Conditions: Duchenne Muscular Dystrophy Cardiomyopathy
Keywords: Duchenne Muscular Dystrophy Cardiomyopathy
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 25
Healthy volunteers: no

Brief summary:
Male participants with cardiomyopathy secondary to Duchenne muscular dystrophy (DMD) meeting all inclusion and no exclusion criteria will be randomized. All participants will be at least 12 years of age. They will be randomized in a 1:1 manner to either intracoronary infusion of CAP-1002 in three coronary arteries supplying the three major cardiac territories of the left ventricle of the heart (anterior, lateral, inferior/posterior) or usual care. In the active treatment arm, all three major cardiac territories will be treated (infused) during a single procedure in an open-label fashion.

Detailed description:
Approximately 24, and not more than 30, participants will be randomized into the study, in two sequential enrollment groups. Safety data from Group 1 will undergo a Data Safety Monitoring Board (DSMB) review prior to initiation of enrollment for Group 2.

The first 6-8 randomized participants will comprise Group 1, and will include a minimum of 3 participants completing intracoronary infusion with CAP-1002. The DSMB will conduct a review of interim safety data through 72 hours post-Day 0 for at least 3 infused participants and for at least 6 participants overall.

Enrollment of Group 2 will begin per DSMB recommendations following their review of the 72 hour safety data from Group 1. Group 2 will include approximately 18 participants. Screening and randomization will continue until at total of 12 participants are infused with CAP 1002 or 30 participants are randomized into the study, whichever comes first.

All participants assigned to the active treatment arm will receive an intended total dose of up to 75 million (M) CAP-1002 cells infused as 25M cells into each of the three left ventricle cardiac territories (anterior, lateral, inferior/posterior).

Participants randomized to receive usual care will continue to be cared for and treated in whatever manner the investigator deems most appropriate for the participant on an ongoing basis, and will receive no infusion.

Randomization will take place within 30 days of the first screening procedure. After completion of the screening procedures, eligible participants randomized to active treatment arm will receive CAP-1002 administered via intracoronary infusion on Day 0. Day 0 for eligible participants randomized to the usual care arm will occur 7 days after the date of randomization. All randomized participants will have a follow-up telephone call on Study Day 3, and study visits at Weeks 2 and 6, and at Months 3, 6 and 12 post Day 0.

Arms:
arm 1: CAP-1002 is an investigational product consisting of allogeneic cardiosphere-derived cells (CDCs). All subjects assigned to the active treatment arm will receive an intended total dose of 75 million (M) CAP-1002 cells infused as 25M cells into each of the three left ventricle cardiac territories (anterior, lateral, inferior/posterior). If any of the three coronary arteries are deemed by the infusing Investigator to supply less than 30% of the left ventricular myocardium, the infusing Investigator may choose to infuse only 12.5M cells into that coronary artery or arteries. Therefore the full dose of CAP-1002 delivered may range from 50M cells to 75M cells provided that all three arteries are infused. arm 2: Subjects randomized to receive usual care will continue to be cared for and treated in whatever manner the investigator deems most appropriate for the subject on an ongoing basis, and will receive no infusion.

Interventions: intervention 1: Allogeneic Cardiosphere-Derived Cells (CAP-1002)
Intervention descriptions: intervention 1: Intracoronary delivery of Allogeneic Cardiosphere-Derived Cells (CAP-1002)

Protocol document:
Prot_000.pdf: 
C O N FI D E N TI A LI T Y S T A T E M E N T
T his d o c u me nt is c o nfi d e ntial a n d pr o prietar y t o Ca pric or, I nc. a n d its affiliates. Acce pta nc e of t his d o c u me nt 
c o nstit utes a gree me nt b y t he reci pie nt t hat n o u n p u blis he d i nf or mati o n c o ntai ne d herei n will b e re pr o d uce d, 
p u blis he d, or ot her wise disse mi nate d or discl ose d or use d wit h o ut t he pri or writte n a p pr o val of Ca pric or, I nc. 
a n d its affiliates, e xce pt t hat t his d o c u me nt ma y be discl ose d i n a n y me di u m t o a p pr o priate cli nical
i n vesti gat ors, I nstit uti o nal Re vie w B o ar ds, a n d ot hers directl y i n v ol ve d i n t he cli nical i n vesti gati o n t hat is t he 
s u bj ect of t his i nf or mati o n u n d er t he c o n diti o n t hat t he y kee p t he i nf or mati o n strictl y c o nfi d e ntial. 
Cli ni c al Tri al Pr ot o c ol: C A P- 1 0 0 2- D M D- 0 1 ( H O P E)
St u d y Title:
A Ra n d o mize d, O pe n-la bel St u d y of t he Safet y a n d Efficac y of M ulti-
Vess el I ntrac or o n ar y Deli ver y of All o ge nei c Car di os p here- D eri ve d 
Cells i n Patie nts wit h Car di o m y o pat h y Sec o n d ar y t o D uc he n ne 
M usc ular D ystr o p h y [ H O P E- D uc he n n e ( H alt car di o m y O Pat h y 
pr o gr Essi o n i n D uc he n n e)] 
St u d y N u m ber:
C A P- 1 0 0 2- D M D- 0 1
St u d y P h ase:
P hase II
Pr o d uct N a me:
C A P- 1 0 0 2 All o ge nei c Car di os p here- Deri ve d Cells
I N D N u m ber:
I n dic ati o n:
Car di o m y o pat h y i n D M D
I n v esti g at ors:
M ulti ce nter
St u d y Pri n ci pal I n vesti gat or:
, M D, M P H 
S p o ns or:
Ca pric or, I n c.
8 8 4 0 Wils hire Bl v d. 2 n d fl o or 
Be verl y Hills, C A  9 0 2 1 1 
S p o ns or C o nt act
& Me dic al 
M o nit or: 
, M D  
, Ca pric or, I n c.
Ori gi n al Pr ot oc ol:
0 1 Ma y 2 0 1 5
A me n d me nt 1. 0:
2 7 J a n uar y 2 0 1 6
A me n d me nt 2. 0:
2 9 Fe br u ar y 2 0 1 6
A me n d me nt 3. 0:
1 8 J ul y 2 0 1 6


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 2 of 1 1 1
S Y N O P SI S
S p o ns or:
Ca pric or, I n c.
N a me of Fi nis he d Pr o d uct:
C A P- 1 0 0 2 All o ge nei c Car di os p here- Deri ve d Cells
N a me of Acti ve I n g re die nt:
Car di os p here- D eri v e d Cells 
St u d y Title:
A Ra n d o mize d, O pe n-la bel St u d y of t he Safet y a n d Efficac y of M ulti- Vessel I ntrac or o nar y 
Deli ver y of All o ge n eic C ar di os p here- Deri ve d Cells i n Patie nts wit h Car di o m y o pat h y 
Sec o n dar y t o D u c he n ne M usc ular D ystr o p h y [ H O P E- D uc he n ne (H alt car di o m y O P at h y 
pr o gr Essi o n i n D uc he n ne )]
St u d y N u m ber:
C A P- 1 0 0 2- D M D- 0 1
St u d y P h ase: P hase II
Pri m ar y O bjecti ve(s):
T o assess t he safet y a n d t olera bilit y of C A P- 1 0 0 2 a d mi nistere d b y m ulti- vessel i ntrac or o nar y 
i nf usi o n i n s u bjects wit h car di o m y o pat h y se c o n dar y t o D u c he n n e m usc ular d ystr o p h y 
( D M D).
Sec o n d ar y O bjecti ve(s):
T o assess efficac y of C A P- 1 0 0 2 a d mi nistere d b y m ulti- vessel i ntrac or o nar y i nf usi o n i n 
s u bjects wit h car di o m y o pat h y sec o n dar y t o D M D b y sta bilizi n g or i m pr o vi n g car dia c 
str uct ure, b y e v al uati n g f u ncti o nal stat us, a n d b y assess me nt of q ualit y of life.
St u d y Desi g n:
Male s u bjects at least 1 2 years of a ge, wit h car di o m y o pat h y sec o n dar y t o D M D, a n d m eeti n g 
all i ncl usi o n a n d n o e x cl usi o n criteria, will be ra n d o mize d. Eac h s u bject t h at meets all 
eli gi bilit y criteria will be ra n d o mize d i n a 1: 1 ma n n er t o eit h er i n vesti gati o nal pr o d uct ( C A P-
1 0 0 2) or us ual care. 
If ra n d o mize d t o i n vesti gati o nal pr o d uct, a s u bject will recei ve a n i ntrac or o nar y i nf usi o n of 
C A P- 1 0 0 2 (i nte n d e d t otal d ose of 7 5 milli o n [ 7 5 M] cells) i n t hree c or o n ar y arteries 
s u p pl yi n g t he t hree maj or car di ac territ ories of t he left v e ntricle of t h e heart (a nteri or, lat eral, 
i nferi or/ p osteri or). All t hree maj or car di ac territ ories will be treate d (i nf use d) d uri n g a si n gle 
pr oce d ure i n a n o pe n-la b el fas hi o n. 
S u bjects ra n d o miz e d t o recei ve us u al care will n ot recei v e a n i nf usi o n.  T he y will c o nti n ue t o 
be care d f or a n d treate d i n w hate ver m a n ner t h e i n vesti gat or d ee ms m ost a p pr o priate f or t he 
s u bject o n a n o n g oi n g b asis, e xce pt t hat us u al care ca n n ot i ncl u de treat me nt wit h C A P- 1 0 0 2
or ot her i n vesti gati o nal treat me nts.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 3 of 1 1 1
A p pr o xi matel y 2 4, a n d n ot m ore t h a n 3 0, s u bjects will be ra n d o mize d i nt o t h e st u d y i n t w o 
se q ue nti al e nr oll me nt gr o u ps. Safet y d ata fr o m Gr o u p 1 will u n der g o a Dat a S afet y 
M o nit ori n g B o ar d ( D S M B) re vi e w pri or t o i nitiati o n of e nr oll me nt f or Gr o u p 2. 
T he first 6- 8 ra n d o mize d s u bjects will c o m prise Gr o u p 1, a n d will i ncl u de a mi ni m u m of 3 
s u bjects c o m pleti n g i ntrac or o nar y i nf usi o n wit h C A P- 1 0 0 2.  T he D S M B will c o n d uct a 
re vie w of i nteri m safet y data t hr o u g h 7 2 h o urs p ost - Da y 0 f or at least 3 i nf use d s u bjects a n d 
f or at least 6 s u bjects o verall.  
E nr oll me nt of Gr o u p 2 will be gi n per D S M B rec o m me n dati o ns f oll o wi n g t h eir re vie w of t h e 
7 2 h o ur safet y d ata fr o m Gr o u p 1.  Gr o u p 2 will i ncl u de a p pr o xi matel y 1 8 s u bjects. 
Scree ni n g a n d ra n d o mizati o n will c o nti n ue u ntil at t otal of 1 2 s u bjects are i nf use d wit h 
C A P- 1 0 0 2 or 3 0 s u bjects are ra n d o mize d i nt o t he st u d y, w hic he ver c o mes first.  
  
  
  
S u bject i nf usi o ns will be sta g gere d b y at least t hree da ys t o all o w f or d etecti o n of ac ute 
pr oce d ure-relate d c o m plicati o ns s h o ul d t he y o cc ur. A d diti o nall y, s u bject i nf usi o ns i n Gr o u p 
2 will n ot be gi n u ntil at least t w o wee ks after t he fi nal i nf usi o n occ urs i n Gr o u p 1, t o all o w 
f or c o m pleti o n of t he Gr o u p 1 safet y data re vie w t hr o u g h 7 2 h o urs p ost D a y 0. 
N o scree ni n g pr oce d ures will ta ke place u ntil t h e s u bject is f ull y i nf or me d of t h e researc h a n d 
si g ns t he i nf or m e d c o nse nt or pr o vi des asse nt. S u bjects 1 8 ye ars of a ge or ol der m ust ha ve 
t he a bilit y t o pr o vi de i nf or me d c o nse nt a n d f oll o w u p wit h pr ot oc ol pr oce d ures. S u bjects at 
least 1 2 years of a ge b ut y o u n ger t ha n 1 8 years of a ge m ust ha ve t he a bilit y t o pr o vi de asse nt 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 4 of 1 1 1 
al o n g wit h t he s u bject’s pare nt or g u ar dia n pr o vi di n g per missi o n f or st u d y partici p ati o n.
Ra n d o mizati o n will ta ke place wit hi n 3 0 da ys of t he first scree ni n g pr oce d ure. Aft er 
c o m pleti o n of t he scree ni n g pr o ce d ures, eli gi ble s u bjects ra n d o miz e d t o acti ve treat m e nt ar m 
will recei v e C A P- 1 0 0 2 a d mi nistere d via i ntrac or o nar y i nf usi o n o n Da y 0. Da y 0 f or eli gi ble 
s u bjects ra n d o mi ze d t o t he us ual care ar m will occ ur 7 da ys after t he d ate of ra n d o mi zati o n. 
All ra n d o mize d s u bjects will ha ve st u d y visits at Da y 3, Wee ks 2 a n d 6, a n d M o nt hs 3, 6 a n d 
1 2 p ost Da y 0. Ke y safet y ass ess m e nts s uc h as s u d de n u ne x pecte d deat h, a n d ot h er maj or 
a d verse car di ac e ve nts ( M A C E), will be assesse d f or all s u bjects, wit h t he e x ce pti o n of t h ose 
o nl y rel e va nt t o s u bjects assi g ne d t o t he acti ve tr eat m e nt ar m, s u c h as  n e w TI MI fl o w 0- 2 or 
TI MI m y o car dial perf usi o n gra de ( T M P G) 0- 2 ( persisti n g > 3 mi n utes after ter mi nati o n of 
cell i nf usi o n). Si nce C A P- 1 0 0 2 is gr o w n fr o m d o n ors u nrelate d t o reci pie nts, h u m oral a n d 
cell ular i m m u ne res p o ns es will als o be e val uat e d. 
D S M B O versi g ht:
T he Data a n d Safet y M o nit ori n g B oar d ( D S M B) will meet per c harter, at least se mia n n uall y t o 
re vie w a vaila ble data, a n d will c o n d uct a n i nteri m re vie w of s afet y d ata f or Gr o u p 1 s u bjects 
t hr o u g h 7 2 h o urs p ost- d a y 0.  T he y will re vie w b ot h safet y a n d efficac y data after all s u bjects 
ha ve c o m plete d 6 m o nt hs of f oll o w- u p.
St u d y P o p ul ati o n a n d R ati o n ale:
A p pr o xi matel y t w e nt y-f o ur ( 2 4), a n d n ot m ore t ha n 3 0, male s u bjects at least 1 2 years of a ge, 
wit h car di o m y o p at h y sec o n dar y t o D M D a n d left ve ntric ular s car as assess e d b y l ate 
ga d oli ni u m e n ha n ce me nt ( L G E) car dia c M RI i n at least 4 se g me nts, will be c o nsi dere d f or 
e nr oll me nt i n t he st u d y.
T his sa m ple size is a de q uate t o s u p p ort a n assess m e nt of safet y a n d 
t olera bilit y of i ntrac or o n ar y i nf usi o n of C A P- 1 0 0 2 i n t his disease p o p ulati o n, as well as a n 
e x pl orat or y ass ess m e nt of efficac y. E nr oll me nt will c o nti n ue u ntil 1 2 s u bjects ha ve 
c o m plete d i nf usi o n wit h C A P- 1 0 0 2 or 3 0 s u bjects ha ve b ee n ra n d o mize d, w hic he ver o cc urs 
first.
Car di o m y o pat h y is c urre ntl y t he lea di n g ca use of deat h i n D M D p atie nts ( S p ur ne y 2 0 1 1,
Passa ma n o, Ta glia et al. 2 0 1 2), ha vi n g rece ntl y s u p pla nte d res pirat or y ca us es as a r es ult of 
treat me nt i m pr o v e me nts f or t hat as pect of t he dis ease. Affli cte d pati e nts lac k a f u ncti o nal 
d ystr o p hi n pr otei n a n d e x perie nce pr o gressi ve m uscle wea k n ess starti n g at a n earl y a ge a n d 
ulti m atel y a n a b bre viate d lifes pa n. Gi ve n t he gl o b al a n d pr o gressi ve nat ure of t he disease, 
rarel y are t hes e patie nts c o nsi dere d f or h eart tr a ns pla nt, use of mec ha nical car diac assist 
de vices is lar gel y e x peri me ntal ( R ya n, J efferies et al. 2 0 1 4), a n d t h e effecti v e ness of t h e 
t hera pies i n use or i n d e vel o p me nt f or D M D o n t h e car di ac ma nifestati o ns of t he disease is 
ge n erall y a s ec o n d ar y c o nsi derati o n. C A P- 1 0 0 2 is i nte n de d t o tar get t he car di o m y o pat h y i n 
D M D as o p p ose d t o t he s keletal m y o p at h y. 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 5 of 1 1 1
I ncl usi o n Criteri a:
Eac h s u bject m ust meet all of t he f oll o wi n g i ncl usi o n crit eria t o be ra n d o mi ze d i n t he st u d y: 
1.
Male s u bjects 1 8 years of a ge or ol d er m ust be a bl e t o pr o vi de i nf or me d c o nse nt a n d 
f oll o w u p wit h pr ot oc ol pr oce d ures. Male s u bjects at least 1 2 years of a g e b ut y o u n ger 
t ha n 1 8 years of a ge m ust be a ble t o pr o vi de ass e nt wit h pare nt or g uar di a n pr o vi di n g 
per missi o n f or st u d y p arti ci pati o n. O nl y male s u bj ects will be ra n d o mize d i nt o t his 
st u d y.
2.
D oc u me nte d dia g n osis of D uc he n ne M us c ular D ystr o p h y b y ge netic m utati o n a nal ysis. 
3.
Car di o m y o pat h y wit h left ve ntric ul ar scar b y L G E i n at least 4 se g me nts as assesse d b y 
c o ntrast-e n h a nce d M RI a n d E F > 3 5 % at t h e ti m e of scree ni n g.  
4.
Use of e vi de nce b ase d m e dical-t hera p y i n acc or d a nce wit h t he “ D M D Care 
C o nsi d erati o ns W or ki n g Gr o u p” g ui deli n es f or t he ma na ge me nt of D M D ( B us h b y, 
Fi n kel et al. 2 0 1 0a, B us h b y, Fi n kel et al. 2 0 1 0 b), f or at least t hree m o nt hs pri or t o 
si g ni n g t he c o nse nt f or m ( or, pr o vi di n g asse nt) or d oc u me nte d c o ntr ai n dicati o n or 
i nt olera nce or patie nt prefere nce.   
5.
S u bjects m ust be ta ki n g s yste mic gl uc o c ortic oi ds f or at least si x m o nt hs pri or t o 
scree ni n g. 
6.
S u bjects m ust be 1 2 years of a ge or ol d er at ti m e of scree ni n g
7.
S u bjects m ust be a p pr o priate ca n di d ates f or car dia c cat heterizati o n a n d i ntrac or o nar y 
i nf usi o n of C A P- 1 0 0 2, i n t h e j u d ge me nt of t he site’s i nter ve nti o nal car di ol o gist.
E xcl usi o n Criteri a:
S u bjects t h at m eet a n y of t h e f oll o wi n g e xcl usi o n criteria will n ot be per mitte d t o e nr oll i nt o 
t he st u d y: 
1.
T hera p y wit h i ntra ve n o us i n otr o pic or vas oacti v e me dicati o ns at t h e ti me of scree ni n g. 
2.
I n a bilit y t o u n der g o car di ac c at heterizati o n a n d/ or M RI wit h o ut ge neral a nest h esia.
3.
I m m u n ol o gic i nc o m pati bilit y wit h all a v aila ble M aster Cell Ba n ks ( M C Bs) b y si n gle-
a nti ge n b ea d ( S A B) s er u m a nti b o d y pr ofili n g.
4.
Pl a n ne d or li kel y maj or s ur ger y i n t he n e xt 1 2 m o nt hs after pla n ne d ra n d o mizati o n. 
5.
Left Ve ntric ul ar Assist D e vices ( L V A D) or t h ose s u bjects acti vel y i n t he pr ocess of 
ac q uiri n g a L V A D.
6.
C o ntrai n dicati o n t o car di ac M RI. 
7.
K n o w n h y p erse nsiti vit y t o c o ntrast a ge nts. 
8.
Esti mate d gl o mer ular filtrati o n rate ( G F R) < 6 0 m L/ mi n, as calc ulate d b y t he C K D- E PI 
c ystati n C e q u ati o n (I n ker, Sc h mi d et al. 2 0 1 2). 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 6 of 1 1 1
9.
Acti ve i nfecti o n n ot res p o nsi ve t o treat m e nt.
1 0.
Acti ve s yst e mic aller gic reacti o n(s), c o n necti ve tiss ue disease or a ut oi m m u ne 
dis or der(s).
1 1.
Hist or y of car di ac t u m or or car di ac t u m or de m o nstrate d o n scree ni n g M RI.
1 2.
Hist or y of pre vi o us ste m cell t h era p y.
1 3.
Hist or y of us e of me dicati o ns liste d i n A p p e n di x 3 wit hi n 3 m o nt hs pri or t o si g ni n g t he 
I C F / Asse nt t hr o u g h c o m pleti o n of t he st u d y i nf usi o n. 
1 4.
K n o w n m o derat e-t o-se vere a ortic ste n osis/i ns ufficie nc y or se v ere mitral 
ste n osis/re g ur gitati o n.
1 5.
C urre nt acti v e alc o h ol or dr u g a b use. 
1 6.
K n o w n hist or y of H u m a n I m m u n o deficie nc y Vir us ( HI V) i nfecti o n.
1 7.
K n o w n hist or y of c hr o ni c viral he patitis.
1 8.
A b n or mal li ver f u ncti o n ( A L T/ A S T > 1 0 ti mes t he u p per refere nce ra n ge) a n d/ or 
wit h o ut a re versi ble, i de ntifia ble ca use.
1 9.
K n o w n h y p erse nsiti vit y t o b o vi ne pr o d ucts.
2 0.
K n o w n h y p erse nsiti vit y t o di met h yl s ulf o xi d e ( D M S O).
2 1.
U nc o ntr olle d dia betes ( H b A 1c > 9. 0).
2 2. I n a bilit y t o c o m pl y wit h pr ot oc ol-relat e d pr oce d ures, i ncl u di n g re q uire d st u d y visits.
2 3.
A n y c o n diti o n or ot h er reas o n t hat, i n t he o pi ni o n of t he I n vesti gat or or M e dical 
M o nit or, w o ul d re n der t h e s u bject u ns uita ble f or t he st u d y.
2 4.
C urre ntl y recei vi n g i n v esti gati o nal treat me nt o n a n ot her cli nical st u d y or e x pa n de d 
access pr ot o c ol, i ncl u di n g a n y of t he f oll o wi n g:
•
Recei ve d i n vesti gati o nal i nter ve nti o n wit hi n 3 0 da ys pri or t o ra n d o mizati o n
•
Treat m e nt a n d/ or a n i nc o m plete f oll o w- u p t o treat me nt wit h a n y i n vesti gati o nal cell 
base d t h era p y wit hi n 6 m o nt hs pri or t o ra n d o miz ati o n
•
Acti ve partici pati o n i n ot her res ear c h t h era p y f or car di o vasc ular re pair/re ge nerati o n


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 7 of 1 1 1
Test Pr o d u ct, D ose, a n d M o de of A d mi nistr ati o n:
C A P- 1 0 0 2 is a n i n vesti gati o nal pr o d uct c o nsisti n g of all o ge neic car di os p h ere- d eri ve d cells 
( C D Cs). Eac h d ose of C A P- 1 0 0 2 is s u p plie d as a c o nce ntrate d s us pe nsi o n of 2 5 milli o n 
C D Cs 
I n cases w h ere a d ose of 1 2. 5 milli o n C D Cs 
is utilize d, t he h alf d ose is a d mi nistere d i n a half v ol u me.
All s u bjects ( Gr o u ps 1 a n d 2) assi g n e d t o t he acti v e treat me nt ar m will recei ve a pr ot oc ol-
defi ne d t otal d ose of C A P- 1 0 0 2 cells i nf use d t o t he l eft v e ntricle car diac territ ories (a nteri or, 
lateral, i nferi or/ p osteri or). A si n gle ma xi m u m d ose a d mi nistrati o n of 2 5 M C A P- 1 0 0 2 cells or 
1 2. 5 M C A P- 1 0 0 2 cells will be d eli v ere d wit h a T E R U M O Fi necr oss T M M G g ui di n g cat h eter 
t o eac h car diac territ or y (i nte n de d t otal d ose t o all t hree territ ories is 7 5 M cells).
A d diti o nall y, a n i nter me diate was h s ol uti o n is a d mi nistere d t o eac h s u bject bet wee n b ol uses 
of C A P- 1 0 0 2. 
Us u al C are:
S u bjects ra n d o miz e d t o us ual care will recei ve o pti mal me dical t h era p y acc or di n g t o t he 
treat me nt pla n of t h eir pri mar y D M D d oct or a n d site i n vesti gat or, i nf or me d b y t h e e vi de nce 
base d m e dical-t hera p y i n acc or da nce wit h t he “ D M D Care C o nsi derati o ns W or ki n g Gr o u p” 
g ui deli nes f or t he m a na ge me nt of D M D ( B us h b y, Fi n kel et al. 2 0 1 0a, B us h b y, Fi n kel et al. 
2 0 1 0 b).  Us ual care s h o ul d n ot i ncl u de ot her i n vesti gati o nal t h era pies u ntil t he M o nt h 1 2 
st u d y visit is c o m plete d.  
D ur ati o n of F oll o w- U p:
All ra n d o mize d s u bjects will be f oll o w e d o ut t o o ne ye ar p ost- Da y 0. A n n u al f oll o w- u p 
p h o ne calls will be c o n d u cte d f or a n a d diti o nal f o ur years after t his ti me f or s u bjects t h at 
pr o vi de c o nse nt a n d/ or asse nt. T hese a n n u al f oll o w- u p p h o ne c alls will c o nti n ue i n c o ncert 
wit h a s u bject’s n or mal, a n n ual cli nical f oll o w- u p w hic h ma y i ncl u de a n n u al car dia c M RI 
w here cli nicall y i n dicate d.
D ue t o t he s mall size of t he trial p o p ulati o n, c o nti n ue d parti ci pati o n f or all s u bjects is cr ucial 
t o data q ualit y. T h eref ore, n o s u bject will be assesse d as “ L ost t o F oll o w- U p” u nless t he site 
has atte m pte d t o c o ntact t he s u bject ( or p are nt/ g uar dia n) b y p h o ne ( or e mail or ot her s u bject-
preferre d m et h o d of c o m m u nicati o n) o n at least 3 differe nt d a ys, pl us a n att e m pt t o c o ntact 
t he s u bject ( or pare nt/ g uar dia n) b y certifie d mail.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 8 of 1 1 1
Effic ac y Assess me nts:
T he f oll o wi n g will be e val uate d as e x pl orat or y efficac y e n d p oi nts at si x- a n d t w el v e- m o nt h 
f oll o w- u p visits:
1.
Car diac Str uct ural: A bs ol ute a n d relati ve c ha n ge i n para meters meas ure d b y car diac 
M RI, i n cl u di n g:
a.
Left ve ntric ular E F ( %);
b.
Left ve ntric ular e n d- di ast olic v ol u me a n d e n d-s yst olic v ol u me;
c.
Left ve ntric ular str o ke v ol u m e;
d.
Re gi o nal left ve ntric ular f u ncti o n assess me nt;
e.
Left ve ntric ular  L G E e x press e d as a perce nt of left ve ntric ular mass;
f.
Left ve ntric ul ar L G E e x presse d i n gra ms;
g.
Left ve ntric ular via ble m ass e x presse d i n gra ms;
h.
Left ve ntric ular circ u mfere nti al strai n;
i.
N u m ber of left v e ntric ular se g me nts wit h L G E.  
2.
F u ncti o nal: S erial c ha n ges i n Perf or ma nce of U p p er Li m b ( P U L) s cale, s pir o metr y, a n d 
6- mi n ute wal k test ( 6 M W T) w he n dee me d a p pr o priate b y t he I n v esti gat or.
3.
Q ualit y of Life: C h a n ge i n Pe ds Q L ( Pe diatric Q u alit y of Life I n ve nt or y), i n cl u di n g t he 
car dia c m o d ule, a n d P O D CI A d ol esce nt Q uesti o n naire.
4.
Bi o mar kers: Oste o p o nti n, S T 2, I L- 1 0, a n d Galecti n- 3; f or s u bjects pr o vi di n g 
c o nse nt/ asse nt, a d diti o nal sa m ples f or e x pl orat or y a nal ys es will be c oll ecte d, arc hi ve d, 
a n d a vaila ble f or f ut ure t esti n g.
S afet y Assess me nts:
T he st u d y will m o nit or t he pr o p orti o n of s u bjects e x peri e nci n g a n y of t he f oll o wi n g e ve nts 
d uri n g or p ost i ntrac or o n ar y i nf usi o n deli ver y. F or c o m paris o n, t hese s a me e ve nts, as 
a p plica ble, will be m o nit ore d i n us ual care s u bjects o n or after Da y 0, usi n g 9: 0 0 a m o n Da y 
0 as t he refere nce ti me p oi nt:
1.
Ne w TI MI fl o w 0- 2 or TI MI m y o car di al perf usi o n gra de ( T M P G) 0- 2, n ot e d 
i m m e diatel y f oll o wi n g i ntrac or o n ar y i nf usi o n of C A P- 1 0 0 2 a n d persisti n g > 3 mi n after 
cell i nf usi o n, des pite i ntrac or o nar y vas o dil at or a d mi nistrati o n.
2.
S u d de n u ne x pecte d deat h wit hi n 7 2 h o urs of i ntrac or o nar y i nf usi o n defi ne d as occ urri n g 
wit hi n o ne h o ur of s y m pt o m o nset, or u n- wit n esse d deat h i n a p ers o n pre vi o usl y 
o bser ve d t o be w ell wit hi n t he prece di n g 2 4 h o urs wit h o ut a n i de ntifie d ca use.
3.
Maj or a d vers e car diac e v e nts ( M A C E) wit hi n 7 2 h o urs of i ntrac or o nar y i nf usi o n, 
i ncl u di n g deat h, n o n-fat al m y ocar dial i nfarcti o n a n d h os pit aliz ati o n f or car di o vasc ular 
e ve nt (i ncl u di n g heart fail ure h os pitalizati o ns). E vi de nce of m y ocar dial i nj ur y will be 
assess e d b y a r ule o ut MI car diac e nz y m e pr ot o c ol perf or me d f oll o wi n g a d mi nistrati o n 
of C A P- 1 0 0 2. Tr o p o ni n a n d C K- M B will be o btai ne d e ver y 8 h o urs ( ± 3 0 mi n utes) at 
mi ni m u m f or 2 0- 2 4 h o urs after C A P- 1 0 0 2 i nf usi o n.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 9 of 1 1 1
T he st u d y will e val uate t h e f oll o wi n g d uri n g t h e si x a n d t wel ve m o nt h f oll o w- u p peri o d:
1.
S u d de n u ne x pecte d deat h defi n e d as o cc urri n g wit hi n o ne h o ur of s y m pt o m o nset, or 
u n wit nesse d deat h i n a p ers o n pre vi o usl y o bser v e d t o be well wit hi n t he prece di n g 2 4 
h o urs wit h o ut a n i de ntifie d ca use.
2.
Maj or a d vers e car diac e v e nts ( M A C E), i n cl u di n g deat h, n o n-fatal m y o car dial i nfarcti o n, 
h os pitalizati o n f or car di o vasc ular e ve nt (i ncl u di n g heart fail ure h os pit aliz ati o ns), 
e mer ge nc y r o o m treat me nt f or heart fail ure (i ncl u di n g o ut patie nt i nf usi o n), left 
ve ntric ul ar assist de vice or heart tr a ns pla nt.
3.
A n y h os pit aliz ati o n d ue t o a car di o v asc ular ca us e.
4.
A n y i nter-c urre nt car di o v asc ular ill ness w hic h pr ol o n gs h os pitalizati o n. 
5.
De vel o p me nt of, or a n i n creas e i n, t he fre q u e nc y of V T wit h d urati o n of 3 0 sec o n ds or 
l o n ger ascertai ne d b y c o nti n u o us car diac r h yt h m m o nit ori n g.
6.
De vel o p me nt of i ncreas e d a nti- H u m a n Le u k o c yt e A nti ge n ( H L A) a nti b o d y le vels wit h 
de vel o p me nt of se nsitizati o n t o H L A a nti ge ns s p ecific t o t he C A P- 1 0 0 2 C D C d o n or at 
i m m u n ol o gicall y si g nifica nt titers.
7.
Pea k c ha n ge fr o m b aseli ne i n tr o p o ni n a n d C K- M B le vels f oll o wi n g C A P- 1 0 0 2 i nf usi o n.
Us u al C are S u bjects – C A P- 1 0 0 2 Access P ost- St u d y:
If t he a v aila ble e vi de n ce s u g gests a n a p pr o priate ris k/ be nefit pr ofile f or t his pr o d uct, 
Ca pric or ma y ( wit h D S M B a gree me nt) o p e n a n o pe n-la bel e xte nsi o n pr ot oc ol t o ma ke C A P-
1 0 0 2 a vaila ble f or Us ual Care s u bjects after t he y c o m plete t h e 1 2- m o nt h st u d y ass ess me nt 
peri o d.  
St atistic al Met h o ds:
Ra n d o mizati o n: A ra n d o mizati o n all ocati o n al g orit h m will be a p plie d b y s u bject s o t h at t h e 
treat me nt all ocati o n of C A P- 1 0 0 2: place b o is 1: 1.
A nal ysis P o p ulati o ns:
•
I nte nt t o Tre at (I T T) P o p ul ati o n: All s u bjects ra n d o mize d. S u bjects will be s u m marize d 
a n d a nal yz e d per t h eir ra n d o mizati o n assi g n me nt, re gar dl ess of t he treat m e nt ( C A P- 1 0 0 2
or us ual care) act u all y recei v e d.
•
M o difie d I T T ( mI T T) P o p ul ati o n : S u bjects i n t he C A P- 1 0 0 2 treat me nt gr o u p w h o 
recei v e d t he I P, a n d all s u bjects i n t he us ual car e treat me nt gr o u p w h o re m ai n o n st u d y as 
of 9: 0 0 a m (s u bject’s ti me z o ne) o n Da y 0. S u bjects will be s u m marize d a n d a nal yze d p er 
t heir ra n d o miz ati o n assi g n me nt, re gar dl ess of t he treat m e nt ( C A P- 1 0 0 2 or us u al care) 
act uall y recei ve d.
•
Per Pr ot oc ol P o p ul ati o n : S u bjects wit h n o maj or pr ot oc ol vi olati o ns. T he list of s u bjects 
wit h maj or pr ot o c ol vi olati o ns will be c o m pile d pri or t o data base l o c k. 
•
S afety P o p ul ati o n : S u bjects ra n d o mi ze d t o C A P- 1 0 0 2 treat me nt w h o recei v e d t h e I P, a n d 
all s u bjects i n t he us ual care tr eat m e nt gr o u p w h o re m ai n o n st u d y as of 9: 0 0 a m 
(s u bject’s ti m e z o ne) o n Da y 0. S u bjects will be s u m marize d a n d a nal yz e d per treat me nt 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 1 0 of 1 1 1
act uall y recei ve d, re gar dless of t heir ra n d o mizati o n assi g n m e nt.
Efficac y A nal yses:
T he pri mar y a nal ysis of efficac y will be perf or me d f or t he mI T T P o p ulati o n as defi n e d 
a b o ve. A d diti o nal a nal ys es will be defi ne d i n t he St atistical A nal ysis Pl a n ( S A P).
Car diac str uct ural res ults will be s u m marize d f or t he i nter ve nti o n a n d c o ntr ol gr o u ps 
f or eac h visit at w hic h t he y are p erf or me d. A bs ol ute a n d relati ve c ha n ges c o m pare d t o 
baseli n e will be s u m mari z e d usi n g descri pti ve statistics.
F u ncti o nal a n d m o bilit y val ues will be s u m m ariz e d usi n g descri pti ve statistics a n d 
c ha n ges fr o m baseli n e will be c o m pare d b et wee n gr o u ps.
I m pr o v e me nts i n q ualit y of life para meters will be liste d a n d s u m m ariz e d usi n g 
descri pti ve statistics a n d c o m p are d b et wee n gr o u ps.
Bi o mar ker res ults f or Ost e o p o nti n, S T 2, I L- 1 0, a n d Galecti n- 3 will be liste d a n d 
s u m marize d usi n g descri pti ve statistics.  
Safet y A nal ysis:
T he pri mar y a nal ysis of safet y will be perf or me d o n t he S afet y P o p ulati o n as defi ne d 
a b o ve. A d diti o nal a nal ys es will be defi ne d i n t he S A P. Safet y a n d t olera bilit y of 
i ntrac or o nar y i nf usi o n of C A P- 1 0 0 2 will be e val uate d b y t he occ urre nce of re d u cti o n 
i n TI MI fl o w a n d maj or car diac e ve nts, fre q u e nc y a n d se verit y of a d vers e e ve nts, a n d 
b y c h a n ges fr o m baseli ne i n la b orat or y ass ess me nts, vital si g ns, p h ysical 
e x a mi nati o n, a n d E C G.
Missi n g Dat a:
Ha n dli n g of missi n g data will be detaile d i n t he S A P.
D ate of O ri gi n al A p pr o ve d P r ot oc ol: 0 1 M a y 2 0 1 5
D ate of M ost R ece nt P r ot oc ol A me n d me nt (if a p pli c a bl e):
2 9 Fe br uar y 2 0 1 6
Pre p are d i n: Micr os oft
W or d 2 0 1 0


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 1 1 of 1 1 1
T A B L E O F C O N T E N T S
S Y N O P SI S ................................................................................................................................. 2
T A B L E O F C O N T E N T S ......................................................................................................... 1 1
LI S T O F I N- T E X T T A B L E S .................................................................................................. 1 5
LI S T O F I N- T E X T FI G U R E S................................................................................................. 1 5
LI S T O F A P P E N DI C E S .......................................................................................................... 1 5
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 .......................................... 1 6
1
I N T R O D U C TI O N ........................................................................................................... 2 1
.......... 2 2
.......... 2 3
.......... 2 3
.......... 2 4
.......... 2 5
..... 2 6
..... 2 6
..... 2 7
..... 2 9
..... 3 0
..... 3 2
..... 3 2
..... 3 3
..... 3 4
..... 3 4
..... 3 5
..... 3 5
..... 3 5
..... 3 7
..... 3 7
..... 3 7
..... 3 8
1. 3 
I nf or mati o n o n C A P- 1 0 0 2 ..................................................................................... 3 8
 
3 9
1. 5 
St u d y P o p ulati o n .................................................................................................... 4 0
1. 6 
C ar diac Ma g n etic Res o n a nce I m a gi n g .................................................................. 4 0
1. 7 
P ote ntial Ris ks a n d Be nefits .................................................................................. 4 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 1 2 of 1 1 1
2
S T U D Y O BJ E C TI V E S .................................................................................................... 4 3
2. 1 
S afet y O bjecti v e ..................................................................................................... 4 3
2. 2 
Efficac y O bjecti ve ................................................................................................. 4 3
3
I N V E S TI G A TI O N A L P L A N .......................................................................................... 4 4
3. 1  
O verall St u d y Desi g n a n d Pl a n .............................................................................. 4 4
3. 2 
E x pl orat or y Effi cac y E n d p oi nts ............................................................................. 4 6
3. 3 
S afet y M o nit ori n g .................................................................................................. 4 7
3. 4 
R ati o nale f or St u d y D esi g n a n d C o ntr ol Gr o u p ..................................................... 4 8
3. 5 
St u d y D urati o n a n d Dates ...................................................................................... 4 8
4
S T U D Y P O P U L A TI O N S E L E C TI O N ........................................................................... 4 9
4. 1 
St u d y P o p ulati o n .................................................................................................... 4 9
4. 2 
I n cl usi o n Criteria ................................................................................................... 4 9
4. 3 
E x cl usi o n Criteria .................................................................................................. 4 9
5
S T U D Y T R E A T M E N T( S) .............................................................................................. 5 2
5. 1 
I n v esti gati o nal Pr o d uct .......................................................................................... 5 2
 
5 2
5. 1. 2  
D S A Scree ni n g............................................................................................. 5 2
 
5 3
5. 2  
Us ual Care .............................................................................................................. 5 3
5. 2. 1 
C A P- 1 0 0 2 Access P ost- St u d y...................................................................... 5 3
5. 3 
R a n d o mi zati o n ....................................................................................................... 5 3
5. 4 
C o nc o mita nt T hera p y............................................................................................. 5 3
5. 5 
Pri or T hera p y E x cl usi o ns/ Pr o hi bite d Me dicati o ns ................................................ 5 4
5. 6 
Treat me nt C o m plia nce ........................................................................................... 5 4
 
5 4
 
5 4
5. 9 
I n v esti gati o nal Pr o d uct R ete nti o n at St u d y Site .................................................... 5 5
6
S T U D Y P R O C E D U R E S ................................................................................................. 5 6
6. 1 
I nf or me d C o nse nt................................................................................................... 5 6
6. 2  
M e dical Hist or y & C o n c o mita nt Me dicati o ns ....................................................... 5 7
6. 3 
C ar diac a n d Li mit e d P h ysical E x a mi nati o ns ......................................................... 5 7
6. 4  
Vital Si g ns .............................................................................................................. 5 7
6. 5 
Cli nical La b orat or y Tests ....................................................................................... 5 7
6. 5. 1 
La b orat or y Para meters ................................................................................. 5 7
6. 5. 2 
S a m ple C ollecti o n, St ora ge, a n d S hi p pi n g .................................................. 5 7
6. 6 
1 2- Lea d E C G ......................................................................................................... 5 8
6. 7 
C o nti n u o us Car diac R h yt h m M o nit ori n g............................................................... 5 8


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 1 3 of 1 1 1
6. 8  
M a g n etic Res o na nce I ma gi n g ................................................................................ 5 9
6. 8. 1 
Ci ne I m a gi n g Pr ot oc ol ................................................................................. 5 9
6. 8. 2  
D ela ye d C o ntrast- E n h a nce me nt Pr ot oc ol .................................................... 5 9
6. 8. 3 
I ma ge A nal ysis............................................................................................. 5 9
6. 8. 4  
Hist orical Car diac M RI ................................................................................ 5 9
6. 9 
Cli nical F u ncti o n a n d Q u alit y of Lif e Meas ures.................................................... 6 0
6. 1 0
I nf usi o n Pr oce d ure ................................................................................................. 6 0
6. 1 0. 1
C A P- 1 0 0 2 I nf usi o n ...................................................................................... 6 0
6. 1 0. 2
I nf usi o n Pr oce d ure St o p pi n g Criteria .......................................................... 6 1
7
S T U D Y A C TI VI TI E S ..................................................................................................... 6 3
7. 1 
S cree ni n g Visit ....................................................................................................... 6 3
7. 2 
R a n d o mi zati o n, Da y 0, a n d Da y 1 ......................................................................... 6 4
7. 3  
D a y 3 P h o ne Visit .................................................................................................. 6 5
7. 4  
W ee k 2 Visit ( Da y 1 4 ± 3 da ys) ............................................................................. 6 5
7. 5  
W ee k 6 Visit ( Da y 4 0 ± 7 da ys) ............................................................................. 6 6
7. 6  
M o nt h 3 Visit ( Da y 9 0 ± 7 da ys) ........................................................................... 6 6
7. 7  
M o nt h 6 Visit ( Da y 1 8 0 ± 1 4 da ys) ....................................................................... 6 7
7. 8  
M o nt h 1 2 Visit ( Da y 3 6 0 ± 3 0 da ys) ..................................................................... 6 8
7. 9  
A n n ual F oll o w- u p P h o ne Call ............................................................................... 6 8
7. 1 0
Re m o val of Patie nts fr o m t h e Trial or St u d y Dr u g ................................................ 6 8
7. 1 1
Earl y T er mi n ati o n Pr oce d ures ............................................................................... 6 9
7. 1 2
L ost t o F oll o w- U p .................................................................................................. 6 9
7. 1 3
A d verse E v e nts Assess me nts ................................................................................. 7 0
7. 1 3. 1
Perf or mi n g A d vers e E ve nts Assess me nts .................................................... 7 0
7. 1 3. 2
Ti mi n g .......................................................................................................... 7 1
7. 1 3. 3
Se verit y ........................................................................................................ 7 1
7. 1 3. 4
R elati o ns hi p ................................................................................................. 7 1
7. 1 3. 5
E x pecte d ness ................................................................................................ 7 2
7. 1 3. 6
Cli nical Si g nifica nce .................................................................................... 7 3
7. 1 3. 7
Cli nical La b orat or y A d v erse E ve nts ............................................................ 7 3
7. 1 3. 8
Seri o us A d verse E v e nts ............................................................................... 7 4
7. 1 3. 8. 1  
D efi niti o n ........................................................................................... 7 4
7. 1 3. 8. 2 
R e p orti n g Seri o us A d v erse E ve nts .................................................... 7 4
7. 1 3. 9
S p o ns or M o nit ori n g of A d vers e E ve nts ....................................................... 7 5
7. 1 3. 1 0
P ost- St u d y A d v erse E v e nts a n d Seri o us A d verse E ve nts ............................ 7 6
8
Q U A LI T Y C O N T R O L A N D A S S U R A N C E ................................................................. 7 6
9
P L A N N E D S T A TI S TI C A L M E T H O D S ........................................................................ 7 7
9. 1  
G e neral C o nsi derati o ns .......................................................................................... 7 7
9. 2  
D eter mi nati o n of Sa m ple Si ze ............................................................................... 7 7


