A Phase II Open-label, Multicenter Extension Study to Assess the Long-term Safety and Efficacy of Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy
Sponsor: ReveraGen BioPharma, Inc.

 
 
 
 
P a ge 1 of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
R E VI S E D  C LI NI C A L S T U D Y P R O T O C O L 
 
D oc u me nt Title:  
Re vis e d Cli nic al Pr ot o c ol # 2 f or a P h ase II O pe n-l a bel, 
 
M ultice nter E xte nsi o n St u d y t o Assess t he L o n g-ter m S afet y 
 
a n d  Effic ac y of V a m or ol o ne in B o ys wit h D uc he n ne M usc ul ar 
 
D ystr o p h y ( D M D ) 
 
Pr ot oc ol N u m be r:  
V B P 1 5- 0 0 3 
D oc u me nt N u m ber:   
V B P 1 5- 0 0 3- R 2 
 
F D A I N D N o.:  
 
1 1 8, 9 4 2 
 
I n vesti g ati o n al Pr o d uct:  
Va m or ol o ne  ( V B P 1 5) 
 
 
S p o ns or: 
 
Re vera Ge n Bi o P har ma, I nc.  
  
1 5 5 Gi b bs Street 
S uite 4 3 3 
R oc k ville, M D. 2 0 8 5 0 
 
St u d y C h air:   
 
Pa ula R. Cle me ns, M D 
  
  
  
  
P h o ne: ( 4 1 2) 3 8 3- 7 2 0 7 
  
 
  
  
E mail: cle m pr @ u p mc.e d u 
 
Me dic al M o nit or:  
 
Be nja mi n D. Sc h wartz, M. D., P h. D. 
 
  
P h o ne: ( 3 1 4) 2 2 0- 7 0 6 7 
 
  
E mail: b dsc h w @ca m de n gr o u p.c o m 
 
 
D oc u me nt D ate:  
 
2 2 Fe br u ar y 2 0 1 7 
 
 
T hi s d oc u me nt re prese nts pr o priet ar y i nf or m ati o n bel o n gi n g t o 
Re ver a Ge n Bi o P h ar m a, I nc.  
U n a ut h orize d re pr o d ucti o n of t he w h ole or p art of t he d oc u me nt b y a n y me a ns is strictl y pr o hi bite d.  
T his pr ot oc ol is pr o vi de d t o y o u as a Pri nci p al I n vesti g at or, p ote nti al I n vesti g at or or c o ns ult a nt f or 
re vie w b y y o u, y o ur st aff a n d I nstit uti o n al Re vie w B o ar d or I n de pe n de nt Et hics C o m mittee .  T he 
i nf or m ati o n c o nt ai ne d i n t his d oc u me nt is pri vile ge d a n d c o nfi de nti al a n d, e xce pt t o t he e xte nt 
necess ar y t o o bt ai n i nf or me d c o nse nt, m ust n ot be discl ose d u nless s uc h discl os ure is re q uire d b y 
fe der al or st ate l a w or re g ul ati o ns.  Pers o ns t o w h o m t he i nf or m ati o n is discl ose d i n c o nfi de nce m ust be 
i nf or me d t h at t he i nf or m ati o n is c o nfi de nti al a n d m ust n ot be discl ose d b y t he m t o a t hir d p art y. 

Va m or ol o ne 
Re vise d Cli nical Pr ot oc ol # 2 
Pr ot oc ol N o. V B Pl 5- 0 0 3 
2 2 Fe br uar y 2 0 1 7 
D o c u m e nt N o. V B P 1 5- 0 0 3- R 2 
I N D 1 1 8. 9 4 2 
SI G N A T U R E S O F A G R E E M E N T F O R V B PI S- 0 0 3- Rl 
Re vise d Cli ni c al Pr ot o c ol # 2 f or a P h as e II O p e n-l a b el, M ulti c e nt er E xt e nsi o n St u d y 
t o Assess t h e L o n g-t er m S af et y a n d Efficac y of V a m or ol o n e i n B o ys wit h D u c h e n n e 
M us c ul ar D ystr o p h y ( D M D) 
Re vie we d a n d A p pr o v e d b y: 
Eric H off ma n, P h. D. 
C hief E xec uti ve Officer 
Re vera Ge n Bi o P har ma, I nc. 
Pa ula R. Cle me ns, M. D. 
St u d y C hair 
U ni versit y of Pitts b ur g h Sc h o ol of Me dici ne 
C o ns ulti n g Me dical M o nit or 
T he Ca m de n Gr o u p, L L C 
La urel J. Me n gle- Ga w, P h. D. 
C o ns ulti n g Cli nical M o nit or 
T he Ca m de n Gr o u p .. L L C 
A vital C naa n, P h. D. 
T Ri N D S, L L C 
2 5 F e br u ar y 2 0 1 7 
Date 
2 4 Fe br uar y 2 0 1 7 
Date 
2 4 F e br u ar y 2 0 1 7 
Date 
2 M ar c h 
2 0 1 7 
Date 
Re vera Ge n Bi o P ha n na. I nc. - C O N FI D E N TI A L 
Pa ge 2 of 1 3 7 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 3 of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
I N V E S TI G A T O R R E VI S E D P R O T O C O L A G R E E M E N T 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Re vise d Cli nic al Pr ot o c ol # 2 f or a P h ase II O pe n-l a bel, M ultice nter E xte nsi o n St u d y 
t o Assess the L o n g-ter m S afet y a n d Effic ac y of V a m or ol o ne i n B o ys wit h D uc he n ne 
M usc ul ar D ystr o p h y ( D M D) 
Pr ot oc ol N u m ber:    
V B P 1 5- 0 0 3 
D oc u me nt N u m ber:    
V B P 1 5- 0 0 3- R 2 
S p o ns or: 
Re ver a Ge n Bi o P h ar m a, I nc. 
D oc u me nt D ate:  
2 2 Fe br u a r y 2 0 1 7 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
By m y si g n at ure, I c o nfir m t h at m y st aff a n d I h ave c ar ef ully re a d a n d u n derst a n d t his 
pr ot oc ol, pr ot oc ol a m e n d m e nt, a m e n de d pr ot oc ol, or revise d pr ot oc ol a n d a gree t o 
c o m ply wit h t he c o n d uct a n d ter ms of t he st u dy s pecifie d herei n a n d wit h a ny ot her 
st u dy c o n d uct pr oce d ures pr ovi de d by Rever a Ge n Bi o P h ar m a, I nc.  
I a gree t o c o n d uct t he st u dy acc or di n g t o t his pr ot oc ol a n d t he o bli g ati o ns a n d 
re q uire m e nts of cli nic al I nvesti g at ors a n d all ot her re q uire m e nts liste d i n 2 1 C F R p art 
3 1 2 a n d all a p plic a ble l oc al, st ate, a n d fe der al re g ul ati o ns a n d I C H g ui deli nes.  I will 
n ot i niti ate t his st u dy wit h o ut t he a p pr ov al of a n I nstit uti o n al Revie w B o ar d (I R B ) or 
I n de pe n de nt Et hics C o m mittee (I E C). 
I un derst a n d t h at, s h o ul d t he decisi o n be m a de by Rever a Ge n Bi o P h ar m a, I nc. t o 
ter min ate pre m at urely or s us pe n d t he st u dy at a ny ti m e f or w h atever re as o n, s uc h 
decisi o n will be c o m m u nic ate d t o m e i n writi n g.  C o nversely, s h o ul d I deci de t o 
wit h dr a w fr o m e xec uti o n of t he st u dy, I will c o m m u nic ate i m m e di ately s uc h decisi o n i n 
writi n g t o Rever a Ge n Bi o P h ar m a, I nc. 
F or pr ot oc ol a m e n d m e nts a n d a m e n de d pr ot oc ols, I a gree n ot t o i m ple m e nt t he 
a m e n d m e nt 
wit h o ut 
a gree m e nt fr o m 
Rever a Ge n 
Bi o P h ar m a, I nc. 
a n d pri or 
s u bmissi o n t o a n d writte n a p pr ov al ( w here re q uire d) fr o m t he I R B/I E C, e xce pt w he n 
necess ary t o eli mi n ate a n i m m e di ate h az ar d t o t he s u bjects, or f or a d mi nistr ative 
as pects of t he st u dy ( w here per mitte d by all a p plic a ble re g ul at ory re q uire m e nts). 
 
 
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I n v esti gat or’s Si g n at ure   
  
  
  
  
Date  
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
I n v esti gat or’s N a me ( Ple ase pri nt)  
A d dress ( Pleas e pri nt): 
 
R E T U R N T H E O RI GI N A L SI G N E D C O P Y T O R E V E R A G E N BI O P H A R M A, I N C. O R 
D E SI G N E E A N D K E E P A X E R O X C O P Y A T Y O U R SI T E. 
 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 4 of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
S E RI O U S A D V E R S E E V E N T C O N T A C T I N F O R M A TI O N 
I n t he e ve nt of a seri o us a d verse e ve nt ( S A E) (see Secti o n 7. 2. 6. 1 ), t he I n vesti g at or 
wil l c o m plete t he S A E electr o nic c ase re p ort f o r m wit hi n 2 4 h o urs of first a w are ness 
of t he e ve nt.  I n t he u nli kel y e ve nt t h at t he electr o nic st u d y d at a b ase is i n accessi ble 
a n d t he I n vesti g at or is u n a ble t o c o m plet e t he S A E electr o nic c as e re p ort f or m 
wit hi n 2 4 h o urs, t he S A E N otific ati o n F or m ( p df) s h o ul d be c o m plete d a n d e m aile d 
or pri nte d/f a xe d t o t he P R A s afet y m a n a ge me nt te a m wit hi n 2 4 h o urs, usi n g t he 
c o nt act i nf or m ati o n bel o w :  
E m ail C H O S afet y @ pr a hs.c o m 
Dr u g S afet y F a x: 1- 8 8 8- 7 7 2- 6 9 1 9 or 1- 4 3 4- 9 5 1- 3 4 8 2 
  
S A E Q uesti o ns: Dr u g S afet y H otli ne: 1- 8 0 0- 7 7 2- 2 2 1 5 or 1 - 4 3 4- 9 5 1- 3 4 8 9 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 5 of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
P R O T O C O L A M E N D M E N T T R A C KI N G 
D oc u me nt  
D oc u me nt N u m ber  
A p pr o v al D ate  
Ori gi nal Pr ot oc ol  
V B P 1 5 -0 0 3  
0 7 Marc h 2 0 1 6  
A me n de d Pr ot oc ol # 1  
V B P 1 5 -0 0 3 -A 1  
3 1  Ma y  2 0 1 6  
Re vise d Pr ot oc ol # 1  
V B P 1 5 -0 0 3 -R 1  
0 1 A u g ust 2 0 1 6  
A me n de d Pr ot oc ol # 2  
V B P 1 5 -0 0 3 -A 2  
2 1 Fe br u ar y 2 0 1 7  
Re vise d Pr ot oc ol # 2  
V B P 1 5 -0 0 3 -R 2  
2 2 Fe br u ar y 2 0 1 7  
N ote: A me n de d pr ot oc ols s h o w all c h a n ges fr o m pre vi o us versi o n i n 
b ol d/stri ke-t hr o u g h f or m at. 
Re as o n f or Re vise d Pr ot oc ol # 2: 
1.  t o i nc or p orate all c ha n ges fr o m A me n de d Pr ot oc ol # 2 i nt o a ne w pr ot oc ol 
d oc u me nt. 
Re as o n s f or A me n de d Pr ot oc ol # 2: 
1.  t o u p date t he n o ncli nical t o xic ol o g y i nf or mati o n wit h res ults of a 2 6- wee k 
t o xic ol o g y st u d y i n mice; 
2.  t o u p date t he st u d y me di cati o n dis pe nsi n g sc he d ule t o reflect a 1 2- wee k s u p pl y t o 
be dis pe nse d at e ac h Treat me nt Peri o d dis pe nsi n g visit;  
3.  t o re m o ve t he re q uire me nt t hat Q Tc m ust be calc ulate d usi n g Fre d ericia’s 
f or m ula;  
4.  t o clarif y t he r ole of t he D S M B i n s afet y dat a re vi e w, i ncl u di n g re m o val of t he 
req uire me nt t hat S A E i nf or mati o n be f or war de d t o t he D S M B wit hi n 2 4 h o urs of 
first a ware ness; 
5.  t o u p date t he bl o o d v ol u mes re q uire d f or cli nical la b orat or y a n d P D bi o mar ker 
a nal ysis; a n d 
6.  t o c orrect t y p o gra p hical err ors. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 6 of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
S T U D Y S Y N O P SI S 
Pr ot oc ol Title  
A  P hase II O pe n-la bel, M ultic e nter E xte nsi o n St u d y t o Assess t he L o n g -ter m 
Safet y  a n d  Efficac y of Va m or ol o ne  i n B o ys wit h D uc he n ne M usc ular 
D ystr o p h y ( D M D)  
Pr ot oc ol N u m ber  
V B P 1 5 -0 0 3  
N a me of S p o ns or  
Re vera Ge n Bi o P har ma , I nc. 
Dr u g S u bst a nce  
delta -1, 4, 9( 1 1) -pre g natrie ne -1 7 -al p ha, 2 1 -di h y dr o x y -1 6 -al p ha -met h yl -3, 2 0 -
di o ne  
I n vesti g ati o n al Dr u g 
Pr o d uct  
Va m or ol o ne , 4 % s us pe nsi o n f or oral d osi n g 
P h ase of 
De v el o p me nt  
P hase II 
I n dic ati o n 
Treat me nt of D uc he n ne m usc ular d ystr o p h y  ( D M D) 
O bjecti ves  
Pri m ary : 
1.  T o e val uate t he 
l o n g-ter m safet y a n d t olera bilit y of va m or ol o ne , 
a d mi nistere d orall y at dail y d oses u p t o 6 . 0 m g/ k g o ver a 
2 4 -wee k 
Treat me nt P eri o d, i n b o ys a ges 4-7  years wit h D M D ;  
2.  T o c o m pare t he efficac y, as meas ure d b y t he T i me t o Sta n d T est 
( T T S T A N D), of va m or ol o ne  a d mi nistere d orall y at dail y d os es u p t o 
6. 0  m g/ k g  o ver a 2 4 -wee k  Treat me nt P eri o d vs. u ntreate d D M D hist orical 
c o ntr ols i n b o ys a ges 4 -7  years wit h D M D; a n d  
3.  T o c o m pare t he safet y, as me as ure d b y b o d y mass i n de x ( B MI) z -sc ore, of 
va m or ol o ne  a d mi nistere d orall y at dail y d oses u p t o 6 . 0 m g/ k g o ver a 
2 4 -wee k  Treat me nt P eri o d vs. pre d nis o ne -treate d hist oric al c o ntr ols i n 
b o ys a ges 4 -7  years wit h D M D . 
Sec o n d ary : 
1.  T o i n vesti gate t he effects of va m or ol o ne , a d mi nistere d ora ll y at dail y d oses 
u p t o 6. 0  m g/ k g  o ver a 2 4 -wee k  Treat me nt P eri o d vs. pre d nis o ne -treate d 
hist orical c o ntr ols , o n ser u m p har mac o d y na mic ( P D) bi o mar kers o f safet y 
(i ns uli n resista nce, a dre nal a xis s u p pressi o n, a n d b o ne t ur n o ver);  
2.  T o i n vesti gate  t he effects of va m or ol o ne , a d mi nistere d orall y at dail y d oses 
u p t o 6. 0  m g/ k g  o ver a 2 4 -wee k  treat me nt peri o d vs. u ntr eate d hist orical 
c o ntr ols, o n ser u m P D bi o mar kers of efficac y (i nfla m mat or y pr otei n 
s u p pressi o n); a n d  
3.  T o i n vesti gate t he effects of va m or ol o ne , a d mi nistere d orall y at dail y d oses 
u p t o 6. 0  m g/ k g  o ver a 2 4 -wee k T reat me nt P eri o d , o n m uscle stre n gt h, 
m o bilit y a n d f u ncti o nal e xercise ca pacit y vs. hist oric al c o ntr ols as 
meas ure d b y Q ua ntitati ve M uscle T esti n g ( Q M T),  Ti me t o R u n/ W al k T est 
( T T R W), N ort h Star A m b ul at or y A ssess me nt ( N S A A), Ti me t o C li m b 
T est ( T T C LI M B) , a n d 6-mi n ute 
Wal k T est ( 6 M W T) i n b o ys a ges 
4 -7  years wit h D M D . 
Ex pl or at ory : 
1.  T o i n vesti gate t he effects of va m or ol o ne  a d mi nistere d orall y at dail y d oses 
u p t o 6. 0  m g/ k g o ver a 2 4 -we e k Treat me nt P er i o d o n a n e xte n de d pa nel of 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 7 of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
P D  bi o mar kers usi n g S o ma Sc a n a pta mer arra ys, a n d pr ote o mic pr ofili n g.  
St u d y Desi g n  
T his P hase II a e xte nsi o n st u d y is a n o pe n -la bel, m ultice nter st u d y t o e val uate 
t he l o n g-ter m safet y, t olera bilit y, cli nical efficac y, a n d P D  of va m or ol o ne  at 
d ose le vels u p t o 6. 0  m g/ k g a d mi nistere d dail y b y li q ui d oral s us pe nsi o n o ver a 
Treat me nt P eri o d of 2 4 wee k s t o b o ys a ges 4-7  years wit h D M D.  S u bj ects w h o 
ha ve c o m plete d t he 
P hase IIa 
V B P 1 5 -0 0 2 
St u d y 
Wee k  4  F oll o w -u p 
assess me nts wit hi n 8 wee ks pri or t o e nr oll me nt are eli gi ble .  
T he st u d y is c o m prise d of a Pretreat me nt Baseli ne P eri o d of u p t o 2 4  h o urs, 
w hic h be gi ns wit h t he si g ni n g of t he e xte nsi o n st u d y -s pecifi c i nf or me d c o nse nt 
f orm (I C F) , a 2 4-wee k Treat me nt P eri o d, a n d a 2 - t o 5-wee k D ose -ta peri n g 
P eri o d f or s u bj ects w h o elect t o tra nsiti o n off va m or ol o ne treat me nt at t he e n d 
of t he st u d y.  
S u bj ects are e nr olle d at t he ti me of I C F si g ni n g.  P are nts or g uar dia ns of 
eli gi ble s u bj ects ma y  pr o vi de 
writte n i nf or me d c o nse nt f or 
V B P 1 5 -0 0 3 
e xte nsi o n st u d y partici pati o n , a n d s u bj ects ma y u n der g o Baseli ne assess me nts, 
at t he fi nal V B P 1 5 -0 0 2 Wee k  4 Visit, f oll o wi n g c o m pleti o n of all V B P 1 5-0 0 2 
W ee k 4 assess me nts .  
Pl a n ne d S a m ple Size  
U p t o a p pr o xi matel y 4 8  s u bj ects w h o c o m plete t he V B P 1 5-0 0 2 c ore st u d y will 
be e nr oll e d; a p pr o xi matel y 1 2 s u bj ects ma y be eli gi ble f or e xte nsi o n st u d y 
d osi n g  at eac h of t he d ose le vels t olerate d i n t he P hase IIa c ore st u d y.   
P o p ul ati o n  
I ncl usi o n Criteri a: 
1.  S u bj ect’s pare nt or le gal g uar dia n has pr o vi de d 
writte n i nf or me d 
c o nse nt/ HI P A A a ut h orizati o n pri or t o a n y e xte nsi o n st u d y-s pecifi c 
pr oce d ures;  
2.  S u bj ect has pre vi o usl y c o m pl ete d st u d y V B P 1 5 -0 0 2 u p t o a n d i ncl u di n g 
t he W ee k 4 F oll o w -u p assess me nts  wit hi n 8 wee ks pri or t o e nr oll me nt ; a n d 
3.  S u bj ect a n d pare nt/ g uar dia n are willi n g  a n d a ble t o c o m pl y wit h sc he d ule d 
visits, st u d y dr u g a d mi nistrati o n pla n, a n d st u d y pr oce d ures.  
E xcl usi o n Criteri a:  
1.  S u bj ect ha d a seri o us or se vere a d verse e ve nt i n st u d y V B P 1 5 -0 0 2 t hat, i n 
t he o pi ni o n of t he I n vesti gat or, was pr o ba bl y or defi nit el y relate d t o 
va m or ol o ne  use a n d precl u des safe use of va m or ol o ne  f or t he s u bj ect i n 
t his st u d y; 
2.  S u bj ect has c urre nt or hist or y of 
maj or re nal or he patic i m pair me nt, 
dia betes mellit us or i m m u n os u p pressi o n;  
3.  S u bj ect has c urre nt or hist or y of c hr o nic s yste mic f u n gal  or viral 
i nfecti o ns; 
4.  S u bj ect has use d mi neral oc ortic oi d rece pt or a ge nts, s uc h as spir o n olact o ne, 
eplere n o ne, ca nre n o ne (ca nr e n oate p otassi u m), p r ore n o ne ( pr ore n oate 
p otassi u m), m e xre n o ne ( me xre n oate p otassi u m) wit hi n 4 wee ks pri or t o 
t he first d ose of st ud y me dicati o n;  
5.  S u bj ect 
has 
e vi de nce 
of 
s y m pt o matic 
car di o m y o p at h y.  [ N ote: 
As y m pt o matic car diac a b n or malit y o n i n vesti gati o n 
w o ul d n ot be 
e xcl usi o nar y];  
6.  S u bj ect is c urre ntl y bei n g tre ate d or has recei ve d pre vi o us treat me nt wit h 
oral gl uc oc ortic oi ds or ot he r i m m u n os u p pressi ve a ge nts.  [ N otes: P ast 
tra nsie nt use of oral gl uc oc ortic oi ds or ot her oral i m m u n os u p pressi ve 
a ge nts f or n o l o n ger t ha n 3 m o nt hs c u m ulati ve, wit h last use at least 
3  m o nt hs pri or t o first d ose of st u d y me dicati o n, will be c o nsi dere d f or 
eli gi bilit y o n a case-b y -case basis.  I n haled  a n d/ or t o pical c ortic oster oi ds 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 8 of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
prescri be d f or  a n i n dicati o n ot her t ha n D M D are per mitt e d b ut m ust be 
a d ministere d at sta ble d ose f or at least 3 m o nt hs pri or t o st u d y dr u g 
a d mi nistrati o n];  
7.  S u bj ect has use d i de be n o ne wit hi n 4 wee ks pri or t o t he first d ose of st u d y 
me dicati o n;  
8.  S u bj ect has a n aller g y or h y perse nsiti vit y t o t he st u d y me dic ati o n or t o a n y 
of its  c o nstit ue nts;  
9.  S u bj ect has se vere be ha vi oral or c o g niti ve pr o ble ms t hat precl u de 
partici pati o n i n t he st u d y,  i n t he o pi ni o n of t he I n vesti gat or; 
1 0.  S u bj ect has pre vi o us or o n g oi n g 
me dical c o n diti o n, 
me dical hist or y, 
p h ysical fi n di n gs or la b orat or y a b n or malities t hat c o ul d affe ct safet y, ma ke 
it u nli kel y t hat treat me nt a n d f oll o w-u p will be c orrectl y c o m plete d or 
i mpair t he assess me nt of st u d y res ults, i n t he o pi ni o n of t he I n vesti gat or;  or  
1 1.  S u bj ect is c urre ntl y ta ki n g a n y i n vesti gati o nal dr u g, or has ta ke n a n y 
i n vesti gati o nal dr u g ot her t ha n va m or ol o ne  wit hi n 3 m o nt hs pri or t o t he 
start of st u d y treat me nt. 
N ote : S u bj ects ma y be re -e val uate d  if i neli gi ble d ue t o a tra nsie nt c o n diti o n 
w hic h w o ul d pre ve nt t he s u bj ect fr o m partici pati n g . 
N u m ber of Ce nters  
T he st u d y wi ll be c o n d ucte d at a p pr o xi matel y 1 0  U nite d States ( U S ) a n d 
n o n -U S  st u d y sites. 
St u d y Peri o d  
First s u bj ec t e nr olle d: 2 Q 2 0 1 6  
Last s u bj ect last visit: 4 Q 2 0 1 7  
St u d y D ur ati o n  
U p t o a p pr o xi mate l y 2 4  m o nt hs  t otal d urati o n 
I n di vi d u al S u bject 
St u d y D ur ati o n  
A p pr o xi matel y  2 4 -2 9  wee ks:  
 
