 
perf or me d.   P atie nts w h o wit h dra w fr o m t he st u d y will n ot be re pla c e d.   

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 4 0  of 7 0  
  
9.  
T R E A T M E N T  O F P A TI E N T S  
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 4 1  of 7 0  
  
9. 6.  
A d mi nistrati o n of I n vesti gati o nal Dr u g Pro d uct  
Refer t o t he P har ma c y Ma n ual f or s pe ci fic inf or matio n re gar din g t he a d ministrati o n of 
in vestigatio nal dr u g pr o d uct. 
D urin g t he d o u ble -b lin d d os e -titratio n perio d, e ligible patie nts will be ra n d o mize d ( 2:1) t o 
re c eive S R P-4 0 4 5 ( n = 8) or pla c e b o ( n = 4) ( Se ctio n  7. 2 ).  P atie nts will re c eive a w e e kly I V 
inf usio n of S R P-4 0 4 5 or pla c e b o at es c alatin g d os e le vels, e a c h f or at le ast 2  w e e ks:  4  m g/ k g in 
We e ks  1 -2; 1 0  m g/ k g in We e ks  3 -4; 2 0  m g/ k g in We e ks  5 -6;  a n d 3 0 m g/ k g be gin nin g o n 
We e k  7.  
D urin g t he o pe n -la bel e xte nsio n perio d, all patie nts will re c eive o pe n -la bel tre at me nt wit h 
S R P -4 0 4 5  3 0  m g/ k g w e e kly  at t he st u d y site or at h o me .  
T he d os e of S R P -4 0 4 5 will be c alc ulate d bas e d o n t he m ost re c e nt patie nt w eig ht o btaine d at t he 
site prior t o t he c urre nt visit.  I nf usio n s olutio ns of S R P -4 0 4 5 are t o be pre pare d b y f ollo win g t he 
ste ps detaile d in t he st u d y-s pe cific P har ma c y Ma n ual. 
D urin g t he d o u ble -blin d d os e -titratio n perio d, patie nts, pare nts/c are givers , a n d st u d y staff n ot 
in v olve d wit h dr u g pr o d uct pre paratio n will be blin de d t o patie nts’ tre at me nt assig n me nts .  
T hr o u g h o ut t he st u d y, st u d y tre at me nt will be a d ministere d b y q ualifie d st u d y staff as a n I V 
inf usio n o ver a perio d of a p pr o xi mately 3 5 t o 6 0 m in utes.  It is re c o m me n de d t hat a t o pic al 
a nest hetic cre a m (e g, lid oc aine 2. 5 %, priloc aine 2. 5 %, L M X4 cre a m, or ot her t o pic al a nest hetic 
cre a m per t he I n vestigat or’s dis cretio n) be a p plie d t o t he inf usio n site prior t o e a c h 
a d ministratio n of st u d y tre at me n t.  A d ditio nal a d ministratio n a n d I P details are a vaila ble in t he 
st u d y-s pe cific P har ma c y Ma n ual. 
A n i m pla nte d ve n o us a c c ess p ort ma y be ins erte d f or st u d y tre at me nt a d ministratio n at t he 
dis cretio n of t he I n vestigat or.  After st u d y tre at me nt a d ministratio n a n d t he s aline flus h, t he p ort 
ma y be flus he d wit h he parin t o he ploc k t he p ort prior t o re m o val of t he inf usio n line.  If st u d y 
tre at me nt is a d ministere d int o a n e xistin g I V line, t he line m ust be flus he d wit h n or mal s aline 
bef ore a n d after a d ministratio n of st u d y tre at me nt.  
N o ot her me dic atio n ma y be a d ministere d c o nc o mita ntly d urin g in vestigatio nal pr o d uct 
inf usio ns, e xc e pt f or he parin if inf usio n is via intra ve n o us p ort .  
A ll patie nts will be clos ely m o nit ore d f or at le ast 1 h o ur f ollo win g t he c o m pleti o n of e a c h 
inf usio n.  If t he patie nt d oes n ot ha ve a n y inf usio n re a ctio ns after 4 8 w e e ks of o pe n -la bel 
tre at me nt, t he I n vestigat or has dis cretio n t o re d uc e t he p ost -inf usio n o bs er vatio n perio d t o 
3 0  min utes.   T he f ollo win g g uidelines f or t he ti min g of d osin g are t o be f ollo w e d t hr o u g h o ut t he 
st u d y: 
1.  P atie nts s h o uld re c eive st u d y tre at me nt o nc e e ver y 7  da ys startin g at t he Bas eline/ We e k  1  
v isit.  
a. After t he first inf usio n  f or t he d uratio n of t he d o u ble -bli n d  pla c e b o -c o ntr olle d perio d, 
a win d o w of ±1  da y ar o u n d t he s c he d ule d w e e kly d osin g date (refere nc e d ba c k t o t he 
first d os e at Bas eline/ We e k  1) is a c c e pta ble.  
b.  D urin g o pe n -la bel d osin g, a win d o w of ± 3 da ys ar o u n d t he s c he d ule d w e e kly d osin g 
date (refere nc e d ba c k t o t he first d os e at Bas eline/ We e k  1) is a c c e pta ble.  

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 4 2  of 7 0  
  
2.  P atie nts ma y n ot re c eive 2  s e parate d os es of st ud y tre at me nt wit hin t he s a me 6 0 -h o ur 
perio d.  
3.  T he Me dic al M o nit or  is t o be c o nta cte d in t he e ve nt of a miss e d d os e.  
Refer t o Se ctio n  9. 7  f or d osin g c o nsideratio ns inclu din g d os e interr u ptio n, s afet y re vie w, a n d 
st o p pin g r ules. 
9. 7.  
D ose M o dific ati o n, Re d uctio n, o r Del a y  
T here is n o pr o visio n f or d os e alteratio n in t his st u d y.  If a patie nt e x perie nc es a n A E t hat 
re q uires interr u ptio n of a d ministratio n of in vestigatio nal dr u g pr o d uct f or > 2 w e e ks, t he 
I n vestigat or will c o ns ult wit h t he Me dic al M o nit or t o deter mine w het her t he patie nt ma y res u me 
tre at me nt or w het her he ne e ds t o be e xclu de d fr o m f urt her d osin g.  Refer t o Se ctio n  9. 8. 2  f or 
s afet y m o nit orin g pr oc e d ures f or d os e es c alatio n.   
9. 8.  
S afet y C o nsi derati o ns  
9. 8.1.  
Ge ne r al S afet y Pre c a uti o ns  
T his st u d y is bein g c o n d ucte d at clinic al trial c e nters e q uip pe d wit h state of t he art me dic al 
e q uip me nt.  Traine d me dic al pers o n nel will be pres e nt d urin g t he e ntire d osin g perio d a n d f or at 
le ast 1 h o ur after e a c h d os e t o m o nit or e a c h patie nt .  If t he patie nt has n ot e x perie nc ed a n 
inf usio n re a ctio n after 4 8 w e e ks of o pe n -la bel tre at me nt, t he I n vestigat or has dis cretio n t o re d uc e 
t he p ost -inf usio n o bs er vatio n perio d t o 3 0 min utes.  Res us citatio n e q uip me nt will be re a dily 
a vaila ble f or i m me diate us e d urin g d os e a d ministratio n a n d f ollo w -u p, a n d patie nts will n ot be 
allo w e d t o le a ve t he clinic u ntil t he in vestigat or or desig nate d p h ysici a n has as c ertaine d t hat t he y 
c a n d o s o s afely.  
Safet y ass ess me nts will inclu de r o utine clinic al a n d la b orat or y e valuatio ns.  Refer t o 
Se ctio n  9. 8. 2  a n d t o t he s c he d ules of e ve nts ( Ta ble  2 ).  I n a d ditio n, E C Gs a n d E C H Os will be 
perf or me d as o utline d in t he s c he d ules of e ve nts.  
T he m ost likely p ote ntial dr u g -relate d A E s bas e d o n t he n o nclinic al s afet y pr ofile of S R P -4 0 4 5 
are e x pe cte d t o be relate d t o re nal f u nctio n.  T hes e p ote ntial e ve nts are re a dily m o nit ore d t hr o u g h 
ass ess me nt of pr otein in t he urine a n d b y m o nit orin g c ha n ges in s er u m cre atinine a n d/ or blo o d 
ure a nitr o ge n ( B U N ).  I n a d ditio n, s er u m c ystatin C will be us e d as a s afet y bio mar ker f or re nal 
cle ara nc e d ue t o t he in here ntly lo w cre atinine le vels in D M D patie nts.  Kid ne y f u nctio n will als o 
be ass ess e d usin g t he urine bio mar ker kid ne y  injur y m ole c ule-1 ( KI M -1) ( H a n 2 0 0 2 ). 
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 4 3  of 7 0  
  
9. 8.2.  
S afet y M o nit o ri n g D uri n g D os e Titr ati o n  
Safet y data re vie w inclu di n g A Es a n d la b orat or y ass ess me nts will be perf or me d o n a n o n g oin g 
basis.  T he f ollo win g pr oc e d ures will be i m ple me nte d t o mini mize t he ris k t o st u d y patie nts 
d urin g d os e titratio n.  
 All s erio us a d vers e e ve nts ( S A Es), re gar dless of relate d ness, will be re p orte d b y t he 
I n vestigat ors t o t he S p o ns or i m me diately a n d n o m ore t ha n wit hin 2 4 h o urs of 
oc c urre nc e.  
 All A Es classifie d as p ossibly/ pr o ba bl y or definitely relate d t o in vestigatio nal dr u g 
pr o d uct, re gar dless of  s e verit y, will be re p orte d b y t he I n vestigat ors t o t he  S p o ns or 
i m me diately, wit hin 4 8 h o urs of oc c urre nc e.  
 T he Me dic al M o nit or will re vie w s afet y data inclu din g clinic al a n d la b orat or y 
inf or matio n o n a n o n g oin g basis.  S u m mar y re p orts of t hes e re vie ws wi ll be 
distrib ute d as w arra nte d t o all participatin g I n vestigat ors, s pe cific ally w he n 
tre at me nt-relate d A Es ha ve be e n re p orte d.  
 Prior t o d os e a d ministrati o n, t he I n vestigat or will re vie w all A Es a n d all la b orat or y 
values f or t he s pe cific patie nt a n d will p r oc e e d wit h d osin g o nly  if he or s he de e ms 
t hat it is s afe t o d o s o bas e d o n all a vaila ble inf or matio n.  
9. 8.3.  
St o p pi n g R ule s  
Safet y data re vie w inclu di n g A Es a n d la b orat or y ass ess me nts will be perf or me d o n a n o n g oin g 
basis.  T he st o p pin g r ules dis c uss e d in t his  s e ctio n will a p ply o nly t o t he d os e titratio n p eriod  of 
t he st u d y.  If d osin g of a n in divi d ual patie nt is s us pe n de d d urin g t he o pe n-la bel perio d, the 
I n vestigat or will c o ns ult wit h t he Me dic al M o nit or t o deter mine w het her t he patie nt ma y res u me 
tre at me nt or w het her he ne e ds t o be e xclu de d fr o m f urt her d osin g .   
D urin g t he st u d y, sites are re q uire d t o re p ort all A Es as define d in Se ctio n  9. 8. 2  a n d Se ctio n  1 0. 4 .  
If s afet y c o nc er ns aris e at a n y ti me, d osin g ma y be st o p pe d u ntil t hes e c o nc er ns ha ve be e n 
a d dress e d.  D osin g will be interr u pte d t o allo w f or re vie w of c u m ulative s afet y data b y t he 
D S M B if a n y of t he f ollo win g c o n ditio ns are met:  
 > 2  s e vere A Es or ≥3  m o derate A Es c o nsidere d t o be p ossibly/ pr o ba bl y or definitely 
relate d t o in vestigatio nal dr u g pr o d uct  
 A n y S A E c o nsidere d t o be p ossibly/ pr o ba bly or definitely relate d t o in vestigatio nal 
dr u g pr o d uct  
 ≥2  patie nts de velo p 2  c o ns e c utive s er u m cre atinine le vels ≥2 X t heir res pe ctive 
a vera ge pre -tre at me nt values  
 ≥2  patie nts de ve lo p 2  c o ns e c utive insta nc es of u ne x plaine d pr otein  in urine > 2 +  
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 4 4  of 7 0  
  
