Systemic Gene Delivery Phase I/IIa Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MHCK7.Micro-dystrophin (microDys-IV-001)
Phase: PHASE1
Conditions: Duchenne Muscular Dystrophy
Sponsor: Sarepta Therapeutics, Inc.

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/
&/,1,&$/678'<35272&2/
'58*
653IRUPHUO\UHIHUUHGWRDV
U$$9UK0+&.PLFURG\VWURSKLQ
678'<180%(5
653
678'<7,7/(
6\VWHPLFJHQHGHOLYHU\3KDVH,,,DFOLQLFDOWULDOIRU
'XFKHQQHPXVFXODUG\VWURSK\XVLQJ
U$$9UK0+&.PLFURG\VWURSKLQ
PLFUR'\V,9
,1'1XPEHU
(8'5$&71XPEHU
1RW$SSOLFDEOH
6321625
6DUHSWD7KHUDSHXWLFV,QF
)LUVW6WUHHW
&DPEULGJH0$86$
3KRQH
&855(179(56,21'$7(
$PHQGPHQW$XJXVW
5(3/$&(69(56,21'$7(
$PHQGPHQW-XQH
&21),'(17,$/,7<67$7(0(17
7KHLQIRUPDWLRQFRQWDLQHGLQWKLVGRFXPHQWLVWKHSURSHUW\RIWKH6SRQVRUDQGLVFRQILGHQWLDO7KLV
LQIRUPDWLRQPD\QRWEHGLVFORVHGUHSURGXFHGRUGLVWULEXWHGWRDQ\RQHRWKHUWKDQSHUVRQQHOGLUHFWO\
LQYROYHGLQWKHFRQGXFWRIWKHVWXG\DQGLQUHVSRQVHWRDUHOHYDQW,QVWLWXWLRQDO5HYLHZ
%RDUG,QGHSHQGHQW(WKLFV&RPPLWWHHDQGUHYLHZE\DUHJXODWRU\DXWKRULW\DVUHTXLUHGE\WKH
DSSOLFDEOHODZVDQGUHJXODWLRQVZLWKRXWWKHZULWWHQDXWKRUL]DWLRQRIWKH6SRQVRUH[FHSWWRWKH
H[WHQWQHFHVVDU\WRREWDLQZULWWHQLQIRUPHGFRQVHQWIURPWKRVHLQGLYLGXDOVWRZKRPWKHGUXJPD\EH
DGPLQLVWHUHG7KHVHUHVWULFWLRQVZLOOFRQWLQXHWRDSSO\DIWHUWKHVWXG\KDV FORVHG
CCI
NCT03375164

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/


6,*1$785(3$*()256321625

3URWRFRO7LWOH
6\VWHPLFJHQHGHOLYHU\3KDVH,,,DFOLQLFDOWULDOIRU'XFKHQQH
PXVFXODUG\VWURSK\XVLQJU$$9UK0+&.PLFURG\VWURSKLQ
PLFUR'\V,9
6WXG\1R
653
&XUUHQW9HUVLRQ'DWH 9HUVLRQ$PHQGPHQW$XJXVW

7KLVVWXG\SURWRFRO9HUVLRQ$PHQGPHQWZDVVXEMHFWWRFULWLFDOUHYLHZDQGKDVEHHQ
DSSURYHGE\WKHDSSURSULDWHSURWRFROUHYLHZFRPPLWWHHRI6DUHSWD7KHUDSHXWLFV,QF7KH
LQIRUPDWLRQFRQWDLQHGLQWKLVSURWRFROLVFRQVLVWHQWZLWK
x
7KHFXUUHQWEHQHILWULVNHYDOXDWLRQRIWKHVWXG\GUXJ
x
7KHHWKLFDODQGVFLHQWLILFSULQFLSOHVJRYHUQLQJFOLQLFDOUHVHDUFKDVVHWRXWLQWKH
'HFODUDWLRQRI+HOVLQNLDQGSULQFLSOHVRI*RRG&OLQLFDO3UDFWLFH*&3DVGHVFULEHG
LQ&RGHRI)HGHUDO5HJXODWLRQV&)5SDUWVDQGDQGWKH(XURSHDQ
&OLQLFDO7ULDO'LUHFWLYH(&
7KH,QYHVWLJDWRUZLOOEHVXSSOLHGZLWKGHWDLOVRIDQ\VLJQLILFDQWRUQHZILQGLQJVLQFOXGLQJ
DGYHUVHHYHQWV$(VUHODWLQJWRWUHDWPHQWZLWKWKHVWXG\GUXJ


 


'DWH
25-Aug-2020 
PPD

SRP-9001 
Protocol 
SRP-9001-101 (Amendment 8, Version 9) 
3 
CONFIDENTIAL 
 
 
INVESTIGATOR’S   AGREEMENT 
 
I have received and read the Investigator’s Brochure for SRP-9001. I have read the 
SRP-9001-101 protocol (Amendment 8, Version 9 dated 25 August 2020) and agree to conduct 
the study as outlined. I agree to maintain the confidentiality of all information received or 
developed about this protocol. 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
Signature of Investigator 
 
 
 
Date 

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/



6<1236,6

1DPHRI6SRQVRU&RPSDQ\
6DUHSWD7KHUDSHXWLFV,QF
)LUVW6WUHHW
&DPEULGJH0$86$
3KRQH 
1DPHRI,QYHVWLJDWLRQDO3URGXFW653
1DPHRI$FWLYH,QJUHGLHQWPLFURG\VWURSKLQ
7LWOHRI6WXG\6\VWHPLFJHQHGHOLYHU\3KDVH,,,DFOLQLFDOWULDOIRU'XFKHQQHPXVFXODUG\VWURSK\
XVLQJU$$9UK0+&.PLFURG\VWURSKLQPLFUR'\V,9
6WXG\&HQWHUV1DWLRQZLGH&KLOGUHQ¶V+RVSLWDO1&+
3ULQFLSDO,QYHVWLJDWRU-HUU\50HQGHOO0'
6WXGLHG3HULRG\HDUV
(VWLPDWHGGDWHILUVWVXEMHFWHQUROOHG
(VWLPDWHGGDWHODVWVXEMHFWFRPSOHWHG
3KDVHRI'HYHORSPHQW3KDVH,,,D
2EMHFWLYHV
3ULPDU\
7KHSULPDU\REMHFWLYHRIWKLVVWXG\LVWKHDVVHVVPHQWRIWKHVDIHW\RILQWUDYHQRXV,9DGPLQLVWUDWLRQ
RIU$$9UK0+&.PLFURG\VWURSKLQIRU'XFKHQQHPXVFXODUG\VWURSK\'0'VXEMHFWYLD
SHULSKHUDOOLPEYHLQ
0HWKRGRORJ\7KHSURSRVHGFOLQLFDOVWXG\LVDQRSHQODEHOVLQJOHGRVHVWXG\XVLQJ
U$$9UK0+&.PLFURG\VWURSKLQIRU'0'VXEMHFWV&RKRUW$ZLOOLQFOXGHVXEMHFWVDJHV
PRQWKVWR\HDUVDQG&RKRUW%ZLOOLQFOXGHVXEMHFWVDJHVWR\HDUVROG$OOVXEMHFWVZLOO
UHFHLYH,9PLFURG\VWURSKLQYHFWRUîYJNJLQDSSUR[LPDWHO\
&RKRUW%
VXEMHFWVZLOOEHHQUROOHGEHIRUH&RKRUW$8SRQFRPSOHWLRQRI&RKRUW%WKHVDIHW\GDWDZLOOEH
SUHVHQWHGWRWKH,QVWLWXWLRQDO5HYLHZ%RDUGDQG'DWD6DIHW\0RQLWRULQJ%RDUGUHTXHVWLQJSHUPLVVLRQ
WRHQUROO&RKRUW$
$OWKRXJKWKLVVWXG\ZDVRULJLQDOO\GHVLJQHGWRHQUROOVXEMHFWVLQWRFRKRUWVDVRXWOLQHGDERYHDV
RIWKLVDPHQGPHQW9HUVLRQDWRWDORIVXEMHFWVKDYHEHHQHQUROOHGDOOLQWR&RKRUW%1RIXUWKHU
VXEMHFWVZLOOEHHQUROOHGLQWRWKHVWXG\
6XEMHFWVZLOOKDYHLQIXVLRQVRIU$$9FDUU\LQJPLFURG\VWURSKLQRYHUDSSUR[LPDWHO\WRKRXUVLQ
WKH3HGLDWULF,QWHQVLYH&DUH8QLWDW1&+7KH%D\OH\,,,*URVV0RWRU6XEWHVWZLOOVHUYHDVWKH
VHFRQGDU\RXWFRPHPHDVXUHIRUDOOFKLOGUHQLQ&RKRUW$%D\OH\6FDOHVRI,QIDQWDQG7RGGOHU
'HYHORSPHQW7KLUG(GLWLRQSXEOLVKHGE\3V\FK&RUS7KH0HWHU7LPHG7HVWPZLOO
EHDSULPDU\PRWRURXWFRPHDQG

7KHPZLOOEH
WKHSULPDU\PRWRURXWFRPHIRU&RKRUW%



)XQFWLRQDODVVHVVPHQWVZLOOEH
DVLQGLFDWHGLQWKH&OLQLFDO(YDOXDWRU
0DQXDO3UHDQGSRVWWUHDWPHQWGD\QHHGOHPXVFOHELRSVLHVZLOOEHGRQHRQ

PXVFOHVZLWKDSSURSULDWHDQHVWKHVLDXQGHUDGYLVHPHQWRIDQHVWKHVLRORJLVWRU
DQHVWKHWLVW(0/$FUHDPRUFRPSDUDEOHOLGRFDLQHSULORFDLQHHPXOVLRQDQGRULQMHFWDEOHDQHVWKHWLF
PD\EHXVHGDWWKHVLWHRIELRSV\0LFURG\VWURSKLQJHQHH[SUHVVLRQZLOOVHUYHDVDVHFRQGDU\
CCI
CCI
CCI
CCI
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/



RXWFRPHPHDVXUH4XDQWLILFDWLRQZLOOEHGRQHXVLQJYDOLGDWHGLPPXQRIOXRUHVFHQFH


)ROORZLQJJHQHWUDQVIHUWKHPRVWUHFHQW)RRGDQG'UXJ$GPLQLVWUDWLRQJXLGDQFHZLOOEHIROORZHG
ZLWKUHJDUGWRORQJWHUPVXEMHFWIROORZXS
1XPEHURIVXEMHFWVSODQQHGVXEMHFWVZHUHSODQQHGKRZHYHUWKHVWXG\ZLOORQO\HQUROO
VXEMHFWV
'LDJQRVLVDQGPDLQFULWHULDIRULQFOXVLRQ
,QFOXVLRQFULWHULD
 $JHRIHQUROOPHQW&RKRUW$Q LVEHWZHHQPRQWKVWR\HDUVRIDJHLQFOXVLYH
&RKRUW%Q LVEHWZHHQWR\HDUVRIDJHLQFOXVLYH
 0ROHFXODUFKDUDFWHUL]DWLRQRIWKH'0'JHQHZLWKIUDPHVKLIWGHOHWLRQRUGXSOLFDWLRQRU
SUHPDWXUHVWRSFRGRQPXWDWLRQEHWZHHQH[RQVWR
 ,QGLFDWLRQRIV\PSWRPDWLFPXVFXODUG\VWURSK\
x
&.HOHYDWLRQ!
8/DQG
x
&RKRUW$%HORZDYHUDJHRQWKH%D\OH\,,,PRWRUDVVHVVPHQWIRUJURVVPRWRUGHILQHGDV
DVFDOHGVFRUHRI &RKRUW%%HORZDYHUDJHRQWKHPGHILQHGDV
SUHGLFWHG
&RQQROO\
 0DOHVRIDQ\HWKQLFJURXSZLOOEHHOLJLEOH
 $ELOLW\WRFRRSHUDWHZLWKPRWRUDVVHVVPHQWWHVWLQJ
 )RU&RKRUW$VXEMHFWV1RSUHYLRXVWUHDWPHQWZLWKFRUWLFRVWHURLGV)RU&RKRUW%VXEMHFWV
6WDEOHGRVHHTXLYDOHQWRIRUDOFRUWLFRVWHURLGVIRUDWOHDVWZHHNVSULRUWRVFUHHQLQJDQGWKH
GRVHLVH[SHFWHGWRUHPDLQFRQVWDQWH[FHSWIRUSRWHQWLDOPRGLILFDWLRQVWRDFFRPPRGDWH
FKDQJHVLQZHLJKWWKURXJKRXWWKHILUVW\HDURIWKHVWXG\
([FOXVLRQFULWHULD
 $FWLYHYLUDOLQIHFWLRQEDVHGRQFOLQLFDOREVHUYDWLRQV
 6LJQVRIFDUGLRP\RSDWK\LQFOXGLQJHFKRFDUGLRJUDPZLWKHMHFWLRQIUDFWLRQEHORZ

 6HURORJLFDOHYLGHQFHRIKXPDQLPPXQRGHILFLHQF\YLUXVLQIHFWLRQRU+HSDWLWLV%RU&
LQIHFWLRQ
 'LDJQRVLVRIRURQJRLQJWUHDWPHQWIRUDQDXWRLPPXQHGLVHDVH
 $EQRUPDOODERUDWRU\YDOXHVFRQVLGHUHGFOLQLFDOO\VLJQLILFDQWJDPPDJOXWDP\OWUDQVIHUDVH
>**7@! îWKHXSSHUOLPLWRIQRUPDOELOLUXELQ
PJG/FUHDWLQLQH
PJG/
KHPRJORELQ RU!
J'OZKLWHEORRGFHOOFRXQW!
SHUFPP
 &RQFRPLWDQWLOOQHVVRUUHTXLUHPHQWIRUFKURQLFGUXJWUHDWPHQWWKDWLQWKHRSLQLRQRIWKH3,
FUHDWHVXQQHFHVVDU\ULVNVIRUJHQH WUDQVIHU
 6XEMHFWVZLWKU$$9UK
DQWLERG\WLWHUV!
DVGHWHUPLQHGE\HQ]\PHOLQNHG
LPPXQRVRUEHQWDVVD\(/,6$ LPPXQRDVVD\
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/



x
,IHQGSRLQWWLWHULVSRVLWLYHDWVFUHHQLQJWHVWLQJPD\EHUHSHDWHGSULRUWRH[FOXVLRQ
x
,ILQIDQWDQGPRWKHUDUHSRVLWLYHIRUVDPHDQWLERG\WLWHUVPRWKHUZLOOEHDVNHGQRWWR
EUHDVWIHHGDQGLQIDQWFDQEHHQUROOHGLIDQWLERGLHV
ZLWKLQZHHNV
 +DVDPHGLFDOFRQGLWLRQRUH[WHQXDWLQJFLUFXPVWDQFHWKDWLQWKHRSLQLRQRIWKH,QYHVWLJDWRU
PLJKWFRPSURPLVHWKHVXEMHFW¶VDELOLW\WRFRPSO\ZLWKWKHSURWRFROUHTXLUHGWHVWLQJRU
SURFHGXUHVRUFRPSURPLVHWKHVXEMHFW¶VZHOOEHLQJVDIHW\RUFOLQLFDOLQWHUSUHWDELOLW\
 6HYHUHLQIHFWLRQHJSQHXPRQLDS\HORQHSKULWLVRUPHQLQJLWLVZLWKLQZHHNVEHIRUHJHQH
WUDQVIHUYLVLWHQUROOPHQWPD\EHSRVWSRQHG
 +DVUHFHLYHGDQ\LQYHVWLJDWLRQDOPHGLFDWLRQRWKHUWKDQFRUWLFRVWHURLGVRUH[RQVNLSSLQJ
PHGLFDWLRQVLQFOXGLQJ(;21'<6H[SHULPHQWDORURWKHUZLVHLQWKHODVWPRQWKV
SULRUWRVFUHHQLQJIRUWKLVVWXG\
 +DVKDGDQ\W\SHRIJHQHWKHUDS\FHOOEDVHGWKHUDS\HJVWHPFHOOWUDQVSODQWDWLRQRU
&5,635&DV
 )DPLO\GRHVQRWZDQWWRGLVFORVHVXEMHFW¶VVWXG\SDUWLFLSDWLRQZLWKSULPDU\FDUHSK\VLFLDQ
DQGRWKHUPHGLFDOSURYLGHUV
,QYHVWLJDWLRQDOSURGXFWGRVDJHDQGPRGHRIDGPLQLVWUDWLRQ
7KHYHFWRUZLOOEHGHOLYHUHGYLDSHULSKHUDOOLPEYHLQ6WXG\VXEMHFWVZLOOUHFHLYHVHGDWLRQLIGHHPHG
QHFHVVDU\IRUWKHSURFHGXUHIROORZLQJWKH1&+GRVLQJSURWRFRO6L[VXEMHFWVLQ&RKRUW$DQG
VXEMHFWVLQ&RKRUW%ZLOOUHFHLYH,9PLFURG\VWURSKLQYHFWRUîYJNJLQ