B aseli ne P eri o d: u p t o 2 4 h o urs i m me diatel y pri or t o a d mi nistrati o n of 
first d ose of st u d y me dicatio n i n V B P 1 5 -0 0 3 e xte nsi o n st u d y  
 
Treat me nt P eri o d: 2 4  wee k s 
 
D ose -ta peri n g P eri o d: 2-5 we e ks ( o nl y f or s u bj ects w h o will tra nsiti o n 
off va m or ol o ne at e n d of st u d y)  
St u d y Dr u g 
F or m ul ati o n, D os a ge 
& A d mi nistr ati o n  
Va m or ol o ne  4 % oral s us pe n si o n will be a d mi nistere d o nce dail y o ver a 
2 4 -wee k  Treat me nt 
P eri o d , at the 
f oll o wi n g 
pla n ne d 
d ose le vels: 
0. 2 5  m g/ k g / da y, 0. 7 5  m g/ k g/ da y, 2. 0  m g/ k g / da y, or 6 . 0 m g/ k g / da y.  S u bj ects 
will recei ve va m or ol o ne t hr o u g h o ut t he 2 4-wee k Treat me nt P eri o d i n  t his st u d y 
at t he sa me d ose le vel t he y re cei ved i n t he P hase IIa V B P 1 5 -0 0 2 st u d y.  
S u bj ects w h o elect t o tra nsiti o n off va m or ol o ne treat me nt at t he e n d of t he 
Treat me nt P eri o d 
will recei ve va m or ol o ne f or a n a d diti o nal 1 -4 
wee ks 
acc or di n g t o a d ose -ta peri n g pr ot oc ol f oll o wi n g t he e n d of t he Treat me nt 
P eri o d.  
T he 
W ee k 1 2 a n d 
Wee k 2 4 d oses will be a d mi nistere d at t he st u d y site; all 
ot her d oses, i ncl u di n g t he first d ose a d mi nistere d o n St u d y Da y  1, will be 
a d mi nistere d at h o me u n der t he s u per v isi o n of t he pare nt or g uar dia n .  St u d y 
dr u g will be a d mi nistere d b y  m o ut h usi n g a  v ol u metric s yri n ge .  F oll o wi n g 
a d mi nistrati o n of t he d ose of st u d y dr u g, t he s yri n ge will be fille d o nce wit h 
water a n d t he water will b e a d mi nistere d b y m o ut h usi n g t he v ol u metric 
s yri n ge.  T he su bj ect will t he n dri n k  a p pr o xi matel y 5 0  m L (a p pr o xi matel y 2 
o u nces) of water  t o e ns ure t he f ull d ose has bee n i n geste d.   
T he dail y d ose of st u d y me dicati o n s h o ul d be ta ke n wit h 8 o u nces of w h ole  
mil k.   If w h ole  mil k is n ot t ol era ble t o t he s u bj ect, a ser v i n g of a n ot her hi g h fat 
f o o d ca n be s u bstit ute d. .  T here are n o f o o d or dri n k restricti o ns b ef ore or after 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 9 of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
d osi n g .   
St u d y S u m m a r y  
T his P hase IIa e xte nsi o n st u d y is a n o pe n -la bel, m ulti ple-d os e st u d y t o e val uate 
t he l o n g-ter m safet y, t olera bilit y, efficac y a n d P D of va m or ol o ne a d mi nistere d 
o nce dail y b y li q ui d oral s us pe nsi o n o ver a Treat me nt P eri o d of 2 4  wee ks t o 
b o ys a ges 4 -7  years wit h D M D.   
O nl y s u bj ects w h o ha ve c o m plete d P hase IIa c ore st u d y V B P 1 5-0 0 2 Wee k  4 
F oll o w -u p Visit assess me nts will be eli g i ble f or partici pati o n i n t his o pe n-la bel 
e xte nsi o n st u d y.  P artici pati o n i n t his e xte nsi o n st u d y will be disc usse d wit h t he 
s u bj ect’s pare nt or g uar dia n pri or t o t he V B P 1 5 -0 0 2 Wee k 4 Visit.  Sta n dar d of 
care treat me nt ( gl uc o c orticoi ds) f or D M D 
ma y be offe r e d t o t he s u bj ect 
f oll o wi n g c o m pleti o n of t he P hase IIa V B P 1 5-0 0 2 st u d y, if t he s u bj ect’s pare nt 
or g uar dia n d oes n ot wis h t o e nr oll t he s u bj ect i n t he e xte nsi o n st u d y a n d/ or t he 
I n vesti gat or feels it t o be i n t he best i nterest of t he s u bj ect.  A t otal of u p t o 
a p pr o xi matel y 4 8  s u bj ects will be e nr olle d i nt o t his e xte nsi o n st u d y.  
T he pare nts or le gal g uar dia ns of s u bj ects w h o c h o ose t o e nr oll i n t his 
e xte nsi o n st u d y will gi ve writte n i nf or me d c o nse nt f or t he e xte nsi o n st u d y at 
t he V B P 1 5-0 0 3 Baseli ne Da y -1  Visit.  T he Baseli ne Da y -1 Visit, i ncl u di n g 
si g ni n g of t he I C F, ma y occ ur at t he c o ncl usi o n of t he V B P 1 5 -0 0 2 
Wee k  4 
Visit f oll o wi n g c o m pleti o n of all 
Wee k 4 assess me nts; a lter nati vel y, t he 
B aseli ne Da y -1 Visit a n d V B P 1 5 -0 0 3 -s pecific I C F si g ni n g ma y occ ur u p t o 8 
wee ks after t he  date of  t he fi nal V B P 1 5-0 0 2 Wee k 4 Visit, at t he c o n ve nie nce 
of t he s u bj ect’s pare nt or le gal g uar dia n a n d discreti o n of t he I n vesti gat or.  
S u bj ects are c o nsi dere d t o be e nr olle d i n t he V B P 1 5 -0 0 3 e xte nsi o n st u d y after 
t he pare nt o r g uar dia n has si g ne d t he V B P 1 5-0 0 3 -s pecific I C F at t he Baseli ne 
Da y  -1 Visit.  Eac h s u bj ect will retai n t he st u d y i de ntificati o n n u m ber assi g ne d 
t o hi m at t he start of t he P hase IIa c ore st u d y. 
F or s u bj ects w h o e nr oll i n t he V B P 1 5 -0 0 3 e xte nsi o n st u d y wit h i n 2 8 da ys after 
c o m pleti o n of all fi nal V B P 1 5 -0 0 2 Wee k 4 assess me nts, ma n y of t he safet y, 
efficac y, a n d P D assess me nts perf or me d f or t he V B P 1 5 -0 0 2 st u d y at t he fi nal 
W ee k  4 Visit will be use d t o deter mi ne e xte nsi o n st u d y eli gi bilit y or t o pr o vi de 
baseli ne  st u d y data f or t he e xt e nsi o n st u d y a n d d o n ot nee d t o be re peate d at t he 
V B P 1 5 -0 0 3 Baseli ne Visit.  F or t hese s u bj e cts, a d diti o nal e xte nsi o n st u d y  
pr oce d ures will still be perf or me d at t he Baseli ne Da y  -1 Visit, wit hi n 2 4 h o urs 
pri or t o a d mi nistrati o n of t he first d ose of st u d y dr u g i n t he e xte nsi o n st u d y.  
S u bj ects w h o e nr oll i n t he V B P 1 5-0 0 3 e xte nsi o n st u d y > 2 8 da ys after t he date 
of t he fi nal V B P 1 5 -0 0 2 Wee k  4 Visit m ust ha ve all sc he d ul e d Baseli ne Da y  -1 
assess me nts perf or me d.  
S u bj ects 
will be gi n d osi n g  i n t his st u d y o n St u d y 
Da y 1 at t he sa me 
va m or ol o ne d ose le vel t he y re cei ve d i n t he P hase IIa c ore st u d y.  S u bj ects will 
c o nti n ue t o recei ve va m or ol o ne at t he d ose recei ve d i n t he P hase IIa c ore st u d y 
f or t he d urati o n of t he 2 4 -wee k Treat me nt P eri o d, u nl e ss ne w safet y data 
i n dicate t he d ose le vel s h o ul d be de-escalate d.   
T he pla n ne d d ose le vels are 0. 2 5  m g / k g ( D ose Le vel Gr o u p 1), 0. 7 5  m g/ k g 
( D ose Le vel 2), 2. 0  m g/ k g ( D ose Le vel Gr o u p 3 ), a n d 6 . 0 m g/ k g ( D ose Le vel 
Gr o u p  4).  A t otal of a p pr o xi matel y 4 8  s ubj ects will be e nr olle d; a  ma xi m u m of 
1 2 s u bj ects ma y be eli gi ble f or e xte nsi o n st u d y d osi n g  at eac h of t he d ose 
le vels t olerate d i n t he P hase II a st u d y.   
If d ose li miti n g t o xicities ar e i de ntifie d i n t he P hase IIa c ore st u d y w hic h 
precl u de c o nfir mati o n o f safet y of  all f o ur pla n ne d d ose le vels, t he d ose le vels 
i n t his e xte nsi o n st u d y will be m o difie d, as nee de d. 
I n t he e ve nt an y cli nical o bser vati o n s u g gests a n i nt olera bilit y f or a n i n di vi d ual 
s u bj ect t o t he st u d y me dicati o n, i n t he o pi ni o n of t he I n vesti gat or, t he s u bj ect’s 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 0  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
d ose le vel ma y be decrease d t o t he ne xt l o wer d ose le vel (e. g., a s u bj ect ta ki n g 
6 . 0 m g/ k g/ da y decrease d t o 2. 0  m g/ k g/ da y) a n d mai ntai ne d at t hat l o wer d ose 
le vel t hr o u g h o ut t he d urati o n of t he Treat me nt P eri o d .  I n t he e ve nt t he ne xt 
l o wer d ose le vel is als o n ot t olerate d a n d is c o nsi dere d a safet y ris k t o t he 
s u bj ect, i n t he o pi ni o n of t he I n vesti gat or, St u d y C hair, a n d Me dical M o nit or,  
t he s u bj ect s h o ul d be wit h dra w n fr o m t he st u d y.   
S u bj ects will be assesse d f or s afet y a n d t olera bi lit y, cli nical efficac y, a n d P D at 
sc he d ule d visits t hr o u g h o ut t he 2 4-wee k Treat me nt P eri o d.  Treat me nt P eri o d 
st u d y visits will occ ur at 
Wee k 2, 
Wee k  4, a n d e ver y 4 wee ks t hereafter 
t hr o u g h 
Wee k 2 4 .  A d verse e ve nts ( A Es), i ncl u di n g seri o us a d verse e ve nts 
(S A Es ), a n d c o nc o mita nt me dicati o ns will be rec or de d t hr o u g h o ut t he st u d y.   
O nce dail y Treat me nt P eri o d st u d y dr u g d osi n g will occ ur fr o m Da y  1 u ntil t he 
W ee k  2 4 Visit.  St u d y dr u g d osi n g will occ ur at h o me o n all da ys e xce pt t he 
da ys of t he Wee k 1 2 a n d W ee k 2 4 Visits, w he n d osi n g will occ ur at t he st u d y 
site.   
S u bj ect diaries will be dis pe nse d at Baseli ne Da y -1 a n d at eac h m o nt hl y st u d y 
visit t o rec or d A Es a n d c o nc o mita nt me dicati o ns ta ke n d uri n g t he st u d y.  
All s u bj ects will ret ur n t o t he cli nical site f or Wee k 2 4 assess me nts.  F oll o wi n g 
c o m pleti o n of t he 2 4 -wee k Treat me nt P eri o d, s u bj ects ma y be offere d f urt her 
e xte n de d treat me nt wit h va m or ol o ne i n a se parate e xte nsi o n st u d y, or s witc h t o 
sta n dar d of care treat me nt (e. g., gl uc oc ortic oids) f or 
D M D, as de e me d 
a p pr o priate f or eac h s u bj ect.  Alter nati vel y, s u bj ects ma y c h o ose t o disc o nti n ue 
va m or ol o ne a n d n ot be gi n sta n dar d of care gl uc oc ortic oi d treat me nt f or D M D.  
S u bj ects w h o s witc h t o sta n dar d of care gl uc o c ortic oi ds f or  D M D or w h o 
disc o nti n ue treat me nt will partici pate i n a D ose -ta peri n g P eri o d of 2-5 wee ks i n 
d urati o n, f oll o wi n g t he e n d of t he Treat me nt P eri o d a n d pri or t o disc har ge fr o m 
t he st u d y; s u bj ects w h o elect t o recei ve f urt her va m or ol o ne treat me nt will be 
disc har ge d fr o m t he V B P -0 0 3 st u d y after  c o m pleti o n of fi nal V B P -0 0 3 st u d y 
assess me nts at t he Wee k 2 4 Visit, pri or t o e nr oll me nt i n a s u bse q ue nt e xte nsi o n 
st u d y.  S u bj ects will be disc har ge d fr o m t he st u d y f oll o wi n g c o m pleti o n of all 
fi nal W ee k 2 4 or D ose -ta peri n g P eri o d assess me nts , as a p pr o priate.   
I n t he e ve nt t hat a n y cli nical or la b orat or y para meters re mai n a b n or mal at t he 
ti me of disc har ge fr o m t he st u d y, t he s u bj ect will be f oll o we d me dicall y as 
cli nicall y i n dicate d.  A n y s u bj ect w h o disc o nti n ues t he st u d y pri or t o t he 
W ee k  2 4 Visit s h o ul d ret ur n t o t he st u d y u nit f or fi nal 
Wee k  2 4 safet y a n d 
efficac y assess me nts at t he ti me of earl y disc o nti n uati o n.  
S afet y M e as ures  
 
P h ysical e xa mi nati o n  
 
W ei g ht  
 
B o d y Mass I n de x ( B MI)   
 
Vital si g ns (s u pi ne bl o o d press ure, heart rate , res pirat or y rate, oral 
te m perat ure) 
 
Cli nical la b orat or y tests  
o  H e mat ol o g y a n d bi oc he mistr y   
o  Uri nal ysis  ( b y di pstic k a n d mi cr osc o pic a nal ysis ) 
o  Li pi d pr ofile (tri gl yceri des, t otal c h olester ol, l o w de nsit y li p o pr otei n 
[L D L ], hi g h de nsit y li p o pr otei n [ H D L ]) 
 
1 2 -lea d electr ocar di o gra m (E C G ) 
 
Cli nical si g ns a n d s y m pt o ms ( A Es a n d S A Es)  
 
Gra di n g of cli nical a n d cli nic al la b orat or y A Es  will be acc or di n g t o t he 
C o m m o n T er mi n ol o g y Criteri a f or A d verse E ve nts  (C T C A E ), v 4. 0. 3  
P h ar m ac o d y n a mic 
M e as ures  
 
Bl o o d will be dra w n f or a ser u m P D bi o mar ke r pa nel at Da y -1, Wee k 8, 
W ee k 1 2, Wee k 1 6,  Wee k 2 4 , a n d at t he e n d of t he D ose-ta peri n g P eri o d, 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 1  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
if a p plica ble, t o e x pl ore t he effect of va m or ol o ne  o n bi o mar kers of 
a dre nal a xis s u p pressi o n, b o ne t ur n o ver, a n d i ns uli n resista nce. 
Cli nic al Effic ac y  
M e as ur es  
 
Q ua ntitati ve M uscle T esti n g ( Q M T)  
 
Ti me t o Sta n d T est ( T T S T A N D)  
 
Ti me t o Cli m b T est ( T T C LI M B)  
 
Ti me t o R u n/ Wal k  T est ( T T R W)  
 
N ort h Star A m b ulat or y Assess me nt ( N S A A)  
 
Si x -mi n ute Wal k  T est ( 6 M W T)  
E x pl or at or y 
M e as ures   
 
Meas ures of ser u m pr otei ns ( S o ma Sca n a pta mer pa nel; pr ote o mics 
pr ofili n g)  
St atistic al M et h o ds  
S a m ple Size:  
T his is a n o pe n -la bel e xte nsi o n st u d y wit h n o place b o ar m.  Hist orical c o ntr ol 
data are a vaila ble f or t he sa me a ge ra n ge ( 4 -7 years), lar gel y c ollecte d at t he 
sa me st u d y sites, wit h t he sa me o utc o me meas ures.  U ntre ate d nat ural hist or y 
c o ntr ol p o p ulati o n data are fr o m t he o n g oi n g 
C o o perati ve I nter nati o nal 
Ne ur o m usc ular Researc h Gr o u p (CI N R G ) D uc he n ne Nat ural Hist or y St u d y of 
a p pr o xi matel y 4 0 0 D M D b o ys.  Pre d nis o ne -treate d hist orical c o ntr ol data are 
fr o m a cli nical trial of pre d nis o ne carrie d o ut b y t he CI N R G gr o u p ( CI N R G 
Pre d nis o ne st u d y) .  V a m or ol o ne is a d mi nistere d dail y i n t his P hase IIa 
e xte nsi o n trial.  T o m ore acc uratel y deter mi ne t he sa m pl e size necessar y t o 
detect a gl uc oc ortic oi d ef fect o n efficac y, sa m ple size calc ulati o ns were li mite d 
t o t he dail y pre d nis o ne tre at me nt ar m of t he CI N R G Pre d nis o ne st u d y 
( n =  1 1 -1 3), at 6 or 1 2 
m o nt hs, f or t hree cli nical efficac y o utc o mes 
( T T S T A N D, T T R W, T T C LI M B) (S y n o psis T a ble 1 ).  S a m ple size was als o 
calc ulate d ass u mi n g t he o bser ve d effect of va m or ol o ne was 1 0 0 %, 8 0 % or 6 0 % 
of t hat o bser ve d wit h dail y gl uc oc ortic oi ds ( S y n o psis T a ble 1 ).   
T he pri mar y p har mac ol o gic al safet y o utc o me pr o p ose d i n t he P hase IIa 
exte nsi o n trial is c ha n ge i n B MI  z-sc ore.  Dail y gl uc oc ortic oi ds s h o w a 
relati vel y  ra pi d  i ncrease  i n  
B MI  
z-sc ore 
( 6-m o nt h 
c ha n ge  i n 
n o n -treate d =  -0. 1 4; 6 -m o nt h c ha n ge i n pre d nis o ne -treate d =  + 0. 5 4) ( S y n o psis 
T a ble 1 ).  Va m or ol o ne is n ot a ntici pate d t o s h o w a n i ncreas e i n B MI. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 2  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
 
S y n o psis T a ble 1.  6 -m o nt h  a n d 1 2 -m o nt h c h a n ges i n o utc o mes i n 
4 -< 7  ye a rs ol d ( at st u d y st art).   
 