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 1 4 of 1 1 1
9. 3  
A nal ysis P o p ulati o ns .............................................................................................. 7 7
9. 4 
Efficac y A nal ysis ................................................................................................... 7 7
9. 4. 1 
C ar diac M RI, M o bilit y, a n d Q ualit y of Life Para meters ............................. 7 7
9. 4. 2 
Bi o mar kers ................................................................................................... 7 8
9. 5 
S afet y A nal ysis ...................................................................................................... 7 8
9. 5. 1 
S afet y E n d p oi nts .......................................................................................... 7 8
9. 5. 2  
A d verse E v e nts ............................................................................................ 7 8
9. 5. 3 
La b orat or y E v al uati o ns ................................................................................ 7 8
9. 6  
Missi n g Data .......................................................................................................... 7 8
9. 7 
St u d y St o p pi n g R ules ............................................................................................. 7 8
1 0  I N D E P E N D E N T O V E R SI G H T C O M MI T T E E S ........................................................... 7 9
1 0. 1
Cli nical E ve nts C o m mittee ( C E C) ......................................................................... 7 9
1 0. 2
Data Safet y M o nit ori n g B oar d ( D S M B) ................................................................ 7 9
1 1  A D MI NI S T R A TI V E C O N SI D E R A TI O N S .................................................................... 8 0
1 1. 1
I n v esti gat ors a n d St u d y A d mi nistrati ve Str uct ure ................................................. 8 0
1 1. 2
I nstit uti o nal Re vie w B oar d (I R B) A p pr o v al .......................................................... 8 0
1 1. 3
Et hical C o n d uct of t h e St u d y ................................................................................. 8 1
1 1. 4
S u bject I nf or mati o n, C o nse nt, a n d Asse nt ............................................................. 8 1
1 1. 5
S u bject C o nfi d e nti alit y .......................................................................................... 8 1
1 1. 6
St u d y M o nit ori n g ................................................................................................... 8 2
1 1. 7
Case R e p ort F or ms a n d St u d y Rec or ds ................................................................. 8 2
1 1. 8
Pr ot oc ol Vi olati o ns/ D e viati o ns .............................................................................. 8 3
1 1. 9
Access t o S o urce D oc u m e ntati o n .......................................................................... 8 3
1 1. 1 0
Data Ge n erati o n a n d A nal ysis ............................................................................... 8 3
1 1. 1 1
Data Rete nti o n ....................................................................................................... 8 3
1 1. 1 2
Fi n a ncial Discl os ure............................................................................................... 8 4
1 1. 1 3
P u blicati o n, Use a n d Discl os ure P olic y ................................................................. 8 4
1 2  R E F E R E N C E LI S T ......................................................................................................... 8 5
A p pe n di x 1  
Sc he d ule of E ve nts ............................................................................. 8 9
A p pe n di x 2  
Cli nical La b orat or y T ests ................................................................... 9 1
A p pe n di x 3  
Pr o hi bit e d Pri or Me dicati o ns ............................................................. 9 2
A p pe n di x 4  
A me n d me nt 3 C ha n ges  ( Pr ot oc ol Versi o n 1 8 J ul y 2 0 1 6) ................ 9 7
A p pe n di x 5  
A me n d me nt 2 C ha n ges  ( Pr ot oc ol Versi o n 2 9 Fe br uar y 2 0 1 6) ......... 9 9
A p pe n di x 6  
A me n d me nt 1 C ha n ges  ( Pr ot oc ol Versi o n 2 7 J a n uar y 2 0 1 6) ......... 1 0 6
A p pe n di x 7  
S p o ns or Si g nat ure ............................................................................ 1 1 0
A p pe n di x 8  
I n v esti gat or’s Si g n at ure ................................................................... 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 1 5 of 1 1 1
LI S T O F I N- T E X T T A B L E S
Ta ble 1.
S u m mar y of E x p os ure b y St u d y ....................................................................... 3 2
Ta ble 2.
L ocal La b orat or y T esti n g, Da y 0 a n d D a y 1 ( C A P- 1 0 0 2 Ar m O nl y) ............... 5 8
Ta ble 3.
Per- Visit Mi ni m u m C o nti n u o us Car diac M o nit ori n g D urati o ns ...................... 5 9
LI S T O F I N- T E X T FI G U R E S
.... 2 3
.... 2 4
.... 2 5
.... 2 6
.... 2 8
.... 2 9
.... 3 1
.... 3 6
Fi g ure 9.
R elati o ns hi p bet wee n m y ocar dial fi br osis, ej ecti o n fracti o n, a n d a ge i n 
D M D patie nts .................................................................................................... 4 1
Fi g ure 1 0. Sc he matic of t h e st u d y d esi g n ........................................................................... 4 6
LI S T O F A P P E N DI C E S
A p pe n di x 1  
Sc he d ule of E ve nts ............................................................................. 8 9
A p pe n di x 2  
Cli nical La b orat or y T ests ................................................................... 9 1
A p pe n di x 3  
Pr o hi bit e d Pri or Me dicati o ns ............................................................. 9 2
A p pe n di x 4  
A me n d me nt 3 C ha n ges  ( Pr ot oc ol Versi o n 1 8 J ul y 2 0 1 6) ................ 9 7
A p pe n di x 5  
A me n d me nt 2 C ha n ges  ( Pr ot oc ol Versi o n 2 9 Fe br uar y 2 0 1 6) ......... 9 9
A p pe n di x 6  
A me n d me nt 1 C ha n ges  ( Pr ot oc ol Versi o n 2 7 J a n uar y 2 0 1 6) ......... 1 0 6
A p pe n di x 7  
S p o ns or Si g nat ure ............................................................................ 1 1 0
A p pe n di x 8  
I n v esti gat or’s Si g n at ure ................................................................... 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 1 6 of 1 1 1
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
6 M W T
6- Mi n ute Wal k Test
µl
Micr oliter
A D C
A di p ose- Deri ve d Cell
A E
A d verse E ve nt
A F
Asse nt F or m
A L B
Al b u mi n
A L K- P
Al kali ne p h os p hatase
A L T
Ala ni ne a mi n otra nsferas e (s a me as S G P T) 
A MI
Ac ute M y ocar dial I nfarcti o n
A S T
As partate a mi n otra nsferase (sa me as S G O T) 
At m
At m os p heres
B P
Bl o o d Press ure
B M M N C 
B o ne Marr o w M o n o n uclear Cell
B U N
Bl o o d urea nitr o ge n
C
Celsi us
C C U
Criti cal ( or C or o nar y) Care U nit
C D C
Car di os p here Deri ve d Cell
C E C
Cli nical E ve nts C o m mittee
C F R
C o de of Fe deral Re g ulati o ns 
C H F
C o n gesti ve Heart Fail ure
C K- M B 
Creati n e p h os p h o ki nase M B is oe nz y me
C M V
C yt o me gal o vir us
C R F
Case Re p ort F or m
C R O
C o ntract Researc h Or ga nizati o n
C S
Cli ni call y Si g nifica nt
C S C
Car diac St e m Cell
C T
C o m p uterize d T o m o gra p h y
D C M
Dilate d Car di o m y o pat h y


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 1 7 of 1 1 1
D M D
D uc he n ne M usc ular D ystr o p h y
D M S O
Di met h yl S ulf o xi de
D S A
D o n or- S pecific A nti b o d y 
D S M B
Data a n d Safet y M o nit ori n g B oar d
E B V
E pstei n- Barr Vir us
E C G
Electr ocar di o gra m
E D C
El ectr o nic Dat a Ca pt ure
E D V
E n d- Diast olic V ol u me
E F
Ej ecti o n Fracti o n
E LI S p ot 
E nz y me- Li n ke d I m m u n os or be nt S p ot
E S R
E x pe dite d Safet y Re p ort
E S V
E n d- S yst olic V ol u me
F
Fa hre n heit
F D A
F o o d a n d Dr u g A d mi nistrati o n
G C P
G o o d Cli nical Practice 
G F R
Gl o mer ular Filtrati o n Rate 
H Bs A g
He patitis B S urface A nti ge n 
Hct
He mat ocrit
H C V
He patitis C Vir us
H F
Heart Fail ure
H g b
He m o gl o bi n
H b A 1c
Gl yc os yl ate d He m o gl o bi n
HI P A A
Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act
HI V
H u ma n I m m u n o deficie nc y Vir us
H L A
H u ma n Le u k oc yte A nti ge n
H R
Heart Rate
I C D
I m pla nta ble Car di o verter Defi brill at or
I C F
I nf or me d C o nse nt F or m
I C H
I nter nati o nal C o nfere n ce o n Har m o nisati o n


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 1 8 of 1 1 1
I E C
I n de pe n de nt Et hics C o m mittee
I g G
I m m u n o gl o b uli n G 
I g M
I m m u n o gl o b uli n M
I L- 1 0
I nterle u ki n 1 0
I N D
I n vesti gati o nal Ne w Dr u g
I N R
I nter nati o nal N or mali ze d Rati o
I P
I n vesti gati o nal Pr o d uct
i P S Cs
I n d uce d pl uri p ote nt ste m cells
I R B
I nstit uti o nal Re vie w B oar d
I S
I nfarct Size
I T T
I nte nt-t o- Treat (ra n d o mize d p o p ulati o n)
K
P otassi u m
K g
Kil o gra m
L A D
Left A nteri or Desce n di n g 
L C X
Left Circ u mfle x
L D H
Lactate de h y dr o ge nase 
L G E
Late ga d oli ni u m e n ha nce me nt
L V
Left Ve ntricle
L V A D
Left Ve ntric ular Assist De vice 
L V E F
Left Ve ntric ular Ej ecti o n Fracti o n 
M
Milli o n
M A C E
Maj or A d verse Car diac E ve nt
M C B
Master cell ba n k
Mc g
Micr o gra m
M C H
Mea n c or p usc ular he m o gl o bi n
M C H C
Mea n c or p usc ular he m o gl o bi n c o nce ntrati o n
M C V
Mea n c or p usc ular v ol u me
Me d D R A  
M e dical Dicti o nar y f or Re g ulat or y Acti vities
M FI
Mea n Fl u oresce nce I nte nsit y


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 1 9 of 1 1 1
MI
M y ocar dial I nfarcti o n
Mi n
Mi n ute 
m L
Milliliter
M L H F Q  
Mi n nes ota Li vi n g wit h Heart Fail ure Q uesti o n naire
M m
Milli meters 
m m ol
Milli m ole
M o A
Mec ha nis m of Acti o n
M O P
Ma n ual of Pr oce d ures (??)
M RI
Ma g netic Res o na nce I ma gi n g
M S C
Mese nc h y mal St e m Cell
Na
S o di u m
N C S
N ot Cli nicall y Si g nifica nt
N H L BI
Nati o nal Heart, L u n g a n d Bl o o d I nstit ute
N T- pr o B N P  
N-ter mi nal pr o- h or m o ne brai n natri ureti c pe pti de
N Y H A
Ne w Y or k Heart Ass ociati o n
O C R
O x y ge n C o ns u m pti o n Rate
O T W
O ver T he Wire
P
Pr o ba bilit y
P CI
Perc uta ne o us C or o nar y I nter ve nti o n
Pe ds Q L 
Pe diatric Q ualit y of Life I n ve nt or y
P G A
Patie nt Gl o bal Assess me nt
P O D CI
Pe diatric O ut c o mes Data C ollecti o n I nstr u me nt
P R A
Pa nel Reacti ve A nti b o di es
P S P
Patie nt S pecific Pr o ba bilit y
P T T
Acti vate d Partial T hr o m b o pl asti n Ti me
P U L
Perf or ma nce of U p per Li m b
Q o L
Q ualit y of Life
R B C
Re d bl o o d cell
R C A
Ri g ht C or o nar y Arter y


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 2 0 of 1 1 1
R N A
Ri b o n ucleic Aci d
R R
Res pirati o n Rate
S A B
Si n gle-a nti ge n bea d
S A E
Seri o us A d verse E ve nt 
S A P
St atistical A nal ysis Pla n 
S D
Sta n dar d De vi ati o n
S E M
Sta n dar d Err or of t he Mea n
S F- 3 6
S h ort F or m ( healt h s ur ve y) - 3 6 q uesti o ns 
S G O T
Ser u m Gl uta mi c O xal oacetic Tra nsa mi nase 
S G P T
Ser u m Gl uta mi c P yr u vi c Tra nsa mi n ase 
S P R O
Seri o us Pr oce d ure Relate d O utc o me
S T 2
Car diac Stress Bi o mar ker (I L- 1 Rece pt or Fa mil y; bi n ds I L- 3 3)
T E A E
Treat me nt- E mer ge nt A d verse E ve nt
TI MI
T hr o m b ol ysis I n M y ocar dial I nfarcti o n
T M P G
TI MI M y ocar dial Perf usi o n Gra de
T nI
Tr o p o ni n I
U A
Uri nal ysis
V F
Ve ntric ular Fi brillati o n
V G E F
Vasc ular E n d ot helial Gr o wt h Fact or
V T
Ve ntric ular T ac h ycar dia
W B C
W hite Bl o o d Cell
W P AI: S H P
W or k Pr o d ucti vit y a n d Acti vit y I m pair me nt Q uesti o n naire: S pecific Healt h 
Pr o ble m


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 2 1 of 1 1 1
1
I N T R O D U C TI O N
D uc he n ne M us c ular D ystr o p h y ( D M D) is a p e diatri c o nset, ge netic disease i n w hi c h patie nts 
lac k d ystr o p hi n, a pr otei n critical f or sta bilizi n g m uscle cell me m bra nes. Affecti n g 1 i n 
3, 5 0 0- 5, 5 0 0 male birt hs, D M D acc o u nts f or 8 0 % of all cases of m usc ular d ystr o p h y. Patie nts 
e x perie nce pr o gressi ve s keletal m uscle wea k ness a n d l oss of a m b ulati o n b y a ge 1 5, e ve nt ual 
res pirat or y a n d car diac fail ure, a n d a n a b bre viate d lifes pa n a vera gi n g o nl y t hree deca d es 
( B us h b y, Fi n kel et al. 2 0 1 0a, B us h b y, Fi n kel et al. 2 0 1 0 b). Wit h c ortic oster oi ds a n d n o n-
i n vasi ve ve ntilati o n, heart fail ure has e m er ge d as t he m ai n ca use of deat h. Yet t h e 
o ver w h el mi n g maj orit y of cli nical trials i n D M D h a ve f oc us e d o n s keletal rat her t ha n c ar diac 
m uscle disease. Wit h o ut a n y f u ncti o nal d ystr o p hi n pr otei n, car di o m y oc yt es e x perie nce a 
disr u pti o n of me m bra ne i nte grit y, lea di n g t o a n o v erl o a d of i ntracell ular cal ci u m, l ea di n g t o 
car di o m y oc yte d eat h. Cell deat h is acc o m pa nie d b y l ocal i nfla m mati o n w hic h ser ves as a 
s o urce of o xi d ati v e stress f or t he re mai ni n g car di o m y oc ytes ( S hir o k o va a n d Ni g gli 2 0 1 3). 
T hese f oci of cell deat h are ofte n e x perie nce d b y p atie nts as micr oi nfar cts, a n d acc o m p a ni e d 
b y c h est pai n a n d t h e release of car dia c e nz y m es, cli nical hall mar ks of MI. T his a m plif yi n g 
pr ocess tri g gers pr o gressi ve scar tiss ue d e p ositi o n a n d lea ds e ve nt uall y t o h eart fail ure. 
I m pr o v e me nts i n t he treat me nt of res pirat or y m us cle disease h a ve ele vate d t h e i n e vit a ble 
car di o m y o pat h y t o t he lea di n g ca use of d eat h i n D M D patie nts ( S p ur ne y 2 0 1 1, Passa ma n o, 
Ta glia et al. 2 0 1 2). 
N o s pecific t hera pies c urre ntl y e xist t o treat D M D car di o m y o pat h y. Gi ve n t he gl o b al a n d 
pr o gressi ve nat ure of t h e dis ease, rarel y are t hese patie nts c o nsi dere d f or h eart tra ns pla nt, us e 
of mec ha nical car di ac assist de vices is lar gel y e x peri m e nt al ( R ya n, J efferies et al. 2 0 1 4), a n d 
t he effecti ve ness of t h e t h era pies i n use or i n de vel o p me nt f or D M D o n t he car diac 
ma nifestati o ns of t he disease is ge n erall y a s ec o n dar y c o nsi derati o n. Sta n dar d of care 
c ortic oster oi d use i n D M D patie nts, ai me d at pr ol o n gi n g a m b ulati o n, has b ee n s h o w n t o 
dela y t he pr o gressi o n of heart disease w he n its us e is i nitiate d pri or t o t he o nset of car di ac 
d ysf u n cti o n ( Mar k h a m, Ki n nett et al. 2 0 0 8). H o w e ver, defi niti ve e vi de nce f or t his a n d t he 
o pti m al ster oi d d osi n g re gi me n are still u n der i n vesti gati o n (e. g. N C T 0 1 6 0 3 4 0 7). T he use of 
a n gi ote nsi n-c o n verti n g e nz y m e i n hi bit ors, a n gi ote nsi n rece pt or bl oc k ers, a n d beta bl oc kers 
o n t o p of ster oi ds has bec o me sta n dar d t hera p y f or t hese patie nts o nce car di ac d ysf u ncti o n 
has set i n (Jefferies, Ei de m et al. 2 0 0 5, Alle n, Fla ni ga n et al. 2 0 1 3). H o w e v er, pr o gressi ve 
decli n e of car di ac f u ncti o n still occ urs i n t h e face of w hat ca n b e c o nsi dere d c urre nt ma xi mal 
me dical ma na ge m e nt ( H or, Maz ur et al. 2 0 1 1). M ost n o vel D M D t hera pies ha ve bee n 
a d va nce d i n de vel o p me nt o n t he b asis of s keletal m uscle effects, a n d h a ve a re d uce d or 
u nc haracterize d effect o n car diac m uscle. Of t h e d o ze ns of rece ntl y c o m plete d or acti ve 
D M D cli nical trials, ver y fe w ha v e a pri mar y car diac e n d p oi nt. 
C A P- 1 0 0 2 is a n i n vesti gati o nal pr o d uct c o nsisti n g of all o ge neic car di os p h ere- d eri ve d cells 
( C D Cs). 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 2 2 of 1 1 1
T he H O P E- D u c he ne P h ase II st u d y will be t he first i n vesti gati o n of C A P- 1 0 0 2 i n male 
s u bjects wit h car di o m y o pat h y sec o n dar y t o D M D a n d t he first trial of t he pr o d uct n ot 
c o n d ucte d e x cl usi v el y i n a d ults. 
    


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 2 3 of 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 2 4 of 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 2 5 of 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 2 6 of 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 2 7 of 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 2 8 of 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 2 9 of 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 3 0 of 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 3 1 of 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 3 2 of 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 3 3 of 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 3 4 of 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 3 5 of 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 3 6 of 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 3 7 of 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 3 8 of 1 1 1
1. 3 
I nf or m ati o n o n C A P- 1 0 0 2
C A P- 1 0 0 2 C D Cs are gr o w n fr o m d o n ors u nrelat e d t o treat me nt reci pie nts. H u ma n Le u k oc yt e 
A nti ge n ( H L A) matc hi n g of t he d o n ors a n d t he s u bjects will n ot be perf or me d. S u bjects will 
be assesse d f or a nti- H L A a nti b o dies at scree ni n g. S u bjects w h o ca n be matc he d (i n t h e se ns e 
t hat n o D S As are prese nt t o o ne or m ore d o n ors) will be ra n d o mize d i nt o t he st u d y. S u bjects 
w h o are mis matc h e d a g ai nst all a vaila ble d o n ors, beca use t he y har b or o ne or m ore a nti- H L A 
a nti b o dies a gai nst eac h d o n or, will be scree n fail ures a n d n ot ra n d o mize d i nt o t his st u d y.  
All ra n d o mize d s u bjects will be m o nit ore d f or de vel o p me nt of i ncrease d a nti- H L A a nti b o d y 
le vels wit h de vel o p me nt of se nsitizati o n t o H L A a nti ge ns s p ecific t o t he C A P- 1 0 0 2 d o n or 
(i.e. D S As).
C A P- 1 0 0 2 is a d mi nistere d as a d ose of 2 5 milli o n cells 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 3 9 of 1 1 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 4 0 of 1 1 1
1. 5 
St u d y P o p ul ati o n 
Car di o m y o pat h y is c urre ntl y t he lea di n g ca use of deat h i n D M D p atie nts ( S p ur ne y 2 0 1 1,
Passa ma n o, Ta glia et al. 2 0 1 2), ha vi n g rece ntl y s u p pla nte d res pirat or y ca us es as a r es ult of 
treat me nt i m pr o v e me nts f or t hat as pect of t he dis ease. Affli cte d pati e nts lac k a f u ncti o nal 
d ystr o p hi n pr otei n a n d e x perie nce pr o gressi ve m uscle wea k n ess starti n g at a n earl y a ge a n d 
ulti m atel y a n a b bre viate d lifes pa n. Gi ve n t he gl o b al a n d pr o gressi ve nat ure of t he disease, 
rarel y are t hes e patie nts c o nsi dere d f or h eart tr a ns pla nt, use of mec ha nical car diac assist 
de vices is lar gel y e x peri me ntal ( R ya n, J efferies et al. 2 0 1 4), a n d t h e effecti v e ness of t h e 
t hera pies i n use or i n d e vel o p me nt f or D M D o n t h e car di ac ma nifestati o ns of t he disease is 
ge n erall y a s ec o n d ar y c o nsi derati o n. C A P- 1 0 0 2 is i nte n de d t o tar get t he car di o m y o pat h y i n 
D M D as o p p ose d t o t he s keletal m y o p at h y. 
1. 6 
C ar di a c M a g n eti c R e s o n a n c e I m a gi n g 
M RI will be use d t o ass ess n u mer o us efficac y e n d p oi nts i n t h e H O P E- D uc he n ne st u d y. 
Car diac M RI is pr o vi n g t o ha ve gre at pr o g n ostic a n d dia g n ostic val u e f or D M D 
car di o m y o pat h y, a n d its use has re veale d s e veral hall mar ks of t h e dis eas e pre vi o usl y 
u n detecta ble b y sta n d ar d ec h ocar di o gra p h y. 
Circ u mfer
cc), assesse d via a n M RI t a g gi n g pr ot oc ol, has bee n s h o w n t o be 
a b n or mal i n y o u n g D M D patie nts wit h still n or mal ejecti o n fracti o n ( E F) a n d n o si g ns of 
m y ocar dial fi br osis, a n d t o w orse n wit h a ge a n d al o n gsi de a decli ne i n E F a n d t he e mer ge n ce 
of m y ocar dial fi br osis ( H or, Wa nsa p ura et al. 2 0 0 9). F urt her m ore, a rece ntl y c o m plete d tri al 
of a mi neral o c ortic oi d rece pt or a nta g o nist use d i n c o nj u ncti o n wit h ma xi mal me dical 
cc e x peri e nce d b y s u bjects wit h s o me de gree of 
m y ocar dial fi br osis pre-e xisti n g at baseli ne c o ul d be atte n uate d wit h i nter ve nti o n, a n d t hat 
cc were acc o m pa ni e d b y i m pr o ve me nts i n E F a n d prece de d b y re d ucti o ns 
i n t h e de gree of m y ocar dial fi br osis prese nt ( Ra m a n, H or et al. 2 0 1 4).  
M y ocar dial fi br osis, ass esse d as late ga d oli ni u m e n ha nce m e nt ( L G E) o n M RI a n d q u a ntifie d 
eit her o n t he basis of se g me ntal i n v ol ve me nt or i n a bs ol ute ter ms, has als o bee n s h o w n t o be 
pre vale nt i n D M D p atie nts, t o i n crease wit h a ge, a n d t o c orrelat e ne gati vel y wit h E F ( H or, 
Ta yl or et al. 2 0 1 3). D ata ill ustrati n g t his relati o ns hi p is s h o w n i n Fi g ure 9. 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 4 1 of 1 1 1
Fi g ur e 9. 
R el ati o n s hi p b et w e e n m y o c ar di al fi br o si s, ej e cti o n fr a cti o n, a n d 
a g e i n D M D p ati e nt s
T he L V E F of L G E ne gati ve ( bl ue dia m o n ds) a n d L G E p ositi ve (re d s q uare) p atie nts are pl otte d a gai nst a ge 
d e m o nstrati n g L G E was ass o ciate d wit h ol d er a ge a n d l o wer L V E F. Fr o m ( H or, T a yl or et al. 2 0 1 3).
1. 7 
P ot e nti al Ri s k s a n d B e n efit s 
Ris ks ass o ciate d wit h a d mi nistrati o n of t he st u d y a ge nt are pri maril y relate d t o placi n g a 
g ui de wire d o w n t he c or o nar y art eries i n or der t o p ositi o n t he i nf usi o n cat h eter. T he ris k of 
c or o n ar y dissecti o n is esti mate d t o be less t ha n 1 % i n t his setti n g (J a nsse ns, D u b ois et al. 
2 0 0 6, Sc hac hi n ger, Er bs et al. 2 0 0 6, Ass m us, Leist ner et al. 2 0 1 4)  
Ot her ris ks of t h e i nf usi o n pr oce d ure i n cl u de t h ose ris ks t hat are p ossi ble wit h dia g n ostic 
c or o n ar y a n gi o gr a p h y. T hese i ncl u de ris ks rel ate d t o i nfecti o n, blee di n g, h y p ote nsi o n, pai n 
a n d  he mat o ma at t he art erial p u nct ure sit e ( 0. 4 %), arr h yt h mia ( 0. 3 8 %), se nsiti vit y or aller g y 
t o ra di o gra p hic c o ntrast ( 0. 3 7 %), e x p os ure t o ra di ati o n, t hr o m b oe m b olis m ( 0. 0 7 %), c o ntrast 
i n d uce d n e p hr o p at h y, m y ocar dial isc h e mia or i nfarcti o n ( 0. 0 5 %). O v erall, t he ris k of a n y 
c o m plicati o n is a p pr o xi matel y 1. 4 %, a n d f or deat h is less t ha n 0. 1 % ( N ot o, J o h ns o n et al. 
1 9 9 1). T hese re p orte d rates of c o m plicati o n i ncl u d e s u bjects wit h si g nifica nt car diac dis ease 
a n d ot her c o m or bi dities.  
C A P- 1 0 0 2 C D Cs are gr o w n fr o m d o nate d h u m a n m y ocar di al tiss ue a n d


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 4 2 of 1 1 1
C o ntrast d ye is use d f or t he a n gi o gra p h y a n d M RI. T here is a s mall ris k of a n aller gic 
reacti o n ca usi n g ras h, itc hi n g, hi ves or w h eezi n g, b ut ver y rarel y ( 0. 0 7 %) are reacti o ns se vere 
( Dill ma n, Ellis et al. 2 0 0 7).  S u bjects will be assesse d f or a n y pre vi o us all er gic reacti o n t o 
c o ntrast pri or t o pr o ce d ures utilizi n g d ye. A nti hista mi ne a n d ster oi d ma y b e use d t o pre-
me dicate s u bjects w h o h a ve a hist or y of s e nsiti vit y or aller g y, acc or di n g t o t he h os pital's
us ual practi ce. T here is als o a s mall ( 5 %) p ossi bilit y of d e vel o pi n g a b n or mal f u ncti o n of t h e 
ki d ne ys ( Katz ber g a n d Ne w h o use 2 0 1 0).  T his a b n or mal ki d ne y f u ncti o n is us uall y 
te m p orar y a n d less li kel y if t here is n o u n derl yi n g ki d ne y f u ncti o n a b n or malit y. A d diti o nall y, 
t he ki d ne y a b n or malit y is ge n erall y res ol ve d b y t h e nat ural eli mi nati o n of t he c o ntrast d ye 
fr o m t he s u bject’s s yste m. Creati ni ne cleara n ce or G F R will b e assesse d pri or t o tests 
re q uiri n g c o ntrast. C o ntrast s ol uti o n a n d ti mi n g of t he test ma y b e a dj uste d i n s u bjects wit h 
i m pair me nt of ki d ne y f u ncti o n. S u bjects will be cl osel y m o nit ore d f or a n y si g ns of aller gic 
reacti o n or decrease i n re nal f u ncti o n as well as a n y ot her si d e effects.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 4 3 of 1 1 1
2
S T U D Y O B J E C TI V E S
2. 1
S af et y O bj e cti v e
T he safet y o bjecti v e of t h e H O P E- D u c he n ne tri al will be t o i n vesti gate t h e safet y a n d 
t olera bilit y of C A P- 1 0 0 2 a d mi nistere d b y m ulti- vessel i ntrac or o n ar y i nf usi o n i n s u bjects wit h 
car di o m y o pat h y sec o n dar y t o D u c he n n e m usc ular d ystr o p h y ( D M D).
2. 2
Effi c a c y O bj e cti v e
T he effi cac y o bj ecti ve of t he H O P E- D u c he n ne tri al will be t o i n vesti gate t he effi cac y of 
C A P- 1 0 0 2 a d mi nistere d b y m ulti- vessel i ntrac or o nar y i nf usi o n i n s u bjects wit h 
car di o m y o pat h y sec o n dar y t o D M D b y st a bilizi n g or i m pr o vi n g car di ac str uct ure, b y 
e val uati n g f u ncti o nal stat us, a n d b y assess me nt of q ualit y of life.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 4 4 of 1 1 1
3
I N V E S TI G A TI O N A L P L A N
3. 1 
O v er all St u d y D e si g n a n d Pl a n 
Male s u bjects wit h car di o m y o pat h y sec o n dar y t o D M D meeti n g all i ncl usi o n a n d n o 
e x cl usi o n criteria will be ra n d o mize d. All s u bjects will be at least 1 2 years of a ge. T h e y will 
be ra n d o mize d i n a 1: 1 ma n ner t o eit h er i ntrac or o n ar y i nf usi o n of C A P- 1 0 0 2 i n t hree 
c or o n ar y arteries s u p pl yi n g t he t hree maj or car di ac territ ories of t h e left ve ntricle of t he heart 
(a nteri or, lat eral, i nferi or/ p osteri or) or us ual care. I n t h e acti ve treat me nt ar m, all t hree maj or 
car dia c territ ories will be treate d (i nf us e d) d uri n g a si n gle pr oce d ure i n a n o pe n-la bel fas hi o n.  
A p pr o xi matel y 2 4, a n d n ot m ore t h a n 3 0, s u bjects will be ra n d o mize d i nt o t h e st u d y, i n t w o 
se q ue nti al e nr oll me nt gr o u ps. Safet y d ata fr o m Gr o u p 1 will u n der g o a Dat a S afet y 
M o nit ori n g B o ar d ( D S M B) re vie w pri or t o i nitiati o n of e nr oll me nt f or Gr o u p 2. 
T he first 6- 8 ra n d o mize d s u bjects will c o m prise Gr o u p 1, a n d will i ncl u de a mi ni m u m of 3 
s u bjects c o m pleti n g i ntrac or o nar y i nf usi o n wit h C A P- 1 0 0 2.  T he D S M B will c o n d uct a 
re vie w of i nteri m safet y data t hr o u g h 7 2 h o urs p ost- Da y 0 f or at least 3 i nf use d s u bjects a n d 
f or at least 6 s u bjects o verall.  
E nr oll me nt of Gr o u p 2 will be gi n per D S M B rec o m me n dati o ns f oll o wi n g t heir re vie w of t he 
7 2 h o ur safet y d ata fr o m Gr o u p 1. Gr o u p 2 will i ncl u de a p pr o xi matel y 1 8 s u bjects. S cree ni n g 
a n d ra n d o mizati o n will c o nti n ue u ntil at t otal of 1 2 s u bjects are i nf us e d wit h C A P- 1 0 0 2 or 3 0 
s u bjects are ra n d o mize d i nt o t he st u d y, w hic he ver c o m es first. 
  
  


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 4 5 of 1 1 1
S u bjects ra n d o miz e d t o recei ve us u al care will c o nti n ue t o be car e d f or a n d treate d i n 
w hate ver m a n ner t h e i n vesti gat or d ee ms m ost a p pr o priate f or t h e s u bject o n a n o n g oi n g 
basis, a n d will recei v e n o i nf usi o n. 
S u bject i nf usi o ns will be sta g gere d b y at least t hree da ys t o all o w f or d etecti o n of ac ute 
pr oce d ure-relate d c o m plicati o ns s h o ul d t he y o cc ur. A d diti o nall y, s u bject i nf usi o ns i n 
Gr o u p 2 will n ot be gi n u ntil at least t w o wee ks aft er t he fi nal i nf usi o n occ urs i n Gr o u p 1, t o 
all o w f or t h e c o m pleti o n of t he Gr o u p 1 safet y dat a re vie w t hr o u g h 7 2 h o urs p ost Da y 0. 
N o scree ni n g pr oce d ures will ta ke place u ntil t h e s u bject is f ull y i nf or me d of t h e researc h a n d 
si g ns t he i nf or m e d c o nse nt or pr o vi des asse nt. S u bjects 1 8 ye ars of a ge or ol der m ust ha ve 
t he a bilit y t o pr o vi de i nf or me d c o nse nt a n d f oll o w- u p wit h pr ot oc ol pr oce d ures. S u bjects at 
least 1 2 years of a ge b ut y o u n ger t ha n 1 8 years of a ge m ust ha ve t he a bilit y t o pr o vi de asse nt 
al o n g wit h t he s u bject’s pare nt or g u ar dia n pr o vi di n g per missi o n f or st u d y partici p ati o n. 
Ra n d o mizati o n will ta ke place wit hi n 3 0 da ys of t he first scree ni n g pr oce d ure. Aft er 
c o m pleti o n of t he scree ni n g pr o ce d ures, eli gi ble s u bjects ra n d o miz e d t o acti ve treat m e nt ar m 
will recei v e C A P- 1 0 0 2 a d mi nistere d via i ntrac or o nar y i nf usi o n o n Da y 0. Da y 0 f or eli gi ble 
s u bjects ra n d o mi ze d t o t he us ual care ar m will occ ur 7 da ys after t he d ate of ra n d o mizati o n, 
a n d a refere nce ti me p oi nt of 9: 0 0 a m o n Da y 0 will be use d i n place of i nf usi o n ti me. All 
ra n d o mize d s u bjects will ha ve a f oll o w- u p t ele p h o ne call o n St u d y D a y 3, a n d st u d y visits at 
Wee ks 2 a n d 6, a n d at M o nt hs 3, 6 a n d 1 2 p ost Da y 0. K e y safet y assess me nts s uc h as 
s u d de n u ne x pecte d deat h, a n d ot h er maj or a d vers e car dia c e ve nts ( M A C E), will be assesse d 
f or all s u bjects, wit h t he e x ce pti o n of t h ose o nl y rele va nt t o s u bjects assi g n e d t o t he acti ve 
treat me nt ar m, s uc h as  n e w TI MI fl o w 0- 2 or TI MI m y ocar dial perf usi o n gra de ( T M P G) 0- 2 
( persisti n g > 3 mi n utes after ter mi nati o n of cell i nf usi o n). Si nce C A P- 1 0 0 2 is all o ge neic,
h u m oral a n d cell ular i m m u ne res p o nses will als o be e val uat e d.   
T he Data a n d Safet y M o nit ori n g B oar d ( D S M B) will meet per c harter, at least se mia n n uall y t o 
re vie w a vaila ble data, a n d will c o n d uct a n i nteri m re vie w of s afet y d ata f or Gr o u p 1 s u bjects 
t hr o u g h 7 2 h o urs p ost- d a y 0.  T he y will re vie w b ot h safet y a n d efficac y data after all s u bjects 
ha ve c o m plete d 6 m o nt hs of f oll o w- u p. 
Fi g ure 1 0 pr o vi d es a sc h e matic re prese ntati o n of t he st u d y d esi g n. F urt her details re gar di n g
s pecific st u d y visits ca n b e f o u n d i n A p pe n di x 1, Sc he d ule of E ve nts .