 A n y u ne x plaine d ga m ma gluta m yl tra nsferas e ( G G T ) > 3 X u p per li mit of n or mal 
( U L N) in c o m binatio n wit h bilir u bi n > 2 X U L N  
 2  c o ns e c utive insta nc es of u ne x plaine d a ctivate d partial t hr o m b o plasti n ti me (a P T T) 
> 4 5  s e c o n ds in t he s a me patie nt  
D urin g t he d os e titratio n p erio d of t he st u d y, t he  D S M B will be n o tifie d b y t he S p o ns or wit hin 
2 4  h o urs of t he S p o ns or le ar nin g of a n y of t he e ve nts liste d a b o ve.  D osin g ma y als o be 
interr u pte d or halte d if w arra nte d at t he dis cretio n of t he S p o ns or or I n vestigat or.  A n y de cisio ns 
relate d t o d os e a djust me nt, dela y, or st o p pin g d urin g d os e titratio n will be c o m m u nic ate d b y t he 
S p o ns or t o all sites i m me diately.  I n a d ditio n, I n vestigat ors ma y, in t he e ve nt of a n e mer ge nc y, 
dire ctly c o nta ct t heir pe ers at ot her sites t o c o m m u nic ate s afet y c o nc er ns.  
9. 8.4.  
D at a S afet y M o nit o ri n g B o ar d  
A n in de pe n de nt D S M B will be e m plo ye d t o re vie w all a vaila ble s afet y data f or all patie nts at t he 
ti me p oint w he n t he last patie nt has c o mplete d 2  inf usio ns at 3 0 m g/ k g (a p pr o xi mately 
We e k  8 ).  
T his a g gre gate data re vie w will be blin de d u nless t he D S M B s pe cific ally re q uests u n blin din g  at 
t he patie nt or gr o u p le vel bas e d o n s afet y data s u m maries.  T he D S M B will be c har ge d wit h 
a d visin g t he S p o ns or a b o ut w het her tra nsitio nin g int o t he o pe n -la bel e xte nsio n perio d of t he 
pr ot oc ol is a p pr o priate bas e d o n a g gre gate s afet y data fr o m t he d o u ble -bli n d d os e -titratio n 
perio d.   Bas e d o n t he res ults of t he D S M B re vie w, t he S p o ns or will deter mine w het her t o r oll 
o ver patie nts int o t he o pe n -la bel e xte nsio n perio d. 
A n y de cisio n t o interr u pt, restart, or dis c o ntin ue t he st u d y will be ma de b y t he S p o ns or in 
c o ns ultatio n wit h t he D S M B.  
A f or mal D S M B me etin g ma y be c o n ve ne d at a n y ti me if re q ueste d b y t he S p o ns or of t his st u d y. 
T he D S M B c harter will pr o vide f urt her detail o n t he me etin g a n d de cisio n -ma ki n g pr oc ess 
in v olvin g t he D S M B. 
T he o utc o me of a n y D S M B me etin g will be c o m m u nic ate d t o t he I n vestigat ors b y t he S p o ns or. 
T he  rele va nt re g ulat or y a ut h orities will be pr o m ptly n otifie d of st u d y s us pe nsio n or 
dis c o ntin uati o n relate d t o s afet y c o nc er ns. A n y s us pe nsio n or dis c o ntin uati o n of t he trial f or a n y  
re as o n will als o be pr o m ptly re p orte d t o t he rele va nt I nstit utio nal Re vie w B oar ds (I R B)/ 
I n de pe n de nt Et hics C o m mitte e (I E C). 
9. 9.  
R a n d o miz ati o n a n d Bli n di n g  
9. 9.1.  
R a n d o miz ati o n  
After q ualif yi n g f or st u d y e ntr y, D M D patie nts wit h a deletio n  c o nfir me d as a me na ble t o e x o n  4 5 
s kip pin g will be ra n d o mize d usin g a 2:1 ratio t o eit her S R P-4 0 4 5 ( 8  patie nts) or pla c e b o 
(4  patie nts).  Ra n d o mizatio n will be perf or me d prior t o d osin g at Bas eline/We e k  1.  
9. 9.2.  
Bli n di n g fo r D os e A d mi nistr ati o n  
T his st u d y inclu des a d o u ble -bli n d, pla c e b o -c o ntr olle d d os e -titratio n perio d of at le ast 1 2  w e e ks 
d urin g w hic h all patie nts, pare nts, I n vestigat ors, a n d site staff n ot in v olve d wit h dr u g pr o d uct 
pre paratio n will be blin de d t o tre at me nt assig n me nt.  A d o u ble -blin d, pla c e b o -c o ntr olle d st u d y 

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 4 5  of 7 0  
  
desig n will be us e d t o re d uc e p ote ntial bias d urin g data c olle ctio n a n d e valuatio n of o utc o me 
para meters.  
Eig ht patie nts will re c eive w e e kly I V d os es of S R P -4 0 4 5 , a n d 4  patie nts will re c eive w e e kly I V 
d os es of pla c e b o in a blin de d fas hio n  u ntil a p pr o xi mately 4  w e e ks after t he la st e nr olle d patie nt 
re c eive d 1 2 w e e ks of tre at me nt.   O nly in divi d uals ( ie, t he q ualifie d p har ma cist a n d ba c k -u p 
p har ma cists) w h o are a ut h orize d t o verif y d os e a n d d os e assig n me nt will be u n blin de d t o 
tre at me nt assig n me nt.  T hes e in divid uals will n ot ha ve intera ctio n wit h st u d y participa nts a n d 
will be instr ucte d n ot t o div ulge ra n d o mizatio n assig n me nt t o ot hers u n der a n y circ u msta nc es , 
u nless dire cte d t o d o s o b y t he I n vestigat or in t he interest of patie nt s afet y.  
9. 9.3.  
U n bli n di n g Pr o c e d ure s  
I n t he e ve nt of a me dic al e mer ge nc y w herein t he k n o wle d ge of t he s u bje ct’s tre at me nt 
assig n me nt ma y influe nc e clinic al de cisio n -ma ki n g, t he I n vestigat or has t he o ptio n t o u n blin d 
tre at me nt assig n me nt.  
T he re as o ns f or a n y u n blin di n g 
m ust be n ote d in t he s o urc e d oc u me ntatio n.  T he I n vestigat or 
m ust n ot dis clos e inf or matio n a b o ut tre at me nt assig n me nt t o a n y o ne w h o d oes n ot ne e d t he 
inf or matio n d ue t o t heir dire ct in v olve me nt in patie nt c are. 
If de e me d ne c ess ar y, t he D S M B ma y re q uest t o re vie w u n blin de d s afet y data f or o ne or m ore 
patie nts at a n y ti me t o e ns ure t he s afet y of a n y in divi d ual patie nt or t he st u d y p o p ulatio n as a 
w h ole. D ata a c c ess will be restricte d t o D S M B me m bers.  
Re g ulat or y a ut h orities a n d/ or t he I R B/I E C ma y re q uest t he u n blin di n g of o ne or m ore pat ie nts’ 
data  at a n y ti me.  
9. 1 0.  
Pri o r a n d C o nc o mit a nt Me dic atio ns a n d T hera pe utic Pro ce d ures  
T he f ollo win g t hera pies ma y be us e d prior t o e nr oll me nt/ra n d o mizatio n a n d t hr o u g h o ut t he st u d y 
at t he dis cretio n of t he I n vestigat or.  H o w e ver, atte m pts s h o uld be ma de t o  ke e p t he d os a ge 
c o nsta nt t hr o u g h o ut t he tre at me nt perio d , e xc e pt t o a c c o m m o date c ha n ges in w eig ht. 
 Oral c ortic oster oids f or tre at me nt of D M D inclu din g, b ut n ot li mite d t o pre d nis olo ne  
a n d pre d nis o ne  
 Oral A C E in hibit ors inclu di n g b ut n ot li mite d t o perin d o pril a n d lisin o pril 
 Oral β -bloc kers inclu din g b ut n ot li mite d t o c ar ve dilol a n d ate n olol  
 A n giote nsin -re c e pt or bloc kers inclu din g b ut n ot li mite d t o los arta n, ir bes arta n, 
vals arta n, a n d c a n des arta n  
 Oral la xatives inclu di n g b ut n ot li mite d t o la ct ulos e, Se n o k ot, a n d M o vic ol 
 Vita min  D a n d c alciu m s u p ple me nts  
 Ale n dr o nate ( F os a ma x) or ot her bis p h os p h o nates us e d t o tre at 
oste o p or osis/ oste o pe nia b y in hibiti n g oste oclasts.  
 O ver -t he-c o u nter pre paratio ns s uc h as her bal/ n o n -her bal s u p ple me nts, vita mins, 
minerals, a n d h o me o pat hic pre paratio ns  

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 4 6  of 7 0  
  
Ot her c o nc o mita nt me dic atio ns ( e xclu din g ot her R N A -a ntis e ns e or ge ne t hera p y a ge nts ) ma y 
als o be ta ke n, if, in t he o pinio n of t he in vestigat or, t he y are n ot de e me d t o interfere wit h st u d y 
pr oc e d ures or t he in vestigatio n of S R P -4 0 4 5 in t his st u d y.  E ver y atte m pt m ust be ma de t o ke e p 
t he d os a ge c o nsta nt t hr o u g h o ut t he st u d y perio d. 
T he f ollo win g t hera pies are n ot  per mitte d d urin g t he c o n d uct of t his st u d y:  
 S yste mic or oral ster oids f or n o n -D M D c o n ditio ns  
 I n vestigatio nal a ge nts f or t he tre at me nt of D M D 
 A n y me dic atio n wit h t he p ote ntial t o affe ct m us cle mass, stre n gt h, a n d/ or f u nctio n, 
s uc h as, b ut n ot li mite d t o, gr o wt h h or m o ne ( h G H) a n d p h os p h o diesteras e t y pe  5 
(P D E -5 ) in hibit ors u nless d oc u me nte d as me dic ally ne c ess ar y (e g , h G H pr es cribe d b y 
pe diatric e n d ocrin olo gist f or tre at me nt of s h ort stat ure)  
 I m m u n os u p press a nts ( ot her t ha n oral or s yste mic c ortic oster oids, as o utline d) 
 S yste mic a min o glyc oside a ntibiotics ( u nless dis c uss e d a n d a gre e d u p o n wit h t he  
I n vestigat or a n d t he Me dic al M o nit or)  
 Statins ( u nless dis c uss e d a n d a gre e d u p o n wit h t he I n vestigat or a n d Me dic al M o nit or)  
9. 1 1.  
Tre at me nt C o m pli a nce  
Tre at me nt c o m plia nc e wit h s c he d ule d w e e kly inf usio ns will be d oc u me nte d o n t he c as e re p ort 
f or m (C R F ). 

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 4 7  of 7 0  
  
1 0.  
S T U D Y A S S E S S M E N T S  
S c he d ule s of st u d y e ve nts are pr o vide d in  Ta ble  2  a n d Ta ble  3 .   
 