N otes:  a) Data f or u ntreate d s u bjects fr o m t h e CI N R G  D uc he n ne Nat ural Hist or y 
St u d y; data f or pre d nis o ne -treate d s u bjects fr o m t h e CI N R G Pre d nis o ne 
st u d y.   
b) All c o m paris o ns are of dail y d ose pre d nis o ne -treate d patie nts t o u ntreate d 
patie nts.  
c) All calc ulati o ns  ass u me a re pe ate d meas ures A N O V A m o del wit h o ne pre -
a n d o ne p ost -meas ure me nt.  C orrelati o n bet wee n re peate d meas ures  was  use d 
as f oll o ws:  0. 7 5 f or hei g ht c ha n ges, 0. 7 0 f or 6 m o nt h B MI c ha n ges, a n d 0. 6 5 
f or 1 2 m o nt h B MI z-sc ore c ha n ges, a n d 0. 5 7 5 f or 6 a n d 1 2 m o nt h vel o cit y 
c ha n ges.  P o wer  =  0. 8 0 a n d al p ha  =  0. 0 2 5 f or all calc ulati o ns t o acc o u nt f or 
m ulti ple gr o u p c o m paris o ns (i.e. t w o va m or ol o ne  d oses, eac h c o m pare d  t o 
pre d nis o ne f or safet y a n d place b o f or effic ac y).  
^ C o nser vati ve c ha n ge esti mat es wer e defi n e d as f oll o ws: F or B MI  z-sc ore, t he 
e x pecte d c ha n ge i n va m or ol o ne  was set t o 0. 0 rat h er t h a n t h e o bser ve d decre ase.  F or 
ti me d tests, t h e e x pecte d c ha n ge i n va m o r ol o ne was set t o 8 0 % of t h e o bser ve d c ha n ge 
i n t he pre d nis o ne gr o u p.   
^ ^ C o nser vati ve c ha n ge esti mates were defi n e d as f oll o ws: F or ti me d tests, t h e e x pecte d 
c ha n ge i n va m or ol o ne  was set t o 6 0 % of t h e o bser ve d c ha n ge i n t h e pre d nis o ne gr o u p 
( wit h S D at 80 %).  
A n al ysis P o p ul ati o ns:   
All a nal yses will be base d o n t he act ual treat me nt eac h s u bj ect recei ve d.  F o ur  
p o p ulati o ns will be defi ne d f or data a nal ysis: t he Safet y P o p ulati o n , t he F ull 
A nal ysis Set , t he co ntr ol p o p ulati o n CI N R G D uc he n ne Nat ural Hist or y  S t u d y, 
a n d t he co ntr ol p o p ulati o n CI N R G P re d nis o ne st u d y. 
Safet y P o p ulati o n  
All s u bj ects w h o recei ve at le ast o ne d ose of va m or ol o ne  st u d y me dicati o n i n 
t he e xte nsi o n st u d y will be i ncl u de d i n t he Safet y P o p ulati o n.  T he Safet y 
P o p ulati o n is t he pri mar y a nal ysis p o p ulati o n f or safet y assess me nts.   T his is 
als o t he m o difie d I nte nti o n t o Treat ( mI T T) p o p ulati o n. 
F ull A nal ysis Set ( F A S)  
All s u bj ects w h o recei ve at le ast o ne d ose of va m or ol o ne  st u d y me dicati o n i n 
t he e xte nsi o n st u d y a n d ha ve at least o ne p ost-b aseli ne assess me nt will be 
i ncl u de d i n t he F A S.  T he F A S is t he pri mar y a nal ysis p o p ulati o n f or cli nical 
efficac y a n d P D assess me nts.   T his is t he mI T T p o p ulati o n, wit h t he a d diti o nal 
restricti o n of ha vi n g at least o ne p ost-baseli ne assess me nt.   S u bj ects w h o 
recei ve at least o ne d ose o f va m or ol o ne b ut ne ver ha ve p ost-baseli ne 
assess me nts will be e xcl u de d.   
C o ntr ol P o p ulati o n CI N R G D uc he n ne Nat ural Hist or y  S t u d y 
T he c o ntr ol p o p ulati o n fr o m t he CI N R G D uc he n ne Nat ural Hist or y S t u d y will 
i ncl u de all s u bj ects wh o were o bser ve d as part of t he st u d y i n a ges ≥ 4 years 
a n d < 7 years of a ge at a start of a n i nter val of o bser vati o n ; o bser ve d f or at least 
o ne year  wit h  at least t w o visits i n a ti me i nter val of n o m ore t ha n 1 5 m o nt hs  

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 3  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
wit h T T S T A N D, T T C LI M B, T T R W, N S A A, 6 M W T a n d Q M T meas ure d; 
re mai ne d gl uc oc ortic oi d-nai ve d uri n g t he e ntire o bser vati o n peri o d; a n d w ere  
a ble t o wal k i n de pe n de n tl y wit h o ut assisti ve de vices, a b le t o c o m plete t he 
T T S T A N D ; a n d lac ke d a n y hist or y of disease , i m pair me nt, or me dicati o ns t hat 
w o ul d h a ve ma de t he m i neli gi ble t o recei ve t he va m or ol o ne i nter ve nti o n as 
defi ne d b y t he  P hase IIa  st u d y e xcl usi o n criteria  at t he start of t he i nter val .  
C o ntr ol P o p ulati o n CI N R G Pre d nis o ne St u d y  
T he c o ntr ol p o p ulati o n fr o m t he CI N R G P re d nis o ne st u d y will i ncl u de all 
s u bj ects w h o were y o u n ger t ha n 7 years ol d at e ntr y a n d w h o were ra n d o mize d 
t o t he dail y pre d nis o ne  ar m.  
Ge ner al St atistic al C o nsi der ati o ns :   
All meas ure me nts will be a nal yze d base d u p o n t he t y pe of distri b uti o n a n d 
descri pti ve statistics prese nt e d b y treat me nt gr o u p a n d ti me p oi nt, as 
a p pr o priate.  N o i nteri m statistical a nal yses are pla n ne d.  Missi n g val ues f or 
safet y a n d e x pl orat or y o utc o mes will be treate d as missi n g.   
B aseli ne meas ure me nt is defi ne d as t he last n o n -missi n g val ue pri or t o t he fi rst 
d ose of st u d y dr u g i n t he e xte nsi o n st u d y.   
Effic ac y  A n al yses:  
T he pri mar y efficac y o utc o me is T T S T A N D .  Sec o n dar y efficac y o utc o mes are 
t he N S A A assess me nt, T T C LI M B, T T R W, Q M T , a n d t he 6 M W T .  T he 
pri mar y o utc o me 
will be c o m pare d bet wee n va m or ol o ne  a n d  hist orical 
u ntreate d c o ntr ols usi n g a mi xe d -effects li near m o del wit h treat me nt gr o u p.  
A ge at st u d y e ntr y will be i ncl u de d as a c o variate.  T he i nitial m o del will 
c o m bi ne va m or ol o ne  d oses a n d a s u bse q ue nt sec o n dar y m o del will l o o k at eac h 
d ose i n c o m pari s o n t o u ntreate d nat ural hi st or y c o ntr ols.  T his will all o w t he 
testi n g of w het her va m or ol o ne  i n ge neral a n d va m or ol o ne  at i n di vi d ual d oses 
ha ve si g nifica nt effects o n t he sl o pe of t he vel ocit y.  A d diti o nal h y p ot heses of 
efficac y will i ncl u de si milar li nea r m o delli n g wit h t he se c o n dar y o utc o mes.  
T he y will als o i ncl u de c o m paris o n gr o u ps i ncl u di n g pr e d nis o ne -treate d or 
u ntreate d nat ural hist or y c o ntr ols.  
P h ar m ac o d y n a mics A n al yses:  
Ser u m P D bi o mar kers of a dre nal  a xis s u p pressi o n, i ns uli n resista nce, a n d b o ne  
t ur n o ver will be assesse d.  L o n git u di nal a nal ysis of P D bi o mar kers will be 
st u die d as a f u ncti o n of treat me nt, wit h c o m paris o n t o pre d nis o ne -treate d a n d 
u ntreate d hist orical c o ntr ols , as a p pr o priate.   
S afet y  A n al yses:  
All e val uati o ns of cli nical safet y w ill be liste d wit h descri pti ve statistics b y 
treat me nt gr o u p prese nte d.  T he pri mar y safet y varia ble will be B MI z-sc ore 
a n d will be assesse d usi n g t he sa me t y pe of statistical m o dels use d f or efficac y.  
A d diti o nal sec o n dar y safet y data will i ncl u de hei g ht  z -sc ore, bl o o d press ure, 
a n d E C G res ults.  As n o c ha n ge i n bl o o d press ure or car diac res ults  is e x pecte d, 
t hese data will be a nal yze d usi n g a n a nal ysis of c o varia nce ( A N C O V A) 
a p pr oac h 
w hic h i ncl u des t he baseli ne val ue f or eac h 
meas ure me nt as a 
c o variate.  C ha n ges i n hei g ht z -sc ores, f or w hic h a n o bser ve d c ha n ge is 
e x pecte d , will be m o del le d usi n g a li near mi xe d effects m o del.  C o nti n u o us, 
q ua ntitati ve la b orat or y val ues will be a nal yze d si milar t o B MI z -sc ores.  
Cate g orize d la b orat or y val ues a n d prese nce or  a bse nc e of 
A Es 
will be 
c o m pare d usi n g a n e xact c hi -s q uare test.  A d verse e ve nts  will be s u m marize d 
o verall a n d b y d ose le vel, s yste m or ga n class ( S O C) a n d preferre d ter m ( usi n g 
t he Me dical Dicti onar y f or Re g ulat or y Acti vities [ Me d D R A ]); b y d ose le vel 
a n d relati o ns hi p t o st u d y me dicati o n;  a n d b y d ose le vel a n d i nte nsit y ( C T C A E 
gra d e).  A d diti o nal h y p ot heses of safet y will i ncl u de si mil ar li near m o delli n g 
wit h t he sec o n dar y a n d e x pl orat or y o utc o mes.   

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 4  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
T A B L E O F C O N T E N T S 
P R O T O C O L A M E N D M E N T T R A C KI N G.................................................................... 5  
S T U D Y S Y N O P SI S ................................ ........................................................................... 6 
LI S T O F T A B L E S ................................ ........................................................................... 1 8 
LI S T O F FI G U R E S ................................ ......................................................................... 1 9 
LI S T O F A B B R E VI A TI O N S ......................................................................................... 2 0  
1  
I N T R O D U C TI O N................................................................................................... 2 4 
1. 1  B A C K G R O U N D A N D U N M E T N E E D ........................................................................ 2 4 
1. 2  N O N C LI NI C A L E X P E RI E N C E  ................................................................................. 2 6 
1. 2. 1  
S afety P h ar m ac ol o gy ................................................................................ 2 6  
1. 2. 2  
P h ar m ac o ki netics a n d Met a b olis m .......................................................... 2 8  
1. 2. 3  
T o xic ol o gy ................................................................................................. 3 2  
1. 3  C LI NI C A L E X P E RI E N C E  ........................................................................................ 4 2 
1. 3. 1  
P h ase I St u dy i n He alt hy A d ult V ol u nteers ............................................. 4 2  
1. 4  R A TI O N A L E F O R S T U D Y D E SI G N .......................................................................... 5 5 
1. 5  O V E R A L L B E N E FI T / RI S K ..................................................................................... 5 7 
2  
S T U D Y O B J E C TI V E S A N D E N D P OI N T S ......................................................... 5 8  
2. 1  S T U D Y O B J E C TI V E S  .............................................................................................. 5 8 
2. 1. 1  
Pri m ary O bjectives .................................................................................... 5 8  
2. 1. 2  
Sec o n d ary O bjectives ................................................................................ 5 9  
2. 1. 3  
E x pl or at ory O bjective ............................................................................... 5 9  
2. 1. 4  
A ncill ary St u dy .......................................................................................... 5 9  
2. 2  S T U D Y E N D P OI N T S  ............................................................................................... 6 0 
2. 2 . 1 
S afety E n d p oi nts ....................................................................................... 6 0  
2. 2. 2  
Cli nic al Effic acy E n d p oi nts ...................................................................... 6 1  
2. 2. 3  
P h ar m ac o dy n a mic E n d p oi nts................................................................... 6 2  
2. 2. 4  
E x pl or at ory E n d p oi nts .............................................................................. 6 2  
2. 2. 5  
E n d p oi nts f or S u bject Re p orte d O utc o m es .............................................. 6 2  
3  
S T U D Y D E SI G N ..................................................................................................... 6 2  
3. 1  O V E R A L L S T U D Y D E SI G N  .................................................................................... 6 2 
3. 2  S T U D Y S U M M A R Y  ................................................................................................. 6 5 
4  
S E L E C TI O N A N D WI T H D R A W A L O F S T U D Y S U B J E C T S ......................... 6 6  
4. 1  S U B J E C T S C R E E NI N G , E N R O L L M E N T , A N D ID E N TI FI C A TI O N L O G  ..................... 6 6 
4. 2  IN C L U SI O N C RI T E RI A  ........................................................................................... 6 6 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 5  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
4. 3  E X C L U SI O N C RI T E RI A  .......................................................................................... 6 7 
4. 4  W
I T H D R A W A L O F S U B J E C T S F R O M S T U D Y  ......................................................... 6 8 
4. 5  R E P L A C E M E N T O F W
I T H D R A W N S U B J E C T S  ........................................................ 6 9 
4. 6  T E R MI N A TI O N O F S T U D Y  ..................................................................................... 6 9 
5  
T R E A T M E N T O F S T U D Y S U B J E C T S .............................................................. 7 0  
5. 1  S T U D Y M
E DI C A TI O N A D MI NI S T E R E D  .................................................................. 7 0 
5. 2  ID E N TI T Y O F IN V E S TI G A TI O N A L P R O D U C T  ......................................................... 7 0 
5. 3  D O S A G E S C H E D U L E A N D A D MI NI S T R A TI O N O F S T U D Y M
E DI C A TI O N  ................ 7 0 
5. 4  R A TI O N A L E F O R D O S E S E L E C TI O N  ..................................................................... 7 2 
5. 5  T R E A T M E N T C O M P LI A N C E  .................................................................................. 7 3 
5. 6  S T U D Y D R U G  D O S E IN T E R R U P TI O N , D E -E S C A L A TI O N , O R D I S C O N TI N U A TI O N . 7 3 
5. 7  P RI O R A N D C O N C O MI T A N T M
E DI C A TI O N S A N D T H E R A PI E S  .............................. 7 4 
5. 7. 1  
Pri or T her a py ............................................................................................ 7 4  
5. 7. 2  
C o nc o mit a nt T her a py ............................................................................... 7 4  
5. 7. 3  
Pr o hi bite d T her a pies ................................................................................. 7 5  
5. 7. 4  
Per mitte d T her a pies .................................................................................. 7 5  
5. 8  S T U D Y M
E DI C A TI O N M
A N A G E M E N T  ................................................................... 7 6 
5. 8. 1  
P ac k a gi n g a n d L a beli n g of St u dy Me dic ati o n ......................................... 7 6  
5. 8. 2  
St or a ge of St u dy Me dic ati o n..................................................................... 7 7  
5. 8. 3  
St u dy Me dic ati o n S hi p pi n g a n d H a n dli n g ............................................... 7 7  
5. 8. 4  
St u dy Me dic ati o n Acc o u nt a bility.............................................................. 7 8  
5. 9  P R O C E D U R E S F O R A S SI G NI N G S U B J E C T S T U D Y N U M B E R S  ................................. 7 8 
6  
S T U D Y S C H E D U L E .............................................................................................. 7 9  
6. 1  T I M E A N D E V E N T S S C H E D U L E  ............................................................................. 7 9 
6. 2  IN F O R M E D C O N S E N T / HI P A A A U T H O RI Z A TI O N  ................................................. 8 3 
6. 3  V I SI T S C H E D U L E A N D P R O C E D U R E S  .................................................................... 8 4 
6. 3. 1  
B aseli ne Peri o d ( D ay - 1) ........................................................................... 8 4  
6. 3. 2  
Tre at m e nt Peri o d D ay 1 ............................................................................ 8 7  
6. 3. 3  
Tre at m e nt Peri o d Wee ks 2- 2 4................................................................... 8 7  
6. 3. 4  
D ose T a peri n g Peri o d ( Wee ks 2 5- 2 9) ....................................................... 8 9  
6. 4  S U B J E C T D IS C O N TI N U A TI O N  ................................................................................ 9 0 
6. 5  S T U D Y C O M P L E TI O N  ............................................................................................ 9 0 
7  
S T U D Y A S S E S S M E N T S A N D M E A S U R E M E N T S .......................................... 9 0  
7. 1  D E M O G R A P HI C A S S E S S M E N T S  ............................................................................. 9 0 
7. 2  S A F E T Y A N D T O L E R A BI LI T Y A S S E S S M E N T S  ........................................................ 9 1 
7. 2. 1  
I nteri m Me dic al Hist ory............................................................................ 9 1 
7. 2. 2  
P hysic al E x a mi n ati o n, Wei g ht, a n d Hei g ht ............................................. 9 1  

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 6  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
7. 2. 3  
Vit al Si g ns ................................................................................................. 9 2  
7. 2. 4  
Cli nic al L a b or at ory Tests.......................................................................... 9 2  
7. 2. 5  
1 2- Le a d E C G ............................................................................................. 9 5  
7. 2. 6  
A dverse Eve nts a n d Seri o us A dverse Eve nts ........................................... 9 6  
7. 2. 7  
St u dy Me dic ati o n Acce pt a bility Assess m e nt .......................................... 1 0 3  
7. 3  C LI NI C A L E F F I C A C Y A N D P H A R M A C O D Y N A MI C A S S E S S M E N T S  ...................... 1 0 4 
7. 3. 1  
Q u a ntit ative M uscle Testi n g ( Q M T) ...................................................... 1 0 4  
7. 3. 2  
Ti m e t o St a n d Test ( T T S T A N D) ............................................................. 1 0 4  
7. 3. 3  
Ti m e t o Cli m b Test ( T T C LI M B) ............................................................. 1 0 4  
7. 3. 4  
Ti m e t o R u n/ W al k Test ( T T R W) ............................................................ 1 0 5  
7. 3. 5  
N ort h St ar A m b ul at ory Assess m e nt ( N S A A) ......................................... 1 0 5  
7. 3. 6  
Si x- mi n ute W al k Test ( 6 M W T)............................................................... 1 0 6  
7. 3. 7  
P h ar m ac o dy n a mic Bi o m ar k er P a nel ..................................................... 1 0 6  
7. 3. 8  
Pe di atric O utc o m es D at a C ollecti o n I nstr u m e nt ................................... 1 0 7  
7. 4  T O T A L B L O O D V O L U M E R E Q UI R E D  .................................................................. 1 0 8 
8  
D A T A C O L L E C TI O N ......................................................................................... 1 0 8  
8. 1  S O U R C E D O C U M E N T S  ......................................................................................... 1 0 8 
8. 2  E L E C T R O NI C C A S E  R E P O R T F O R M C O M P L E TI O N  ............................................ 1 0 9 
8. 3  D A T A P R O C E S SI N G  ............................................................................................. 1 1 0 
8. 4  S U B J E C T D IA RI E S  ............................................................................................... 1 1 0 
9  
S T A TI S TI C A L M E T H O D S A N D P L A N N E D A N A L Y S E S ............................ 1 1 0  
9. 1  S A M P L E S IZ E D E T E R MI N A TI O N  ......................................................................... 1 1 0 
9. 2  S T A TI S TI C A L A N D A N A L Y TI C A L P L A N ( S A P) ................................................... 1 1 2 
9. 2. 1  
Devi ati o ns fr o m t he St atistic al A n alysis Pl a n ........................................ 1 1 2  
9. 3  A N A L Y SI S P O P U L A TI O N S .................................................................................... 1 1 3 
9. 3. 1  
S afety P o p ul ati o n .................................................................................... 1 1 3  
9. 3. 2  
F ull A n alysis Set ( F A S) .......................................................................... 1 1 3  
9. 3. 3  
C o ntr ol P o p ul ati o n D N H S St u dy ........................................................... 1 1 3  
9. 3. 4  
C o ntr ol P o p ul ati o n Pre d nis o ne St u dy .................................................... 1 1 4  
9. 4  M
E A S U R E S T A K E N T O A V OI D / MI NI MI Z E B I A S ................................................. 1 1 4 
9. 5  IN T E RI M A N A L Y S I S ............................................................................................ 1 1 4 
9. 6  M
I S SI N G, U N U S E D , A N D S P U RI O U S D A T A  .......................................................... 1 1 4 
9. 7  S T A TI S TI C A L A N A L Y S I S ..................................................................................... 1 1 4 
9. 7. 1  
Ge ner al C o nsi der ati o ns .......................................................................... 1 1 4  
9. 7. 2  
S u bject Dis p ositi o n, De m o gr a p hics, a n d B aseli ne C h ar acteristics ...... 1 1 5  
9. 7. 3  
S afety A n alyses ........................................................................................ 1 1 5  
9. 7. 4  
Cli nic al Effic acy a n d P h ar m ac o dy n a mic A n alyses ............................... 1 1 6  