2QHGD\SULRUWRJHQHWUDQVIHUVXEMHFWVLQ&RKRUW$ZLOOEHVWDUWHGRQSUHGQLVRORQHSUHGQLVRQHRU
GHIOD]DFRUWDFFHSWDEOHPJNJDQGPDLQWDLQHGIRUGD\V

,IWKHOLYHUHQ]\PH**7LVHOHYDWHGDWGD\
VWHURLGVZLOOEHPDLQWDLQHGXQWLO**7OHYHOVGURSEHORZ
8/
&RKRUW%VXEMHFWVUHFHLYLQJGDLO\JOXFRFRUWLFRLGPHGLFDWLRQZLOOEHPDLQWDLQHGRQDVWDEOHGRVHRI
FRUWLFRVWHURLGVWKURXJKRXWWKHILUVW\HDURIWKHVWXG\EXWWKHGRVHPD\EHLQFUHDVHGIRUDVKRUWWLPHLI
**7LVHOHYDWHG!8/RUWKHUHDUHRWKHUFOLQLFDOO\VLJQLILFDQWOLYHUIXQFWLRQDEQRUPDOLWLHV7KRVH
RQZHHNHQGGRVLQJPD\UHFHLYHDQDGGHGGDLO\GRVHHTXLYDOHQWWRPJNJIRUXSWRGD\V
6WXG\GXUDWLRQ:HZLOOHYDOXDWHVDIHW\RYHUD\HDUSHULRG6XEMHFWVZLOOEHWHVWHGDWEDVHOLQHDQG
UHWXUQIRUIROORZXSYLVLWVRQGD\V

DQGPRQWKV


DQG8QVFKHGXOHGYLVLWVDQGDGGLWLRQDOEORRGGUDZVDW1&+RUORFDOWRVXEMHFW¶VKRPHPD\RFFXU
LIWKH3,GHWHUPLQHVWKH\DUHQHFHVVDU\IRUWKHVXEMHFW¶VVDIHW\DQGZHOOEHLQJ


5HIHUHQFHWKHUDS\GRVDJHDQGPRGHRIDGPLQLVWUDWLRQ1RQH
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/



&ULWHULDIRUHYDOXDWLRQ
3ULPDU\RXWFRPH
6DIHW\LVWKHSULPDU\RXWFRPHIRUWKLVFOLQLFDOJHQHWUDQVIHUVWXG\
$GGLWLRQDORXWFRPHV
7KHIROORZLQJHIILFDF\RXWFRPHPHDVXUHVZLOOEHGRQHDWGHVLJQDWHGWLPHSRLQWV
x
7LPHSRLQWVIRUVHFRQGDU\RXWFRPHVGD\V

PRQWKV

DQG


x
7KH%D\OH\6FDOHVRI,QIDQWDQG7RGGOHU'HYHORSPHQW7KLUG(GLWLRQ*URVV0RWRU
6XEWHVW%D\OH\,,,VFRUHVZLOOVHUYHDVWKHVHFRQGDU\RXWFRPHPHDVXUHIRUWKLVVWXG\IRU
&RKRUW$&RQWUROGDWDIRU'0'LQIDQWVDWWKLVDJHXVLQJWKH%D\OH\,,,*URVV0RWRU
6FDOHKDVEHHQREWDLQHGDQGSXEOLVKHGIURPGDWDFROOHFWHGLQWKH0'$1HWZRUN&OLQLFDO
&HQWHUV0HQGHOO2QJRLQJGDWDLVEHLQJFROOHFWHGLQER\VXSWR\HDUVRIDJHZLWK
'0'LQWKH0'$FOLQLFDW1&+7KH%D\OH\,,,LVGHVLJQHGWRDVVHVVWKHGHYHORSPHQWDO
IXQFWLRQLQJRILQIDQWVDQG\RXQJFKLOGUHQWRPRQWKVRIDJH%D\OH\1%D\OH\
6FDOHVRI,QIDQWDQG7RGGOHU'HYHORSPHQW7KLUG(GLWLRQSXEOLVKHGE\ 3V\FK&RUS
x
3K\VLFDO7KHUDS\$VVHVVPHQWV7KHPZLOOEHDSULPDU\PRWRURXWFRPHLQLWLDWHGIRU
&RKRUW$DVVRRQDVWKHFKLOGLV\HDUVRIDJH

7KHPZLOOEH
WKHSULPDU\PRWRURXWFRPHIRU&RKRUW%

x
%DVHOLQHPXVFOHELRSVLHVZLWKXOWUDVRXQGJXLGDQFHWRDVVHVVPLFURG\VWURSKLQH[SUHVVLRQ
ZLOOEHGRQHSUHWUHDWPHQWRQDOOVXEMHFWV$OOVXEMHFWVZLOOKDYHDSRVWWUHDWPHQWELRSV\
DWGD\0LFURG\VWURSKLQJHQHH[SUHVVLRQZLOOEHTXDQWLILHGLPPXQRIOXRUHVFHQFHDQG
ZHVWHUQEORWDQDO\VLVDQGFRPSDUHGLQSUHDQGSRVWPXVFOHELRSVLHV0LFURG\VWURSKLQ
H[SUHVVLRQZLOODOVRVHUYHDVDVHFRQGDU\RXWFRPHPHDVXUHIRUERWKFRKRUWV
x

6WDWLVWLFDOPHWKRGV
6DPSOHVL]H
7ZHOYH'0'VXEMHFWV&RKRUW$Q &RKRUW%Q ZLOOEHHQUROOHGDW1&+IRUWKHJHQHWUDQVIHU
VWXG\6XEMHFWVZLOOHQFRPSDVVPDOHVRIDQ\HWKQLFRUUDFLDOEDFNJURXQG&RKRUW$ZLOOLQFOXGH
VXEMHFWVDJHGPRQWKVWR\HDUVLQFOXVLYHDWWKHWLPHRIHQUROOPHQW&RKRUW%ZLOOLQFOXGHVXEMHFWV
DJHGWR\HDUVLQFOXVLYHDWWKHWLPHRIHQUROOPHQWDQGZLOOSUHIHUHQWLDOO\EHHQUROOHGWRUHFHLYH
JHQHGHOLYHU\SULRU&RKRUW$
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/



6WDWLVWLFDODQDO\VLV
7KLVLVD3KDVH,,,DVWXG\ZLWKVDIHW\DVWKHSULPDU\PHDVXUH%D\OH\,,,SUHDQGSRVWJHQHWUDQVIHU
ZLOOEHWKHSULPDU\PRWRURXWFRPHIRU&RKRUW$7KHPZLOOEHDSULPDU\PRWRURXWFRPH


7KHPZLOOEHWKHSULPDU\PRWRURXWFRPHIRU&RKRUW%


$VWKHVDPSOHVL]HLVVPDOO
DQGWKHPRWRURXWFRPHVZLOOGLIIHUEHWZHHQFRKRUWVDVZHOODVRYHUWLPHIRUVRPHVXEMHFWVZLWKLQ
&RKRUW$DOODQDO\VHVZLOOEHGHVFULSWLYHLQQDWXUHDQGZLOOQRWHPSOR\LQIHUHQWLDOVWDWLVWLFV
7KHPXVFOHELRSVLHVZLOOEHSURFHVVHGLQWKH
ZKLFKRSHUDWHV
XQGHUD&ROOHJHRI$PHULFDQ3DWKRORJLVWV&OLQLFDO/DERUDWRU\,PSURYHPHQW$PHQGPHQWVOLFHQVHIRU
WKHLUGLDJQRVWLFQHXURPXVFXODUWHVWLQJ7KHUHZLOOEHDQDVVLJQHGEOLQGHGLGHQWLILHUIRUHDFKVXEMHFW
)UR]HQVHFWLRQVZLOOEHVWDLQHGIRUG\VWURSKLQXVLQJLQGLUHFWLPPXQRIOXRUHVFHQFH

ZLOOEHXVHGWRTXDQWLI\WKHLQWHQVLW\RIG\VWURSKLQH[SUHVVLRQFRPSDUHGWR
QRUPDOFRQWUROV






3HULRGLFVDIHW\DQGHIILFDF\DQDO\VHVDUHSHUIRUPHGIRUVDIHW\PRQLWRULQJUHYLHZV,QYHVWLJDWRU¶V
%URFKXUHXSGDWHVUHJXODWRU\VXEPLVVLRQVVXFKDV'HYHORSPHQW6DIHW\8SGDWH5HSRUWDQGUHJXODWRU\
PHHWLQJEULHILQJGRFXPHQWVDQGVFLHQWLILFGLVFORVXUHV7KHVHSHULRGLFDQDO\VHVDUHGHVFULEHGLQ
VHSDUDWHGRFXPHQWV
CCI
CCI
CCI
CCI
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/

7$%/(2)&217(176
7$%/(2)&217(176

7,7/(3$*(
6,*1$785(3$*()256321625

6<1236,6

7$%/(2)&217(176

/,672)$%%5(9,$7,216$1''(),1,7,2162)7(506

,1752'8&7,21

&OLQLFDO6WXG\6LWH

%DFNJURXQGDQG6LJQLILFDQFH

'LVHDVHDQG&KDUDFWHULVWLFV

'LVHDVH3DWKRJHQHVLV

7UHDWPHQWIRU'XFKHQQH0XVFXODU'\VWURSK\

678'<2%-(&7,9(6$1'385326(

,19(67,*$7,21$/3/$1

2YHUDOO6WXG\'HVLJQ

6WXG\(QGSRLQWV

3ULPDU\(QGSRLQWV


6WXG\&RPPLWWHHV

'DWD6DIHW\0RQLWRULQJ%RDUG

'DWD6DIHW\0RQLWRULQJ%RDUG5HSRUWLQJDQG0HHWLQJV

0HPEHUVKLS

6(/(&7,21$1':,7+'5$:$/2)68%-(&76

6XEMHFW,QFOXVLRQ&ULWHULD

6XEMHFW([FOXVLRQ&ULWHULD

6XEMHFW:LWKGUDZDO&ULWHULD

75($70(172)68%-(&76

7UHDWPHQW$GPLQLVWHUHG

*HQH7UDQVIHU3URWRFRO

9HFWRU$GPLQLVWUDWLRQ3URWRFRO
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/

'RVH/LPLWLQJ3ODQ

6WRSSLQJ'LVFRQWLQXDWLRQ5XOHV

'RVLQJ6FKHGXOH

5DQGRPL]DWLRQDQG%OLQGLQJ

&RQFRPLWDQW0HGLFDWLRQV

7UHDWPHQW&RPSOLDQFH

,'(17,7<2),19(67,*$7,21$/352'8&76



3DFNDJLQJDQG/DEHOLQJ

6WRUDJH

678'<$66(660(176

3UH7UHDWPHQW$VVHVVPHQWV


%HIRUH *HQH7UDQVIHU

3UH7UHDWPHQWDQG3RVW7UHDWPHQW0XVFOH%LRSV\



3UH7UHDWPHQW,PPXQRVXSSUHVVLYHV




*HQH7UDQVIHUDQG9HFWRU$GPLQLVWUDWLRQ3URWRFRO

3RVW*HQH7UDQVIHU0RQLWRULQJ



([WHQGHG)ROORZXS

$VVHVVPHQWRI6DIHW\



7R[LFLW\0RQLWRULQJ3RVW*HQH7UDQVIHU

$VVHVVPHQWRI(IILFDF\

$'9(56((9(176$1'6(5,286$'9(56((9(176

'HILQLWLRQVRI$GYHUVH(YHQWV

$GYHUVH(YHQW

6HULRXV$GYHUVH(YHQW

2YHUGRVH

0HGLFDWLRQ(UURU

$FFLGHQWDO2FFXSDWLRQDO([SRVXUH
'HVFULSWLRQRI6WXG\'UXJ
,PPHGLDWHO\)ROORZLQJ*HQH7UDQVIHU
CCI
CCI
CCI
CCI
CCI
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/



&ROOHFWLRQRI$GYHUVH(YHQWV

&OLQLFDO/DERUDWRU\$EQRUPDOLWLHV

&ODVVLILFDWLRQRI$GYHUVH(YHQWV

5HODWLRQVKLSWR6WXG\$JHQW6WXG\3URFHGXUHVDQGWKH6XEMHFW¶V3UH
H[LVWLQJ'LVHDVH

6HYHULW\RI$GYHUVH(YHQWV

2XWFRPHVRI$GYHUVH(YHQWV

$FWLRQ7DNHQ5HJDUGLQJWKH6WXG\'UXJ

([SHFWHGQHVVRI$GYHUVH(YHQWV

5HFRUGLQJ$GYHUVH(YHQWV

5HSRUWLQJ6HULRXV$GYHUVH(YHQWV

6HULRXV$GYHUVH(YHQWV

6XVSHFWHG8QH[SHFWHG6HULRXV$GYHUVH5HDFWLRQV686$5V

5HSRUWLQJ6SHFLDO6LWXDWLRQV

2YHUGRVH

0HGLFDWLRQ(UURU

$FFLGHQWDO2FFXSDWLRQDO([SRVXUH

0LVFHOODQHRXV

5HVSRQVLELOLWLHVRIWKH,QYHVWLJDWRU

5HVSRQVLELOLWLHVRIWKH6SRQVRU

67$7,67,&6

5(*8/$725<(7+,&$/$1'678'<29(56,*+7
&216,'(5$7,216

5HJXODWRU\DQG(WKLFDO&RQVLGHUDWLRQV

)LQDQFLDO'LVFORVXUH

,QIRUPHG&RQVHQW

'DWD0DQDJHPHQWDQG6WXG\)RUPV

3XEOLFDWLRQ3ROLF\

6WXG\5HSRUWV

)LQDO6WXG\5HSRUW

$QQXDO6WXG\5HSRUWV

/,672)5()(5(1&(6

SRP-9001 
Protocol 
SRP-9001-101 (Amendment 8, Version 9) 
12 
CONFIDENTIAL 
 
 
LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms .......................................................................... 13 
Table 2: 
Schedule of Events .................................................................................................... 19 
Table 3: 
Treatment Cohorts ..................................................................................................... 25 

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/



/,672)$%%5(9,$7,216$1''(),1,7,2162)7(506
7KHIROORZLQJDEEUHYLDWLRQVDQGVSHFLDOLVWWHUPVDUHXVHGLQWKLVVWXG\SURWRFRO
7DEOH
$EEUHYLDWLRQVDQG6SHFLDOLVW7HUPV

$EEUHYLDWLRQRU6SHFLDOLVW7HUP
([SODQDWLRQ
P
0HWHU7LPHG7HVW
$$9
DGHQRDVVRFLDWHG YLUXV
$'/
DFWLYLWLHVRIGDLO\OLYLQJ
$(
DGYHUVHHYHQW
$/7
DODQLQHDPLQRWUDQVIHUDVH
$67
DVSDUWDWHDPLQRWUDQVIHUDVH
%0'
%HFNHUPXVFXODUG\VWURSK\
%81
EORRGXUHDQLWURJHQ
&$3
&ROOHJHRI$PHULFDQ3DWKRORJLVWV
&%&
FRPSOHWHEORRGFRXQW
&)5
&RGHRI)HGHUDO5HJXODWLRQV


&/,$
&OLQLFDO/DERUDWRU\,PSURYHPHQW$PHQGPHQWV
&5)
&DVH5HSRUW)RUP
&7&$(
&RPPRQ7HUPLQRORJ\&ULWHULDIRU$GYHUVH(YHQWV
'0'
'XFKHQQHPXVFXODUG\VWURSK\
'60%
'DWD6DIHW\0RQLWRULQJ%RDUG
(&+2
HFKRFDUGLRJUDP
(&*
HOHFWURFDUGLRJUDP
H&5)
HOHFWURQLFFDVHUHSRUWIRUP
(/,6$
HQ]\PHOLQNHGLPPXQRVRUEHQWDVVD\
(/,6327
HQ]\PHOLQNHGLPPXQRVSRW
)'$
)RRGDQG'UXJ$GPLQLVWUDWLRQ
**7
JDPPDJOXWDP\OWUDQVIHUDVH
++'
KDQGKHOGG\QDPRPHWU\
+,9
KXPDQLPPXQRGHILFLHQF\YLUXV
,&+
,QWHUQDWLRQDO&RXQFLOIRU+DUPRQLVDWLRQ
,1'
,QYHVWLJDWLRQDO1HZ'UXJ
,15
LQWHUQDWLRQDOQRUPDOL]HGUDWLR
CCI
CCI