 
  
1 0. 1.  
Scree ni n g  Assess me nts  
Writte n inf or me d c o ns e nt a n d ass e nt will be o btaine d fr o m t he patie nt a n d/ or pare nt as ne e de d, 
b y t he I n vestigat or or dele gate d st u d y staff d urin g t he Scre e nin g perio d.  T he I n vestigat or a n d 
st u d y staff will als o re vie w all inclusio n a n d e xclusio n criteria, me dic al hist or y, me dic atio n 
hist or y, p h ysiot hera pe utic inter ve ntio n hist or y, a n d d oc u me ntatio n of D M D dia g n osis d urin g t he 
Scre e nin g perio d.  
I n a d ditio n, at t he Scre e nin g v isit, all patie nts will u n der g o a d ditio nal pre -tre at me nt tests a n d 
pr oc e d ures a c c or din g t o t he ti min g o n t he s c he d ules of e ve nts ( Ta ble  2 ).  T hes e tests a n d 
pr oc e d ures are liste d belo w.  
 W h ole blo o d f or ge n ot y pe/ sin gle n ucle otide p oly m or p his m (S N P ) 
 T he 6 M W T ( A T S 2 0 0 2 ) will o nly be perf or me d at t he s cre e nin g visit t o deter mine 
eligibilit y (Ta ble  2 ).  P atie nts will be as ke d t o w alk a s et c o urs e of 2 5  meters f or 
6  min utes (ti me d) w here t he dista nc e w alke d (in meters) will be re c or de d.  
 F ull  p h ysic al e xa minatio n ( Se ctio n  1 0. 3. 2 ) 
 Vital sig ns ( Se ctio n  1 0. 3. 1 ), as w ell as heig ht a n d w eig ht 
 1 2 -le a d E C G ( Se ctio n  1 0. 3. 5. 1 ) 
 E C H O ( Se ctio n  1 0. 3. 5. 2 ) 
 Blo o d a n d urine s a m ples f or clinic al la b orat or y ass ess me nts ( Se ctio n  1 0. 3. 3 ) 
1 0. 2.  
B aseli ne/ Wee k 1 Assess me nts  
T he f ollo win g Bas eline/ We e k  1 ass ess me nts m ust be perf or me d a n d res ults revie w e d prior t o  
ra n d o mizatio n t o c o nfir m t he patie nt is still eligible : 
 F ull p h ysic al e xa minatio n ( Se ctio n  1 0. 3. 2 ) 
O nc e st u d y eligibilit y has be e n c o nfir me d at t he Bas eline/We e k  1 visit, patie nts will be 
ra n d o mize d ( 2:1) t o blin de d tre at me nt wit h S R P-4 0 4 5 or pla c e b o.  P atie nts will be gin  d osin g at 
Bas eline/ We e k  1 ( Ta ble  2 ). 
C CI
C CI
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 4 8  of 7 0  
  
A d ditio nal a ss ess me nts t o be perf or me d at Bas eline/ We e k  1 prior t o d osin g inclu de:  
 E C G ( Se ctio n  1 0. 3. 5. 1 ) 
 Clin ical la b orat or y ass ess me nts  
 Pre -d os e P K s a m ple c oll e ctio n 
A ss ess me nts t o be perf or me d at Bas eline/ We e k 1  after d osin g inclu de:  
 Plas ma a n d urine c olle ctio n f or P K ( Se ctio n  1 0. 5 ) 
 P ost -inf usio n vital sig ns a n d o bs er vatio n perio d 
Sa m plin g f or P K will be perf or me d a c c or din g t o t he pr oc e d ures a n d ti mes o utline d in 
Se ctio n  1 0. 5  a n d Ta ble  2 .  
1 0. 3.  
S afet y Assess me nts  
1 0.3. 1.  
Vit al Si g ns i ncl u di n g Wei g ht a n d H ei g ht  
Vital sig ns inclu din g oral te m perat ure, he art rate, res pirat or y rate a n d blo o d press ure  as w ell as  
heig ht a n d w eig ht will be me as ure d at t he ti me p oints s pe cifie d in t he s c he d ule of e ve nts  
(Ta ble  2 ). 
F or inf usio n visits, vital sig ns are t o be c olle cte d wit hin a p pr o xi mately 3 0  min utes prior t o t he 
start of t he inf usio n, a n d a p pr o xi mately 5, 3 0, a n d 6 0  min utes after t he e n d of t he inf usio n  (ie , 
after in vestigatio nal pr o d uct has be e n flus he d t hr o u g h t he I V line) .  If t he patie nt has n ot 
e x perie nc e d a n inf usio n re a ctio n after 4 8  w e e ks of o pe n -la bel tre at me nt, c olle ct vital sig ns prior 
t o inf usio n a n d at 5 a n d 3 0 min utes p ost -inf usio n. 
Vital sig ns  will be perf or me d after patie nts ha ve re maine d s e ate d f or 5  min utes .  P uls e rate a n d 
res pirat or y rate are t o be me as ure d o ver 1 min ute.  
Te m perat ure is t o be re p orte d in de gre es Celsius (° C). 
Weig ht is t o be re p orte d in kilo gra ms.  If a patie nt’s w eig ht varies b y m ore t ha n 1 0 % fr o m t he 
prior visit, t he patie nt is t o be re -w eig he d t o c o nfir m t he res ult, a n d a n e x pla natio n of t he c ha n ge 
m ust be d oc u me nte d.  
H eig ht is t o be me as ure d wit h s h oes off.  Ulna le n gt h s h o uld be c olle cte d  me as ure d  w he n heig ht 
is o btained f or all patie nts.   If sta n din g heig ht c a n n ot be o btaine d, heig ht is t o be c alc ulate d usin g 
t he f ollo win g e q uatio n (Ga uld 2 0 0 4 ) f or e ntr y int o t he s pir o metr y s yste m:  
H eig ht (c m) = 4. 6 0 5 U + 1. 3 0 8 A + 2 8. 0 0 3  
w here U  is t he le n gt h of t he ulna in c e nti meters me as ure d usin g a n a nt hr o p o meter or c alipers, 
a n d A  is t he patie nt’s a ge in ye ars. 
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 4 9  of 7 0  
  
1 0.3. 2.  
P h ysic al E x a mi n ati o n  
P h ysic al e xa minatio ns will be perf or me d b y t he I n vestigat or or q ualifie d st u d y staff prior t o d os e 
a d ministratio n a c c or din g t he s c he d ule of e ve nts d urin g t he d os e -titratio n a n d e xte nsio n st u d y 
perio d  (Ta ble  2 ) a n d t he o pe n-la bel intr o d uctio n st u d y perio d (Ta ble  3 ).  T he ass ess me nts in 
Ta ble  3  will oc c ur d urin g t he first 8 w e e ks of t he o pe n -la bel tre at me nt perio d a n d are in a d ditio n 
t o t he ass ess me nts in Ta ble  2 .  D u plic ate ass ess me nts at t he s a me st u d y visit s h o uld n ot be 
perf or me d.  
A f ull p h ysic al e xa minatio n  will inclu de re vie w of ge neral a p pe ara nc e, he a d, e yes, e ars, n os e, 
a n d t hr oat ( H E E N T), he art, lu n gs, a b d o me n, s kin, ly m p h n o des, m us c ulos keletal, a n d 
ne ur olo gic al s yste ms.  A brief p h ysic al e xa minatio n will inclu de e xa minatio n of ge neral 
a p pe ara nc e, H E E N T, he art, c hest, a b d o me n, a n d s kin.    
1 0.3. 3.  
Cli nic al L a b o r at o r y As s ess me nts  
All la b orat or y ass ess me nts , wit h t he e xc e ptio n of P K s a m plin g, m ust be perf or me d prior t o d os e 
a d ministratio n f or all tre at me nt visits.   
R o utine clinic al la b orat or y testin g will oc c ur a c c or din g t he s c he d ule of e ve nts d urin g t he 
d os e -titratio n a n d e xte nsio n st u d y perio d (Ta ble  2 ) a n d t he o pe n-la bel intr o d uctio n st u d y perio d 
(Ta ble  3 ).  T he ass ess me nts in Ta ble  3  will oc c ur d urin g t he first 8  w e e ks of t he o pe n -la bel 
tre at me nt perio d a n d are in a d ditio n t o t he ass ess me nts in Ta ble  2 .  I n t he c as e of a d u plic ate 
ass ess me nt s pe cifie d b y Ta ble  2  a n d Ta ble  3  at t he s a me st u d y visit, o nly o ne  ass ess me nt s h o uld 
be perf or me d.  
D urin g  Scre e nin g , s afet y la b orat or y ass ess me nts m ust be perf or me d wit hin 2  w e e ks prior t o t he 
Bas eline/ We e k  1 visit, a n d res ults m ust be re vie w e d prior t o d osin g.  If Scre e nin g s afet y 
la b orat or y s a mples w ere c olle cte d m ore t ha n 2  w e e ks prior t o t he B as eline/ We e k 1 visit, s a m ples 
m ust be c olle cte d a gain a n d res ults m ust be re vie w e d bef ore patie nt s ma y be d os e d at 
Bas eline/ We e k  1.  
Bef ore patie nts ma y be gin d osin g in t he o pe n -la bel e xte nsio n perio d, s afet y la b orat or y 
ass ess me nts m ust be perf or me d wit hin 2  w e e ks prio r t o first d os e, a n d t he res ults of t h os e la bs 
re vie w e d prior t o first d os e.  If s afet y la b orat or y s a mples w ere c olle cte d m ore t ha n 2  w e e ks prior 
t o t he first o pe n-la bel e xte nsio n visit, s a m ples m ust be c olle cte d a gain a n d res ults m ust be 
re vie w e d bef ore d osin g.  
La b orat or y res ults will be a nalyze d b y a n a c cre dite d c e ntral la b orat or y s ele cte d b y t he S p o ns or 
( Sare pta T hera pe utics).  Ass ess me nts a n d s hip me nt will be pre pare d a c c or din g t o t he La b orat or y 
Ma n ual pr o vide d f or t he st u d y.  S pe cific la b orat or y para m eters t o be a nalyze d are pres e nte d in 
t he s u bs e ctio ns belo w. 

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 5 0  of 7 0  
  
1 0.3. 3. 1.  H e m at ol o g y  
H e mat olo g y para meters t o be a nalyze d inclu de t he f ollo win g:  
Re d blo o d c ells ( R B C)  
L y m p h oc ytes  
W hit e blo o d c ells ( W B C)  
M o n oc ytes  
He m o glo bin  
E osin o p hils  
He m at ocrit  
Bas o p hils  
Ne utr o p hils  
Platelets  
1 0.3. 3. 2.  C o a g ul ati o n  
C oa g ulatio n para meters t o be a nalyze d inclu de t he f ollo win g:  
Pr ot hr o m bin ti me  
I nter natio nal N or malize d Ratio (I N R) 
Activat e d partial 
t hr o m b o plastin ti me (aP T T)  
 
1 0.3. 3. 3.  Se r u m C he mistr y  
Ser u m c he mistr y para meters t o be a nalyze d inclu de t he f ollo win g: 
S o diu m  
Alkaline p h os p hatas e  
C hloride  
A m ylas e  
P ot assiu m  
Ala nine a min otr a nsf er as e ( A L T)  
Calciu m  
As partate a min otr a nsf er as e ( A S T),  
Gluc os e  
Ga m ma -gluta m yl tr a nsf er as e ( G G T)  
Cr eatinine  
Lactas e de h y dr o ge nas e ( L D H)  
B lo o d ur ea nitr o ge n ( B U N) 
C -r eactive pr otein ( C R P) 
Alb u min  
Cr eatine kinas e ( C K)  
Uric acid  
T otal bilir u bin  
C yst atin C  
 
1 0.3. 3. 4.  U ri n al ysis  
T he f ollo win g para meters will be a nalyze d:  
p H 
Urine micr os c o p y  
S pecific gr a vit y  
He m o glo bin  
Pr ot ein  
Kid ne y injur y m olec ule -1 ( KI M -1)  
Gluc os e  
Ket o nes  
A n y la b orat or y value(s) o utside of t he c urre nt refere nc e ra n ge will be fla g ge d.  