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 7  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
9. 7. 5  
C o nc urre nt Me dic ati o ns ......................................................................... 1 1 7  
1 0  
S T U D Y M A N A G E M E N T A N D E T HI C A L A N D R E G U L A T O R Y 
R E Q UI R E M E N T S................................................................................................ 1 1 7  
1 0. 1  R E G U L A T O R Y A P P R O V A L A N D G O O D C LI NI C A L P R A C TI C E  ............................ 1 1 7 
1 0. 2  IN V E S TI G A T O R R E S P O N SI BI LI TI E S  .................................................................... 1 1 8 
1 0. 2. 1  
S u bject I nf or m ati o n a n d I nf or m e d C o nse nt .......................................... 1 1 8  
1 0. 2. 2  
I nstit uti o n al Revie w B o ar d/I n de pe n de nt Et hics C o m mittee A p pr ov al 
a n d Ot her I nstit uti o n al Re q uire m e nts ................................................... 1 1 9  
1 0. 2. 3  
St u dy D oc u m e nt ati o n .............................................................................. 1 2 0  
1 0. 2. 4  
Dele g ati o n of I nvesti g at or Res p o nsi bilities ............................................ 1 2 1  
1 0. 3  P R O T O C O L D E VI A TI O N S A N D V I O L A TI O N S ....................................................... 1 2 2 
1 0. 3. 1  
Pr ot oc ol Devi ati o n a n d Vi ol ati o n Defi niti o ns ....................................... 1 2 2  
1 0. 3. 2  
Re p orti n g Devi ati o ns/ Vi ol ati o ns............................................................. 1 2 2  
1 0. 4  S T U D Y R E C O R D S R E T E N TI O N A N D D I R E C T A C C E S S T O S O U R C E D O C U M E N T S 1 2 2  
1 0. 5  S T U D Y M
O NI T O RI N G  .......................................................................................... 1 2 4 
1 0. 6  Q U A LI T Y A S S U R A N C E  ........................................................................................ 1 2 5 
1 0. 7  S T U D Y T E R MI N A TI O N A N D S I T E C L O S U R E ........................................................ 1 2 5 
1 0. 8  S I T E T E R MI N A TI O N  ............................................................................................ 1 2 6 
1 0. 9  D I SC O N TI N U A TI O N O F S T U D Y  ............................................................................ 1 2 7 
1 1  
DI S C L O S U R E O F D A T A .................................................................................... 1 2 7  
1 1. 1  C O N FI D E N TI A LI T Y  ............................................................................................. 1 2 7 
1 1. 2  P U B LI C A TI O N  ..................................................................................................... 1 2 8 
1 2  
I N V E S TI G A T O R’ S P R O T O C O L A G R E E M E N T ........................................... 1 2 9 
1 3  
R E F E R E N C E S ...................................................................................................... 1 3 0  
1 4  
A P P E N DI C E S ....................................................................................................... 1 3 4  
A P P E N DI X 1 4. 1  V A M O R O L O N E D O S E C A L C U L A TI O N W
O R K S H E E T A N D B U L K  
D I S P E N SI N G G UI D E  ...................................................................................................... 1 3 5 
 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 8  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
LI S T O F T A B L E S 
T a ble 1  
S u m m ar y of p h ar m ac o ki netic p ar a meters f or v a m o r ol o ne after or al 
a d mi nistr ati o n of si n gle d oses of 0. 1, 0. 3, 1. 0, 3. 0, 8. 0, a n d 2 0. 0 m g/ k g t o 
he alt h y s u bjects u n der f aste d c o n diti o ns ................................................. 4 5  
T a b le 2 
S u m m ar y of p h ar m ac o ki netic p ar a meters f or v a m o r ol o ne after si n gle 
d ose or al a d mi nistr ati o n of 8 m g/ k g t o he alt h y s u bjects u n der fe d a n d 
f aste d c o n diti o ns ......................................................................................... 4 7 
T a b le 3 
S u m m ar y of p h ar m ac o ki netic p ar a meters f or v a m o r ol o ne d uri n g or al 
a d mi nistr ati o n of 1, 3, 9, a n d 2 0 m g/ k g d oses o nce d ail y f or 1 4 d a ys t o 
he alt h y s u bjects u n der f aste d c o n diti o ns ................................................. 4 8  
T a b le 4 
Bi o m ar kers pre vi o usl y defi ne d t o be res p o nsi ve t o c hr o nic d oses of 
gl u c oc ortic oi ds i n D M D b o ys .................................................................... 5 6  
T a b le 5 
Pl a n ne d D ose Le vel C o m p ositi o n .............................................................. 6 4  
T a b le 6 
Sc he d ule of St u d y Acti vities ...................................................................... 8 1  
T a b le 7 
V a m or ol o ne D ose T a peri n g ....................................................................... 8 9  
T a b le 8 
He m at ol o g y, C he mist r y, a n d Li pi ds Cli nic al L a b or at or y Tests ............ 9 4  
T a b le 9 
Uri n al ysis Cli nic al L a b or at or y Tests ........................................................ 9 4  
T a b le 1 0 
P h ar m a c o d y n a mi c Bi o m a r kers .............................................................. 1 0 7  
T a b le 1 1 
Bl o o d S a m ple N u m ber a n d V ol u me ....................................................... 1 0 8  
T a b le 1 2 
6- m o nt h a n d 1 2- m o nt h C h a n ges i n O utc o mes i n 4- < 8 ye ar- ol d D M D 
B o ys  ............................................................................................................ 1 1 2 
 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 9  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
LI S T O F FI G U R E S 
Fi g ure 1  
Arit h metic me a n ± st a n d ar d err or pl as m a c o nce ntr ati o ns of 
v a m o r ol o ne ( V B P 1 5) after or al a d mi nistr ati o n of si n gle d oses of 0. 1, 
0. 3, 1, 3, 8, a n d 2 0 m g/ k g t o he alt h y s u bjects u n der f aste d c o n diti o ns - 
li ne ar pl ot (t o p); se mi-l o g arit h mi c pl ot ( b ott o m) .................................... 4 4  
Fi g u re 2  
Rel ati o ns hi p bet wee n i n di vi d u al s u bject v a m or ol o ne A U C( i nf) a n d d ose 
after or al a d mi nistr ati o n of si n gle d oses of 0. 1, 0. 3, 1, 3, 8, a n d 2 0 m g/ k g 
t o he alt h y s u bjects u n der f aste d c o n diti o ns ............................................. 4 5 
Fi g u re 3  
Arit h metic me a n ± st a n d ar d err or pl as m a c o nce ntr ati o ns of 
v a m o r ol o ne ( V B P 1 5) after si n gle d ose or al a d mi nistr ati o n of 8 m g/ k g t o 
he alt h y s u bjects u n der fe d a n d f aste d c o n diti o ns - li ne ar (t o p p a nel) 
a n d  se mi-l o g arit h mic ( b ott o m p a nel) a xes ............................................... 4 6 
Fi g u re 4  
Arit h metic me a n ± st a n d ar d err or pl as m a c o nce ntr ati o ns of 
v a m o r ol o ne ( V B P 1 5) o n D a ys 1 a n d 1 4 d uri n g or al a d mi nistr ati o n of 
1, 3, 9, a n d 2 0 m g/ k g d oses o nce d ail y f or 1 4 d a ys t o he alt h y s u bjects 
u n der f aste d c o n diti o ns (li ne ar a xes) ................................ ........................ 4 9 
Fi g u re 5  
M or ni n g c ortis ol me as u res i n t he v a m or ol o ne P h ase I M A D 
v ol u nteers. * ................................ ................................................................. 5 1 
Fi g u re 6  
F asti n g ser u m gl uc ose d uri n g t he P h ase I M A D peri o d (t w o wee ks d ail y 
tre at me nt) .................................................................................................... 5 3 
 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 2 0  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
LI S T O F A B B R E VI A TI O N S 
A b bre vi ati o n  
Defi niti o n/ Ter m  
 
 
A C T H  
a dre n oc ortic otr o pic h or m o ne  
A D L  
acti vities of dail y li vi n g  
A E  
ad verse eve nt  
A L P  
al kali ne p h os p hatase  
A L T  
ala ni ne ami n otra nsfer as e  
A N C O V A  
a nal ysis of c o varia nce  
A S T  
as partate ami n otra nsferas e  
A U C  
area u n d er t he c o nce ntrati o n -ti me c ur ve 
A U C 0 -2 4 hr 
area u n der t he  c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o 2 4 h o urs  
A U C 0 -t 
area u n der t he  c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o ti me t 
A U C i nf 
area u n der t he  c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o i nfi nit y 
A U C last 
area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o 
t he last o bser ve d meas ura ble c o nce ntrati o n 
B MI  
b o d y mass i n de x  
B U N  
bl o o d urea nitr o ge n  
C  
Celsi us  
C D 2 3  
cl uster desi g nati o n 2 3 
C F R  
C o de of Fe d eral Re g ul ati o ns  
CI N R G  
C o o perati ve I nter nati o nal Ne ur o m usc ular Res earc h Gr o u p  
C K  
creati ne ki n ase  
C L  
cleara nce  
C o n A  
co nc an a vali n A  
c m 
ce nti meter  
C ma x  
ma xi m u m o bser ve d plas ma c o nce ntr ati o n  
C Q M S  
CI N R G Q u a ntitati ve Meas u re me nt S yste m 
C T C A E  
C o m m o n Ter mi n ol o g y Criteria  f or A d verse E ve nts 
C T M  
Cli nical Trial Material  
C T X  
car b o x y-t er mi nal tel o pe pti de 
C Y P  
cyt o c hr o me P 4 5 0  
d L  
deciliter  
D M D  
D uc he n ne m us c ular d ystr o p h y  
D S M B  
Data a n d Safet y M o nit ori n g B oar d  
E C G  
electr ocar di ogra m  
e C R F 
electr o nic case re p ort f or m  

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 2 1  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
A b bre vi ati o n  
Defi niti o n/ Ter m  
 
 
E D C  
electr o nic d ata ca pt ure 
F  
Fa hre n heit  
F, F %  
bi oa vaila bilit y, perce nt bi oa vaila bilit y  
F A S  
F ull A nal ysis Set  
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 G T  
g a m ma g l uta m yl tra nsferase 
G L P  
G o o d  La b orat or y Practice  
H b A 1c  
h e m o gl o bi n A 1 c  
H D L  
hi g h de nsit y li p o pr otei 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  
hr  
h o ur  
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 nce o n Har m o nisati o n 
I E C 
I n d e pe n de nt Et hics C o m mittee  
I G F B P-2  
i ns uli n-li ke gr o wt h f act or-bi n di n g pr otei n 2  
I G F B P-5  
i ns uli n-li ke gr o wt h f act or-bi n di n g pr otei n 5  
I L-2 2 B P  
i nterle u ki n-2 2 bi n di n g pr otei n  
I N D 
I n v esti gati o nal Ne w Dr u g 
I R B 
I nstit uti o nal Re vie w B oar d 
K 2-E D T A  
d i p otassi u m et h yl e ne dia mi netetraacetic aci d 
k g  
kil o gra m  
λ z 
eli mi nati o n rate c o nsta nt  
L  
liter 
L L C  
Li mite d Lia bilit y C o m pa n y  
L C -M S  
Li q ui d C hr o mat o gra p h y –  Mass S pec tr o metr y 
L D H  
lactate de h y dr o ge nas e 
L D L  
l o w de nsit y li p o pr otei n 
m  
meter  
M A D  
m ulti ple asce n di n g d os e (st u d y)  
m dx  
m o use m o del lac ki n g d ystr o p hi n  
Me d D R A  
Me dical Dicti o nar y f or R e g ul at or y Acti vities  
m g  
milli gra m  
mi n  
mi n ute  
MI S T  
Meta b olites i n Safet y Testi n g  

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 2 2  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
A b bre vi ati o n  
Defi niti o n/ Ter m  
 
 
mI T T  
m o difie d I nt e nti o n t o Treat  
m L  
milliliter  
M M P -3  
matri x metall o pr otei nase -3  
M M P -1 2  
matri x metall o pr otei nase -1 2  
M S Ba n d  
Micr os oft Ba n d  
N A D P H  
nic oti na mi de a de ni ne di n ucle oti de p h os p hate  
N F -κ B  
n uclear fact or k a p pa -li g ht-c hai n -e n h a ncer of acti vate d B cells  
n g  
na n o gra m  
N o. , n 
n u m ber  
N O A E L  
n o o bser ve d a d v erse effect le vel  
N S A A  
N ort h Star A m b ulat or y Assess me nt  
O T C  
o ver -t he-co u nter ( n o n -prescri pti o n me dicati o n)  
% C V  
perce nt a ge c o effi cie nt of variati o n  
P 1 N P  
ser u m a mi n oter mi nal pr o pe pti de of t y p e I c olla ge n  
P B L  
peri p heral bl o o d le u k oc ytes  
P D  
p har mac o d y n a mics  
P HI  
Pr otecte d Healt h I nf or mati o n  
P K  
p har mac o ki netics  
P R [ P Q]  
i nter val fr o m o nset of P wa ve t o start of t he Q R S c o m ple x 
Q  
q uarter  
Q M T  
Q ua ntitati ve M uscle Testi n g  
Q R S  
i n electr ocar di o gra p h y, t he c o m ple x c o nsisti n g of Q, R, a n d S 
wa ves, c orres p o n di n g t o de p olarizati o n of ve ntricl es [c o m ple x]  
Q S A R  
q ua ntitati ve str uct ure -acti vit y relati o ns hi p  
Q T  
i n car di ol o g y, t h e i nter val bet wee n t he start of t he Q wa ve a n d 
e n d of t he T wa ve  
Q T c 
correcte d Q T i nter val  
R B C  
Re d Bl o o d Cell  
R R  
i n electr ocar di o gra p h y, t he i nter val bet wee n s uccessi ve R 
wa ve s ( pea ks of Q R S c o m ple x es) 
6 M W T  
Si x -mi n ute Wal k Test  
S A D  
si n gle as ce n di n g d ose (st u d y) 
S A E  
Ser i o us A d verse E v e nt 
S A P  
statistical a nal ysis pla n 
S D  
sta n dar d de viati o n 
S O C  
s yste m or ga n class 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 2 3  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
A b bre vi ati o n  
Defi niti o n/ Ter m  
 
 
S O P  
sta n dar d o perati n g pr oce d ures 
S S L  
sec ure s o c ket la yers 
t1/ 2 
ter mi nal half-life 
T E A E  
treat me nt-e mer ge nt a d verse e ve nt  
T ma x  
ti me t o ma xi m u m o bser ve d plas ma c o nce ntrati o n 
T T C LI M B  
Ti me t o Cli m b ( Test)  
T T S T A N D  
Ti me t o Sta n d ( Test)  
T T R W  
Ti me t o R u n/ Wal k ( Test)  
U S  
U nite d States  
vs.  
vers us  
V ss 
v ol u me of distri b uti o n at stea d y st ate  
V z 
ter mi nal p hase v ol u me of distri b uti o n 
W B C  
W hite Bl o o d Cell  
W H O  
W orl d  Healt h Or ga nizati o n  