SRP-9001 
Protocol 
SRP-9001-101 (Amendment 8, Version 9) 
14 
CONFIDENTIAL 
 
 
 
Abbreviation or Specialist Term 
Explanation 
IRB 
Institutional Review Board 
IV 
Intravenous(ly) 
MRI 
magnetic resonance imaging 
NCH 
Nationwide Children’s Hospital 
NSAA 
North Star Ambulatory Assessment 
PBMC 
peripheral blood mononuclear cell 
PCR 
polymerase chain reaction 
PI 
Principal Investigator 
PICU 
Pediatric Intensive Care Unit 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
SAE 
serious adverse event 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TUG 
Timed Up and Go modified for children 
ULN 
upper limit of normal 

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/



,1752'8&7,21

&OLQLFDO6WXG\6LWH
7KHVWXG\ZLOOEHDVLQJOHFHQWHUVWXG\FDUULHGRXWDW7KH5HVHDUFK,QVWLWXWHDW1DWLRQZLGH
&KLOGUHQ¶V+RVSLWDO1&+LQ&ROXPEXV2KLR'U-HUU\0HQGHOO3URIHVVRURI3HGLDWULFVDQG
1HXURORJ\ZLOOVHUYHDVWKH3ULQFLSDO,QYHVWLJDWRU3,'U0HQGHOOEULQJVWRWKLVVWXG\PRUH
WKDQ\HDUVRIFOLQLFDOVWXG\H[SHULHQFHLQQHXURPXVFXODUGLVRUGHUV:LWKUHJDUGWRJHQH
WKHUDS\KHZDVWKHILUVWWRGRYLUDOPHGLDWHGJHQHWUDQVIHUVWXGLHVIRUPXVFXODUG\VWURSK\DVWKH
3,LQYLUDOPHGLDWHGJHQHWUDQVIHUVWXGLHVLQ'XFKHQQHPXVFXODUG\VWURSK\'0'
,QYHVWLJDWLRQDO1HZ'UXJ
XVLQJDK\EULGDGHQRDVVRFLDWHGYLUXV>$$9@FRQVLVWLQJ
RI$$9ZLWKDPLQRDFLGVXEVWLWXWLRQVIURP$$9&09SURPRWHUDQGPLQLG\VWURSKLQ
0HQGHOODQGWKHRWKHULQ/LPE*LUGOH0XVFXODU'\VWURSK\W\SH'/*0''
$$9W0&.SURPRWHUDQGDOSKDVDUFRJO\FDQJHQH0HQGHOO+H
FRQGXFWHGDJHQHWKHUDS\VWXG\XVLQJU$$9&09)6
LQJURXSVVSRUDGLF
LQFOXVLRQERG\P\RVLWLVDQG%HFNHUPXVFXODUG\VWURSK\%0'7KHUHVXOWVRIWKH%0'DQG
V,%0VWXGLHVKDYHEHHQSXEOLVKHG0HQGHOO0HQGHOO+HDOVRFRQGXFWHGDJHQH
WKHUDS\VWXG\LQLQIDQWVZLWK60$W\SHDQGVKRZLQJVLJQLILFDQWHIILFDF\
7KH
UHVXOWVLQWKLVVDPHJURXSXVLQJWKHVDPHGRVHIRULQIXVLRQKDYHEHHQVDIHSUHVHQWHGDWWKH
3UHVLGHQWLDO6\PSRVLXPRIWKH$6*&7DQGODWHEUHDNLQJDEVWUDFWV:06
0HQGHOO(IILFDF\DQGVDIHW\KDYHEHHQGRFXPHQWHGJLYHQWKDWWKLVGRVHRI$$9
GHOLYHULQJWKH601JHQHWRVXEMHFWVKDVVDYHGWKHOLYHVRIDOOSDUWLFLSDQWVDQGWKLVVWXG\OHG
WRWKHDSSURYDOLQRIWKLVJHQHWKHUDS\IRUFRPPHUFLDOXVH$VRIWKHFXWRIIGDWHRI
$XJXVWKDYHVXUYLYHGSDVWPRQWKVFRPSDUHGWRLQQDWXUDOKLVWRU\VWXGLHV
KDYHUHDFKHGPRQWKVVXUYLYDODQGKDYHUHDFKHGPRQWKVVXUYLYDO
)XUWKHUPRUHDUHIHHGLQJWKHPVHOYHVVXEMHFWVDUHFUDZOLQJDUHVWDQGLQJZLWKVXSSRUWDQG
VXEMHFWVDUHZDONLQJLQGHSHQGHQWO\

%DFNJURXQGDQG6LJQLILFDQFH

'LVHDVHDQG&KDUDFWHULVWLFV
'XFKHQQHPXVFXODUG\VWURSK\LVWKHPRVWFRPPRQVHYHUHFKLOGKRRGIRUPRIPXVFXODU
G\VWURSK\,QKHULWDQFHIROORZVDQ;OLQNHGUHFHVVLYHSDWWHUQ%LUWKSUHYDOHQFHKDVEHHQ
HVWLPDWHGDWLQOLYHPDOHELUWKV0HQGHOO$SSUR[LPDWHO\RQHWKLUGRIFDVHV
UHSUHVHQWQHZPXWDWLRQVRIWKH'0'JHQHZLWKWKHUHPDLQLQJLQKHULWHGRQWKH;FKURPRVRPH
IURPDFDUULHUPRWKHU4XHVWLRQVXVXDOO\EHJLQWRVXUIDFHEHWZHHQDJHVWRUHJDUGLQJUHGXFHG
PRWRUVNLOOVWKDWDOHUWDQHHGIRUGLDJQRVWLFHYDOXDWLRQ(DUOLHUUHFRJQLWLRQUHVXOWVIURPGHOD\LQ
PRWRUPLOHVWRQHVRUIDPLO\KLVWRU\'XFKHQQHPXVFXODUG\VWURSK\LVUHOHQWOHVVO\SURJUHVVLYH
ZLWKORVVRIDPEXODWLRQE\DJH%URRNH+LVWRULFDOO\SDWLHQWVGLHGIURPUHVSLUDWRU\
FRPSOLFDWLRQV1RZDYDULHW\RIIDFWRUVSURWHFWWKHUHVSLUDWRU\V\VWHPUHODWHGWRLPSURYHG
VXSSRUWLYHHTXLSPHQWDQWLELRWLFVYDFFLQHVDQGRWKHUDQFLOODU\PHWKRGV(DJOH
3URORQJLQJOLIHXQPDVNVGHFOLQHLQFDUGLDFIXQFWLRQZLWKFRPSOLFDWLRQVRIGLODWHG
FDUGLRP\RSDWK\7KLVSRVHVIXUWKHUFOLQLFDOFKDOOHQJHVDQGDQHHGIRUUHFRJQLWLRQDQGPHGLFDO
LQWHUYHQWLRQWKDWGLGQRWSUHYLRXVO\H[LVW1RQSURJUHVVLYHFRJQLWLYHG\VIXQFWLRQPLJKWEH
SUHVHQWLQ'0'DQG%0'
CCI
CCI
CCI
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/



'LVHDVH3DWKRJHQHVLV
0RUHWKDQ\HDUVDJRWKH'0'JHQHZDVFORQHGGHILQLQJWKHPROHFXODUEDVLVRIWKHGLVHDVH
.RHQLJ7KHLGHQWLILFDWLRQRIG\VWURSKLQDVWKHGHILFLHQWSURWHLQIROORZHGFORVHO\RQWKH
KHHOVRIWKLVGLVFRYHU\'HQW'\VWURSKLQLVDN'DF\WRVNHOHWDOSURWHLQUHTXLUHGIRU
PXVFOHILEHUVWDELOLW\/RVVRIWKLVSURWHLQUHVXOWVLQVXVFHSWLELOLW\WRUHSHDWHGF\FOHVRIQHFURVLV
DQGUHJHQHUDWLRQZLWKVDWHOOLWHFHOOGHSOHWLRQGLPLQLVKHGUHJHQHUDWLYHFDSDFLW\RIWKHPXVFOH
HQGLQJLQIDWDQGFRQQHFWLYHWLVVXHUHSODFHPHQWILEURVLV7KHPXWDWLRQVSHFWUXPZLWKLQWKH
'0'JHQHUHYHDOVWKDWGHOHWLRQVRIRQHRUPRUHH[RQVDUHIRXQGLQaRIFDVHVFOXVWHUHGLQ
KRWVSRWUHJLRQV)ODQLJDQ'HWHFWLRQRIGXSOLFDWLRQVUHSUHVHQWVRIWKH'0'
PXWDWLRQV$GGLWLRQDOWRROVLGHQWLI\WKHIXOOVSHFWUXPRIPXWDWLRQVGHOHWLRQVGXSOLFDWLRQV
VSOLFHVLWHDQGSRLQWPXWDWLRQV


7UHDWPHQWIRU'XFKHQQH0XVFXODU'\VWURSK\
'HVSLWHYLUWXDOO\KXQGUHGVRIFOLQLFDOVWXGLHVLQ'0'RQO\RQHWUHDWPHQWKDVFRQVLVWHQWO\
GHPRQVWUDWHGHIILFDF\8QHTXLYRFDOHYLGHQFHIRUJOXFRFRUWLFRLGLQGXFHGLPSURYHPHQWZDV
HVWDEOLVKHGWKURXJKDGRXEOHEOLQGUDQGRPL]HGFRQWUROOHGVWXG\LQDODUJHFRKRUWRIVXEMHFWV
Q &RUWLFRVWHURLGVDUHQRZFRQVLGHUHGWKHVWDQGDUGRIFDUHKRZHYHUWKHVLGHHIIHFWSURILOH
PD\SUHFOXGHWUHDWPHQWIRUVRPHER\V7KHRQO\RWKHUWUHDWPHQWWKDWVHHPVWRVKRZDQHIIHFWLV
H[RQVNLSSLQJ
0HQGHOO
7KHWUHDWPHQWGRHVQRWLQFUHDVHVWUHQJWKEXWVORZVWKHSURJUHVVLRQRIWKHGLVHDVH7KLVZDV
GHPRQVWUDWHGLQDVWXG\GRQHDW1&+DQGWKLVROLJRQXFOHRWLGHHWHSOLUVHQKDVEHHQDSSURYHGE\
WKH)RRGDQG'UXJ$GPLQLVWUDWLRQ)'$IRUWKHWUHDWPHQWRI'0'0HQGHOO
*HQHUHSODFHPHQWWKHUDS\KDVEHHQVWXGLHGIRUWKHSDVW\HDUVDQGVKRZVYHU\IDYRUDEOH
UHVXOWVLQSUHFOLQLFDOVWXGLHVLQPLFHDQGFDQLQHVSHFLHVGHILFLHQWLQG\VWURSKLQ,QWKHILUVW
JHQHWKHUDS\FOLQLFDOVWXG\LQ'0'ZDVGRQHDW1&+DQGWKHUHVXOWVZHUHSXEOLVKHGLQWKH1HZ
(QJODQG-RXUQDORI0HGLFLQHEHFDXVHRIWKHSRWHQWLDOLPSDFWRIWKHILQGLQJV0HQGHOO
,PSRUWDQWO\WKHG\VWURSKLQF'1$LVN%DQGRXUYHKLFOHIRUJHQHWUDQVIHU$$9FDQRQO\KROG
N%7KXVWKHG\VWURSKLQJHQHPXVWEHVFDOHGGRZQLQRUGHUWRILWZLWKLQWKHSDFNDJLQJ
FRQVWUDLQWVRI$$9SDUWLFOHV7KLVPLQLDWXUL]HGWUDQVJHQHZDVWHUPHGPLQLG\VWURSKLQDQGZDV
GHOLYHUHGE\LQWUDPXVFXODULQMHFWLRQWR'0'VXEMHFWV
FORVHG$VWKLVZDVD
FOLQLFDOVWXG\VXEMHFWV¶LPPXQHV\VWHPVZHUHVHQVLWLYHWRWKHVOLJKWFKDQJHVWKDWRFFXUUHGZKHQ
WKHJHQHZDVH[SUHVVHGLQWKHLUPXVFOH:KHQWKLVZDVGRQHLQZHGLVFRYHUHGWKDWLI\RX
LQMHFWWKHJHQHLQWRDVXEMHFWZLWKDGHOHWLRQRIWKH'0'JHQHDVWKHFDXVHRIWKHGLVHDVHLW
FRXOGFDXVHDQLPPXQHUHVSRQVHDQGUHMHFWWKHJHQH7KLVKDSSHQHGLQVXEMHFWVZLWKGHOHWLRQV
LQUHJLRQVRIG\VWURSKLQWKDWZHUHSUHVHQWLQWKH0LQL'\VWURSKLQJHQH)URPWKLVVWXG\DQHZ
YHUVLRQRIWKHWUXQFDWHGG\VWURSKLQJHQHZDVFUHDWHGWHUPHGPLFURG\VWURSKLQZKLFKUHWDLQV
GLIIHUHQWUHJLRQRIWKHQDWLYHJHQHWKDQPLQLG\VWURSKLQ7KHPLFURG\VWURSKLQWUDQVJHQHXVHGLQ
WKLVVWXG\LVWKHVDPHWKDWZDVXVHGLQDFOLQLFDOVWXG\HYDOXDWLQJVDIHW\DQGH[SUHVVLRQRI
LQWUDPXVFXODULQMHFWLRQVRIWKHSURGXFWU$$9UK0&.PLFURG\VWURSKLQ
7KLV
FRQVWUXFWGHPRQVWUDWHGSUHOLPLQDU\VDIHW\LQWKHFOLQLFDOVWXG\
2XUFXUUHQWGHVLJQLVUHODWLYHO\VLPSOHEXWFDUHIXOO\SODQQHG:HZLOOHQVXUHWKDWWKH
PLFURG\VWURSKLQDQGWKHVXEMHFW¶VPXWDWLRQDUHFRPSDWLEOHVRWKDWZHFDQDFKLHYHH[SUHVVLRQRI
RXUWUDQVJHQHZLWKRXWLQGXFLQJLPPXQHUHMHFWLRQ:HZLOODOVRSUHWHVWVXEMHFWVIRUSUHH[LVWLQJ
LPPXQLW\WR$$9VRWKDWZHFDQDYRLGUHMHFWLRQZKHQZHWUDQVIHUWKHJHQH
CCI
CCI
CCI

SRP-9001 
Protocol 
SRP-9001-101 (Amendment 8, Version 9) 
17 
CONFIDENTIAL 
 
 
6. 
STUDY OBJECTIVES AND PURPOSE 
The objective of this study is the assessment of the safety of intravenous (IV) administration of 
rAAVrh74.MHCK7.micro-dystrophin for DMD subjects via peripheral limb vein. 