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 5 1  of 7 0  
  
1 0.3. 4.  
C o nc o mit a nt M e dic ati o ns a n d P h ysi ot he r a pe utic I nte r v e nti o n  
C o nc o mita nt me dic atio ns, c ha n ges in d os a ge of c o nc o mita nt me dic atio ns, a n d c o nc o mita nt 
t hera pies will be re vie w e d a n d re c or de d at e a c h visit  (Ta ble  2 ) fr o m t he ti me t he 
pare nt(s)/ g uar dia n(s) sig n(s) t he inf or me d c o ns e nt a n d t he patie nt sig ns t he ass e nt f or m (if 
a p plic a ble) . I nf or matio n o n a n y p h ysiot hera pe utic inter ve ntio n m ust be c olle cted in detail f or t his 
st u d y. 
1 0.3. 5.  
Ot he r S afet y As s ess me nts  
1 0.3. 5. 1.  Ele ctr o c ar di o g r a m ( E C G)  
A 1 2 -le a d E C G will be perf or me d at t he ti me p oints s pe cifie d in t he s c he d ule of e ve nts f or t he 
d os e -titratio n a n d e xte nsio n st u d y perio d (Ta ble  2 ) a n d t he o pe n-la bel intr o d uctio n st u d y perio d 
(Ta ble  3 ).  T he ass ess me nts in Ta ble  3  will oc c ur d urin g t he first 8  w e e ks of t he o pe n -la bel 
tre at me nt perio d a n d are in a d ditio n t o t he ass ess me nts in Ta ble  2 .  D u plic ate ass ess me nts at t he 
s a me st u d y visit s h o uld n ot be perf or me d.   
E C Gs are t o be perf or me d at a c o nsiste nt ti me of da y t hr o u g h o ut t he st u d y.  E C Gs will be 
perf or me d o nly after t he patie nt is p ositio ne d s u pine, restin g, a n d is q uiet f or a mini m u m of 
1 5  min utes.  T he E C G will be ma n ually re vie w e d a n d inter prete d b y me dic ally q ualif ie d 
pers o n nel usin g a c e ntral ve n d or a c c or din g t o pre -s pe cifie d criteria.  T he I n vestigat or will re vie w 
t he res ults of t he c e ntrally re a d E C G re p ort a n d deter mine if a b n or mal fin din gs are clinic all y 
sig nific a nt. 
1 0.3. 5. 2.  Ec h o c ar di o g r a p h y ( E C H O)  
A sta n dar d 2 -di me nsio nal ( 2 D) E C H O will be perf or me d at t he ti me p oints s pe cifie d in t he 
s c he d ule of e ve nts (Ta ble  2 ).  E C H Os will be perf or me d at a c o nsiste nt ti me  of da y t hr o u g h o ut 
t he st u d y.  T he E C H O will be re vie w e d a n d inter prete d b y me dic ally q ualifie d pers o n nel usin g a 
c e ntral ve n d or a c c or din g t o pre -s pe cifie d criteria.  Eje ctio n fra ctio n ( E F) will be n ote d.  T he 
I n vestigat or will re vie w t he res ults of t he E CH O re p ort a n d deter mine if a b n or mal fin din gs are 
clinic all y sig nific a nt.  
1 0.3. 5. 3.  A d v e rs e E v e nts  
T he c olle ctio n of A Es is des cribe d in Se ctio n  1 1 . 
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 5 2  of 7 0  
  
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 5 3  of 7 0  
  
1 0. 5.  
P h ar m ac o ki netic Assess me nts  
1 0.5. 1.  
Bl o o d S a m ple C olle cti o n  
B lo o d c olle ctio n f or s erial P K deter minatio n will oc c ur at t he ti me p oints s pe cifie d in t he 
s c he d ule of e ve nts (Ta ble  2 ):  i m me diately pre-inf usio n, at ap pr o xi mately 5  t o 1 0 min utes after 
t he e n d of inf usio n, a n d t he n at a p pr o xi mately 1, 1. 5, 2, 4, 6, 8, 1 2, 1 6, a n d 2 4  h o urs after t he e n d 
of inf usio n at Bas eline/ We e k  1  a n d We e ks  3, 5, 7 , a n d 6 0 .  
 
 
 
 
  
Blo o d c olle ctio n f or P K m ust be dra w n fr o m t he ar m c o ntralateral t o t he tre at me nt inf usio n. 
P har ma c o kinetic  s a m ples ma y n ot be dra w n fr o m a patie nt’s i m pla nte d ve n o us p ort if tre at me nt 
is inf us e d via t he p ort.  
1 0.5. 2.  
U ri ne S a m ple C olle cti o n  
Urine f or P K deter minatio n will be c olle cte d o n a c u m ulative basis, d urin g t he f ollo win g ti me 
inter vals at t he ti me p oints s pe cifie d in t he s c he d ule of e ve nts (Ta ble  2 ) bas e d o n start ti me of 
st u d y dr u g inf usio n:  0  t o 4 h o urs, 4  t o 8 h o urs, 8  t o 1 2 h o urs, 1 2  t o 2 4 h o urs , a n d a d ditio nall y at 
We e k  7, 2 4 -3 6  h o urs .  P atie nts will be as ke d t o v oid t heir bla d der prior t o start of st u d y dr u g 
inf usio n.  
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 5 4  of 7 0  
  
1 1.  
A D V E R S E E V E N T S  
1 1. 1.  
C ollecti o n of A d verse Eve nts  
All A Es fr o m t he ti me of inf or me d c o ns e nt t hr o u g h t he e n d of st u d y visit ( or e arly ter minatio n 
fr o m t he st u d y) will be re c or de d in e a c h in divi d ual patie nt’s ele ctr o nic c as e re p ort f or m ( e C R F ).  
F or patie nts w h o pre mat urely dis c o ntin ue fr o m t he st u d y (s e e Se ctio n  8. 3 ), A Es will c o ntin ue t o 
be re c or de d u ntil 4  w e e ks after t he last inf usio n.  O ver t he e ntire d uratio n of t he st u d y, site 
pers o n nel will e ns ure t hat all A Es are re c or de d a p pr o priately.  If a n A E oc c urs, t he pri mar y 
c o nc er n is f or patie nt s afet y a n d t he in vestigat or will us e his/ her ju d g me nt a n d e x pertis e t o 
deter mine t he a p pr o priate c o urs e of a ctio n.  
If, at a n y ti me after t he patie nt has c o m plete d participatio n in t he st u d y (s e e  Se ctio n  8. 3 ), t he 
I n vestigat or or st u d y staff be c o mes a w are of a n S A E t hat t he I n vestigat or belie ves is 
p ossibly/ pr o ba bly or definitely relate d t o t he in vestigatio na l dr u g pr o d uct (Se ctio n  1 1. 3. 1 ) or is 
p ossibly/ pr o ba bly or definitely relate d t o a st u d y pr oc e d ure ( Se ctio n  1 1. 3. 2 ), t he n t he e ve nt a n d 
a n y k n o w n details m ust be re p orte d pr o m ptly t o t he S p o ns or.  
1 1. 2.  
Defi niti o n of A d verse Eve nts  
1 1.2. 1.  
A d v e rs e E v e nt ( A E)  
A n A E is a n y u nt o w ar d me dic al oc c urre nc e in a clinic al trial participa nt, w hic h d oes n ot 
ne c ess arily ha ve a c a us al relatio ns hip wit h t he in vestigatio nal dr u g.  A n A E c a n, t heref ore, be 
a n y u nfa v ora ble a n d u ninte n de d s y m pt o m, sig n, dis e as e, c o n ditio n, or test a b n or malit y t hat 
oc c urs d urin g or after a d ministr atio n of a n in vestigatio nal dr u g pr o d uct w het her or n ot 
c o nsidere d relate d t o t he in vestigatio nal dr u g pr o d uct.  A d vers e e ve nts inclu de:  
 S y m pt o ms des cribe d b y t he patie nt or sig ns o bs er ve d b y t he I n vestigat or or me dic al 
staff. 
 Test a b n or malities (la b orat or y tests, E C G, X -ra ys, etc) t hat res ult in a n alteratio n in 
me dic al c are ( dia g n ostic or t hera pe utic).  
A b n or malities pres e nt at Scre e nin g are c o nsidere d Me dic al Hist or y.  T hes e a b n or malities will be 
c o nsidere d A Es o nly if t he y re oc c ur after res olutio n or w or s e n after sig nin g c o ns e nt.  
1 1.2. 2.  
Se ri o us A d v e rs e E v e nt ( S A E)  
A n S A E is define d as a n y A E t hat res ults in a n y of t he f ollo win g:  
D e at h:   T he patie nt die d as t he res ult of t he e ve nt.  
Life -t hre ate ni n g e v e nt:  A n y A E t hat pla c es t he patie nt, in t he vie w of t he I n ves tigat or or 
S p o ns or, at i m me diate ris k of de at h fr o m t he A E as it oc c urre d, ie,  d oes n ot inclu de a n A E t hat 
ha d it oc c urre d in a m ore s e vere f or m, mig ht ha ve c a us e d de at h.  
R e q uire d o r pr ol o n g e d i n p atie nt h os pit aliz ati o n:   T he A E res ulte d in h os pitalizati o n or 
pr olo n ge d a n e xistin g h os pitalizati o n.  Sinc e h os pitalizatio n ma y be part of t he st u d y, o nly 
h os pitalizati o ns t hat are lo n ger t ha n e x pe cte d bas e d o n I n vestigat or ju d g me nt, will be c o nsidere d 
pr olo n ge d h os pitalizatio ns.  

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 5 5  of 7 0  
  
Pe rsiste nt o r si g nific a nt dis a bili t y/i nc a p acit y:  A n A E t hat res ults in a s u bsta ntial disr u ptio n of 
a pers o n’s a bilit y t o c o n d uct n or mal life f u nctio ns.  
C o n g e nit al a n o m al y/ birt h defe ct:   A c o n ge nital a n o maly/ birt h defe ct t hat oc c urs in t he 
offs prin g of a patie nt e x p os e d t o t he in vestigatio nal pr o d uct.  
I m p o rt a nt me dic al e v e nts:  A n A E t hat ma y n ot res ult in de at h, be life -t hre ate nin g, or re q uire 
h os pitalizati o n 
ma y be c o nsidere d a n S A E w he n, bas e d u p o n a p pr o priate me dic al ju d g me nt, t he 
e ve nt ma y je o par dize t he patie nt a n d ma y re q uire me dic al or s ur gic al inter ve ntio n t o pre ve nt o ne 
of t he o utc o mes liste d a b o ve.  
1 1. 3.  
Cl assific ati o n of A d verse Eve nts  
Ea c h A E w het her s erio us or n o n -s erio us will be classifie d b y t he I n vestigat or a c c or din g t o t he 
f ollo win g r ules a n d definitio ns. 
1 1.3. 1.  
R el ati o ns hi p t o I n v e sti g ati o n al D r u g Pr o d uct  
F or e a c h A E t he I n vestigat or deter mines w het her t here is a re a s o na ble likeli h o o d t hat t he A E 
ma y ha ve be e n c a us e d b y t he st u d y tre at me nt a c c or din g t o t he c ate g ories belo w:  
U nrel ate d:  
T he e ve nt is cle arly n ot relate d t o t he in vestigatio nal dr u g 
pr o d uct  
P os si bl y/ Pr o b a bl y R el ate d:  T he e ve nt c o uld be relate d/is likely t o be relate d  t o t he 
in vestigatio nal dr u g pr o d uct 
D efi nitel y R el ate d:   
T he e ve nt is cle arly relate d t o t he in vestigatio nal dr u g pr o d uct 
A d vers e e ve nts t hat t he I n vestigat or or S p o ns or c o nsiders t o be p ossibly/ pr o ba bl y or definitely 
relate d t o t he in vestigatio nal dr u g pr o d uct will be c o nsidere d a d vers e dr u g re a ctio ns.  
1 1.3. 2.  
R el ati o ns hi p t o St u d y Pr o c e d ure s  
F or e a c h A E t he I n vestigat or deter mines w het her t here is a re as o na ble p ossibilit y t hat t he A E 
ma y ha ve be e n c a us e d b y t he st u d y pr oc e d ures a c c or din g t o t he c ate g o ries belo w: 
U nrel ate d:  
T he e ve nt is cle arly n ot  relate d t o st u d y pr oc e d ures 
P os si bl y/ Pr o b a bl y R el ate d:  T he e ve nt c o uld be relate d/is likely t o be relate d t o st u d y 
pr oc e d ures  
D efi nitel y R el ate d:   
T he e ve nt is cle arly relate d t o st u d y pr oc e d ures 
1 1.3. 3.  
R el ati o ns hi p  t o U n de rl yi n g Dis e as e 
F or e a c h A E t he I n vestigat or deter mines w het her t here is a re as o na ble p ossibilit y t hat t he A E 
ma y be relate d t o t he u n derlyin g dis e as e a c c or din g t o t he c ate g ories belo w:  
U nrel ate d:  
T he e ve nt is cle arly n ot relate d t o u n derlyin g dis e as e 
P os si bl y/ Pr o b a bl y R el ate d:  T he e ve nt c o uld be relate d/is likely t o be relate d  t o u n derlyin g 
dis e as e  
D efi nitel y R el ate d:   
T he e ve nt is cle arly relate d t o u n derlyin g dis e as e 