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 2 4  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
1  
I N T R O D U C TI O N 
1. 1  
B ac k gr o u n d a n d U n met Nee d 
D uc he n ne m us c ular d ystr o p h y ( D M D) is a ra pi dl y pr o gressi ve f or m of m usc ular 
d ystr o p h y t hat occ urs pri maril y i n males a n d ma nifests pri or t o t he a ge of si x years.  
D uc he n ne m us c ular d ystr o p h y affects a p pr o xi matel y 1 i n 3, 6 0 0 t o 9, 3 0 0 male birt hs 
w orl d wi de. 1  Duc he n ne m usc ular d ystr o p h y is ca use d b y m utati o ns i n t he d ystr o p hi n 
ge n e w hic h c o des f or a pr otei n t hat pr o vi des str uct ural sta bilit y t o t he d ystr o gl yca n 
c o m ple x o n m uscle cell me m bra nes. 2  T he lac k of d ystr o p hi n r e d uces plas ma me m bra ne 
sta bility.  M e m bra ne d est a biliz ati o n res ults i n altere d mec ha ni cal pr o perties a n d a berra nt 
si g nali n g, w hic h c o ntri b ute t o me m bra ne fra gilit y, necr osis, i nfla m mati o n, a n d 
pr o gre ssi ve m uscle wasti n g. 3 
I n a d diti o n t o t he si g nifica nt c o ntri b uti o n of me m bra ne dest a bilizati o n a n d mec ha nical 
i nj ur y i n D M D, a b erra nt i ntracell ular si g nali n g casca des t hat re g ulate i nfla m mat or y a n d 
i m m u ne pr ocesses als o c o ntri b ute t o D M D pat h o p h ysi ol o g y.  U p-re g ulate d i nfla m mat or y 
ge n e e x pressi o n a n d acti vate d i m m u ne cell i nfiltrates, at least partiall y me diate d b y 
n uclear fact or k a p pa-li g ht-c hai n-e n h a ncer of acti vate d B cells (N F -κ B ) acti vati o n, are 
e vi de nt d uri n g earl y dise ase sta ges a n d pla y a si g nifica nt r ole i n m uscle wasti n g. 3  N F - κ B 
ha s bee n s h o w n t o r e g ulate t he e x pressi o n of n u mer o us i nfla m mat or y ge n es i n i m m u ne 
cells a n d m uscle fi bers, 4 ,5 ,6 ,7 a n d t he i nfiltrati o n a n d acti vati o n of t hese cells ca n tri g ger 
m uscle f i ber deat h.8 ,9 
Alt h o u g h si g nifica nt a d v a nces ha ve bee n ma de i n u n dersta n di n g t he eti ol o g y of D M D, a 
c ure has n ot b ee n f o u n d, a n d c urre nt treat me nt o pti o ns are all me dicati o ns use d “ off-
la bel” t o alle viate t he s y m pt o ms of D M D.  Des pite scie ntific a d va n ces, o nl y 
gl uc o c ortic oi ds, s uc h as pre d nis o ne, ha v e c o nsiste ntl y de m o nstr ate d efficac y i n cli nical 
trials.1 0  F urt her, ma n y disease m o dif yi n g tec h n ol o gies t h at are c urre ntl y i n de vel o p me nt 
f oc us o n s u bsets of dystr o p hi n m utati o ns a n d t heref ore d o n ot a d dress t he u n met nee d i n 
all pers o ns wit h D M D.  H o we ver, it is li kel y t hat gl uc oc ortic oi ds will nee d t o be 
c o-a d mi nistere d wit h ma n y of t hes e c o m p o u n ds f or ma xi m u m effect a n d gl uc oc ortic oi ds 
ha ve e xte nsi ve si de effect pr ofiles, ofte n li miti n g l o n g-ter m a d mi nistrati o n.  T he c urre nt 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 2 5  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
g oal of D M D researc h is t o fi n d a m utati o n-i n de pe n de nt treat me nt t hat matc hes or 
e x cee ds t he efficac y of gl uc oc ortic oi ds wit h a si g nifica ntl y l o w er si de effect pr ofile. 
Va m or ol o ne is a first ge n erati o n delta- 9, 1 1 c he mi cal c o m p o u n d bel o n gi n g t o t he 
str uct ural class of s y nt hetic ster oi dal dr u gs, w hic h i ncl u des t he gl u c ortic oi ds pre d nis o ne, 
met h yl pre d nis o n e, a n d d e x a met has o ne. 1 1  T he c he mical str uct ure of va m or ol o ne has 
o pti mi ze d f o ur s u bacti vities of tra diti o nal gl u c oc ortic oi d dr u gs, n a mel y tra nsacti vati o n, 
tra nsrepressi o n, p h ysi o c h e mical me m bra n e pr o perties, a n d mi neral oc ortic oi d rece pt or 
a nta g o nis m. 1 1  B y re d u ci n g tra ns acti vati o n s u b pr o perties, retai ni n g tr a nsre pressi o n, 
i m parti n g me m bra ne sta bilizi n g pr o perties, a n d i n hi biti n g t he mi neral oc orti c oi d rece pt or 
pat h wa y, va m or ol o ne h as fa v ora ble effi cac y a n d si de effect pr ofiles relati v e t o classic 
gl uc o c ortic oi ds i n n o ncli nical m o dels a n d is a ntici pate d t o be a n attracti ve ca n di date f or 
t he treat me nt of D M D i n pe diatric patie nts. 
I n vitr o a n d n o ncli nical d ata t o date s u g gest t hat v a m or ol o ne ma y offer a m u c h nee d e d 
alter nati ve t o t he c urre nt gl uc o c ortic oi ds w hic h are sta n dar d of care f or D M D, 1 2 wit h 
a d ministrati o n be gi n ni n g ar o u n d t he a ge of 5 years i n m ost de vel o pe d c o u ntries, or e ve n 
earlier i n s o me cases. 
T he si g nifica nt effects of gl uc o c ortic oi ds o n gr o wt h a n d de vel o p me nt, h o w e ver, pre ve nt 
t heir r o uti ne a d mi nistrati o n i n i nfa nc y or ‘t o d dler’ years, des pite e vi de nce t hat t he earlier 
t he a d mi nistrati o n, t he better t he o verall f u ncti o nal o utc o me.1 3  T he c u m ulati ve si de 
effects of gl uc oc ortic oi ds, i ncl u di n g e x cess wei g ht, dela ye d p u bert y, fra gile s ki n, l oss of 
b o ne mi neral de nsit y, br uisi n g, a n d C us hi n g oi d a p peara n ce c o nti n ue t o ne gati vel y i m pact 
o n t he q ualit y of lif e of t he i n di vi d ual, lea di n g t o si g nifica nt v ariati o ns i n cli nical 
practice. 1 4  Gl uc oc ortic oi ds als o c o ntri b ute t o f urt her m uscle da m a ge wit h l o n g-ter m 
a d ministrati o n.   Va m or ol o ne has s h o w n fe w if a n y of t he si de effects of tr a diti o nal 
gl uc o c ortic oi ds i n m o use m o dels of D M D. 1 1 ,1 5 ,1 6 
T his st u d y is tar gete d t o e x pl ore w het her va m or ol o ne will s h o w at least e q ual effic ac y t o 
gl uc o c ortic oi d s wit h a m ore fa v ora ble si de effect pr ofile, t here b y i m pr o vi n g t he q ualit y 
of life f or D M D patie nts.  T his pr ofile w o ul d e na ble use of va m or ol o ne i n D M D b o ys 
w h o are at a y o u n ger a ge t ha n w he n gl uc oc ortic oi d  treat me nt is c urre ntl y i nitiate d.  I n 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 2 6  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
a d diti o n, va m or ol o ne c o ul d be prescri b e d i n later sta ge n o n -a m b ula nt y o u n g me n wit h 
D M D a n d f or a l o n ger peri o d of ti me, w here t h e ris k: be nefit bala nce of gl u c oc ortic oi d s is 
ofte n less fa v ora ble.  
Efficac y ma y als o be i m pr o ve d o ver classic gl uc oc ortic oi d s i n t he l o n ger t er m.  I n 
a d diti o n t o t he a nti -i nfla m mat or y pr o perties of v a m or ol o ne as a res ult of N F-B pat h wa y 
i n hi biti o n, va m or ol o ne ma y als o i m pr o ve efficac y o ver c o n ve nti o nal gl uc oc ortic oi d s d ue 
t o t he lac k of i nterfere nce i n t he A K T 1/ F O X O pat h wa y, a ke y feat ure of gl uc oc ortic oi d  
t hera p y w hic h le a ds i n t he l o n g ter m t o m uscle wasti n g a n d atr o p h y.1 7  F urt her, 
va m or ol o ne has bee n rece ntl y de m o nstr ate d t o i m pr o ve as y nc hr o n o us re m o deli n g, 
belie ve d t o be a c o m p o ne nt of pr o gressi ve m uscle wea k ness a n d wasti n g i n D M D 1 8 a n d 
ma y als o pre ve nt m uscle me m bra ne da m a ge, t here b y del a yi n g pr o gressi o n of t he disease 
f urt her.  V a m or ol o ne is a n a nta g o nist t o t he mi neral oc ortic oi d rece pt or, w hereas 
gl uc o c ortic oi ds are t y pi call y a g o nists.  A n a nt a g o nist f or t he mi neral oc orti c oi d rece pt or, 
e pler o n o ne, w as r ece ntl y s h o w n t o si g nifica ntl y i m pr o ve D M D heart f u n cti o n. 1 9  Fi nall y, 
va m or ol o ne i m parts p h ysical sta bilit y t o m y ofi b er plas ma me m bra nes, w h ereas 
pre d nis o ne desta biliz es me m bra nes.  T his pr o pert y a d dresses t he pri mar y defect of 
me m bra ne i nsta bilit y i n d ystr o p hi n deficie nt m y ofi bers i n D M D. 1 5 
P ote ntiall y,  t h e a d mi nistrati o n of va m or ol o ne t o a D M D patie nt ma y be gi n s o o n after 
birt h t o sl o w t he d ystr o p hic pr ocess of m us cle, ret ai ni n g re ge nerati ve ca pacit y a n d 
s u bsta ntiall y i m pr o vi n g p atie nt q ualit y of life. 
1. 2  
N o ncli nic al E x perie nce 
T he safet y p h ar mac ol o g y, p har mac o ki netics ( P K) a n d meta b olis m, a n d t o xic ol o g y of 
va m or ol o ne ha ve b ee n e val uate d i n m ulti ple n o ncli nical st u dies i n vitr o a n d i n mice, rats, 
bea gle d o gs, a n d c y n o m ol g us m o n ke ys i n viv o.  
1. 2. 1  
S afety P h ar m ac ol o gy 
St u nte d gr o wt h is a si g nifica nt si de effect of c hr o nic gl uc oc ortic oi d use i n c hil dre n. 2 0 ,2 1  
C hr o nic treat me nt wit h gl uc oc ortic oi ds ne gati vel y affects b o ne gr o wt h a n d de vel o p me nt 
a n d ca n ca use oste o p or osis. 2 2 ,2 3 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 2 7  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
T he effect of v a m or ol o ne as c o m pare d t o pre d nis ol o ne o n b o ne gr o wt h a n d de vel o p me nt 
was e val uat e d i n t he m dx m o use m o del of D M D t hat lac ks d ystr o p hi n d ue t o a pre mat ure 
c hai n-ter mi nati n g m utati o n i n t he m o use h o m ol o g ue of t he d ystr o p hi n ge ne.  I n t he pre-
s y m pt o matic m dx  st u d y, ti bia le n gt h was me as ure d t o deter mi ne if va m or ol o ne i n hi bite d 
b o ne gr o wt h.  Pre d nis ol o ne si g nifica ntl y d ecreas e d ti bia le n gt h w hereas v a m or ol o ne di d 
n ot affect ti bia le n gt h at a n y c o nce ntrati o n teste d.  Micr o-c o m p ute d t o m o gra p h y was 
perf or me d o n fe m urs t o e x a mi ne b o ne de nsit y a n d str uct ure.  C o m paris o n of ve hicle, 
pre d nis ol o ne, a n d t he hi g hest va m or ol o ne d ose s h o we d pre d nis ol o ne t o si g nifica ntl y 
re d uce tra bec ular t hic k n ess c o m pare d t o ve hicl e, w hile va m or ol o ne di d n ot.1 5 
I n n or mal, male C D- 1®  mice, t hese effects were re pr o d uce d.  U nli ke C D- 1 mice treate d 
wit h pre d nis ol o ne, C D- 1 mice recei vi n g v a m or ol o ne di d n ot e x perie nce ti bia le n gt h 
s h orte ni n g.1 6  H o we ver, at t he hi g h est va m or ol o n e d ose teste d, mice di d h a ve 
si g nifica ntl y re d uce d b o d y le n gt h, t h o u g h t o a less er e xte nt as c o m pare d t o pre d nis ol o ne. 
D uc he n ne m us c ular d ystr o p h y is ass oci ate d wit h car di o m y o p at h y t h at ca n b ec o me life 
t hreate ni n g, a n d i ncreas e d fi br osis wit h pre d nis o ne treat me nt i n heart m uscle of t he m dx  
m o use has bee n re p orte d. 2 4  Hist ol o gicall y, clear fi br osis was e vi de nt i n 5 0 % of y o u n g 
( 8- wee k) pre d nis ol o ne-tr eate d m o use hearts c o m p are d t o n o i nci de nce of fi br osis 
i de ntifie d i n t he ot her gr o u ps ( wil d t y pe; m dx  ve hi cle, a n d va m or ol o n e -treate d). 
P ha r mac ol o gicall y, gl uc o c ortic oi ds s h o w i m m u n os u p pressi ve a n d i m m u n ot o xic 
pr o pe rties t hat li mit t hera pe utic wi n d o ws a n d l o n g-ter m use.  Va m or ol o ne ( 5, 1 5, 3 0 
m g/ k g/ da y) was be nc h m ar ke d a gai nst pre d nis ol o ne ( 5 m g/ k g/ da y) t o deter mi ne if si milar 
pr o perties were o bs er ve d. 1 5  U ntreate d m dx  mice s h o we d i ncrease d n u m bers of peri p heral 
bl o o d le u k oc yt es ( P B L) a n d e nlar ge d s plee ns res ulti n g fr o m o n g oi n g m uscle da ma ge 
c o m pare d t o wil d t y pe mice.  Va m or ol o ne treat me nt re d uce d s plee n mass a n d P B L 
c o u nts i n a d ose- de p e n de nt ma n ner.  T his fi n di n g is attri b ute d t o a re d ucti o n i n m uscle 
da ma ge b y va m or ol o n e t hat decreases s plee n size t o le vels rese m bli n g t h os e i n wil d t y pe 
mice.  Pre d nis ol o ne re d u ce d t hese meas ures b el o w wil d t y pe, s u g gesti n g 
i m m u n os u p pressi ve a n d/ or i m m u n ot o xic pr o perties.  F urt her, pre d nis ol o ne si g nifica ntl y 
dec rease d via bl e s ple n oc yt es per gra m of tiss ue ( p0. 0 0 5), w hereas t his decreas e was n ot 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 2 8  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
o bser ve d f or a n y va m or ol o ne d ose teste d ( Re v era Ge n Re p ort N o. M D X- R B P- V B P 1 5-
0 2). 1 5 
T o f urt her q u er y t he p ote ntial i m m u ne m o d ulati o n, t he effects of va m or ol o ne a n d 
pre d nis ol o ne o n c o u nts of s ple nic B a n d T-l y m p h oc yt es is olate d fr o m treat e d m dx  mice 
were  e x a mi ne d.  C D 4 + T-cell acti vati o n was assa ye d b y sti m ulati o n of s ple n oc yt es wit h 
t he T-cell mit o ge n, c o nca na vali n A ( C o n A).  S ple n oc yt es o btai ne d fr o m pre d nis ol o ne-
treate d mice dis pla ye d a si g nifica nt r e d ucti o n of t he perce nta ge of s ple nic acti vate d 
C D 4 + C D 2 5 + T-cells u p o n C o n A sti m ulati o n w hile s ple n oc ytes deri ve d fr o m 
va m or ol o ne-treate d mice di d n ot ( Re vera Ge n Re p ort N o. M D X- R B P- V B P 1 5- 0 2). 
Ta ke n t o get her, t hese fi n di n gs s u g gest t hat w hile pre d nis ol o ne treat me nt lea ds t o a 
re d ucti o n i n T-cell n u m ber a n d acti vati o n stat us, va m or ol o ne m o d ulates i nfla me d m dx  
i m m u ne s yste ms t o war ds a wil d t y pe st at e wit h o ut c o m pr o misi n g T-cell acti vati o n stat us. 
1. 2. 2  
P h ar m ac o ki netics a n d Met a b olis m 
1. 2. 2. 1  
Si n gle  D ose 
Va m or ol o ne P K pr ofiles were d eter mi ne d i n male C D- 1 mice, S pra g ue Da wle y rats a n d 
bea gle d o gs after a si n gle i ntra ve n o us i njecti o n of 1 0 m g/ k g a n d after a si n gle oral d ose 
of 5 0 m g/ k g i n mice a n d rats a n d 3 0 m g/ k g i n d o gs. 
P ha r mac o ki netic res ults f or va m or ol o ne f oll o wi n g a si n gle i ntr a ve n o us a d mi nistrati o n of 
1 0 m g/ k g i n Crl: C D 1(I C R) mice de m o nstrate d a cleara n ce ( C L) of 1 8. 8 m L/ mi n/ k g.  T h e 
ter minal half-life (t ½ ) was 0. 3 5 h o urs.  V ol u me of distri b uti o n at stea d y stat e ( Vss) was 
0. 7 6 L/ k g.  F oll o wi n g oral a d mi nistrati o n of 5 0 m g/ k g i n mice, t he ma xi m u m o bser ve d 
plas ma c o nce ntrati o n ( C ma x ) of 6 7 8 7 n g/ m L was o bser ve d at 2 h o urs (ti me t o ma xi m u m 
o bser ve d plas ma c o nce ntrati o n [ T ma x ]) after dr u g a d mi nistrati o n, a n d perce nt 
bi oa vaila bilit y ( F %) was 7 4. 5 %.  F oll o wi n g oral a d mi nistrati o n of 1 5 m g/ k g via c herr y 
s yr u p, t he Cma x  of 1 5 2 7 n g/ m L was o bs er ve d at 2 h o urs after dr u g a d mi nistrati o n a n d 
bi oa vail a bilit y was 4 7. 7 % ( Re vera Ge n Re p ort N o. P H- D P M K- V B P- 1 0- 0 0 4). 
P har mac o ki netic res ults f or va m or ol o ne f oll o wi n g a si n gle i ntr a ve n o us a d mi nistrati o n of 
5 0  m g/ k g i n S pra g ue D a wle y rats i n dicate d a C L of 2 0. 2 m L/ mi n/ k g. T h e t
½  was 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 2 9  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
0. 5 8  h o urs.  V ss was 0. 7 7 L/ k g, w hic h was si milar t o t hat o bser ve d i n mice.  After oral 
a d ministrati o n of 5 0 m g/ k g i n rats, a C ma x  of 2 5 4 3 n g/ m L was o bs er ve d at 4 h o urs after 
d ose a d mi nistrati o n, a n d bi oa vaila bilit y was 4 7. 8 % ( Re vera Ge n Re p ort N o. P H- D P M K-
V B P- 1 0- 0 0 7). 
I n bea gle d o gs, v a m or ol o ne ha d a C L  of 2 4. 7 m L/ mi n/ k g.  T he t½  was 5. 4 2 h o urs a n d Vss 
was 1. 9 3 L/ k g.  After oral a d mi nistrati o n of 3 0 m g/ k g i n d o gs, a C ma x  of 8 1 4 n g/ m L was 
o bser ve d at 6 h o urs after d ose a d mi nistrati o n a n d bi oa vaila bilit y was 5 3. 2 % ( Re vera Ge n 
Re p ort N o. 4 8 5 0 4- 1 0- 4 6 4). 
Va m or ol o ne cle ara nce w as t heref ore c o m para bl e i n all 3 s pecies st u die d 
( 1 9- 2 5 m L/ mi n/ k g).  Bi oa vaila bilit y ra n ge d fr o m a p pr o xi matel y 5 0 % i n m o use (c herr y 
s yr u p), rat, a n d d o g t o 7 5 % i n t he m o use ( 3 0 % La brafil) ( Re v era Ge n Re p ort N os. 
P H - D P M K- V B P- 1 0- 0 0 4, P H- D P M K- V B P- 1 0- 0 0 7, 4 8 5 0 4- 1 0- 4 6 4). 
1. 2. 2. 2  
M ulti ple D ose 
C rl: C D 1(I C R) mice w ere a d mi nistere d va m or ol o n e or ve hicle o n ce d ail y f or 
2 8 c o nsec uti ve da ys.  Va m or ol o ne e x p os ure (as assesse d b y t he C ma x  a n d area u n der t h e 
c o nce ntr ati o n-ti me c ur ve [ A U C ]) i ncrease d wit h i ncreasi n g d os e o n St u d y Da ys 1 a n d 2 8.  
Re peate d d osi n g of va m or ol o ne o ver a 2 8- da y d urati o n was ass ociate d wit h decreases i n 
mea n va m or ol o ne A U C last val ues i n t he 3 0 a n d 1 0 0 m g/ k g d ose gr o u ps c o m pare d t o 
Da y  1, i n dicati n g p ossi ble e nz y me i n d u cti o n.  O n St u d y Da y 2 8, mea n A U Clast val ues 
were  1. 8 1-f ol d a n d 5. 0 2-f ol d l o wer c o m pare d t o St u d y Da y 1 f or t he 3 0 a n d 1 0 0 m g/ k g 
d ose gr o u ps, res p ecti vel y.  T he o bser ve d differe nce i n e x p os ure relati ve t o Da y 1 
i ncreas e d wit h t he i ncrease i n a d mi nistere d d ose of va m or ol o ne ( Re v era Ge n Re p ort N o. 
1 9 9 8- 0 0 9). 
Be a gl e d o gs were eit her a d mi nistere d va m or ol o ne or ve hicle o nce dail y f or 2 8 
c o nsecuti ve da ys.  Va m or ol o ne e x p os ure i n d o gs (as assesse d b y C ma x  a n d A U Clast) 
ge n erall y i ncreas e d wit h i ncreasi n g d ose o n St u d y Da ys 1 a n d 2 8.  F or t h e 2 a n d 1 0 
m g/ k g d ose gr o u ps, e x p os ure o n Da y 2 8 was ge n erall y hi g her t ha n o n Da y 1, i n dicati n g 
p ossi ble i n hi biti o n of meta b olis m of va m or ol o ne at t hese d ose le vels.  O n Da y 2 8, mea n 
A U C last val ues were 2. 3 5-f ol d a n d 2. 4 3-f ol d ( males) a n d 3. 0 3-f ol d a n d 3. 2 3-f ol d 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 3 0  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
(fe males) hi g h er c o m p are d t o St u d y Da y 1 f or t he 2 a n d 1 0 m g/ k g/ da y d os e gr o u ps, 
res pecti vel y.  F or t he 5 0 m g/ k g d ose gr o u p, e x p os ure o n Da y 2 8 was si milar t o t hat o n 
Da y 1.  At t he 5 0 m g/ k g d ose, A U C last val ues i n males were 1. 7 1-f ol d l o w er w hereas 
fe males w ere 1. 2 2 hi g her o n Da y 2 8 c o m pare d t o Da y 1 ( Re vera Ge n Re p ort N o. 
0 3 1 3 0 2). 
N o n- naï ve c y n o m ol g us m o n ke ys w ere a d mi nistere d va m or ol o ne ( 3 0 0 a n d 
6 0 0 m g/ k g/ da y) or v e hicl e o nce d ail y f or 7 c o nsec uti ve da ys.  Va m or ol o ne e x p os ure (as 
assessed b y C ma x  a n d A U Clast) ge nerall y i ncrease d wit h i ncreasi n g d ose o n St u d y Da ys 1 
a n d 7 wit h t he e x ce pti o n of male m o n ke ys o n Da y 7, w hic h s h o we d n o cl ear i ncrease i n 
e x p os ure bet wee n t he 3 0 0 a n d 6 0 0 m g/ k g/ da y d os e le vels.  Re peate d d osi n g o ver t he 
7- da y st u d y d urati o n was ass ociate d wit h decreases i n mea n plas ma va m or ol o ne A U C last 
val ues f or fe male a n d male m o n ke ys i n dicati n g p ossi ble meta b olic i n d ucti o n.  O n Da y 7, 
mea n A U C last val ues were 1. 6 0-f ol d, 2. 1 9-f ol d, a n d 2. 0 2-f ol d l o wer i n fe males a n d 
1. 2 0-f ol d, 2. 0 9-f ol d, a n d 2. 8 8-f ol d l o wer i n males c o m pare d t o St u d y Da y 1 f or t he 1 0 0, 
3 0 0 a n d 6 0 0 m g/ k g/ da y d ose gr o u ps, res p ecti vel y ( Re vera Ge n Re p ort N os. 1 9 9 8- 0 0 1, 
S W 1 1- 0 4 1 8). 
1. 2. 2. 3  
Distri b uti o n 
In t he pl as ma pr otei n bi n di n g st u dies, perce nt b o u n d was si milar i n h u ma n a n d m o use 
cells i n c ult ure ( 8 8. 0 6 % a n d 8 6. 7 1 %, res p ecti vel y).  I n t he bl o o d partiti o n e x peri me nt 
d o ne ex viv o, t he bl o o d t o plas ma rati o was si milar bet wee n h u m a n a n d m o use ( 0. 8 7 a n d 
0. 6 8, res pecti vel y), b ut t h e re d bl o o d cell t o plas ma rati o f or t he m o us e ( 0. 3 3) was less 
t ha n half t hat of t he h u m a n ( 0. 7 4).  H u ma n i n viv o data are pres e nte d i n Secti o n 1. 3  
( V B P 1 5- 0 0 1).  I n t he bl o o d/ brai n c o nce ntrati o n m o use e x peri me nt i n viv o, t he plas ma 
c o nce ntr ati o ns of va m or ol o ne were hi g h er t ha n brai n c o nce ntrati o ns wit h t h e A U C a n d 
C ma x  a p pr o xi matel y 2-f ol d hi g her i n plas m a t ha n i n brai n ( Re vera Ge n Re p ort N os. 
A D M E - N C G-P P B - N C 1 3 5, A D M E- V B P-P P B - V 0 0 2, A D M E- N C G-B P - N C 1 3 4, N C A T S 
2 0 1 3- 3 8). 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 3 1  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
1. 2. 2. 4  
Met a b olis m 
T he i n vitr o a n d i n viv o d ata de m o nstrate t h at va m or ol o ne ca n b e meta b olize d via 
m ulti ple me ta b olic pat h wa ys, i ncl u di n g gl uc ur o ni dati o n, h y dr o x ylati o n, a n d re d ucti o n.  
Gl uc ur o ni dati o n a p peare d t o be t he maj or meta b olic pat h wa y i n h u ma n cells i n vitr o.  All 
meta b olites o bser ve d i n h u ma n i n vitr o were o bser ve d i n m o n ke y i n vitr o.  M ost h u ma n 
meta b olites i de ntifie d i n vitr o were als o f o u n d i n m o use a n d d o g.  T h us, t here is n o 
u ni q ue h u ma n meta b olite i de ntifie d f or va m or ol o n e. 
T he meta b olic sta bilit y of va m or ol o ne was assess e d i n n o n- G o o d La b orat or y Practice 
( G L P) st u dies.  Bas e d o n t he data ge n erate d, va m or ol o ne was hi g hl y sta ble f or u p t o 
6 0 mi n utes i n h u ma n, m o n ke y, d o g, a n d m o use li ver micr os o mes i n t he prese nce or 
a bse nce of nic oti na mi de a de ni ne di n ucle oti de p h os p hate ( N A D P H) a n d sta ble f or u p t o 
6 0 mi n utes i n rat li ver i n t he a bse nce of N A D P H.  M o derate met a b olis m was a p pare nt i n 
rat li ver micr os o mes i n t he prese n ce of N A D P H sti m ulati o n ( 3 5 % re mai ni n g), s u g gesti n g 
t hat rat was a hi g h met a b olizer of va m or ol o ne rel ati ve t o ot her s pecies ( m o use, d o g, 
h u ma n) ( Re vera G e n Re p ort N os. NI H- R 2 5 2 6, a n d A D M E- V B P- L M - V 0 0 3). 
Va m or ol o ne di d n ot si g nifica ntl y i n hi bit a n y of t h e c yt oc hr o me P 4 5 0 ( C Y P) e nz y m e 
is of or ms teste d ( C Y P 1 A 2, 2 B 6, 2 C 8, 2 C 9, 2 C 1 9, 2 D 6, a n d 3 A 4).  Va m or ol o ne 
m o deratel y i n d uce d C Y P 3 A 4 ( 2 4 % t o 4 2 %), i n dicati n g t hat va m or ol o n e is a p ote ntial 
i n d ucer of C Y P 3 A 4 ( Re v era G e n Re p ort N os. A D M E- V B P-I n hi biti o n- V 0 0 5, A D M E-
V B P-I n d u cti o n- V 0 0 6, A D M E- V B P-I n d ucti o n- V 0 0 9). 
1. 2. 2. 5  
E xcreti o n 
Va m or ol o ne s h o we d hi g h plas ma cleara nce i n rats b ut, c o nsiste nt wit h t he e xte nsi ve 
meta b olis m i n he pat oc yt es fr o m t his s pecies, t he biliar y a n d uri nar y e x creti o n of t he 
pare nt c o m p o u n d w as l o w wit h a n a vera ge of < 0. 0 5 % of t he d ose rec o v ere d i n bile a n d 
a p pr o xi matel y 0. 1 % i n uri ne.  O verall, va m or ol o ne s h o we d hi g h plas ma cl eara n ce a n d 
e xtre mel y l o w biliar y a n d uri nar y e x creti o n ( Re v era Ge n Re p ort N o. N C A T S 2 0 1 3- 4 4). 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 3 2  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
1. 2. 3  
T o xic ol o gy 
1. 2. 3. 1  
Si n gle D ose 
Crl: C D 1(I C R) mice w ere a d mi nistere d va m or ol o n e o nce via oral ga v a ge at 5 0, 1 2 5, 2 5 0, 
a n d 5 0 0 m g/ k g a n d o bs er ve d f or a b n or malities.  All a ni mals s ur vi ve d t o t heir sc he d ule d 
ter minati o n, a n d t here were n o si g nifica nt a b n or malities o bser ve d.  T here was a sli g ht 
decrease i n b o d y w ei g ht attri b ute d t o va m or ol o ne i n b ot h males a n d fe males at d oses 
a b o ve 1 2 5 m g/ k g.  A d os e de pe n d e nt decreas e i n f o o d c o ns u m pti o n relate d t o 
va m or ol o ne was als o o bser ve d i n males a n d fe mal es.  N o ot her a b n or malities were 
o bser ve d i n e x peri me ntal mice ( Re vera Ge n R e p ort N o. 1 9 9 8- 0 0 2). 
Bea gl e d o gs recei ve d si n gle 6 0, 1 8 0, 3 6 0, a n d 7 5 0 m g/ k g d oses of va m or ol o ne usi n g a n 
escalati o n st u d y desi g n wit h a 4- da y was h o ut peri o d bet wee n d oses.  All a ni mals 
s ur vi ve d d ose escalati o n.  Cli nical si g ns attri b ute d t o va m or ol o ne ( 7 5 0 m g/ k g) i ncl u d e d 
re d disc ol orati o n of t he ears a n d face.  T his effect occ urre d wit hi n a fe w h o urs of d osi n g 
a n d was tra nsi e nt.  T he hi g hest d ose als o res ulte d i n i ncrease d w hite bl o o d cell c o u nt 
(i ncrease d ne utr o p hils a n d m o n oc ytes [fe mal e o nl y] a n d decrease d l y m p h o c yt es a n d 
e osi n o p hils [ male a n d fe male]).  At t he 3 6 0 a n d 7 5 0 m g/ k g d ose le vels, sli g ht ele v ati o ns 
i n al b u mi n were o bser ve d.  A mil d ele vati o n i n c h olester ol at t he 7 5 0 m g/ k g (a n d 
p ossi bl y 3 6 0 m g/ k g) d os e le vel was als o o bser ve d ( Re vera Ge n Re p ort N o. 1 3 7 8 8. 0 1. 0 1). 
I n c y n o m ol g us m o n ke ys, si n gle oral d oses of u p t o 5 0 0 m g/ k g were well t olerate d wit h 
n o si g nifica nt a b n or malities o bser ve d ( R e vera Ge n Re p ort N o. 1 9 9 8- 0 0 1). 
1. 2. 3. 2  
M ulti ple D ose 
Va m or ol o ne or v e hicle w as a d mi nistere d t o Crl: C D 1(I C R) mice o nce dail y f or 2 8 
c o nsecuti ve da ys at d oses of 1 0, 3 0 a n d 1 0 0 m g/ k g/ da y.  All a ni mals s ur vi ve d t o t heir 
sc he d ule d necr o ps y wit h t he e x ce pti o n of a fe m ale m o use ( 1 0 0 m g/ k g/ da y d ose gr o u p) 
t hat was f o u n d dea d o n Da y 1 6.  T he ca use of deat h was c o nsi dere d i nci d e ntal a n d 
attri b ute d t o a d osi n g i nj ur y b ase d o n t he a m o u nt of re d fl ui d i n t he t h oraci c ca vit y. 
N o effects attri b uta ble t o va m or ol o ne were o bser ve d i n f o o d c o ns u m pti o n, o p ht hal mic 
e x a mi nati o n, or uri nal ysis d uri n g t he st u d y.  D ose- de pe n de nt d ecrease i n b o d y wei g ht 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 3 3  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
gai n w as o bser v e d at all d oses; h o we ver, wei g ht was f ull y re gai n e d d uri n g t he rec o v er y 
peri o d.  A dre n al gla n d wei g hts were v aria ble bet wee n gr o u ps a n d ge nerall y decrease d, 
b ut wit h o ut a d ose res p o nse relati o ns hi p, a n d c orrelate d micr osc o pi call y wit h mi ni mal t o 
m o derate vac u olar d e ge n erati o n a n d c ortical atr o p h y.  After t he 2- wee k rec o ver y peri o d 
t here was e vi de nce of vac u olar de ge nerati o n of t he a dre n al gla n d.  Li ver wei g hts were 
si g nifica ntl y i ncreas e d at t he 1 0 0 m g/ k g/ da y d ose le vel.  He pat o cell ular h y pertr o p h y, 
i ncreas e d vac u ol ati o n, a n d necr osis (si n gle cell) were see n i n a fe w male mi ce at 
3 0 m g/ k g/ da y.  T here w as e vi de nce of li pi d a n d gl yc o ge n acc u m ulati o n.  Ser u m ala ni ne 
a min otra nsferase a n d as p artate a mi n otra nsferase l e vels were hi g her wit h ass ociate d 
micr osc o pic h y pertr o p h y/ vac u olati o n/ necr osis at 1 0 0 m g/ k g/ da y.  S plee n wei g hts 
decrease d i n a d os e- de p e n de nt ma n ner a n d c orrelate d wit h a decreas e d n u m ber of 
l y m p h oc ytes i n s plee n.  T h y m us wei g hts de creas e d i n a d ose de p e n de nt m a n ner a n d were 
ass ociate d micr os c o picall y wit h l y m p h oi d atr o p h y.  Mice ha d d ose- de pe n d e nt re d ucti o ns 
i n ser u m l y m p h oc ytes w hic h were si g nifica nt i n t he 1 0 0 m g/ k g d ose gr o u p.  After t he 
rec o ver y peri o d, all para meters ret ur n e d t o n or mal ( u ntreate d) e x ce pt f or t h y m us wei g hts, 
w hic h were i ncrease d. 
Base d o n t he li ver-relat e d fi n di n gs i n t his st u d y, t he n o o bser ve d a d verse effect le vel 
( N O A E L) f or va m or ol o ne i n mice is 3 0 m g/ k g/ da y ( Re v era Ge n Re p ort N o. 1 9 9 8- 0 0 9). 
A G L P- c o m plia nt st u d y was carrie d o ut t o e val u ate t he t o xicit y of t he t est article, 
va m or ol o ne, i n Crl: C D 1 ® (I C R) mice after a d mi nistrati o n f or 2 6 wee ks, i ncl u di n g 
e val uati o n of t he re versi bilit y, pr o gressi o n, or del a ye d a p peara n ce of a n y o bser ve d 
c ha n ges f oll o wi n g a 4- w ee k p ost- d ose o bser vati o n peri o d.  Assess me nt of t o xicit y was 
base d o n m ortalit y, cli nical o bser vati o ns, b o d y wei g ht, a n d f o o d c o ns u m pti o n; 
o p ht hal m osc o pic e x a mi nati o ns; a n d cli nical a n d a nat o mic pat h ol o g y.  T o xic o ki netic 
assess me nt was c o n d u cte d f or t he test articl e. 
T here w ere n o v a m or ol o ne-rel ate d effects o n m ortalit y, detaile d cli nical o bser vati o ns, 
f o o d c o ns u m pti o n, o p ht hal m ol o g y, s per m e val uati o ns, or b o ne le n gt hs (fe m ur or ti bi a). 
Fi ve test articl e-treate d mice were u nsc he d ul e d d eat hs (e ut ha nize d i n extr e mis or f o u n d 
dea d) d uri n g t he d osi n g p hase.  T hree of t hes e were c o nsi dere d t o be p ote ntiall y d ue t o 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 3 4  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
d osi n g i nj ur y base d o n micr osc o pic fi n di n gs i n me diasti n u m, e picar di u m, or l u n g.  O ne 
of t hese u nsc h e d ule d deat hs was attri b ute d t o m o derate pr o gressi ve n e p hr o pat h y; a 
s p o nta ne o us bac k gr o u n d fi n di n g.  T he d eat h of o n e male at t he 5 m g/ k g/ da y d ose was 
u n deter mi ne d si nce t h ere were n o maj or pat h ol o gic fi n di n gs t o e x plai n t he u nsc he d ule d 
deat h of t his a ni mal; t here was n o tar get or ga n t o xicit y i n t he m o use.  Tar get or ga n 
t o xicit y was n ot c o nsi dere d a c o ntri b ut or t o t he d eat h of t hese a ni mals a n d t here was n o 
d ose-relati o ns hi p i n i nci d e nce. 
A va m or ol o ne-relate d i n creas e i n b o d y wei g ht gai n was o bser v e d relati ve t o c o ntr ols i n 
males ( + 1 4 %) a n d fe mal es ( + 2 3 %) at t he 4 5 m g/ k g/ da y d os e.  I ncreas es i n b o d y wei g hts 
at 4 5 m g/ k g/ da y w ere n ot c o nsi dere d t o be a d verse d ue t o t he ge neral healt h of t he 
a ni mals o verall.  D uri n g t he rec o v er y p has e, b o d y wei g hts i n males ret ur ne d t o 
c o m para ble l e vels as c o ntr ols, h o we ver fe male b o d y wei g hts r e mai ne d i ncrease d 
c o m pare d t o f e male c o ntr ols. 
E vi de nce of a mi ni mal t o mil d va m or ol o ne-relate d he patic effects were o bser ve d i n males 
at d oses ≥5 m g/ k g/ da y a n d fe males at 4 5 m g/ k g/ da y, i n dicat e d b y mil d t o m o derate 
i ncreas es i n al kali ne p h os p hatase, ala ni n e a mi n otr a nsferase, as p artate a mi n otra nsferase 
acti vities, a n d/ or t otal bilir u bi n, as relate d t o micr osc o pic he pat ocell ular vac u olati o n, 
i nfla m mati o n, a n d/ or necr osis i n males at ≥ 1 5 m g/ k g/ da y a n d fe males at 4 5 m g/ k g/ da y; 
t hese cha n ges ha d ge n erall y res ol ve d at rec o ver y c ollecti o ns wit h t he e x ce pti o n of 
mi ni mal i ncreases i n ala ni ne a mi n otra nsferase acti vit y i n fe males at 4 5 m g/ k g/ da y, w hi c h 
ma y  h a ve c orrel ate d t o micr osc o pic li ver p at h ol o g y. 
A mil d va m or ol o ne-relat e d i ncrease i n ne utr o p hil c o u nts was o bser v e d i n b ot h se xes at 
4 5 m g/ k g/ da y wit h c o nc urre nt decreases i n l y m p h oc yt e c o u nts i n fe mal es at 
4 5  m g/ k g/ da y c o nsiste nt wit h a gl uc oc ortic oi d-li k e effect, as relate d t o micr osc o pic 
l y m p h oi d de pleti o n.  H o we ver, a n i nfla m mat or y sti m ul us ma y h a ve c o ntri b ute d t o 
i ncreas es i n ne utr o p hil c o u nts, as relate d t o micr osc o pic li ver i nfla m mati o n; t hese 
c ha n ges ha d ge nerall y res ol ve d at rec o v er y c ollecti o ns. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 3 5  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
A mil d va m or ol o ne -relat e d decreas e i n c hl ori de was o bser ve d i n males at d oses 
≥ 5 m g/ k g/ d a y a n d fe mal es at d oses ≥ 1 5 m g/ k g/ d a y t h at lac ke d c orrelati ve fi n di n gs 
a m o n g ot her st u d y e n d p oi nts; res ol uti o n f or t his o bser vati o n c o ul d n ot be d eter mi ne d. 
A mil d va m or ol o ne -relat e d i ncrease i n al b u mi n was o bser ve d i n males at d oses 
≥ 5 m g/ k g/ d a y a n d fe mal es at 4 5 m g/ k g/ da y wit h c o nc urre nt mil d i ncreas es i n gl o b uli n i n 
fe males at 4 5 m g/ k g/ da y; t hese c ha n ges ha d res ol ve d at rec o ver y c ollecti o ns. 
A mi n or va m or ol o ne -rel ate d alterati o n i n li pi d meta b olis m was o bser ve d i n b ot h se x es at 
t he 4 5 m g/ k g/ da y d ose a n d fe males at t he 1 5 m g/ k g/ da y d os e i n dicate d b y i ncreas es i n 
tri glyceri de a n d/ or c h olester ol; t hese c ha n ges ha d res ol ve d at rec o ver y c ollecti o ns. 
Va m or ol o ne-relate d ma cr osc o pic fi n di n gs occ urre d i n t he li ver of mice at t he 
4 5 m g/ k g/ da y d ose.  T a n disc ol orati o n occ urre d i n o ne fe male a n d f o ur m ales at t his d ose 
i n t he d osi n g p hase.  T his c orrel ate d wit h micr o vesic ular/ macr o vesic ular he pat oc yt e 
vac u olati o n.  T here were n o test article-relate d macr osc o pic fi n di n gs i n rec o ver y a ni mals. 
Test article-relate d micr osc o pic fi n di n gs o cc urre d i n a dre nal gla n d (c ortical atr o p h y wit h 
c orrel ati n g d ecreases i n a dre nal wei g hts i n fe m ales), li ver (i ncrease d s e verit y of 
ce ntril o b ular h y pertr o p h y; he p at oc yte vac u olati o n; a n d i nfla m mati o n/ necr osis), l y m p h oi d 
tiss ues (t h y m us, s plee n, ma n di b ular l y m p h n o de, mese nteric l y m p h n o de, a n d g ut 
ass ociate d l y m p h oi d tiss ue [ G A L T]) s ki n, a n d pa ncreatic islets ( mi ni mal t o mil d 
h y pertr o p h y).  O bs er ve d c ha n ges i n t hese tiss ues are c o nsi dere d 
p har ma c ol o gic all y- m e diate d a n d n ot a d verse. 
A n i ncreas e d i nci de n ce of decrease d a na ge n hair f ollicles occ urre d i n mice at t he 
4 5 m g/ k g/ da y d ose.  D ecrease d a na ge n hair f ollicl es were d oc u me nte d f or i n di vi d u al 
a ni mals w he n t here were n o a na ge n h air f ollicles i n t he secti o n of s ki n.  I nci de nce i n 
c o ntr ols a n d mice at t he 5 a n d 1 5 m g/ k g/ da y d oses were si milar.  A s e verit y sc ore was 
n ot gi ve n t o t he de crease as t his ma y ha v e bee n s o me w hat de pe n d e nt o n size of s ki n 
sa m ple.  T his c ha n ge is n ot c o nsi dere d a d v erse. 
T here w as f ull re v ersi bilit y of l y m p h oi d c ha n ges i n t h y m us, s plee n, mese nt eric l y m p h 
n o de, ma n di b ular l y m p h n o de, a n d G A L T.  T here n o mea ni n gf ul differe nces bet wee n 
treate d a ni mals a n d c o ntr ols at t he e n d of t he rec o ver y tiss ues f or t hes e l y m p h oi d tiss ues.  