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/



,19(67,*$7,21$/3/$1

2YHUDOO6WXG\'HVLJQ
7KHSURSRVHGFOLQLFDOVWXG\LVDQRSHQODEHOVLQJOHGRVHVWXG\XVLQJU$$9UK0+&.PLFUR
G\VWURSKLQIRU'0'VXEMHFWV&RKRUW$ZLOOLQFOXGHVXEMHFWVDJHVPRQWKVWR\HDUVDQG
&RKRUW%ZLOOLQFOXGHVXEMHFWVDJHVWR\HDUVROG$OOVXEMHFWVZLOOUHFHLYH,9PLFUR
G\VWURSKLQYHFWRUîYJNJLQDSSUR[LPDWHO\

&RKRUW%VXEMHFWVZLOOEHHQUROOHGEHIRUH&RKRUW$8SRQFRPSOHWLRQRI&RKRUW%WKHVDIHW\
GDWDZLOOEHSUHVHQWHGWRWKH,QVWLWXWLRQDO5HYLHZ%RDUG,5%DQG'DWD6DIHW\0RQLWRULQJ
%RDUG'60%UHTXHVWLQJSHUPLVVLRQWRHQUROO&RKRUW$
$OWKRXJKWKLVVWXG\ZDVRULJLQDOO\GHVLJQHGWRHQUROOVXEMHFWVLQWRFRKRUWVDVRXWOLQHG
DERYHDVRIWKLVDPHQGPHQW9HUVLRQDWRWDORIVXEMHFWVKDYHEHHQHQUROOHGDOOLQWR
&RKRUW%1RIXUWKHUVXEMHFWVZLOOEHHQUROOHGLQWRWKHVWXG\
6XEMHFWVZLOOKDYHLQIXVLRQVRIU$$9FDUU\LQJPLFURG\VWURSKLQRYHUDSSUR[LPDWHO\KRXUVLQ
WKH3HGLDWULF,QWHQVLYH&DUH8QLW3,&8DW1&+7KH%D\OH\,,,*URVV0RWRU6XEWHVWZLOOVHUYH
DVWKHVHFRQGDU\RXWFRPHPHDVXUHIRUDOOFKLOGUHQLQ&RKRUW$%D\OH\6FDOHVRI,QIDQWDQG
7RGGOHU'HYHORSPHQW7KLUG(GLWLRQSXEOLVKHGE\3V\FK&RUS7KH0HWHU7LPHG7HVW
PZLOOEHDSULPDU\PRWRURXWFRPH

7KH
PZLOOEHWKHSULPDU\PRWRURXWFRPHIRU&RKRUW%


3UHDQGSRVWWUHDWPHQWGD\
QHHGOHPXVFOHELRSVLHV7DUQRSROVN\ZLOOEHGRQH

PXVFOHVZLWKDSSURSULDWHDQHVWKHVLDXQGHUDGYLVHPHQWRIDQHVWKHVLRORJLVWRUDQHVWKHWLVW
(0/$&UHDPRUFRPSDUDEOHOLGRFDLQHSULORFDLQHHPXOVLRQDQGRULQMHFWDEOHDQHVWKHWLFPD\EH
XVHGDWWKHVLWHRIELRSV\0LFURG\VWURSKLQJHQHH[SUHVVLRQZLOOVHUYHDVDVHFRQGDU\RXWFRPH
PHDVXUH4XDQWLILFDWLRQZLOOEHGRQHXVLQJYDOLGDWHGLPPXQRIOXRUHVFHQFH

7KHVFKHGXOHRIHYHQWVLVSUHVHQWHGLQ7DEOH
CCI
CCI
CCI
CCI
CCI


653
3URWRFRO
653$PHQGPHQW9HUVLRQ


&21),'(17,$/
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/




6WXG\(QGSRLQWV

3ULPDU\(QGSRLQWV
7KHSULPDU\HQGSRLQWRIWKHVWXG\LVVDIHW\DVDVVHVVHGE\DGYHUVHHYHQWV$(VFKDQJHVLQ
ODERUDWRU\SDUDPHWHUVKHPDWRORJ\VHUXPFKHPLVWU\>3DOPHULD5RVDOHV@XULQDO\VLV
LPPXQRORJLFUHVSRQVHWRU$$9UKDQGPLFURG\VWURSKLQDQGUHSRUWHGKLVWRU\DQG
REVHUYDWLRQVRIV\PSWRPV


2WKHU(QGSRLQWV
(IILFDF\DVVHVVHGE\JHQHH[SUHVVLRQLVDFULWLFDOVHFRQGDU\RXWFRPHPHDVXUHMXGJHGE\
PLFURG\VWURSKLQJHQHH[SUHVVLRQRQPXVFOHELRSVLHV,QDGGLWLRQHIILFDF\ZLOOEHPHDVXUHGE\
WKH%D\OH\,,,*URVV0RWRU6XEWHVW&RKRUW$RQO\7KHPZLOOEHDSULPDU\PRWRURXWFRPH

7KHPZLOOEHWKHSULPDU\PRWRURXWFRPHIRU&RKRUW%



%DVHOLQHPXVFOHELRSVLHVZLWKXOWUDVRXQGJXLGDQFHWRDVVHVVG\VWURSKLQH[SUHVVLRQZLOO
EHGRQHSUHWUHDWPHQWRQDOOVXEMHFWV$OOVXEMHFWVZLOOKDYHDSRVWWUHDWPHQWELRSV\DWGD\
0LFURG\VWURSKLQJHQHH[SUHVVLRQZLOOEHTXDQWLILHGLPPXQRIOXRUHVFHQFHDQGZHVWHUQEORW
DQDO\VLVDQGFRPSDUHGLQSUHDQGSRVWPXVFOHELRSVLHV'\VWURSKLQZLOODOVRVHUYHDVD
VHFRQGDU\RXWFRPHPHDVXUHIRUERWKFRKRUWV



6WXG\&RPPLWWHHV

'DWD6DIHW\0RQLWRULQJ%RDUG
7KH'60%ZLOODFWLQDQDGYLVRU\FDSDFLW\WRUHYLHZSDUWLFLSDQWVDIHW\DQGVWXG\SURJUHVVIRU
WKHFOLQLFDOVWXG\5HVSRQVLELOLWLHVRIWKH'60%DUHWR
x
5HYLHZWKHUHVHDUFKSURWRFROLQIRUPHGFRQVHQWGRFXPHQWVDQGSODQVIRUGDWDDQG
VDIHW\PRQLWRULQJ
x
(YDOXDWHWKHSURJUHVVRIWKHVWXG\LQFOXGLQJSHULRGLFDVVHVVPHQWVRIGDWDTXDOLW\DQG
WLPHOLQHVVSDUWLFLSDQWUHFUXLWPHQWDFFUXDODQGUHWHQWLRQSDUWLFLSDQWULVNYHUVXV
EHQHILWVWXG\VLWHSHUIRUPDQFHDQGRWKHUIDFWRUVWKDWFDQDIIHFWVWXG\RXWFRPH
x
&RQVLGHUIDFWRUVH[WHUQDOWRWKHVWXG\ZKHQUHOHYDQWLQIRUPDWLRQEHFRPHVDYDLODEOH
VXFKDVVFLHQWLILFRUWKHUDSHXWLFGHYHORSPHQWVWKDWPD\KDYHDQLPSDFWRQSDUWLFLSDQW
VDIHW\RUWKHHWKLFVRIWKHVWXG\
x
5HYLHZVWXG\SHUIRUPDQFHPDNHUHFRPPHQGDWLRQVDQGDVVLVWLQWKHUHVROXWLRQRI
SUREOHPVUHSRUWHGE\WKH6SRQVRU
x
3URWHFWWKHVDIHW\RIWKHVWXG\SDUWLFLSDQWV
x
5HYLHZVDIHW\GDWDWRGHWHUPLQHZKHWKHUWRUHFRPPHQGGRVHHVFDODWLRQ
CCI
CCI
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/


x
(QVXUHWKHFRQILGHQWLDOLW\RIWKHVWXG\GDWDDQGWKHUHVXOWVRIPRQLWRULQJDQG
x
$VVLVWE\FRPPHQWLQJRQDQ\SUREOHPVZLWKVWXG\FRQGXFWHQUROOPHQWDQGVDPSOH
VL]HDQGRUGDWDFROOHFWLRQ


'DWD6DIHW\0RQLWRULQJ%RDUG5HSRUWLQJDQG0HHWLQJV
5HSRUWVGHVFULELQJWKHVWDWXVRIWKHVWXG\ZLOOEHSUHSDUHGE\WKH6SRQVRU¶VVWDIIDQGVHQWDWWKH
'60%¶VUHTXHVW7KH'60%ZLOOPHHWSULRUWRGRVLQJWKHILUVWVXEMHFW7KH'60%ZLOOEH
SURYLGHGZLWKDUHSRUWDIWHUVXEMHFW DQGDWHOHFRQIHUHQFHZLOORFFXUDIWHUVXEMHFW 
$PHHWLQJHLWKHUE\WHOHFRQIHUHQFHRUZHEFDVWZLWKWKH'60%ZLOOEHVFKHGXOHGDIWHU

YLVLWRIWKH
VXEMHFWRUDWWKH'60%¶VUHTXHVW5HSRUWVZLOOEHVXEPLWWHGSULRUWRD
VFKHGXOHGPHHWLQJIRUUHYLHZE\WKH'60%
5HSRUWVZLOOLQFOXGHWKHIROORZLQJ
x
$EULHIQDUUDWLYHRIWKHVWXG\VWDWXVLQFOXGLQJWKHWDUJHWHQUROOPHQWFXUUHQWDQG
SURMHFWHGWLPHWRFRPSOHWLQJHQUROOPHQW$Q\VLJQLILFDQWHYHQWVDQGRUGLIILFXOWLHV
VKRXOGEHEULHIO\GHVFULEHGLQWKLVQDUUDWLYH
x
$EULHIQDUUDWLYHIRUHDFKSDUWLFLSDQWGHVFULELQJJHQGHUDJHUDFHDQGHWKQLFLW\DQG
RWKHUUHOHYDQWGHPRJUDSKLFFKDUDFWHULVWLFV7KHQDUUDWLYHIRUHDFKSDUWLFLSDQWVKRXOG
EULHIO\GHVFULEHKLVKHUVWXG\VWDWXVLHGRVHOHYHOYLVLWQXPEHU$(LQIRUPDWLRQ
x
$WLPHOLQHRXWOLQLQJWKHVWXG\SURJUHVVUHODWLYHWRYLVLWQXPEHUIRUHDFKSDUWLFLSDQW
DVZHOODVWLPHSRLQWVIRUHDFKVHULRXVDGYHUVHHYHQW6$(GRVHOLPLWLQJWR[LFLW\$
WRWDOIRU$(VIRUHDFKSDUWLFLSDQWVKRXOGEHLQFOXGHG
x
$VXPPDU\RI$(VE\VHYHULW\OHYHOV
x
$OLVWLQJRI$(GHWDLOVJURXSHGE\SDUWLFLSDQW
x
$OLVWLQJRI6$(GHWDLOVJURXSHGE\SDUWLFLSDQW
x
$OLVWLQJRIGHDWKV
x
$VXPPDU\RIFOLQLFDOO\VLJQLILFDQWODERUDWRU\WHVWUHVXOWV
x
$OLVWLQJRISURWRFROGHYLDWLRQV

0HPEHUVKLS
7KH'60%PHPEHUVKLSZLOOFRQVLVWRISHUVRQVFRPSOHWHO\LQGHSHQGHQWRIWKH,QYHVWLJDWRUZKR
KDYHQRILQDQFLDOVFLHQWLILFRURWKHUFRQIOLFWVRILQWHUHVWZLWKWKHVWXG\&XUUHQWRUSDVW
FROODERUDWRUVRUDVVRFLDWHVRI'U0HQGHOOPXVWQRWHDQ\FRQIOLFWRILQWHUHVWEHIRUHWKHLU
HOLJLELOLW\WRVHUYHRQWKH'60%LVDSSURYHG7KH'60%ZLOOLQFOXGHFOLQLFLDQWUDQVODWLRQDO
VFLHQWLVWVIDPLOLDUZLWKJHQHWKHUDS\
,QGLYLGXDOVLQYLWHGWRVHUYHRQWKH'60%DVHLWKHUYRWLQJRUQRQYRWLQJPHPEHUVPXVWGLVFORVH
DQ\SRWHQWLDOFRQIOLFWVRILQWHUHVWZKHWKHUUHDORUSHUFHLYHG&RQIOLFWVRILQWHUHVWFDQLQFOXGH
SURIHVVLRQDOSURSULHWDU\DQGPLVFHOODQHRXVLQWHUHVWVDVGHVFULEHGLQWKH1DWLRQDO,QVWLWXWHVRI
+HDOWK*UDQW3ROLF\6WDWHPHQWDQG&RGHRI)HGHUDO5HJXODWLRQV&)53DUW3RWHQWLDO
CCI
CCI
CCI
CCI

SRP-9001 
Protocol 
SRP-9001-101 (Amendment 8, Version 9) 
22 
CONFIDENTIAL 
 
 
conflicts that develop during a member’s tenure on a DSMB must also be disclosed. Written 
documentation attesting to an absence of conflict of interest is required annually. 

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/





6(/(&7,21$1':,7+'5$:$/2)68%-(&76

6XEMHFW,QFOXVLRQ&ULWHULD
$VXEMHFWPXVWPHHWDOORIWKHIROORZLQJFULWHULDWREHHOLJLEOHWRSDUWLFLSDWHLQWKLVVWXG\
 $JHRIHQUROOPHQW&RKRUW$Q LVEHWZHHQPRQWKVWR\HDUVRIDJHLQFOXVLYH
&RKRUW%Q LVEHWZHHQWR\HDUVRIDJHLQFOXVLYH
 0ROHFXODUFKDUDFWHUL]DWLRQRIWKH'0'JHQHZLWKIUDPHVKLIWGHOHWLRQRUGXSOLFDWLRQRU
SUHPDWXUHVWRSFRGRQPXWDWLRQEHWZHHQH[RQVWR
 ,QGLFDWLRQRIV\PSWRPDWLFPXVFXODUG\VWURSK\
x
&.HOHYDWLRQ!
8/DQG
x
&RKRUW$EHORZDYHUDJHRQWKH%D\OH\,,,PRWRUDVVHVVPHQWIRUJURVVPRWRUGHILQHG
DVDVFDOHGVFRUHRI &RKRUW%EHORZDYHUDJHRQWKHPGHILQHGDV

SUHGLFWHG&RQQROO\
 0DOHVRIDQ\HWKQLFJURXSZLOOEHHOLJLEOH
 $ELOLW\WRFRRSHUDWHZLWKPRWRUDVVHVVPHQWWHVWLQJ
 )RU&RKRUW$VXEMHFWV1RSUHYLRXVWUHDWPHQWZLWKFRUWLFRVWHURLGV)RU&RKRUW%
VXEMHFWV6WDEOHGRVHHTXLYDOHQWRIRUDOFRUWLFRVWHURLGVIRUDWOHDVWZHHNVSULRUWR
VFUHHQLQJDQGWKHGRVHLVH[SHFWHGWRUHPDLQFRQVWDQWH[FHSWIRUSRWHQWLDOPRGLILFDWLRQV
WRDFFRPPRGDWHFKDQJHVLQZHLJKWWKURXJKRXWWKHILUVW\HDURIWKHVWXG\


6XEMHFW([FOXVLRQ&ULWHULD
$VXEMHFWZKRPHHWVDQ\RIWKHIROORZLQJFULWHULDZLOOEHH[FOXGHGIURPWKLVVWXG\
 $FWLYHYLUDOLQIHFWLRQEDVHGRQFOLQLFDOREVHUYDWLRQV
 6LJQVRIFDUGLRP\RSDWK\LQFOXGLQJHFKRFDUGLRJUDP(&+2ZLWKHMHFWLRQIUDFWLRQ
EHORZ

 6HURORJLFDOHYLGHQFHRIKXPDQLPPXQRGHILFLHQF\YLUXV+,9LQIHFWLRQRU+HSDWLWLV%
RU&LQIHFWLRQ
 'LDJQRVLVRIRURQJRLQJWUHDWPHQWIRUDQDXWRLPPXQHGLVHDVH
 $EQRUPDOODERUDWRU\YDOXHVFRQVLGHUHGFOLQLFDOO\VLJQLILFDQWJDPPDJOXWDP\O
WUDQVIHUDVH>**7@!
WKHXSSHUOLPLWRIQRUPDO>8/1@ELOLUXELQ
PJG/
FUHDWLQLQH
PJG/KHPRJORELQ RU!
J'OZKLWHEORRGFHOOFRXQW!
SHU
FPP
 &RQFRPLWDQWLOOQHVVRUUHTXLUHPHQWIRUFKURQLFGUXJWUHDWPHQWWKDWLQWKHRSLQLRQRIWKH
3,FUHDWHVXQQHFHVVDU\ULVNVIRUJHQHWUDQVIHU
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/


 6XEMHFWVZLWKU$$9UK
DQWLERG\WLWHUV!
DVGHWHUPLQHGE\HQ]\PH
OLQNHGLPPXQRVRUEHQWDVVD\(/,6$LPPXQRDVVD\
x
,IHQGSRLQWWLWHULVSRVLWLYHDWVFUHHQLQJWHVWLQJPD\EHUHSHDWHGSULRUWRH[FOXVLRQ
x
,ILQIDQWDQGPRWKHUDUHSRVLWLYHIRUVDPHDQWLERG\WLWHUVPRWKHUZLOOEHDVNHGQRWWR
EUHDVWIHHGDQGLQIDQWFDQEHHQUROOHGLIDQWLERGLHVGURS
ZLWKLQZHHNV
 +DVDPHGLFDOFRQGLWLRQRUH[WHQXDWLQJFLUFXPVWDQFHWKDWLQWKHRSLQLRQRIWKH
,QYHVWLJDWRUPLJKWFRPSURPLVHWKHVXEMHFW¶VDELOLW\WRFRPSO\ZLWKWKHSURWRFROUHTXLUHG
WHVWLQJRUSURFHGXUHVRUFRPSURPLVHWKHVXEMHFW¶VZHOOEHLQJVDIHW\RUFOLQLFDO
LQWHUSUHWDELOLW\
 6HYHUHLQIHFWLRQHJSQHXPRQLDS\HORQHSKULWLVRUPHQLQJLWLVZLWKLQZHHNVEHIRUH
JHQHWUDQVIHUYLVLWHQUROOPHQWPD\EHSRVWSRQHG
 +DVUHFHLYHGDQ\LQYHVWLJDWLRQDOPHGLFDWLRQRWKHUWKDQFRUWLFRVWHURLGVRUH[RQVNLSSLQJ
PHGLFDWLRQVLQFOXGLQJ(;21'<6H[SHULPHQWDORURWKHUZLVHLQWKHODVWPRQWKV
SULRUWRVFUHHQLQJIRUWKLVVWXG\
 +DVKDGDQ\W\SHRIJHQHWKHUDS\FHOOEDVHGWKHUDS\HJVWHPFHOOWUDQVSODQWDWLRQRU
&5,635&DV
 )DPLO\GRHVQRWZDQWWRGLVFORVHVXEMHFW¶VVWXG\SDUWLFLSDWLRQZLWKSULPDU\FDUH
SK\VLFLDQDQGRWKHUPHGLFDOSURYLGHUV