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 5 6  of 7 0  
  
A d vers e e ve nts of dis e as e pr o gressio n ma y be c o nsidere d A Es, bas e d o n t he in vesti gat or’s 
dis cretio n.  
1 1.3. 4.  
Se v e rit y of A d v e rs e E v e nts  
N ote t hat s e verit y is n ot t he s a me as “s erio us ness ” , w hic h is define d in Se ctio n  1 1. 2. 2  a n d w hic h 
s er ves as a g uide f or definin g re g ulat or y re p ortin g o bligatio ns.  
T he I n vestigat or will ass ess t he s e verit y of all A Es as Mild, 
M o derate, or Se vere, bas e d o n t he 
f ollo win g definitio ns.  
Mil d:  
T he e ve nt d oes n ot interfere wit h t he patie nt’s us ual a ctivities.  
M o de r ate:  
T he e ve nt interferes wit h t he patie nt’s us ual a ctivities.  
Se v e re:  
T he e ve nt pre ve nts t he patie nt fr o m u n derta kin g t heir us ual a ctivities a n d 
re q uires t hera pe utic inter ve ntio n or c ess atio n of t he in vestigatio nal dr u g pr o d uct. 
1 1.3. 5.  
O utc o me  
All A Es will be f ollo w e d f or 4  w e e ks after t he last d os e of in vestigatio nal dr u g pr o d uct.  Serio us 
A Es will be f ollo w e d u ntil res olutio n or u ntil t he c o n ditio n sta bilizes or ret ur ns t o  bas eline stat us 
or u ntil n o f urt her f ollo w -u p is e x pe cte d.  T he I n vestigat or will re c or d all inf or matio n re gar din g 
t he o utc o me of e a c h A E or S A E. 
1 1.3. 6.  
A cti o n T a k e n R e g ar di n g t he I n v e sti g ati o n al D r u g Pr o d uct  
T he I n vestigat or will pr o vide inf or matio n re gar din g t he a ctio n ta ke n wit h res pe ct t o t he 
in vestigatio nal pr o d uct in res p o ns e t o t he A E. 
1 1.3. 8.  
S us pe cte d U ne x pe cte d Se ri o us A d v e rs e R e acti o ns ( S U S A R)  
S us p e cte d u ne x pe cte d s erio us a d vers e r e a ctio ns  ( S U S A Rs) will be ha n dle d b y a p pr o priate 
pers o n nel at t he S p o ns or or desig ne e a n d re p orte d wit hin t he re q uire d ti melines in a n u n blin de d 
fas hio n t o re g ulat o ry a ut h or ities a n d I R B/I E C(s) per t he re q uire me nts of  t he c o nce r ne d 
c o mp ete nt b o dies.  S U S A Rs will be re p orte d t o st u d y I n vestigat ors in a blin de d fas hio n.  
1 1. 4.  
Rec o r di n g A d verse Eve nts  
All A Es e x perie nc e d fr o m t he ti me of inf or me d c o ns e nt/ass e nt t o t he last f ollo w -u p ( ie, 4  w e e ks 
after t he last d os e of in vestigatio nal dr u g pr o d uct) will be re c or de d wit hin e a c h patie nt’s e C R F.  
I nf or matio n s h o uld inclu de:  a c o ncis e des criptio n of t he e ve nt; date a n d ti me of e ve nt o ns et a n d 
res olutio n; deter minatio n of s erio us ness, s e verit y, c orre ctive tre at me nt, o utc o me, a n d 
relatio ns hip t o in vestigatio nal pr o d uct or st u d y pr oc e d ure or u n derlyin g dis e as e; a n d a n y a ctio n 
ta ke n will be re c or de d.  Res olutio n oc c urs w he n t he patie nt has ret ur ne d t o his bas eline state of 
he alt h or f urt her i m p r o ve me nt or w ors e nin g of t he e ve nt is n ot e x pe cte d.  
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 5 7  of 7 0  
  
W he ne ver p ossible, a dia g n osis will be re c or de d as a n A E, rat her t ha n s y m pt o ms or is olate d 
la b orat or y a b n or malities relate d t o t hat dia g n osis.  Se veral s y m pt o ms or la b orat or y res ults t hat 
are relate d t o t he s a me dia g n osis c a n t h us be part of t he s a me A E.  
A me dic al or s ur gic al pr oc e d ure is n ot a n A E; rat her t he c o n ditio n le a din g t o t he pr oc e d ure 
s h o uld be re c or de d as t he A E.  Si milarly, de at h is n ot a n A E, b ut is rat her t he o utc o me of t he 
A E(s) t hat res ulte d in de at h.  If t he A E(s) le a din g t o de at h are n ot k n o w n, t he n de at h m ust be 
re p orte d as a n A E.  All A Es will be f ollo w e d u ntil t he res olutio n of A E, c o m pletio n of t he 
patie n t’s st u d y participatio n, or st u d y ter minatio n, w hic he ver oc c urs first.  Serio us A Es will be 
f ollo w e d u ntil res olutio n or u ntil t he c o n ditio n sta bilizes or ret ur ns t o bas eline stat us or u ntil n o 
f urt her f ollo w-u p is e x pe cte d.  
1 1. 5.  
Re p o rti n g Seri o us A d verse Eve nts  
It is t he res p o nsibilit y of t he I n vestigat or t hat re p ortin g is d o ne a de q uately.  I n or der t o me et 
Re g ulat or y re p ortin g ti melines, t he st u d y site is o bligate d t o re p ort a n y S A E(s) t o t he S p o ns or or 
desig ne e i m me diately a n d n o later t ha n 2 4  h o urs afte r re c eivin g inf or matio n of a n e ve nt t hat 
me ets at le ast o ne of t he criteria f or s erio us ness as define d in Se ctio n  1 1. 2. 2 .  As t his is a 
first-in-h u ma n m ultic e nter st u d y, a n y S A E m ust be re p orte d t o all sites b y t he S p o ns or or 
desig ne e in a n e x pe dite d fas hio n.   C o nta cts f or S A E re p ortin g are pr o vide d o n t he S A E re p ortin g 
f or m.   
1 1. 6.  
S peci al Sit u ati o ns  
1 1.6. 1.  
O v e r d os e  
C urr e ntly, t her e is n o basis f or deter minin g a clinic ally  mea nin gf ul definitio n of o ver d os e f or 
S R P -4 0 4 5.  T her ef or e, as a pr eli minar y criterio n, a n y d os e > 1 0 % a b o ve t he assig ne d d os e le vel will 
be c o nsider e d a n o ver d os e.  
A n o ver d os e is n ot a n A E.  A n o ver d os e will be d oc u me nte d e ve n if it d oes n ot  res ult in a n A E.  
A n o ver d os e will be re c or de d in t he s o urc e d oc u me nts a n d re p orte d t o t he S p o ns or or desig ne e 
wit hin 2 4  h o urs after it has be e n ide ntifie d.  
1 1.6. 2.  
D e at h  
D e at h is a n o utc o me of a n e ve nt.  All c a us es of de at h are S A Es.  I n t he e ve nt of de at h, e very 
eff ort s h o uld be ma de t o o btain a de at h c ertific ate a n d if p ossible, a n a ut o ps y re p ort.  If t he c a us e 
of de at h is u n k n o w n, de at h will be re c or de d as t he e ve nt.  
1 1.6. 3.  
U n bli n di n g d ue t o a M e dic al E me r g e nc y  
I n t he e ve nt of a me dic al e mer ge nc y w herein t he k n o wle d ge of t he s u bje ct’s tre at me nt 
assig n me nt ma y influe nc e clinic al de cisio n -ma ki n g, t he I n vestigat or has t he o ptio n t o u n blin d 
tre at me nt assig n me nt.  
T he  re as o ns f or u n blin di n g 
m ust be n ote d in t he s o urc e d oc u me ntatio n.  T he in vestigat or s h o uld 
n ot dis clos e inf or matio n a b o ut tre at me nt assig n me nt t o a n y o ne w h o d oes n ot ne e d t he 
inf or matio n d ue t o t heir dire ct in v olve me nt in patie nt c are.  

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 5 8  of 7 0  
  
1 1.6. 4.  
R e s p o nsi bilitie s of t he I n v e sti g at o r  
T he res p o nsibilities of t he I n vestigat or a n d his or her staff inclu de t he f ollo win g:  
 M o nit or a n d re c or d all A Es/ S A Es  
 D eter mine s erio us ness, s e verit y, a n d relatio ns hip t o in vestigatio nal dr u g pr o d uct 
a n d/ or st u d y pr oc e d ure a n d/ or u n derlyin g dis e as e  
 D eter minatio n of t he o ns et a n d e n d date of e a c h e ve nt  
 Pr o vide initial re p ort o n all S A Es wit hin 2 4  h o urs of k n o wle d ge t o t he S p o ns or or 
desig ne e  
 Pr o vide f ollo w -u p inf or matio n o n S A E in a ti mely a n d pr oa ctive ma n ner  
 Res p o n d t o a q ueries re gar din g A Es a n d S A Es in a ti mely ma n ner  
 E ns ure s o urc e d oc u me ntatio n f or all  A Es/ S A Es are a c c urate a n d c o m plete  
1 1.6. 5.  
R e s p o nsi bilitie s of t he S p o ns o r  
T he res p o nsibilities of t he st u d y S p o ns or ( Sare pta T hera pe utics) inclu de t he f ollo win g:  
 Trainin g of I n vestigat or a n d site staff o n A E definitio ns, s afet y ass ess me nts, a n d site 
o bligatio ns relate d t o s afet y m o nit orin g a n d re p ortin g of A E 
 Trainin g wit h re gar d t o t he a c c urate a n d le gal re p ortin g of S A Es t o all a p plic a ble 
Re g ulat or y b o dies, I R B/I E C(s), clinic al trial sites, a n d ot her parties as a p pr o priate a n d 
re q uire d wit hin t he re g ulate d ti min g  
 E ns urin g a c c urate re c or din g of A Es a n d S A Es  
 N otific atio n of e x pe dite d S A Es t o sites  
 Re p ortin g of all S U S A Rs t o re g ulat or y a ut h orities a n d I R B/I E C(s) a c c or din g t o 
re gio nal re q uire me nts 
 A n n ual s afet y re p ortin g t o re g ulat or y a ut h orities a n d I R B/I E C(s) a c c or din g t o 
re gio nal re q uire me nts 