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 4 6 of 1 1 1
Fi g ur e 1 0.
S c h e m ati c of t h e st u d y d e si g n
3. 2
E x pl or at or y Effi c a c y E n d p oi nt s
E x pl orat or y efficac y e n d p oi nts will be e val uate d at t h e si x- a n d t wel ve- m o nt h f oll o w- u p
visits. T he e x pl orat or y efficac y e n d p oi nts i ncl u de:
1.
Car diac Str uct ural: A bs ol ute a n d relati ve c ha n ge i n para meters meas ure d b y car diac 
M RI, i n cl u di n g:
a.
Left ve ntric ular E F ( %);
b.
Left ve ntric ular e n d- di ast olic v ol u me a n d e n d-s yst olic v ol u me;
c.
Left ve ntric ular str o ke v ol u m e;
d.
Re gi o nal left ve ntric ular f u ncti o n assess me nt;
e.
Left ve ntric ular  L G E e x press e d as a perce nt of left ve ntric ular mass;
f.
Left ve ntric ul ar L G E e x presse d i n gra ms;
g.
Left ve ntric ular via ble m ass e x presse d i n gra ms;
h.
Left ve ntric ular circ u mfere nti al strai n;
i.
N u m ber of left v e ntric ular se g me nts wit h L G E.  
2.
F u ncti o nal: S erial c ha n ges i n Perf or ma nce of U p p er Li m b ( P U L) s cale, s pir o metr y,
a n d 6- mi n ute w al k test ( 6 M W T) w he n dee me d a p pr o priate b y t he I n v esti gat or.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 4 7 of 1 1 1
3.
Q ualit y of Life: C h a n ge i n Pe ds Q L ( Pe diatric Q u alit y of Life I n ve nt or y), i n cl u di n g 
t he car diac m o d ule, a n d P O D CI A d oles ce nt Q u esti o n naire.
4.
Bi o mar kers: Oste o p o nti n, S T 2, I L- 1 0, a n d Galecti n- 3; f or s u bjects pr o vi di n g 
c o nse nt/ asse nt, a d diti o nal sa m ples f or e x pl orat or y a nal ys es will b e c ollecte d, 
arc hi v e d, a n d a vaila bl e f or f ut ure testi n g.
3. 3
S af et y M o nit ori n g
T he st u d y will m o nit or t he pr o p orti o n of s u bjects e x peri e nci n g a n y of t he f oll o wi n g e ve nts 
d uri n g or p ost i ntrac or o n ar y i nf usi o n deli v er y. F or c o m paris o n, t hese sa me e ve nts will be 
m o nit ore d i n us u al care s u bjects usi n g 9: 0 0 a m o n Da y 0 as t he refere n ce ti me p oi nt:
1.
Ne w TI MI fl o w 0- 2 or TI MI m y o car di al perf usi o n gra de ( T M P G) 0- 2, n ot e d 
i m m e diatel y f oll o wi n g i ntrac or o n ar y i nf usi o n of C A P- 1 0 0 2 a n d persisti n g > 3 mi n 
after cell i nf usi o n, des pite i ntrac or o n ar y vas o dilat or a d mi nistrati o n.
2.
S u d de n u ne x pecte d deat h wit hi n 7 2 h o urs of i ntrac or o nar y i nf usi o n defi ne d as 
occ urri n g wit hi n o ne h o ur of s y m pt o m o nset, or u n- wit nesse d deat h i n a p ers o n 
pre vi o usl y o bs er ve d t o b e w ell wit hi n t he prece di n g 2 4 h o urs wit h o ut a n i de ntifie d 
ca use.
3.
Maj or a d vers e car diac e v e nts ( M A C E) wit hi n 7 2 h o urs of i ntrac or o nar y i nf usi o n, 
i ncl u di n g deat h, n o n-fat al m y ocar dial i nfarcti o n a n d h os pit aliz ati o n f or 
car di o vasc ular e v e nt (i ncl u di n g heart fail ure h os pitalizati o ns). E vi de nce of 
m y ocar dial i nj ur y will be assesse d b y a r ul e o ut MI car di ac e nz y me pr ot oc ol 
perf or me d f oll o wi n g a d mi nistrati o n of C A P- 1 0 0 2. Tr o p o ni n a n d C K- M B will be 
o btai ne d e ver y 8 h o urs ( ± 3 0 mi n utes) at mi ni m u m f or 2 0- 2 4 h o urs after C A P- 1 0 0 2
i nf usi o n.
T he st u d y will e val uate t h e f oll o wi n g d uri n g t h e si x a n d t wel ve m o nt h f oll o w- u p peri o d:
1.
S u d de n u ne x pecte d deat h defi n e d as o cc urri n g wit hi n o ne h o ur of s y m pt o m o nset, or 
u n wit nesse d deat h i n a p ers o n pre vi o usl y o bser v e d t o be well wit hi n t he prece di n g 2 4 
h o urs wit h o ut a n i de ntifie d ca use.
2.
Maj or a d vers e car diac e v e nts ( M A C E), i n cl u di n g deat h, n o n-fatal m y o car dial 
i nfarcti o n, h os pitalizati o n f or car di o vasc ular e ve nt (i ncl u di n g heart fail ure 
h os pitalizati o ns), e mer ge nc y r o o m treat m e nt f or h eart fail ure (i ncl u di n g o ut p atie nt 
i nf usi o n), left ve ntric ul ar assist de vice or heart tra ns pla nt.
3.
A n y h os pit aliz ati o n d ue t o a car di o v asc ular ca us e.
4.
A n y i nter-c urre nt car di o v asc ular ill ness w hic h pr ol o n gs h os pitalizati o n. 
5.
De vel o p me nt of, or a n i n creas e i n t he fre q ue n c y of V T wit h d urati o n of 3 0 sec o n ds or 
l o n ger ascertai ne d b y c o nti n u o us car diac r h yt h m m o nit ori n g. 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 4 8 of 1 1 1
6.
De vel o p me nt of i ncreas e d a nti- H u m a n Le u k o c yt e A nti ge n ( H L A) a nti b o d y le vels 
wit h de vel o p me nt of se nsiti zati o n t o H L A a nti ge ns s pecific t o t he C A P- 1 0 0 2 C D C 
d o n or at i m m u n ol o gicall y si g nifica nt titers.
7.
Pea k c ha n ge fr o m b aseli ne i n tr o p o ni n a n d C K- M B le vels f oll o wi n g C A P- 1 0 0 2
i nf usi o n.
3. 4
R ati o n al e f or St u d y D e si g n a n d C o ntr ol Gr o u p
Male s u bjects wit h car di o m y o pat h y sec o n dar y t o D M D are b ei n g recr uite d f or t his trial. 
D M D is a n x-li n ke d disease. Fe males o nl y de vel o p D M D w he n t h e y are h o m oz y g o us f or t he 
c o n diti o n. T his is s o e xtre mel y rare t hat t he c ha nce of recr uiti n g e n o u g h fe male s u bjects t o 
t his trial t o ma ke a n y s afet y c o ncl usi o ns ma kes t h e e x cl usi o n of fe males a p pr o priate i n t his 
sit u ati o n.
A n o pe n c o ntr ol gr o u p recei vi n g us u al care has b ee n c h ose n f or t his st u d y i n or der t o ha v e a 
clear c o m parat or f or s afet y efficac y. It was n ot felt reas o na ble t o h a ve c o ntr ol s u bjects 
u n der g o eit h er m ulti- vess el place b o i nf usi o n or a s ha m pr oce d ure. 
Car diac i n v ol v e me nt ca n start i n c hil d h o o d or a d olesce nce a n d pr o gress at a varia ble rate. 
W hile m ost a d ults wit h D M D ha ve si g nifica nt e vi de nce of car di ac i n v ol ve me nt, a si g nifica nt 
pr o p orti o n of a d olesce nts ha ve pr o gressi ve si g nifica nt car diac i n v ol ve me nt s u p p orti n g t he 
nee d t o i n vesti gate t he safet y a n d effecti ve ness of t his treat m e nt i n s u bjects at least 1 2 years 
of a ge. 
3. 5
St u d y D ur ati o n a n d D at e s
N o st u d y-relate d pr oce d ures will be perf or me d u ntil a s u bject pr o vi des c o ns e nt or asse nt 
al o n g wit h pare ntal or g u ar dia n per missi o n. After war ds, a si n gle s u bject’s parti ci pati o n is 
e x pecte d t o last a p pr o xi matel y t hirtee n m o nt hs fr o m t he ti m e of t he first scree ni n g pr oce d ure. 
T he st u d y will re q uire u p t o se ve n sc he d ule d visits t o t he st u d y site: Scree ni n g, I nf usi o n, 
Wee ks 2 a n d 6, a n d M o nt hs 3, 6, a n d 1 2. A n n ual f oll o w- u p p h o ne calls will be c o n d ucte d f or 
a n a d diti o nal f o ur years o nl y if t he s u bject pr o vi des se parate c o nse nt or asse nt. 
It is esti mate d t hat 1 2 m o nt hs of accr u al will be re q uire d t o e nr oll t he tar get sa m ple size f or 
t his P hase II st u d y. 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 4 9 of 1 1 1
4
S T U D Y P O P U L A TI O N S E L E C TI O N
4. 1
St u d y P o p ul ati o n
A p pr o xi matel y t w e nt y-f o ur ( 2 4) male s u bjects wit h car di o m y o pat h y sec o n dar y t o D M D a n d
left ve ntric ular s car b y l ate ga d oli ni u m e n ha nce m e nt ( L G E) car dia c M RI i n at least 4 
se g me nts will be c o nsi dere d f or e nr oll me nt i n t he st u d y.
4. 2
I n cl u si o n Crit eri a
Eac h s u bject m ust meet all of t he f oll o wi n g i ncl usi o n crit eria t o be ra n d o mi ze d i n t he st u d y:
1.
Male s u bjects 1 8 years of a ge or ol d er m ust be a bl e t o pr o vi de i nf or me d c o nse nt 
a n d f oll o w u p wit h pr ot oc ol pr oce d ures. Male s u bjects at least 1 2 years of a ge 
b ut y o u n ger t h a n 1 8 years of a ge m ust be a ble t o pr o vi de asse nt wit h pare nt or 
g uar dia n pr o vi di n g per missi o n f or st u d y partici pati o n. O nl y male s u bjects will be 
ra n d o mize d i nt o t his st u d y.
2.
D oc u me nte d dia g n osis of D uc he n n e M us c ular D ystr o p h y b y ge neti c m utati o n 
a nal ysis.
3.
Car di o m y o pat h y wit h left ve ntric ul ar scar b y L G E i n at least 4 se g me nts as 
assess e d b y c o ntrast-e n h a nce d M RI, a n d E F > 3 5 % at t h e ti me of scree ni n g.
4.
Use of e vi de nce b ase d m e dical-t hera p y i n acc or d a nce wit h t he “ D M D Care 
C o nsi d erati o ns W or ki n g Gr o u p” g ui deli n es f or t he ma na ge me nt of D M D, f or at 
least t hree m o nt hs pri or t o si g ni n g t h e c o nse nt f or m ( or, pr o vi di n g asse nt) or 
d oc u me nte d c o ntr ai n dicati o n or i nt olera nce or p atie nt prefere n ce.
5.
S u bjects m ust be ta ki n g s yste mic gl uc o c ortic oi ds f or at least si x m o nt hs pri or t o 
scree ni n g.
6.
S u bjects m ust be 1 2 years of a ge or ol d er at scree ni n g.
7.
S u bjects m ust be a p pr o priate ca n di d ates f or car dia c cat heterizati o n a n d 
i ntrac or o nar y i nf usi o n of C A P- 1 0 0 2, i n t he j u d ge me nt of t he site’s i nter ve nti o nal
car di ol o gist.
4. 3
E x cl u si o n Crit eri a
S u bjects t h at m eet a n y of t h e f oll o wi n g e xcl usi o n criteria will n ot be per mitte d t o e nr oll i nt o 
t he st u d y: 
1.
T hera p y wit h i ntra ve n o us i n otr o pic or vas oacti ve me dicati o ns at t h e ti me of 
scree ni n g.
2.
I n a bilit y t o u n der g o car di ac c at heterizati o n a n d/ or M RI wit h o ut ge neral 
a nest h esia.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 5 0 of 1 1 1
3.
I m m u n ol o gic i nc o m pati bilit y wit h all a v aila ble M aster C ell B a n ks ( M C Bs) b y 
si n gle-a nti ge n b ea d ( S A B) ser u m a nti b o d y pr ofili n g.
4.
Pl a n n e d or li kel y maj or s ur ger y i n t he ne xt 1 2 m o nt hs after pla n n e d 
ra n d o mizati o n.
5.
Left Ve ntric ul ar Assist D e vices ( L V A D) or t h ose s u bjects acti vel y i n t he pr ocess 
of ac q uiri n g a L V A D.
6.
C o ntrai n dicati o n t o car di ac M RI.
7.
K n o w n h y p erse nsiti vit y t o c o ntrast a ge nts.
8.
Esti mate d gl o mer ular filtrati o n rate ( G F R) < 6 0 m L/ mi n, as calc ulate d b y t he 
C K D- E PI c ystati n C e q u ati o n (I n ker, Sc h mi d et al. 2 0 1 2).
9.
Acti ve i nfecti o n n ot res p o nsi ve t o treat m e nt.
1 0.
Acti ve s yst e mic aller gic reacti o n(s), c o n necti ve tiss ue dis ease or a ut oi m m u ne 
dis or der(s).
1 1.
Hist or y of car di ac t u m or or car di ac t u m or de m o nstrate d o n scree ni n g M RI.
1 2.
Hist or y of pre vi o us ste m cell t h era p y.
1 3.
Hist or y of us e of me dicati o ns liste d i n A p p e n di x 3 wit hi n 3 m o nt hs pri or t o 
si g ni n g t he I C F / Ass e nt t hr o u g h c o m pleti o n of t he st u d y i nf usi o n. 
1 4.
K n o w n m o derat e-t o-se vere a ortic ste n osis/i ns ufficie nc y or se v ere mitral 
ste n osis/re g ur gitati o n.
1 5.
C urre nt acti v e alc o h ol or dr u g a b use. 
1 6.
K n o w n hist or y of H u m a n I m m u n o deficie nc y Vir us ( HI V) i nfecti o n.
1 7.
K n o w n hist or y of c hr o ni c viral he patitis.
1 8.
A b n or mal li ver f u ncti o n ( A L T/ A S T > 1 0 ti mes t he u p per refere nce ra n ge) a n d/ or 
st u dies wit h o ut a re versi ble, i de ntifia ble ca us e.
1 9.
K n o w n h y p erse nsiti vit y t o b o vi ne pr o d ucts.
2 0.
K n o w n h y p erse nsiti vit y t o di met h yl s ulf o xi de ( D M S O).
2 1.
U nc o ntr olle d dia betes ( H b A 1c > 9. 0).
2 2. I n a bilit y t o c o m pl y wit h pr ot oc ol-relat e d pr oce d ures, i ncl u di n g re q uire d st u d y 
visits.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 5 1 of 1 1 1
2 3.
A n y c o n diti o n or ot h er reas o n t hat, i n t he o pi ni o n of t he I n vesti gat or or M e dical 
M o nit or, w o ul d re n der t h e s u bject u ns uita ble f or t he st u d y.
2 4.
C urre ntl y recei vi n g i n v esti gati o nal treat me nt o n a n ot her cli nical trial or 
e x pa n d e d access pr ot oc ol, i ncl u di n g a n y of t h e f oll o wi n g:
•
Recei ve d i n vesti gati o nal i nter ve nti o n wit hi n 3 0 da ys pri or t o ra n d o mizati o n
•
Treat m e nt a n d/ or a n i nc o m plete f oll o w- u p t o treat m e nt wit h a n y 
i n vesti gati o nal cell base d t h era p y wit hi n 6 m o nt hs pri or t o ra n d o mi zati o n
•
Acti ve partici pati o n i n ot her res ear c h t h era p y f or car di o vasc ular 
re pair/re ge nerati o n


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 5 2 of 1 1 1
5
S T U D Y T R E A T M E N T( S)
5. 1 
I n v e sti g ati o n al Pr o d u ct 
C A P- 1 0 0 2 is a n i n vesti gati o nal pr o d uct (I P) c o nsisti n g of all o ge neic car di os p here- d eri v e d 
cells ( C D Cs).
5. 1. 2  
D S A S cr e e ni n g
C A P- 1 0 0 2 C D Cs will b e gr o w n fr o m d o n ors u nrel ate d t o t he reci pie nts. All ra n d o mize d 
s u bjects will be m o nit ore d d uri n g t h e c o urse of t he st u d y f or de v el o p me nt of i ncrease d a nti-
h u ma n le u k oc yte a nti ge n ( H L A) a nti b o d y le v els wit h de vel o p me nt of se nsiti zati o n t o H L A 
a nti ge ns s p ecific t o t he C A P- 1 0 0 2 C D C d o n or at i m m u n ol o gicall y si g nifica nt titers ( b y s oli d 
p hase i m m u n oassa y). W hile t he H L A t y p e of t h e reci pie nt s u bject, d o n or a n d t he C A P- 1 0 0 2 
C D Cs will be teste d a n d k n o w n, pri maril y f or pr o d uct i de ntificati o n p ur p oses, H L A 
matc hi n g of t h e d o n or a n d t he reci pie nt s u bjects will n ot be perf or me d. I nst ea d, s u bjects wit h 
meas ura ble d o n or s pecifi c a nti b o dies a gai nst (as m eas ure d b y t he S A B ass a y d uri n g 
scree ni n g) d o n or s pecific H L A i n all a vaila ble C A P- 1 0 0 2 master cell ba n ks are e x cl u de d 
fr o m t he st u d y.  


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 5 3 of 1 1 1
5. 2 
U s u al C ar e 
Us ual care will i ncl u de a n y a p pr o priate treat me nt(s) per t h e i n vesti gat or’s discreti o n, e xce pt 
t hat us ual care ca n n ot i n cl u de treat m e nt wit h C A P- 1 0 0 2, ot her ste m cell treat me nts, or ot her 
i n vesti gati o nal t hera pies d uri n g t he s u bject’s 1 2 m o nt h st u d y peri o d.  
S u bjects ra n d o miz e d t o us ual care will recei ve o pti mal me dical t h era p y acc or di n g t o t he 
treat me nt pla n of t h eir pri mar y D M D d oct or a n d site i n vesti gat or, i nf or me d b y t h e e vi de nce 
base d m e dical-t hera p y i n acc or da nce wit h t he “ D M D Care C o nsi derati o ns W or ki n g Gr o u p” 
g ui deli nes f or t he m a na ge me nt of D M D ( B us h b y, Fi n kel et al. 2 0 1 0a, B us h b y, Fi n kel et al. 
2 0 1 0 b).  
5. 2. 1  
C A P- 1 0 0 2 A c c e s s P o st- St u d y
If t he a v aila ble e vi de n ce s u g gests a n a p pr o priate ris k/ be nefit pr ofile f or t his pr o d uct, 
Ca pric or ma y ( wit h D S M B a gree me nt) o p e n a n o pe n-la bel e xte nsi o n pr ot oc ol t o ma ke C A P-
1 0 0 2 a vaila ble f or Us ual Care s u bjects after t he y c o m plete t h e 1 2- m o nt h st u d y ass ess me nt 
peri o d.  
5. 3 
R a n d o mi z ati o n  
C o nse nte d, eli gi ble s u bjects will b e ra n d o mize d 1: 1 t o recei ve eit h er C A P- 1 0 0 2 or us ual 
care.
5. 4 
C o n c o mit a nt T h er a p y 
All me dicati o n t hera pies recei v e d fr o m t he ti me of si g ni n g c o nse nt will be c ollecte d
( be gi n ni n g wit h t he Scree ni n g visit). Me dic ati o ns i n use fr o m i nitiati o n of t h e i nf usi o n 
pr oce d ure f or acti v e t h era p y s u bjects, or 9a m o n D a y 0 f or us u al care s u bj ects,  are 
c o nsi dere d c o nc o mita nt t hera pies. C o nc o mita nt t h era pies will be rec or de d at eac h st u d y visit.  


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 5 4 of 1 1 1
5. 5 
Pri or T h er a p y E x cl u si o n s/ Pr o hi bit e d M e di c ati o n s
S u bjects w h o ha ve ha d a n y of t he f oll o wi n g pri or t h era pies will n ot b e eli gi ble t o partici pate 
i n t h e st u d y: 
T hera p y wit h i ntra ve n o us i n otr o pic or vas oacti v e me dicati o ns at t he ti me of scree ni n g 
( E xcl usi o n Crit eri o n 1)
Left Ve ntric ul ar Assist D e vices or acti vel y i n t he pr ocess of ac q uiri n g a L V A D
( E xcl usi o n Crit eri o n 5)
Pre vi o us ste m cell t hera p y ( E xcl usi o n Criteri o n 1 2)
Me dicati o ns liste d i n A p pe n di x 3 are pr o hi bite d wit hi n 3 m o nt hs pri or t o si g ni n g t he I C F / 
Asse nt t hr o u g h c o m pleti o n of t he st u d y i nf usi o n/ St u d y Da y 0. ( E xcl usi o n Crit eri a 1 3)
T he f oll o wi n g m e di cati o ns are pr o hi bite d fr o m 3 0 da ys pri or t o ra n d o mi zati o n, t hr o u g h t he 
M o nt h 1 2/ E arl y T er mi nati o n st u d y visit:
A n y ste m cell t hera pi es ot her t ha n C A P- 1 0 0 2 
A n y i n vesti gati o nal treat me nts ot her t h a n C A P- 1 0 0 2  
5. 6 
Tr e at m e nt C o m pli a n c e 
Treat m e nt i n H O P E- D uc he n ne is a o ne-ti m e pr oce d ure. T h eref ore, c o nti n ue d c o m plia nce 
wit h t h e i n vesti gati o nal pr o d uct is n ot a p plica ble. St u d y site p ers o n nel will d oc u m e nt 
c o m plia nce wit h a n y c o n c o mita nt me dicati o ns a n d st u d y f oll o w- u p pr o ce d ures at e ac h st u d y 
visit.
  


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 5 5 of 1 1 1
5. 9 
I n v e sti g ati o n al Pr o d u ct R et e nti o n at St u d y Sit e 
Si n ce pr o d uct will be deli vere d as- n ee d e d o n a per s u bject basis, t here will be n o pr o d uct t o 
retai n at t he site.  


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 5 6 of 1 1 1
6
S T U D Y P R O C E D U R E S
6. 1
I nf or m e d C o n s e nt
All s u bjects t h at are at least of 1 8 years of a g e m ust pr o vi d e writte n c o nse nt pri or t o 
perf or mi n g a n y st u d y-relate d pr oce d ure. All s u bjects t hat are at least 1 2 years of a ge, b ut less 
t ha n 1 8, m ust pr o vi de writte n asse nt al o n g wit h pare ntal or g uar dia n writt e n per missi o n pri or 
t o perf or mi n g a n y st u d y-relate d pr o ce d ure.  A n I nf or me d C o nse nt F or m (I C F) will be 
pr o vi de d t o a n a d ult s u bject f or t heir c o nsi derati o n. A n Asse nt F or m ( A F) will be pr o vi de d t o 
a n a d olesce nt s u bject a n d t he s u bject’s pare nt(s) or g uar di a n(s) f or t h eir c o nsi derati o n. Eac h 
f or m will c o ntai n all U nite d States fe d erall y re q uire d ele me nts, all I C H-re q uire d ele me nts, 
a n d Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y A ct ( HI P A A) a ut h orizati o n i nf or mati o n 
i n la n g ua ge t h at is u n dersta n da ble t o t he s u bject a n d s u bject’s  pare nt(s) or g uar dia n(s), if 
a p plica ble. T h e pr ocess of o btai ni n g i nf or me d c o ns e nt or asse nt will be i n c o m pli a nce wit h 
all fe deral re g ulati o ns, I nter n ati o nal C o nfere nce o n Har m o nisati o n (I C H) re q uire me nts, a n d 
l ocal la ws.  
T he I n vesti gat or a n d/ or desi g n ee m ust disc uss t he st u d y wit h eac h s u bje ct a n d t h e s u bject’s 
pare nt(s) or g uar di a n(s), if a p pli ca ble. T h e dis c ussi o n will i ncl u de t h e nat ure, sc o pe, 
pr oce d ures, a n d p ossi ble c o nse q ue nces of t he s u bject's partici pati o n i n t he st u d y. T he I C F/ A F 
a n d disc ussi o n will be i n a f or m u n derst a n da ble t o t h e s u bject a n d t he s u bject’s pare nt(s) or 
g uar dia n(s). T he s u bject a n d s u bject’s pare nt(s) or g uar dia n(s) m ust b e gi v e n a de q uate ti m e 
t o re vie w t he I C F/ A F a n d as k q uesti o ns re gar di n g t he I P, pr o ce d ures, ris ks a n d ot h er 
treat me nt.  F or s u bjects at least 1 8 years of a ge, a n I C F m ust be si g n e d a n d date d b y t he 
s u bject a n d t he I n v esti gat or or desi g nee bef ore partici pati o n i n t h e st u d y. F or s u bjects t hat are 
at least 1 2 years of a ge, b ut less t ha n 1 8, a n A F m ust be si g ne d a n d date d b y t he s u bject, t he 
s u bject’s pare nt(s) or g u ar dia n(s), a n d t h e I n vesti gat or or desi g nee bef ore t h e s u bject ca n 
partici pate i n t he st u d y. T he s u bject will rec ei ve a c o p y of t he si g ne d a n d date d I C F, a n d t he 
ori gi nal will be retai ne d i n t he site st u d y files. T he s u bject a n d pare nt(s) or g uar dia n(s) will 
recei v e a c o p y of t h e si g ne d a n d date d A F, a n d t he ori gi n al will be retai n e d i n t he st u d y sit e 
files. T he I n vesti gat or or desi g nee will e m p hasize t o t h e s u bject a n d s u bject’s pare nt(s) or 
g uar dia n(s) t h at st u d y partici pati o n is e ntirel y v ol u ntar y a n d t hat c o ns e nt a n d/ or asse nt 
re gar di n g st u d y partici pati o n ma y be wit h dra w n at a n y ti me wit h o ut pe nalt y or l oss of 
be nefits t o w hic h t he s u bject is ot her wise e ntitl e d.
M o dificati o ns t o t he st u d y desi g n, a dj ust me nts t o t he met h o d of st u d y c o n d uct, or release of 
ne w s afet y i nf or mati o n ma y o cc ur d uri n g t h e c o urse of t he st u d y t hat ma y re q uire a n 
a me n de d I C F a n d/ or A F. T he a me n d e d I C F a n d/ or A F will c o ntai n all U nit e d States fe d erall y 
re q uire d ele me nts, all I C H-re q uire d ele me nts, a n d H ealt h I ns ura nce P orta bilit y a n d 
Acc o u nta bilit y Act ( HI P A A) a ut h orizati o n i nf or mati o n i n la n g ua ge t h at is u n dersta n da ble t o 
t he s u bject a n d s u bject’s pare nt(s) or g u ar di a n(s). T he site m ust use t he a m e n de d I C F a n d/ or 
A F f or all ne w s u bjects. All o n g oi n g s u bjects m ust re peat t he c o nse nt a n d/ or asse nt pr ocess 
wit h t h e I n v esti g at or or d esi g nee usi n g t he a me n d e d I C F a n d/ or A F. 
O n g oi n g s u bje cts t h at m at ure t o at least 1 8 years of a ge d uri n g t he c o urse of t he st u d y ma y b e 
re q uire d t o pr o vi de writte n i nf or me d c o ns e nt (i.e., I C F) de p e n di n g o n t he re q uire me nts of t he 
re vie wi n g I R B, as w ell as l ocal re g ulati o ns. 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 5 7 of 1 1 1
6. 2
M e di c al Hi st or y & C o n c o mit a nt
M e di c ati o n s
T he ge neral a n d car diac-s pecific me dical hist ories (e. g., si g nifica nt pr oce d ures, me dicati o ns, 
t hera pies, aller gies) of s u bjects ra n d o mize d i n t he st u d y will be d oc u me nt e d as part of t h e 
Scree ni n g Visit a n d re vi e w e d d uri n g all s u bse q ue nt visits f or a n y m o dificati o ns (i.e., 
assess me nt f or p ote ntial a d vers e e ve nts).  G e neral a n d car dia c healt h, as w ell as c o nc o mita nt 
me dicati o ns, will be re vi e we d a n d ass esse d at eac h visit a n d ne w i nf or mati o n will be u p date d 
i n t h e s u bject’s st u d y d o c u me ntati o n.
6. 3
C ar di a c a n d Li mit e d P h y si c al E x a mi n ati o n s
A q ualifie d p h ysicia n, eit her t h e I n vesti gat or or S u b-I n vesti gat or, will perf or m a
car di o vasc ular p h ysical e x a mi nati o n at eac h st u d y visit.  
A li mit e d p h ysi cal e x a mi nati o n will be c o n d ucte d at t he scree ni n g visit a n d t he 1 2 M o nt h 
f oll o w- u p visit. 
Wei g ht a n d hei g ht will be c ollecte d at Scree ni n g, 6- m o nt h, a n d 1 2- m o nt h visits. Hei g ht al o ne 
will als o be assesse d at t h e 6- wee k a n d 3- m o nt h visits. If sta n di n g hei g ht ca n n ot be 
meas ure d, h ei g ht will be calc ul ate d usi n g a m eas ure me nt of ul na le n gt h ( G a ul d et al 2 0 0 4).
6. 4
Vit al Si g n s
Te m perat ure, heart rate (seate d), bl o o d press ure (s eate d) a n d res pir ati o n rat e will b e rec or de d 
at eac h visit.
6. 5
Cli ni c al L a b or at or y T e st s
6. 5. 1 
L a b or at or y P ar a m et er s
Cli nical la b orat or y tests will i ncl u de t h ose liste d i n 6. 1 0. 1 C A P- 1 0 0 2 I nf usi o n, A p pe n di x 1 
( Sc he d ule of E v e nts), a n d A p pe n di x 2 ( Cli nical La b orat or y T ests). S u bjects will be i n a 
seate d or s u pi ne p ositi o n d uri n g bl o o d c oll ecti o n.
6. 5. 2 
S a m pl e C oll e cti o n, St or a g e, a n d S hi p pi n g
All cli nical la b orat or y testi n g i n t his trial will b e perf or me d b y ce ntr al la b orat or y facilities, 
e x ce pt t h ose perf or m e d o n Da ys 0 a n d 1 f or s u bjects ra n d o mize d t o C A P- 1 0 0 2 o nl y. All 
sa m ples will be c ollecte d, pr ocesse d, st ore d a n d s hi p pe d (as a p plic a ble) acc or di n g t o 
i nstr ucti o ns i n t he Cli nical La b orat or y M a n ual f or t his trial.
F or s u bjects ra n d o mi ze d t o C A P- 1 0 0 2, t he cli nical sit e s h o ul d c oll ect a n d pr ocess sa m ples 
f or t h e f oll o wi n g tests i n acc or da nce wit h t heir i nstit uti o nal p olicies t o a p pr o priatel y m o nit or 
s u bject safet y pre a n d p ost i nf usi o n:


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 5 8 of 1 1 1
T a bl e 2. 
L o c al L a b or at or y T e sti n g, D a y 0 a n d D a y 1 ( C A P- 1 0 0 2 Ar m O nl y)
P re-I nf usi o n
P ost-I nf usi o n
Tr o p o ni n I
Tr o p o ni n I (seri al c ollecti o n)
C K- M B 
C K- M B (seri al c ollecti o n)
Ser u m C h e mistr y *
Ser u m C he mistr y *
He mat ol o g y *
He mat ol o g y *
Uri nal ysis *
Uri nal ysis *
P T T & I N R (if ta ki n g warfari n)
* See A p p e n di x 2 f or details
Ser u m f or t h e d o n or s p ecific a nti b o d y ( D S A) m o nit ori n g, H L A t y pi n g a n d bl o o d f or t h e 
E LI S p ot assa y will be c ollecte d a n d pr o cesse d at eac h sit e a n d t he n s hi p pe d t o a ce ntral c ore 
la b orat or y f or a n al ysis wit hi n 2 4 h o urs of o btai ni n g t he s peci me ns ( See La b orat or y Ma n u al 
f or s hi p pi n g i nstr ucti o ns). S u bjects will be m o nit ore d f or t h e de vel o p me nt of a cell ular
i m m u ne res p o nse usi n g t he E LI S p ot (e nz y me-li n k e d i m m u n os or be nt s p ot) assa y. T he
E LI S p ot assa y will be perf or me d at scree ni n g a n d at t h e
Wee k 6 st u d y visit.
Ser u m f or researc h p ur p oses ( bi o mar kers) will be c ollecte d a n d pr ocesse d at eac h site t he n 
s hi p pe d t o a ce ntral c ore la b t hat will t he n s hi p t o Ca pric or f or fi nal st ora ge a n d a nal ysis (if 
s u bject has pr o vi d e d c o nse nt).
F or s u bjects w h o pr o vi de c o nse nt a n d/ or ass e nt, ser u m f or cli nical researc h i nt o bi o mar kers 
will b e c ollecte d at e ver y sc he d ule d visit (e x cl u di n g i nf usi o n) a n d se nt t o t h e S p o ns or, or 
desi g nee, f or st ora ge a n d/ or a nal ysis (i ncl u di n g a n d f ut ure a n al ysis). Per t he C o de of Fe deral 
Re g ulati o ns ( 2 1 C F R 3 2 0. 3 8), s er u m sa m ples c oll ecte d fr o m st u d y s u bjects will be 
mai ntai ne d i n st ora ge f or at least fi ve ( 5) years f oll o wi n g t he date o n w hic h t he I N D 
a p plicati o n or s u p ple me ntal a p plicati o n is a p pr o ve d. If s uc h a p plicati o n or s u p ple me ntal 
a p plicati o n is n ot a p pr o v e d, ser u m sa m ples will b e mai ntai ne d i n st ora ge f or at least 5 years 
f oll o wi n g t h e dat e of c o m pleti o n of t h e cli nical researc h st u d y.
6. 6
1 2- L e a d E C G
Be gi n ni n g at t he scree ni n g visit, a 1 2- Lea d E C G will be perf or me d at e ver y st u d y visit t o 
assess f or r h yt h m dist ur b a nces a n d n e w m y ocar di al is c he mia or i nfarcti o n. S u bse q ue nt E C Gs 
will b e c o m pare d wit h t h e scree ni n g E C G f or a n y c ha n ges i n r h yt h m a n d c o n d ucti o n. All 
c ha n ges a n d a n y ass o ciate d cli nical si g nifica nce will be e val uate d a n d d o c u me nte d o n t he 
case re p ort f or ms.
6. 7
C o nti n u o u s C ar di a c R h yt h m M o nit ori n g
T he s p o ns or will pr o vi de a weara ble, wireless de vice f or c o nti n u o us car dia c r h yt h m 
m o nit ori n g. S u bjects will wear a m o nit ori n g de vi ce f or d efi ne d s h ort-ter m i nter vals, starti n g 
at scree ni n g, o n Da y 1, a n d at t he Wee k 6, M o nt h 6, a n d M o nt h 1 2 st u d y visits. Ta ble 3 
details t he c o nti n u o us m o nit ori n g d urati o n re q uire d at eac h st u d y visit. T h e m o nit ori n g is 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 5 9 of 1 1 1
use d t o detect a n d rec or d arr h yt h mias. All c ha n ges a n d a n y ass ociate d cli nical si g nifi ca nce 
will b e e val u ate d a n d d oc u me nte d o n t he case re p ort f or m.
T a bl e 3. 
P er- Vi sit Mi ni m u m C o nti n u o u s C ar di a c M o nit ori n g D ur ati o n s
St u d y Visit
Mi ni m u m C o nti n u o us 
M o nit ori n g D ur ati o n
Scree ni n g
2 4 h o urs
Da y 1 
7 2 h o urs
Wee k 6
7 2 h o urs
M o nt h 6
7 da ys
M o nt h 1 2
7 2 h o urs
6. 8
M a g n eti c R e s o n a n c e I m a gi n g 
All s u bjects will u n der g o c o ntrast-e n h a nce d M RI at scree ni n g a n d t he M o nt h 6 a n d 1 2 st u d y 
visits ( or, Earl y T er mi nati o n Visit). It is a ntici pate d t hat t he d urati o n of eac h M RI sessi o n 
will b e 4 5- 6 0 mi n utes. Ac q uisiti o n para m eters a n d tec h ni q ues are s pecifie d i n t he M RI 
I ma gi n g
M a n ual. T he sit e- base d M RI t ec h n ol o gists will be trai ne d a n d certifie d i n t he 
c o m m o n ac q uisiti o n pr ot oc ol pri or t o i niti ati o n of e nr oll me nt at eac h site.
6. 8. 1  
Ci n e I m a gi n g Pr ot o c ol
A ci n e i m a gi n g pr ot oc ol will be utili ze d f or gl o bal ejecti o n fracti o n a n d L V v ol u mes a n d 
mass deter mi n ati o n. Ac q uisiti o n para meters a n d t ec h ni q ues are s pecifie d i n t he M RI I m a gi n g
Ma n ual. T he site- b ase d M RI tec h nicia ns will be trai ne d a n d certifie d i n t h e c o m m o n 
ac q uisiti o n pr ot oc ol pri or t o i nitiati o n of e nr oll me nt at eac h site.
6. 8. 2  
D el a y e d C o ntr a st- E n h a n c e m e nt Pr ot o c ol
S u bjects will u n der g o a sta n dar dize d ac q uisiti o n pr ot oc ol i ncl u di n g a n i ntra ve n o us i njecti o n 
of ga d oli ni u m c o ntrast as defi ne d i n t h e M RI I ma gi n g Ma n u al c o nsiste nt wit h i nstit uti o nal 
g ui deli nes. 
6. 8. 3 
I m a g e A n al y si s
All st u d y i ma ges a n d a p plica ble i ma gi n g d ata will be se nt t o a n d ce ntrall y rea d at a n 
i n de pe n de nt i m a gi n g c ore b y car di o v asc ular ra di ol o g y e x perts. M RI will be perf or me d o n 
sta n dar d p ha nt o ms f or q u alit y ass ura nce a n d t o detect a n y c h a n ges i n s yste m se nsiti vit y o ver 
ti m e.
6. 8. 4  
Hi st ori c al C ar di a c
M RI
If a s u bject h as a hist orical car diac
M RI sca n a vail a ble pri or t o Scree ni n g d ate, t he site 
s h o ul d re q uest t hat t his hist orical car diac
M RI be se nt t o t he i ma gi n g c ore l a b f or t his trial, t o 
p ote ntiall y deter mi ne t he rate of car diac diseas e pr o gressi o n at t he ti m e of s cree ni n g. If 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 6 0 of 1 1 1
m ulti ple hist orical c M RIs are a vaila ble, t he m ost rece nt sca n t hat occ urre d at least 6 wee ks pri or 
t o scree ni n g s h o ul d be tra nsferre d.
6. 9 
Cli ni c al F u n cti o n a n d Q u alit y of Lif e M e a s ur e s  
At t he scree ni n g, 6 Wee ks, 3 M o nt hs, 6 M o nt hs, a n d 1 2 M o nt hs ( or Earl y Ter mi nati o n) st u d y 
visits, t he s u bject will be as ke d t o c o m plete t h e Perf or ma nce of U p p er Li m b ( P U L) 
assess me nt a n d s pir o metr y. B ot h t he s u bject a n d t h e pare nt/ g uar di a n will be as ke d t o 
c o m plete t he Pe diatric Q ualit y of Life I n ve nt or y ( Pe ds Q L) a n d t he P O D CI A d olesce nt 
Q uesti o n naire ( P O D CI). 
I n a d diti o n, s u bjects assesse d b y t he I n vesti gat or as ca pa ble of perf or mi n g t he Si x Mi n ute
Wal k Test ( 6 M W T) will d o s o at scree ni n g, 6 We e ks, 3 M o nt hs, 6 M o nt hs, a n d 1 2 M o nt hs 
( or, E arl y T er mi n ati o n) st u d y visits. S u bjects u na ble t o perf or m t he Si x Mi n ute Wal k Test at 
scree ni n g will n ot be re q uire d t o perf or m t he test at a n y s u bse q u e nt visit.   
6. 1 0
I nf u si o n Pr o c e d ur e
6. 1 0. 1
C A P- 1 0 0 2 I nf u si o n
E ver y atte m pt s h o ul d be ma de t o i nf use t h e t hree maj or car di ac territ ories of t he left v e ntricle 
(a nteri or territ or y, lateral territ or y, a n d i nferi or/ p osteri or territ or y).  A d diti o nall y, t h e i nf usi n g 
I n v esti gat or ma y alter t he i nf usi o n pla n d uri n g t h e i nf usi o n pr oce d ure w he n dee me d 
cli nicall y necessar y. T he pr oce d ure will be perf or m e d as f oll o ws: 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 6 1 of 1 1 1
  
F oll o wi n g i ntrac or o n ar y i nf usi o n, s u bjects will be o bser ve d i n t he h os pital f or 2 0- 2 4 h o urs 
wit h c o nti n u o us car diac (tele metr y) m o nit ori n g. Tr o p o ni n a n d C K- M B l a b orat or y st u dies a n d 
vital si g ns (te m perat ure, H R, B P, a n d R R) will be m o nit ore d e ver y 8 h o urs ( ± 3 0 mi n utes) 
fr o m t he e n d of t he i nf usi o n. A t otal of t hree sets of car di ac e nz y mes will be e val uate d t o r ule 
o ut car diac i nj ur y d uri n g t he p ost-i nf usi o n h os pital sta y t hr o u g h disc h ar ge.  If t he s u bject is 
disc har ge d pri or t o 2 4 h o urs, car dia c e nz y m es will b e dra w n j ust pri or t o disc har ge. 
Pri or t o dis c har ge fr o m t he h os pital, a p h ysi cal assess me nt will be perf or me d w hic h will 
i ncl u de c hest pai n ass ess me nt, re vie w of l a b orat or y res ults, 1 2-lea d E C G, a n d arterial 
p u nct ure sit e as w ell as assess me nt of a d vers e e v e nts. I n t he a bse nce of seri o us a d verse 
e ve nts, s u bjects will be dis c har ge d p er sta n dar d of care practice.
6. 1 0. 2 
I nf u si o n Pr o c e d ur e St o p pi n g Crit eri a
T he o perat or will c o nti n u o usl y m o nit or f or t h e f oll o wi n g St o p pi n g Criteria. If a n y St o p pi n g 
Criteria are met, t he i nf usi n g I n vesti gat or m ust st o p t h e i nf usi o n a n d assess f or cli nical 
si g nifica nce. T h e i nf usi n g I n v esti gat or ma y c o nti n ue wit h t he i nf usi o n if, base d o n t h e 
i nf usi n g I n v esti gat or’s me dical j u d ge me nt a n d cli nical c o nte xt, n o a d diti o nal ris k is prese nt e d 
t o t h e s u bject.  
1.
De vel o p me nt of TI MI fl o w 0- 2 or TI MI m y o car dial perf usi o n gra d e ( T M P G) 0- 2 
persisti n g f or > 3 mi n utes after a c ycl e of i nf usi o n, des pit e a d mi nistrati o n of 
i ntrac or o nar y vas o dilat ors;  
2.
S ustai ne d h y p ote nsi o n u nres p o nsi v e t o fl ui ds a n d/ or atr o pi ne/ vas o press or 
a d mi nistrati o n;
3.
E vi de nce of cere br o v asc ular acci de nt;
4.
E vi de nce of car di ac ta m p o na de;
5.
He m o peri car di u m re q uiri n g pericar di oce ntesis; 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 6 2 of 1 1 1
6.
S ustai ne d V T/ V F t hat re q uires car di o v ersi o n/ defi brill ati o n or a d mi nistrati o n of a n 
a ntiarr h yt h mic;
7.
E vi de nce of t hr o m b us i n t h e a orta t hat w as n ot pre vi o usl y see n;
8.
S us pect e d or c o nfir me d a ortic dissecti o n;
9.
S us pect e d or c o nfir me d c or o nar y dissecti o n; 
1 0. Ot her e vi de nce of ac ute m y ocar dial i nfarcti o n;
1 1. Ac ute o nset of ri g ors (s y m pt o ms i n dicati v e of ac ute se nsiti vit y or i nfecti o n).


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 6 3 of 1 1 1
7
S T U D Y A C TI VI TI E S
Refer t o A p p e n di x 1 f or t he S c he d ule of E v e nts f or t he c o n d uct of t his st u d y.
7. 1
S cr e e ni n g Vi sit 
Writte n i nf or me d c o nse nt or asse nt m ust be o btai ne d fr o m t he s u bject pri or t o perf or mi n g 
a n y st u d y-relate d t as ks. After w ar ds scree ni n g peri o d f or t hat s u bject will be gi n a n d t h e 
f oll o wi n g scree ni n g pr o ce d ures will be perf or me d ( n ot m ore t ha n 3 0 da ys pri or t o 
ra n d o mizati o n):
•
Re vie w of I ncl usi o n / E x cl usi o n Criteria ( Secti o n 4. 2 a n d Secti o n 4. 3)
•
C oll ecti o n of de m o gra p hic i nf or mati o n
•
Re vie w of me dical a n d car diac hist or y, a n d c o nc o mita nt me dicati o ns
•
Meas ure me nt of vital si g ns ( b o d y te m p erat ure, H R, B P, a n d R R), w ei g ht a n d hei g ht
•
1 2-lea d E C G
•
2 4- h o ur E C G via s p o ns or- pr o vi d e d c o nti n u o us car diac r h yt h m m o nit ori n g s yst e m
•
Car diac a n d li mit e d p h ysical e x a mi nati o n
•
Car diac M RI
•
Ve n o us bl o o d will be c ollecte d f or t h e f oll o wi n g:
-
Cli nical la b orat or y tests: ser u m c he mistr y, he mat ol o g y, a n d s er ol o g y ( H bs A g,
a nti- H C V, a nti- HI V 1/ 2), C ystati n C, Tr o p o ni n a n d C K- M B
-
Bi o mar kers: Oste o p o nti n, S T 2, I L- 1 0, a n d Gal ecti n- 3
-
E x pl orat or y bi o mar kers (if c o nse nt/asse nt pr o vi de d)
-
I m m u n oass a y: H L A, D S A, a n d E LI S P O T
-
See 6. 5 f or a d diti o nal i nf or mati o n o n cli nical la b orat or y testi n g.
•
A uri ne sa m ple will be c ollecte d f or uri n al ysis 
•
P U L Scale
•
6 M W T (if ca pa ble)
•
Pe diatric Q o L I n ve nt or y ( Pe ds Q L)
•
P O D CI
•
S pir o metr y
•
A d vers e E v e nt Assess me nt
•
S u b missi o n of hist orical car diac M RI
S u bjects m ust c o nti n ue t o meet all of t he i ncl usi o n a n d n o ne of t h e e x cl usi o n crit eria b ef ore 
pr ocee di n g t o ra n d o mizati o n. S u bjects w h o d o n ot pr ocee d t o ra n d o mizati o n f or a n y reas o n 
d uri n g scree ni n g will be wit h dra w n fr o m t he st u d y as s cre e n fail ures a n d will ha ve n o f urt h er 
f oll o w u p.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 6 4 of 1 1 1
7. 2
R a n d o mi z ati o n, D a y 0, a n d D a y 1
S u bjects t h at c o nti n ue t o meet eli gi bilit y will be ra n d o miz e d ( 1: 1) t o eit her t he acti ve 
treat me nt ar m ( C A P- 1 0 0 2) or us u al care ar m. 
F or s u bjects t hat are ra n d o miz e d t o t he us ual care ar m, Da y 0 will be defi ne d as se ve n ( 7)
da ys after t h e date of ra n d o miz ati o n. F or s u bjects t hat are ra n d o mize d t o t he acti ve treat me nt 
ar m, Da y 0 will be defi ne d as t he date of t h e i ntrac or o nar y i nf usi o n of C A P- 1 0 0 2.
F or s u bjects r a n d o mize d t o C A P- 1 0 0 2 o nl y, t he i nf usi o n visit will i ncl u de tests a n d 
assess me nts as descri be d bel o w a n d i n acc or da nce wit h t he site’s sta n dar d o perati n g 
pr oce d ures.
Pre-I nf usi o n:
•
Eli gi bilit y Re vie w
•
Re vie w of me dical a n d car diac hist or y, a n d c o nc o mita nt me dicati o ns
•
Car diac p h ysical e x a mi nati o n
•
Meas ure me nt of vital si g ns (te m perat ure, H R, B P, a n d R R) 
•
1 2- Lea d E C G 
•
Ve n o us bl o o d will be c ollecte d f or t h e f oll o wi n g:
-
Cli nical la b orat or y tests: c he mistr y, h e mat ol o g y 
-
C o a g ulati o n if s u bject is ta ki n g w arfari n
•
Serial ve n o us c oll ecti o n f or car di ac e nz y mes ( Tr o p o ni n a n d C K- M B)
•
A uri ne sa m ple will be c ollecte d f or uri n al ysis
•
A d vers e e ve nt assess me nt
I nf usi o n
Refere n ce Se cti o n 6. 1 0 f or c o m plete i nf usi o n details
P ost-i nf usi o n ( D 0- D 1):
•
Serial c ollecti o n of vital si g ns (te m perat ure, H R, B P, a n d R R) e ver y 8 h o urs ( ± 3 0 
mi n utes) fr o m t he e n d of t he i nf usi o n. 
•
Car diac P h ysical E x a mi nati o n 
•
1 2-lea d E C G 
•
Serial ve n o us c oll ecti o n f or car di ac e nz y mes ( Tr o p o ni n a n d C K- M B)
•
Ve n o us bl o o d will be c ollecte d f or cli nical la b orat or y tests: c h e mistr y, 
he mat ol o g y, a n d uri n al ysis
F oll o wi n g i ntrac or o n ar y i nf usi o n, s u bjects will be o bser ve d i n t he h os pital f or 2 0- 2 4 h o urs 
wit h c o nti n u o us car diac (tele metr y) m o nit ori n g. Tr o p o ni n a n d C K- M B l a b orat or y st u dies 
will b e m o nit ore d e ver y 8 h o urs ( ± 3 0 mi n utes) fr o m t he e n d of t he i nf usi o n. A t otal of t hree 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 6 5 of 1 1 1
sets of car di ac e nz y mes will be e val uate d t o r ule o ut car diac i nj ur y d uri n g t h e p ost-i nf usi o n 
h os pital sta y t hr o u g h dis c har ge.  If t he s u bject is disc har ge d pri or t o 2 4 h o urs, car diac 
e nz y mes will be dra w n j ust pri or t o disc har ge.
D ay 1 Pri or t o H os pit al Dis c h ar ge:
•
Re vie w of c o n c o mita nt me dicati o ns
•
A d vers e e ve nt assess me nt
•
P h ysical ass ess me nt (c hest pai n, i nf usi o n/arterial p u nct ure sit e(s))
•
Re vie w of la b res ults a n d 1 2-lea d E C G
Pri or t o dis c har ge fr o m t he h os pital, a p h ysi cal assess me nt will be perf or me d w hic h will 
i ncl u de c hest pai n ass ess me nt, re vie w of l a b orat or y res ults, 1 2-lea d E C G, a n d arterial 
p u nct ure sit e as w ell as assess me nt of a d vers e e v e nts. I n t he a bse nce of seri o us a d v erse 
e ve nts, s u bjects will be dis c har ge d p er sta n dar d of care practice.
D a y 1 f or A L L S U B J E C T S:
•
I niti ate 7 2- h o ur c o nti n u o us car diac r h yt h m m o nit ori n g usi n g s p o ns or-s u p plie d 
m o nit or s yste m (i n dicate d f or h o me use)
•
N o st u d y visit is re q uire d f or Da y 1, as s u bjects will recei ve pri or i nstr ucti o n o n 
use of t h e m o nit ori n g s yste m
7. 3
D a y 3 P h o n e Vi sit 
T he i n v esti gat or’s site staff will c o ntact t he s u bject ( or pare nt/ g u ar dia n) b y tele p h o ne o n St u d y 
Da y 3 ( 3 da ys p ost Da y 0) f or safet y f oll o w- u p. St u d y Da y 3 is 3 da ys p ost-i nf usi o n f or 
s u bjects ra n d o mize d t o C A P- 1 0 0 2.  F or s u bjects ra n d o mize d t o us ual care, St u d y Da y 3 is te n 
da ys aft er ra n d o mizati o n.
T he sit e will i n q uire as t o t he s u bj ect’s o verall healt h a n d w het her t he s u bject has ha d a n y 
a d verse e ve nts, es peciall y a n y re q uiri n g h os pitalizati o n or ot her me dical i nter ve nti o n, i n t he 
prece di n g 2 da ys (i.e., Da y 1 – Da y 3).  
If necessar y, t he p h o ne call ma y be c o n d ucte d o n St u d y Da ys 4, 5, or 6.
If t he site is u na ble t o reac h t he s u bject b y tele p h o ne, t he site s h o ul d m a ke t w o m ore atte m pts 
t o c o nt act t he s u bject, o ne eac h o n t he ne xt t w o da ys.
7. 4
W e e k 2 Vi sit ( D a y 1 4 ± 3 d a y s) 
S u bjects will ret ur n t o t he cli nical sit e a n d c o m plete t he f oll o wi n g pr oce d ures:
•
A d vers e e ve nt assess me nt
•
Re vie w of c o n c o mita nt me dicati o ns 
•
Meas ure me nt of vital si g ns (te m perat ure, H R, B P, a n d R R)