6XEMHFW:LWKGUDZDO&ULWHULD
$Q\VXEMHFWFDQZLWKGUDZIURPVWXG\SDUWLFLSDWLRQDWDQ\WLPHIRUDQ\UHDVRQ,QDGGLWLRQWKH
6SRQVRUPD\GHFLGHWRVWRSWKHVWXG\SDUWLFLSDWLRQRIDQ\VXEMHFWDVGHHPHGQHFHVVDU\7KH
,QYHVWLJDWRUPD\DOVRVWRSWKHVWXG\SDUWLFLSDWLRQRIDQ\VXEMHFWDWDQ\WLPH5HDVRQVIRUVWXG\
ZLWKGUDZDOLQFOXGHEXWDUHQRWOLPLWHGWR
x
7KHVXEMHFWZDVHUURQHRXVO\LQFOXGHGLQWKHVWXG\LHZDVIRXQGWRKDYHQRWPHWWKH
HOLJLELOLW\FULWHULD
x
7KHVXEMHFWH[SHULHQFHVDQLQWROHUDEOHRUXQDFFHSWDEOH$(
x
7KHVXEMHFWLVXQDEOHWRFRPSO\ZLWKWKHUHTXLUHPHQWVRIWKHSURWRFRO
x
7KHVXEMHFWSDUWLFLSDWHVLQDQRWKHULQYHVWLJDWLRQDOVWXG\ZLWKRXWWKHSULRUZULWWHQ
DXWKRUL]DWLRQRIWKH6SRQVRU
7KH,QYHVWLJDWRURUVWXG\VWDIIZLOOGRFXPHQWWKHUHDVRQVIRUWUHDWPHQWGLVFRQWLQXDWLRQRQWKH
FDVHUHSRUWIRUP&5)
CCI
CCI
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/



75($70(172)68%-(&76

7UHDWPHQW$GPLQLVWHUHG

*HQH7UDQVIHU3URWRFRO
6XEMHFWVZLOOEHDGPLWWHGWR1&+IRUJHQHWUDQVIHUHLWKHU3,&8RU3XOPRQDU\3,&8WKHQLJKW
EHIRUHJHQHWUDQVIHUDQGZLOOEHH[DPLQHGE\HLWKHUWKH3,RUFR,QYHVWLJDWRUVGD\2QWKH
GD\RIJHQHWUDQVIHUGD\WKHSKDUPDF\ZLOOSUHSDUHU$$9UK0+&.PLFURG\VWURSKLQ
JHQHYHFWRUDFFRUGLQJWRWKH6WXG\2SHUDWLRQV0DQXDO7KHUHVHDUFKSKDUPDFLVWZLOOWUDQVSRUW
WKHYHFWRUWRWKHFOLQLFDOVHWWLQJLQDYHFWRUFRQWDLQLQJV\ULQJHDWURRPWHPSHUDWXUHDQGWKH
YHFWRUQHHGVDGPLQLVWHUHGWRWKHVXEMHFWZLWKLQKRXUVRISUHSDUDWLRQ7KHILQDOYROXPHZLOOEH
DGPLQLVWHUHGWRWKHVXEMHFWE\WKH3,RUGHVLJQHHLQWKHVXEMHFW¶VKRVSLWDOURRP$OOVXEMHFWVZLOO
UHFHLYH,9PLFURG\VWURSKLQYHFWRUîYJNJLQYROXPHRIDSSUR[LPDWHO\
7KLV
LVWKHVDPHYROXPHWKDWSURYHGVDIHLQWKH60$LQIDQWJHQHWKHUDS\VWXG\'RFXPHQWDWLRQRIWKH
GLOXWLRQZLOOEHFRPSOHWHGE\WKHSKDUPDF\IROORZLQJVWDQGDUGSKDUPDF\SURWRFRODQGKDQGOLQJ
RIWKHU$$9UK0+&.PLFURG\VWURSKLQJHQHZLOOIROORZFRPSOLDQFHVWDQGDUGVIRU
%LRVDIHW\/HYHOYHFWRUV


9HFWRU$GPLQLVWUDWLRQ3URWRFRO
9HFWRUDGPLQLVWUDWLRQZLOOEHWKURXJKDSHULSKHUDOOLPEYHLQ,WLVXQOLNHO\WKDWFRQVFLRXV
VHGDWLRQRUDVHGDWLYHOLNHORUD]HSDPZLOOEHUHTXLUHGEXWWKLVZLOOEHGHWHUPLQHGEDVHGRQ3,
REVHUYDWLRQDQGFRQVXOWDWLRQZLWKSDUHQWV7KHVNLQRYHUWKHLQMHFWLRQVLWHIRUJHQHWUDQVIHUZLOO
EHSUHWUHDWHGZLWKDOLGRFDLQHSULORFDLQHHXWHFWLFPL[WXUHLQFRUSRUDWHGLQDFUHDPEDVH(0/$
FUHDPRUDFHOOXORVHGLVN(0/$SDWFK&RPSDUDEOHFUHDPEDVHGDQHVWKHVLDVXFKDV[\ORFDLQH
FUHDPPLJKWEHXVHG,QWUDYHQRXVFDWKHWHUSODFHPHQWZLOOEHSHUIRUPHGIROORZLQJ1&+SROLF\
DQG,9VZLOOEHSODFHG2QH,9FDWKHWHUZLOOEHIRULQIXVLRQDQGRQHIRUDVHFRQGDU\VLWHLQWKH
HYHQWWKDWWKHUHDUHFRPSOLFDWLRQVZLWKWKHILUVWVLWH7KHWRWDOGRVHRIYHFWRULQYROXPHRI
DSSUR[LPDWHO\
WREHLQIXVHGZLOOEHîYJNJRYHUDSSUR[LPDWHO\KRXUV
0RQLWRULQJRIVXEMHFWVGXULQJYLUDODGPLQLVWUDWLRQZLOOLQFOXGHEORRGSUHVVXUHKHDUWUDWH
UHVSLUDWRU\UDWHDQGWHPSHUDWXUH
7DEOH
7UHDWPHQW&RKRUWV



&RKRUW


$JH


1
9HFWRU
'RVH
YJNJ

9ROXPH
PONJ


&RUWLFRLG6WHURLGV
$
±
PRQWKV

î

PJNJJOXFRFRUWLFRLGPDLQWDLQHGIRU
GD\VSRVWLQIXVLRQXQOHVV**7UHPDLQV
HOHYDWHG
%
±\HDUV

î

6WDEOHGRVHRIRUDOFRUWLFRVWHURLGVZHHNV
SULRUWRDQGWKURXJKRXWWKHILUVW\HDURIWKH
VWXG\
CCI
CCI
CCI
CCI

S R P -9 0 0 1  
Pr ot oc ol  
S R P -9 0 0 1 -1 0 1 ( A me n d me nt 8, Versi o n 9)  
2 6  
C O N FI D E N TI A L  
 
 
9.1.3. 
D ose -Li miti n g  Pl a n  
A d ose-li miti n g t o xicit y is defi ne d as a n y u na ntici pate d S A E t hat is p ossi bl y, pr o ba bl y, or 
defi nitel y relate d t o t he st u d y dr u g. T his w o ul d i ncl u de a n y Gra d e   A E acc or di n g t o t he 
defi niti o n pr o vi de d i n Secti o n 1 2. 3. 2 . 
St u d y e nr oll me nt will be halte d b y t he I n vesti gat ors w he n a n y s u bject e x perie nces 1 or m ore 
≥Gra de   A E t o xicit y t hat is u na ntici pate d a n d p ossi bl y, pr o ba bl y, or defi nitel y relate d t o st u d y 
dr u g. T he e v e nt will t he n be re vie w e d b y t he D S M B a n d e val uate d t o det er mi ne if t he st u d y 
s h o ul d be ter mi nate d earl y f oll o wi n g t he st o p pi n g/ disc o nti n uati o n r ules. 
La b orat or y tests wit h val ues wit hi n t he cli nicall y si g nifica nt ra n ge will be re peate d d uri n g t he 
sa me visit w he ne ver p ossi ble. If t he test res ult ret ur ns after t h e s u bject lea v es t he cli nic, t he 
s u bject will be i m me diatel y c o ntacte d. L o cal resi de nts will be as ke d t o ret ur n t o t he o ut s u bject 
cli nic f or a r e peat test. F or n o n -l ocal r esi de nts, arra n ge me nts will be ma de t o ha ve t he bl o o d test 
re- dr a w n i n a la b orat or y cl ose t o h o me or b y t heir pri mar y care p h ysicia n. T o a v oi d a n y 
c o nf usi o n, t he pri mar y care p h ysicia n will be i nf or me d ( wit h per missi o n fr o m t he s u bject) of t he 
s u bject’s partici pati o n i n t he st u d y at t he ti me of ge ne tra nsfer. If t he A E re q uires treat me nt, t his 
will be carri e d o ut b y t he pri mar y care p h ysicia n or a d oct or of c h oice s electe d b y t he s u bject. 
C o pies of re peat la b orat or y tests a n d a n y rele va nt me dical rec or ds will be o btai ne d a n d a d d e d t o 
t he s u bject’s res ear c h c h art. 
T he S p o ns or will f ulfill t he re p orti n g r es p o nsi bilities u n der 2 1 C F R 3 1 2. 3 2(c), t o n otif y t he F D A 
i n a n I N D safet y re p ort of p ote ntiall y seri o us ris ks, as s o o n as p ossi ble, b ut n o later t ha n 
1 5 cale n dar da ys after t h e I n vesti gat or recei ves t he safet y i n f or mati o n a n d deter mi nes t hat t he 
i nf or mati o n q ualifies f or re p orti n g. T he I n v esti gat or will c o nfer wit h t he D S M B, I R B, a n d 
Ce nter f or Bi ol o gics E val uati o n/ F D A bef ore c o nti n ui n g e nr oll me nt. 
 
9.1.4. 
St o p pi n g/ Disc o nti n u ati o n  R ules  
A n i n de pe n de nt D S M B will m o nit or safet y data o n a c o nti n ual basis t hr o u g h o ut t he st u d y. T he 
D S M B ca n rec o m me n d earl y ter mi nati o n of t he st u d y f or reas o ns of s afet y. St u d y e nr oll me nt will 
be halte d b y t he I n v esti gat ors w he n a n y s u bj ect e x perie nces  or m ore Gr a de  , or hi g her A E 
t o xicit y t hat are u n a ntici p ate d a n d p ossi bl y, pr o b a bl y, or defi nitel y rel ate d t o t he st u d y dr u g. 
T his will i ncl u de a n y s u bject deat h n ot rel ate d t o u n derl yi n g disease c o n diti o n, i m p orta nt cli nical 
la b orat or y fi n di n g, or a n y se vere l o cal c o m plicati o n i n t he i njecte d area relate d t o a d mi nistrati o n 
of t he st u d y a ge nt. If after re vie w b y t h e D S M B, I R B, a n d F D A, t he decisi o n is ma de t o 
c o nti n ue, t he st u d y will pr ocee d. If t he li ver e nz y me G G T is ele vat e d at da y 3 0, ster oi ds will be 
mai ntai ne d u ntil G G T le vels dr o p bel o w  
 U/ L. 
 
 
9.1.5. 
D osi n g  Sc he d ule  
T here will be at least a 
 d osi n g i nter val b et wee n s u bjects f or C o h ort B. T here will be at 
least a 
 d osi n g i nter val bet w ee n s u bjects f or C o h ort A. D ose es calati o n will be c o nsi dere d 
i n c olla b orati o n wit h F D A a n d D S M B. 
T he I n vesti gat ors will c o nfer wit h t he I R B a n d D S M B o n all Gra de   or hi g her A Es wit h i n 
 t hat are u n a ntici pate d a n d p ossi bl y, pr o ba bl y, or defi nitel y relate d t o t he st u d y a ge nt 
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

SRP-9001 
Protocol 
SRP-9001-101 (Amendment 8, Version 9) 
27 
CONFIDENTIAL 
 
 
before continuing enrollment. Based on the outcome of the safety and efficacy analysis of the 
event, decision will be made to proceed with additional subjects. 
9.2. 
Randomization and Blinding 
This study is open-label. 
9.3. 
Concomitant  Medications 
All subjects will be asked to refrain from using concomitant medications that may interfere with 
the study objectives. This includes the FDA-approved exon skipping therapy EXONDYS 51. If, 
during the duration of this study, a subject begins use of EXONDYS 51 their data after use of an 
exon-skipping drug will no longer be included in study outcomes. We will ask that their study 
visits for safety assessments be continued for the remainder of the study. 
9.4. 
Treatment Compliance 
The vector will be administered under the direct supervision of trained staff. 

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/

,'(17,7<2),19(67,*$7,21$/352'8&76

'HVFULSWLRQRI6WXG\'UXJ
653ZLOOEHSURYLGHGDVDVWHULOHIUR]HQOLTXLGLQDVLQJOHXVHP/YLDOFRQWDLQLQJ
U$$9UK0+&.PLFURG\VWURSKLQJHQHYHFWRU653ZLOOEHWKDZHGDWURRP
WHPSHUDWXUHSULRUWRDGPLQLVWUDWLRQ5HIHUWRWKH6WXG\2SHUDWLRQV0DQXDOIRUIXUWKHUGHWDLOV

3DFNDJLQJDQG/DEHOLQJ
3UHSDUDWLRQVKRXOGEHFRPSOHWHGLQDFFRUGDQFHZLWKORFDOQDWLRQDODVHSWLFWHFKQLTXHV
3UHSDUDWLRQRI653VKRXOGEHFRPSOHWHGRQWKHVDPHGD\DVWKHGRVLQJSURFHGXUH
7KHFOLQLFDOSKDUPDFLVWZLOOSUHSDUHWKH653SURGXFWDVHSWLFDOO\LQD&ODVV,,ELRVDIHW\
FDELQHWXQGHUVWHULOHFRQGLWLRQV653YLDOVDUHWKDZHGDWWKHKRVSLWDOSKDUPDF\DWURRP
WHPSHUDWXUH&WR&
7KDZHGYHFWRUYLDOVDUHZLSHGZLWKDOFRKRODQGSODFHGLQWKHELRVDIHW\FDELQHW653IRU,9
LQIXVLRQZLOOEHVXSSOLHGLQDYLDOP/SHUYLDO7KHWRWDOYJGRVHZLOOEHFDOFXODWHGEDVHGRQ
VXEMHFW¶VERG\ZHLJKW7KHDSSURSULDWHQXPEHURIYLDOVZLOOEHGHWHUPLQHGIRUHDFKVXEMHFWEDVHG
RQERG\ZHLJKWDWWKHHTXLYDOHQWRIîYJNJDVZHOODVSURGXFWWLWHUIRUWKHVSHFLILF653
SURGXFWORWRI
7KHDFWXDOYJFRQFHQWUDWLRQSHUP/YJP/ZLOOEH
SURYLGHGRQWKH&HUWLILFDWHVRI$QDO\VLVDQGWKHYLDOFRQWDLQLQJWKH,QYHVWLJDWLRQDO3URGXFW

6WRUDJH
653PXVWEHVWRUHGEHORZÛ&
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/



678'<$66(660(176

3UH7UHDWPHQW$VVHVVPHQWV

$IWHUREWDLQLQJLQIRUPHGFRQVHQWDQGFRPSOHWLQJWKHUHJLVWUDWLRQSURFHGXUHVDEDVHOLQHVXEMHFW
KLVWRU\ZLOOEHFROOHFWHGLQFOXGLQJUHFRUGVRIDOOPHGLFDWLRQVDQGVXSSOHPHQWVWKDWWKHVXEMHFWLV
WDNLQJ7KHIROORZLQJDVVHVVPHQWVZLOOEHSHUIRUPHGWRFRQILUPVXEMHFWHOLJLELOLW\IRUWKLVVWXG\
%DVHOLQHWHVWVZKLFKPXVWEHFRPSOHWHGSULRUWRWUHDWPHQWDGPLQLVWUDWLRQLQFOXGHWKRVHOLVWHG
EHORZ