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 5 9  of 7 0  
  
1 2.  
S T A TI S TI C S  
1 2. 1.  
Ge neral C o nsi derati o ns  
T his s e ctio n des cribes t he r ules, c o n ve ntio ns, statistic al a nalysis, a n d pres e ntatio n of data f or t his 
st u d y, Pr ot oc ol 4 0 4 5 -1 0 1.   F ull details will be pr o vide d in t he final Statistic al A n alysis Pla n 
( S A P) f or t his st u d y. 
Re visio ns d urin g t he st u d y ma y be ma de t o a c c o m m o date pr ot oc ol a me n d me nts a n d t o ma ke 
c ha n ges t o a da pt t o u ne x pe cte d iss ues in st u d y e xe c utio n t hat c o uld affe ct pla n ne d a nalys es.  A n y 
re visio ns will be bas e d o n blin de d re vie w of t he data, as a p plic a ble.  A f or mal S A P f or t he 
a nalysis a n d pres e ntatio n of data fr o m t his st u d y will be pre pare d a n d iss ue d bef ore data bas e 
loc k.  D e viatio ns fr o m t he statistic al a nalys es o utline d in t his pr ot oc ol will be in dic ate d in t his 
pla n; a n y f urt her m o dific atio ns will be n ote d in t he clinic al st u d y re p ort ( C S R).  All statistic al 
a nalys es will be perf or me d b y or u n der s u per visio n of t he S p o ns or . 
All a vaila ble data will be inclu de d in data listin gs a n d ta b ulatio ns.  N o i m p utatio n of values f or  
missin g data will be perf or me d  u nless state d e x plicitly f or a n a nalysis . 
P erc e nta ges of s u bje cts wit h la b orat or y t o xicities will be bas e d o n n o n -missin g values.  
Bas eline will ge nerally be define d as t he last a vaila ble value bef ore d osin g.  
1 2. 2.  
Deter mi n ati o n of  S a m ple Size  
T he s a m ple size f or t his st u d y is bas e d u p o n q ualitative c o nsideratio ns; n o f or mal s a m ple size 
c alc ulatio ns w ere perf or me d.  T he s ele cte d s a m ple size is c o nsidere d s ufficie nt t o pr o vide initial 
s afet y e valuatio n of S R P -4 0 4 5 a n d t o pr o vide a de q uate data t o allo w f or esti matio n of P K 
para meters.  
1 2. 3.  
A n al ysis Sets  
T hre e  a nalysis s ets will be utilize d:   
S afet y Set:   All ra n d o mize d patie nts w h o re c eive a n y a m o u nt of in vestigatio nal dr u g pr o d uct.  
P h ar m ac o ki netic Set:   All ra n d o mize d patie nts w h o re c eive  t he f ull d os e of in vestigatio nal dr u g 
pr o d uct a n d f or w h o m t here are a de q uate P K s a m ples fr o m w hic h t o esti mate P K para meters.  
Effic ac y  Set:   All ra n d o mize d patie nts w h o ha ve at le ast 1  p ost -b as eline  e n d p oint ass ess me nt.  
1 2. 4.  
St atistic al A n al ysis  
1 2.4. 1.  
Pr ot o c ol D e vi ati o ns  
A listin g of pr ot oc ol de viatio ns will be pr o vide d.  T his de viatio n listin g will be bas e d o n t he 
blin de d re vie w of st u d y data prior t o loc kin g t he data bas e a n d will inclu de t he nat ure of t he 
de viatio n (e g, inclusio n/e xcl usio n, pr o hibite d t hera pie s). 

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 6 0  of 7 0  
  
1 2.4. 2.  
Dis p ositi o n, D e m o gr a p hics, a n d B as eli ne C h ar acte ristics  
T he n u m ber a n d perc e nta ge of patie nts c o m pletin g or pre mat urely dis c o ntin uin g t he st u d y will 
be s u m marize d b y tre at me nt gr o u p a n d o verall.  Re as o ns f or pre mat ure dis c o ntin uati o n will als o 
be s u m ma rize d. 
D e m o gra p hic a n d bas eline c hara cteristics s uc h as a ge ( ye ars), heig ht (c m), w eig ht ( k g), b o d y 
mass in de x ( B MI ; k g/ m 2), 
 will be s u m marize d per tre at me nt gr o u p.  
D e m o gra p hic data a n d bas eline c hara cteristics will be pres e nte d in data listin gs. 
1 2.4. 3.  
Pri o r a n d C o nc o mit a nt M e dic ati o ns  
All prior a n d c o nc o mita nt me dic atio ns will be pres e nte d in data listin gs.  
1 2.4. 4.  M e dic al Hist o r y  
Me dic al  hist or y will pres e nte d in data listin gs.  
1 2.4. 5.  D osi n g  
T h e  c u m ulative e x p os ure t o S R P -4 0 4 5, t otal v olu me of dr u g a d ministere d ( m L), t he t otal n u m ber 
of inf usio ns re c eive d, a n d t he c u m ulative a m o u nt of dr u g re c eive d will be s u m marize d b y d os e 
gr o u p f or all tre ate d patie nts.  D osin g inf or matio n will be pr o vide d in a data listin g.  
1 2.4. 6.  S afet y Vari a ble s  
T he s afet y a n d t olera bilit y of S R P -4 0 4 5 will be ass ess e d b y t he re vie w of:  
 T he t y pe, fre q ue nc y, s e verit y, ti min g, a n d relatio ns hip t o in vestigatio nal dr u g pr o d uct 
of A Es, S A Es, a n d dis c o ntin uati o ns d ue t o A Es.  A d vers e e ve nts will be c o de d usin g 
t he Me dic al Dictio nar y f or Re g ulat or y A ctivities ( Me d D R A) a n d will be re p orte d b y 
pri mar y s yste m or ga n class ( S O C) a n d preferre d ter m ( P T)  
 A d vers e e ve nts will be classifie d as tre at me nt -e mer ge nt ( T E A E) a n d n o n-e mer ge nt. 
T E A Es are t h os e A Es t hat de velo p or w ors e n d urin g t he o n -tre at me nt perio d.  
N o n -e mer ge nt e ve nts are t h os e t hat de velo p d urin g t he pre -tre at me nt perio d 
 Safet y la b orat or y testin g inclu din g he mat olo g y, c oa g ulatio n, s er u m c he mistr y, a n d 
urinalysis   
 Vital sig ns  
 P h ysic al e xa minatio ns  
 1 2 -le a d E C Gs 
 E C H O  
1 2.4. 7.  S afet y A n al ys e s  
Safet y a nalys es will be des criptive in nat ure.  
O nly T E A Es will be s u m marize d.  N o n -e mer ge nt e ve nts will be re c or de d in data listin gs.  F or all 
A E ta bles, t he n u m ber a n d perc e nt of s u bje cts re p ortin g A Es ( gr o u pe d b y Me d D R A b o d y s yste m 
a n d P T) will be s u m marize d b y tre at me nt gr o u p a n d o verall.  I n ge neral, ta bles will ha ve e ve nts 
c ate g orize d int o all T E A Es a n d tre at me nt -relate d T E A Es. 
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 6 1  of 7 0  
  
M ultiple oc c urre nc es of t he s a me A E (at t he P T le vel) in t he s a me s u bje ct will be c o u nte d o nly 
o nc e in fre q ue n c y ta bles.  If a s u bje ct e x perie nc es m ultiple e pis o des of t he s a me e ve nt wit h 
differe nt relatio ns hip/s e verit y, t he e ve nt wit h t he str o n gest relatio ns hip or ma xi m u m s e verit y t o 
in vestigatio nal dr u g pr o d uct will be us e d t o s u m marize A Es b y relatio ns hip a n d se verit y.   
T he f ollo win g s u m mar y ta bles will be pr o d uc e d:  
 Tre at me nt -e mer ge nt a d vers e e ve nts  
 Tre at me nt -e mer ge nt a d vers e e ve nts b y s e verit y  
 Tre at me nt -relate d tre at me nt-e mer ge nt a d vers e e ve nts  
 Tre at me nt -relate d tre at me nt-e mer ge nt a d vers e e ve nts b y s e verit y  
 Tre at me nt -e mer ge nt serio us a d vers e e ve nts  
I n a d ditio n, all S A Es, re gar dless of t heir tre at me nt-e mer ge nt stat us will be s u m marize d b y S O C 
a n d P T.  
T he f ollo win g listin gs will be pr o d uc e d:  
 N o n -T E A Es  
 All T E A Es  
 A Es le a din g t o dis c o ntin uati o n 
 
 S A E s 
D es criptive statistics f or E C G, E C H O, vital sig ns, p h ysic al e xa minatio ns, a n d s afet y la b orat or y 
para meters will be ge nerate d.   All s afet y data will be pres e nte d in t he data listin gs.  A d ditio nall y, 
s hift a n d fre q ue nc y ta bles of pre define d c ha n ge in a b n or mal values f or  s ele ct s afet y para meters 
will be ge nerate d.  
1 2.4. 8.  
P h ar m ac o ki netic A n al ys e s  
T he P K pr ofile of S R P -4 0 4 5 will be deter mine d fr o m m ultiple plas ma s a m ples c olle cte d s erially 
bef ore a n d after t he first w e e kly inf usio n at e a c h d os e le vel in t he d os e titratio n p has e at 
We e ks  1 , 3, 5, a n d 7 a n d als o at We e k  6 0 in t he o pe n -la bel e xte nsio n.  I n a d ditio n, m ultiple urine 
s a m ples will be c olle cte d s erially after t he first inf usio n at e a c h d os e le vel in t he d os e titratio n 
p has e a n d at We e k  1 2 . I n divid ual plas ma le vels of S R P-4 0 4 5 will be liste d wit h t he 
c orres p o n din g ti me relate d t o in vestigatio nal dr u g pr o d uct a d ministratio n a n d s u m mar y statistics 
will be ge nerate d b y per -pr ot oc ol ti me of c olle ctio n.  P har ma c o kinetic para meters f or S R P -4 0 4 5 
will be c alc ulate d usin g n o n -c o m par t me ntal a nalysis.  A ct ual s a m plin g ti mes will be us e d in all 
final P K a nalys es.  P er -pr ot oc ol ti mes will be us e d t o c alc ulate me a n plas ma c o nc e ntratio ns f or 
gra p hic al dis pla ys.  T he P K para meters t hat will be deter mine d o nly f or We e ks  1, 3, 5, 7 , a n d 6 0  
inclu de : 
 C m a x  
 T m a x  
 A U C  
 V ss 

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 6 2  of 7 0  
  
 t½  
 C L  
 M R T  
 C L R  
 
  A vaila ble patie nt c hara cteristics ( de m o gra p hics, la b orat or y 
varia bles, ge n ot y pes, c o nc o mi ta nt me dic atio ns, etc) will be teste d as p ote ntial c o variates 
affe ctin g P K para meters.  
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 6 3  of 7 0  
  