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 3 6  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
T here w as rec o ver y of a dre nal gla n d fi n di n gs i n fe males a n d partial rec o v er y of a dre n al 
gla n d fi n di n gs i n males.  I n a d diti o n, t here was partial re versi bilit y of li ver fi n di n gs f or 
males a n d fe m ales.  Mi n or c ha n ges p ersiste d i n t he pa ncreas a n d s ki n. 
S yste mic e x p os ure t o va m or ol o ne a p peare d t o be se x- de pe n de nt o n Da y 1 ( males > 
fe males) a n d a p peare d t o be i n de pe n de nt of s e x o n Da y 1 7 9.  F oll o wi n g dail y 
a d mi nistrati o n of va m or ol o ne i n fe males a n d m ales, s yste mic e x p os ure ( A U C 0- 2 4 hr) a n d 
C ma x  val ues of va m or ol o ne i ncrease d wit h i ncreasi n g d ose i n a great er t ha n 
d ose- pr o p orti o nal ma n ner o n Da y 1 a n d i n a n a p pr o xi matel y d ose- pr o p orti o nal ma n ner 
o n Da y 1 7 9.  S yste mic e x p os ure t o va m or ol o ne i n fe males a p peare d t o i ncrease f oll o wi n g 
re peat e d a d mi nistrati o n of va m or ol o ne at 5 m g/ k g/ da y, di d n ot a p p ear t o c h a n ge 
f oll o wi n g re peat e d a d mi nistrati o n of va m or ol o ne at 1 5 m g/ k g/ da y, a n d a p p eare d t o 
dec rease f oll o wi n g re peate d a d mi nistrati o n of va m or ol o ne at 4 5 m g/ k g/ da y.  S yste mic 
e x p os ure t o va m or ol o ne i n males a p peare d t o decrease f oll o wi n g re peat e d a d mi nistrati o n 
of va m or ol o ne. 
T he o nce d ail y a d mi nistrati o n of va m or ol o ne via oral ga va ge t o mice f or 2 6 wee ks at 5, 
1 5, a n d 4 5 m g/ k g/ da y di d n ot pr o d uce a n y a d verse effects.  T heref ore, t he N O A E L is 
c o nsidere d t o be 4 5 m g/ k g/ da y u n d er t he c o n diti o ns of t his st u d y. 
Va m or ol o ne or v e hicle w as a d mi nistere d t o bea gl e d o gs o nce dail y f or 2 8 c o nsec uti ve 
da y s at d oses of 2, 1 0 a n d 5 0 m g/ k g/ da y.  All a ni mals s ur vi ve d t o t heir sc he d ule d 
ter mi nati o n a n d n o effect of va m or ol o ne was n ote d o n gr oss vis ual i ns pecti o n, b o d y 
wei g ht, b o d y te m p erat ur e, f o o d c o ns u m pti o n, o p ht hal m ol o g y, electr ocar di o gra p h y or 
uri nal ysis para meters at necr o ps y.  A d os e- de p e n de nt decrease i n t he e x pecte d n or mal 
b o d y w ei g ht gai n was o bser ve d at all d oses b ut wei g hts ge n erall y i ncreas e d t o a n or mal 
le vel d uri n g t h e rec o ver y peri o d. 
A dre nal gla n d wei g hts decrease d wit h va m or ol o n e treat me nt, w hic h c orrel ate d wit h mil d 
or m o derate diff use bilat eral atr o p h y of t he a dre n al c orte x, mil d m ultif ocal bilateral 
vac u olati o n of t he a dre n al c orte x, i ncrease d w hite bl o o d cell a n d ne utr o p hil c o u nts, a n d 
decrease d e osi n o p hil c o u nts.  Li ver wei g hts i ncrease d i n t he 5 0 m g/ k g/ da y d ose gr o u p, 
w hic h c orrelate d wit h diff use h y pertr o p h y a n d va c u olati o n a n d i ncreas e d le vels of 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 3 7  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
al kali ne p h os p hatase a n d ga m ma gl uta m yltra nsferase.  S plee n wei g hts de crease d, w hic h 
c orrel ate d wit h l y m p h oi d de pleti o n.  T h y m us w ei g hts decrease d, w hic h c orres p o n de d t o 
diff use l y m p h oi d de pl eti o n.  Wit h t he e x ce pti o n of diff use de pl eti o n of l y m p h oc yt es i n 
t h y m us i n t he 5 0 m g/ k g gr o u p, all a b n or mal para meters ret ur n e d t o n or mal d uri n g t he 
reco ver y peri o d. 
T he N O A E L was c o nsi d ere d b y t he st u d y direct or t o be 1 0 m g/ k g/ da y.  Alt h o u g h 
re versi ble, t he li ver c h a n ges were c o nsi der e d a d v erse at 5 0 m g/ k g/ da y beca use t he 
se verit y sc ore was m o derate a n d t he c ha n ges w ere diff use i n nat ure i n all a ni mals treate d 
at t he hi g h d ose.  T his deter mi nati o n is i n c o ntrast t o t he c o ncl usi o n dra w n b y t he st u d y 
pat h ol o gist, w h o c o nsi dere d t he N O A E L t o be 5 0 m g/ k g/ da y d ue t o r e versi bilit y 
f oll o wi n g cessati o n of d osi n g ( Re v era Ge n Re p ort N o. 3 1 3 0 2). 
Va m or ol o ne or v e hicle w as a d mi nistere d t o bea gl e d o gs o nce dail y f or 3 9 wee ks at d oses 
of 2, 1 0 a n d 5 0 m g/ k g/ da y.  Si x d o gs of eac h se x recei ve d eac h d ose or place b o, a n d t w o 
of t he si x d o gs of eac h se x at eac h d ose or place b o were f oll o we d f or a n a d diti o nal 
4 wee ks t o e v al uate re versi bilit y, pr o gressi o n, or d ela ye d a p p eara nce of a n y o bser ve d 
c han ges.  O n e male d o g t hat recei ve d 5 0 m g/ k g/ d a y was e ut ha nize d i n e xtre mis o n Da y 
2 7 3 d ue t o par a p hi m osis (a n e xte n de d pe nis).  All ot her a ni mals s ur vi ve d t o t heir 
sc hed ule d ter mi nati o n.   
Detaile d c li nical o bser vati o ns c o nsi dere d test articl e-rel ate d at 5 0 m g/ k g/ da y, a n d 
re versi ble, i ncl u d e d decrease d acti vit y (c o nsi d ere d a d verse), str u g gli n g d uri n g d osi n g, 
feces s oft, li m b f u ncti o n i m paire d, i nter di gital c ysts, a n d u n ke m pt a p peara n ce 
(c o nsi dere d a d verse).  T est article-relate d, d ose- de pe n de nt i ncreases i n b o d y wei g ht gai ns 
c orrel ati n g wit h i ncreas es i n f o o d c o ns u m pti o n were o bser ve d relati ve t o c o ntr ols i n 
males at a ll d ose le vels a n d i n fe males at 1 0 a n d 5 0 m g/ k g/ da y.  Test article-rel ate d, 
re versi ble i ncreases i n a v era ge m ea n f o o d c o ns u m pti o n, relati ve t o c o ntr ols, o ver t he 
c o urse of t he 3 9- wee k d ose p hase were o bs er ve d i n b ot h se x es at 1 0 a n d 5 0 m g/ k g/ da y.   
N o test ar ticle-relate d o p ht hal m ol o gical effects were n ote d.  N o test-articl e-relate d 
c han ges w ere n ot e d i n res pirat or y rates or rectal te m perat ures.  T h ere m a y ha ve bee n a 
mil d d os e-relate d re versi ble i ncreas e i n t he heart rate at t he ter mi nal p ost- d ose i nter val 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 3 8  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
t hat was si g nifica ntl y differe nt fr o m ve hicle i n b ot h se xes f oll o wi n g t he 5 0 m g/ k g/ da y 
d ose.  S e me n a nal ysis/e v al uati o n f or test article affects c o ul d n ot be c o n d ucte d as t here 
were  n ot e n o u g h via ble s a m ples c ollecte d. 
Test article-relate d effects o n cli nical pat h ol o g y e n d p oi nts wit h micr osc o pic c orrelates 
i ncl u de d t he f oll o wi n g: 
 A he pat oc ell ular a n d he p at o biliar y effect i n males at 1 0 m g/ k g/ da y a n d b ot h se xes 
at 5 0 m g/ k g/ da y, w hic h i ncl u de d i ncrease d al kali ne p h os p hatase, ga m ma 
gl ut a m yltra nsf eras e, ala ni ne a mi n otra nsferase, a n d as partate a mi n otra nsferase 
acti vit y.  T hes e c h a n ges c orrel ate d wit h micr osc o pic c ha n ges i n t he li ver, bile 
d uct , a n d gall bla d der.  T his s pectr u m of c ha n ges was c o nsi dere d a d v erse i n b ot h 
se xes at 5 0 m g/ k g/ d a y.   
 T here w as als o e vi de n ce of a n i nfla m mat or y res p o nse i n b ot h se xes at 
5 0 m g / k g/ da y, w hic h i ncl u de d i ncrease d t otal le u k oc yt e, ne utr o p hil, a n d 
m o n oc y te c o u nts, a n d i ncrease d fi bri n o ge n a n d/ or gl o b uli n c o nce ntrati o ns.  T he 
i nflam mat or y res p o nse was li kel y sec o n dar y t o i nfla m mati o n i n t he li ver 
ass ociate d wit h he p at ocell ular necr osis.  Platelet c o u nts were als o i ncreas e d i n 
b ot h se x es at 5 0 m g/ k g/ d a y a n d ma y ha v e bee n sec o n dar y t o t he i nfla m mat or y 
res p o nse. 
F oll o wi n g a 4- w ee k rec o ver y peri o d, all n ote d cli nical pat h ol o gi cal c ha n ges res ol ve d, 
wit h t he e x ce pti o ns of i ncreas e d ala ni n e a mi n otra nsferas e acti vit y i n b ot h se xes at 
5 0 m g/ k g/ da y, a n d i ncrease d gl o b uli n i n males at 5 0 m g/ k g/ da y. 
Re versi ble, test article-relate d macr osc o pic fi n di n gs i ncl u de d mil dl y t o m o deratel y 
e nlar ge d li vers i n males a n d fe males at 5 0 m g/ k g/ d a y, w hic h c orrelat e d micr osc o picall y 
wit h pa nl o b ular he pat oc ell ular h y pertr o p h y a n d/ or he pat ocell ular v ac u olati o n; 
he m orr ha ge i n t he gall bla d der of o n e 5 0 m g/ k g/ d a y fe male, t h at was ass o ciate d wit h 
m o derate ac ute i nfla m mati o n a n d mil d vasc ular necr osis, a n d c o nsi dere d t o be a d vers e; 
re d f ocus/f o ci wit hi n t he p yl or us of t h e st o mac h of o ne 5 0 m g/ k g/ da y fe mal e a n d o ne 
male a t 1 0 m g/ k g/ da y, w hic h c orrelate d micr osc o picall y wit h mil d ac ute i nfla m mati o n i n 
t he female.   