%HIRUH*HQH7UDQVIHU
x
3K\VLFDOH[DPLQDWLRQ
x
0HGLFDOKLVWRU\
x
9LWDOV
x
&DUGLDFPDJQHWLFUHVRQDQFHLPDJLQLQJ05,YDOXHRI05,RIKHDUWKDVEHHQ
H[WHQVLYHO\VWXGLHGLQRXU0'$&OLQLFVKRZLQJLQFUHDVHGDELOLW\WRGHWHFWILEURVLV
DQGPRUHSUHFLVHPHDVXUHVRIHMHFWLRQIUDFWLRQ&RKRUW%RQO\
x
(OHFWURFDUGLRJUDP(&*
x
(&+2
x
&KHVW;UD\
x
+HSDWLWLV%	&VFUHHQ
x
+,9VFUHHQ
x
&RPSOHWHEORRGFRXQW&%&GLIIHUHQWLDOSODWHOHWZLWKVPHDU
x
7RWDOSURWHLQ
x
6HUXP**7
x
$ODQLQHDPLQRWUDQVIHUDVH$/7
x
$VSDUWDWHDPLQRWUDQVIHUDVH$67
x
7RWDOELOLUXELQ
x
*OXFRVH
x
(OHFWURO\WHV&&KORULGH3RWDVVLXPDQG6RGLXP
x

x
&UHDWLQLQHEORRGXUHDQLWURJHQ%81
x
&\VWDWLQ&
x
$ONDOLQHSKRVSKDWDVH
x
$P\ODVH
CCI
CCI
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/
x
3URWKURPELQWLPH373DUWLDOWKURPERSODVWLQWLPH377LQWHUQDWLRQDOQRUPDOL]HG
UDWLRQ,15
x
8ULQDO\VLV
x
6HUXPDQWLERG\WRU$$9UK
x

x
3K\VLFDOWKHUDS\DVVHVVPHQWV
x


x
$(UHSRUWLQJ
x
3KRWRJUDSKRILQMHFWLRQVLWH
x
&RQFRPLWDQWPHGLFDWLRQV

1RWHXVHRI(;21'<6ZLOOGLVTXDOLI\SDUWLFLSDQWVIURPLQFOXVLRQLQWKLV
VWXG\
x
0XVFOHELRSV\WREHFRPSOHWHGGD\

 **7ZLOOEHXVHGWRPRQLWRUOLYHUHQ]\PHVUDWKHUWKDQ$/7RU$67EHFDXVHRIWKHVRXUFHRI
WKHVHHQ]\PHVIURPGDPDJHGPXVFOHLQ'0'ZKHUHOHYHOVFDQUHDFK
;8/1$ODQLQH
DPLQRWUDQVIHUDVHDQG$67FDQYDU\E\
IURPGD\WRGD\PDNLQJLQWHUSUHWDWLRQGLIILFXOW
*DPPDJOXWDP\OWUDQVIHUDVHLVQRWDIIHFWHGE\PXVFOHGLVHDVH5RVDOHV

3UH7UHDWPHQWDQG3RVW7UHDWPHQW0XVFOH%LRSV\


3UHJHQHWUDQVIHUPXVFOHELRSV\ZLWKXOWUDVRXQGJXLGDQFHZLOOEHGRQHDIWHUHVWDEOLVKLQJ
HOLJLELOLW\LQFOXGLQJDSSURSULDWHODERUDWRU\WHVWLQJ,IDSUHYLRXVPXVFOHELRSV\VSHFLPHQZDV
REWDLQHGZLWKLQ\HDUSULRUWRHQUROOPHQWWKH3,ZLOOXVHGLVFUHWLRQZKHWKHURUQRWWKHILUVW
ELRSV\QHHGVWREHFRPSOHWHGGXULQJWKHVFUHHQLQJSHULRG1HHGOH
PXVFOHELRSVLHVZLWK
XOWUDVRXQGJXLGDQFHZLOOEHXVHGWRTXDQWLI\WUDQVJHQHH[SUHVVLRQFRPSDULQJEDVHOLQHWRGD\
7KHELRSVLHVZLOOEHGRQHRQWKHRSSRVLWHOHJDVWKHRULJLQDOELRSVLHV7KHPXVFOHVWREHELRSVLHG
DWERWKWLPHSRLQWVZLOOHLWKHUEHWKH
DWWKHGLVFUHWLRQRIWKH
,QYHVWLJDWRU7KHELRSVLHVZLOOEHGRQHE\WKHDSSURSULDWHVWDIIDW1&+
7KHPXVFOHELRSVLHVZLOOEHSURFHVVHGLQWKH
ZKLFK
RSHUDWHVXQGHUD&ROOHJHRI$PHULFDQ3DWKRORJLVWV&$3&OLQLFDO/DERUDWRU\,PSURYHPHQW
$PHQGPHQWV&/,$OLFHQVHIRUWKHLUGLDJQRVWLFQHXURPXVFXODUWHVWLQJ7KHUHZLOOEHDQ
DVVLJQHGEOLQGHGLGHQWLILHU
IRUHDFKVXEMHFW%OLQGHGDQDO\VLVZLOOLQFOXGH
SRO\PHUDVHFKDLQUHDFWLRQ3&5DQDO\VLVIRUYLUDO'1$DQGTXDQWLWDWLYH:HVWHUQEORWRQIUR]HQ
PXVFOHELRSV\VKDYLQJV4XDQWLWDWLYHSURWHLQDQDO\VLVIRUPLFURG\VWURSKLQXVLQJDYDOLGDWHG
:HVWHUQEORWPHWKRGZLOOEHVKLSSHGWR6DUHSWD7KHUDSHXWLFVWRSHUIRUP
)UR]HQVHFWLRQVZLOOEHVHFWLRQHGDQGVWDLQHGIRUG\VWURSKLQXVLQJLQGLUHFWLPPXQRIOXRUHVFHQFH
ZLOOEHXVHGWRTXDQWLI\WKHLQWHQVLW\RIG\VWURSKLQH[SUHVVLRQ
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/


FRPSDUHGWRQRUPDOFRQWUROV




3UH7UHDWPHQW,PPXQRVXSSUHVVLYHV
6XEMHFWVLQ&RKRUW$QRWWDNLQJJOXFRFRUWLFRLGVXSRQHQUROOPHQWSHULQFOXVLRQFULWHULDZLOOEH
VWDUWHGRQDQRUDOGRVHRISURSK\ODFWLFSUHGQLVRORQHSUHGQLVRQHJOXFRFRUWLFRLGGD\SULRUWR
JHQHWUDQVIHU,QPRVWFDVHVWKLVZLOOEHSUHGQLVRORQHPJNJGD\EXWSUHGQLVRQHDWWKHVDPH
GRVHLVDFFHSWDEOHDVZHOODVDFRPSDUDEOHJOXFRFRUWLFRLGDGPLQLVWHUHGYLD,9LILWZHUHWREH
UHTXLUHG,WLVWKHLQWHQWIRUWKLVWRVHUYHDVDQLPPXQRVXSSUHVVLYHWRGDPSHQKRVWLPPXQH
UHVSRQVHWR$$9RUWUDQVJHQH,I**7LVEHORZ
8/DWGD\VWHURLGVZLOOEHZHDQHGRYHU
ZHHN
6XEMHFWVLQ&RKRUW%ZLOOUHPDLQRQWKHLUVWDEOHGRVHRIFRUWLFRVWHURLGVWKURXJKRXWWKHILUVW\HDU
RIWKHVWXG\EXWPD\EHLQFUHDVHGIRUVKRUWWLPHLI**7OHYHOLV!
8/RUWKHUHDUHRWKHU
FOLQLFDOO\VLJQLILFDQWOLYHUIXQFWLRQDEQRUPDOLWLHV7KRVHRQZHHNHQGGRVLQJPD\UHFHLYHDGDLO\
GRVHRIPJNJRIJOXFRFRUWLFRLGIRUDSSUR[LPDWHO\
GD\VLQDGGLWLRQWRWKHLUUHJXODUZHHNHQG
GRVLQJ

&DUGLDF0DJQHWLF5HVRQDQFH,PDJLQJ
&DUGLDF05,VZLOORQO\EHSHUIRUPHGRQVXEMHFWVJUHDWHUWKDQ\HDUVRIDJH&RKRUW%DWWKH
WLPHRIHQUROOPHQW7KHFDUGLDF05,VZLOOEHSHUIRUPHGZLWKRXWDQ\W\SHRIDQHVWKHVLD,IWKLVLV
QRWSRVVLEOHGXHWRWKHDELOLW\RIWKHVXEMHFWWKH05,ZLOOQRWEHFRPSOHWHG7KHFDUGLDF05,
ZLOORFFXUDWEDVHOLQHPRQWKVDQG\HDUSRVWJHQHWUDQVIHU






*HQH7UDQVIHUDQG9HFWRU$GPLQLVWUDWLRQ3URWRFRO
5HIHUWR6HFWLRQVDQG

3RVW*HQH7UDQVIHU0RQLWRULQJ







CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/



([WHQGHG)ROORZXS
6XEMHFWVZLOOUHWXUQIRUIROORZXSYLVLWVRQGD\V

DQG
ELRSVLHVZLOORFFXUDW
DQGDWPRQWKV

DQG)ROORZXSYLVLWVWKURXJKGD\ZLOO
EHGRQHDW1&+DVZLOOWKHPXVFOHELRSV\SUHDQGSRVWJHQHWUDQVIHU8QVFKHGXOHGYLVLWVPD\
RFFXULIWKH3,GHWHUPLQHVWKH\DUHQHFHVVDU\IRUWKHVXEMHFW¶VVDIHW\DQGZHOOEHLQJ


7R[LFLW\PRQLWRULQJRQHDFKRIWKHVHGDWHV
LVGHVFULEHGLQWKHIROORZLQJVHFWLRQVRIWKHSURWRFRO:HZLOOIROORZWKHPRVWUHFHQW)'$
JXLGHOLQHVZLWKUHJDUGWRORQJWHUPVXEMHFWIROORZXSIROORZLQJJHQHWUDQVIHU

:HZLOOKRZHYHU
HYDOXDWHVDIHW\RYHUD\HDUSHULRGWKDWLQFRUSRUDWHVWKHDFWLYHSKDVHRIWKHSURWRFROVHH
DVVHVVPHQWRIHQGSRLQWVEHORZ,IQHZO\LGHQWLILHGULVNVDUHDVVRFLDWHGZLWKRXUSURGXFWRULI
WKHVXEMHFWVVXIIHUDQ\DGYHUVHUHDFWLRQVGXULQJWKLVSHULRGZHZLOOLQLWLDWHDORQJWHUP
IROORZXSDFFRUGLQJWRWKH)'$JXLGHOLQHV


$VVHVVPHQWRI6DIHW\




0RQLWRULQJZLOORFFXUDWGD\

DQGDQGDWPRQWKV


$PXVFOHELRSV\ZLOOWDNHSODFHDWGD\7KHIROORZLQJSDUDPHWHUVZLOO
EHLQFOXGHGDWWKHPRQLWRULQJHYDOXDWLRQV
x
3K\VLFDOH[DPLQDWLRQ
x
9LWDOV
x
6HUXP**7
x
$/7
x
$67
x
7RWDOELOLUXELQ
x
*OXFRVH
x
37377,15
x
&%&GLIIHUHQWLDOSODWHOHWZLWKVPHDU
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/


x


x
&UHDWLQLQH%81
x
&\VWDWLQ&
x
$ONDOLQHSKRVSKDWDVH
x
$P\ODVH
x
(OHFWURO\WHV&&KORULGH3RWDVVLXPDQG6RGLXP
x
7RWDOSURWHLQ
x
8ULQDO\VLV
x

x

x
&DUGLDF05,DWDQGPRQWKYLVLW&RKRUW%RQO\
x
3KRWRJUDSKRILQMHFWLRQVLWHVXUURXQGLQJDUHDXSWKURXJKGD\YLVLW
x
$(UHSRUWLQJ
x
&RQFRPLWDQWPHGLFDWLRQV
x
(&+2(&*DWGD\DQG\HDUVDQG

$VVHVVPHQWRI(IILFDF\
7KH%D\OH\,,,*URVV0RWRU6XEWHVWZLOOEHVFRUHGIRU&RKRUW$RQHYHU\IROORZXSYLVLWVWDUWLQJ
DWGD\DQGIROORZHGRQGD\
DQG
DQGDWPRQWKV
DQGVHUYH
DVDVHFRQGDU\RXWFRPHIRUWKLVVWXG\$Q\VXEMHFWWKDWLVPRQWKVRIDJHLQFOXVLYHDWWLPH
RIVFUHHQLQJZLOOKDYHWKHVFDOHGVFRUHFDOFXODWHGFRPSDUHGWRQRUPDWLYHGDWDIRUPRQWKROG
FKLOGUHQ7KH%D\OH\,,,SURYLGHVQRUPDWLYHGDWDIRUFKLOGUHQPRQWKVRIDJH
7KHPZLOOEHDSULPDU\PRWRURXWFRPH

7KHPZLOOEHWKHSULPDU\PRWRU
RXWFRPHIRU&RKRUW%



0XVFOHELRSVLHVZLWKXOWUDVRXQGJXLGDQFHZLOOEHXVHGWRTXDQWLI\WUDQVJHQHH[SUHVVLRQ
FRPSDULQJEDVHOLQHWRGD\7KHELRSVLHVZLOOEHGRQHRQWKHVDPHOHJDVWKHRULJLQDOELRSVLHV
+RZHYHULQVRPHFDVHVDWWKHGLVFUHWLRQRIWKH3,WKHRSSRVLWHH[WUHPLW\PD\EHSUHIHUUHGLILW
ZLOOEHOHVVWUDXPDWLFWRWKHVXEMHFW,WLVDOVRLPSRUWDQWWRHPSKDVL]HWKDWWKHELRSVLHVZLOOEH
UHDGEOLQGHGDQGZLOOQRWEHLGHQWLILHGDVSUHRUSRVWWUHDWPHQW7KHELRSVLHVZLOOEHGRQHE\WKH
DSSURSULDWHVWDIIDW1&+
7KHPXVFOHELRSVLHVZLOOEHSURFHVVHGLQWKH
ZKLFK
RSHUDWHVXQGHUD&$3&/,$OLFHQVHIRUWKHLUGLDJQRVWLFQHXURPXVFXODUWHVWLQJ7KHUHZLOOEHDQ
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/


DVVLJQHGEOLQGHGLGHQWLILHUIRUHDFKVXEMHFW)UR]HQVHFWLRQVZLOOEHVWDLQHGIRUG\VWURSKLQXVLQJ
LQGLUHFWLPPXQRIOXRUHVFHQFH
ZLOOEHXVHGWRTXDQWLI\WKHLQWHQVLW\
RIG\VWURSKLQH[SUHVVLRQFRPSDUHGWRQRUPDOFRQWUROV





CCI
CCI
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/



$'9(56((9(176$1'6(5,286$'9(56((9(176

'HILQLWLRQVRI$GYHUVH(YHQWV

$GYHUVH(YHQW
$Q$(LVDQ\XQWRZDUGPHGLFDORFFXUUHQFHLQDFOLQLFDOVWXG\VXEMHFWWKDWGRHVQRWQHFHVVDULO\
KDYHDFDXVDOUHODWLRQVKLSZLWKWKHVWXG\GUXJ$Q$(FDQWKHUHIRUHEHDQ\XQIDYRUDEOHDQG
XQLQWHQGHGV\PSWRPVLJQGLVHDVHFRQGLWLRQRUWHVWDEQRUPDOLW\WKDWRFFXUVGXULQJRUDIWHU
DGPLQLVWUDWLRQRIDVWXG\GUXJZKHWKHURUQRWFRQVLGHUHGUHODWHGWRWKHVWXG\GUXJ
$GYHUVHHYHQWVLQFOXGH
x
6\PSWRPVGHVFULEHGE\WKHVXEMHFWRUVLJQVREVHUYHGE\WKH,QYHVWLJDWRURUPHGLFDO
VWDII
x
7KHRQVHWRIQHZLOOQHVVDQGWKHH[DFHUEDWLRQRISUHH[LVWLQJPHGLFDOFRQGLWLRQV
x
7HVWDEQRUPDOLWLHVODERUDWRU\WHVWV(&*HWFGHHPHGFOLQLFDOO\VLJQLILFDQW
$EQRUPDOLWLHVSUHVHQWDWVFUHHQLQJZLOOEHFROOHFWHGDVSDUWRIPHGLFDOKLVWRU\DQGDUHFRQVLGHUHG
$(VRQO\LIWKH\UHRFFXUDIWHUUHVROXWLRQRUZRUVHQGXULQJWKH$(FROOHFWLRQSHULRG