1 3.  
D A T A C O L L E C TI O N, Q U A LI T Y A S S U R A N C E, A N D 
M A N A G E M E N T  
1 3. 1.  
Rec o r di n g of D at a  
Clinic al data f or t his st u d y will be c a pt ure d in a n ele ctr o nic f or mat.  Ele ctr o nic data c a pt ure 
( E D C) will be pr o vide d b y a c o ntra ct res e arc h or ga nizatio n.  T he I n vestigat or, or pers o n nel 
dele gate d b y t he I n vestigat or, will perf or m pri mar y data c olle ctio n/ perf or m ass ess me nts bas e d o n 
t he pr ot oc ol desig n a n d c a pt ure d ins o urc e d oc u me ntatio n.  All re q uire d st u d y infor matio n 
m ust 
be re c or de d o n t he a p pr o priate C R F s cre e ns/f or ms usin g t he C R F C o m pletio n Guideli nes f or t he 
st u d y.  A C R F m ust be c o m plete d f or e a c h patie nt t hat is e nr olle d.  T he st u d y m o nit or will 
c o n d uct 1 0 0 % s o urc e data verific atio n t o e ns ure ma xi m u m da ta inte grit y.  All data m ust be 
c aref ully e ntere d in a ti mely fas hio n t o per mit me a nin gf ul inter pretatio n a n d st u d y o versig ht.  
1 3. 2.  
Q u alit y Ass ura nce  
T he C R Fs will be re vie w e d at re g ular inter vals b y a clinic al m o nit or fr o m t he S p o ns or or a 
re pres e ntative of t he S p o ns or per t he a gre e d u p o n M o nit orin g Pla n a gainst t he s o urc e 
d oc u me ntatio n f or ide ntific ati o n a n d clarific atio n of a n y dis cre pa ncies.  A ut o mate d a n d ma n ual 
q ualit y c he c ks will be in pla c e t o ide ntif y dis cre pa ncies, s uc h as missin g data, pr ot oc ol 
de viat io ns, o ut-of -ra n ge data, ot her data inc o nsiste ncies a n d c o m plia nc e.  Re q uests f or data 
clarific atio n or c orre ctio n will be d oc u me nte d as ele ctr o nic q ueries wit hin t he C R F a n d f or t he 
I n vestigat or or st u d y c o or dinat or t o res olve.  All c ha n ges t o t he C R Fs will be tra c ke d in a n 
ele ctr o nic a u dit trail.  Site St u d y Files will be re vie w e d f or c o m plia nc e t hr o u g h o ut t he st u d y.  
A u dits ma y be c arrie d o ut b y t he S p o ns or’s re pres e ntatives, a n d ins pe ctio ns ma y be perf or me d 
b y I R Bs/I E Cs or re g ulat or y a ut h orities bef ore, d urin g, or after t he st u d y.  T he I n vestigat or will 
allo w a n d assist t he S p o ns or’s re pres e ntatives a n d a n y re g ulat or y a ge nc y t o ha ve dire ct a c c ess t o 
all st u d y re c or ds, C R Fs, patie nt me dic al re c or ds a n d ot her s o urc e d oc u me ntatio n, I P dis pe nsin g 
re c or ds a n d I P st ora ge are a, st u d y fa cilities, a n d a n y ot her s o urc e d oc u me ntatio n.  
T he I n vestigat or m ust ma ke st u d y files a n d data a c c essible t o t he st u d y m o nit or, t o ot her 
a ut h orize d re pres e ntatives of t he S p o ns or, a n d t o t he a p pr o priate re g ulat or y a ut h orit y ins pe ct ors 
s uc h as t he U S F o o d a n d Dr u g A d ministratio n ( F D A).  
1 3. 3.  
Rete nti o n of St u d y D o c u me nts  
At st u d y c o m pletio n, all C R F data f or a n in divid ual site will be c o pie d o nt o a c o m pa ct dis c ( C D) 
a n d pr o vide d t o t he I n vestigat or f or rete ntio n in t he St u d y Files.  T he s u p p ortin g Site St u d y Files 
m ust be retaine d b y t he I n vestigat or f or a perio d of 2  ye ars f ollo win g t he date a mar ketin g 
a p plic atio n is a p pr o ve d f or t he dr u g f or t he in dic atio n f or w hic h it is bein g in vestigate d; or, if n o 
a p plic atio n is t o be file d, or if t h e a p plic atio n is n ot a p pr o ve d f or s uc h in dic atio n, u ntil 2  ye ars 
after t he in vestigatio n is dis c o ntin ue d a n d re g ulat or y a ut h orities are n otifie d.  
H o w e ver, t hes e d oc u me nts s h o uld be retaine d f or a lo n ger perio d, if re q uire d b y t he a p plic a ble 
re g ulat or y re q uire me nts or b y a n a gre e me nt wit h t he S p o ns or.  N o st u d y d oc u me nts will be 
destr o ye d or m o ve d t o a ne w loc atio n wit h o ut prior writte n a p pr o val fr o m t he S p o ns or.  If t he 
I n vestigat or reloc ates, retires, or wit h dra ws fr o m t he clinic al st u d y f or a n y re as o n, all re c or ds 
t hat are re q uire d t o be maintaine d f or t he st u d y s h o uld be tra nsferre d t o a n a gre e d u p o n desig ne e. 

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 6 4  of 7 0  
  
P atie nt re c or ds or ot her s o urc e data m ust be ke pt f or t he ma xi m u m perio d of ti me ma n date d b y 
t he h os pital, instit utio n, or private pra ctic e, b ut n ot less t ha n 1 5 ye ars.  
If off-site arc hivin g is us e d, all re c or ds s h o uld be retrie ve d a n d ma de a vaila ble f or re vie w at t he 
ti me of a n a u dit or re g ulat or y a ut h orit y ins pe ctio n. 
1 3. 4.  
Ter mi n ati o n of St u d y o r St u d y Site  
If t he S p o ns or, t he I n vestigat or, t he Me dic al M o nit or , t he st u d y m o nit or, I R B/I E C, or a p pr o priate 
re g ulat or y officials dis c o ver c o n ditio ns arisin g d urin g t he st u d y t hat in dic ate t he st u d y s h o uld be 
halte d or t hat t he st u d y c e nter s h o uld be ter minate d, a p pr o priate a ctio n ma y be ta ke n after 
c o ns ultatio n a m o n g (at a mini m u m) t he S p o ns or, t he I n vestigat or, I R B/I E C a n d t he Me dic al 
M o nit or . 
C o n ditio ns t hat ma y w arra nt ter minatio n of t he st u d y or a n in divid ual site inclu de, b ut are n ot 
li mite d t o, t he f ollo win g: 
 T he dis c o ver y of a n u ne x pe cte d, s erio us, or u na c c e pta ble ris k t o patie nts e nr olle d in 
t he st u d y 
 A de cisio n b y t he S p o ns or t o s us pe n d or dis c o ntin ue testin g, e valuatio n, or 
de velo p me nt of t he pr o d uct  
 Failure of t he I n vestigat or t o e nr oll patie nts int o t he st u d y at a n a c c e pta ble rate  
 Failure of t he I n vestigat or t o c o m ply wit h pertine nt re g ulatio ns of I R B/I E C or 
a p pr o priate re g ulat or y a ut h orities  
 S u b missio n of k n o win gly fals e inf or matio n fr o m t he res e arc h fa cilit y t o t he S p o ns or, 
t he st u d y m o nit or, I R B/I E C or re g ulat or y a ut h orit y 
 I ns ufficie nt a d here nc e t o pr ot oc ol re q uire me nts c o nsiste nt wit h 2 1 C F R  3 1 2 or t he 
E ur o pe a n Clinic al Trial Dire ctive 2 0 0 1/ 2 0/ E C  
St u d y ter minatio n a n d f ollo w -u p will be perf or me d in c o m plia nc e wit h t he c o n ditio ns s et f ort h in 
I nter natio nal C o u ncil f or H ar m o nis atio n (I C H) E 6 o n Go o d Clinic al Pra ctic e ( G C P) as w ell as 
2 1  C F R  3 1 2. 5 6 b a n d t he E ur o pe a n Clinic al Trial Dire ctive 2 0 0 1/ 2 0/ E C , w hic h re q uire a S p o ns or 
t o e ns ure a n I n vestigat or’s c o m plia nc e wit h t hes e re q uire me nts a n d t o pr o m ptly s e c ure a pla n f or 
c o m plia nc e or  dis c o ntin ue s hip me nts of t he I P t o t he I n vestigat or a n d e n d t he I n vestigat or’s 
participatio n in t he in vestigatio n.  

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 6 5  of 7 0  
  
1 4.  
S P E CI A L R E Q UI R E M E N T S A N D P R O C E D U R E S  
1 4. 1.  
C o m pli a nce wit h Et hic al a n d Re g ul at o ry G ui deli nes  
T his st u d y w as desig ne d a n d will be c o n d ucte d in a c c or da nc e wit h t he et hic al principles t hat 
ha ve t heir origins in t he D e claratio n of H elsin ki a n d in c o nf or ma nc e wit h I C H a n d G C P  E 6 
g uida nc e d oc u me nts. T his st u d y will c o m ply wit h t he re q uire me nts t hat are e n u nciate d in t he 
E ur o pe a n Clinic al Trial Dire ctive 2 0 0 1/ 2 0/ E C a n d in t he U S C o de of Fe deral Re g ulatio ns ( C F R).  
1 4. 2.  
Re g ul at o ry a n d I n de pe n de nt Et hics C o m mittee Re vie w  
T his st u d y will be c o n d ucte d in f ull c o m plia nc e  wit h t he I R B re g ulatio ns in 2 1  C F R 5 6 a n d/ or 
t he E ur o pe a n Clinic al Trial Dire ctive 2 0 0 1/ 2 0/ E C.  Bef ore e nr oll me nt of patie nts int o t he st u d y, 
t he pr ot oc ol a n d inf or me d ass e nt (f or patie nts, if a p plic a ble) a n d inf or me d c o ns e nt (f or 
pare nts/le gal g uar dia ns) d oc u me nts w ill be re vie w e d a n d a p pr o ve d b y t he a p pr o priate I R B/I E C 
a n d re g ulat or y a ut h orit y.  A me n d me nts t o t he pr ot oc ol will be s u bje cte d t o t he s a me I R B/I E C 
a n d re g ulat or y a ut h orit y re vie w re q uire me nts as t he original pr ot oc ol.  T he I n vestigat or will 
pr o m ptly n otif y t he I R B/I E C a n d S p o ns or of a n y S A Es or of a n y ot her inf or matio n t hat mig ht 
affe ct t he s afe us e of t he I P d urin g t he st u d y.  I R B a p pr o vals/I E C p ositive o pinio ns a n d 
re g ulat or y a ut h orities’ a p pr o vals m ust be s e nt t o t he S p o ns or, or its desig ne e, bef ore initiatio n of 
t he st u d y or bef ore a n a me n d me nt is instit ute d.  All c orres p o n de nc e wit h t he I R B/I E C a n d t he 
re g ulat or y a ut h orit y s h o uld be retaine d in t he st u d y re g ulat or y files. 
1 4. 3.  
I nf o r me d C o nse nt/ Asse nt  
Writte n inf or me d c o ns e nt fr o m e a c h patie nt’s pare nt(s) or le gal g uar dia n(s) a n d writte n ass e nt 
fr o m e a c h patie nt, if a p plic a ble, m ust be o btained bef ore a n y st u d y -s pe cific s cre e nin g or 
Bas eline  perio d e valuatio ns are perf or me d.  O ne c o p y of t he sig ne d inf or me d c o ns e nt/ass e nt 
d oc u me nts will be give n t o t he patie nt; t he I n vestigat or will retain t he original c o pies of t hes e 
d oc u me nts.  
T he inf or me d c o ns e nt/ass e nt d oc u me nts, as pre pare d b y t he S p o ns or or desig ne e, m ust be 
re vie w e d a n d a p pr o ve d b y t he I R B/I E C a n d re g ulat or y a ut h orities, as a p plic a ble, bef ore initiatio n 
of t he st u d y.  T he inf or me d c o ns e nt d oc u me nt m ust c o ntain t he basic re q uire d ele me nts of 
c o ns e nt a n d a d ditio nal ele me nts, as a p plic a ble, as s pe cifie d in t he 2 1  C F R  5 0. 2 5 a n d t he 
E ur o pe a n Clinic al Trial Dire ctive 2 0 0 1/ 2 0/ E C.  
1 4. 4.  C o m pli a nce wit h t he Prot o c ol  
All pr oc ess es a n d pr oc e d ures define d in t his pr ot oc ol will be a d here d t o.  E mer ge nc y de p art ures 
fr o m t he pr ot oc ol t hat eli minate a n a p pare nt i m me diate ha zar d t o a partic ular patie nt a n d t hat are 
de e me d b y t he I n vestigat or as cr ucial f or t he s afet y a n d w ellbein g of t hat patie nt ma y be 
instit ute d f or t hat patie nt o nly a n d d oc u me nte d as de viations.  T he I n vestigat or will c o nta ct t he 
Me dic al M o nit or  as s o o n as p ossible re gar din g s uc h a de viatio n.  T hes e de part ures d o n ot re q uire 
pre a p pr o val b y t he instit uti o nal re vie w b oar d/in de pe n de nt et hics c o m mitte e (I R B/I E C); h o w e ver, 
t he I R B/I E C a n d Me dic al M o nit or  m ust be n otifie d in writin g as s o o n as p ossible in a c c or da nc e 
wit h t he I R B/I E C p olicies after t he de part ure has be e n ma de.  

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 6 6  of 7 0  
  
1 4. 5.  
C o nfi de nti alit y  
1 4.5. 1.  
D at a  
All inf or matio n re gar din g t he nat ure of t he pr o p os e d in vestigatio n t hat is pr o vide d t o t he 
I n vestigat or b y t he S p o ns or, t he S p o ns or’s desig ne e, or t he st u d y m o nit or, wit h t he e xc e ptio n of 
inf or matio n t hat is re q uire d b y la w or re g ulatio ns t o be dis clos e d t o t he I R B/I E C, t he patie nt’s 
pare nt(s) or le gal g uar dia n(s) or t he a p pr o priate re g ulat or y a ut h orit y, m us t be ke pt in c o nfide nc e 
b y t he I n vestigat or in a c c or da nc e wit h c urre nt H e alt h I ns ura nc e P orta bilit y a n d A c c o u nta bilit y 
A ct ( HI P A A) sta n dar ds a n d/ or E ur o pe a n sta n dar ds.  
1 4.5. 2.  
P atie nt A n o n y mit y  
T he a n o n y mit y of participatin g patie nts will be maintaine d t o t he e xte nt re q uire d b y a p plic a ble 
la ws a n d in a c c or da nc e wit h c urre nt HI P A A sta n dar ds.  P atie nts will be ide ntifie d b y t heir 
initials a n d a n assig ne d patie nt ide ntific atio n n u m ber o n t he C R Fs a n d ot her data c olle cte d b y t he 
S p o ns or.  T he I n vestigat or m ust maintain  all d oc u me nts relate d t o t he st u d y t hat ide ntif y t he 
patie nt (e g , t he sig ne d inf or me d c o ns e nt d oc u me nt) in strict c o nfide nc e, e xc e pt t o t he e xte nt 
ne c ess ar y t o allo w a u ditin g b y t he a p pr o priate re g ulat or y a ut h orities, t he I R B/I E C, t he st u d y 
m o nit or, or t h e S p o ns or or its re pres e ntatives.  