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 6 6 of 1 1 1
•
1 2- Lea d E C G
•
Car diac P h ysical E x a mi nati o n
•
Ve n o us bl o o d will be c ollecte d f or t h e f oll o wi n g:
-
Cli nical la b orat or y tests: ser u m c he mistr y, he mat ol o g y 
-
Car di ac e nz y mes: Tr o p o ni n a n d C K- M B
-
Bi o mar kers: Oste o p o nti n, S T 2, I L- 1 0, a n d Gal ecti n- 3
-
E x pl orat or y bi o mar kers (if c o nse nt/asse nt pr o vi de d)
-
I m m u n oass a y: D S A
•
A uri ne sa m ple will be c oll ecte d f or uri n al ysis
7. 5
W e e k 6 Vi sit ( D a y 4 0 ± 7 d a y s) 
S u bjects will ret ur n t o t he cli nical sit e a n d c o m plete t he f oll o wi n g pr oce d ures:
•
A d vers e e ve nt assess me nt
•
Re vie w of c o n c o mita nt me dicati o ns 
•
Meas ure me nt of vital si g ns (te m perat ure, H R, B P, a n d R R) a n d hei g ht
•
1 2- Lea d E C G
•
Car diac P h ysical E x a mi nati o n
•
7 2- h o ur c o nti n u o us car diac r h yt h m m o nit ori n g usi n g s p o ns or-s u p pli e d d e vi ce
•
Ve n o us bl o o d will be c ollecte d f or t h e f oll o wi n g:
-
Cli nical la b orat or y tests: ser u m c he mistr y, he mat ol o g y 
-
Bi o mar kers: Oste o p o nti n, S T 2, I L- 1 0, a n d Gal ecti n- 3
-
E x pl orat or y bi o mar kers (if c o nse nt/asse nt pr o vi de d)
-
I m m u n oass a y: D S A a n d E LI S p ot
•
A uri ne sa m ple will be c oll ecte d f or uri n al ysis
•
P U L Scale
•
6 M W T (if ca pa ble)
•
Pe diatric Q L I n ve nt or y
•
P O D CI
•
S pir o metr y
7. 6
M o nt h 3 Vi sit ( D a y 9 0 ± 7 d a y s)
•
S u bjects will ret ur n t o t he cli nical sit e a n d c o m plete t he f oll o wi n g pr oce d ures:
•
A d vers e e ve nt assess me nt
•
Re vie w of c o n c o mita nt me dicati o ns 
•
Meas ure me nt of vital si g ns (te m perat ure, H R, B P, a n d R R) a n d hei g ht
•
1 2- Lea d E C G
•
Car diac P h ysical E x a mi nati o n


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 6 7 of 1 1 1
•
Ve n o us bl o o d will be c ollecte d f or t h e f oll o wi n g:
-
Cli nical la b orat or y tests: ser u m c he mistr y, he mat ol o g y 
-
Bi o mar kers: Oste o p o nti n, S T 2, I L- 1 0, a n d Gal ecti n- 3
-
E x pl orat or y bi o mar kers (if c o nse nt/asse nt pr o vi de d)
-
I m m u n oass a y: D S A
•
A uri ne sa m ple will be c oll ecte d f or uri n al ysis
•
P U L Scale
•
6 M W T (if ca pa ble)
•
Pe diatric Q L I n ve nt or y
•
P O D CI
•
S pir o metr y
7. 7
M o nt h 6 Vi sit ( D a y 1 8 0 ± 1 4 d a y s) 
S u bjects will ret ur n t o t he cli nical sit e a n d c o m plete t he f oll o wi n g pr oce d ures:
•
A d vers e e ve nt assess me nt
•
Re vie w of c o n c o mita nt me dicati o ns 
•
Meas ure me nt of vital si g ns (te m perat ure, H R, B P, a n d R R), wei g ht a n d hei g ht
•
1 2- Lea d E C G
•
Car diac P h ysical E x a mi nati o n
•
Car diac M RI
•
Se ve n da y c o nti n u o us car diac r h yt h m m o nit ori n g usi n g s p o ns or-s u p plie d d e vice
•
Ve n o us bl o o d will be c ollecte d f or t h e f oll o wi n g:
-
Cli nical la b orat or y tests: ser u m c he mistr y, he mat ol o g y, a n d c ystati n C
-
Bi o mar kers: Oste o p o nti n, S T 2, I L- 1 0, a n d Gal ecti n- 3
-
E x pl orat or y bi o mar kers (if c o nse nt/asse nt pr o vi de d)
-
I m m u n oass a y: D S A
-
Car di ac e nz y mes: Tr o p o ni n a n d C K- M B
•
A uri ne sa m ple will be c oll ecte d f or uri n al ysis
•
P U L Scale
•
6 M W T (if ca pa ble)
•
Pe diatric Q L I n ve nt or y
•
P O D CI
•
S pir o metr y


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 6 8 of 1 1 1
7. 8
M o nt h 1 2 Vi sit ( D a y 3 6 0 ± 3 0 d a y s) 
S u bjects will ret ur n t o t he cli nical sit e a n d c o m plete t he f oll o wi n g pr oce d ures:
•
A d vers e e ve nt assess me nt
•
Re vie w of c o n c o mita nt me dicati o ns 
•
Meas ure me nt of vital si g ns (te m perat ure, H R, B P, a n d R R), wei g ht a n d hei g ht
•
1 2- Lea d E C G
•
Car diac a n d li mit e d p h ysical e x a mi nati o ns
•
Car diac M RI
•
7 2 h o ur c o nti n u o us car di ac r h yt h m m o nit ori n g usi n g s p o ns or-s u p pli e d d e vi ce
•
Ve n o us bl o o d will be c ollecte d f or t h e f oll o wi n g:
-
Cli nical la b orat or y tests: ser u m c he mistr y, he mat ol o g y, a n d c ystati n C
-
Bi o mar kers: Oste o p o nti n, S T 2, I L- 1 0, a n d Gal ecti n- 3
-
E x pl orat or y bi o mar kers (if c o nse nt/asse nt pr o vi de d)
-
I m m u n oass a y: D S A
-
Car di ac e nz y mes: Tr o p o ni n a n d C K- M B
•
A uri ne sa m ple will be c oll ecte d f or uri n al ysis
•
P U L Scale
•
6 M W T (if ca pa ble)
•
Pe diatric Q L I n ve nt or y
•
P O D CI
•
S pir o metr y
7. 9
A n n u al F oll o w- u p P h o n e C all 
F oll o wi n g a s u bject’s last site visit, a n n u al f oll o w- u p p h o ne calls will be c o n d ucte d f or a n 
a d diti o nal f o ur years f or s u bjects t hat pr o vi de c o nse nt a n d/ or asse nt. S u bjects will be c o nt acte d 
b y p h o ne a n n uall y ( ± 2 w ee ks) o n t he a n ni versar y of t heir Da y 0 t hr o u g h year 5 t o assess f or 
ac ute or pla n ne d pr o ce d ure a n d/ or a d missi o n f or car diac ca use as well as s ur vi val. T hes e 
a n n ual f oll o w- u p p h o ne calls will c o nti n ue i n c o ncert wit h a s u bject’s n or mal, a n n ual cli nical 
f oll o w- u p w hic h ma y i n cl u de a n n ual car diac M RI w here cli nicall y i n dicate d.
7. 1 0
R e m o v al of P ati e nt s fr o m t h e Tri al or St u d y Dr u g
T he I n vesti gat or ma y wit h dra w a s u bje ct fr o m partici pati o n i n t he st u d y f or a n y of t he 
f oll o wi n g reas o ns:
•
A si g nific a nt pr ot o c ol vi olati o n occ urs,
•
A n i nt olera ble a d v erse e ve nt o cc urs, t hat affects c o nti n uati o n of s u bject’s 
partici pati o n i n t h e st u d y,
•
T he S p o ns or or I n vesti gat or ter mi n ates t he st u d y, or
•
T he s u bject re q u ests t o be disc o nti n ue d fr o m t he st u d y.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 6 9 of 1 1 1
If a s u bject wis h es t o disc o nti n ue st u d y partici pati o n s olel y f or t h e p ur p ose of e nr olli n g i n 
a n ot her cli nical trial or e x pa n de d access pr ot oc ol, t he i n vesti gat or s h o ul d ma ke e ver y atte m pt 
t o c o nti n ue t o c ollect f oll o w- u p me dical i nf or m ati o n f or t he s u bject per t his trial’s sc he d ule. 
T his s pecific cate g or y of pr ot oc ol vi olati o n (rec ei pt of pr o hi bite d me dicati o ns) will be 
ma na ge d as d efi ne d i n t h e S A P.
7. 1 1
E arl y T er mi n ati o n Pr o c e d ur e s
E ver y reas o na ble eff ort will be ma de t o retai n s u bjects i n t he st u d y. I n t he e ve nt t hat a s u bject 
m ust be wit h dra w n fr o m t he st u d y earl y, st u d y p ers o n nel s h o ul d atte m pt t o o btai n testi n g a n d
data re q uir e d f or t h e 1 2 M o nt h Visit (see Secti o n 7. 8) as well as t he reas o n f or wit h dra w al, if 
k n o w n. A Car diac M RI will be c o n d ucte d pr o vi d e d t h e s u bject’s m ost rece nt st u d y-relate d 
Car diac M RI w as c o n d ucte d at least t hree m o nt hs (i.e., 1 2 wee ks) pri or t o t he Earl y 
Ter mi n ati o n Visit.
If t he s u bject per mits, he or s he s h o ul d be c o ntacte d b y st u d y pers o n n el at t h e ti me of t h eir 
us ual st u d y visits (a n d a n n uall y t hr o u g h 5 years p ost-i nf usi o n), as descri b e d i n t h e pr ot oc ol.
7. 1 2
L o st t o F oll o w- U p
A s u bject ca n b e c o nsi dere d “l ost t o f oll o w- u p” if he misses a visit a n d st u d y pers o n nel are 
u na ble t o c o ntact hi m, or pare nt(s)/ g u ar dia n(s) as a p pli ca ble, i n a ti mel y ma n ner wit h a 
mi ni m u m of t hree d o c u me nte d p h o ne calls. If c o nt act wit h t he s u bject, or 
pare nt(s)/ g u ar dia n(s) as a p pli ca ble, is n ot acc o m plis he d, st u d y pers o n nel s h o ul d f oll o w- u p
wit h certifie d mail i n t h e f oll o wi n g ma n ner:
1.
Mail a certifie d letter wit h ret ur n recei pt re q uesti n g c o nt act a n d e x pressi n g c o ncer n f or 
t he s u bject’s well- b ei n g.
2. If t h e s u bject, or p are nt(s)/ g uar dia n(s) as a p plica ble, d oes n ot res p o n d wit hi n se ve n da ys, 
mail a n ot her certifie d letter wit h ret ur n recei pt st ati n g t hat t he s u bject’s parti ci pati o n i n 
t he st u d y has b ee n ter mi n ate d.
3. If a si g ne d maili n g recei pt f or t h e sec o n d letter is ret ur ne d, rec or d t he t er mi n ati o n date as 
t he date t he s u bject, or pare nt(s)/ g uar di a n(s) as a p plica ble, si g n e d it. Ot her wise, rec or d
t he ter mi nati o n date as t h e date t he sec o n d letter w as maile d.
If, des pite t he eff orts n ot e d a b o ve, it is necessar y t o classif y a s u bject as l ost t o f oll o w- u p,
t hat s u bject’s E n d of St u d y ( E O S) is t he date/ti m e of last c o ntact or k n o w n e ve nt (i n cl usi v e 
of st u d y visits, tele p h o ne c o ntacts, or ot her v erificati o n of s u bject s ur vi val or m ortalit y).


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 7 0 of 1 1 1
7. 1 3
A d v er s e E v e nt s A s s e s s m e nt s
7. 1 3. 1
P erf or mi n g A d v er s e E v e nt s A s s e s s m e nt s
A n A d verse E ve nt ( A E) is a n y u nt o w ar d me dic al occ urre nce i n a s u bject or cli nical 
i n vesti gati o n s u bject te m p orall y ass o ciate d wit h t he use of a m e dici nal pr o d uct, w het her or 
n ot c o nsi dere d relate d t o t he me dici nal pr o d uct. T he occ urre n ce d oes n ot n ecessaril y h a ve t o 
ha ve a ca usal relati o ns hi p wit h t his treat m e nt. A n A E ca n t h eref ore be a n y u nfa v ora bl e a n d 
u ni nte n de d si g n (i n cl u di n g a n a b n or mal la b orat or y fi n di n g, f or e xa m ple), s y m pt o m, or 
disease ( ne w or e xacer bate d) te m p orall y ass ociate d wit h t he use of a me dici nal pr o d uct, 
w het h er or n ot c o nsi dere d relate d t o t he m e dici n al pr o d uct.
E x a m ples of a n A E i ncl u de:
•
E x acer bati o n of a c hr o ni c or i nter mitte nt pre-e xisti n g c o n diti o n i ncl u di n g eit h er a n 
i ncreas e i n fre q u e nc y or i nte nsit y of t he c o n diti o n.
•
Si g nifica nt or u n e x pecte d w orse ni n g or e x acer bati o n of t he c o n diti o n/i n dicati o n 
u n der st u d y.
•
A ne w c o n diti o n detecte d or dia g n ose d after st u d y t hera p y a d mi nistrati o n e ve n 
t h o u g h it ma y ha ve b ee n prese nt pri or t o t he st art of t he st u d y.
•
Pre- or p ost-treat me nt e v e nts t hat occ ur as a res ult of pr ot oc ol- ma n date d pr oce d ures 
(e. g., i n vasi v e pr ot oc ol- d efi n e d pr oce d ures, m o dificati o n of a s u bject’s pre vi o us 
treat me nt re gi me n).
A n A E d oes n ot i n cl u de:
•
Me dical or s ur gical pr oce d ures (e. g., c ol o n osc o p y, bi o ps y). T h e me dical c o n diti o n 
t hat lea ds t o t he pr oc e d ure is a n A E.
•
S ocial or c o n ve nie n ce h os pital a d missi o ns w here a n u nt o war d me dical occ urre nce di d 
n ot occ ur.
•
Da y t o da y fl uct uati o ns of pre-e xisti n g disease or c o n diti o ns prese nt or det ecte d at t he 
start of t he st u d y t h at d o n ot w orse n.
•
T he disease/ dis or der bei n g st u die d or e x pecte d pr o gressi o n, si g ns, or s y m pt o ms of t he 
disease/ dis or der b ei n g st u die d u nless m ore se vere t ha n e x pecte d f or t he s u bject’s 
c o n diti o n.
T he I n vesti gat or will re vi e w all d oc u m e ntati o n (e. g., h os pital pr o gress n otes, la b orat or y, or 
dia g n ostic re p orts) relati ve t o t he e ve nt bei n g re p orte d. T he I n v esti gat or will t he n rec or d all 
rele va nt i nf or m ati o n re gar di n g a n A E/ S A E i nt o t he data s yste m. It is n ot acce pta ble f or t h e 
I n v esti gat or t o se n d p h ot oc o pies of t h e s u bjects’ m e dical rec or ds i n lie u of c o m pleti o n of t he 
a p pr o priate A E/ S A E pa ges. H o w e ver, t here ma y b e i nsta nces w h e n t he Me dical M o nit or (a n 
i n de pe n de nt p h ysicia n w h o is n ot partici pati n g i n t h e cli nical st u d y), re q u ests c o pies of 
me dical rec or ds f or certai n cases. I n t his i nsta nce, all s u bject i de ntifiers will be bli n de d o n 
t he c o pies of t h e m e di cal rec or ds pri or t o s u b missi o n t o t he Me dical M o nit or.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 7 1 of 1 1 1
T he I n vesti gat or will atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, s y m pt o ms, 
a n d/ or ot her cli nical i nf or mati o n. I n s u c h cases, t he dia g n osis s h o ul d be d oc u me nte d as t he 
A E/ S A E a n d n ot t he i n di vi d ual si g ns a n d s y m pt o ms.
7. 1 3. 2
Ti mi n g
A d vers e e ve nt assess me nt a n d d oc u me ntati o n will occ ur at e ver y st u d y visit fr o m s cree ni n g 
t hr o u g h o ut t h e st u d y. O n t he da y of treat me nt a d mi nistrati o n, a s u bject’s me dical c o m plai nt 
will b e c o nsi dere d t o be a treat me nt-e mer ge nt a d v erse e ve nt if t he e ve nt occ urs a n y ti me after 
t he first e x p os ure of i n vesti gati o nal pr o d uct at t he be gi n ni n g of t he cat heterizati o n f or t he 
i nf usi o n of C A P- 1 0 0 2.  F or s u bjects recei vi n g us ual care, a n e v e nt is c o nsi dere d tr eat m e nt-
e mer ge nt if it occ urs o n or after 9: 0 0 a m (i n t h e s u bject’s ti me z o ne) o n D a y 0.
7. 1 3. 3
S e v erit y
T he I n vesti gat or will ma ke a n assess me nt of i nte nsit y f or eac h A E a n d S A E re p orte d d uri n g 
t he st u d y. T he ass ess me nt will be base d o n t h e I n v esti gat or’s cli nical j u d g m e nt. T he i nte nsit y 
of eac h A E a n d S A E will be assi g ne d t o o n e of t he f oll o wi n g cate g ories:
Mil d:
A n e ve nt t hat is easil y t olerate d b y t he s u bject, ca usi n g mi ni mal disc o mf ort 
a n d   n ot i nterferi n g wit h e ver y da y acti vities.
M o der ate:
A n e ve nt t hat is s ufficie ntl y disc o mf orti n g t o i nterfere wit h n or mal e ver y d a y 
acti vities.
Se vere:
A n e ve nt t hat pre ve nts n or mal e ver y da y acti viti es.
A n A E t hat is assesse d as se vere will n ot be c o nf use d wit h a n S A E. Se verit y is a cate g or y 
utili ze d f or rati n g t he i nte nsit y of a n e v e nt; a n d b ot h A Es a n d S A Es ca n b e assesse d as 
se vere. A n e ve nt is descri be d as ‘seri o us’ w he n it meets o ne of t he pre- d efi ne d o utc o mes as 
descri b e d i n t he Se cti o n 7. 1 3. 8 Seri o us A d v erse E ve nts.
7. 1 3. 4
R el ati o n s hi p
T he I n vesti gat or is o bli gate d t o assess t he relati o ns hi p bet w ee n st u d y t hera p y a n d t h e 
occ urre nce of eac h A E/ S A E. T he I n vesti gat or will use cli nical j u d g me nt t o deter mi ne if t here 
is a reas o na bl e p ossi bilit y t hat t he p h ar mac ol o gical acti o n of t he st u d y a ge nt, or t he i nf usi o n 
pr oce d ure itself, was res p o nsi ble f or t h e A E/ S A E bei n g re p orte d. Alter nati ve ca uses s u c h as 
nat ural hist or y of t he u n d erl yi n g diseases, c o n c o mita nt t hera p y, ot her ris k fact ors, a n d t he 
te m p oral relati o ns hi p of t he e ve nt t o t he st u d y a ge nt will be c o nsi dere d a n d i n vesti gate d. T h e 
I n v esti gat or will als o c o ns ult t h e I n vesti gat or’s Br oc h ure a n d/ or Pr o d uct I nf or mati o n, f or 
mar kete d pr o d ucts, i n t he deter mi nati o n of his/ her assess me nt.
All A E/ S A E t hat occ ur d uri n g t he c o urse of t he cli nical st u d y will be e val uate d. F or eac h 
A E/ S A E, t he i n vesti gat or will ma ke a deter mi n ati o n of relate d n ess t o t he i n vesti gati o nal 
pr o d uct a n d, se p aratel y, assess relate d ness t o t he pr oce d ure.  Eac h will be defi ne d acc or di n g 
t o o ne of t he f oll o wi n g cate g ories:


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 7 2 of 1 1 1
Defi nite:
T he A E/ S A E is clearl y relate d t o t he i n vesti gati o n al pr o d uct or pr o ce d ure.
Pr o b a bl e:
T he A E/ S A E is li kel y relate d t o t he i n vesti gati o nal pr o d uct or pr oce d ure.
P ossi ble:
T he A E/ S A E ma y be relate d t o t he i n vesti gati o nal pr o d uct or pr o ce d ure. All 
A Es a n d S A Es t hat occ ur wit hi n 2 4 h o urs of i nter v e nti o n will, beca use of t h e
te m p oral relati o ns hi p, be c o nsi dere d as at least p ossi bl y relate d t o t h e 
pr oce d ure a n d will be re p orte d t o t he D S M B.
U nli k el y:
T he A E/ S A E is d o u btf ull y relate d t o t he i n vesti gati o nal pr o d uct or 
pr oce d ure.
U nrel ate d: T he A E/ S A E is clearl y N O T relate d t o t he i n vesti gati o nal pr o d uct or 
pr oce d ure.
T here ma y be sit uati o ns w he n a n S A E has o cc urre d a n d t he I n v esti gat or h as mi ni mal 
i nf or mati o n t o i ncl u de i n t he i niti al re p ort. H o we ver, it is ver y i m p orta nt t hat t he I n vesti gat or
ma ke a n assess me nt of ca usalit y
7. 1 3. 5
E x p e ct e d n e s s
T he f oll o wi n g a d vers e e v e nts are c o nsi dere d t o be e x pecte d as a res ult of t he cat het erizati o n 
a n d i nf usi o n pr oce d ure:
•
S o me pre mat ure ve ntric ular c o ntracti o ns, n o n-s ust ai ne d ve ntric ul ar tac h yc ar dia ( < 3 0 
sec d urati o n)
•
H y p ote nsi o n ( S yst olic Bl o o d Press ure < 8 0 m m H g) a n d/ or bra d ycar dia ( Heart R ate 
< 5 0 beats/ mi n) t hat res p o n ds ra pi dl y t o fl ui d, atr o pi ne a n d p ossi bl y vas o press or 
a d mi nistrati o n, if re q uir e d
•
Re d ucti o n of c or o nar y bl o o d fl o w, TI MI fl o w gra de I or II, persisti n g < 3 mi n after 
ball o o n deflati o n, d uri n g cell i nf usi o n
•
A n gi na, d urati o n < 1 0 mi n d uri n g cell i nf usi o n
•
S T ele vati o ns, d urati o n < 3 mi n d uri n g cell i nf usi o n, tr o p o ni n ele vati o ns a b o ve t h e 9 9 t h
perce ntile b ut n ot m ore t ha n 3 x, at a n y ti me d uri n g t h e first 2 4 h o urs after cell 
i nf usi o n
•
Dissecti o n of o ne or m ore of t h e i nf use d arteri es
•
Blee di n g, br uisi n g a n d/ or he mat o ma f or mati o n at t h e sit e of vasc ular access f or t he 
cell i nf usi o n pr oce d ure, at a n y ti me wit hi n t he first 2 4 h o urs after cell i nf usi o n
All a d verse e ve nts e x pecte d or ot her wise, s h o ul d be re p ort e d i n t he s u bject data. Seri o us 
A d vers e E v e nts ( S A Es) s h o ul d be re p orte d t o t he S p o ns or wit hi n 2 4 h o urs of t he site lear ni n g 
of t he e ve nt.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 7 3 of 1 1 1
7. 1 3. 6
Cli ni c al Si g nifi c a n c e
A n a b n or mal la b val u e or test res ult s h o ul d be dee me d cli nicall y si g nifica nt if eit h er of t he 
f oll o wi n g c o n diti o ns is met:
•
T he a b n or malit y s u g gests a disease a n d/ or or ga n t o xicit y t hat is ne w or h as w orse ne d 
fr o m baseli n e.
•
T he a b n or malit y is of a d e gree t h at re q uires a d diti o nal acti v e ma n a ge me nt, e. g., 
c ha n ge of d os e, dis c o nti n uati o n of a dr u g, cl ose o bser vati o n, m ore fre q ue nt f oll o w- u p
assess me nts, or f urt h er di a g n ostic i n vesti gati o n.
A q ualifie d p h ysicia n at t he i n vesti gati ve site, eit h er t h e I n v esti gat or or a S u b-I n vesti gat or, 
will re vie w all st u d y-relate d la b orat or y a n d ot h er t est res ults. T he re vie wi n g I n v esti g at or will 
use his/ her me dical j u d g me nt t o classif y a n d d o c u me nt a n y res ults t h at are o utsi de of t he 
n or mal res ults ra n ge. T he I n v esti gat or will i n dicate w het her eac h a b n or mal res ult is cli nicall y 
si g nifica nt ( C S) or n ot cli nicall y si g nifica nt ( N C S) o n t h e s o urce d o c u me nt a n d case re p ort 
f or m.
O nce t he I n v esti gat or dee ms a n a b n or mal val ue t o be cli nicall y si g nifi ca nt ( C S), he or s he 
will d eter mi ne w het her t here is a cli nical e xa m fi n di n g or s y m pt o m ( n e w or pre-e xisti n g) t hat
e x plai ns t he a b n or mal val ue. A pr o gress n ote s u m marizi n g t he fi n di n gs, i ncl u di n g t h e 
reas o n(s) w h y t h e res ults are dee me d C S will be writte n t o pr o vi de d oc u me ntati o n f or a n 
a d verse e ve nt re p ort. If t he I n vesti gat or is a ble t o pr o vi de a differe ntial dia g n osis f or t h e C S 
res ult, he or s he s h o ul d d escri be t h e A E acc or di n gl y, e. g., uri nar y tract i nfecti o n or s us pecte d 
a ne mia. I n t he a bse nce of a n ass ociate d cli nical si g n or s y m pt o m, a n d if o nl y a si n gle v al ue is 
dee me d C S, list t he a b n or mal val ue itself as t he A E, e. g., ele vate d p otassi u m or decrease d 
calci u m. As m ore i nf or m ati o n a b o ut t h e a b n or mal val ue is k n o w n t hat pr o vi des a dia g n osis, 
t he A E s h o ul d be u p date d i n t he electr o nic d ata s yste m t o reflect t h e di a g n osis.
7. 1 3. 7
Cli ni c al L a b or at or y A d v er s e E v e nt s
A b n or mal la b orat or y fi n di n gs (e. g. cli nical c he mistr y, he mat ol o g y, a n d uri n al ysis) t hat are 
j u d ge d b y t he I n vesti gat or as cli nicall y si g nifica nt ( C S) will be d oc u me nte d as d escri be d i n 
Secti o n 7. 1 3. 1 a n d will be rec or d e d as A Es or S A Es if t h e y meet t h e defi niti o n of a n A E as 
defi ne d i n Secti o n 7. 1 3. 1 or S A E, as defi n e d i n Secti o n 7. 1 3. 8.
Cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs t h at are detecte d d uri n g t he st u d y or are 
prese nt at scree ni n g a n d si g nifica ntl y w orse n f oll o wi n g t he start of t he st u d y will be re p orte d 
as A Es or S A Es. H o w e ver, cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs t h at are 
ass ociate d wit h t he disease bei n g st u die d, u nless j u d ge d b y t h e I n vesti gat or as m ore se vere 
t ha n e x pecte d f or t he s u bject’s c o n diti o n, or t hat are pres e nt or detecte d at t he start of t h e 
st u d y b ut d o n ot w orse n, will n ot be re p orte d as A Es or S A Es.
T he I n vesti gat or will e xercise me dic al j u d g me nt i n deci di n g w het her a b n or mal la b orat or y 
val ues are cli nicall y si g nifica nt.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 7 4 of 1 1 1
7. 1 3. 8
S eri o u s A d v er s e E v e nt s
7. 1 3. 8. 1  
D efi niti o n
A seri o us a d verse e v e nt ( S A E) is defi n e d b y fe deral re g ulati o n as a n y A E o cc urri n g at a n y 
d ose t hat res ults i n a n y of t he f oll o wi n g o ut c o mes: deat h, life-t hreate ni n g A E, h os pitalizati o n 
or pr ol o n gati o n of e xisti n g h os pitalizati o n, a persiste nt or si g nific a nt disa bilit y/i n ca pacit y, or 
a c o n ge nital a n o mal y/ birt h defect.
I m p orta nt me dical e v e nts t hat ma y n ot res ult i n deat h, be life t hreate ni n g, or re q uire 
h os pitalizati o n ma y b e c o nsi dere d a n S A E w he n, base d u p o n a p pr o priate me dical j u d g me nt, 
t he y m a y je o par diz e t h e s u bject a n d ma y re q uire me dical or s ur gical i nter ve nti o n t o pre ve nt 
o ne of t h e o utc o mes liste d i n t his defi niti o n. E xa m ples of s uc h me dical e v e nts i ncl u de 
aller gic br o n c h os pas m re q uiri n g i nte nsi ve treat m e nt i n a n e mer ge n c y r o o m or at h o me, bl o o d 
d yscrasias or c o n v ulsi o ns t hat d o n ot res ult i n i n patie nt h os pitalizati o n, or t he de vel o p me nt of 
dr u g d e pe n de nc y or dr u g a b use.
C o m plicati o ns t hat occ ur d uri n g h os pitalizati o n are A Es.  If a c o m pli cati o n pr ol o n gs 
h os pitalizati o n or f ulfills a n y ot h er seri o us criteria, t h e e ve nt is seri o us.  H os pitalizati o n f or 
electi ve treat me nt of a pre-e xisti n g c o n diti o n t h at di d n ot w orse n fr o m b aseli ne is n ot
c o nsi dere d t o be a n A E.
T he ter m disa bilit y mea ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit y t o c o n d uct n or mal life 
f u ncti o ns.  T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie nces of relati vel y mi n or me dical 
si g nifica nce s u c h as u nc o m plicate d hea dac he, na usea, v o miti n g, diarr hea, i nfl ue nza, 
acci d e nt al tra u ma (i. e., s prai n e d a n kle) t hat ma y i nterfere or pre ve nt e ver y da y life f u ncti o ns 
b ut d o n ot c o nstit ute a s u bsta ntial disr u pti o n.
7. 1 3. 8. 2  
R e p orti n g S eri o u s A d v er s e E v e nt s
All S A Es, i ncl u di n g a n y fatal or life-t hreat e ni n g e ve nt, m ust be re p orte d wit hi n 2 4 h o urs 
fr o m t he ti me t he I n v esti gat or is ma de a ware of t h e e ve nt. If t he I n vesti gat or d oes n ot h a ve 
all i nf or mati o n re gar di n g a n S A E, he/s he will n ot wait t o recei ve a d diti o nal i nf or mati o n 
bef ore rec or di n g t h e e ve nt i n t he d ata s yste m a n d c o m pleti n g as m uc h i nf or mati o n k n o w n at 
t he ti me of t he s u b missi o n. 
T o re p ort t h e e v e nt, a n S A E fr o m m ust be c o m plete d a n d s u b mitte d t o t h e data ma na ge me nt 
gr o u p wit hi n t h e a p pr o priate re p orti n g ti meli nes as f urt her descri be d i n t he st u d y ma n ual. 
A d diti o nall y, t h e Me dical M o nit or s h o ul d be c o ntacte d a n d i nf or me d of t h e e ve nt, prefera bl y 
b y fa x, as f oll o ws:
U nite d Bi o S o urce C or p orati o n
P h o ne: 1- 8 0 0- 8 2 9- 6 1 7 0
Fa x: 1- 8 7 7- 2 0 0- 2 9 4 5
E mail: Ca pric or Safet y @ u nite d bi os o urce.c o m