6HULRXV$GYHUVH(YHQW
$Q6$(LVGHILQHGDVDQ\$(WKDWUHVXOWVLQDQ\RIWKHIROORZLQJ
x
'HDWK7KHVXEMHFWGLHGDVWKHUHVXOWRIWKHHYHQW
x
/LIHWKUHDWHQLQJHYHQW$Q\$(WKDWSODFHVWKHVXEMHFWLQWKHYLHZRIWKH
,QYHVWLJDWRURU6SRQVRUDWLPPHGLDWHULVNRIGHDWKIURPWKH$(DVLWRFFXUUHG
LHGRHVQRWLQFOXGHDQ$(WKDWKDGLWRFFXUUHGLQDPRUHVHYHUHIRUPPLJKWKDYH
FDXVHGGHDWK
x
5HTXLUHGRUSURORQJHGLQSDWLHQWKRVSLWDOL]DWLRQ7KH$(UHVXOWHGLQ
KRVSLWDOL]DWLRQRUSURORQJHGDQH[LVWLQJKRVSLWDOL]DWLRQ

+RVSLWDOL]DWLRQVWKDWDUHSDUWRIWKHVWXG\SURFHGXUHVDUHH[HPSWXQOHVVWKH
KRVSLWDOL]DWLRQLVSURORQJHGEDVHGRQWKHMXGJPHQWRIWKH,QYHVWLJDWRUGXHWRDQ
HYHQW

3UHSODQQHGKRVSLWDOL]DWLRQVDUHQRWFRQVLGHUHG6$(VXQOHVVSURORQJHGGXHWRDQ
$(
x
3HUVLVWHQWRUVLJQLILFDQWGLVDELOLW\LQFDSDFLW\$Q$(WKDWUHVXOWVLQSHUVLVWHQWRU
VLJQLILFDQWGLVDELOLW\RUGLVUXSWLRQRIDSHUVRQ¶VDELOLW\WRFRQGXFWQRUPDOOLIH
IXQFWLRQV
x
&RQJHQLWDODQRPDO\ELUWKGHIHFW$FRQJHQLWDODQRPDO\ELUWKGHIHFWWKDWRFFXUVLQ
WKHRIIVSULQJRIDVXEMHFWH[SRVHGWRWKHVWXG\GUXJRUWKHSDUWQHURIDVXEMHFW
H[SRVHGWRWKHVWXG\GUXJ
,PSRUWDQWPHGLFDOHYHQW0HGLFDODQGVFLHQWLILFMXGJPHQWVKRXOGEHH[HUFLVHGLQGHFLGLQJ
ZKHWKHURWKHUVLWXDWLRQVVKRXOGEHFRQVLGHUHGVHULRXVVXFKDVLPSRUWDQWPHGLFDOHYHQWVWKDW

SRP-9001 
Protocol 
SRP-9001-101 (Amendment 8, Version 9) 
36 
CONFIDENTIAL 
 
 
might not be immediately life-threatening or result in death or hospitalization but might 
jeopardize the subject or might require intervention to prevent one of the other outcomes listed in 
the definition above. 
 
12.1.3. 
Overdose 
An overdose is defined as administration of a quantity of a medicinal product given that is above 
the maximum recommended dose according to the authorized product information. 
12.1.4. 
Medication Error 
A medication error is any preventable incident that may cause or lead to inappropriate study 
treatment use or subject harm while the study drug is in the control of the healthcare professional 
or, in certain cases, the subject. Such incidents may be due to healthcare professional practice, 
product labeling, packaging and preparation, procedures for administration, and systems, 
including the following: prescribing, order communication, dispensing, nomenclature, 
compounding, distribution, administration, education, monitoring, and use. 
 
12.1.5. 
Accidental/Occupational Exposure 
Accidental/occupational exposure is the unintentional exposure to a study treatment as a result of 
one’s professional or nonprofessional occupation, or accidental exposure to a nonprofessional to 
whom exposure was not intended (eg, study drug given to wrong subject). 
12.2. 
Collection of Adverse Events 
All AEs, regardless of the source of identification (eg, physical examination, laboratory 
assessment, ECG, reported by subject), must be collected and documented in the electronic case 
report form (eCRF). 
All AEs will be collected and recorded from the time of informed consent/assent through the last 
follow-up visit. 
All AEs and SAEs experienced by a subject, irrespective of the suspected causality, will be 
monitored until the AE or SAE has resolved, any abnormal laboratory values have returned to 
baseline or normal levels, the event has stabilized and there is a satisfactory explanation for the 
changes observed, the subject is lost to follow-up, or the subject has died. 
All AEs will be followed until the resolution of the AE, completion of the subject’s study 
participation, or study termination, whichever occurs first. All SAEs will be followed until 
resolution or until the condition stabilizes or returns to screening/baseline status. 
Concomitant illnesses that existed before entry into the study will not be considered AEs unless 
the illness worsens during the treatment period. Pre-existing conditions will be recorded in the 
eCRF, as well as on the SAE Report Form’s medical history section. 
For subjects who are found to be ineligible for the study during the pre-infusion period and are 
not enrolled (ie, screen failures), only SAEs (Section 12.1.2) will be reported (Section 12.5). 
If, at any time after the subject has completed participation in the study, the Investigator or study 
staff become aware of an SAE that the Investigator assesses as related to the study drug or 

SRP-9001 
Protocol 
SRP-9001-101 (Amendment 8, Version 9) 
37 
CONFIDENTIAL 
 
 
related to a study procedure (Section 12.3.1), then the event and any known details must be 
reported promptly to the Sponsor, no later than within 24 hours of awareness. 
 
12.2.1. 
Clinical Laboratory Abnormalities 
A laboratory abnormality deemed clinically significant by the Investigator should be recorded as 
an AE. Whenever possible, the underlying medical diagnosis (eg, anemia) should be recorded as 
the AE term. Repeated additional tests and/or other evaluations required to establish the 
significance and etiology of an abnormal result should be obtained when clinically indicated. 
 
12.3. 
Classification of Adverse Events 
All AEs, whether serious or nonserious, will be classified by the Investigator according to the 
following rules and definitions. 
 
12.3.1. 
Relationship to Study Agent, Study Procedures and the Subject’s Pre-existing 
Disease 
Association or relatedness to the study agent, study procedures and the subject 's pre-existing 
disease will be graded as follows: 5 = unrelated, 4 = unlikely, 3 = possibly, 2 = probably, and 
1 = definitely related. 
 
12.3.2. 
Severity of Adverse Events 
The Investigator will assess the severity of all AEs using the National Cancer Institute Common 
Terminology Criteria for Adverse Events (CTCAE) scale, Version 5.0. Events not listed in the 
CTCAE will be assessed according to the following scale. 
 
Grade 1: 
Mild, asymptomatic or mild symptoms, clinical or diagnostic observations 
only, intervention not indicated 
Grade 2: 
Moderate, minimal, local or noninvasive intervention indicated, limiting 
age-appropriate instrumental activities of daily living (ADL) 
Grade 3: 
Severe or medically significant but not immediately life-threatening, 
hospitalization or prolongation of hospitalization indicated, disabling, limiting 
self-care ADL 
Grade 4: 
With life-threatening consequences, urgent intervention indicated 
Grade 5: 
Death related to AE 
 
Note that severity is not the same as “seriousness,” which is defined in Section 12.1.2 and which 
serves as a guide for defining regulatory reporting obligations. 
In addition, laboratory or vital signs-based events that are defined as Grade 4 in the CTCAE 
solely by laboratory or vital sign measurements are not automatically clinically life-threatening; 
the Investigator must make this clinical assessment regardless of grade. 

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/

2XWFRPHVRI$GYHUVH(YHQWV
³2XWFRPH´GHVFULEHVWKHVWDWXVRIWKH$(7KH,QYHVWLJDWRUZLOOSURYLGHLQIRUPDWLRQUHJDUGLQJ
WKHVXEMHFWRXWFRPHIRUHDFK$(2XWFRPHFDWHJRULHVZLOOLQFOXGH³UHFRYHUHG´³UHFRYHUHGZLWK
VHTXHODH´³QRWUHFRYHUHG´³IDWDO´DQG³XQNQRZQ´

$FWLRQ7DNHQ5HJDUGLQJWKH6WXG\'UXJ
7KH,QYHVWLJDWRUZLOOSURYLGHLQIRUPDWLRQUHJDUGLQJWKHDFWLRQWDNHQZLWKUHVSHFWWRWKHVWXG\
WUHDWPHQWLQUHVSRQVHWRWKH$(&DWHJRULHVIRUDFWLRQWDNHQUHJDUGLQJVWXG\WUHDWPHQWZLOO
LQFOXGH³QRQH´³GUXJLQWHUUXSWHG´³GUXJZLWKGUDZQ´DQG³QRWDSSOLFDEOH´

([SHFWHGQHVVRI$GYHUVH(YHQWV
7KHH[SHFWHGQHVVRIDOO$(VZLOOEHGHWHUPLQHGE\WKH6SRQVRUDFFRUGLQJWRWKHPRVWUHFHQW
YHUVLRQRIWKH,QYHVWLJDWRU¶V%URFKXUHIRU653

5HFRUGLQJ$GYHUVH(YHQWV
$OO$(VIURPWKHWLPHRISURYLGLQJVLJQHGLQIRUPHGFRQVHQWDVVHQWWKURXJKWKHODVWIROORZXS
YLVLWZLOOEHUHFRUGHGLQHDFKHQUROOHGVXEMHFW¶VH&5)$OO6$(VDQGRWKHUVDIHW\LQIRUPDWLRQ
VXFKDVWKDWSHUWDLQLQJWRVSHFLDOVLWXDWLRQV6HFWLRQZLOODOVREHUHFRUGHGRQWKH&OLQLFDO
7ULDO6DIHW\5HSRUWLQJ)RUPDQGUHSRUWHGWRWKH6SRQVRUYLDHPDLOWR
ZLWKLQ
KRXUVRIDZDUHQHVV
,QIRUPDWLRQUHFRUGHGVKRXOGLQFOXGHWKHIROORZLQJDFRQFLVHGHVFULSWLRQRIWKHHYHQWGDWHRI
HYHQWRQVHWDQGUHVROXWLRQGHWHUPLQDWLRQRIVHULRXVQHVVVHYHULW\FRUUHFWLYHWUHDWPHQWRXWFRPH
DQGUHODWLRQVKLSWRVWXG\GUXJVWXG\SURFHGXUHDQGXQGHUO\LQJGLVHDVHDQGDQ\DFWLRQWDNHQ
5HVROXWLRQRFFXUVZKHQWKHVXEMHFWKDVUHWXUQHGWRWKHEDVHOLQHVWDWHRIKHDOWKRUZKHQIXUWKHU
LPSURYHPHQWRUZRUVHQLQJRIWKHHYHQWLVQRWH[SHFWHG
:KHQHYHUSRVVLEOHDGLDJQRVLVZLOOEHUHFRUGHGDVDQ$(UDWKHUWKDQV\PSWRPVRULVRODWHG
ODERUDWRU\DEQRUPDOLWLHVUHODWHGWRWKDWGLDJQRVLV6HYHUDOV\PSWRPVRUODERUDWRU\UHVXOWVWKDWDUH
DVVRFLDWHGZLWKWKHVDPHGLDJQRVLVFDQWKXVEHSDUWRIWKHVDPH$($PHGLFDORUVXUJLFDO
SURFHGXUHLVQRWDQ$(UDWKHUWKHFRQGLWLRQOHDGLQJWRWKHSURFHGXUHVKRXOGEHUHFRUGHGDVWKH
$(
6LPLODUO\GHDWKLVQRWDQ$(EXWUDWKHUWKHRXWFRPHRIWKH$(VWKDWUHVXOWHGLQGHDWK,IWKH
$(VOHDGLQJWRGHDWKDUHQRWNQRZQWKHQ³GHDWK´PXVWEHUHSRUWHGDVDQ$($OOFDXVHVRI
GHDWKDUH6$(V,QWKHHYHQWRIGHDWKHYHU\HIIRUWVKRXOGEHPDGHWRREWDLQDGHDWKFHUWLILFDWH
DQGLISRVVLEOHDQDXWRSV\UHSRUW,IWKHFDXVHRIGHDWKLVXQNQRZQGHDWKZLOOEHUHFRUGHGDVWKH
HYHQW
$Q\6$(DVVHVVHGDVUHODWHGWRWKHVWXG\GUXJRFFXUULQJDIWHUWKHVXEMHFWFRPSOHWHVWKHVWXG\
VKRXOGEHUHFRUGHGRQD&OLQLFDO7ULDO6DIHW\5HSRUWLQJ)RUPDQGUHSRUWHGDVSHUWKHLQVWUXFWLRQV
IRU6$(VSURYLGHGLPPHGLDWHO\EHORZ
PPD

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/

5HSRUWLQJ6HULRXV$GYHUVH(YHQWV

6HULRXV$GYHUVH(YHQWV

6XVSHFWHG8QH[SHFWHG6HULRXV$GYHUVH5HDFWLRQV686$5V
$OO686$5VZLOOEHKDQGOHGE\DSSURSULDWH6SRQVRURUGHVLJQHHSHUVRQQHODQGUHSRUWHGZLWKLQ
WKHUHTXLUHGWLPHOLQHVLQDQXQEOLQGHGIDVKLRQWRUHJXODWRU\DXWKRULWLHVDQGWKH,5%SHUWKH
UHTXLUHPHQWVRIWKHFRQFHUQHGFRPSHWHQWDXWKRULWLHV

5HSRUWLQJ6SHFLDO6LWXDWLRQV

2YHUGRVH
$QRYHUGRVHLVQRWDQ$($QRYHUGRVHZLOOEHUHSRUWHGHYHQLILWGRHVQRWUHVXOWLQDQ$($Q
RYHUGRVHZLOOEHUHFRUGHGRQWKHDSSURSULDWHIRUPDQGVHQWWRWKH6SRQVRURUGHVLJQHHZLWKLQ
KRXUV

0HGLFDWLRQ(UURU
$Q\PHGLFDWLRQHUURULVWREHUHSRUWHGWRWKH6SRQVRURQWKH&OLQLFDO7ULDO6DIHW\5HSRUWLQJ
)RUPVHQWYLDHPDLOWR
ZLWKLQKRXUVRIEHFRPLQJDZDUHDFFRUGLQJWRWKH
SURFHVVIRUUHSRUWLQJ6$(V6HFWLRQ

$FFLGHQWDO2FFXSDWLRQDO([SRVXUH
$Q\DFFLGHQWDORFFXSDWLRQDOH[SRVXUHLVWREHUHSRUWHGWRWKH6SRQVRURQWKH&OLQLFDO7ULDO
6DIHW\ 5HSRUWLQJ )RUP VHQW YLD HPDLO WR
 ZLWKLQ  KRXUV RI
EHFRPLQJDZDUHDFFRUGLQJWRWKHSURFHVVIRUUHSRUWLQJ6$(V6HFWLRQ

0LVFHOODQHRXV

5HVSRQVLELOLWLHVRIWKH,QYHVWLJDWRU
7KHUHVSRQVLELOLWLHVRIWKH,QYHVWLJDWRULQFOXGHEXWDUHQRWOLPLWHGWRWKHIROORZLQJ
x
0RQLWRULQJDQGUHFRUGLQJDOO$(V
x
'HWHUPLQLQJWKHVHULRXVQHVVVHYHULW\DQGUHODWLRQVKLSWRVWXG\GUXJVWXG\
SURFHGXUHDQGXQGHUO\LQJGLVHDVHIRUHDFK$(
x
'HWHUPLQLQJWKHRQVHWDQGHQGGDWHRIHDFKHYHQW
x
3URYLGLQJWKHLQLWLDOUHSRUWRIDOO6$(VDQGVSHFLDOVLWXDWLRQVWRWKH6SRQVRUYLDHPDLO
WR
RUGHVLJQHHZLWKLQKRXUVRIILUVWNQRZOHGJH
x
3URYLGLQJIROORZXSLQIRUPDWLRQRQ6$(VLQDWLPHO\DQGSURDFWLYHPDQQHU
7KH,QYHVWLJDWRUPXVWUHSRUWDOO6$(VYLDHPDLOWR
ZLWKLQKRXUVRI
EHFRPLQJDZDUHRIWKHLQLWLDO6$(RUDQ\IROORZXSLQIRUPDWLRQUHJDUGLQJWKH6$(DVSHUWKH
LQIRUPDWLRQSULQWHGRQWKH&OLQLFDO7ULDO6DIHW\5HSRUWLQJ)RUPDQGLQWKH6$(&RPSOHWLRQ
JXLGHOLQH
PPD
PPD
PPD
PPD