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 3 9  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
Test article-relate d or ga n wei g ht c ha n ges at t he ter mi nal necr o ps y i ncl u de d decreases i n 
a dre nal gla n d wei g hts i n b ot h se x es at ≥ 2 m g/ k g/ da y ( micr osc o pic c orrelat e of bilateral 
c ortical atr o p h y); i n creas es i n li ver wei g hts i n b ot h se x es at ≥ 1 0 m g/ k g/ da y ( micr osc o pic 
c orrel ates of pa nl o b ular he pat ocell ular h y p ertr o p h y a n d/ or he pat ocell ular vac u olati o n); 
i ncreas es i n ki d ne y wei g hts i n fe males at ≥ 1 0 m g/ k g/ da y a n d m ales at 5 0 m g/ k g/ da y 
( micr osco pic c orrel ate of bilateral t u b ular vac u olati o n); decreases i n pr ostate gla n d 
wei g hts i n males at 5 0 m g/ k g/ da y ( micr osc o pic c orrelate of decrease d secret or y pr o d u ct).  
T he se or ga n wei g ht c ha n ges were all re v ersi ble, e x ce pt f or t he decreas es i n t he pr ostate 
gla n d.   Micr osc o pic e v al uati o n re veal e d t he f oll o wi n g test article-relate d c ha n ges: 
a dre nal gla n ds (atr o p h y of t he z o na fascic ul ata a n d z o na retic ularis a n d 
h y pertr o p h y/ h y per plasi a of t he z o n a gl o mer ul osa i n b ot h se xes at ≥ 1 0 m g/ k g/ da y a n d 
atr o p h y was c o nsi d ere d a d verse); es o p h a g us a n d p yl or us of t h e st o mac h 
(er osi o n/ ulcerati o n i n a fe w a ni mals of b ot h se x es at 5 0 m g/ k g/ da y); gall bl a d der 
( h yp ertr o p h y/ h y per plasia of t he m uc osal e pit heli u m i n b ot h se x es at ≥ 1 0 m g/ k g/ da y a n d 
c yt o plas mic v ac u olati o n of t he m uc osal e pit heli u m i n males at ≥ 1 0 m g/ k g/ da y a n d 
fe males at ≥ 2 m g/ k g/ da y); li ver ( he pat o cell ular vac u olati o n i n males at ≥ 1 0 m g/ k g/ da y 
a n d females at ≥ 2 m g/ k g/ da y, p a nl o b ular h y pertr o p h y i n males at 5 0 m g/ k g/ da y a n d 
fe males at ≥ 1 0 m g/ k g/ da y, a n d i nfl a m mati o n/ necr osis i n b ot h se x es at 5 0 m g/ k g/ da y a n d 
c o nsidere d a d vers e, bile d uct h y p er plasia i n b ot h se x es at 5 0 m g/ k g/ d a y, bile d uct 
h y pertr o p h y i n males at 5 0 m g/ k g/ da y a n d fe males at ≥ 1 0 m g/ k g/ da y, a n d c yt o plas mic 
vac u olati o n of t he bile d u ct e pit heli u m i n b ot h se xes at ≥ 1 0 m g/ k g/ da y); ki d ne ys 
( bilateral t u b ular v ac u olati o n i n males at 5 0 m g/ k g/ da y a n d fe mal es at ≥ 1 0 m g/ k g/ da y 
a n d an i ncrease d i n ci de n ce of bilateral bas o p hilic t u b ules i n males a n d fe m ales at 
5 0  m g/ k g/ da y); l y m p h oi d de pleti o n i n b ot h se x es at 5 0 m g/ k g/ d a y i n ma n di b ular a n d 
mese nter ic l y m p h n o des, t h y m us a n d s plee n ( wit h e xtra me d ullar y h e mat o p oiesis i n 
5 0 m g/ k g/ da y fe m ales); b o ne marr o w i n t he ster n u m (i ncreas e d a di p oc ytes i n males at 
≥ 2 m g / k g/ d a y a n d fe m al es at 5 0 m g/ k g/ da y); t estes (s per mat o c yt e/s per mati d 
de ge nerati o n i n males at 5 0 m g/ k g/ da y); e pi di d y mi des ( oli g os per mia/ ger m cell de bris i n 
males at 5 0 m g/ k g/ da y); o varies (a bs e nt c or p ora l utea i n fe males at ≥ 2 m g/ k g/ da y a n d 
c o nsidere d a d vers e); t he ma m mar y gl a n d a n d ot her tiss ues i n t he fe male re pr o d ucti ve 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 4 0  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
tract ( uter us, cer vi x, a n d va gi n a) of t hes e a ni mals were c o nsiste nt wit h a ni mals t hat ha ve 
n ot o v ulate d; vac u olati o n i n t he e pit heli u m of t he ma m mar y gl a n d d uct i n fe males at 
5 0 m g/ k g/ da y; par oti d sali var y gla n d (c yt o plas mic alterati o n i n b ot h se xes at 
≥ 1 0 m g / k g/ d a y); bice ps fe m oris (atr o p h y of t he s keletal m uscle i n b ot h se x es at 
5 0 m g/ k g/ da y); s ki n (atr o p h y a n d al o peci a/ h y p otri c h osis i n males at 5 0 m g/ k g/ da y a n d 
fe males at ≥ 1 0 m g/ k g/ da y); pr ostat e gla n d ( d ecrease d secret or y pr o d u ct i n males at 
5 0 m g/ k g/ da y); t h yr oi d gla n ds ( bilateral i ncreas e d c oll oi d i n males at ≥ 1 0 m g/ k g/ da y). 
Ma n y  of t he fi n di n gs were felt b y t he St u d y Direct or t o be c o nsiste nt wit h t he 
p har mac ol o g y of t h e test article i ncl u di n g c ortical atr o p h y of t he a dre nal gl a n ds (affecti n g 
t he z o na fascic ulata a n d retic ularis), ge n eralize d l y m p h oi d de pleti o n i n l y m p h oi d tiss ues 
(t h y m us, s plee n, a n d l y m p h n o des), i ncrease d a di p oc yt es i n t he b o ne marr o w, atr o p h y of 
t he s keletal m uscle, al o p ecia/ h y p otric h osis a n d atr o p h y of t he s ki n (t hi n ni n g of t he 
der ma l c olla ge n a n d atr o p h y of h air f ollicles a n d a d ne x a), a n a bs e nce of c or p ora l utea i n 
t he o vary (li kel y i n dicati ve of dela ye d p u bert y), decrease d secret or y pr o d u ct i n t he 
pr ostate  gla n d, a n d m ulti ple c ha n ges i n t he li ver.  T he li ver ha d p a nl o b ular h y pertr o p h y 
a n d vac u olati o n of h e pat oc yt es c o nsiste nt wit h gl yc o ge n acc u m ulati o n.  D ue t o t he 
ma g nit u de of h y p ertr o p h y a n d v ac u olati o n, t here were (li kel y s ec o n dar y) f oci of 
he pat ocell ular n ecr osis a n d i nfla m mati o n. 
Test article-relate d micr osc o pic fi n di n gs at t he rec o ver y necr o ps y were prese nt i n t he 
a dre nal gla n ds, li ver, gall bla d der, ki d ne ys, st o mac h ( p yl or us), fe m ale re pr o d ucti ve tract 
( o varies), m ale re pr o d ucti ve tract (testes, e pi di d y mi des, pr ostate gl a n d), m ese nteric  
l ym p h n o de, s kelet al m uscle ( bice ps fe m oris), a n d par oti d sali var y gla n d. 
T he N o  O bser ve d A d v erse Effect Le vel was 2 m g/ k g/ da y f or males; a N o O bser ve d 
A d verse  Effect Le vel w as n ot o bser ve d f or fe males ( Re vera Ge n Re p ort N o. 1 9 9 8- 0 1 4).  
N o n- nai ve c y n o m ol g us m o n ke ys w ere a d mi nistere d va m or ol o ne or ve hicl e o nce d ail y f or 
7 c o nsec uti ve da ys at d oses of 1 0 0, 3 0 0, a n d 6 0 0 m g/ k g.  All a ni mals s ur vi ve d u ntil t he 
e n d of t he st u d y peri o d.  T here were effects o n cli nical o bser vati o ns, f o o d c o ns u m pti o n, 
a n d uri nal ysis attri b uta ble t o va m or ol o ne t hat are descri be d b el o w. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 4 1  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
T here w as a d ose pr o p orti o nal decrease i n b o d y wei g ht gai n o bser ve d i n m ales a n d 
fe males at eac h d os e ( u p t o 1 1 % a n d 9 % res pecti v el y) relat e d t o va m or ol o n e.  A 
cessati o n of t he b o d y w ei g ht l oss i n treat me nt was o bser ve d d uri n g t he rec o ver y p hase 
b ut n o rec o ver y of b o d y wei g ht l ost d uri n g t he 7 da ys of d osi n g was o bser ve d. 
At ter mi nati o n t here w ere n o nsi g nifica nt i ncreases i n re d cell mass a n d d ecreases i n 
l y m p h oc ytes ( u p t o 5 6 %) i n t he 6 0 0 m g/ k g/ da y d ose gr o u p.  H o we v er, m ost i n di vi d ual 
a ni mals, i ncl u di n g c o ntr ols, ha d decreases i n l y m p h oc yt es ( u p t o 8 1 %) at ter mi nati o n 
relati ve t o t heir res pecti v e pretest.  T he y h a d res ol ve d b y t h e rec o ver y i nter val i n b ot h 
se x es. 
I n b ot h se x es recei vi n g ≥ 3 0 0 m g/ k g/ da y, t here was i ncrease d urea nitr o ge n ( u p t o 1 4 1 %), 
creati ni ne ( u p t o 5 8 %), t otal pr otei n ( u p t o 1 5 %), al b u mi n ( u p t o 1 1 %), gl o b uli n ( u p t o 
2 5 %), a n d/ or p otassi u m ( u p t o 3 9 %) wit h c o nc urre nt decreases i n s o di u m ( u p t o 1 0 %) 
a n d c hl ori de ( u p t o 1 0 %) relati ve t o c o ntr ols.  At t he rec o v er y i nter v al, t he maj orit y of 
t hese effects ha d res ol ve d ( Re vera Ge n Re p ort N o. 1 9 9 8- 0 0 1). 
1. 2. 3. 3  
Ge n ot o xicity 
T he  m uta ge nic a n d ge n ot o xic p ote ntial of va m or ol o ne was ass esse d i n se veral assa ys.  A 
n o n- G L P A m es scree n w as ne gati ve f or bact erial m utati o ns ( Re vera Ge n Re p ort N o. 
BI O- V B P- 0 0 1- A M E S).  I n a G L P A mes test, n o b ac k gr o u n d la w n t o xicit y was o bser v e d; 
h o we ver, a re d u cti o n i n re verta nt c o u nts w as o bser ve d ( Re vera Ge n Re p ort N o. 
A D 7 9 D T. 5 0 2I C H. B T L).  Va m or ol o ne was ne gati ve f or i n d uci n g c hr o m os o mal 
a berrati o ns i n c ult ure d m o use l y m p h oc ytes wit h o ut a n d wit h meta b olic acti vati o n 
( Re vera Ge n Re p ort N o. A D 7 9 D T. 7 0 4. B T L). 
Fe m oral b o n e marr o w was micr osc o picall y e v al u ate d f or t he prese n ce of p ol yc hr o m atic 
er yt hr oc ytes ( P C Es) c o ntai ni n g micr o n uclei.  N o si g nifica nt re d ucti o ns i n t he P C Es/ E C 
(t otal eryt hr oc ytes) rati o were o bs er ve d i n t he v a m or ol o ne gr o u ps c o m pare d t o t he 
ve hicle c o ntr ol gr o u p.  Alt h o u g h statisticall y si g nifica nt i ncreases i n t he i nci de nce of 
micr o n ucleate d P C Es i n t he va m or ol o ne tr eate d gr o u ps were o bs er ve d, n o d ose res p o nse 
was o bser v e d wit h res pect t o ot her gr o u ps a n d t he val ues of micr o n ucl ei f or t he 
i n di vi d ual a ni mals were wit hi n t he hist orical ra n ge.  T heref ore, t he statisticall y 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 4 2  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
si g nifica nt i ncreas e was c o nsi dere d as bi ol o gicall y i nsi g nifica nt ( Re vera Ge n Re p ort N o. 
A D 7 6 B K. 1 2 3 0 1 2I C H. B T L). 
A st u d y w as perf or me d t o e val uate t he p ot e ntial m uta ge ni cit y of t w o t h e oretical e p o xi de 
i m p urities relate d t o t he dr u g s u bsta n ce v a m or ol o ne (f or merl y V B P 1 5), w hic h is a 
ster oi d-li ke str uct ure c o ntai ni n g a d elta 9, 1 1 d o u ble b o n d.  T he delta 9, 1 1 e p o xi de 
str uct ures e val uate d w ere V B P 1 5- B- 3, w hic h is str uct urall y si milar t o va m or ol o ne e x ce pt 
f or t he e p o xi de m oiet y, a n d V B P 1 5- B- 2, w hic h h as a 2 1-acetate s u bstit uti o n ( va m or ol o ne 
a n d V B P 1 5- B- 3 c o ntai n a 2 1- h y dr o x y m oiet y).  T w o vali date d a n d c o m ple me ntar y 
i n silic o pre dicti o n met h o d ol o gies were us e d f or assessi n g m uta ge nic p ote ntial.  T he 
statistics- base d q ua ntitati ve str uct ure-acti vit y relati o ns hi p ( Q S A R) pr o gra m M ulti C A S E 
C A S E Ultra was use d, e m pl o yi n g f o ur differe nt m o d ules ( G T 1 _ A 7 B, G T 1 _ A T _ E C O LI, 
P H A R M _ E C O LI, a n d P H A R M _ S A L) desi g n e d t o c o ver a wi de ra n ge of m olec ular 
s u bstr uct ures c ollect e d fr o m b ot h pr o prietar y a n d p u blic c o m p o u n ds.  I n a d diti o n, t he 
e x pert r ule- base d S A R pr o gra m Dere k Ne x us was use d t o deter mi ne if t he t he oretical 
i m p urities c o ntai ne d str uct ural alerts ass ociate d wit h k n o w n ge n ot o xica nts.  C A S E Ultra 
pre dicte d b ot h V B P 1 5- B- 2 a n d V B P 1 5- B- 3 as ne gati ve f or m uta ge ni cit y [ Re vera Ge n 
Re p ort “I n Silic o M uta ge nicit y E val uati o n of Delta 9, 1 1 E p o xi de Str uct ures of V B P 1 5: 
V B P 1 5- B- 2 ( 2 1- Acet ate) a n d V B P 1 5- B- 3 ( 2 1- H y dr o x y)”]. 
Ta ke n t o get her, t hes e data i n dicate va m or ol o ne has n ot ge nerate d a m uta ge nic si g n al 
base d o n t hese si m ulati o ns. 
1. 3  
Cli nic al E x perie nce 
1. 3. 1  
P h ase I St u dy i n He alt hy A d ult V ol u nteers 
Cli nical e x perie nce is li mite d t o a si n gle P hase I cli nical trial of va m or ol o ne i n healt h y 
a d ult v ol u nteers ( V B P 1 5 -0 0 1).  T his st u d y e val uate d t he safet y, t olera bilit y, a n d P K of  
va m or ol o ne i n a P hase I ra n d o mize d, place b o -c o ntr olle d, d o u ble -bli n d, si n gle asce n di n g 
d ose ( S A D) a n d m ulti ple asce n di n g d ose ( M A D) st u d y.  I n t he S A D p orti o n of t he st u d y, 
C o h orts 1 t hr o u g h 5 a n d C o h ort 7 we re c o m prise d of ei g ht s u bjects eac h; si x s u bjects i n 
eac h c o h ort recei ve d  a si n gle oral d ose of v a m or ol o ne ( 0. 1  m g/ k g, 0. 3  m g/ k g, 1. 0  m g/ k g, 
3. 0  m g/ k g, 8. 0 m g/ k g , a n d 2 0 m g/ k g, res p ecti vel y) a n d t w o s u bjects i n eac h c o h ort 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 4 3  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
recei v e d place b o u n der faste d c o n diti o ns.  I n C o h ort 6, si x s u bjects recei ve d a si n gle oral 
d ose of  8. 0 m g/ k g v a m or ol o ne wit hi n 3 0 mi n utes of be gi n ni n g a hi g h fat/ hi g h cal orie 
meal.  T he M A D p orti o n of t he st u d y h a d f o ur c o h orts ( 6 dr u g, 2 place b o i n eac h ) 
recei vi n g 1 4 dail y d oses of va m or ol o ne ( 1. 0, 3. 0, 9. 0 a n d 2 0. 0 m g/ k g/ da y).  T he cli nical 
c o n d uct f or all se ve n S A D c o h orts, a n d all f o ur M A D c o h orts has b ee n c o m plete d; data 
a nal ysis is o n g oi n g. 
T he pri mar y o bje cti ves of t he P hase I st u d y were t o e val uate t he s afet y a n d t olera bilit y of 
si n gle an d m ulti ple oral d oses of va m or ol o ne, a n d t o e val uate t he P K of si n gle d oses a n d 
m ulti ple d oses of va m or ol o ne.  A sec o n d ar y o bjecti ve was t o e val uat e t h e effect of f o o d 
o n t he a bs or pti o n a n d P K of va m or ol o ne.  Ot her o bjecti ves were t o o btai n sa m ples fr o m 
s u bjects o n Da y 1 ( pre- d ose) a n d Da y 1 4 of t he M A D c o h orts f or us e i n Meta b olites i n 
Safet y Testi n g ( MI S T) assess me nts, a n d t o test bac k- u p P K sa m ples fr o m a s u bset of 
M A D s u bjects f or p h ar m ac o d y na mic ( P D) bi o mar kers. 
1. 3. 1. 1  
S A D C o h orts  
1. 3. 1. 1. 1  
S A D C o h orts –  P h ar m ac oki netics F aste d 
Va m or ol o ne  P K data s h o ws str o n g a d here nce t o d ose li nearit y a n d d ose pr o p orti o nalit y, 
wit h relati vel y little s u bject -s u bject v ariati o n (Fi g ure 1 , T a ble 1 , Fi g ure 2 ).  T he half-life 
wa s a b o ut 2 h o urs f or d oses 0. 1- 1. 0 m g/ k g.  D os es at 3. 0, 8. 0 a n d 2 0. 0 m g/ k g s h o w e d a n 
e x te n de d tail, i ncreasi n g half-life t o 2. 5, 3. 8 a n d 3. 8 h o urs, res pecti vel y (Fi g ure 1 ). 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 4 4  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
Fi g ure 1  
Arit h metic me a n ± st a n d ar d err or pl as m a c o nce ntr ati o ns of 
v a m o r ol o ne ( V B P 1 5) after or al a d mi nistr ati o n of si n gle d oses of 0. 1, 0. 3, 
1, 3, 8, a n d 2 0 m g/ k g t o he alt h y s u bjects u n der f aste d c o n diti o ns - li ne ar 
pl ot ( t o p); se mi-l o g arit h mic pl ot ( b ott o m) 
 