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 7 5 of 1 1 1
T he Me dical M o nit or will re vie w all i nf or m ati o n pr o vi de d a n d c o nta ct t h e I n vesti gat or f or 
a d diti o nal i nf or mati o n, as necessar y.
Per I C H E 2 A a n d 2 1 C F R 3 1 2, re g ul at or y a ge ncies will be n otifie d b y t h e S p o ns or b y 
tele p h o ne or fa x of a n y u ne x pecte d, S A E p ote ntiall y ass o ciate d wit h treat me nt as s o o n as 
p ossi ble, b ut i n n o e ve nt later t h a n 1 5 cale n dar da ys after t he S p o ns or’s i nitial recei pt of t he 
i nf or mati o n; fatal or life-t hreate ni n g u ne x pecte d S A Es ass ociate d wit h treat me nt will be 
re p orte d t o re g ulat ors wit hi n 7 cale n dar da ys. F oll o w- u p i nf or mati o n will be pr o vi de d as 
re q uire d.
All A Es a n d S A Es d oc u me nte d at a pre vi o us visit/ c o ntact t hat are desi g nate d as o n g oi n g will 
be re vie w e d at s u bse q u e nt visits/c o ntacts.
All A Es (i ncl u di n g S A Es) will be f oll o w e d u ntil res ol uti o n, u ntil n o f urt her c ha n ges i n t he 
e ve nt are e x pecte d (i.e. t he p oi nt at w hic h a s u bject e x perie nci n g a n a d v ers e e ve nt is treate d 
s uccessf ull y a n d sta bilize d e ve n t h o u g h t he y ma y c o nti n ue t o e x perie nce s e q uelae) as 
c o nfir me d b y t he I n v esti gat or, u ntil t he s u bject is l ost t o f oll o w- u p, or u ntil t he s u bject’s 1 2 
M o nt h Visit. S u bjects will be c o ntacte d b y p h o n e a n n uall y t hr o u g h year 5 p ost-i nf usi o n t o 
assess f or ac ute or pl a n ne d pr oce d ure a n d/ or a d missi o n f or car di ac c a use as well as s ur vi val. 
If a s u bject dies d uri n g p artici pati o n i n t he st u d y or d uri n g a rec o g nize d f oll o w- u p peri o d, t he 
Me dical M o nit or will be pr o vi de d wit h a c o p y of a n y p ost- m orte m fi n di n gs, i ncl u di n g 
hist o pat h ol o g y.
Ne w or u p d ate d i nf or mati o n will be rec or d e d b y m o dif yi n g t he A E f or ms i n t he data s yst e m.
T he I n vesti gat or will pr o m ptl y re p ort all S A Es wit hi n t h e ti mefra mes s pecifie d i n t his 
pr ot oc ol. T he I n vesti gat or will c o m pl y wit h t he a p plica ble l ocal re g ulat or y re q uire me nts 
relate d t o re p orti n g of S A Es t o his or her I nstit uti o nal Re vie w B oar d (I R B) or I n de pe n de nt 
Et hics C o m mittee (I E C).
T his pr ot oc ol is bei n g fil e d u n der a n I n v esti gati o nal Ne w Dr u g (I N D) a p pli cati o n wit h t he 
F D A i n t he U S as w ell as wit h ot her i nter n ati o nal re g ul at or y a ge ncies.  A gi ve n S A E ma y 
q ualif y f or a n E x pe dite d Safet y R e p ort ( E S R) if t h e S A E is b ot h attri b uta ble t o st u d y t hera p y 
a n d u ne x pecte d. I n t his case, all I n vesti gat ors parti ci pati n g i n t he st u d y will recei v e t h e E S R. 
T he p ur p ose of t h e E S R is t o f ulfill s pecific re g ulat or y a n d G o o d Cli nical Practi ce ( G C P) 
re q uire me nts re gar di n g t he pr o d uct u n der i n vesti gati o n.
7. 1 3. 9
S p o n s or M o nit ori n g of A d v er s e E v e nt s
T he f oll o wi n g list s u m marizes t he S p o ns or’s r ole i n m o nit ori n g A E/ S A Es:
•
All S A Es will be re vie we d b y t h e S p o ns or’s
Me di cal M o nit or or desi g nee wit hi n 1 
b usi ness da y of recei vi n g t he seri o us a d verse e ve nt f or m fr o m t he cli nical ce nter.
•
If t he Me dical M o nit or re q uires a d diti o nal i nf or mati o n t o ma ke his/ her assess me nt, 
t he cli nical ce nters will h a ve 2 b usi ness da ys t o res p o n d t o t h e re q uest f or a d diti o nal 
i nf or mati o n.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 7 6 of 1 1 1
7. 1 3. 1 0
P o st- St u d y A d v er s e E v e nt s a n d S eri o u s A d v er s e E v e nt s
T he I n vesti gat or s h o ul d n otif y t he Me di cal M o nit or of a n y d eat h or S A E o cc urri n g at a n y 
ti me after a s u bject has c o m plete d or ter mi n ate d a cli nical trial, w he n s uc h deat h or S A E ma y 
reas o na bl y b e relate d t o t he st u d y t hera p y use d i n t his i n vesti gati o nal trial. I n v esti gat ors are 
n ot o bli gate d t o acti vel y see k A Es fr o m f or m er st u d y partici pa nts.
8
Q U A LI T Y C O N T R O L A N D A S S U R A N C E
Data will be e ntere d usi n g a v ali d ate d data s yst e m. A d etaile d descri pti o n of t h e data 
c ollecti o n t o ols a n d data ma na ge me nt pr ocess ca n be f o u n d i n t h e case re p ort f or m
c o m pl eti o n g ui deli nes a n d ot h er data ma n a ge me nt materials t hat will be pr o vi de d t o eac h 
site.  T he sit e m ust e ns ure a p pr o priate s o urce d ata d oc u me ntati o n. T he I n v esti gat or or 
desi g nee m ust e nter all re q uire d s u bject data i n t he data s yst e m i n a ti mel y fas hi o n ( wit hi n 3 
wee ks of st u d y visit) a n d a n e x pla nati o n m ust be d oc u me nte d f or a n y missi n g data.
A site i niti ati o n visit will be c o n d ucte d at eac h site parti ci pati n g i n t he st u d y.  D uri n g t his 
visit, t here will be a re vie w of t h e st u d y pr ot oc ol, st u d y pr oce d ures, t he case re p ort f or ms, t he 
data c ollecti o n a n d s u b missi o n pr ocess, a n d t he sit e’s re g ulat or y o bli g ati o ns as well as a n y 
s pecial pr oce d ures wit h t he ce nter pers o n nel. A re prese ntati ve fr o m t he S p o ns or, or desi g nee, 
will lea d t he sit e i nitiati o n visits. All trai ni n g will be d oc u me nte d. A f or mal, ce ntraliz e d 
i n vesti gat or m eeti n g m a y be hel d pri or t o i nitiati o n of t he st u d y, b ut will n ot re m o ve t h e 
re q uire me nt f or c o n d u cti n g a sit e i nitiati o n visit at eac h p arti ci pati n g site. 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 7 7 of 1 1 1
9
P L A N N E D S T A TI S TI C A L
M E T H O D S
9. 1
G e n er al C o n si d er ati o n s
A n y c ha n ges m a de t o t he a nal ysis of t h e data n ot state d i n t he pr ot oc ol will be descri b e d i n 
t he Statistical A nal ysis Pl a n.
9. 2
D et er mi n ati o n of S a m pl e Si z e
T his sa m ple size is a de q uate t o s u p p ort a n assess m e nt of safet y a n d t olera bilit y of 
i ntrac or o nar y i nf usi o n of C A P- 1 0 0 2 i n t his dis ease p o p ulati o n, as well as a n e x pl orat or y 
assess me nt of efficac y.
9. 3
A n al y si s P o p ul ati o n s 
•
I nte nt t o Treat (I T T) P o p ulati o n: All s u bjects ra n d o mize d. S u bjects will be s u m mariz e d 
a n d a nal yz e d per t h eir ra n d o mizati o n assi g n me nt, re gar dl ess of t he treat m e nt ( C A P- 1 0 0 2
or us ual care) act u all y recei v e d.
•
M o difie d I T T ( mI T T) P o p ulati o n: S u bjects i n t he C A P- 1 0 0 2 treat m e nt gr o u p w h o 
recei v e d t he I P, a n d all s u bjects i n t he us ual car e treat me nt gr o u p w h o re m ai n o n st u d y as 
of 9: 0 0 a m (s u bject’s ti me z o ne) o n Da y 0. S u bjects will be s u m marize d a n d a nal yze d p er 
t heir ra n d o miz ati o n assi g n me nt, re gar dl ess of t he treat m e nt ( C A P- 1 0 0 2 or us u al care) 
act uall y recei ve d.
•
Per Pr ot oc ol P o p ulati o n: S u bjects wit h n o maj or pr ot oc ol vi olati o ns. T he list of s u bjects 
wit h maj or pr ot o c ol vi olati o ns will be c o m pile d pri or t o data base l o c k. 
•
Safet y P o p ulati o n: S u bjects ra n d o mi ze d t o C A P- 1 0 0 2 treat me nt w h o recei v e d t he I P, a n d 
all s u bjects i n t he us ual care tr eat m e nt gr o u p w h o re m ai n o n st u d y as of 9: 0 0 a m 
(s u bject’s ti m e z o ne) o n Da y 0. S u bjects will be s u m marize d a n d a nal yz e d per treat me nt 
act uall y recei ve d, re gar dless of t heir ra n d o mizati o n assi g n m e nt.
9. 4
Effi c a c y A n al y si s
T he pri mar y a nal ysis of efficac y will be perf or me d f or t he mI T T P o p ulati o n as defi n e d 
a b o ve. A d diti o nal a nal ys es will be defi ne d i n t he S A P.
9. 4. 1  
C ar di a c M RI,
M o bilit y, a n d Q u alit y of Lif e P ar a m et er s
Car diac str uct ural res ults will be s u m marize d f or t he i nter ve nti o n a n d c o ntr ol gr o u ps f or eac h 
visit at w hic h t he y are p erf or me d. A bs ol ute a n d relati ve c ha n ges c o m pare d t o baseli n e will 
be s u m mariz e d usi n g descri pti ve statistics.
F u ncti o nal a n d m o bilit y val ues will be s u m m ariz e d usi n g descri pti ve statistics a n d c ha n ges 
fr o m baseli ne will b e c o m pare d bet w ee n gr o u ps.
I m pr o v e me nts i n q ualit y of life para meters will be liste d a n d s u m m ariz e d usi n g descri pti ve 
statisti cs a n d c o m pare d b et wee n gr o u ps.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 7 8 of 1 1 1
9. 4. 2 
Bi o m ar k er s 
Bi o mar ker res ults f or Ost e o p o nti n, S T 2, I L- 1 0, a n d Galecti n- 3 will be liste d a n d s u m marize d 
usi n g descri pti v e statistics.  
9. 5
S af et y A n al y si s 
T he pri mar y a nal ysis of safet y will be perf or me d o n t he S afet y P o p ulati o n as defi ne d a b o v e. 
A d diti o nal a nal ys es will be defi ne d i n t he S A P.
9. 5. 1 
S af et y E n d p oi nt s
Safet y a n d t olera bilit y of i ntrac or o nar y i nf usi o n of C A P- 1 0 0 2 will be e val uate d b y t he 
occ urre nce of re d ucti o n i n TI MI fl o w a n d m aj or car diac e ve nts, fre q ue nc y a n d se verit y of 
a d verse e ve nts, a n d b y c ha n ges fr o m b aseli ne i n la b orat or y assess me nts, vital si g ns, p h ysical 
e x a mi nati o n, a n d E C G.
9. 5. 2 
A d v er s e E v e nt s 
A d vers e e ve nts will be c o de d usi n g t he M e d D R A dicti o nar y a n d ta b ulate d. 
Treat m e nt- e mer ge nt a d v erse e v e nts ( T E A Es) are defi n e d as a n y A E t hat st arte d after t h e first 
e x p os ure of i n vesti gati o n al pr o d uct or starte d pri or t o t he first e x p os ure b ut i ncreas e d i n 
se verit y or fre q ue n c y aft er i nf usi o n. F or t h os e s u bjects ra n d o mize d t o us ual care, T E A Es are
defi ne d as a n y a d verse e ve nt be gi n ni n g o n or after 9: 0 0 a m (s u bject’s ti me z o ne) o n Da y 0 or
t hat i ncreas e d i n se verit y or fre q u e nc y after t h at ti me. T he i n ci de nce of T E A Es will be 
prese nte d b y s yste m or ga n class a n d preferre d ter m. A d verse e ve nts will als o be s u m marize d 
b y se v erit y a n d relati o ns hi p t o t he i n vesti gati o nal pr o d uct a n d pr oce d ure.
T he i nci d e nce of T E A Es l ea di n g t o wit h dra wal fr o m t h e st u d y will be prese nte d. 
Listi n gs of a n y seri o us a d verse e ve nts ( S A Es), deat hs, a n d A Es or a b n or mal la b orat or y 
val ues lea di n g t o disc o nti n uati o n of a s u bject fr o m t he st u d y will be prese nt e d.  
9. 5. 3 
L a b or at or y E v al u ati o n s 
La b orat or y v al ues at eac h c oll ecti o n ti me will b e liste d a n d s u m m ariz e d usi n g descri pti ve 
statisti cs. E ac h p ost-treat me nt la b orat or y val u e will be c o m pare d t o bas eli n e (last val ue pri or 
t o starti n g treat m e nt).  
9. 6
Mi s si n g D at a 
Ha n dli n g of missi n g data will be detaile d i n t he S A P. 
9. 7
St u d y St o p pi n g R ul e s
T he st u d y will be h alte d if c o nti n uati o n re prese nts a n u nacce pta ble ris k/ b e nefit pr ofile f or 
st u d y s u bjects, as d eter mi n e d b y t he s p o ns or, t he D S M B, or a p plic a ble re g ulat or y a ut h oriti es.
St u d y st o p pi n g r ules, fi n aliz e d b y c o nse ns us of t h e D S M B, are detaile d i n t he D S M B 
C harter.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 7 9 of 1 1 1
1 0 I N D E P E N D E N T O V E R SI G H T C O M MI T T E E S
1 0. 1
Cli ni c al E v e nt s C o m mitt e e ( C E C)
T he c har ge of t h e Cli nical E ve nts C o m mittee ( C E C) is t o re vie w s o urce d o c u me nts a n d t o 
a dj u dicate (a) all pri mar y a n d sec o n dar y safet y e n d p oi nt e ve nts, ( b) all seri o us, all pr ot o c ol-
defi ne d, a n d i nter ve nti o n-relate d a d v ers e e v e nts, t he s e verit y a n d relate d n ess of t he a d vers e 
e ve nts, a n d (c) t he ca uses of m ortalit y e v e nts. T he i n di vi d uals w h o will ser ve o n t h e 
c o m mitt ee are u n affili ate d wit h t he cli nical site a n d t he st u d y dr u g ma n ufact urer ( Ca pric or, 
I n c.), a n d will be a p p oi nte d b y t h e S p o ns or.  T he c o m mittee will c o nsist of, at least, a heart 
fail ure car di ol o gist a n d i nter v e nti o nal car di ol o gists.  A d diti o nal e x perts i n i m m u n ol o g y will 
be c o ns ulta nts t o t he c o m mittee as necess ar y. T he C E C will m eet e ver y 6 m o nt hs or as 
nee de d t o a dj u dicate a d v erse e v e nts a n d o utc o mes data f or eac h s u bject ra n d o miz e d.
1 0. 2
D at a S af et y M o nit ori n g B o ar d ( D S M B) 
T o meet t h e st u d y's et hical res p o nsi bilit y t o its s u bjects, a n i n de pe n d e nt D S M B will m o nit or 
res ults d uri n g t he st u d y. T he b oar d c o nsists of p h ysicia ns a n d bi ostatisticia n(s), w h o ha v e n o 
f or mal i n v ol ve me nt or c o nflict of i nterest wit h t he s u bjects, ma n ufact urer ( Ca pric or, I n c.), 
t he i n vesti gat ors, or t he cli nical sites, a n d will be a p p oi nte d b y t he s p o ns or. T he D S M B will 
act i n a se ni or a d vis or y ca pacit y t o t he s p o ns or re gar di n g d ata a n d s afet y m atters t hr o u g h o ut 
t he d urati o n of t h e st u d y. T he b oar d will meet o n a peri o dic basis acc or di n g t o t he D S M B
c harter t o m o nit or t he a v aila ble i nf or mati o n re gar di n g safet y, efficac y, a n d q ualit y of trial 
c o n d uct. As n ote d i n Secti o n 3. 1, t he D S M B will re vie w t he 7 2 h o ur safet y data f or Gr o u p 1,
t o deter mi ne w het her e nr oll me nt f or Gr o u p 2 ma y i niti ate. I n a d diti o n, t h e D S M B will 
re vie w i nteri m s u m mar y res ults of t h e acc u m ulati n g dat a fr o m t he Cli nical E ve nts
C o m mittee e ver y 6 m o nt hs.  T he y will c o m m u nicate t heir fi n di n gs directl y wit h t he s p o ns or.  
T he cli nical ce nt ers will ha ve n o c o ntact wit h t he me m bers of D S M B a n d n o v oti n g me m ber 
of t he c o m mittee ma y partici pate i n t he st u d y as a n i n vesti gat or.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 8 0 of 1 1 1
1 1
A D MI NI S T R A TI V E C O N SI D E R A TI O N S
1 1. 1 I n v e sti g at or s a n d St u d y A d mi ni str ati v e Str u ct ur e 
A c o m plete list of parti ci pati n g I n v esti gat ors a n d i nstit uti o ns will be mai ntai ne d b y t he 
S p o ns or a n d will be p oste d at htt p:/ w w w.cli nicaltrials. g o v i n t he listi n g f or t his st u d y.
S h o ul d a q uesti o n aris e d uri n g t h e st u d y fr o m t he I n v esti gat or or st u d y staff, t he staff ma y 
c o ntact t he S p o ns or staff usi n g t he c urre nt st u d y c o ntact i nf or mati o n as pr o vi de d o n 
htt p:/ w w w.cli nicaltrials. g o v i n t he listi n g f or t his st u d y.
C o ntact i nf or mati o n f or t he M e dical M o nit or f or t he st u d y is pr o vi de d b el o w: 
S p o ns or Me dical M o nit or: 
, M D   
, Ca pric or I n c.
St u d y M o nit ors ( Cli nical R esearc h Ass ociates) will als o be assi g ne d t o t his st u d y a n d c o ntact 
i nf or mati o n will be pr o vi de d t o t he sites t hr o u g h o ut t he st u d y. 
C o ntract researc h or ga ni zati o ns ( C R Os) will be use d, at t h e S p o ns or’s directi o n, f or site 
m o nit ori n g, data ma n a ge me nt, a nal ysis a n d/ or re p orti n g f or t he st u d y.  A c ore i m a gi n g gr o u p 
will b e use d t o ce ntrall y rea d all M RIs a n d a c ore l a b orat or y will be use d t o a nal yze s a m ples 
f or H L A t y pi n g, D S A m o nit ori n g a n d cell ular i m m u ne res p o nse ( E LI S p ot). C o ntact 
i nf or mati o n f or t hese gr o u ps will be pr o vi de d t o t he sites pri or t o t he st art of t h e st u d y. 
I n or der t o e ns ure q u alit y a n d c o nti n ua nc e of patie nt care, it is hi g hl y rec o m me n de d t h at t h e 
s u bject i nf or m his/ her pri m ar y care p h ysicia n of his parti ci pati o n i n t he st u d y 
1 1. 2 I n stit uti o n al R e vi e w B o ar d (I R B) A p pr o v al 
It is t he I n v esti gat ors’ res p o nsi bilit y t o e ns ure t h at t his pr ot oc ol is re vie we d a n d a p pr o ve d b y 
t he a p pr o priat e l ocal I nstit uti o nal Re vie w B oar d (I R B) pri or t o i nitiati n g t his st u d y. T he 
c o m p ositi o n a n d c o n d uct of t his c o m mitt ee m ust c o nf or m t o t he U nite d States C F R a n d 
I C H E 6.
T he I R B m ust als o re vi e w a n d a p pr o v e t h e sit e’s i nf or me d c o nse nt f or m (I C F), asse nt f or m 
( A F), a n d ot her writte n i nf or mati o n pr o vi de d t o t he s u bject a n d all a d v ertis e me nts t hat ma y 
be use d f or s u bject recr uit me nt. 
If it is necessar y t o a me n d t h e pr ot oc ol, t he I C F, or A F d uri n g t he st u d y, t h e I n vesti gat or will 
be res p o nsi ble f or e ns uri n g t hat t he I R B re vie ws a n d a p pr o ves t hes e a me n d e d d oc u me nts. A n 
I R B a p pr o v al of t he a m e n de d pr ot o c ol a n d/ or I C F/ A F m ust be o btai ne d i n writi n g bef ore 
i m ple me ntati o n of t he a me n de d pr oce d ures a n d bef ore n e w s u bjects c o ns e nt/ pr o vi de asse nt 
t o partici pate i n t he st u d y usi n g t he a me n d e d versi o n of t he I C F/ A F. 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 8 1 of 1 1 1
1 1. 3
Et hi c al C o n d u ct of t h e St u d y
T his st u d y will be c o n d ucte d i n acc or da n ce wit h G o o d Cli nical Practice ( G C P) re q uire me nts 
descri b e d i n t he c urre nt re visi o n of I nter nati o nal C o nfere nce o n Har m o nisati o n of Tec h nic al 
Re q uire me nts of P h ar m ace uticals f or H u ma n Use (I C H) G ui d eli n es a n d all a p plica ble 
re g ulati o ns, i n cl u di n g c urre nt U nite d States C o de of Fe d eral Re g ulati o ns ( C F R), Title 2 1, 
Parts 1 1, 5 0, 5 4, 5 6, a n d 3 1 2 a n d Title 4 5, Part 1 6 4. C o m plia nce wit h t hese re g ulati o ns a n d 
g ui deli nes als o c o nstit utes c o m plia nce wit h t he et hical pri nci ples descri b e d i n t he c urre nt 
re visi o n of t he D eclarati o n of Helsi n ki. T his st u d y will als o be carrie d o ut i n acc or da nce wit h 
l ocal le gal re q uire me nts.
1 1. 4
S u bj e ct I nf or m ati o n, C o n s e nt, a n d A s s e nt
Bef ore bei n g a d mitt e d t o t he cli nical st u d y, all s u bjects m ust c o nse nt i n writi n g t o parti ci pat e. 
A n I C F will be gi v e n t o eac h s u bject, w hic h will c o ntai n all U nite d States fe derall y re q uire d 
ele me nts, all I C H-re q uire d ele me nts, a n d Healt h I ns ura nce P ort a bilit y a n d Acc o u nta bilit y
Act ( HI P A A) a ut h oriz ati o n i nf or mati o n i n la n g u a ge t h at is u n dersta n da ble t o t he s u bject.
T he pr ocess of o btai ni n g t h e i nf or me d c o nse nt a n d/ or asse nt will be i n c o m plia nce wit h all 
fe deral re g ulati o ns, I C H re q uire me nts, a n d l o cal l a ws.
T he I n vesti gat or will re vi e w t he st u d y wit h eac h s u bject, a n d as a p pli ca ble pare nt(s) a n d/ or 
g uar dia n(s). T he re vie w will i ncl u de t he nat ure, s c o pe, pr oce d ures, a n d p ossi ble 
c o nse q u e nces of t he s u bj ect's partici pati o n i n t h e st u d y. T he I C F a n d/ or A F a n d re vie w will 
be i n a f or m u n dersta n da ble t o t he s u bject. T he I n vesti gat or or d esi g n ee a n d t he s u bject, a n d 
as a p plica ble t he p are nt(s) a n d/ or g uar di a n(s), m ust b ot h si g n a n d date t he I C F a n d/ or A F 
after re vi e w a n d bef ore t he s u bject ca n p arti ci pate i n t h e st u d y. T he s u bje ct, a n d as a p pli ca bl e 
t he pare nt(s) or g uar dia n(s) will recei ve a c o p y of t he si g ne d a n d d ate d f or m, a n d t h e ori gi nal 
will b e retai ne d i n t h e sit e st u d y files. T h e I n vesti gat or or his/ her desi g nee will e m p hasiz e t o 
t he s u bject , a n d as a p plica ble pare nt(s) or g uar di a n(s), t hat st u d y partici pati o n is e ntirel y 
v ol u ntar y a n d t hat c o nse nt re gar di n g st u d y partici pati o n ma y b e wit h dra w n at a n y ti m e 
wit h o ut p e nalt y or l oss of be nefits t o w hic h t he s u bject is ot her wise e ntitle d.
If t he I C F a n d/ or A F is a me n de d d uri n g t he st u d y, t he I n v esti gat or m ust f oll o w all a p plica ble 
re g ulat or y re q uire me nts pertai ni n g t o a p pr o val of t he a me n de d I C F a n d/ or A F b y t he 
I R B/I E C. T he site m ust use t he a me n d e d c o nse nt/asse nt f or m f or all ne w s u bjects a n d re peat 
t he c o nse nt pr ocess wit h t h e a me n de d I C F/ A F f or a n y o n g oi n g s u bjects
1 1. 5
S u bj e ct C o nfi d e nti alit y
S u bjects’ na mes will re mai n c o nfi de ntial; o nl y s u bject n u m b er a n d birt h date will be 
rec or d e d i n t he data base. If t he s u bject na me a p p ears o n a n y ot h er d o c u me nt c oll ecte d (e. g., 
h os pital disc har ge s u m mar y), t he n a me will be o blit erate d bef ore t he d oc u me nt is 
tra ns mitte d. All st u d y fi n di n gs will be st ore d i n electr o nic data bases. T he s u bjects will gi v e 
e x plicit per missi o n f or re prese ntati ves of t he S p o ns or, re g ulat or y a ut h orities, a n d t he I R B t o 
i ns pect t heir me dical rec or ds t o verif y t he i nf or mati o n c ollecte d.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 8 2 of 1 1 1
S u bjects will be i nf or me d t hat all pers o nal i nf or mati o n ma de a vaila bl e f or i ns pecti o n will be 
ha n dle d i n t he strictest c o nfi de nce a n d i n acc or da n ce wit h all st ate, l ocal, a n d fe deral data 
pr otecti o n/ pri v ac y la ws, i ncl u di n g, wit h o ut li mitati o n, t he HI P A A.
All partici pa nts i n t he st u d y will pr o vi d e writte n a ut h orizati o n t o discl ose pri vate healt h 
i nf or mati o n eit h er as a part of t he writte n I C F or as a se parate a ut h orizati o n f or m.  T he 
a ut h orizati o n will c o ntai n all re q uire d ele me nts s pecifie d b y 4 5 C F R 1 6 4 a n d I C H E 6 as 
a p plica ble, a n d will c o ntai n a wai ver of s u bject access t o st u d y-relate d pri v ate healt h 
i nf or mati o n u ntil t h e c o ncl usi o n of t he cli nical st u d y. T he a ut h orizati o n will re mai n vali d a n d 
i n f ull f orce a n d effect u ntil t he first t o occ ur of ( 1) t he e x pirati o n of 2 years after t h e st u d y 
t hera p y is a p pr o v e d f or t he i n dicati o n bei n g st u die d, or ( 2) t he e x pirati o n of 2 years after t h e 
researc h pr o gra m is disc o nti n ue d. I n di vi d ual s u bject me dical i nf or mati o n o btai n e d d uri n g 
t his st u d y is c o nfi de ntial a n d its discl os ure t o t hir d parti es ( ot her t h a n t h ose me nti o ne d i n t his 
secti o n) is strictl y pr o hi bite d. I n a d diti o n, me dical i nf or mati o n o btai ne d d uri n g t his st u d y
ma y b e pr o vi d e d t o t he s u bject's pers o nal p h ysicia n or t o ot her a p pr o priate me dical pers o n n el 
w he n re q uir e d i n c o n necti o n wit h t he s u bject's c o nti n ue d healt h a n d welf are.
T he S p o ns or will mai ntai n a pers o nal s u bje ct i d e ntificati o n list (s u bject a n d treat me nt 
n u m bers wit h t he c orres p o n di n g s u bject na mes) t o e na ble rec or ds t o be i d e ntifie d.
1 1. 6
St u d y M o nit ori n g
T he S p o ns or will pr o vi de st u d y m o nit ors a n d will d eter mi ne t he fre q ue nc y of m o nit ori n g
visits pri maril y base d o n i n di vi d ual site e nr oll me nt a n d site c o m plia nce wit h pr ot oc ol-
dictate d pr oce d ures, wit h visits ge nerall y occ urri n g o nce e ver y 2- 4 m o nt hs.  All sites will be 
m o nit ore d s h ortl y after t he first s u bject at t h e sit e c o m pletes t he I nf usi o n Visit. A d diti o nall y, 
st u d y m o nit ors will c o nti n u o usl y re vie w t he c o m pleti o n of st u d y d oc u me nts, data a n d
a d verse e ve nt re p orti n g i n a ti mel y ma n n er.
1 1. 7
C a s e R e p ort F or m s a n d St u d y R e c or d s
All case re p ort f or ms ( C R F) will be c o m plete d i n acc or da nce wit h G C P g ui d eli n es a n d as 
s o o n as p ossi ble after eac h cli nical trial visit. A data ca pt ure s yste m will be utilize d t o rec or d 
all of t he pr ot oc ol re q uire d i nf or mati o n t o be re p orte d t o t he S p o ns or o n eac h trial s u bject. 
St u d y p ers o n nel fr o m eac h site will be trai ne d i n h o w t o access a n d us e t he data s yste m t o 
e nter a n d tra ns mit data f or t he st u d y. St u d y p ers o n nel will be gi v e n a “si g n i n” a n d p ass w or d 
u ni q ue t o t he m w hic h will n ot be use d b y a n y ot her pers o n nel.  St u d y pers o n nel will be 
trai ne d re gar di n g pr o p er c orrecti o n of d ata e ntries i n t he data s yst e m.
St u d y p ers o n nel are res p o nsi ble t o e ns ure t hat all e ntries are acc urate, le gi ble a n d verifi a ble 
wit h t h e s o urce dat a i n t he me dical rec or d. A s o urce d oc u me nt is defi ne d as t he place i n t h e 
me dical rec or d w here a gi ve n data p oi nt first a p pears. 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 8 3 of 1 1 1
1 1. 8
Pr ot o c ol Vi ol ati o n s/ D e vi ati o n s
As t he y o cc ur, pr ot oc ol vi olati o ns (i.e., e ve nts t hat ha ve p ote ntial t o i m pact i nter pretati o n of 
data f or i nte n d e d p o p ulati o n, s uc h as vi olati o ns of i n cl usi o n/e x cl usi o n crit eria) a n d de viati o ns 
(i.e., variati o ns fr o m pr ot o c ol-s pecifie d pr o cess es u nli kel y t o i m pact i nter pretati o n of data f or 
i nte n de d p o p ulati o n) will be d oc u me nte d at eac h sit e a n d re p ort e d t o t he S p o ns or. U p o n 
detecti o n of a vi olati o n, t he S p o ns or will e ns ure re p orti n g t o t he pr o p er l ocal a n d fe deral 
re g ulat or y a ut h orities i n acc or da nce wit h all a p pli ca ble f e deral a n d l ocal re g ulati o ns. T he 
S p o ns or will deter mi ne t he c o urse of acti o n base d o n t he se verit y of t he d e viati o n or 
vi olati o n. T hese ma y i ncl u de b ut are n ot li mite d t o, wit h dra wal of t he s u bje ct, a d diti o nal 
trai ni n g at t he site, a d diti o nal site m o nit ori n g, etc.  I n a d diti o n, t h e me dical m o nit or a n d
statisti cia n will re vie w t h e circ u msta n ces of eac h vi olati o n (i n a bli n de d fas hi o n) t o deter mi ne 
w het h er t h e d ata ca n reas o na bl y b e i ncl u de d i n t he s u bject data i n t h e fi nal st u d y a n al ysis.
1 1. 9
A c c e s s t o S o ur c e D o c u m e nt ati o n
T he I n vesti gat or, S p o ns or’s m o nit or a n d site cli nical st u d y p ers o n nel will be a ble t o access 
t he s o urce d oc u me ntati o n. De-i de ntifie d s o urce d o c u me ntati o n ma y be accesse d b y t he
S p o ns or (e. g., i n e val uati o n of a n S A E). I n a d diti o n, t he st u d y site m ust all o w trial-relat e d
m o nit ori n g a u dits, I R B re vi e w, a n d re g ul at or y i ns pecti o n(s), wit h direct access t o s o urce dat a 
a n d d oc u me nts.
1 1. 1 0 D at a G e n er ati o n a n d A n al y si s
C o ntract researc h or ga ni zati o ns ( C R Os) will pr o vi de data ma na ge me nt a n d a nal ysis a n d 
re p orti n g ser vices t o t he S p o ns or.  A vali d ate d data s yste m pr o prietar y t o t h e C R O will be 
utili ze d t o c ollect data a n d ge nerate a dat a base. St u d y sites will be res p o nsi ble f or e nteri n g 
data c ollecte d at t he site. E xter nal data s o urces (i.e., ce ntral la bs a n d c ore i ma gi n g ce nter) are 
e x pecte d eit h er t o pr o vi d e data sets f or electr o nic u pl oa d i nt o t he data base or e nter t h e 
a p pr o priate d ata directl y i nt o t he s yste m.  Data q u eries will b e ge n erate d b y t he d ata s yste m, 
C R O data ma na gers, a n d st u d y m o nit ors, t h e n f or war de d t o t h e sit es f or res ol uti o n.  
Rete nti o n of Data
1 1. 1 1 D at a R et e nti o n
I n acc or da nce wit h 2 1 C F R 3 1 2. 6 2, a n I n vesti gat or partici pati n g i n t his st u d y s hall retai n 
rec or ds, i ncl u di n g t he cas e re p ort f or ms a n d s u p p orti n g data i n cl u di n g si g ne d a n d date d 
c o nse nt f or ms, a n d me di cal rec or ds, pr o gr ess n otes of t h e p h ysi cia n, t h e i n di vi d ual's h os pital 
c hart(s), a n d t he n urses' n otes. Rec or ds are re q uire d t o be mai ntai ne d f or a peri o d of 2 years 
f oll o wi n g t h e date t he mar keti n g a p plicati o n is a p pr o ve d or, if n o a p plicati o n is t o be file d or 
if t h e a p plicati o n is n ot a p pr o ve d b y t he F D A, u ntil 2 years after t h e i n vesti gati o n is 
disc o nti n ue d a n d F D A is n otifie d. I n a n y case, t h e S p o ns or s h o ul d be n otifie d pri or t o t h e 
destr ucti o n of a n y st u d y rec or ds.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 8 4 of 1 1 1
1 1. 1 2 Fi n a n ci al Di s cl o s ur e
I n acc or da nce wit h F D A re g ulat or y re q uire me nts, 2 1 C F R 5 4. 4, t h e Cli nical I n vesti gat ors 
a n d S u b-I n vesti gat ors at eac h sit e will be re q uire d t o c o m plete a fi na ncial discl os ure f or m
pr o vi de d b y t he S p o ns or pri or t o parti ci pati o n i n t he st u d y. E ac h Cli nical I n vesti gat or/ S u b-
I n v esti gat or s hall pr o vi de t o t he S p o ns or of t he st u d y s ufficie nt acc urate fi n a ncial 
i nf or mati o n t o all o w t he S p o ns or t o s u b mit c o m plete a n d acc urate certificati o n or discl os ure 
state me nts ( F or ms 3 4 5 4 a n d/ or 3 4 5 5) as re q uire d b y t he F D A re g ulati o ns. E ac h Cli nical 
I n v esti gat or/ S u b-I n vesti gat or s hall pr o m ptl y u p d ate t his i nf or mati o n if a n y rele va nt c ha n ges 
occ ur i n t h e c o urse of t he st u d y or f or 1 year f oll o wi n g c o m pleti o n of t he st u d y
1 1. 1 3 P u bli c ati o n, U s e a n d Di s cl o s ur e P oli c y
U nless t he S p o ns or has gi v e n its writte n c o nse nt i n a d va nce or u nless ot her wis e pr o vi de d i n 
t he Cli nical Trial A gree me nt e xec ute d b y t h e parties wit h res pect t o t he st u d y, neit her t he 
I nstit uti o n w here t h e st u d y is bei n g c o n d ucte d n or a n y Cli nical I n vesti gat or/ S u b-I n v esti gat or 
or st u d y pers o n nel ma y p u blis h S p o ns or c o nfi de ntial i nf or mati o n or st u d y d ata, discl ose 
S p o ns or c o nfi de ntial i nf or mati o n or st u d y d ata t o a n y t hir d part y, or use S p o ns or c o nfi de ntial 
i nf or mati o n or st u d y d ata f or a n y p ur p os e ot h er t h a n t h e perf or ma nce of t h e st u d y.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 8 5 of 1 1 1
1 2
R E F E R E N C E LI S T
•
Alle n, H. D., K. M. Fl a ni ga n, P. T. T hr us h, I. D v orc hi k, H. Yi n, C. Ca nter, A. M. 
C o n n oll y, M. Parris h, C. M. Mc D o nal d, E. Bra u nli n, S. D. C ola n, J. Da y, B. Darras a n d 
J. R. M e n dell ( 2 0 1 3). " A ra n d o mize d, d o u ble- bli n d trial of lisi n o pril a n d l osarta n f or t h e 
treat me nt of car di o m y o p at h y i n d uc h e n ne m usc ul ar d ystr o p h y." P L o S C urr 5 .
•
Ass m us, B., D. M. Leist n er, V. Sc hac hi n ger, S. Er bs, A. Elsass er, W. Ha ber b osc h, R. 
Ha m brec ht, D. Se d di n g, J. Y u, R. C orti, D. G. M at he y, C. Bart h, C. Ma yer- We hrstei n, I. 
B urc k, T. S uesel bec k, T. Dill, C. W. Ha m m, T. T o n n, S. Di m meler, A. M. Zei h er a n d R.-
A. S. Gr o u p ( 2 0 1 4). " L o n g-ter m cli nical o utc o me aft er i ntrac or o n ar y a p pli cati o n of b o ne 
marr o w- d eri ve d m o n o n u clear cells f or ac ute m y o car dial i nfarcti o n: mi grat or y ca pacit y of 
a d mi nistere d cells deter mi nes e ve nt-free s ur vi v al." E ur H eart J 3 5 ( 1 9): 1 2 7 5- 1 2 8 3. 
•
B us h b y, K., R. Fi n kel, D. J. Bir n kra nt, L. E. Cas e, P. R. Cle me ns, L. Cri p e, A. Ka ul, K. 
Ki n nett, C. M c D o nal d, S. Pa n d ya, J. P o ys k y, F. S ha pir o, J. T o mezs k o, C. C o nsta nti n a n d 
D. M. D. C. C. W. Gr o u p ( 2 0 1 0a ). " Dia g n osis a n d ma na ge me nt of D u c he n n e m usc ular 
d ystr o p h y, part 1: dia g n osis, a n d p har mac ol o gical a n d ps yc h os ocial m a na ge m e nt." 
La n cet N e ur ol 9 ( 1): 7 7- 9 3. 
•
B us h b y, K., R. Fi n kel, D. J. Bir n kra nt, L. E. Cas e, P. R. Cle me ns, L. Cri p e, A. Ka ul, K. 
Ki n nett, C. M c D o nal d, S. Pa n d ya, J. P o ys k y, F. S ha pir o, J. T o mezs k o, C. C o nsta nti n a n d 
D. M. D. C. C. W. Gr o u p ( 2 0 1 0 b ). " Dia g n osis a n d ma na ge me nt of D u c he n n e m usc ular 
d ystr o p h y, part 2: i m ple me ntati o n of m ulti dis ci pli n ar y care." La n cet Ne ur ol 9 ( 2): 1 7 7-
1 8 9.
•
Dill m a n, J. R., J. H. Ellis, R. H. C o ha n, P. J. Str o use a n d S. C. J a n ( 2 0 0 7). " Fre q u e nc y 
a n d se verit y of ac ute aller gic-li ke reacti o ns t o ga d oli ni u m-c o ntai ni n g i. v. c o ntrast me dia 
i n c hil dre n a n d a d ults." AJ R. A merica n j o ur nal of r oe nt ge n ol o g y 1 8 9 ( 6): 1 5 3 3- 1 5 3 8. 
•
Ga ul d L. M., Ka p pers J., Carli n J. B., R o berts o n C. F. Hei g ht pre dicti o n fr o m ul na le n gt h. 
( 2 0 0 4). D e v M e d C hil d Ne ur ol. 2 0 0 4 J ul; 4 6( 7): 4 7 5- 8 0. 
htt p:// w w w. nc bi. nl m. ni h. g o v/ p u b me d/ 1 5 2 3 0 4 6 1


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 8 6 of 1 1 1
•
H or, K. N., W. Maz ur, M. D. Ta yl or, H. R. Al- K hali di, L. H. Cri pe, J. L. J efferies, S. V. 
Ra ma n, E. S. C h u n g, K. J. Ki n nett, K. Willia ms, W. M. G ottlie bs o n a n d D. W. Be ns o n 
( 2 0 1 1). " Effects of ster oi ds a n d a n gi ote nsi n c o n verti n g e nz y m e i n hi biti o n o n 
circ u mfere nti al strai n i n b o ys wit h D uc h e n n e m us c ular d ystr o p h y: a cr oss-secti o nal a n d 
l o n git u di nal st u d y utili zi n g car di o vasc ular m a g n etic res o na nce." J Car di o vasc Ma g n 
Res o n 1 3 : 6 0. 
•
H or, K. N., M. D. T a yl or, H. R. Al- K hali di, L. H. Cri pe, S. V. Ra ma n, J. L. J efferies, R. 
O' D o n n ell, D. W. Be ns o n a n d W. Maz ur ( 2 0 1 3). " Pre vale nce a n d distri b uti o n of late 
ga d oli ni u m e n ha n ce me nt i n a lar ge p o p ulati o n of p atie nts wit h D uc he n ne m usc ular 
d ystr o p h y: effect of a ge a n d left ve ntric ular s yst oli c f u n cti o n." J Car di o vasc Ma g n Res o n 
1 5 : 1 0 7. 
•
H or, K. N., J. Wa nsa p ura, L. W. Mar k h a m, W. Maz ur, L. H. Cri pe, R. Flec k, D. W. 
Be ns o n a n d W. M. G ottlie bs o n ( 2 0 0 9). " Circ u mfere nti al strai n a nal ysis i de ntifies strata 
of car di o m y o pat h y i n D u c he n ne m usc ular d ystr o p h y: a car diac ma g n etic res o na nce 
ta g gi n g st u d y." J A m C oll Car di ol 5 3 ( 1 4): 1 2 0 4- 1 2 1 0. 
•
I n k er, L. A., C. H. Sc h mi d, H. Ti g hi o uart, J. H. Ec kfel dt, H. I. Fel d ma n, T. Gree n e, J. W. 
K use k, J. Ma nzi, F. Va n Le nt e, Y. L. Z ha n g, J. C ores h, A. S. Le ve y a n d C.- E. 
I n v esti gat ors ( 2 0 1 2). " Esti mati n g gl o mer ular filtrati o n rate fr o m ser u m creati ni ne a n d 
c ystati n C." N E n gl J Me d 3 6 7 ( 1): 2 0- 2 9. 
•
J a nsse ns, S., C. D u b ois, J. B o gaert, K. T he u nisse n, C. Der o ose, W. Des met, M. Kala ntzi, 
L. H er b ots, P. Si n nae ve, J. De ns, J. Maerte ns, F. Ra de ma kers, S. D y mar k o ws ki, O. 
G he yse ns, J. Va n Cl ee m p ut, G. B or ma ns, J. N u yts, A. Bel m a ns, L. M ortel ma ns, M. 
B o o gaerts a n d F. Va n d e Werf ( 2 0 0 6). " A ut ol o g o us b o ne marr o w- deri v e d ste m-cell 
tra nsfer i n p atie nts wit h S T-se g m e nt ele vati o n m y o car dial i nfarcti o n: d o u ble- bli n d, 
ra n d o mise d c o ntr olle d tri al." La n cet 3 6 7 ( 9 5 0 5): 1 1 3- 1 2 1. 
•
J efferies, J. L., B. W. Ei d e m, J. W. Bel m o nt, W. J. Crai ge n, S. M. W are, S. D. Fer n bac h, 
S. R. Neis h, E. O. S mit h a n d J. A. T o w bi n ( 2 0 0 5). " Ge n etic pre di ct ors a n d re m o deli n g of 
dilate d car di o m y o pat h y i n m usc ular d ystr o p h y." Circ ulati o n 1 1 2 ( 1 8): 2 7 9 9- 2 8 0 4. 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 8 7 of 1 1 1
•
Katz ber g, R. W. a n d J. H. Ne w h o use ( 2 0 1 0). "I ntra ve n o us c o ntrast me di u m-i n d uce d 
ne p hr ot o xicit y: is t he m e dical ris k reall y as great as we ha ve c o me t o belie ve?" 
Ra di ol o g y 2 5 6 ( 1): 2 1- 2 8. 
•
K o wal, J., M. T kac h a n d C. T her y ( 2 0 1 4). " Bi o ge nesis a n d secreti o n of e x os o mes." C urr 
O pi n Cell Bi ol 2 9 C : 1 1 6- 1 2 5. 
•
Malliaras, K., T. S. Li, D. L ut hri n ger, J. T err o vitis, K. C he n g, T. C h a kra v art y, G. G ala n g, 
Y. Z h a n g, F. Sc h o e n h off, J. Va n E y k, L. Mar ba n a n d E. Mar ba n ( 2 0 1 2). " Safet y a n d 
effic ac y of all o ge neic cell t hera p y i n i nfarcte d rats tra ns pla nte d wit h mis m atc he d 
car di os p here- deri ve d cells." Circ ulati o n 1 2 5 ( 1): 1 0 0- 1 1 2. 
•
Mar k h a m, L. W., K. Ki n nett, B. L. W o n g, D. W o o dr o w Be ns o n a n d L. H. Cri pe ( 2 0 0 8). 
" C ortic oster oi d treat me nt retar ds de vel o p me nt of v e ntric ular d ysf u n cti o n i n D uc he n ne 
m usc ular d ystr o p h y." Ne ur o m usc ul Dis or d 1 8 ( 5): 3 6 5- 3 7 0. 
•
N ot o, T. J., Jr., L. W. J o h ns o n, R. Kr o ne, W. F. Wea ver, D. A. Cl ar k, J. R. Kra m er, Jr. 
a n d G. W. Vetr o vec ( 1 9 9 1). " Car diac cat heterizati o n 1 9 9 0: a re p ort of t he Re gistr y of t h e 
S ociet y f or Car diac A n gi o gr a p h y a n d I nt er ve nti o ns ( S C A &I)." Cat heterizati o n a n d
car di o vasc ular dia g n osis 2 4 ( 2): 7 5- 8 3. 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 8 8 of 1 1 1
•
Passa ma n o, L., A. Ta glia, A. Palla di n o, E. Vi g gia n o, P. D' A m br osi o, M. Sc utifer o, M. 
R osaria Ceci o, V. T orre, D. E. L. F, E. Pi cill o, O. P aciell o, G. Pil us o, G. Ni gr o a n d L. 
P olita n o ( 2 0 1 2). "I m pr o v e me nt of s ur vi v al i n D uc he n ne M usc ular D ystr o p h y: 
retr os pecti v e a nal ysis of 8 3 5 patie nts." A cta M y ol 3 1 ( 2): 1 2 1- 1 2 5. 
•
Ra ma n, S. V., K. N. H or, W. Maz ur, N. J. Hal n o n, J. T. Kissel, X. He, T. Tra n, S. S mart, 
B. Mc Cart h y, M. D. T a yl or, J. L. J efferies, J. A. Rafael- F ort n e y, J. L o we, S. L. R o ble a n d 
L. H. Cri p e ( 2 0 1 4). " E plere n o ne f or earl y car di o m y o pat h y i n D u c he n ne m usc ular 
d ystr o p h y: a ra n d o mise d, d o u ble- bli n d, place b o-c o ntr olle d trial." La ncet N e ur ol.
•
R ya n, T. D., J. L. J efferies, H. Sa w na ni, B. L. W o n g, A. G ar d n er, M. Del C orral, A. L orts 
a n d D. L. M oral es ( 2 0 1 4). "I m pla ntati o n of t he H eart M ate II a n d H eart Ware left 
ve ntric ul ar assist de vices i n patie nts wit h d uc he n n e m usc ular d ystr o p h y: less o ns lear ne d 
fr o m t he first a p plicati o ns." A S AI O J 6 0 ( 2): 2 4 6- 2 4 8. 
•
Sc hac hi n ger, V., S. Er bs, A. Els asser, W. Ha ber b osc h, R. Ha m brec ht, H. H olsc her m a n n, 
J. Y u, R. C orti, D. G. Mat he y, C. W. H a m m, T. S usel bec k, B. Ass m us, T. T o n n, S. 
Di m meler a n d A. M. Zei her ( 2 0 0 6). "I ntrac or o nar y b o ne m arr o w- deri v e d pr o g e nit or cells 
i n ac ute m y ocar dial i nfarcti o n." T he N e w E n gla n d j o ur nal of me dici ne 3 5 5 ( 1 2): 1 2 1 0-
1 2 2 1.
•
S hir o k o va, N. a n d E. Ni g gli ( 2 0 1 3). " Car di ac p he n ot y pe of D uc he n ne M usc ular 
D ystr o p h y: i nsi g hts fr o m cell ular st u dies." J M ol Cell Car di ol 5 8 : 2 1 7- 2 2 4. 
•
S p ur ne y, C. F. ( 2 0 1 1). " C ar di o m y o pat h y of D uc h e n ne m usc ular d ystr o p h y: c urre nt 
u n dersta n di n g a n d f ut ure directi o ns." M uscl e Ner ve 4 4 ( 1): 8- 1 9. 
•


C A P -1 0 0 2 All o ge neic Car di os p here -Deri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 8 9 of 1 1 1
A p p e n di x 1
S c h e d ul e of E v e nt s
Pr oce d ure / E ve nt
Scree ni n g
I nf usi o n 
( C A P- 1 0 0 2 
o nl y) 1
D a y 1 
( H o me)
D a y 3 
( P h o ne)
Wee k 2
Wee k 6
M o nt h 3
M o nt h 6
M o nt h 
1 2
E arl y 
Ter mi n ati o n 2
St u d y Da y
pri or t o 
ra n d o mizati o n
Da y 0
Da y 1 3
Da y 3 
( + 3)
Da y 1 4 
( ± 3)
Da y 4 0 
( ± 7)
Da y 9 0 
( ± 7)
Da y 1 8 0 
( ± 1 4)
Da y 3 6 0 
( ± 3 0)
As Nee de d
P R E
P O S T
I nf or me d C o nse nt
X
Eli gi bilit y Ass ess me nt
X
X
De m o gra p hics
X
M e dical Hist or y
X
X
Car diac Hist or y
X
X
C o nc o mita nt Me dicati o ns
X
X
X
X
X
X
X
X
X
Vital Si g ns
X
X
X
X
X
X
X
X
X
Wei g ht 
X
X
X
X
Hei g ht 4
X
X
X
X
X
X
1 2- Lea d E C G
X
X
X
X
X
X
X
X
X
Li mite d P h ysical E xa mi n ati o n 
X
X
X
Car diac P h ysical E x a mi n ati o n
X
X
X
X
X
X
X
X
X
Car diac M RI
X
X
X
X
C o nti n u o us car diac r h yt h m 
m o nit ori n g
X
X
X
X
X
X
Cli nical La b orat or y Tests 
(i n cl u d es C he mistr y, 
He mat ol o g y, Uri nal ysis)
X
X
X
X
X
X
X
X
X
Ser ol o g y 5
X
Oste o p o nti n
X
X
X
X
X
X
X
S T 2 
X
X
X
X
X
X
X
I L- 1 0
X
X
X
X
X
X
X
Gal ecti n- 3
X
X
X
X
X
X
X
E x pl orat or y Bi o mar k ers 
X
X
X
X
X
X
X


C A P -1 0 0 2 All o ge neic Car di os p here -Deri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y 2 0 1 6
C o nfi d e ntial
P a ge 9 0 of 1 1 1
Pr oce d ure / E ve nt
Scree ni n g
I nf usi o n 
( C A P- 1 0 0 2 
o nl y) 1
D a y 1 
( H o me)
D a y 3 
( P h o ne)
Wee k 2
Wee k 6
M o nt h 3
M o nt h 6
M o nt h 
1 2
E arl y 
Ter mi n ati o n 2
St u d y Da y
pri or t o 
ra n d o mizati o n
Da y 0
Da y 1 3
Da y 3 
( + 3)
Da y 1 4 
( ± 3)
Da y 4 0 
( ± 7)
Da y 9 0 
( ± 7)
Da y 1 8 0 
( ± 1 4)
Da y 3 6 0 
( ± 3 0)
As Nee de d
P R E
P O S T
H L A
X
D S A
X
X
X
X
X
X
X
E LI S p ot
X
X
P U L scale
X
X
X
X
X
X
6 M W T
X
X
X
X
X
X
P e diatric Q L I n ve nt or y
X
X
X
X
X
X
P O D CI
X
X
X
X
X
X
S pir o metr y
X
X
X
X
X
X
C o a g ulati o n
X
Ser u m Tr o p o ni n & C K- M B
X
X
X
X
X
X
X
I ntrac or o n ar y I nf usi o n
X
A d verse E ve nt Assess me nt
X
X
X
X
X
X
X
X
X
X
1 Da y 0 is t he i nf usi o n date f or s u bjects ra n d o mi ze d t o C A P- 1 0 0 2. All it e ms liste d f or I nf usi o n visit a n d assess me nts o n Da y 0 are o nl y a p plica ble 
f or s u bjects ra n d o mize d t o C A P- 1 0 0 2. S u bj ects ra n d o mi ze d t o Us ual Care d o n ot ha ve a Da y 0 visit.
2 Earl y Ter mi nati o n Visit pr oce d ures t o be c o m plete d at ti me of wit h dra wal, s h o ul d s u bj ect be wit h dra w n bef ore M o nt h 1 2 Visit. . A Car diac M RI 
will be c o n d u cte d pr o vi de d t he s u bj ect’s m ost rece nt st u d y-relate d Car diac M RI was c o n d ucte d at least t hree m o nt hs (i.e., 1 2 wee ks) pri or t o t he 
Earl y T er mi nati o n Visit.
3 F or eli gi ble s u bjects ra n d o mize d t o t h e us u al care ar m, Da y 1 is esta blis he d as 8 da ys after t he date of ra n d o mizati o n, wit h o ut a n act ual Da y 1
visit.
All st u d y s u bjects i nitiat e 7 2- h o ur c o nti n u o us car di ac r h yt h m m o nit ori n g o n Da y 1.
4 If sta n di n g hei g ht ca n n ot be meas ure d, h ei g ht will be calc ulate d usi n g a meas ure me nt of ul na le n gt h ( Ga ul d et al 2 0 0 4).
5 Ser ol o g y i ncl u des HI V a n d he patitis testi n g