SRP-9001 
Protocol 
SRP-9001-101 (Amendment 8, Version 9) 
40 
CONFIDENTIAL 
•
Responding to queries regarding AEs and SAEs in a timely manner
•
Ensuring that source documentation for all AEs is accurate and complete
•
Ensuring that the study is conducted as defined in this protocol and according to
applicable regulations and guidelines
Investigators may also report improvement of pre-existing DMD conditions or unexpected 
therapeutic responses. 
12.7.2. 
Responsibilities of the Sponsor 
The responsibilities of the Sponsor include, but are not limited to, the following: 
•
Training of Investigator on AE/SAE definitions, safety assessments, and site
obligations related to safety monitoring and reporting of AEs/SAEs
•
Training with regard to the accurate and legal reporting of SAEs to all applicable
regulatory authorities, IRBs, clinical study sites, and other parties, as appropriate and
required within the regulated timing
•
Ensuring accurate recording of AEs and SAEs
•
Submission of expedited serious, unexpected, and related AEs to regulatory
authorities per regulatory requirements
•
Notification of blinded unexpected and related SAEs to sites
•
Annual safety reporting to regulatory authorities and IRB according to regional
requirements

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/

67$7,67,&6
7KLVLVD3KDVH,,,DVWXG\ZLWKVDIHW\DVWKHSULPDU\PHDVXUH%D\OH\,,,SUHDQGSRVWJHQH
WUDQVIHUZLOOEHWKHSULPDU\PRWRURXWFRPHIRU&RKRUW$7KHPZLOOEHDSULPDU\PRWRU
RXWFRPH

7KHPZLOOEHWKHSULPDU\PRWRURXWFRPHIRU&RKRUW%


$VWKHVDPSOHVL]HLV
VPDOODQGWKHPRWRURXWFRPHVZLOOGLIIHUEHWZHHQFRKRUWVDVZHOODVRYHUWLPHIRUVRPHVXEMHFWV
ZLWKLQ&RKRUW$DOODQDO\VHVZLOOEHGHVFULSWLYHLQQDWXUHDQGZLOOQRWHPSOR\LQIHUHQWLDO
VWDWLVWLFV
3HULRGLFVDIHW\DQGHIILFDF\DQDO\VHVDUHSHUIRUPHGIRUVDIHW\PRQLWRULQJUHYLHZV,QYHVWLJDWRU¶V
%URFKXUHXSGDWHUHJXODWRU\VXEPLVVLRQVVXFKDV'HYHORSPHQW6DIHW\8SGDWH5HSRUWDQG
UHJXODWRU\PHHWLQJEULHILQJGRFXPHQWVDQGVFLHQWLILFGLVFORVXUHV7KHVHSHULRGLFDQDO\VHVDUH
GHVFULEHGLQVHSDUDWHGRFXPHQWV
CCI
CCI

SRP-9001 
Protocol 
SRP-9001-101 (Amendment 8, Version 9) 
42 
CONFIDENTIAL 
 
 
14. 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS 
14.1. 
Regulatory and Ethical Considerations 
The study will be monitored in compliance with the relevant parts of 21 CFR and according to 
the International Council for Harmonisation (ICH) Good Clinical Practices Guidelines. The 
procedures outlined in the protocol and case report forms will be carefully reviewed by the PI 
and staff prior to study initiation to ensure appropriate interpretation and implementation. No 
deviations from the protocol shall be made except in emergency situations where alternative 
treatment is necessary for the protection, proper care and wellbeing of subjects. 
Amendments will be submitted to the NCH IRB for their review and approval prior to 
implementation. When an amendment to a protocol substantially alters the study design or 
increases potential risk to the study subject, the Informed Consent Form will be revised and if 
applicable, subject 's consent to continue participation will again be obtained. 
14.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow Sarepta to submit complete and accurate financial certification 
or disclosure statements to the appropriate regulatory authorities. Investigators are responsible 
for providing information on financial interests during the course of the study and for 1 year after 
completion of the study. 
 
14.3. 
Informed Consent 
Legally effective and properly executed written informed consent, in compliance with 21 CFR 
50 and the ICH guidelines, will be obtained from each subject before the subject is entered into 
the study or before any unusual or non-routine procedure is performed that involves risk to the 
subject. The informed consent will be signed prior to study procedures and will require IRB 
approval. Attention will be directed to the basic elements that are required for incorporation into 
the informed consent under US Federal Regulations for Protection of Human Patients [21CFR 
50.25(a)]. The final IRB-approved document as well as any subsequent approved modified 
consent document(s) must be provided to correspondent agencies for regulatory purposes. If new 
information related to the study arises, subjects will be asked to sign a revised document. Signed 
consent forms will remain in each subject's research chart and will be available for verification 
by study monitors at any time. Subjects will be given a signed, dated copy of their consent form. 
 
14.4. 
Data Management and Study Forms 
All subjects will be given a unique sequentially assigned subject number. Subjects will be 
identified by number only to protect identity. 
All data and observations will be documented on electronic CRFs from source documentation. A 
Study Monitor will have access to the data to monitor adherence to the protocol and to applicable 
FDA regulations, and the maintenance of adequate and accurate clinical records. An electronic 
CRF will be completed for every subject that was registered for participation in the study. Case 

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/


UHSRUWIRUPVZLOOEHFRPSOHWHGDVLQIRUPDWLRQEHFRPHVDYDLODEOHRUZLWKLQGD\VRID6WXG\
9LVLW
&DVH5HSRUW)RUPVZLOOEHUHYLHZHGLQGHWDLOE\WKHVWXG\PRQLWRURQDUHJXODUEDVLVIRUZKLFK
WKHVWXG\PRQLWRUZLOOKDYHDFFHVVWRVXEMHFWPHGLFDOUHFRUGVODERUDWRU\GDWDDQGRWKHUVRXUFH
GRFXPHQWDWLRQ7KHVWXG\PRQLWRUZLOOPDNHDGHFLVLRQDVWRZKHWKHUWKHGDWDDUHDFFHSWDEOH,I
HUURUVRURPLVVLRQVDUHIRXQGLQWKHFRXUVHRIDGDWDDXGLWRULIFODULILFDWLRQRIGDWDLVUHTXLUHG
WKHH&5)LQTXHVWLRQZLOOEHTXHULHG
7KH,QYHVWLJDWRUZLOOVLJQWKHH&5)V7KLVVLJQDWXUHZLOOLQGLFDWHWKDWWKRURXJKLQVSHFWLRQRIWKH
GDWDWKHUHLQKDVEHHQPDGHDQGZLOOWKHUHE\FHUWLI\WKHFRQWHQWVRIWKHIRUP
$QH[WHUQDO&RQWUDFW5HVHDUFK2UJDQL]DWLRQZLOODOVRPRQLWRUWKHVWXG\LQDUHJXODUEDVLVWR
PDNHVXUHWKHVWXG\LVFRQGXFWHGLQFRPSOLDQFHZLWKDOOUHJXODWRU\DVSHFWVRIWKHSURWRFRO

3XEOLFDWLRQ3ROLF\

6WXG\5HSRUWV


)LQDO6WXG\5HSRUW
7KHILQDOVWXG\UHSRUWZLOOLQFOXGHGDWDWKURXJKWKHILQDOVWXG\YLVLWWKURXJK<HDU


$QQXDO6WXG\ 5HSRUWV
:LWKLQGD\VDIWHUWKH\HDUDQQLYHUVDU\RIWKHGDWHRQZKLFKWKH,1'DSSOLFDWLRQZHQWLQWR
HIIHFWDQGDIWHUHDFKVXEVHTXHQWDQQLYHUVDU\XQWLOWKHVWXG\LVFRPSOHWHGWKH6SRQVRUZLOO
VXEPLWLQIRUPDWLRQWRWKH)'$VHWIRUWKDVIROORZV
D
&OLQLFDO7ULDO,QIRUPDWLRQ

7KLVZLOOEHDEULHIVXPPDU\RIWKHVWDWXVRIWKHVWXG\LQSURJUHVVRUFRPSOHWHG
GXULQJWKHSUHYLRXV\HDU7KHVXPPDU\ZLOOLQFOXGHWKHIROORZLQJLQIRUPDWLRQIRU
WKHVWXG\WKHWLWOHDQGSXUSRVHRIWKHVWXG\FOLQLFDOVLWHVWKH
LQYHVWLJDWRUVFOLQLFDOSURWRFROLGHQWLILHUVLQFOXGLQJWKH1&+,5%DQG,%&6&
SURWRFROQXPEHUVDQGWKH)'$,1'DSSOLFDWLRQQXPEHUSDUWLFLSDQW
SRSXODWLRQVXFKDVGLVHDVHLQGLFDWLRQDQGJHQHUDODJHJURXSWKHWRWDO
QXPEHURISDUWLFLSDQWVSODQQHGIRULQFOXVLRQLQWKHVWXG\WKHQXPEHUHQWHUHGLQWR
WKHVWXG\WRGDWHWKHQXPEHUZKRVHSDUWLFLSDWLRQLQWKHVWXG\ZDVFRPSOHWHGDQG
WKHQXPEHUZKRGURSSHGRXWRIWKHVWXG\ZLWKDEULHIGHVFULSWLRQRIWKHUHDVRQV
WKHVWDWXVRIWKHVWXG\HJRSHQWRDFFUXDORIVXEMHFWVFORVHGEXWGDWD
FROOHFWLRQRQJRLQJRUIXOO\FRPSOHWHGDQGLIWKHVWXG\KDVEHHQFRPSOHWHGD
EULHIGHVFULSWLRQRIDQ\VWXG\UHVXOWV
E 3URJUHVV5HSRUWDQG'DWD$QDO\VLV

,QIRUPDWLRQREWDLQHGGXULQJWKHSUHYLRXV\HDU
VFOLQLFDODQGQRQFOLQLFDO
LQYHVWLJDWLRQVLQFOXGLQJDQDUUDWLYHRUWDEXODUVXPPDU\VKRZLQJWKHPRVW
IUHTXHQWDQGPRVWVHULRXVDGYHUVHH[SHULHQFHVE\ERG\V\VWHPDVXPPDU\RI
DOO6$(VVXEPLWWHGGXULQJWKHSDVW\HDUDVXPPDU\RI6$(VWKDWZHUH
H[SHFWHGRUFRQVLGHUHGWRKDYHFDXVHVQRWDVVRFLDWHGZLWKWKHXVHRIWKHJHQH

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/


WUDQVIHUSURGXFWVXFKDVGLVHDVHSURJUHVVLRQRUFRQFXUUHQWPHGLFDWLRQVLIDQ\
GHDWKVKDYHRFFXUUHGWKHQXPEHURISDUWLFLSDQWVZKRGLHGGXULQJSDUWLFLSDWLRQLQ
WKHLQYHVWLJDWLRQDQGFDXVHVRIGHDWKDQGDEULHIGHVFULSWLRQRIDQ\
LQIRUPDWLRQREWDLQHGWKDWLVSHUWLQHQWWRDQXQGHUVWDQGLQJRIWKHJHQHWUDQVIHU
SURGXFW¶VDFWLRQLQFOXGLQJIRUH[DPSOHLQIRUPDWLRQDERXWGRVHUHVSRQVH
LQIRUPDWLRQIURPFRQWUROOHGVWXGLHVDQGLQIRUPDWLRQDERXWELRDYDLODELOLW\
F
$FRS\RIWKHXSGDWHGFOLQLFDOSURWRFROLQFOXGLQJDWHFKQLFDODQGQRQWHFKQLFDO
DEVWUDFW

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/



/,672)5()(5(1&(6

%URRNH0+)HQLFKHO*0*ULJJV5&HWDO&OLQLFDOLQYHVWLJDWLRQLQ'XFKHQQHG\VWURSK\
'HWHUPLQDWLRQRIWKHSRZHURIWKHUDSHXWLFWULDOVEDVHGRQWKHQDWXUDOKLVWRU\0XVFOH1HUYH

&RQQROO\$0)ORUHQFH-0&UDGRFN00HWDO0RWRUDQGFRJQLWLYHDVVHVVPHQWRILQIDQWVDQG
\RXQJER\VZLWK'XFKHQQHPXVFXODUG\VWURSK\UHVXOWVIURPWKH0XVFXODU'\VWURSK\
$VVRFLDWLRQ'0'&OLQLFDO5HVHDUFK1HWZRUN1HXURPXVFXO'LVRUG
'HQW.0'XQQ'0YRQ1HLGHUKDXVHUQ$&HWDO,PSURYHGPROHFXODUGLDJQRVLVRI
G\VWURSKLQRSDWKLHVLQDQXQVHOHFWHGFOLQLFDOFRKRUW$P-0HG*HQHW$
(DJOH0%DXGRXLQ69&KDQGOHU&HWDO6XUYLYDOLQ'XFKHQQHPXVFXODUG\VWURSK\
LPSURYHPHQWVLQOLIHH[SHFWDQF\VLQFHDQGWKHLPSDFWRIKRPHQRFWXUQDOYHQWLODWLRQ
1HXURPXVFXO'LVRUG
)ODQLJDQ.0YRQ1LHGHUKDXVHUQ$'XQQ'0HWDO5DSLGGLUHFWVHTXHQFHDQDO\VLVRIWKH
G\VWURSKLQJHQH$P-+XP*HQHW(SXE0DU

.RHQLJ0HWDO&RPSOHWHFORQLQJRIWKH'XFKHQQHPXVFXODUG\VWURSK\'0'F'1$DQG
SUHOLPLQDU\JHQRPLFRUJDQL]DWLRQRIWKH'0'JHQHLQQRUPDODQGDIIHFWHGLQGLYLGXDOV&HOO
GRL>SLL@
0HQGHOO-55RGLQR.ODSDF/55RVDOHV4XLQWHUR;HWDO/LPEJLUGOHPXVFXODUG\VWURSK\W\SH
'JHQHWKHUDS\UHVWRUHVDOSKDVDUFRJO\FDQDQGDVVRFLDWHGSURWHLQV$QQ1HXURO
0HQGHOO-5&DPSEHOO.5RGLQR.ODSDF/HWDO'\VWURSKLQLPPXQLW\LQ'XFKHQQH
VPXVFXODU
G\VWURSK\1(QJO-0HG
0HQGHOO-56KLOOLQJ&/HVOLH1'HWDO(YLGHQFHEDVHGSDWKWRQHZERUQVFUHHQLQJIRU
'XFKHQQHPXVFXODUG\VWURSK\$QQ1HXURO
0HQGHOO-55RGLQR.ODSDF/56DKHQN=HWDO(WHSOLUVHQIRUWKHWUHDWPHQWRI'XFKHQQH
PXVFXODUG\VWURSK\$QQ1HXURO
0HQGHOO-56DKHQN=0DOLN9HWDO$SKDVHDIROOLVWDWLQJHQHWKHUDS\WULDOIRU%HFNHU
PXVFXODUG\VWURSK\0RO7KHU
0HQGHOO-5$O=DLG\66KHOO5HWDO*HQH7KHUDS\IRU6SLQDO0XVFXODU$WURSK\7\SH
6KRZV3RWHQWLDOWR,PSURYH6XUYLYDODQG0RWRU)XQFWLRQDO2XWFRPHV0RO7KHU6
0HQGHOO-56DKHQN=$O=DLG\6HWDO)ROOLVWDWLQ*HQH7KHUDS\IRU6SRUDGLF,QFOXVLRQ%RG\
0\RVLWLV,PSURYHV)XQFWLRQDO2XWFRPHV0RO7KHU
0HQGHOO-5$O=DLG\66KHOO5HWDO6LQJOH'RVH*HQH5HSODFHPHQW7KHUDS\IRU6SLQDO
0XVFXODU$WURSK\1(QJO-0HG
CCI
CCI

653
3URWRFRO
653$PHQGPHQW9HUVLRQ

&21),'(17,$/


3DOPHLUD34XLQHOOR&6LOYHLUD/HVVD$/HWDO,J*SODFHQWDOWUDQVIHULQKHDOWK\DQG
SDWKRORJLFDOSUHJQDQFLHV&OLQ'HY,PPXQRO(SXE2FW
5RVDOHV;46KLOOLQJ&:DOO&HWDO)LGHOLW\RI6HUXP*DPPDJOXWDP\OWUDQVIHUDVHLQ
GLIIHUHQWLDWLQJVNHOHWDOPXVFOHIURPOLYHUGLVHDVHLQ'XFKHQQHPXVFXODUG\VWURSK\-&KLOG
1HXURO
7DUQRSROVN\0$3HDUFH(6PLWK.HWDO6XFWLRQPRGLILHG%HUJVWURPPXVFOHELRSV\
WHFKQLTXHH[SHULHQFHZLWKSURFHGXUHV0XVFOH1HUYH

CCI



Signature: 
Email: 
Title: 
Company: 
PPD