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 6 7  of 7 0  
  
1 5.  
S T U D Y D O C U M E N T A TI O N A N D G E N E R A L IN F O R M A TI O N  
1 5. 1.  
Esse nti al St u d y D o c u me nts  
T he f ollo win g d oc u me ntatio n will be c olle cte d prior t o st u d y e nr oll me nt:  
 Sig ne d F or m F D A  1 5 7 2, or e q uivale nt  
 C urric ulu m vita e f or e a c h pers o n o n t he F o r m F D A 1 5 7 2 or e q uivale nt  
 Sig ne d Fina ncial Dis clos ure F or ms f or e a c h pers o n liste d o n t he F or m F D A  1 5 7 2 or 
e q uivale nt 
 I R B/I E C a p pr o val f or all st u d y materials (inf or me d c o ns e nt f or m [I C F], p r ot oc ol, a n y 
re cr uit me nt materials, etc) a n d I R B/I E C me m bers hip list 
 Clinic al la b orat or y n or mals, w he n a p pr o priate  
 Clinic al la b orat or y lic e ns es ( C olle ge of A meric a n P at h olo gists [C A P ]/Clinic al 
La b orat or y I m pr o ve me nt A me n d me nts  [C LI A ] or ot her)  
 Sig ne d final pr ot oc ol pa ge  
 In vestigat or’s B r oc h ure a c k n o wle d ge me nt  
 A bla n k c o p y of t he I R B -/I E C-a p pr o ve d inf or me d c o ns e nt (a n d ass e nt d oc u me nts, if 
a p plic a ble) a n d a ut h orizatio n 
 A f ully e xe c ute d Clinic al Trial A gre e me nt a n d C o nfide ntialit y A gre e me nt  
Ess e ntial d oc u me ntatio n per G C P/I C H are re q uire d bef ore st u d y e nr oll me nt is t o oc c ur.  C o pies 
of t hes e d oc u me nts, as w ell as s u p ple me ntal inf or matio n, s uc h as t he I n vestigat or’s Br oc h ure, 
P har ma c y Ma n ual, C R F C o m pletio n Guidelines, final pr ot oc ol, as s pe cifie d in t he Clinic al 
O peratio ns Ma n ual a n d/ or Re g ulat or y Bin der, m ust be ke pt o n -site in a desig nate d st u d y site file.  
T he st u d y site files will als o c o ntain, patie nt a c c o u nta bilit y re c or ds, dr u g a c c o u nta bilit y 
(re c eipt/ dis pe nsin g) re c or ds, S p o ns or/I n vestigat or c orres p o n de nc e, I R B/I E C c orres p o n de nc e, 
de viatio ns, biolo gic al s a m ple re c o r ds, a n d S A E a n d I n vestigatio nal N e w Dr u g (I N D) s afet y 
re p orts / Safet y Alert Letters. 
1 5. 2.  
Ge neral I nf o r m ati o n  
T he I n vestigat or s h o uld refer t o t he c urre nt I n vestigat or’s Br oc h ure alo n g wit h s u bs e q ue nt Safet y 
Alert Letters, t he Clinic al St u d y O peratio ns Ma n ual , P har ma c y Ma n ual, La b orat or y Ma n ual, 
C R F C o m pletio n Guidelines, a n d all ot her st u d y -s pe cific inf or matio n t hat is pr o vide d d urin g t he 
st u d y initiati o n visit or b y t he st u d y m o nit or.  
1 5. 3.  
Disse mi n ati o n of St u d y Res ults  
T he inf or matio n t hat is de velo pe d d urin g t h e c o n d uct of t his clinic al st u d y is c o nsidere d t o be 
strictly c o nfide ntial.  T his inf or matio n ma y be dis clos e d o nly as de e me d ne c ess ar y b y Sare pta 
T hera pe utics I nc.  H o w e ver, at t he c o nclusio n of t his clinic al st u d y, a clinic al st u d y re p ort will be 
pre pare d.  I n a d ditio n, a ma n us cript will be pre pare d f or p u blic atio n in a re p uta ble s cie ntific 
jo ur nal u n der t he dire ctio n of t he S p o ns or.  Sare pta T hera pe utics I nc., will p u blis h a n d 

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 6 8  of 7 0  
  
c o m m u nic ate t he clinic al st u d y res ults, irres pe ctive of p ositive or ne gative f in din gs.  D ata 
ge nerate d f or t his st u d y will be e xclusively o w ne d b y Sare pta T hera pe utics I nc., as detaile d in 
t he Clinic al Trial A gre e me nt.  T he st u d y will be re gistere d o n Clinic al Trials. g o v.  After 
c o m pletio n of t he st u d y, res ults will be diss e minate d t hr o u g h Clinic al Trials. g o v.  
1 5. 4.  
Pro d uct H a n dli n g a n d C o m pl ai nts Re p orti n g  
If t here are a n y iss ues d urin g t he c o urs e of t he st u d y relate d t o t he q ualit y of t he in vestigatio nal 
pr o d uct, t he I n vestigat or, clinic al site p har ma cist or p har ma c y desig ne e m ust c o nta ct t he S p o ns or 
or desig nate d c o ntra ct res e arc h or ga nizatio n (C R O ). 

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 6 9  of 7 0  
  
1 6.  
LI S T O F R E F E R E N C E S  
A A O S. htt p:// w w w. a a os. or g/ 
We bsite a c c ess e d o n: Fe br uar y 2 0 1 4.  
 
 
 
A arts ma -R us, F o k ke ma I, V ers c h u ure n J, Ginja ar I, V a n D e ute k o m J, V a n O m me n GJ, e t a l. 
T he oretic a p plic a bilit y of a ntis e ns e -m e diate d e x o n skip pin g f or D uc he n ne m us c ular d ystr o p h y 
m utatio ns . H u m M utat. 2 0 0 9; 3 0( 3):2 9 3-9.  
A T S C o m mitte e o n Pr oficie nc y sta n dar ds f or Clinic al P ul m o nar y F u nctio n La b orat ories. A T S 
state me nt: g uideli nes f or t he six-min ute w alk test. A m  J Res p C rit C are M e d. 2 0 0 2; 1 6 6( 1): 1 1 1-7.  
Be e na k ker E A, F oc k J M, V a n T ol M J, Ma urits N M, K o o p ma n H M, Br o u w er O F, e t a l. 
I nter mitte nt p re d nis o ne thera p y in D uc he n ne m us c ular d ystr o p h y: a ra n d o mize d c o ntr olle d trial. 
Arc h  N e ur ol. 2 0 0 5; 6 2( 1):1 2 8 -3 2.  
Big gar W D, H arris V A, Elias o p h L, Al ma n B. L o n g -ter m be nefits of defla za c ort tre at me nt f or 
b o ys wit h D uc he n ne m us c ular d ystr o p h y in t heir s e c o n d de c a de. N e ur o m us c ul Dis or d. 
2 0 0 6; 1 6( 4):2 4 9 -5 5 . 
Br o o ke M H, Fe nic hel G M, Grig gs R C, Me n dell J R, M o xle y R, Flore nc e J, e t a l. D uc he n ne 
m us c ular d ystr o p h y: p atter ns of c linic al p r o gressio n a n d e ffe cts of su p p ortive thera p y. N e ur ol. 
1 9 8 9; 3 9( 4):4 7 5 -8 1.  
Br o o ke M G, Grig gs R C, Me n dell J R, Fe nic hel, G M, S h u mate J B , P e lle grin o RJ. Clinic al trial in 
D uc he n ne d ystr o p h y. I T he d esig n of t he p r ot oc ol. 
M us cle N er ve. 1 9 8 1;4:1 8 6 -9 7.  
B us h b y K M , Gar d ner -Me d win D . T he c linic al, g e netic a n d d ystr o p hin c hara cteristics of Be c ker 
m us c ular d ystr o p h y. I. N at ural Hist or y. J  N e ur ol. 1 9 9 3; 2 4 0( 2): 9 8 -1 0 4.  
C D C -M M W R. Pre vale nc e of D uc he n ne/ Be c ker m us c ular d ystr o p h y a m o n g m ales a ge d  
5 -2 4  Y e ars --- fo ur states, 2 0 0 7. M M W R M or b M ortal W kly Re p. 2 0 0 9; 1 1 1 9 -2 2.  
Ea gle M, Ba u d o uin S V, C ha n dler C, Gid din gs D R, B ulloc k R, B us h b y K. S ur vival in D uc he n ne 
m us c ular d ystr o p h y: im pr o ve me nts in life e x pe cta nc y sinc e 1 9 6 7 a n d t he im pa ct of h o me 
n oct ur nal v e ntilatio n. N e ur o m us c ular Dis. 2 0 0 2 D e c; 1 2( 1 0):9 2 6 -9.  
E mer y A E. P o p ulatio n fre q ue ncies of in herite d n e ur o m us c ular d is e as es--a w orld sur ve y. 
N e ur o m us c ul Dis or d . 1 9 9 1; 1( 1):1 9-2 9.  
 
 
 
Ga uld L M, K a p pers J, Carlin J B, R o berts o n C F. H eig ht p re dictio n fr o m u lna le n gt h. D e v Me d 
C hild N e ur ol. 2 0 0 4; 4 6:4 7 5 -8 0.  
H a n W K, Bailly V, A bic ha n da ni R, T ha d ha ni R, B o n ve ntre J V. Kid ne y I njur y M ole c ule-1 
( KI M-1): a n o vel b io mar ker f or h u ma n re nal p r o xi mal tu b ule injur y. Kid ne y I nt. 2 0 0 2 
J ul; 6 2( 1):2 3 7-4 4 . 
C CI
C CI

Sare pta T hera pe utics, I nc.  
Pr ot oc ol 4 0 4 5 -1 0 1, V ersi o n 4. 0  
 
P a ge 7 0  of 7 0  
  
 
 
 
K o hler  M,  Clare n ba c h C F,  Ba hler C,  Bra c k T,  R ussi E W , Bloc h K E. Dis a bilit y a n d sur vival in 
D uc he n ne m us c ular d ystr o p h y. J N e ur ol N e ur os ur g Ps yc hiatr y. 2 0 0 9; 8 0( 3):3 2 0 -5.  
Ma nz ur A Y, K u ntzer T, Pike M, S w a n A . Gluc oc ortic oi d c ortic oster oids f or D uc he n ne m us c ular 
d ystr o p h y. C oc hra ne D ata bas e S yst Re v. 2 0 0 4;( 2): C D 0 0 3 7 2 5.  
 
 
Pra d ha n S D, Gh os h  D , Srivasta va N K, K u mar A, P a n de y C M, Sin g h U.  Pre d nis olo ne in 
D uc he n ne m us c ular d ystr o p h y wit h im mine nt 
loss of a m b ulatio n. J N e ur ol. 
2 0 0 6; 2 5 3( 1 0):1 3 0 9 -1 6.  
Wils o n S H, C o o ke N T, E d w ar ds R H, S pir o S G. Pre dicte d n or mal values f or ma xi mal res pirat or y 
press ures in Ca uc asia n  a d ults a n d c hildre n. T h ora x. 1 9 8 4; 3 9( 7):5 3 5 -8.  
 
C CI
C CI