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 9 1 of 1 1 1
A p p e n di x 2  
Cli ni c al L a b or at or y T e st s
Cli nical la b orat or y tests are t o i ncl u de t he f oll o wi n g.  All s u bjects will ha ve t he sa me 
sa m ples dra w n a n d t he sa me ass ess me nts perf or me d at eac h st u d y visit, e xce pt at D 0 a n d D 1 
w hic h are n ot st u d y visits f or s u bjects ra n d o mize d t o us ual care.
Ser u m C he mistry
A L T ( S G P T)
A S T ( S G O T) 
B U N
Creati ni ne
e G F R ( C K D- E PI C ystati n C [ 2 0 1 2])
Gl uc ose
Lactate de h y dr o ge nase ( L D H)
S o di u m 
P otassi u m
C hl ori de
Bilir u bi n
Al b u mi n
He m at ol o gy
W B C
R B C
He m o gl o bi n
He mat o crit
Platelet c o u nt
W B C (t otal a n d differe ntial c o u nts)
Ser ol o gy
He patitis B s urface a nti ge n ( H Bs A g) 
He patitis C Vir us a nti b o d y (a nti- H C V)
H u ma n I m m u n o deficie nc y Vir us a nti b o d y 
( HI V) 
A d diti o n al
H b A 1c
Tr o p o ni n I
C K- M B
C ystati n C
Uri n al ysis
A p peara nce
Bilir u bi n
C ol or 
Nitrite
Occ ult bl o o d 
p H
Pr otei n
S pecific gra vit y
Gl uc ose
K et o nes
Mi cr osc o pic e xa mi n ati o n of se di me nt
C o a g ul ati o n
I nf usi o n Visit o nly f or s u bj ects t aki n g w arf ari n
P T T
I N R
I m m u n o ass a y L a b or at ories
D S A
H L A
E LI S p ot
Bi o m arkers
Galecti n- 3
I L- 1 0
Oste o p o nti n
S T 2
E x pl orat or y Bi o mar kers ( if c o nse nt/ asse nt 
pr ovi de d )
All st u d y s peci me ns f or t his trial will be e x a mi ne d b y ce ntral la b orat or y facilities, e xce pt as 
necessar y o n Da y 0 a n d Da y 1 f or s u bjects u n der g oi n g i nf usi o n wit h C A P- 1 0 0 2.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 9 2 of 1 1 1
A p p e n di x 3 
Pr o hi bit e d Pri or
M e di c ati o n s
As t he y m a y i nterfere wit h t h e f u ncti o n of C D Cs, t he f oll o wi n g me di cati o ns are pr o hi bite d 
fr o m t hree m o nt hs pri or t o t he scree ni n g visit, t hr o u g h St u d y Da y 0
G E N E RI C N A M E
T R A D E N A M E
A baca vir
E pzic o m ®
A baca vir
Zia ge n ®
A baca vir s ulfate, La mi v u di ne, a n d Zi d o v u di ne 
Trizi vir ®
A dali m u ma b
H u mira ®
Al desle u ki n
Pr ole u ki n ®
Altreta mi ne
He x ale n ®
A mi n o gl utet hi mi de
C yt a dre n ®
A na ki nra
Ki neret ®
A nastr oz ole
Ari mi de x ®
As para gi nas e
Els par ®
Ataza na vir s ulfate
Re yat a x ®
Azat hi o pri ne
I m ura n ®
Azat hi o pri ne
Azasa n
Basili xi ma b
Si m ulect ®
Ble o m yci n
Ble n o x a ne ®
B us ulfa n
M ylera n ®
Ca pecita bi ne
Xel o da ®
Car b o plati n
Para plati n ®
Car m usti ne
Bi C N U ® ( B C N U)
Cert oliz u ma b pe g ol
Ci mzia ®
C hl ora m b ucil
Le u k era n ®
Ci d of o vir
Visti de ®
Cis plati n
Pl ati n ol ®
Cla dri bi n e
Le ust ati n ®
C ycl o p h os p ha mi de
C yt o x a n ®
C ycl o p h os p ha mi de
Ne osar ®
C ycl os p ori ne
G e n graf ®
C ycl os p ori ne
N e oral ®
C ycl os p ori ne
S a n di m m u ne ®
C yt ara bi ne
C yt ara bi ne
C yt ara bi ne
De p o C yt ®
Dacar bazi ne
D TI C- D o m e ®
Dacliz u ma b
Ze n o p a x ®


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 9 3 of 1 1 1
G E N E RI C N A M E
T R A D E N A M E
Dacti n o m yci n
C os me ga n ®
Dar u na vir
Prezista ®
Dasati ni b
S pr yc el ®
Da u n or u bici n
Cer u bi di ne ®
Dela vir di ne
Rescri pt or ®
De nile u ki n diftit o x
O nta k ®
Di da n osi ne
Vi de x ®
D ocet a xel
Ta x otere ®
D ocet a xel
D ocefrez ®
D o x or u bici n
A dria m yci n ®
D o x or u bici n
D o xil ®
Efa vire nz
S usti va ®
Efa vire nz/e mtricita bi ne/t e n of o vir dis o pr o xil f u marate
Atri pla ®
E mtricita bi ne
E mtri va ®
E mtricita bi ne/te n of o vir dis o pr o xil f u marate
Tr u v a da ®
E nf u virti de
F uzei o n ®
E pir u bici n
Elle nce ®
Erl oti ni b
Tarce va ®
Estra m usti ne
E mc yt ®
Eta nerc e pt
E n brel ®
Et o p osi d e
Et o p o p h os ®
Et o p osi d e
Ve Pesi d ®
Etra viri ne
I ntele nce ®
E ver oli m us
Afi nit or ®
E ver oli m us
Z ortress ®
E x e mesta ne
Ar o masi n ®
Fl o x uri di n e
Fl u or o de o x y uri di ne ®
Fl o x uri di n e
A nc o b o n ®
Fl u dara bi n e
Of orta ®
Fl u dara bi n e
Fl u dara ®
F osa m pre na vir calci u m
Le xi va ®
Ge mcita bi ne
Ge mzar
G oli m u ma b i njecti o n
Si m p o ni
H y dr o x yc hl or o q ui ne
Pla q ue nil ®
H y dr o x y urea
Dr o xia ®
H y dr o x y urea
H y drea ®
I d ar u bici n
I d a m yci n ®
If os p ha mi de
Ife x ®


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 9 4 of 1 1 1
G E N E RI C N A M E
T R A D E N A M E
I mati ni b mes ylate
Glee v ac
I n di na vir
Cri xi va n ®
I nfli xi m a b
Re mica de ®
I nterfer o n alfa- 2a
R ofer o n- A ®
I nterfer o n alfa- 2 b
I ntr o n- A ®
I nterfer o n alfac o n- 1)
I nfer ge ®
I nterfer o n beta- 1a
A v o ne x ®
I nterfer o n beta- 1 b
Betas er o n ®
I nterfer o n beta- 1 b
E xta via ®
I nterfer o n beta-l b
Betas er o n ®
I nterfer o n ga m m a- 1 b
Acti m m u ne ®
I nterle u ki n- 2
Pr ole u ki n
Iri n ot eca n
Ca m pt osar
La mi v u di ne
E pi vir ®
La mi v u di ne & Zi d o v u di ne
C o m bi vir ®
La nre oti de
S o mat uli ne ® De p ot
La p ati ni b
T y ker b ®
Lefl u n o mi d e
Ara va ®
Le n ali d o mi de
Re vli mi d
Letr oz ole
Fe mara ®
Le u pr oli de
L u pr o n ®
Le u pr oli de
Eli gar d ®
L o m usti ne
Cee N u ® ( C C N U)
Mara vir oc
Selze ntr y
Mec hl oret ha mi ne H CI
M ustar ge n ®
Me gestr ol
Me gace ®
Mel p hala n
Al kera n ®
Merca pt o p uri n e
P uri net h ol ®
Met h otre x ate
R he u matre x ®
Met h otre x ate
Tre x all ™
Mit o m yci n
M uta m yci n ®
Mit ota ne
L ys o dre n ®
Mit o x a ntr o ne
N o va ntr o n e ®
M ur o m o na b- C D 3
Ort h ocl o ne- O K T 3
M yc o p h e n olate
Cell Ce pt ®
Nelfi na vir
Virace pt ®
Ne vira pi n e
Vira m u ne ®
Nil oti ni b
Tasi g n a ®


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 9 5 of 1 1 1
G E N E RI C N A M E
T R A D E N A M E
Octre oti d e acetat e
Sa n d ostati n ®
Paclita x el
Ta x ol ®
Paclita x el
A bra xa ne ®
Paz o pa ni b
V otrie nt ®
Pe gas p ar gase
O ncas par ®
Pe gi nterfer o n alfa- 2a
Pe gas ys ®
Pe gi nterfer o n alfa- 2 b
Pe g-I ntr o n ®
Pe nicilla mi ne
C u pri mi ne ®
Pr ocar bazi ne
Mat ula ne ®
Ralte gra vir
Ise ntress ®
Ri b a viri n
C o pe g us ®
Ril o nace p
Arcal yst ™
Rit o na vir
N or vir ®
Rit o na vir/ L o pi n o vir
Kaletra ®
Rit u xi ma b
Rit u x a n ®
Sa q ui na vir
I n virase ®
Sar gra m osti m
Le u ki n e ®
Sir oli m us
Ra pa m u ne ®
S orafe ni b
N e xa var ®
Sta v u di ne
Zerit ®
Stre pt o z oci n
Za n os ar ®
S ulfasalazi ne
A z ulfi di ne E N-ta bs ®
S u niti ni b malate
S ute nt ®
Tacr oli m us
Pr o graf ®
Ta m o xife n citrate
N ol va de x
Te m oz ol o mi d e
Te m o dar ®
Te msir oli m us i njecti o n
T orisel ®
Te ni p osi de
V u m o n ®
Te n of o vir dis o pr o xil f u marat e
Virea d ®
T hali d o mi de
T hal o mi d ®
T hi o g ua ni ne
T a bl oi d ®
T hi ote pa
T hi ote pa
Ti pra na vir
A pti v us ®
T ociliz u ma b
Acte mra ®
T o p oteca n
H yca mti n ®
T ore mife ne citrate
Farest o n ®
Trast u z u ma b
Herce pti n ®
Treti n oi n
Vesa n oi d ®


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 9 6 of 1 1 1
G E N E RI C N A M E
T R A D E N A M E
Valr u bici n
Valstar ®
Vi n blasti ne
Vi n blasti ne
Vi ncristi ne
Vi ncristi ne
Vi n orel bi n e
Na vel bi n e ®
V ori n ostat
Z oli nza ®
Zal cit a bi n e
Hi vi d ®
Zi d o v u di n e
Retr o vir ®


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 9 7 of 1 1 1
A p p e n di x 4  
A m e n d m e nt 3 C h a n g e s 
( Pr ot o c ol V er si o n 1 8 J ul y 2 0 1 6)
T he f oll o wi n g t a ble pres e nts a c o m plete list of c o nte nt c ha n ges i n t his pr ot oc ol a me n d me nt. 
T o a v oi d re d u n da n c y, t he “secti o ns affect e d” c ol u m n d oes n ot list t he pr ot oc ol s y n o psis as a n 
affecte d secti o n. 
Descri pti o n of C h a n ge
R ati o n ale/ J ustific ati o n
Secti o ns Affecte d
St u d y Assess me nts
“ 2 4- h o ur a m b ulat or y E C G 
m o nit ori n g” is re place d b y 
“c o nti n u o us car diac r h yt h m
m o nit ori n g” f or 7 da ys at 
M o nt h 6, a n d f or 7 2 h o urs at 
Da y 1, Wee k 6, a n d M o nt h 1 2.
T he pr ot o c ol alrea d y pr o vi de d f or n o n-
i n vasi ve car diac e ve nt m o nit ori n g at 
t h ese ti me p oi nts as a ke y safet y 
assess me nt. T he d urati o n f or eac h of 
t h ese m o nit ori n g assess me nts is bei n g 
e xte n de d t o pr o vi d e a d diti o nal 
i nf or mati o n o n t he fre q ue nc y a n d 
i nte nsit y of arr h yt h mi as i n D M D 
patie nts wit h car di o m y o pat h y.  
S y n o psis
3. 3 Safet y M o nit ori n g
6. 7 P ort a ble E C G 
M o nit or
7. 1 Scree ni n g Visit
7. 2 Ra n d o mi zati o n 
a n d Da y 0
7. 5 Wee k 6 Visit
7. 7 M o nt h 6 Visit
7. 8 M o nt h 1 2 Visit
A p pe n di x 1 Sc he d ule 
of E ve nts
“a m b ulat or y E C G m o nit ori n g 
via H olter M o nit or or ZI O ®
Patc h” is re place d b y “s p o ns or-
s u p pli e d c o nti n u o us car diac 
r h yt h m m o nit ori n g”.
Pre vi o usl y, t he a m b ul at or y E C G 
m o nit ori n g s yste m was deter mi n e d b y 
t h e sta n dar d of care at t he st u d y site.  
Wit h t he decisi o n t o e xte n d t he d urati o n 
of t he car diac m o nit ori n g assess me nts, 
t h e s p o ns or will pr o vi de m o nit ori n g 
de vices t o e ns ure c o nsist e nc y of 
assess me nts at all st u d y sites.
Cl arific ati o ns/ C orrecti o ns
E ve nts “ P ost-I nf usi o n” are 
n o w di vi d e d t o “ P ost-I nf usi o n 
( D 0- D 1)” vers us “ Pre- H os pit al 
Disc har ge ( D 1)”
T his e dit orial c ha n ge is ma de t o clarif y 
t h e se parati o n of i n- h os pital E C G 
m o nit ori n g o n Da y 0 (f or C A P- 1 0 0 2
patie nts o nl y) vers us 7 2- h o ur 
c o nti n u o us car diac r h yt h m m o nit ori n g 
o n Da y 1 (f or all patie nts).
7. 2 Ra n d o mi zati o n 
a n d Da y 0
T otal d ose recei ve d is 6 2. 5 M 
cells, n ot 6 7. 5 M cells as state d 
pre vi o usl y, f or s pecial cases 
w here i nf usi o n of 1 2. 5 M cells 
f or t hat car diac territ or y is 
warra nte d rat her t ha n t h e us ual 
d ose of 2 5 M cells. 
C orrecti o n t o arit h meti c err or i n pri or 
versi o ns of t h e pr ot oc ol.  I n cases 
w here t he i nf usi n g I n vesti gat or d ee ms 
t h at o ne of t he t hree c or o nar y arteries 
s u p pli es less t ha n 3 0 % of t he left 
ve ntric ular m y ocar di u m, t he i nf usi n g 
I n vesti gat or ma y c h o ose t o i nf use o nl y 
1 2. 5 M cells i nt o t hat c or o nar y arter y or 
arteries.
S y n o psis
3. 1 O verall St u d y 
Desi g n a n d Pla n
5. 1. 1 C A P- 1 0 0 2
D osi n g C o nsi derati o ns


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 9 8 of 1 1 1
Descri pti o n of C h a n ge
R ati o n ale/ J ustific ati o n
Secti o ns Affecte d
T e xt a d de d t o clarif y t h e 
ti mi n g of serial c ollecti o n of 
vit al si g ns p ost-i nf usi o n.
Pre vi o usl y, Secti o n 7. 2 s pecifie d " P ost-
i nf usi o n: seri al c ollecti o n of vit al 
si g ns (t e m p, H R, B P, R R)" b ut di d n ot 
s pecif y ti mi n g.  Te xt n o w a d de d t o 
clarif y as "e ver y 8 h o urs +/- 3 0 mi n utes 
fr o m t he e n d of i nf usi o n", c o nsiste nt 
wit h e xisti n g C R F c o m pleti o n 
g ui d eli n es a n d site trai ni n g d oc u me nts.
secti o ns 6. 1 0. 1 C A P-
1 0 0 2 I nf usi o n
7. 2 Ra n d o mi zati o n 
a n d Da y 0
A p pe n di x 1 Sc he d ule 
of E ve nts


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 9 9 of 1 1 1
A p p e n di x 5  
A m e n d m e nt 2 C h a n g e s 
( Pr ot o c ol V er si o n 2 9 F e br u ar y 2 0 1 6)
T he f oll o wi n g t a ble pres e nts a c o m plete list of c o nte nt c ha n ges i n t his pr ot oc ol a me n d me nt. 
T o a v oi d re d u n da n c y, t he “secti o ns affect e d” c ol u m n d oes n ot list t he pr ot oc ol s y n o psis as a n 
affecte d secti o n. F or c ha n ges s h o w n v er bati m, delete d te x t is s h o w n i n stri ket hr o u g h f o nt,
a n d ne w text is s h o w n i n re d it alicize d f o nt.
Descri pti o n of C h a n ge
R ati o n ale/ J ustific ati o n
Secti o ns Affecte d
M o dific ati o ns t o Eli gi bilit y a n d E a rl y Ter mi n ati o n Criteri a
Re m o val of i ncl usi o n criteri o n 
re q uiri n g s u bject b o d y wei g ht 
> 5 0 k g.
T he ori gi n al b o d y wei g ht criteri o n was 
a n ar bitrar y t hres h ol d i nte n d e d t o 
e xcl u de s u bjects t o o s mall t o safel y 
u n der g o car diac cat heteri zati o n. 
H o we ver, m ore a p pr o priate criteria 
e xist t o pr o vi de mea ni n gf ul pre dict ors 
of safet y, wit h o ut e xcl u di n g s u bjects 
w h o w o ul d be ot her wise eli gi ble f or t he 
trial.
I ncl usi o n Criteri o n 6:
3. 1 O verall St u d y 
Desi g n a n d Pla n
4. 2 I ncl usi o n Crit eria
Ne w i ncl usi o n criteri o n: 
S u bjects m ust be a p pr o pri at e 
c a n di d ates f or c ar di a c 
c at heteriz ati o n a n d 
i ntr ac or o n ary i nf usi o n of C A P-
1 0 0 2, i n t he j u d ge me nt of t he 
site’s i nt erve nti o n al 
c ar di ol o gist.
T his crit eri o n is a d de d as a m ore 
mea ni n gf ul safe g uar d t ha n t h e pri or 
i n cl usi o n criteri o n of 5 0 k g mi ni m u m 
b o d y wei g ht.
I ncl usi o n Criteri o n 7: 
3. 1 O verall St u d y 
Desi g n a n d Pla n
4. 2 I ncl usi o n Crit eria
E dit orial clarificati o n:
A si n gl e, c o m p o u n d i ncl usi o n 
crit eri o n ( # 4) is s e parate d t o 
t w o disti nct ite ms ( # 4 a n d # 5), 
as s h o w n at ri g ht:
4. Use of e vi d e nce base d me dical-
t h era p y i n acc or da nce wit h t h e “ D M D 
Care C o nsi derati o ns W or ki n g Gr o u p” 
g ui d eli n es f or t h e ma na ge me nt of 
D M D, f or at l east t hree m o nt hs pri or t o 
si g ni n g t h e c o nse nt f or m ( or, pr o vi di n g 
asse nt) or d oc u me nte d c o ntrai n di cati o n 
or i nt olera nce or patie nt prefere nce. 
A d diti o nall y, 
5. S u bjects m ust be ta ki n g s yste mi c 
gl u c oc ortic oi ds f or at least si x m o nt hs 
pri or t o scree ni n g
I ncl usi o n Criteria 4, 5: 
4. 2 I ncl usi o n Crit eria
Ne w E xcl usi o n Criteri o n:  
C urre ntly receivi n g 
i n vesti g ati o n al tre at me nt o n 
a n ot h er cli ni c al tri al or 
ex p a n de d access pr ot o c ol.
Treat me nt wit h ot her i n vesti gati o nal 
a ge nts w o ul d c o nf o u n d data fr o m b ot h 
trials.
E xcl usi o n Crit eri o n 
2 4: 
4. 3 E xcl usi o n Criteri a


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 1 0 0 of 1 1 1
Descri pti o n of C h a n ge
R ati o n ale/ J ustific ati o n
Secti o ns Affecte d
M o dific ati o ns t o Eli gi bilit y a n d E a rl y Ter mi n ati o n Criteri a (c o nti n ue d)
Cl arifi cati o n of E xcl usi o n 
Criteri o n 8 as f oll o ws: 
Esti mate d gl o mer ular filtrati o n 
rate ( G F R) < 6 0 m L/ mi n , as 
c alc ul at e d by t he C K D- E PI 
cyst ati n C e q u ati o n (I nker et al 
N EJ M 2 0 1 2) .
Cl arifi cati o n t o e ns ure c o nsiste nt 
assess me nt f or all s u bj ects 
E xcl usi o n Crit eri o n 8: 
4. 3 E xcl usi o n Criteri a
A p pe n di x 2 Cli nical 
La b orat or y T ests
Delete d state me nt:
S u bj ects ra n d o mize d t o C A P-
1 0 0 2 b ut n ot i nf use d f or a n y 
reas o n will be as ke d t o 
c o m plete t h e Earl y 
T er mi nati o n Visit. 
Ra n d o mi ze d s u bj ects will n ot be 
re place d. T his is c o nsist e nt wit h t h e 
a nal ysis p o p ulati o ns defi ne d i n t his 
a me n d me nt a n d f urt her detaile d i n t he 
S A P.
3. 1 O verall St u d y 
Desi g n a n d Pla n
Us u al C a re
Ne w secti o n defi ni n g “ us ual 
care”.
Pr ot oc ol di d n ot pre vi o usl y defi ne 
treat me nt a vaila ble t o s u bj ects 
ra n d o mize d t o recei ve us ual care.
5. 2 Us ual Care
Sti p ulati o n t hat, if 
rec o m me n de d b y t he D S M B, 
c o ntr ol s u bj ects c o m pleti n g 1 2
m o nt hs f oll o w- u p wit h us ual 
care ma y be eli gi ble t o recei ve 
C A P- 1 0 0 2 i n a n o pe n-la bel 
e xte nsi o n st u d y.
O pe n-l a bel access t o C A P- 1 0 0 2 after 
i n di vi d ual s u bjects c o m plete t he 
1 2- m o nt h assess me nt ma y e nc o ura ge
s u bj ect c o m pli a nce, f or t h e s u bj ects 
ra n d o mize d t o us ual care. T his access 
w o ul d n ot i m pact t h e i nte grit y of 
assess me nts f or t h e pri mar y a n d 
sec o n dar y st u d y o bj ecti ves, as all of 
t h ese are base d o n o bser vati o ns 
c ollecte d wit hi n 1 2 m o nt hs o n st u d y.
5. 2 Us ual Care
C o nc o mit a nt/ Pr o hi bite d Me dic ati o ns
Ot her i n vesti gati o nal t hera pi es 
are n o w pr o hi bite d fr o m 3 0 
da ys pre-ra n d o mizati o n 
t hr o u g h t he M o nt h 1 2 st u d y 
visit.
T his c ha n ge is necessar y t o pre ve nt 
c o nf o u n di n g of trial dat a.
3. 4 Rati o nal e f or 
St u d y Desi g n a n d 
C o ntr ol Gr o u p
5. 2 Us ual Care
5. 5 Pri or T hera p y 
E xcl usi o ns/ Pr o hi bite d 
Me dicati o ns
I n vesti gati o nal treat me nts a n d 
st e m cell t hera pi es are ne wl y 
liste d as pr o hi bit e d 
me dicati o ns.
T hese me dicati o ns are pr o hi bite d o n 
st u d y t o a v oi d c o nf o u n di n g st u d y data.
5. 2 Us ual Care
5. 5 Pri or T hera p y 
E xcl usi o ns/ Pr o hi bite d 
Me dicati o ns


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 1 0 1 of 1 1 1
Descri pti o n of C h a n ge
R ati o n ale/ J ustific ati o n
Secti o ns Affecte d
C o nc o mit a nt/ Pr o hi bite d Me dic ati o ns (c o nti n ue d)
C o nc o mit a nt t hera pies 
re defi ne d as t h ose recei ve d o n 
or after Da y 0 ( pre vi o usl y were 
ti e d t o scree ni n g a n d/ or 
i nf or me d c o nse nt).
Da y 0 is first da y of pr o d uct e x p os ure. 
5. 4 C o nc o mit a nt 
T hera p y
N ote t hat s u bjects s h o ul d n ot 
be re m o ve d fr o m t h e trial 
s ol el y f or use of pr o hi bite d 
me dicati o ns (i ncl u di n g ot her 
i n vesti gati o nal t hera pies). 
A nal ysis of dat a fr o m s u bj ects 
wit h t his class of si g nifica nt 
pr ot oc ol vi olati o n will be 
ma na ge d as detaile d i n t he 
S A P.
St u d y treat me nt i n t his trial c o nsists of 
o nl y a si n gle i nf usi o n f or s u bj ects 
ra n d o mize d t o C A P- 1 0 0 2, a n d o nl y 
us ual care f or ot her s u bj ects. Treat me nt 
wit h pr o hi bite d me dicati o ns (s uc h as 
ot h er i n vesti gati o nal t hera pies) 
t h eref ore is hi g hl y u nli kel y t o prese nt 
a n y s pecial safet y ris k f or t he s u bjects, 
alt h o u g h it i m pacts t he i nt e grit y of t he 
st u d y data. Gi ve n t he seri o us ness of t h e 
dis ease state, h o we ver, s o me s u bjects 
ma y feel c o m pelle d t o see k ot her 
i n vesti gati o nal treat me nts. I n s uc h 
cases, it w o ul d be m ore usef ul t o 
c o nti n ue t o f oll o w t hese s u bj ects t ha n 
t o recei ve n o f urt her data fr o m t h e m.  
S uc h c o nti n ue d f oll o w- u p s h o ul d n ot 
e ntail a n y si g nifica nt ris k t o st u d y 
s u bj ects.
7. 1 0 Re m o val of 
Patie nts fr o m t he Trial 
or St u d y Dr u g
St atisti c al A n al yses
Efficac y a nal ysis p o p ulati o ns 
re defi ne d as I T T, mI T T, a n d
Per- Pr ot oc ol. 
T he ne w d efi niti o ns are a better fit wit h 
I C H E 9.
Ne w te xt als o s p ecifies t hat 
s u bj ects will be a nal yze d f or efficac y as 
ra n d o mize d, re gar dless of act ual 
treat me nt recei ve d.
9. 3 A nal ysis 
P o p ulati o ns
Safet y a nal ysis p o p ulati o n 
clarifie d (starti n g p oi nts f or 
b ot h st u d y ar ms).
Ne w t e xt is better bala nce d b et wee n 
st u d y gr o u ps (i nitiati o n of vasc ular 
access f or s u bjects ra n d o mize d t o 
C A P- 1 0 0 2 i nf usi o n, vers us 9: 0 0 a m o n 
Da y 7 f or us ual care s u bjects). Ne w t e xt 
als o s pecifies t hat s u bj ects will be 
a nal yze d f or s afet y as act u all y treate d, 
re gar dless of ra n d o mizati o n.
9. 3 A nal ysis 
P o p ulati o ns
Efficac y a nal ysis pla n o utli ne d. 
Pri mar y a nal ysis of efficac y 
will utilize t he mI T T 
p o p ulati o n.
T his cl arificati o n is c o nsiste nt wit h t he 
i nte nti o n as s u g geste d i n t he pri or 
versi o ns of t h e pr ot oc ol.
9. 4 Effi cac y A n al ysis


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 1 0 2 of 1 1 1
Descri pti o n of C h a n ge
R ati o n ale/ J ustific ati o n
Secti o ns Affecte d
St atisti c al A n al yses (c o nti n ue d)
Safet y a nal ysis pla n o utli ne d. 
Pri mar y a nal ysis of efficac y 
will utilize t he Pr o d uct Safet y 
p o p ulati o n.
Safet y a nal ysis pla n was n ot pre vi o usl y 
o utli ne d i n t he pr ot oc ol.
9. 5 Safet y A nal ysis
H a n dli n g of missi n g d at a will 
be det aile d i n t he St atistic al 
A n alysis Pl a n ( S A P). N o 
i m p utati o ns will be ma de f or 
missi n g data.
I m p utati o ns f or missi n g data ma y be 
necessar y.
9. 6
Missi n g Data
T his s a m ple size is a de q u ate t o 
s u p p ort a n assess me nt of s af ety 
a n d t ol er a bility of 
i ntr ac or o n ary i nf usi o n of C A P-
1 0 0 2 i n t his dise ase 
p o p ul ati o n, as well as a n 
ex pl or at ory assess me nt of 
effi c acy. T we nt y-f o ur patie nts 
(ra n d o mize d 1: 1) will be 
e val uate d as e x pl orat or y 
efficac y e n d p oi nts at si x- a n d 
t wel ve- m o nt h f oll o w- u p visits.
T he f or mer te xt di d n ot disc uss t h e 
sa m ple si ze rati o nale i n t er ms of t he 
pri mar y st u d y o bj ecti ve (safet y).
9. 2 Deter mi n ati o n of 
Sa m pl e Size
Re d u n da nt te xt re m o ve d fr o m 
defi niti o ns of safet y 
p o p ulati o ns.
Pre vi o usl y, i de ntical te xt was s u p plie d 
i n b ot h secti o ns 9. 3. 2 a n d 9. 4. 1.
9. 3. 2 Safet y 
P o p ulati o n
T E A E defi niti o n i niti ates wit h 
pr o d uct e x p os ure ( pre vi o usl y 
i nitiate d wit h vasc ular access)
Cl arifi cati o n t o matc h T E A E defi niti o n 
as prese nt i n secti o n 9. 5. 2 ( A d verse 
E ve nts)
7. 1 3. 2 Ti mi n g
St u d y assess me nts
Hist orical M RI data ( 6 t o 1 5 
m o nt hs pri or t o scree ni n g), if 
a vail a ble, will be c ollecte d a n d 
se nt t o t he M RI c ore la b f or 
assess me nt.
If a vail a ble, t his data will be use d t o 
p ote ntiall y deter mi ne t he rate of car diac 
dis ease pr o gressi o n at t he ti me of 
scree ni n g.
6. 8. 4 Hist orical 
Car diac
M RI
7. 1 Scree ni n g Visit
A d diti o n of Da y 3 p h o ne 
assess me nt
T o assess A Es f or b ot h st u d y ar ms
bet wee n D 0 a n d t he Wee k 2 visit.
3. 1 O verall St u d y 
Desi g n a n d Pla n
7. 3 Da y 3 P h o ne Visit
A p pe n di x 1 Sc he d ule 
of E ve nts


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 1 0 3 of 1 1 1
Descri pti o n of C h a n ge
R ati o n ale/ J ustific ati o n
Secti o ns Affecte d
St u d y assess me nts (c o nti n ue d)
All st u d y assess me nts will be 
perf or me d b y ce ntral 
la b orat ori es, e xce pt f or l ocal 
la b ass ess me nts as nee de d f or 
s u bj ect safet y o n t h e da y of 
a n d da y after i nf usi o n wit h 
C A P- 1 0 0 2.
Ce ntral la b orat or y ser vices are a d de d t o 
i m pr o ve c o nsiste nc y of assess me nts 
bet wee n st u d y sites. L ocal la b orat or y 
assess me nts o n Da y 0 a n d Da y 1 f or 
s u bj ects recei vi n g C A P- 1 0 0 2 are 
i n dicate d t o ma na ge s u bj ect safet y.
6. 5. 2 Sa m ple 
C ollecti o n, St ora ge, 
a n d S hi p pi n g
A p pe n di x 2 Cli nical 
La b orat or y T ests
Assess me nt of hei g ht a d de d 
(scree ni n g, 6 wee ks, 3 m o nt hs, 
6 m o nt hs, a n d 1 2 m o nt hs). If 
st a n di n g hei g ht ca n n ot be 
meas ure d, hei g ht will be 
calc ul at e d usi n g a 
meas ure me nt of ul na le n gt h 
( Ga ul d et al 2 0 0 4)
S u bj ects as y o u n g as 1 2 years ol d ma y 
be eli gi ble f or t his st u d y. At t his a ge, 
trac ki n g of hei g ht is a sta n dar d 
c o m p o ne nt of r o uti n g p h ysical 
e xa mi n ati o ns a n d ma y be i nf or mati ve 
re gar di n g s u bj ect healt h. Hei g ht is 
a d de d at e ver y st u d y visit w here 
s pir o metr y is meas ure d. 
6. 3 Car diac a n d 
Li mite d P h ysical 
E xa mi nati o ns
7. 1 Scree ni n g Visit
7. 5
Wee k 6 Visit ( Da y 
4 0 ± 7 da ys)
7. 6
M o nt h 3 Visit 
( Da y 9 0 ± 7 da ys)
7. 7
M o nt h 6 Visit 
( Da y 1 8 0 ± 1 4 da ys)
7. 8
M o nt h 1 2 Visit 
( Da y 3 6 0 ± 3 0 da ys)
A p pe n di x 1 Sc he d ule 
of E ve nts
Tr o p o ni n a n d C K- M B will be 
o btai ne d e ver y 8 h o urs ( ± 3 0 
mi n utes) at mi ni m u m f or 2 0- 2 4
h o urs aft er C A P- 1 0 0 2 i nf usi o n.
T his 3 0- mi n ute wi n d o w f or eac h 
assess me nt is n o w s pecifie d i n t he 
pr ot oc ol t o all o w s o me fle xi bilit y i n t he 
ti mi n g of s peci me n c oll ecti o ns, w hile 
still pr o vi di n g a p pr o pri ate f oll o w- u p f or 
e vi de nce of m y ocar dial i nfarcti o n 
i nj ur y p ost-i nf usi o n.
3. 3 Safet y M o nit ori n g
6. 1 0. 1 C A P- 1 0 0 2
I nf usi o n
7. 2 Ra n d o mizati o n,
Da y 0
A n n ual f oll o w- u p p h o ne call 
ti e d t o a n ni versar y of Da y 0 f or 
b ot h st u d y ar ms. 
C h a n ge i m ple me nte d f or parit y 
bet wee n ar ms. Pre vi o usl y, f oll o w- u p
call was tie d t o i nf usi o n date f or C A P-
1 0 0 2 s u bj ects, b ut t o ra n d o mizati o n f or 
us ual care s u bjects.
7. 9 A n n ual F oll o w- u p
P h o ne Call
Ur o bili n o ge n re m o ve d fr o m 
uri nal ysis assess me nts
T his para meter n ot a c o m p o ne nt of t he 
ce ntral la b orat or y’s uri nal ysis 
assess me nt. Ur o bili n o ge n is u nli kel y t o 
be affect e d b y treat me nt wit h 
C A P- 1 0 0 2.
A p pe n di x 2 Cli nical 
La b orat or y T ests


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 1 0 4 of 1 1 1
Descri pti o n of C h a n ge
R ati o n ale/ J ustific ati o n
Secti o ns Affecte d
St u d y assess me nts (c o nti n ue d)
A d diti o n of clarif yi n g te xt 
re gar di n g w hic h assess me nts 
are f or b ot h st u d y ar ms vers us 
assess me nts f or C A P- 1 0 0 2
o nl y, a n d w hic h assess me nts 
are perf or me d b y ce ntral vs. 
l o cal la b
Cl arifi cati o n t o e ns ure t hat a p pr o priate 
la b orat or y assess me nts are perf or me d 
f or us ual care s u bjects, a n d t hat 
assess me nts are perf or me d b y t he 
ce ntral la b orat or y f or c o nsist e nc y.
A p pe n di x 2 Cli nical 
La b orat or y T ests
M o difie d te xt re gar di n g ke y 
safet y assess me nts t o be 
perf or me d t hr o u g h t he st u d y 
f or all s u bjects.
Cl arifi cati o n t hat ke y safet y 
assess me nts will be perf or me d f or all 
s u bj ects, wit h t he e xce pti o n of t h ose 
p ost-i nf usi o n assess me nts rele va nt o nl y 
t o s u bjects recei vi n g C A P- 1 0 0 2.
3. 1 O verall St u d y 
Desi g n a n d Pla n
S u bjects will be ev al u at e d 
over all, o nce all s u bjects 
e nr olle d i n t he st u dy h ave 
re ac he d t he Week 6 visit. 
is re place d wit h te xt defi ni n g 
D S M B re vie ws f or Gr o u p 1 
( 7 2- h o ur data) a n d f or all 
s u bj ects ( 6- m o nt h data).
T his te xt is c ha n ge d t o be c o nsist e nt 
wit h t he safet y re vie w pla n esta blis he d 
b y t h e D S M B, as defi ne d i n t he c urre nt 
D S M B c hart er v 1. 0.
3. 1 O verall St u d y 
Desi g n a n d Pla n
Cl arifi cati o n: A 2 4 h o ur 
a m b ulat or y E C G m o nit or … 
will be perf or me d at t he 
scree ni n g visit ( all s u bjects),
d uri n g t he 2 4- h o urs f oll o wi n g 
release ( disc har ge) fr o m t he 
h os pit al (f or s u bjects receivi n g 
C A P- 1 0 0 2 i nf usi o n o nl y) a n d 
als o f or all s u bjects at t h e 
Wee k 6, M o nt h 6, a n d M o nt h 
1 2 st u d y visits.
Cl arifi cati o n t hat all s u bj ects will 
recei ve t his E C G m o nit ori n g at 
ti me p oi nts as pre vi o usl y i n dicat e d i n 
A p pe n di x 1 Sc he d ule of E ve nts – wit h 
t h e e xce pti o n of p ost-i nf usi o n 
m o nit ori n g w hic h is o nl y f or s u bj ects 
recei vi n g C A P- 1 0 0 2.
6. 7 C o nti n u o us 
Car diac R h yt h m 
M o nit or
Cl arifi cati o n t hat b ot h t he 
pare nt/ g uar dia n a n d t he s u bj ect 
( n ot t he s u bject al o ne) 
c o m plete t h e Q o L assess me nts
T he Pe ds Q L a n d t he P O D CI 
assess me nts are desi g n e d t o be use d f or 
b ot h t he s u bject a n d t h e pare nt/ g uar dia n
6. 9 Cli nical F u ncti o n 
a n d Q ualit y of Life 
Meas ures
Cl arifi cati o n t hat t he PI will 
se paratel y assess rel ati o ns hi p 
of t he A E t o t he C A P- 1 0 0 2 
pr o d uct, a n d relati o ns hi p t o t h e 
i nf usi o n pr oce d ure.
Pre vi o usl y, A E re p orti n g f or ms 
re q uire d assess me nt of A E relati o ns hi p 
t o t he i nf usi o n pr oce d ure; h o we ver, t his 
was n ot s pecifie d i n t he pr ot o c ol.
7. 1 3. 4 Rel ati o ns hi p
Cl arif yi n g i nf or mati o n a d de d 
re gar di n g pr o d uct descri pti o n, 
rec o nstit uti o n, a n d st ora ge.
T e xt a d de d t o clarif y ha n dli n g of t h e 
pr o d uct.
5. 1 I n vesti gati o nal 
Pr o d uct
S u b hea di n gs a d de d t o t his 
secti o n
S u b hea di n gs a d de d t o e xisti n g t e xt i n 
t his secti o n t o se parate disti nct t o pics
5. 1 I n vesti gati o nal 
Pr o d uct


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 1 0 5 of 1 1 1
Descri pti o n of C h a n ge
R ati o n ale/ J ustific ati o n
Secti o ns Affecte d
Ot her Cl arific ati o ns a n d Mi n or C h a n ges
Cl arifi cati o n i n cite d secti o ns 
t h at 9 a m o n Da y 0 is defi ne d, 
f or us ual care s u bjects, as t he 
e q ui vale nt ti me p oi nt t o t he 
st art of i nf usi o n f or s u bjects 
recei vi n g C A P- 1 0 0 2 
A us ual-care e q ui vale nt t o t he start of 
i nf usi o n ti me was esta blis he d i n 
A me n d me nt 1 f or parit y bet wee n st u d y 
ar ms, t o t he e xte nt p ossi ble.  T hese 
c ha n ges are c orrecti o ns t o clarif y t he 
i m ple me ntati o n of t h e pri or c ha n ge. 
3. 1 O verall St u d y 
Desi g n a n d Pla n
7. 1 3. 2 Ti mi n g
7. 2 Ra n d o mizati o n, 
Da y 0
9. 5. 2 A d verse E ve nts
Cl arifi cati o n t hat f or L T F 
s u bj ects, E n d of St u d y date is 
date/ti me of last c o ntact or 
k n o w n e ve nt. Ne w s u b hea di n g 
“ L ost t o F oll o w- U p” hi g hli g hts 
t his secti o n. 
Cl arifi cati o n as pri or te xt di d n ot 
s pecif y assess me nt of “e n d of st u d y” 
date f or L T F s u bjects.
Ne w s u b hea di n g is a d de d t o hi g hli g ht 
pri or te xt re gar di n g ma na ge me nt of 
s u bj ects w h o ma y be l ost t o f oll o w- u p. 
7. 1 2 L ost t o F oll o w-
U p
N o s u bject has e x perie nce d a 
T E A E cl assifi e d as  c o nsi dere d 
relate d t o C A P- 1 0 0 2 b ut t h at 
w as n ot als o cl assifie d as 
rel at e d t o t he cat heteri zati o n 
a n d i nf usi o n  pr oce d ure. 
1. 2. 3. 2 Treat me nt 
E mer ge nt A d verse 
E ve nts ( T E A Es)
E dit orial clarificati o n
1. 2. 5. 1 Efficac y 
C o ncl usi o ns
p- val u e a d de d t o le ge n d of 
Fi g ure 7
T he p- val ue was n ot pre vi o usl y liste d 
Fi g ure 7
D S A = d o n or s pecifi c 
a nti b o dy , n ot d o n or-s pecific 
a nti ge n
C orrecti o n i n t his secti o n o nl y (t his 
a b bre viati o n a n d ter m pre vi o usl y were 
c orrect i n ot her pr ot oc ol secti o ns, 
i n cl u di n g t h e list of a b bre viati o ns) 
…tec h ni q ues will be 
pr ot oc olle d are s pecifie d i n t h e 
M RI I m a gi n g M a n u al .
E dit orial clarificati o n
6. 8
M a g netic 
Res o na nce I ma gi n g 
“e nr olle d” c ha n ge d t o 
“r a n d o miz e d” i n m ost 
i nsta nces pertai ni n g t o t h e 
H O P E trial 
“ra n d o mize d” is a m ore acc urate a n d 
precis e ter m t ha n “e nr olle d” i n t h e 
i nsta nces re place d
M ulti pl e secti o ns
Refere nce a d diti o ns: Ga ul d et 
al 2 0 0 4, I n ker et al 2 0 1 2 
Ga ul d refere nce: hei g ht esti mati o n per 
ul n a; I n ker refere nce: e G F R esti mati o n
1 2 Refere nce List


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 1 0 6 of 1 1 1 
A p p e n di x 6  
A m e n d m e nt 1 C h a n g e s 
( Pr ot o c ol V er si o n 2 7 J a n u ar y 2 0 1 6) 
T he f oll o wi n g t a ble pres e nts a c o m plete list of c o nte nt c ha n ges i n t his pr ot oc ol a me n d me nt. 
T o a v oi d re d u n da n c y, t he “secti o ns affect e d” c ol u m n d oes n ot list t he pr ot oc ol s y n o psis as a n 
affecte d secti o n. F or c ha n ges s h o w n v er bati m, delete d te x t is s h o w n i n stri ket hr o u g h f o nt, 
a n d ne w text is s h o w n i n re d it alicize d f o nt.
Descri pti o n of C h a n ge
R ati o n ale/ J ustific ati o n
Secti o ns Affecte d
Cli nic al D at a U p d ates: Ot her Tri als wit h C A P -1 0 0 2
  
