Conditions: Duchenne Muscular Dystrophy
Keywords: Duchenne muscular dystrophy Exon Skipping
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 12
Healthy volunteers: no

Brief summary:
This is a first-in-human dose-titration and open-label extension study to assess safety, tolerability, and pharmacokinetics of SRP-4045 in advanced-stage Duchenne muscular dystrophy (DMD) patients with deletions amenable to exon 45 skipping.

Detailed description:
This is a randomized, placebo-controlled dose-titration study to assess safety, tolerability, and pharmacokinetics of 4 dose levels of SRP-4045 in genotypically confirmed advanced-stage DMD patients with deletions amenable to exon 45 skipping.

After completion of the dose-titration portion of the study and SRP-4045 is determined to be safe, all patients will be evaluated on open-label SRP-4045 for the duration of the study.

Safety, including adverse event monitoring, routine laboratory assessments, and cardiac testing will be monitored through the duration of the dose-titration and open-label portions of the study.

Clinical efficacy will be assessed at regularly scheduled study visits via quality of life questionnaires and tests of pulmonary and upper extremity function through the duration of the dose-titration and open-label portions of the trial.

Arms:
arm 1: Participants with genotypically confirmed Duchenne muscular dystrophy (DMD) characterized by deletions amenable to exon 45 skipping will receive placebo-matching to casimersen intravenous (IV) infusions, once weekly over approximately 12 weeks in the double-blind period. arm 2: Participants with genotypically confirmed DMD characterized by deletions amenable to exon 45 skipping will receive weekly IV infusions of casimersen at four escalating dose levels, each for at least 2 weeks: 4 milligrams per kilograms (mg/kg) during Week 1 to Week 2, followed by 10 mg/kg during Week 3 to Week 4, followed by 20 mg/kg during Week 5 to Week 6, followed by 30 mg/kg beginning at Week 7 and continue over approximately Week 12 in the double-blind period. arm 3: All participants who completed double blind period will be enrolled to receive casimersen 30 mg/kg once weekly, for up to Week 144 in the open label extension period.

Interventions: intervention 1: SRP-4045 intervention 2: Placebo
Intervention descriptions: intervention 1: SRP-4045 solution for IV infusion. intervention 2: SRP-4045 placebo-matching solution for IV infusion.

Protocol document:
Prot_000.pdf: 
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
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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  
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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 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  
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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 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 
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 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

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