Si nce t he ori gi nal pr ot o c ol was iss ue d, 
cli ni cal e x perie nce wit h t he pr o d uct f or 
treat me nt use has e x pa n de d. A d diti o nal 
safet y a n d efficac y data fr o m t he 
o n g oi n g trials s u p p ort a n i m pr o ve d 
ris k/ be nefit pr ofile f or t h e pr o d uct.
1. 2 S u m mar y of 
Cli ni cal Data
Fi g ure 7
M o dific ati o ns t o Eli gi bilit y Criteri a
A ge ra n ge eli gi ble f or 
ra n d o mizati o n i nt o Gr o u p 1 is 
e x pa n de d t o i ncl u de males 
1 2 + years ol d.
I ncl usi o n Criteri o n 5:
3. 1 O verall St u d y 
Desi g n a n d Pla n
4. 2 I ncl usi o n Criteria 
M RI assess me nt at 6- 1 5
m o nt hs pri or t o scree ni n g n o 
l o n ger re q uire d; i nstea d, 
eli gi bilit y assess me nt will 
utili ze c o ntrast-e n ha nce d M RI 
at Scree ni n g
Hist orical M RI sca n was pre vi o usl y 
re q uire d s olel y t o assist i n st u d y 
stratificati o n, b ut has bee n a barrier t o 
st u d y e ntr y f or s u bjects ot her wise 
eli gi ble. Gi ve n t h e s mall n u m ber of 
a vail a ble s u bjects a n d t he s mall st u d y 
si ze, t he utilit y of stratif yi n g t he 
p o p ulati o n di d n ot j ustif y e xcl u di n g 
s u bj ects s ol el y f or a bse nce of M RI 
hist or y.  
I ncl usi o n Criteri o n 3:
4. 2 I ncl usi o n Criteria 
T hera p y wit h c hr o nic 
i n otr o pes, or c urre ntl y 
recei vi n g i ntra ve n o us i n otr o pic 
or vas oacti ve me dicati o ns at 
t h e ti me of scree ni n g. 
E dit orial clarificati o n
E x cl usi o n criteri o n 1:
4. 3 E xcl usi o n Criteri a 
5. 4 Pri or T hera p y 
E xcl usi o ns 
… s u bj ects m ust be ta ki n g 
s yst e mic gl uc oc ortic oi ds f or at 
least si x m o nt hs pri or t o 
si g ni n g t h e c o nse nt a n d/ or 
asse nt scree ni n g. 
Re visi n g t he defi niti o n t o 6 m o nt hs of 
gl u c oc ortic oi d t hera p y pri or t o scree ni n g 
is me dicall y rel e va nt; t h e pri or 
re q uire me nt was n ot.
I ncl usi o n crit eri o n 4:
4. 2 I ncl usi o n Criteria 


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 1 0 7 of 1 1 1
Descri pti o n of C h a n ge
R ati o n ale/ J ustific ati o n
Secti o ns Affecte d
Scree ni n g a n d R a n d o miz ati o n
E nr oll me nt will c o nti n ue u ntil 
1 2 s u bj ects are i nf use d or 3 0 
s u bj ects are e nr oll e d. N o 
s u bj ects will be re place d. 
Pre vi o usl y, e nr oll me nt tar get 
was 1 2 i nf use d a n d 1 2 c o ntr ol 
s u bj ects, wit h re place me nt of 
s u bj ects ra n d o mize d t o C A P-
1 0 0 2 b ut w h o di d n ot c o m plete 
i nf usi o n.
Pri or e nr oll me nt pla n all o we d f or 
re place me nt of s u bj ects o n o nl y o ne 
st u d y ar m.  Ne w pl a n is m ore bal a nce d, 
as n o ra n d o mize d s u bjects will be 
re place d.
3. 1 O verall St u d y 
Desi g n a n d Pla n
9. 2 Deter mi n ati o n of 
Sa m pl e Si ze
Ra n d o mi zati o n will be 
si m plifi e d a n d will n o l o n ger 
atte m pt t o stratif y assi g n me nts 
base d o n hist orical M RI 
rea di n gs or c hr o nic use of 
st er oi ds.
T he st u d y size ( 2 4 s u bjects) is t o o s mall
t o s u p p ort stratifi cati o n, a n d t h e 
re q uire me nt f or hist orical M RI is bei n g 
re m o ve d (as e x plai ne d a b o ve).
3. 1 O verall St u d y 
Desi g n a n d Pla n
5. 2 Ra n d o mizati o n
A d diti o nal la b orat or y tests at 
scree ni n g: ve n o us bl o o d 
assess me nts f or Tr o p o ni n, C K-
M B ( pre vi o usl y t hese 
para meters were assesse d p ost-
scree ni n g o nl y)
Scree ni n g val ues f or t hese para meters 
will pr o vi de a bas eli ne f or t he 
assess me nts c ollecte d later i n t he st u d y.
7. 1 Scree ni n g Visit
A p pe n di x 1 Sc he d ule 
of E ve nts
A p pe n di x 2 Cli nical 
La b orat or y T ests
Ne w t esti n g f or C yst ati n C at 
scree ni n g, M 6, a n d M 1 2.
C ystati n C is a d de d as a t o ol f or 
m o nit ori n g car di o vasc ular disease.
Ve n o us bl o o d s p eci me n f or 
E LI S P O T i m m u n oassa y 
c ollecte d at Scree ni n g i nstea d 
of pre-i nf usi o n
Ti mi n g f or c ollecti o n of t his sa m ple is
a dj uste d t o i m pr o ve bala nce bet wee n 
st u d y ar ms
7. 1 Scree ni n g Visit
7. 2 Ra n d o mizati o n 
a n d Da y 0
A p pe n di x 1 Sc he d ule 
of E ve nts
S af et y a n d Effic ac y A n al ys es
Ne w t e xt dis c ussi n g 
I n de pe n de nt O versi g ht 
C o m mittees ( D S M B a n d C E C)
Ori gi nal pr ot oc ol di d n ot e x plicitl y state 
t h at st u d y w o ul d be o versee n b y a 
D S M B, a n d di d n ot disc uss t he C E C.
3. 1 O verall St u d y 
Desi g n a n d Pl a n
1 0 I n d e pe n de nt 
O versi g ht 
C o m mittees
St u d y st o p pi n g r ules are n o w 
defi ne d b y refere nce t o t he 
D S M B C harter.
Ori gi nal Pr ot oc ol di d n ot defi ne st u d y 
st o p pi n g r ules. T he st u d y st o p pi n g r ules 
ha ve n o w b ee n esta blis he d b y 
u na ni m o us v ote of t he D S M B, a n d are 
detaile d i n t he D S M B C harter.
9. 8 St u d y St o p pi n g 
R ules
Bi o mar kers f or t he st u d y are 
n o w defi ne d ( Galecti n- 3, I L-
1 0, Oste o p o nti n, S T 2)
Bi o mar kers t o be assesse d i n t h e 
pr ot oc ol were n ot liste d pre vi o usl y. 
A p pe n di x 2 Cli nical 
La b orat or y T ests


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 1 0 8 of 1 1 1
Descri pti o n of C h a n ge
R ati o n ale/ J ustific ati o n
Secti o ns Affecte d
T he st u d y will m o nit or t h e 
pr o p orti o n of s u bj ects 
e x perie nci n g a n y of t he 
f oll o wi n g e ve nts d uri n g or p ost 
i ntrac or o nar y i nf usi o n 
deli ver y. F or c o m p aris o n, 
t h ese s a me eve nts will be 
m o nit or e d i n us u al c are 
s u bj ects usi n g 9: 0 0 a m o n D ay 
0 as t h e refere nce ti me p oi nt :
Ori gi nal pr ot oc ol di d n ot e x plicitl y state 
a met h o d f or c o m paris o n of safet y 
bet wee n i nf use d s u bj ects a n d c o ntr ol 
s u bj ects, f or t he peri o d d uri n g a n d 
i m me diatel y f oll o wi n g i ntrac or o nar y 
i nf usi o n of t he s u bjects recei vi n g C A P-
1 0 0 2.
3. 3 Safet y M o nit ori n g
Cl arific ati o ns, A d mi nistr ati ve C h a n ges a n d U p d ates
C h a n ge of S p o ns or C o nt act 
a n d Me dical M o nit or
Pers o n nel c ha n ge
7. 1 1. 8. 2 Re p orti n g 
Seri o us A d verse 
E ve nts
1 1 . 1 I n vesti gat ors a n d 
St u d y A d mi nistrati ve 
Str uct ure
St u d y Da y 0 re defi ne d as date 
of pr o d uct i nf usi o n f or C A P-
1 0 0 2 s u bj ects, a n d as 7 da ys 
after ra n d o mizati o n f or c o ntr ol 
s u bj ects. Pre vi o usl y, da y 0 was 
t h e date of ra n d o mizati o n.
Re defi ni n g Da y 0 as t he date of i nitial 
pr o d uct e x p os ure is m ore mea ni n gf ul 
t h a n ra n d o mizati o n date f or statisti cal 
assess me nts of safet y a n d pr o d uct 
efficac y. “ Da y 0” f or c o ntr ol s u bjects is 
defi ne d as “ra n d o mizati o n + 7 da ys” t o 
be as c o nsist e nt as p ossi ble wit h t he 
ot h er st u d y ar m (i nf usi o n date is 
a ntici pate d t o occ ur 7 da ys aft er 
ra n d o mizati o n, b ut s o me sc he d ule 
variati o ns ma y occ ur).
3. 1 O verall St u d y 
Desi g n a n d Pla n
Fi g ure 1 0
7. 2 Ra n d o mizati o n 
a n d Da y 0
7. 1 1. 2 Ti mi n g
9. 6. 1 Safet y E n d p oi nts
9. 6. 2 A d verse E ve nts
T ar get i nf usi o n ti mes f or was h 
s ol uti o n, I P ( C A P- 1 0 0 2) a n d 
2 n d was h s ol uti o n n o w defi ne 
wi n d o ws ( ± 5- 3 0 sec o n ds) 
per mitte d f or eac h ste p.  
Ori gi nal pr ot o c ol di d n ot defi n e 
per mitte d ra n ge of de viati o n fr o m tar get 
i nf usi o n ti mes.
6. 1 0. 1 C A P- 1 0 0 2
I nf usi o n
Efficac y Ass ess me nt 2 
( F u ncti o nal): Seri al c ha n ges i n 
m o bilit y meas ure me nts a n d 
Perf or ma nce of U p per Li m b 
( P U L) scale, s pir o metr y, a n d 
6- mi n ute wal k t est ( 6 M W T) 
w he n dee me d a p pr o priat e b y 
t h e I n vesti gat or.
Cl arifi cati o n of f u ncti o nal ass ess me nts 
t o be perf or me d
3. 2 E x pl orat or y 
Efficac y E n d p oi nts
A d diti o n of ter ms t o t he “ List 
of A b bre viati o ns a n d 
Defi niti o ns” ( C E C, D S M B, 
L G E, T E A E, T M P G)
T hese a b bre viati o ns i n t he pr ot oc ol were 
n ot pre vi o usl y defi ne d i n t his secti o n
List of A b bre viati o ns 
a n d Defi niti o ns


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 1 0 9 of 1 1 1
Descri pti o n of C h a n ge
R ati o n ale/ J ustific ati o n
Secti o ns Affecte d
Visit wi n d o ws pre vi o usl y 
defi ne d i n A p pe n di x 1 a n d 
Secti o n 7 are n o w refere nce d 
i n Secti o n 3. 1 als o 
Visit wi n d o ws pre vi o usl y were defi ne d 
i n t he pr ot oc ol b ut were o mitte d i n 
secti o n 3. 1
3. 1 O verall St u d y 
Desi g n a n d Pla n
Fi g ure 4 – defi niti o n of X-a xis
X-a xis para meters f or t his fi g ure were 
n ot la bel e d pre vi o usl y.
Fi g ure 4
A Es will b e re gar de d as 
‘ pretreat me nt’ if t h e y occ ur 
pri or t o t he first e x p os ure t o 
treat me nt. 
T e xt re m o ve d was re d u n da nt wit h t h e 
para gra p h i m me diatel y f oll o wi n g, w hi c h 
defi ne d T E A Es. 
9. 6. 2 A d verse E ve nts
Refere nce a d diti o n: 
1 2 Refere nce List


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 1 1 0 of 1 1 1
A p p e n di x 7 
S p o n s or Si g n at ur e
St u d y Title:
A Ra n d o mize d, O pe n-la bel St u d y of t he Safet y a n d Efficac y of 
M ulti- Vessel I ntrac or o nar y Deli ver y of All o ge neic Car di os p here-
Deri ve d Cells i n Patie nts wit h C ar di o m y o pat h y Sec o n dar y t o 
D uc he n ne M us c ular D ystr o p h y [ H O P E - D uc he n n e (H alt 
car di o m yO P at h y pr o grE ssi o n i n D uc he n ne)]  
St u d y N u m ber:
C A P- 1 0 0 2- D M D- 0 1
Ori gi n al Pr ot oc ol:
0 1 Ma y 2 0 1 5
A me n d me nt 3. 0:
1 8 J ul y 2 0 1 6
T his cli nical st u d y pr ot oc ol was s u bject t o critical re vie w a n d h as bee n a p pr o ve d b y t h e 
s p o ns or.  
Si g ne d:
Date:
1 8 J ul y 2 0 1 6
, M D
 & Me dical M o nit or 
Ca pric or, I n c.


C A P- 1 0 0 2 All o ge neic Car di os p here- D eri ve d Cells
Cli nical Trial Pr ot oc ol: C A P- 1 0 0 2- D M D- 0 1, A me n d me nt 3. 0
Ca pric or, I nc.
1 8 J ul y, 2 0 1 6
C o nfi d e ntial
P a ge 1 1 1 of 1 1 1
A p p e n di x 8 
I n v e sti g at or’ s Si g n at ur e
St u d y Title:
A Ra n d o mize d, O pe n-la bel St u d y of t he Safet y a n d Efficac y of 
M ulti- Vessel I ntrac or o nar y Deli ver y of All o ge neic Car di os p here-
Deri ve d Cells i n Patie nts wit h C ar di o m y o pat h y Sec o n dar y t o 
D uc he n ne M us c ular D ystr o p h y [ H O P E - D uc he n n e (H alt 
car di o m yO P at h y pr o grE ssi o n i n D uc he n ne)]
St u d y N u m ber:
C A P- 1 0 0 2- D M D- 0 1
Ori gi n al Pr ot oc ol:
0 1 Ma y 2 0 1 5
A me n d me nt 3. 0:
1 8 J ul y 2 0 1 6
I h a ve r ea d t h e pr ot oc ol descri be d a b o ve. I a gree t o c o m pl y wit h all a p plica ble re g ulati o ns 
a n d t o c o n d uct t he st u d y as descri be d i n t he pr ot o c ol.
Si g ne d:
Date:
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
Na me, Cre de ntials

SAP_001.pdf: 
Ca pric or T hera pe utics Pr ot oc ol C A P- 1 0 0 2- D M D- 0 1 P hase 2  
Statistical A nal ysis Pla n Versi o n 1. 0, Ja n uar y 6, 2 0 1 7                                                                 C O N FI D EN TI A L 
 
Pa ge 1  of 3 8  
 
 
 
S T A TI S TI C A L A N A L Y SI S P L A N 
 
 
Pr ot oc ol Title: 
A Ra n d o mize d, O pe n- La bel St u d y of  t he Safet y a n d Efficac y of M ulti-
Vessel I ntrac or o nar y Deli ver y of A ll o ge neic Car di os p here- Deri ved Cells 
i n Patie nts wit h Car di o m y o pat h y Sec o n dar y t o D uc he n ne M usc ular 
D ystr o p h y  
 
Pr ot oc ol Versi o n: 
A me n d me nt 3. 0, J ul y 1 8, 2 0 1 6 
 
Pr ot oc ol N u m ber: 
C A P- 1 0 0 2- D M D- 0 1 
 
St atistic al A n al ysis 
Pl a n Versi o n: 
Versi o n 1. 0 
Rele ase D ate: 
Ja n uar y 6, 2 0 1 7 
Versi o n Hist or y:  
-- 
 
St u d y N a me: 
H O P E- D uc he n ne ( H alt car di o m y O P at h y pr o gr E ssi o n i n D uc he n ne) 
 
St u d y P h ase: 
P hase 2 
 
Pr o d uct N a me: 
C A P- 1 0 0 2 All o ge neic Car di os p here- Deri ve d Cells 
 
I n dic ati o n: 
Car di o m y o pat h y i n D uc he n ne M usc ular D ystr o p h y 
 
Pri nci ple  
I n vesti g at or:   
, M D, M P H  
 
 
S p o ns or:  
 
Ca pric or T hera pe utics 
8 8 4 0 Wils hire Bl v d, 2 n d Fl o or 
Be verl y Hills, C A 9 0 2 1 1 
 
 
 
P P D


Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, January 6, 2017                                                                 CONFIDENTIAL 
 
Page 2 of 38 
 
 
 
CONFIDENTIALITY STATEMENT 
 
This document is confidential and proprietary to Capricor, Inc. and its affiliates. No information 
contained herein shall be reproduced, published, or otherwise disseminated or disclosed or used 
without the prior written approval of Capricor, Inc. and its affiliates.  
 
 


Capricor Therapeutics Protocol C A P-1002- D M D-01 Phase 2 
Statistical A nal ysis Pla n Versi o n 1. 0, Ja n uar y 6, 2 0 1 7 
C O N FI D E N TI A L 
111113 of 38 
P P D


Ca pric or T hera pe utics Pr ot oc ol C A P- 1 0 0 2- D M D- 0 1 P hase 2  
Statistical A nal ysis Pla n Versi o n 1. 0, Ja n uar y 6, 2 0 1 7                                                                 C O N FI D EN TI A L 
 
Pa ge 4  of 3 8  
 
R E VI SI O N HI S T O R Y 
 
Versi o n  
D ate  
A ut h or(s)  
S u m m ar y of Re visi o n(s) 
1. 0  
0 6Ja n 2 0 1 7 
  
Ne w d oc u me nt 
 
 
P P D


 
 
Page 5 of 38 
 
Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, January 6, 2017
CONFIDENTIAL 
 
TABLE OF CONTENTS 
APPROVALS .................................................................................................................. 3 
REVISION HISTORY ...................................................................................................... 4 
LIST OF ABBREVIATIONS ............................................................................................ 7 
PREFACE ....................................................................................................................... 9 
1. 
INTRODUCTION ................................................................................................ 10 
2. 
STUDY OBJECTIVES, TREATMENTS, AND ENDPOINTS .............................. 10 
2.1 
Objectives ........................................................................................................... 10 
2.2 
Treatment Group Comparisons .......................................................................... 10 
2.3 
Study Assessments ............................................................................................ 10 
2.3.1 
Safety Assessments ............................................................................... 10 
2.3.2 
Exploratory Efficacy Endpoints ............................................................... 12 
3. 
STUDY DESIGN AND SCHEDULE OF EVENTS .............................................. 13 
4. 
SAMPLE SIZE .................................................................................................... 14 
5. 
RANDOMIZATION ............................................................................................. 14 
6. 
ANALYSIS POPULATIONS ............................................................................... 14 
7. 
DATA MANAGEMENT, PRESENTATION, AND ANALYSIS 
CONSIDERATIONS ...................................................................................................... 15 
7.1 
Programming Environment ................................................................................. 15 
7.2 
Tables, Figures, and Listings .............................................................................. 15 
7.2.1 
Tables and Figures ................................................................................. 15 
7.2.2 
Listings ................................................................................................... 15 
7.3 
Data Analysis ...................................................................................................... 15 
7.4 
Subgroups .......................................................................................................... 16 
7.5 
Missing Data ....................................................................................................... 16 
7.6 
Study Period and Time Point Definitions ............................................................ 17 
7.7 
Visit Windows ..................................................................................................... 17 
8. 
STUDY POPULATION PARAMETERS ............................................................. 18 
8.1 
Analysis Populations .......................................................................................... 18 
8.2 
Eligibility and Informed Consent ......................................................................... 18 
8.3 
Baseline Characteristics ..................................................................................... 19 
8.4 
Medical History ................................................................................................... 19 
8.5 
Serology and Coagulation .................................................................................. 19 


 
 
Page 6 of 38 
 
Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, January 6, 2017
CONFIDENTIAL 
8.6 
IP Administration ................................................................................................ 19 
8.7 
Subject Study Progress ...................................................................................... 19 
8.8 
Subject Disposition ............................................................................................. 19 
9. 
SAFETY ANALYSIS .......................................................................................... 20 
9.1 
Adjudicated Clinical Events ................................................................................ 20 
9.2 
Adverse Events .................................................................................................. 20 
9.3 
Concomitant Medications ................................................................................... 21 
9.4 
Safety Laboratory Evaluations ............................................................................ 21 
9.5 
Vital Signs, Height, Weight, and BMI .................................................................. 22 
9.6 
Physical Examination ......................................................................................... 23 
9.7 
12-Lead ECG and Continuous Cardiac Monitoring ............................................. 23 
10. 
EXPLORATORY EFFICACY ANALYSIS .......................................................... 23 
10.1 
MRI Parameters ................................................................................................. 24 
10.2 
Mobility Parameters ............................................................................................ 26 
10.2.1  PUL Scale .............................................................................................. 26 
10.2.2  Spirometry .............................................................................................. 26 
10.2.3  6MWT ..................................................................................................... 26 
10.3 
QoL ..................................................................................................................... 26 
10.3.1  PedsQL – DMD Module .......................................................................... 26 
10.3.2  Pediatric Outcomes Data Collection Instrument (PODCI) ...................... 27 
11. 
OTHER DATA COLLECTED ............................................................................. 29 
11.1 
Missed Visits and Assessments ......................................................................... 29 
11.2 
Protocol Violations/Deviations ............................................................................ 29 
12. 
CLINICAL EVENTS COMMITTEE ..................................................................... 30 
13. 
SEQUENCE OF PLANNED ANALYSES ........................................................... 31 
13.1 
Interim Safety Reviews ....................................................................................... 31 
13.2 
Administrative Interim Analyses .......................................................................... 31 
13.2.1  Pre-Month 6 ............................................................................................ 31 
13.2.2  Month 6 .................................................................................................. 31 
13.3 
Final Analysis ..................................................................................................... 31 
14. 
DSMB ................................................................................................................. 32 
15. 
DEVIATIONS FROM STATISTICAL METHODS IN THE PROTOCOL ............. 32 
REFERENCES .............................................................................................................. 33 
APPENDIX A:  SCHEDULE OF EVENTS .................................................................... 34 
APPENDIX B: TABLES OF CONTENTS FOR TABLES, FIGURES, AND LISTINGS 36 
 


 
 
Page 7 of 38 
 
Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, January 6, 2017
CONFIDENTIAL 
LIST OF ABBREVIATIONS 
ABBREVIATION 
DEFINITION
6MWT 
Six-Minute Walk Test 
AE 
adverse event 
BMI 
body mass index 
CEC 
Clinical Events Committee 
CI 
confidence interval 
CK-MB 
creatine phosphokinase MB isoenzyme 
CSR 
Clinical Study Report 
DMD 
Duchenne muscular dystropy 
DSMB 
Data Safety Monitoring Board 
DSA 
donor specific antibodies 
ECG 
electrocardiogram 
ELISPOT 
enzyme-linked immunosorbent spot 
EOS 
end of study 
FBS 
fetal bovine serum 
FEF25-75% 
forced expiratory flow at 25-75% of FVC 
FET 
forced expiratory time 
FEV1 
forced expiratory volume in 1 second 
FVC 
forced vital capacity 
HbA1c 
glycosylated hemoglobin 
HBsAg 
hepatitis B surface antigen 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HLA 
human leukocyte antigen 
ICH 
International Conference on Harmonisation 
IL-10 
Interleukin 10 
IP 
investigational product 
ITT 
intent-to-treat 
LGE 
late gadolinium enhancement 
LS 
least-squares 
LTFUP 
Long-Term Follow-up 
LV 
left ventricular 
LVEDV 
LV end diastolic volume 
LVEF 
left ventricular ejection fraction 
LVESV 
LV end systolic volume 
M 
million 
MACE 
major adverse cardiac event 
MAR 
missing at random 


 
 
Page 8 of 38 
 
Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, January 6, 2017
CONFIDENTIAL 
MedDRA 
Medical Dictionary for Regulatory Activities 
MFI 
mean fluorescence intensity 
MI 
myocardial infarction 
mITT 
modified intent-to-treat 
ML 
maximum likelihood 
MNAR 
missing not at random 
MRA 
mineralocorticoid receptor antagonist 
MRI 
magnetic resonance imaging 
PedsQL 
Pediatric Quality of Life 
PEF 
peak expiratory flow 
PHA 
phytohemagglutinin 
PODCI 
Pediatric Outcomes Data Collection Instrument 
PT 
Preferred Term 
PUL 
Performance of Upper Limb 
QoL 
quality of  life 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
standard deviation 
SDF1 
stromal cell derived factor 1 
SOC 
System Organ Class 
TEAE 
treatment-emergent adverse event 
TFLs 
tables, figures, and listings 
TMPG 
TIMI myocardial perfusion grade 
VT 
ventricular tachycardia 
WHO-DD 
World Health Organization Drug Dictionary 
 
 
 
 
 


 
 
Page 9 of 38 
 
Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, January 6, 2017
CONFIDENTIAL 
PREFACE 
The purpose of this statistical analysis plan (SAP) is to describe the planned statistical analyses 
and reporting for Capricor Protocol CAP-1002-DMD-01 (HOPE). The planned analyses 
identified in this SAP may be included in future manuscripts. Exploratory analyses not 
necessarily identified in this SAP may be performed to support planned analyses. Any post-hoc 
or unplanned analyses not specified in this SAP will be clearly identified as such in the Clinical 
Study Report (CSR) and manuscripts for publication. 
The SAP is a supplement to the study protocol, which should be referred to for additional details 
on study design, study conduct, and other operational aspects of the study. 
The structure and content of the SAP provides sufficient detail to meet the requirements 
identified by the Food and Drug Administration and International Conference on Harmonisation 
(ICH) E9: Guidance on Statistical Principles in Clinical Trials.1 All work planned and described 
in the SAP will follow internationally accepted guidelines published by the American Statistical 
Association. The following documents were also considered in preparation for writing this SAP:  
 
 Clinical Research Protocol CAP-1002-DMD-01, Amendment 3.0, July 18, 2016 
 ICH E3 Guideline: Structure and Content of Clinical Study Reports2 
 ICH E6 Guideline on Good Clinical Practice3 
 ICH E8 General Considerations for Clinical Trials4 
 
 
 


 
 
Page 10 of 38 
 
Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, January 6, 2017
CONFIDENTIAL 
1. 
INTRODUCTION 
Duchenne muscular dystrophy (DMD) is a pediatric-onset, genetic disease in which patients 
lack dystrophin, a protein critical for stabilizing muscle cell membranes. Affecting 1 in 
3,500-5,500 male births, DMD accounts for 80% of all cases of muscular dystrophy. Patients 
experience progressive skeletal muscle weakness and loss of ambulation by age 15, eventual 
respiratory and cardiac failure, and an abbreviated lifespan. With the use of corticostertoids and 
noninvasive ventilation to treat respiratory muscle disease, heart failure has emerged as the main 
cause of death in DMD patients. Approved therapies for the underlying disease currently are 
limited to eteplirsen, an exon 51 skipping agent in dystrophin pre-mRNA to enable the synthesis 
of a shortened and functional form of dystrophin protein. Allogeneic cardiosphere-derived cells 
(CAP-1002) are an investigational product consisting of allogeneic cardiosphere-derived cells, 
known to secrete numerous bioactive elements upon delivery, which is thought to lead to global 
cardiovascular benefits. The HOPE-Duchenne Phase 2 trial will be the first investigation of 
CAP-1002 in male subjects with cardiomyopathy secondary to DMD and the first trial of the 
product not conducted exclusively in adults. The delivery approach will be multivessel 
intracoronary infusion to distribute the cells throughout the myocardium. 
2. 
STUDY OBJECTIVES, TREATMENTS, AND ENDPOINTS 
2.1 
Objectives 
The primary objective of HOPE is to evaluate the safety and tolerability of CAP-1002 
administered by multi-vessel intracoronary infusion in subjects with cardiomyopathy secondary 
to DMD. 
 
The secondary objective of HOPE is to explore the efficacy of CAP-1002 administered by multi-
vessel intracoronary infusion in subjects with cardiomyopathy secondary to DMD. 
2.2 
Treatment Group Comparisons 
Two treatment groups will be compared in the study: 
 
 CAP-1002 (single administration of 75 million (M) cells split into a triple vessel infusion 
of 25 M cells each) 
 Usual Care 
2.3 
Study Assessments 
2.3.1 Safety Assessments 
Safety will be assessed at 6 and 12 months post infusion or reference date unless otherwise 
noted. For usual care subjects, the reference time point will be randomization date + 7 days at 
9:00 a.m. (subject’s local time). 
 
1) Adjudicated clinical events: 
a) The following events occurring during or post infusion or reference time point: 
 


 
 
Page 11 of 38 
 
Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, January 6, 2017
CONFIDENTIAL 
 For subjects who receive CAP-1002 only, new TIMI flow 0-2 or TIMI myocardial 
perfusion grade (TMPG) 0-2, noted immediately following intracoronary infusion of 
investigational product (IP) and persisting > 3 min after IP infusion, despite 
intracoronary vasodilator administration. 
 
 Within 72 hours of intracoronary infusion or reference time point, sudden unexpected 
death defined as occurring within 1 hour of symptom onset, or unwitnessed death in a 
person previously observed to be well within the preceding 24 hours without an 
identified caused. 
 
 Major adverse cardiac events (MACE) within 72 hours of intracoronary infusion or 
reference time point, including death, non-fatal myocardial infarction and 
hospitalization for cardiovascular event (including heart failure hospitalizations). 
Evidence of myocardial injury will be assessed by a rule out myocardial infarction 
(MI) cardiac enzyme protocol following IP administration. Among subjects who 
receive CAP-1002, troponin and creatine phosphokinase MB isoenzyme (CK-MB) 
will be obtained every 8 hours for 20-24 hours after IP infusion. 
 
b) Sudden unexpected death defined as occurring within one hour of symptom onset, or 
unwitnessed death in a person previously observed to be well within the preceding 24 
hours without an identified cause. 
c) MACE, including death, non-fatal myocardial infarction, hospitalization for 
cardiovascular event (including heart failure hospitalizations), emergency room treatment 
for heart failure, left ventricular assist device or heart transplant. 
d) Any hospitalization due to a cardiovascular cause. 
e) Any inter-current cardiovascular illness which prolongs hospitalization.  
f) Development of, or an increase in the frequency of, ventricular tachycardia (VT) with 
duration of 30 seconds or longer ascertained by protocol mandated continuous cardiac 
monitoring via Holter Monitor or ZIO® Patch. 
g) Development of increased anti human leukocyte antigen (HLA) antibody levels with 
development of sensitization to HLA antigens specific to the CAP-1002 CDC donor. 
Elevation of donor-specific antibodies (DSA) is defined as mean fluorescence intensity 
(MFI) above a threshold of 5000; a threshold of 1000 MFI will also be used to evaluate 
elevation of DSA. See Section 9.1 for details related to comparison between CAP-1002 
and usual care subjects. 
2) Adverse events (AEs) 
3) Concomitant medications 
4) Change from baseline in laboratory evaluations 
5) Peak elevation in troponin and CK-MB levels following IP infusion or on reference date 


 
 
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6) Changes from baseline in vital signs, weight, and body mass index (BMI) 
7) Changes from baseline on general and cardiac physical examinations 
8) Changes from baseline in electrocardiogram (ECG), both 12-lead ECG and continuous 
cardiac monitoring 
2.3.2 Exploratory Efficacy Endpoints 
The following exploratory efficacy endpoints will be assessed at 6 and 12 months post infusion 
or reference date: 
 
1) Change from baseline in cardiac structural parameters measured by magnetic resonance 
imaging (MRI), including: 
 LV  late gadolinium enhancement (LGE) expressed as a percent of LV mass 
 LV LGE expressed in grams  
 LV viable mass expressed in grams  
 Number of LV segments with LGE 
 LV circumferential strain  
 Left ventricular ejection fraction (LVEF) 
 LV end diastolic volume (LVEDV) and LV end systolic volume (LVESV) 
 LV stroke volume 
 Regional LV function assessment 
LGE and circumferential strain will be assessed both overall as well as by individual segment 
and by groups of segments (e.g., infusion location, septum, base, LV free wall). 
2) Rate of change since baseline compared to rate of change from historical MRI to baseline in 
LV LGE (overall and by individual segment and groups of segments) 
 expressed as a percent of LV mass  
 expressed in grams 
3) Change from baseline in functional parameters: 
 Performance of Upper Limb (PUL) scale 
 Spirometry 
 6-minute walk test (6MWT) in ambulatory patients 
4) Change from baseline quality of life (QoL) parameters: 
 Pediatric Quality of Life Inventory (PedsQL), including the cardiac module 
 Pediatric Outcomes Data Collection Instrument (PODCI) Adolescent Questionnaire 
5) Change from baseline in biomarkers: 
 Osteopontin 
 ST2 
 Interleukin 10 (IL-10) 
 Galectin-3 


 
 
Pa ge 1 3  of 3 8  
 
Ca pric or T hera pe utics Pr ot oc ol C A P- 1 0 0 2- D M D- 0 1 P hase 2  
Statistical A nal ysis Pla n V ersi o n 1. 0, Ja n uar y 6, 2 0 1 7
C O N FI D E N TI A L 
3.  
S T U D Y D E SI G N A N D S C H E D U L E O F E V E N T S 
T his is a ra n d o mize d, o pe n-la be l, c o ntr olle d p hase 2 trial desig ne d t o e val uate t he safet y a n d 
t olera bilit y a n d e x pl ore t he efficac y of C A P- 1 0 0 2 a d mi nistere d b y m ulti- vessel i ntrac or o nar y 
i nf usi o n i n s u bjects wit h car dio m y o pat h y sec o n dar y t o D M D. A p pr o xi matel y 2 4, a n d n ot m ore 
t ha n 3 0, s u bjects will be ra n d o mize d 1: 1 t o recei ve C A P- 1 0 0 2 or us ual care. S u bjects 
ra n d o mize d t o recei ve us ual care will c o nti n ue t o be care d f or a n d treate d o n a n o n g oi n g basis i n 
w hate ver ma n ner t he i n vesti gat or dee ms m ost a p pr o priate f or t he  s u bject. T he first 6 s u bjects 
e nr olle d ( Gr o u p 1) will be ol der t ha n 1 8 years of a ge. E nr oll me nt of t he re mai ni n g s u bjects 
( Gr o u p 2) will be gi n at least t w o wee ks after t he fi nal i nf usi on occ urs i n Gr o u p 1 t o all o w a 
re vie w of Gr o u p 1 safet y data thr o u g h 7 2 h o urs p ost i nf usi o n. S u bjects i n Gr o u p 2 will be at least 
1 2 years of a ge. 
 
 
A nat o micall y 
o ne of t he t hree c or o nar y arterie s i nf use d m ust s u p pl y m ore t han 3 0 % of t he L V m y ocar di u m.   
 
 
 
 
 
 
S u bjects will u n der g o pr ot oc ol a ssess me nts t hr o u g h 1 2 m o nt hs p ost i nf usi o n or refere nce date. 
Re vie ws b y a Data Safet y M o nit o ri n g B oar d ( D S M B) will be d o ne after Gr o u p 1 c o m pletes 7 2 
h o urs of f oll o w- u p a n d t hr o u g h o ut t he  trial per c harter b ut at least se mi-a n n uall y.  T he D S M B 
will re vie w b ot h safet y a n d efficac y data after all s u bjects c o m plete 6 m o nt hs of f oll o w- u p or 
wit h dra w fr o m t he st u d y. I n a d diti o n, t here will be o ne a d mi nis trati ve i nteri m efficac y a nal ysis 
after M o nt h 6 M RI meas ure me nts are  a vaila ble f or at least 1 4 s ubjects. S u bjects will be f oll o we d 
a n n uall y f or 5 years p ost i nf usi o n or refere nce date. T he Sc he d ule of E ve nts is s h o w n i n 
A p pe n di x A . A sc he matic of t he st u d y desi g n is as f oll o ws: 
 
C CI
C CI


 
 
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4. 
SAMPLE SIZE  
The sample size of approximately 12 subjects per treatment group is adequate to assess safety 
and tolerability and to explore efficacy. 
5. 
RANDOMIZATION 
Randomization will be done by a dominant biased coin design5 within each of 5 blocks of 6 
subjects each.  This design allows decreasing predictability as more subjects become enrolled. 
For a given block, let DN = nc – nu, where nc = number randomized to CAP-1002 and nu = 
number randomized to usual care, and N = total randomized to date, N=0 to 5.  For block = B, 
B=1 to 5, let pN+1 = probability the next assignment will be CAP-1002. Then pN+1 varies 
according to the following rules: 
 
pN+1 = 0.5 if DN = 0 
pN+1 = pB if DN  > 0 
pN+1 = 1-pB if DN < 0 
 
The specific values of pB (for each block) will be known only to the study statistician until after 
database lock. 
6. 
ANALYSIS POPULATIONS 
The following analysis populations are defined for the trial: 
Safety Population: Subjects randomized to CAP-1002 treatment who received the IP on Day 0, 
and all subjects in the usual care treatment group who remain on study as of the reference time 
point. Subjects will be summarized and analyzed per treatment actually received, regardless of 
their randomization assignment. 


 
 
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Intent to Treat (ITT) Population: All subjects randomized. Subjects will be summarized and 
analyzed per their randomization assignment, regardless of the treatment (CAP-1002 or usual 
care) actually received. 
Modified ITT (mITT) Population for Efficacy Parameter X: Subjects in the safety population 
who have at least one post-baseline observation for Parameter X. Subjects will be summarized 
and analyzed per their randomization assignment, regardless of the treatment actually received. 
Per Protocol Population: Subjects with no major protocol violations. The list of subjects with 
major protocol violations will be compiled prior to database lock.  
7. 
DATA MANAGEMENT, PRESENTATION, AND ANALYSIS 
CONSIDERATIONS 
7.1 
Programming Environment 
SAS® version 9.4 or higher (SAS Institute, Cary, North Carolina) will be used for statistical 
analyses and the production of tables, figures, and listings (TFLs).  
7.2 
Tables, Figures, and Listings 
Tables of contents for TFLs to be produced are shown in Appendix B. All TFLs will be 
appended to the final CSR. 
7.2.1 Tables and Figures 
 Tables and figures will present data summaries and/or analyses for the appropriate study 
population; e.g., summaries of safety parameters will be shown for the safety population 
only. 
 Treatment group order in tables and figures will be usual care, CAP-1002, and “All 
Subjects.” Note: not all tables and figures will show data summarized for “All Subjects.” 
 Tables and figures will present summaries/analyses by study visit window, if applicable. 
 Table column headers and figure legends will include subgroup sample sizes. 
7.2.2 Listings 
 Listings will present all data collected for all subjects unless the listing applies only to a 
specific analysis population (e.g., a listing of treatment-emergent AEs applies only to the 
safety population). 
 Listings will be ordered by unique subject identifier, study visit window (see 
Section 7.7), date, and data collection time. 
7.3 
Data Analysis 
 The anchor date used for summaries and analyses will depend on the analysis population, 
as follows: 
 ITT population:  randomization date 
 mITT population: IP administration or reference date 


 
 
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 Safety population: IP administration or reference date 
 Per protocol population: IP administration or reference date 
 Categorical variables will be summarized as frequencies and percentages in each 
category. Percentages will be reported to one decimal place. Unless otherwise noted in 
Sections 8-10, categorical variables will be analyzed using chi square tests of association 
or, if any contingency table cell has less than 5 subjects, Fisher’s exact test. 
 Continuous variables will be summarized by numbers of subjects, means, standard 
deviations, medians, and ranges. The number of decimal places for minimums and 
maximums will be the same as the original data. The number of decimal places for 
means, medians, and interquartile ranges will be the same as the original data plus one. 
The number of decimal places for measures of variance will be the same as the original 
data plus two. Unless otherwise noted in Sections 8-10, continuous variables will be 
analyzed using t-tests or, if appropriate, analysis of covariance with baseline as a 
covariate. Non-parametric tests and data transformations will be considered for variables 
with distributions that violate parametric assumptions. 
 Data with qualifiers (e.g., “<”) will be listed with but summarized without the qualifier. 
 P-values will be presented to two decimal places if > 0.01, to three places if < 0.01 but 
> 0.001, and to four places if < 0.001 but > 0.0001. P-values < 0.0001 will be presented 
as “< 0.0001.” 
 Statistical tests will be two-sided and tested at the 0.05 significance level unless 
otherwise noted in Sections 8-10. 
 It is understood that statistical non-significance is not an indicator of equivalence.   
7.4 
Subgroups 
Differences in safety and/or efficacy by subgroups defined by the following classifiers may 
be explored as part of the final analysis:  
 Ambulatory vs. non-ambulatory 
 LVEF: > 55% vs. < 55% 
 Initiation of eteplirsen while on trial  
 Baseline DSA MFI < 500 vs. 500-1000 and/or DSA quartiles 
 Donor, stromal cell derived factor 1 (SDF1) level of lot received, master cell bank, and/or 
other identified measures of potential cell potency 
In addition, differences in safety and/or efficacy based on exposure to various heart failure 
medications, such as mineralocorticoid receptor antagonist (MRA), may be explored. 
7.5 
Missing Data 
 Listings will present data as reported. 
 Missing or partially missing dates that are required for date-dependent definitions (e.g., 
treatment-emergent AEs, concomitant medications) will be assumed to be the most 
conservative date possible. For example, an AE with a completely missing start date will 


 
 
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be considered treatment-emergent; similarly, an AE that started the same month and year 
as IP administration but with missing start day will be considered treatment-emergent.  
 Handling of missing endpoint data in summaries and analyses for each endpoint is 
described in Sections 8-10. 
7.6 
Study Period and Time Point Definitions 
 
The following study periods and time points are defined: 
 
Screening Period: the 30-day time period before IP infusion or the reference time point. 
 
Baseline: for a given parameter for a given subject, the last observation before IP infusion or the 
reference time point. 
 
Day 0: for a given subject, the day of planned IP infusion or the reference day. 
 
(Nominal Visit) Analysis Time Point: analysis based on data collected at the (nominal visit) time 
point, where nominal visits are as shown below in Section 7.7. 
 
End of Study (EOS), Subject Level: subject-level EOS is reached after completion of the Month 
12 visit or discontinuation for any reason. 
 
EOS, Study-Level: EOS is reached when all randomized subjects have either completed the 
Month 12 visit or have discontinued from the study for any reason. 
 
Long-Term Follow-Up (LTFUP) Period, Subject-Level: the LTFUP period begins after 
completion of the Month 12 visit and continues until 4 more annual visits have been completed. 
7.7 
Visit Windows 
Study visits will include Screening, Day 0, and nominal week or month indicated in the table 
below. Visit windows will be used in data listings, summaries and analyses and will be based on 
study day of the observation, defined as: 
study day = date of observation – Day 0 date 
Visit windows per protocol and to be used in listings, summaries and analyses are as follows: 
Nominal Visit 
Nominal 
Day 
Min Day Per 
Protocol 
Max Day Per 
Protocol 
Min Day for 
Analyses 
Max Day for 
Analyses 
Week 2 
14 
11 
17 
1 
29 
Week 6 
42 
33 
47 
30 
61 
Month 3 
90 
83 
97 
62 
153 
Month 6 
180 
166 
194 
154 
275 
Month 12 
360 
330 
390 
276 
427 
where cell entries are study days as defined above. For example, per protocol the Month 3 visit 
will occur between 83 and 97 days post infusion (Day 0), but for purposes of listings, summaries 


 
 
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and analysis all observations dated between 62 and 153 days post infusion will be included in the 
Month 3 visit window. 
Efficacy assessments that occur too late to be included in the Month 12 analysis window will be 
included in “last observation” analyses (see Section 10).  
For ITT summaries and analyses, study day will be defined as: 
study day = date of observation – randomization date - X 
where X is the number of days between randomization and Day 0. 
For example, for a subject who received IP 5 days after randomization and who had an 
assessment 65 days after randomization, the study day for that assessment would be 60 and the 
assessment would therefore fall into the Week 6 analysis window. 
In addition, visit windows based on time of data collection will be defined for assessments done 
during the 24 hours post IP administration as follows: 
Nominal Visit 
Nominal 
Hour 
Min Hour for 
Analyses 
Max Hour for 
Analyses 
8 Hours Post 
8 
4.01 
12.00 
16 Hours Post 
16 
12.01 
20.00 
24 Hours Post 
24 
20.01 
28.00 
 If multiple valid, non-missing observations exist within a given window, the observation to be 
used will be: 
1. the observation closest to the nominal visit day in question, or 
2. the latest observation if the multiple observations are equidistant from the nominal visit 
day, or 
3. the average (arithmetic or geometric, as appropriate) of the observations if the multiple 
observations have the same actual time point. In instances of multiple observations with 
the same time point from different laboratories, only observations from the central 
laboratory will be used. 
8. 
STUDY POPULATION PARAMETERS 
Listings will be done for the ITT population and summaries for the safety population.  Some or 
all summaries may also be done for other analysis populations defined in Section 6. Study 
population parameters to be listed and summarized are described below. 
8.1 
Analysis Populations 
The analysis populations defined in Section 6 will be described in terms of the identification of 
subjects in each population and the frequency distribution of each population. 
8.2 
Eligibility and Informed Consent 
Eligibility and informed consent parameters will be listed and will include protocol version, date 
of informed consent, and inclusion and/or exclusion criteria that were not met. Satisfaction of 
inclusion/exclusion criteria will be summarized. 


 
 
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8.3 
Baseline Characteristics 
Demographic and other baseline characteristics will be listed and summarized and will include 
study site, age, race, ethnicity, Latin or Hispanic origin, DMD genetic analysis, and frequency of 
wheelchair use. Age will be computed in SAS as follows: 
AGE = floor((intck('MONTH', bdt, rdt) - (day(rdt) < day(bdt))) / 12) 
where bdt = birth date in SAS date format and rdt = randomization date in SAS date format. 
Differences in baseline parameters by treatment group will be analyzed and p-values will be 
included in the summary table. 
8.4 
Medical History 
General medical history and cardiac history will be listed and summarized separately. The 
general medical history summary will include frequency of subjects with each condition. For 
cardiac history, the number of subjects with each condition and other condition-specific details 
will be summarized. Differences in medical and cardiac history by treatment group will be 
analyzed and p-values (for frequencies only) will be included in the summary table. 
8.5 
Serology and Coagulation 
Serology laboratory evaluations will include human immunodeficiency virus (HIV), hepatitis B 
surface antigen (HBsAg), and hepatitis C virus (HCV) and will be done at screening. 
Coagulation laboratory evaluations will be done pre-infusion (CAP-1002 subjects only). 
Serology and coagulation parameters will be listed and summarized. 
8.6 
IP Administration 
Details of IP administration will be listed. Successful completion of IP administration, reason for 
non-completion, combination of coronary territories infused, total dosage, and final TIMI flow 
score per artery infused will be summarized. 
8.7 
Subject Study Progress 
A listing of subject study progress will show dates of screening, informed consent, 
randomization, IP administration, study visits, and EOS. Number of subjects who completed 
each visit will be summarized. 
8.8 
Subject Disposition 
A listing of subject disposition will include dates of randomization and IP administration (or 
attempt) or reference date, whether or not the subject completed the Month 12 visit, subject-level 
EOS date, reason for study discontinuation (if applicable), and whether or not the subject 
consented to annual LTFUP. Frequencies and percentages of subjects who discontinued and 
reasons for discontinuation as well as duration of follow-up will be summarized. Duration of 
follow-up will be calculated as: 
 
 
 
 
duration = date of last known status – randomization date + 1 
 


 
 
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where date of last known status is the maximum date among AE start and end dates, concomitant 
medication start and stop dates, visit dates (including unscheduled visits), and EOS date. 
 
The summary table will include a p-value for treatment group comparison of discontinuation for 
any reason and, if appropriate, for duration of follow-up based on a log rank test. 
9. 
SAFETY ANALYSIS 
Listings, summaries, and analyses of safety parameters will be done for the safety population.  
Some or all summaries may also be done for other analysis populations defined in Section 6. 
Safety parameters are described below. 
9.1 
Adjudicated Clinical Events 
Clinical events, described in Section 2.3.1, will be adjudicated by an independent Clinical Events 
Committee (CEC) (see Section 12). Each event will be summarized as frequency and percentage 
of subjects who experienced the event.  In addition, a composite event will be defined as new 
TIMI flow 0-2 or TMPG 0-2 (CAP-1002 subjects only), sudden death, or MACE during or 
following IP administration or reference time point.  For the composite and its components, 
summaries will include exact 90% confidence intervals (CIs) for both treatment groups.  For 
peri-procedural events other than TIMI flow 0-2 or TMPG 0-2, summaries will include a 90% CI 
for the difference in proportions between treatment groups, and the one-sided p-value from an 
exact binomial test of the difference between treatment groups. For all other clinical events, 
assessed over the length of the trial, event rates per 100 subject-years will be calculated and, if 
applicable, treatment groups will be compared using negative binomial regression with an offset 
for days of follow-up (log transformed). If the dispersion parameter is not significantly different 
from zero, Poisson regression will be used instead.  
For the analysis of development of increased HLA antibodies to HLA antigens specific to the 
CAP-1002 donor, incidence of increased HLA antibody levels specific to the donor will be 
summarized and analyzed; for usual care subjects, a random donor will be selected from those 
that were matched to the subject during screening.  Elevated levels of donor specific antibodies 
will also be summarized and analyzed by time point for all nominal time points at which samples 
were collected for DSA testing. Analyses will be performed using both 1000 and 5000 MFI as 
the threshold for defining increased HLA antibodies.   
9.2 
Adverse Events 
AEs reported from screening through EOS will be coded according to MedDRA® (Medical 
Dictionary for Regulatory Activities) version 19.0. Each reported AE will be mapped to a 
Preferred Term (PT) and a System Organ Class (SOC). A subset of AEs (indicated below) will 
also be adjudicated by the independent CEC. 
A treatment-emergent AE (TEAE) will be defined as an AE that began or worsened during or 
after the IP administration procedure or on or after the reference time point. AEs with 
insufficient date or time information to determine whether or not they were treatment-emergent 
will be considered treatment-emergent and the ambiguity regarding start time/date for these AEs 
will be footnoted in summary tables. 


 
 
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All TEAEs will be listed as reported. A separate listing will be done for TEAEs as adjudicated 
by the CEC. In addition, separate listings will be done for deaths, non-treatment-emergent AEs 
and serious AEs (SAEs), treatment-emergent SAEs (adjudicated), TEAEs within 24 hours of IP 
administration (adjudicated if judged to be related to IP or IP administration procedure), and 
TEAEs that resulted in study discontinuation (excluding deaths); these listings will be “as 
adjudicated,” as applicable.  Deaths will be listed by primary cause as adjudicated by the CEC. 
Incidence and number of TEAEs will be summarized by SOC and PTs within SOCs, both overall 
and by relationship to IP, relationship to IP administration, and severity. Relationship status 
“possibly,” “probably,” or “definitely” will be considered related and will be adjudicated. 
Missing relationship will be considered related for subjects in the CAP-1002 group and missing 
severity will be considered severe; the lack of assigned relationships for these AEs will be 
footnoted in summary tables. Only the most related TEAE per subject for a given PT will be 
counted in summaries by relationship; similarly, only the most severe TEAE will be counted in 
summaries by severity. Separate summaries will be done for treatment-emergent SAEs, TEAEs 
within 24 hours of IP administration, treatment-emergent deaths, and TEAEs resulting in study 
discontinuation (excluding deaths). Each summary table will include a p-value for the 
comparison of incidence for each SOC and PT, as well as overall, between treatment groups, if 
applicable.  Summary tables and analyses will be based on TEAEs as adjudicated by the CEC. 
9.3 
Concomitant Medications 
Medication use from consent through EOS will be coded to generic terms using the World 
Health Organization Drug Dictionary (WHO-DD), version June 1, 2016. Listings will include IP 
administration date, WHO-DD drug class, WHO-DD preferred drug name, generic/trade drug 
name, start and stop dates, dose, route, frequency, indication, and associated AE and SAE 
number, if applicable. Frequencies and percentages of subjects reporting or receiving each 
medication will be summarized by WHO-DD drug class and preferred name within drug class. 
Any pre-infusion/reference date medications reported will be listed and summarized separately 
from concomitant medications. Cardiac and steroid medications will also be listed and 
summarized separately. Medications that were stopped no later than the day before IP 
administration or reference day will be considered “pre-infusion.” All other medications will be 
considered “concomitant.” Medications recorded with insufficient exposure dates to determine 
whether or not they were concomitant will be considered concomitant. 
9.4 
Safety Laboratory Evaluations 
Specific laboratory evaluations to be performed are detailed in Appendix 2 of the protocol.  
Listings of safety laboratory evaluations will include study visit, date and time of collection, 
normal ranges, observed values with out-of-range values flagged, and changes from baseline. 
Separate series of listings will show out-of-range observations.  
Observed values and changes from baseline will be summarized by study visit. A separate series 
of summaries will show incidence of out-of-range observations by study visit. Shift tables will 
summarize shifts from one out-of-range category at baseline to another out-of-range category at 
each subsequent study visit and will include p-values for treatment group differences. 
Listings and summaries will be done separately for each of the following laboratory evaluations 
or groups of evaluations: 


 
 
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 Serum chemistry (basic metabolic and comprehensive hepatic panels) 
 Hematology 
 Urinalysis 
 Glycosylated hemoglobin (HbA1c) 
 Cardiac (troponin I, troponin T, CK-MB) 
 Immunogenicity (HLA, DSA, enzyme-linked immunosorbent spot (ELISPOT))  
 Exploratory biomarkers, if available 
 
For DSA, the raw data will be provided by the core laboratory and a listing of HLA antibodies 
and specific alleles will be provided to the independent clinical immunologist to make the 
final determination of which are DSA caused by sensitization to the donor cells, and which 
are non-specific changes that are not due to donor-specific sensitization. Any summary tables 
or analyses of DSA will be based on DSA as adjudicated by the independent clinical 
immunologist.    
The results of the ELISPOT assay for the tested samples will be reported as number of 
spots/400,000 cells/well.  In addition, the results will be expressed as mean and standard 
deviation (SD) of the triplicate (or duplicate) wells for serum-free medium wells, fetal bovine 
serum (FBS)-containing medium wells, and antigen-stimulated wells.  For phytohemagglutinin 
(PHA)-stimulated wells the result will be the spot number/400,000 cells from the single well.  
If the cell number would be insufficient and the testing will be performed in a single well for 
a given variant, then the result will be the spot number/400,000 cells from the single well.  A 
positive or negative response to each antigen (cardiac cell lines) will be determined based on 
the results of each individual sample.  A positive response will be defined as greater than Y + 
2SD of Y number of spots after exposure to Antigen (X) and more than 10 spots, whereby:  
Y:  Average spot number in the FBS-medium control (cells and no antigen) 
X:  Average spot number to the given antigen (cells and antigen) 
The antigen specific response = antigen positive response = X - (SD of X) – [Y + (2SD of Y)] 
and has to be greater than the numerical value 3.  All negative values generated by the 
formula above will be reported as 0 spot values, as negative values are biologically irrelevant. 
The results for the control sample will be reported as number of spots/400,000 cells/well.  In 
addition, the results will be expressed as mean and SD of the triplicate wells for medium 
wells, antigen-stimulated wells and PHA wells.   
Any clinical sample that will produce below 100 interferon-gamma spots in response to the 
mitogen (positive control) PHA will be flagged as non-functional and the ELISPOT results 
for that sample should be excluded from further analysis. 
9.5 
Vital Signs, Height, Weight, and BMI 
Vital signs will include systolic and diastolic blood pressure, heart rate, respiratory rate, and 
body temperature. Listings of vital signs, height, weight, and BMI will include study visit, date 
and time of collection, observed values, and changes from baseline. Observed values and 
changes from baseline will be summarized by study visit. BMI will be calculated as:  


 
 
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9.6 
Physical Examination 
General and cardiac physical examination findings will be listed and summarized separately. 
General physical examination findings will be summarized either as frequencies of 
normal/abnormal indicators at each visit or, if appropriate (i.e., if data are not too sparse), as 
shifts from baseline in normal/abnormal indicators for each body system. For cardiac physical 
examination findings, the number of subjects with each condition and other condition-specific 
details will be summarized; shifts from baseline in present/absent and normal/abnormal 
indicators will also be summarized, as will murmur grade. 
9.7 
12-Lead ECG and Continuous Cardiac Monitoring  
Listings of 12-lead ECG parameters will include study visit, date and time of ECG, and observed 
values. Observed values and changes from baseline in ventricular rate and interval parameters 
(QRS, PR, QT, QTc) will be summarized by study visit. Overall interpretation of 12-lead ECG 
will also be summarized.  
 
Listings of continuous cardiac monitoring  parameters will include study visit, start and stop 
date/time, and observed values. Observed values and changes from baseline in QRS complexes, 
paced QRS complexes, ventricular ectopic beats, supraventricular ectopic beats, heart rates, and 
longest RR will be summarized by study visit. Presence of atrial fibrillation, including number of 
episodes and longest run, will also be summarized. 
10. 
EXPLORATORY EFFICACY ANALYSIS 
Listings of efficacy parameters will be done for the ITT population. Summaries and analyses will 
primarily be done for the mITT population; some or all summaries and/or analyses may also be 
done for other analysis populations defined in Section 6. In addition, “last observation” analyses 
will be done for certain parameters for which some subjects’ final assessments were done too 
late to be included in the Month 12 analysis window. 
 
Unless otherwise noted, for the final analysis changes from baseline will be analyzed using 
general linear models with baseline values as covariates. Analyses of the effect of treatment 
group, time (baseline, Month 6, Month 12), and their interaction will be done using mixed effects 
linear regression, with subject as a random effect, time and treatment group as fixed effects, and 
baseline as a covariate. Study site may also be included as a random effect if there is evidence of 
correlation within study sites (per the interclass correlation coefficient from the unconditional 
model) and/or if doing so appreciably improves the model fit (e.g., per Akaike’s Information 
Criterion). Residuals will be evaluated for substantial departure from normality and independent 
and constant variance and appropriate remedies (e.g., data transformations, detecting and 
assessing the influence of outliers, alternative analytical approaches) will be attempted when 
necessary. An unstructured covariance will be the default covariance structure but other 
structures (e.g., compound symmetry) may be used to evaluate sensitivity to the choice of 
structure or, if necessary, to achieve convergence. 


 
 
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Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, January 6, 2017
CONFIDENTIAL 
 
For the analysis of LV LGE rate of change since baseline compared to rate of change from 
historical MRI to baseline, rate of change RC(ti) for time point ti, i = 1 to 3 (baseline, Month 6, 
Month 12, respectively), will be calculated as 
 
 
 
 
 
RC(ti) = (X(ti) – R(ti)) / D(ti) 
where X(ti) is observed LGE at ti, R(ti) is observed LGE at the reference time point for ti, and 
D(ti) is the number of days between ti and the reference time point for ti.  The reference time 
point will be the date of historical MRI for i = 1 and baseline for i > 1. The mixed effects model 
to be used for the final analysis will be similar to that described above, with historical LGE 
included as a covariate. The LSMEANS  procedure in PROC MIXED will be used to compare 
RC(t2) and RC(t3) to RC(t1) within each treatment group, and tests for interaction along with 
descriptive statistics will be used to evaluate differences by treatment group. 
 
Assuming missing observations are “missing at random” (MAR), i.e., the fact that they are 
missing is unrelated to the missing variable but can be related to another variable on which data 
have been collected, the maximum likelihood (ML) approach is able to handle subjects with 
either Month 6 or Month 12 changes from baseline missing, but not both. Therefore, for final 
analyses based on the mITT population, missing data will be addressed using ML. Final analyses 
based on the ITT population may include subjects with both Month 6 and Month 12 changes 
from baseline missing; under these circumstances, multiple imputation will be used based on all 
observations and will use a fully conditional specification method with 20 burn-in iterations and 
the regression method of imputation. Variables in the imputer’s model will be baseline 
observation (because baseline is used as a covariate in analyses), Month 6 change from baseline, 
Month 12 change from baseline, and treatment group. Because the MAR assumption is not 
testable, and because it seems possible that subjects with poorer outcome may be more likely to 
miss trial assessments, a sensitivity analysis under a “missing not at random” (MNAR) 
assumption may be done (for the final analysis only) for any efficacy endpoint for which all 
change from baseline measurements are missing for some subjects. For the MNAR model, 
multiple imputation will use the pattern-mixture model approach to address missing values; i.e., 
the imputation will be based on a pre-specified subset of subjects: for this MNAR analysis, only 
subjects randomized to usual care. Because very few missing observations are expected in this 
trial, 5 imputed data sets will be used for all analyses using multiple imputation. 
 
For all analyses of all efficacy parameters, tests of treatment effect will be based on comparisons 
of least-squares (LS) means with no adjustment for multiple comparisons. 
 
Efficacy parameters are described below. 
10.1 
MRI Parameters 
Data for MRI parameters detailed in Section 2.3.2 will be delivered in a raw file provided by the 
MRI Core Lab. Observed values, absolute changes from baseline, and percent changes from 
baseline will be listed and summarized. Summary tables will include p-values for treatment 
group comparisons of changes from baseline. 
 


 
 
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Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, January 6, 2017
CONFIDENTIAL 
Regional wall motion will be analyzed using average (over slices) end diastolic wall thickness, 
end systolic wall thickness, and wall thickening. Sixteen-segment data correspond to coronary 
region as follows: 
 
 Left anterior descending artery = segments 1, 2, 7, 8, 13, and 14. 
 Left circumflex artery = segments 5, 6, 11, 12, and 16. 
 Right coronary artery = 3, 4, 9, 10, and 15. 
 
Different coronary anatomy will be associated with specific segments on a case-by-case basis. 
Analysis parameters will be observations averaged over the infused segments.  For example, if 
the infused segment is via the right coronary artery, wall thickening for that location will be the 
mean “average” wall thickening over segments 3, 4, 9, 10, and 15. 
 
Regional wall motion will also be analyzed according to circumferential location as follows: 
 
 Anterior = 1, 7, and 13 
 
Lateral = 5, 6, 11, 12 and 16 
 Inferior = 4, 10, and 15  
 Septal = 2, 3, 8, 9, and 14 
 
Of note, segments 2 and 3 will be excluded for all wall thickness analyses.   
 
Scar size, non-viable tissue, and circumferential strain will be analyzed both overall as well as by 
individual segments and the following groups of segments: 
 
 By coronary artery territory as follows: 
o Left anterior descending artery = segments 1, 2, 7, 8, 13, and 14 
o Left circumflex artery = segments 5, 6, 11, 12, and 16 
o Right coronary artery = 3, 4, 9, 10, and 15 
 
 By circumferential location as follows: 
o Anterior = 1, 7, and 13 
o Lateral = 5, 6, 11, 12 and 16 
o Inferior = 4, 10, and 15  
o Septal = 2, 3, 8, 9, and 14 
 
Listings of MRI parameters will include observed values, changes from baseline, and percent 
changes from baseline. A summary table will include p-values for treatment group comparisons 
of changes from baseline. 
 
MRI overreaders will be blinded to treatment assignment but not to temporal order of the 
images; e.g., readers will have access to and will use baseline and Month 6 images when reading 
Month 12 images (informed reading). 


 
 
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Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, January 6, 2017
CONFIDENTIAL 
10.2 
Mobility Parameters 
10.2.1 PUL Scale 
The PUL Scale consists of an entry item to define the starting functional level and 21 items 
subdivided into shoulder level (4 items, maximum score = 16), middle level (9 items, maximum 
score = 34), and distal level (8 items, maximum score = 24) dimensions.  The three dimensions 
will be summed to derive an overall score (maximum = 74) as well as an overall score that 
excludes the shoulder dimensions (maximum = 58). The minimum score for all three dimensions 
is 0. Increasing scores over time indicate improvement. Observed values and absolute changes 
from baseline, overall and for each dimension separately, will be listed and summarized. A 
summary table will include p-values for treatment group comparisons of changes from baseline. 
10.2.2 Spirometry 
Spirometry parameters include peak expiratory flow (PEF), forced expiratory volume in 1 
second (FEV1), forced vital capacity (FVC), FEV1/FVC x 100, forced expiratory flow at 25-75% 
of FVC (FEF25-75%), and forced expiratory time (FET). Observed values, percent of predicted, 
and absolute and percent changes from baseline will be listed and summarized. A summary table 
will include p-values for treatment group comparisons of changes from baseline. Extreme 
outliers, defined as any observation outside the range [q1 – 3(q3 – q1), q3 + 3(q3 – q1)] where 
q1 and q3 are the 25th and 75th percentiles, respectively, over all observations for a given 
parameter (regardless of time point) will be excluded from summaries and analyses.6 
10.2.3 6MWT  
For distance walked in the 6MWT of the subset of ambulatory subjects, observed values, 
absolute changes from baseline, and percent changes from baseline will be listed and 
summarized. A summary table will include p-values for treatment group comparisons of changes 
from baseline. Because of potential differences in 6MWT administration procedures across study 
sites, “site” will be carefully considered as a potential source of excess variation and will be 
included in the statistical model as a random effect if warranted. 
10.3 
QoL 
The following QoL measurement instruments, although routinely used for DMD trials, have not 
been validated for young adults, and this trial will enroll subjects > 18 years old. 
10.3.1 PedsQL – DMD Module 
The PedsQL-DMD Module consists of 18 items and results in scores for each of 4 scales (Daily 
Activities, Treatment Barriers, Worry, Communication) and a total summary score. Separate 
inventories are typically used for respondents 13-18 years old and for respondents 8-12 years 
old, as well as for parent responders for each age category; however, in this trial, only the 
inventories for 12-18 year-olds will be used, despite the lower age limit for trial inclusion being 
12 years. While responses to all 18 items will be listed, only these 4 scales and the total score 
will be summarized. Summary tables and listings will include observed values and changes from 
baseline; tables will also include p-values for treatment group comparisons of change from 
baseline.   
 


 
 
Pa ge 2 7  of 3 8  
 
Ca pric or T hera pe utics Pr ot oc ol C A P- 1 0 0 2- D M D- 0 1 P hase 2  
Statistical A nal ysis Pla n V ersi o n 1. 0, Ja n uar y 6, 2 0 1 7
C O N FI D E N TI A L 
T he Pe ds Q L is sc ore d as f oll o ws: 
 
1)  Tra nsf or m 0- 4 scale ite ms t o 0- 1 0 0 as f oll o ws:  0 = 1 0 0, 1 = 7 5, 2 = 5 0, 3 = 2 5, 4 = 0. 
 
2)  A sc ore f or eac h scale is calc ulate d as t he mea n of t he n o n- mis si n g ite ms t hat c o m prise t hat 
scale. 
 
3)  T he T otal s u m mar y sc ore is t h e mea n of all n o n- missi n g ite ms. 
 
Decreasi n g sc ores o ver ti me i n dicate i m pr o ve me nt. 
1 0. 3. 2  Pe di atric O utc o mes D at a C o llecti o n I nstr u me nt ( P O D CI) 
T he P O D CI c o nsists of 8 3 ite ms a n d res ults i n b ot h sta n dar dize d  a n d n or mati ve sc ores f or eac h 
of 6 scales.  Decreasi n g sc ores o ve r ti me i n dicate i m pr o ve me nt. Se parate i n ve nt ories are use d f or 
s u bjects a n d f or pare nt res p o n ders. W hile res p o nses t o all 8 3 ite ms will be liste d, o nl y t he 6 
scales will be s u m marize d. S u m mar y ta bles a n d listi n gs will i ncl u de o bser ve d val ues a n d 
c ha n ges fr o m baseli ne; ta bles wi ll als o i ncl u de p- val ues f or treat me nt gr o u p c o m paris o ns of 
c ha n ge fr o m baseli ne.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
C CI


 
 
Pa ge 2 8  of 3 8  
 
Ca pric or T hera pe utics Pr ot oc ol C A P- 1 0 0 2- D M D- 0 1 P hase 2  
Statistical A nal ysis Pla n V ersi o n 1. 0, Ja n uar y 6, 2 0 1 7
C O N FI D E N TI A L 
 
 
 
 
   
  
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
C CI


 
 
Pa ge 2 9  of 3 8  
 
Ca pric or T hera pe utics Pr ot oc ol C A P- 1 0 0 2- D M D- 0 1 P hase 2  
Statistical A nal ysis Pla n V ersi o n 1. 0, Ja n uar y 6, 2 0 1 7
C O N FI D E N TI A L 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 1.  
O T H E R D A T A C O L L E C T E D 
1 1. 1  
Misse d Visits a n d Assess me nts 
A listi n g of misse d visits a n d assess me nts will s h o w visit a n d/ or assess me nt misse d. 
1 1. 2  
Pr ot oc ol Vi ol ati o ns/ De vi ati o ns 
Pr ot oc ol e xc ursi o ns will be class ifie d as eit her vi olati o ns or de viati o ns.  Per I C H E 3 ( Str uct ure 
a n d C o nte nt of Cli nical St u d y Re p orts), 2 vi olati o ns will be defi ne d as: 
 E nr olli n g i nt o t he trial wit h o ut  meeti n g all i ncl usi o n/e xcl usi on criteria a n d wit h o ut 
o btai ni n g a wai ver f or a n y de viati o ns fr o m t he pr ot oc ol- defi ne d  e ntr y criteria; 
 C o nti n ui n g i n t he trial after de vel o pi n g a wit h dra wal criteri o n  (see Pr ot oc ol Secti o n 
7. 1 0); 
 Recei vi n g a n i nc orrect d ose or  i nc orrect treat me nt; or  
 Ta ki n g a pr o hi bite d c o nc o mita nt m e dicati o n (see Pr ot oc ol Secti o n 5. 5). 
S u bjects wit h pr ot oc ol vi olati o ns  will be e xcl u de d fr o m t he per pr ot oc ol p o p ulati o n. All ot her 
pr ot oc ol discre pa ncies will be c o nsi dere d de viati o ns a n d will b e cate g orize d f or p ur p oses of 
C CI


 
 
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Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, January 6, 2017
CONFIDENTIAL 
summarization. Some protocol deviations may prohibit subjects from being in the per protocol 
population; this will be determined on a case-by-case basis before database lock.  
 
In addition to the listings of inclusion/exclusion criteria detailed in Section 8.2 and missed visits 
and assessments detailed in Section 11.1, a separate listing will show all other protocol violations 
and will include protocol version, the category of the violation (to be determined), and an 
indicator for per protocol exclusion. Frequency and percentage of subjects in each violation 
category and excluded from the per protocol population will be summarized. 
12. 
CLINICAL EVENTS COMMITTEE 
In order to apply some level of consistency and standardization, the following will be 
adjudicated by a CEC: 
 
 Clinical event endpoints  
 
 AEs occurring within 24 hours of IP administration or reference time point (peri-
procedural AEs) 
 
 AEs judged by the investigator as possibly, probably or definitely related to the IP or IP 
administration procedure (related AEs) 
 
 Treatment-emergent SAEs 
 
The CEC will follow consensus definitions of cardiovascular endpoint events.7 In the case where 
the protocol explicitly provides an endpoint definition, the CEC will adjudicate the clinical event 
according to the protocol definition and then, separately, according to the consensus definition. 
In the case where the protocol provides only a partial definition (e.g., “emergency room 
treatment for heart failure”) or is silent on the definition of the endpoint, the consensus 
definition, if it exists, will be used.  
 
For safety endpoints, a hierarchy will be applied for a clinical event that could be adjudicated in 
multiple categories so that a clinical event is counted only once. The hierarchy, from highest 
severity to lowest, will be death > heart failure hospitalization > cardiovascular-related 
hospitalization.  
 
For any AE submitted to the CEC, all of the above characteristics will be adjudicated. In 
addition, the CEC can combine AEs reported separately into a single AE, can change the event 
description (i.e., the term used to report the AE), and can change the status of the reported event 
to a non-AE.  
 
Any adjudicated event not otherwise named in the consensus definitions, as well as changed 
event descriptions, will be MedDRA-coded. 


 
 
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Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, January 6, 2017
CONFIDENTIAL 
13. 
SEQUENCE OF PLANNED ANALYSES 
13.1 
Interim Safety Reviews 
The DSMB will conduct an interim safety review after all subjects in Group 1 have completed at 
least 72 hours of observation (or withdrawn) and will make a recommendation on proceeding to 
Group 2 enrollment. Thereafter, the DSMB will conduct interim safety reviews at least every 6 
months. For each DSMB meeting, the clinical study database will be reviewed, all data queries 
will be submitted to sites and resolved if possible, and a cut of the database will be taken on a 
specified date and used to produce TFLs for the DSMB.   
13.2 
Administrative Interim Analyses 
13.2.1 Pre-Month 6 
An administrative interim efficacy analysis will be performed when Month 6 MRI assessments 
are available for at least 14 subjects. Results from the interim efficacy analysis will be used for 
business planning activities to assure availability of therapeutic product and to plan subsequent 
clinical trials and will have no effect on the design or conduct of the trial. As such, there will be 
no statistical penalty applied to the final efficacy analysis as a result of the interim efficacy 
analysis.  Personnel with access to unblinded data and analysis results will be detailed in an 
unblinding memorandum to be filed in the Trial Master File and to be submitted to regulatory 
agencies. Unblinded interim data and analysis results will be kept confidential from other 
company personnel involved with the trial conduct and from investigators, patients, and their 
families. 
13.2.2 Month 6 
An administrative interim efficacy analysis will be performed when all subjects in the mITT 
population have completed the Month 6 visit or have discontinued from the study. Results from 
the interim efficacy analysis will be used for business planning activities to assure availability of 
therapeutic product and to plan subsequent clinical trials and will have no effect on the design or 
conduct of the trial. As such, there will be no statistical penalty applied to the final efficacy 
analysis as a result of the interim efficacy analysis.  A safety review similar to those done for the 
DSMB will also be done at this time. Top line results of the Month 6 administrative interim 
analysis will be reported publically. Clinical site trial personnel engaged in trial conduct and data 
collection will remain blinded to the complete interim data and analysis results, including patient 
level data. Imaging Core Lab personnel will remain blinded to treatment assignment and to all 
non-imaging patient level data until the final 12 month analyses.   
13.3 
Final Analysis 
The final analysis will occur when all subjects have reached EOS (completed the Month 12 visit 
or discontinued), all clinical data have been entered into the data capture system, AE and 
concomitant medication data have been coded, quality control checks have been completed, all 
data queries have been resolved, protocol violations and the per protocol population have been 
identified, and the database has been locked. 


 
 
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Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, January 6, 2017
CONFIDENTIAL 
14. 
DSMB 
The DSMB will be appointed by the sponsor and will consist of physicians and at least one 
biostatistician who have no formal involvement or conflict of interest with the subjects, the 
sponsor, the investigators, or the clinical sites. The DSMB will communicate their findings 
directly to the sponsor.  
 
Data on the following, in the form of TFLs and/or narratives, will be provided to the DSMB for 
review: 
 
 Subject disposition 
 Demographic and other baseline characteristics 
 IP administration details 
 Clinical event endpoints 
 Treatment-emergent AEs and SAEs 
 Safety laboratory evaluations 
 Concomitant cardiac and steroid medications 
 Continuous cardiac monitoring  
 
In addition, the DSMB will be provided with TFLs from the Month 6 administrative interim 
efficacy analysis. 
15. 
DEVIATIONS FROM STATISTICAL METHODS IN THE 
PROTOCOL 
Section 9 of the protocol defines the mITT population differently than the SAP, as follows: 
 
Protocol 
Deviation 
Modified ITT (mITT) Population: Subjects in 
the CAP-1002 treatment group who received 
the IP, and all subjects in the usual care 
treatment group who remain on study as of 9:00 
am (subject’s time zone) on Day 0.  
Modified ITT (mITT) Population for Efficacy 
Parameter X: Subjects in the safety population 
who have at least one post-baseline observation 
for Parameter X. 
 
 


 
 
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Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, January 6, 2017
CONFIDENTIAL 
REFERENCES 
1. International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonised Tripartite Guideline, Statistical Principles 
for Clinical Trials (E9), September 1998. 
2. International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonised Tripartite Guideline, Structure and 
Content of Clinical Study Reports (E3), November 1995. 
3. International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonised Tripartite Guideline, Good Clinical 
Practice (E6), April 1996. 
4. International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonised Tripartite Guideline, General 
Considerations for Clinical Trials (E8), July 1997. 
5. Antognini & Zagoraiou, Balance and randomness in sequential clinical trials: the dominant 
biased coin design, Pharm Stat 2014 (13), pp 119–127. 
6. Tukey JW (1977). Exploratory Data Analysis. Addison-Wesley Publishing Company. 
7. Hicks KA, Tcheng, JE, Bozkurt, B, et al. 2014 ACC/AHA key data elements and definitions 
for cardiovascular endpoint events in clinical trials: a report of the American College of 
Cardiology/American Heart Association Task Force on Clinical Data Standards (writing 
committee to develop cardiovascular endpoints data standards). J Am Coll Cardiol 
2015;66:403-69.   


 
 
  
 
 
 
 
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Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, November xx, 2015
CONFIDENTIAL 
APPENDIX A:  SCHEDULE OF EVENTS 
Procedure / Event 
Screening 
Infusion 
Week 2 
Week 6 
 Month 3 
Month 6 
Month 12 
Early 
Termination1 
Study Day 
Day -30 to -1 
Day 0 
Day 14 (±3) 
Day 40 (±7) 
Day 90 (±7) 
Day 180 (±14) 
Day 360 (±30) 
As Needed 
PRE 
POST 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Eligibility Assessment 
X 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
Medical History 
X 
X 
 
 
 
 
 
 
 
Cardiac History 
X 
X 
 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight  
X 
 
 
 
 
 
X 
X 
X 
12-Lead ECG 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Limited Physical Examination  
X 
 
 
 
 
 
 
X 
X 
Cardiac Physical Examination 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Cardiac MRI 
X 
 
 
 
 
 
X 
X 
X 
24-Hour Ambulatory ECG via 
Holter Monitor or ZIO® Patch 
X 
 
X 
 
X 
 
X 
X 
X 
Clinical Laboratory Tests 
(includes Chemistry, 
Hematology, Urinalysis) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serology2 
X 
 
 
 
 
 
 
 
 
Osteopontin 
X 
 
 
X 
X 
X 
X 
X 
X 
ST2  
X 
 
 
X 
X 
X 
X 
X 
X 
IL-10 
X 
 
 
X 
X 
X 
X 
X 
X 
Galectin-3 
X 
 
 
X 
X 
X 
X 
X 
X 
Exploratory Biomarkers  
X 
 
 
X 
X 
X 
X 
X 
X 
HLA 
X 
 
 
 
 
 
 
 
 


 
 
  
 
 
 
 
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Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, November xx, 2015
CONFIDENTIAL 
Procedure / Event 
Screening 
Infusion 
Week 2 
Week 6 
 Month 3 
Month 6 
Month 12 
Early 
Termination1 
Study Day 
Day -30 to -1 
Day 0 
Day 14 (±3) 
Day 40 (±7) 
Day 90 (±7) 
Day 180 (±14) 
Day 360 (±30) 
As Needed 
PRE 
POST 
DSA  
X 
 
 
X 
X 
X 
X 
X 
X 
ELISpot  
 
X 
 
 
X 
 
 
 
 
PUL scale  
X 
 
 
 
X 
X 
X 
X 
X 
6MWT 
X 
 
 
 
X 
X 
X 
X 
X 
Pediatric QL Inventory 
X 
 
 
 
X 
X 
X 
X 
X 
PODCI  
X 
 
 
 
X 
X 
X 
X 
X 
Spirometry 
X 
 
 
 
X 
X 
X 
X 
X 
Coagulation 
 
X 
 
 
 
 
 
 
 
Serum Troponin & CK-MB 
 
X 
X 
X 
 
 
X 
X 
X 
Intracoronary Infusion 
 
X 
 
 
 
 
 
 
Adverse Event Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1 Early Termination Visit procedures to be completed at time of withdrawal, should subject be withdrawn before Month 12 Visit. A 
Cardiac MRI will be conducted provided the subject’s most recent study-related Cardiac MRI was conducted at least three months 
(i.e., 12 weeks) prior to the Early Termination Visit. 
2 Serology includes HIV and hepatitis testing


 
 
 
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Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, November xx, 2015
CONFIDENTIAL 
APPENDIX B: TABLES OF CONTENTS FOR TABLES, FIGURES, AND 
LISTINGS 
 
TABLES 
STUDY POPULATION 
14.1.1 
Number of Subjects by Study Visit 
14.1.2 
Subject Disposition 
14.1.3.1 
Inclusion/Exclusion Criteria Not Met 
14.1.3.2 
Protocol Violations 
14.1.4 
Analysis Populations 
14.1.5 
Demographics and Baseline Characteristics 
14.1.6.1 
General Medical History 
14.1.6.2 
Cardiac Medical History 
14.1.7 
Screening Labs 
14.1.8 
Investigational Product Administration 
EFFICACY 
14.2.1 
MRI 
14.2.2 
PUL 
14.2.3 
6MWT 
14.2.4 
Spirometry 
14.2.5.1 
PedsQL, Subject 
14.2.5.2 
PedsQL, Parent 
14.2.6.1 
PODCI, Subject 
14.2.6.2 
PODCI, Parent 
SAFETY 
14.3.1.1.1 
Composite Clinical Safety Endpoint 
14.3.1.1.2 
Other Clinical Safety Endpoints 
14.3.1.2 
Summary of Treatment-Emergent Adverse Events 
14.3.1.3 
Treatment-Emergent Adverse Events 
14.3.1.4 
Treatment-Emergent Adverse Events Within 24 Hours of IP Administration 
14.3.1.5 
Treatment-Emergent Adverse Events in Subjects with Peri-Procedural Troponin Elevations 
14.3.1.6 
Treatment Emergent AEs Resulting in Study Discontinuation 
14.3.1.7 
Treatment Emergent SAEs 
14.3.1.8 
Treatment-Emergent SAEs in Subjects with Peri-Procedural Troponin Elevations 
14.3.1.9 
Treatment-Emergent Deaths 
14.3.1.10 
Treatment-Emergent Adverse Events -- Preferred Terms in Order of Descending Incidence 
14.3.5.1.1 
Serum Chemistry 
14.3.5.1.2 
Serum Chemistry Out of Range 
14.3.5.1.3 
Serum Chemistry Shifts From Baseline 
14.3.5.2.1 
Renal Functioin 
14.3.5.2.2 
Renal Function Out of Range 
14.3.5.2.3 
Renal Function Shifts From Baseline 
14.3.5.3.1 
Hepatic Function 
14.3.5.3.2 
Hepatic Function Out of Range 
14.3.5.3.3 
Hepatic Function Shifts From Baseline 
14.3.5.4.1 
Hematology 
14.3.5.4.2 
Hematology Out of Range 
14.3.5.4.3 
Hematology Shifts From Baseline 
14.3.5.5.1 
Cardiac Biomarkers 
14.3.5.5.2 
Cardiac Biomarkers Out of Range 
14.3.5.5.3 
Cardiac Biomarkers Shifts From Baseline 
14.3.5.6.1.1 
Urinalysis (continuous) 


 
 
 
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Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, November xx, 2015
CONFIDENTIAL 
14.3.5.6.1.2 
Urinalysis (categorical) 
14.3.5.6.2 
Urinalysis Out of Range 
14.3.5.6.3 
Urinalysis Shifts From Baseline 
14.3.5.7.1 
Exploratory Biomarkers 
14.3.5.7.2 
Exploratory Biomarkers Out of Range 
14.3.5.7.3 
Exploratory Biomarkers Shifts From Baseline 
14.3.5.8 
DSA 
14.3.5.9 
ELISpot 
14.3.6.1.1 
Concomitant Medications 
14.3.6.1.2 
Concomitant Cardiac and Steroid Medications 
14.3.6.2 
Vital Signs 
14.3.6.3 
Weight, Height, Body Mass Index 
14.3.6.4.1 
General Physical Examination 
14.3.6.4.2 
Cardiac Physical Examination 
14.3.6.5.1 
12-Lead Electrocardiogram 
14.3.6.5.2.1 
Continuous Cardiac Monitoring (contiuous) 
14.3.6.5.2.1 
Continuous Cardiac Monitoring (categorical) 
 
LISTINGS 
STUDY POPULATION 
16.2.1.1 
Critical Dates and Scheduled Visits 
16.2.1.2 
Subject Study Visits 
16.2.1.3 
Subject Disposition 
16.2.2.1 
Informed Consent 
16.2.2.2 
Eligibility & Randomization 
16.2.2.3 
Protocol Violations 
16.2.2.4 
Missed Visits and Assessments 
16.2.3 
Analysis Populations 
16.2.4.1 
Demographics 
16.2.4.2.1 
General Medical History 
16.2.4.2.2 
Cardiac Medical History 
16.2.4.3.1 
Pre-Treatment AEs 
16.2.4.3.2 
Pre-Treatment SAEs 
16.2.4.4.1 
Pre-Treatment General Medications 
16.2.4.4.2 
Pre-Treatment Cardiac and Steroid Medications 
16.2.4.5 
Screening Labs 
16.2.5 
Investigational Product Administration 
EFFICACY 
16.2.6.1 
MRI Parameters 
16.2.6.2 
PUL Scale 
16.2.6.3 
6MWT 
16.2.6.4 
Spirometry 
16.2.6.5.1 
PedsQL - Subject 
16.2.6.5.2 
PedsQL - Parent 
16.2.6.6.1 
PODCI - Subject 
16.2.6.6.2 
PODCI - Parent 
SAFETY 
16.2.7.1.1 
Composite Clinical Safety Endpoint 
16.2.7.1.2 
Other Clinical Safety Endpoints 
16.2.7.2.1 
Treatment Emergent AEs as Reported 
16.2.7.2.2 
Treatment Emergent AEs as Adjudicated 
14.3.2.1 
Treatment Emergent SAEs 
14.3.2.2 
Treatment Emergent AEs Resulting in Study Discontinuation 
14.3.2.3 
Treatment-Emergent AEs in Subjects with Peri-Procedural Troponin Elevations 
14.3.2.4 
Treatment-Emergent AEs Resulting in Death 


 
 
 
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Capricor Therapeutics Protocol CAP-1002-DMD-01 Phase 2  
Statistical Analysis Plan Version 1.0, November xx, 2015
CONFIDENTIAL 
14.3.2.5 
Treatment Emergent AEs Within 24 Hours 
14.3.2.6 
Cause of Death 
16.2.8.1 
Serum Chemistry 
14.3.4.1 
Serum Chemistry Out of Range 
16.2.8.2 
Renal Function 
14.3.4.2 
Renal Function Out of Range 
16.2.8.3 
Hepatic Function 
14.3.4.3 
Hepatic Function Out of Range 
16.2.8.4 
Hematology 
14.3.4.4 
Hematology Out of Range 
16.2.8.5 
Cardiac Biomarkers 
14.3.4.5 
Cardiac Biomarkers Out of Range 
16.2.8.6 
Urinalysis 
14.3.4.6 
Urinalysis Out of Range 
16.2.8.7 
Exploratory Biomarkers 
14.3.4.7 
Exploratory Biomarkers Out of Range 
16.2.8.8 
DSA 
16.2.8.9 
ELISpot 
16.2.9.1.1 
Concomitant Medications 
16.2.9.1.2 
Concomitant Cardiac and Steroid Medications 
16.2.9.2 
Vital Signs 
16.2.9.3 
Weight, Height, Body Mass Index 
16.2.9.4.1 
General Physical Examination 
16.2.9.4.2 
Cardiac Physical Examination 
16.2.9.5.1 
12-Lead Electrocardiogram 
16.2.9.5.2 
Continuous Cardiac Monitoring 
 
FIGURES 
EFFICACY 
 
14.2.1.X 
MRI: Parameter X 
14.2.2 
6MWT 
14.2.3.X 
Spirometry: Parameter X 
14.2.4.X 
PUL: Parameter X 
14.2.5.X.1 
PEDS, Subject: Parameter X 
14.2.5.X.2 
PEDS, Parent: Parameter X 
SAFETY 
14.3.5.1.X 
Serum Chemistry Box Plots, Parameter X 
14.3.5.2.X 
Renal Box Plots, Parameter X 
14.3.5.3.X 
Hepatic Box Plots, Parameter X 
14.3.5.4.X 
CBC Box Plots, Parameter X 
14.3.5.5.1.1.X 
Cardiac Biomarkers Box Plots, Parameter X 
14.3.5.5.1.2.X 
Cardiac Biomarker Box Plots, Parameter X -- Change from BL, non Post Infusion visits 
14.3.5.5.2.X 
Cardiac Biomarker Spaghetti Plot, Parameter X -- Post Infusion, CAP-1002 only