 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 4 5  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
T a ble 1   
S u m m ar y of p h ar m ac o ki netic p ar a meters f or v a m o r ol o ne after or al 
a d mi nistr ati o n of si n gle d oses of 0. 1, 0. 3, 1. 0, 3. 0, 8. 0, a n d 2 0. 0 m g/ k g t o 
he alt h y s u bjects u n der f aste d c o n diti o ns 
 
C ma x  = ma xi m u m o bser ve d plas ma c o nce ntrati o n; T ma x  = ti me t o ma xi m u m o bser ve d plas ma c o nce ntrati o n; A U C ( 0-t) = 
area u n der c o nce ntrati o n -time c ur ve fr o m ti me 0 t o ti me t; A U C (i nf) = area u n der c o nce ntrati o n -ti me c ur ve fr o m ti me 0 
t o i nfi nit y; z = eli mi n ati o n rate c o nsta nt;  t½  = ter mi n al half -life; C L/ F = a p pare nt t otal cleara nce fr o m plas ma; Vz/ F = 
a p pare nt v ol u me of distri b uti o n d uri n g ter m i n al p hase. 
Fi g ure 2  
Rel ati o ns hi p bet wee n i n di vi d u al s u bject v a m or ol o ne A U C( i nf) a n d d ose 
after or al a d mi nistr ati o n of si n gle d oses of 0. 1, 0. 3, 1, 3, 8, a n d 2 0 m g/ k g 
t o he alt h y s u bjects u n der f aste d c o n diti o ns 
 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 4 6  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
1. 3. 1. 1. 2  
S A D C o h orts –  P h ar m ac oki netics Fe d 
F or t he f o o d effect gr o u p, a hi g h fat meal ( 4 5 gra ms fat) was gi ve n t o a c o h ort of P hase I 
S A D v ol u nteers wit h t he 8. 0 m g/ k g d ose of va m or ol o ne.  T hese dat a were t he n c o m pare d 
t o t he faste d 8. 0 m g/ k g c o h ort data.  T his s h o we d t hat a bs or pti o n was i ncrease d b y 2. 5-
f ol d b y t he hi g h fat meal, c o nsiste nt wit h t he li p o p hilic c haracter of va m or ol o ne (ster oi dal 
c o m p o u n d) ( Fi g ure 3 , T a ble 2 ). 
Fi g ure 3  
Arit h metic me a n ± st a n d ar d err or pl as m a c o nce ntr ati o ns of 
v a m o r ol o ne ( V B P 1 5) after si n gle d ose or al a d mi nistr ati o n of 8 m g/ k g t o 
he alt h y s u bjects u n der fe d a n d f aste d c o n diti o ns - li ne ar (t o p p a nel) a n d 
se mi-l o g arit h mic ( b ott o m p a nel) a xes 
 
 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 4 7  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
T a ble 2   
S u m m ar y of p h ar m ac o ki netic p ar a meters f or v a m o r ol o ne after si n gle 
d ose or al a d mi nistr ati o n of 8 m g/ k g t o he alt h y s u bjects u n der fe d a n d 
f aste d c o n diti o ns 
 
* Ge o metric mea n ( % C V) ( N) e xce pt T ma x f or w hic h t h e me dia n ( N) is re p orte d. 
† Rati o of t h e ge o metric mea ns. 
C ma x  = ma xi m u m o bser ve d plas ma c o nce ntrati o n; T ma x  = ti me t o ma xi m u m o bser ve d plas ma c o nce ntrati o n; A U C ( 0-t) = 
area u n der c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o ti me t; A U C(i nf) = area u n der c o nce ntrati o n -ti me c ur ve fr om ti me 0 
t o i nfi nit y; z = eli mi n ati o n rate c o nsta nt;  t½  = ter mi n al half -life; C L/ F = a p pare nt t otal cleara nce fr o m plas ma; Vz/ F = 
a p pare nt v ol u me of distri b uti o n d uri n g ter mi n al p hase.  
1. 3. 1. 1. 3  
S A D C o h orts –  A dverse Eve nts 
O ne s u bject i n t he S A D 8. 0 m g/ k g s h o we d a dela ye d mil d ele v ati o n of li ver e nz y m es.  
T his was n ot  felt t o be dr u g-relate d d u e t o ti mi n g of t he ele vati o ns, a n d it is n ot k n o w n if 
t his was a dr u g-tr eate d or place b o s u bject (st u d y re mai ns bli n de d).  T here were n o ot her 
a d verse e ve nts ( A Es) see n i n a n y d os e gr o u p. 
1. 3. 1. 2  
M A D C o h orts   
T he  P hase I M A D treat m e nt pla n was disc usse d i n li g ht of t he i nitial P K data.  T he 
relati vely s h ort half-life of va m or ol o ne ( 2- 4 h o urs), c o u ple d wit h t he pla n ne d dail y d os e 
sc hed ule, w o ul d be e x pecte d t o gi v e P K data o n eac h si n gl e d ose, n ot c u m ulati ve d ose, as 
t he d osi n g i nter val was > 5 × t½ .  T h us, t he M A D c o m p o ne nt w o ul d be a st u d y of 
i n di vi d ual dail y d oses, rat her t ha n d ose-relate d acc u m ulati o n a n d p har mac o distri b uti o n 
relate d t o c u m ulati ve dr u g e x p os ure.  I n ot h er w or ds, a t y pical g o al of a M A D st u d y is t o 
deter mi ne stea d y stat e dr u g le vels after m ulti ple d oses; yet wit h t he s h ort h alf-life of 
va m or ol o ne, usef ul i nf or mati o n w o ul d n ot be e x pecte d t o be gai ne d wit h t he c urre nt dail y 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 4 8  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
d osi n g sc he d ul e.  Safet y a n d t olera bilit y are a d diti o nal g o als of t he M A D st u d y, a n d t h ese 
re mai n i m p orta nt e n d p oi nts i n de pe n de nt of t he P K st u dies. 
1. 3. 1. 2. 1  
M A D C o h orts –  P h ar m ac oki netics F aste d  
T he  ori gi nal desi g n f or t h e P hase I  M A D was m o difie d t o re m o ve t he t w o l o west d oses 
( 0. 1, 0. 3 m g/ k g/ da y), a n d t o be gi n d osi n g at 1. 0 m g/ k g/ da y.  T he cli nical c o n d uct of all 
f o ur c o h orts has b ee n c o m plete d ( 1. 0 m g/ k g/ da y, 3. 0 m g/ k g/ da y, 9. 0 m g/ k g/ da y, 
2 0. 0  m g/ k g/ da y) f or t he M A D  st u d y (T a ble  3 ).    
T a ble  3  
S u m m ar y of p h ar m ac o ki netic p ar a meters f or v a m o r ol o ne d uri n g or al 
a d mi nistr ati o n of 1, 3, 9, a n d 2 0 m g/ k g d oses o nce d ail y f or 1 4 d a ys t o 
he alt h y s u bjects u n der f aste d c o n diti o ns  
 
V a m or ol o ne D ose  
1 m g/ k g  
3 m g/ k g  
9 m g/ k g  
2 0 m g/ k g  
Da y 1  
C ma x  ( n g/ m L) 
1 5 3  ( 1 5. 9) 
2 8 1 ( 3 6. 9)  
1, 0 8 2 ( 2 3. 3)  
2, 4 1 6 ( 5 1. 1)  
T ma x  ( hr) 
3. 0 4  
2. 0 1  
1. 7 5  
1. 0 0  
[ 1. 5 0 –  4. 0 0]  
[ 1. 0 0 –  3. 0 0]  
[ 1. 0 0 –  6. 0 0]  
[ 0. 5 0 –  3. 0 0]  
A U C ( 0-t) 
( hrxn g/ m L)  
6 8 6 ( 2 2. 4)  
1, 4 7 1 ( 2 3. 6)  
5, 7 0 9 ( 2 9. 9)  
1 0, 1 8 2 ( 2 8. 1)  
A U C ( 0-2 4) 
( hr× n g/ m L)  
6 8 6 ( 2 2. 4)  
1, 4 7 1 ( 2 3. 6)  
5, 7 0 9 ( 2 9. 9)  
1 0, 1 8 2 ( 2 8. 1)  
A U C (i nf) 
( hr× n g/ m L)  
6 9 5 ( 2 2. 1)  
1, 4 8 7 ( 2 3. 7)  
5, 7 4 5 ( 2 9. 5)  
1 0, 1 9 0 ( 2 7. 0)  
z ( 1/ hr) 
0. 3 8 4 8 ( 1 0. 9)  
0. 2 9 1 8 ( 1 8. 1)  
0. 2 3 1 7 ( 2 2. 6)  
0. 1 7 4 7 ( 4 4. 3)  
t½  ( hr) 
1. 8 0 ( 1 0. 9)  
2. 3 8 ( 1 8. 1)  
2. 9 9 ( 2 2. 6)  
3. 9 7 ( 4 4. 3)  
C L/ F ( L/ hr/ k g)  
1. 4 4 ( 2 2. 1)  
2. 0 2 ( 2 3. 7)  
1. 5 7 ( 2 9. 5)  
1. 9 6 ( 2 7. 0)  
V z/ F ( L/ k g) 
3. 7 4 ( 1 6. 9)  
6. 9 1 ( 3 4. 8)  
6. 7 6 ( 4 6. 9)  
1 1. 2 ( 7 7. 6)  
Da y 1 4  
C ma x  ( n g/ m L) 
2 0 3 ( 3 0. 1)  
2 7 6 ( 3 5. 6)  
9 3 5 ( 4 8. 3)  
2, 4 9 1 ( 2 7. 9)  
T ma x  ( hr) 
2. 9 6  
2. 5 0  
1. 2 5  
2. 0 0  
[ 1. 5 0 –  3. 0 0]  
[ 1. 0 0 –  4. 0 0]  
[ 0. 5 5 –  3. 0 0]  
[ 1. 0 0 –  2. 0 0]  
A U C ( 0-2 4) 
(hr × n g/ m L)  
7 9 4 ( 2 2. 3)  
1, 4 9 4 ( 1 8. 6)  
4, 3 6 6 ( 2 0. 2)  
9, 3 0 9 ( 3 8. 8)  
z ( 1/ hr) 
0. 3 9 9 3 ( 2 0. 4)  
0. 3 2 7 3 ( 2 5. 2)  
0. 1 6 2 9 ( 6 3. 5)  
0. 1 8 7 9 ( 3 1. 6)  
t½ ( hr) 
1. 7 4 ( 2 0. 4)  
2. 1 2 ( 2 5. 2)  
4. 2 5 ( 6 3. 5)  
3. 6 9 ( 3 1. 6)  
C L/ F ( L/ hr/ k g)  
1. 2 6 ( 2 2. 3)  
2. 0 1 ( 1 8. 6)  
2. 0 6 ( 2 0. 2)  
2. 1 5 ( 3 8. 8)  
V z/ F ( L/ k g) 
3. 1 5 ( 2 0. 6)  
6. 1 4 ( 3 9. 7)  
1 2. 7 ( 7 9. 9)  
1 1. 4 ( 4 9. 1)  
C ma x  = ma xi m u m o bser ve d plas ma c o nce ntrati o n; T ma x  = ti me t o ma xi m u m o bser ve d plas ma c o nce ntrati o n; A U C ( 0-t) = 
area u n der c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o ti me t; A U C ( 0-2 4) = area u n der c o nce ntra ti o n-ti me c ur ve fr o m ti me 0 
t o 2 4 h o urs; A U C (i nf) = ar ea u n der c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o i nfi nit y; z = eli mi n ati o n rate c o nsta nt;  t½  = 
ter mi n al half-life; C L/ F = a p pare nt t otal cleara nce fr o m plas ma; Vz/ F = a p pare nt v ol u me of distri b uti o n d uri n g ter mi n al 
p hase.  

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 4 9  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
Ta ki n g i nt o acc o u nt t he s mall n u m bers a n d differe nt s u bjects, t he ge o metric mea n val ues 
f or Cma x , A U C(0 -t), a n d A U C(i nf) are n ot differe nt f or t he S A D a n d M A D c o h orts.  Wit hi n 
t he M A D, t here is g o o d a gree me nt bet w ee n Da ys 1 a n d 1 4 at all d ose gr o u ps.  T here is n o 
acc u m ulati o n —  t he ge o metric mea n Cma x  a n d A U C ( 0-2 4 ) o n Da ys 1 a n d 1 4 are n ot 
differe nt, c o nsiste nt wit h t he t ½  ( ~ 2 h o ur) a n d d osi n g i nter val ( 2 4 h o urs) (F i g ure 4; 
T a ble  3 ).  
Fi g ure 4  
Arit h metic me a n ± st a n d ar d err or pl as m a c o nce ntr ati o ns of 
v a m o r ol o ne ( V B P 1 5) o n D a ys 1 a n d 1 4 d uri n g or al a d mi nistr ati o n of 
1, 3, 9, a n d 2 0 m g/ k g d oses o nce d ail y f or 1 4 d a ys t o he alt h y s u bj ects 
u n der f aste d c o n diti o ns (li ne ar a xes) 
 
 
1. 3. 1. 2. 2  
M A D C o h orts –  A dverse Eve nts  
T hre e s u bjects ha ve disc o nti n ue d d osi n g; o ne s u bject ( 1. 0 m g/ k g/ da y gr o u p) wit h dre w 
c o nse nt o n Da y 1 0 s o t hat he c o ul d recei ve care f or a n e x acer bati o n of a pre vi o usl y 
e xisti n g de ntal c o n diti o n.  D osi n g was disc o nti n ue d i n a sec o n d s u bject o n Da y 9 ( o n 
place b o i n t he 1. 0 m g/ k g/ da y c o h ort after c o m pleti n g 8 da ys of d osi n g) d ue t o a n i ncreas e 
i n ala ni ne ami n otra nsf erase ( A L T).  T h e s u bject’s baseli ne val ue was 4 0 ( n or mal ≤ 5 0); 
o n Da y s 7, 8, a n d 9, it was 7 0, 8 6, a n d 1 0 6, res pecti vel y.  F oll o wi n g cessati o n of d osi n g, 
t he A LT has sl o wl y decli ne d a n d is c o nti n ui n g t o be f oll o we d.  As partate 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 5 0  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
a mi n otra nsferase ( A S T) was wit hi n n or mal li mits wit h t he e x ce pti o n of a val ue of 4 7 o n 
Da y 9 ( n or ma l ≤ 4 5), w hic h was a gai n n or mal t he f oll o wi n g da y.  Al kali ne p h os p hatase, 
bilir u bi n, a n d c oa g ulati o n para meters ha ve re mai ne d wit hi n n or mal li mits a n d t he s u bject 
has re mai ne d as y m pt o matic.  A t hir d s u bject w h o was o n acti ve dr u g i n t he 2 0 m g/ k g 
d ose gr o u p was disc o nti n ue d after 9 da ys of d osi n g d ue t o a n i ncrease i n A L T.  T he 
s u bject’s baseli ne v al ue was 4 3 ( n or mal ≤ 5 0) at scree ni n g; o n D a ys 7, 8, a n d 9, it was 
5 6, 6 0, a n d 7 3, r es pecti vel y.  F oll o wi n g cessati o n of d osi n g, t he A L T i ncrease d t o 9 6 a n d 
1 0 4 o n Da ys 1 0 a n d 1 2; o n Da y 1 7, it ha d decli ne d t o 8 5.  T he s u bject c o nti n ues t o be 
f oll o we d an d has re mai n e d as y m pt o matic.  As part ate a mi n otra nsferas e was wit hi n 
n or mal l i mits wit h t he e xce pti o n of a val u e of 4 7 o n Da y 1 2 ( n or mal ≤ 4 5); t otal bilir u bi n 
was 0. 7  at scree ni n g ( n or mal 0. 2- 1. 2); it was i ncrease d at 1. 4, 1. 9, a n d 1. 4 o n Da ys 1, 2, 
a n d 3, res pecti vel y, a n d wit hi n n or mal li mits f or t he re mai n der of d osi n g a n d f oll o w- u p.  
N o s u bject i n t he 3. 0 or 9. 0 m g/ k g/ da y c o h orts h a d t o disc o nti n ue d osi n g f or a n A E. 
1. 3. 1. 2. 3  
P h ar m ac o dy n a mic S af ety Bi o m arkers 
Va m or ol o ne has s h o w n i m pr o ve d safet y pr ofiles relati ve t o pre d nis o ne i n n o ncli nical 
testi n g, b ot h i n vitr o a n d i n viv o.1 5 ,1 7  Safet y c o n cer ns wit h gl uc oc ortic oi ds i ncl u de 
s u p pressio n of t he a dre nal a xis a n d i ns uli n resista nce.  P har mac o d y na mic bi o mar ker 
assa ys of s u p pressi o n of t he a dre n al a xis (ser u m c ortis ol) a n d i ns uli n resista nce (ser u m 
gl uc ose) were me as ure d i n t he P hase I M A D st u di es of va m or ol o ne. 
S u p pressi o n of t he a dre n al a xis.  Pre d nis o ne directl y i m pi n ges o n c ortis ol r e g ul at or y 
pat h wa ys (a dre nal a xis) b ot h ac utel y a n d c hr o nicall y.  Ac ute s u p pressi o n of a dre n al 
f u ncti o n is see n wit hi n h o urs of d oses of a si n gle 0. 1 m g/ k g/ da y (a p pr o xi mate) d ose of 
pre d nis o ne, as e vi de nce d b y re d ucti o ns i n a dre n o c ortic otr o pic h or m o ne  (A C T H) le vels i n 
n or mal v ol u nteers. 2 5  M ore c hr o ni c s u p pressi o n of t he a dre n al a xis, c haract erize d as 
se vere, is t y picall y dia g n ose d w he n m or ni n g c ortis ol is < 1 0 0 n m ol/ L ( < 3. 6 
mic r o gra m/ d L) w h e n dra w n > 2 4 hrs after t he last d ose of p har m ac ol o gical ster oi ds. 
M or ni n g se r u m c ortis ol le vels were meas ure d i n t he va m or ol o ne P hase I M A D c o h orts, at 
baseli ne ( pri or t o dr u g a d mi nistrati o n), 2 4 h o urs after t he first d ose ( Da y 1), a n d 2 4 h o urs 
after t he 1 4- da y d ose ( Da y 1 5) ( Fi g ure 5 ).  Acti ve s u bsta nce v ol u nteers at f o ur M A D 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 5 1  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
d ose le vels are s h o w n ( 1. 0 m g/ k g/ da y; 3. 0 m g/ k g/ da y; 9. 0 m g/ k g/ d a y; 2 0. 0 m g/ k g/ da y); 
all s u bjects were treate d f or 1 4 da ys wit h dail y d osi n g.  T he re d hat c he d li ne o n eac h 
gra p h s h o ws a t y pic al t hres h ol d f or a dre nal a xis s u p pressi o n ( < 1 0 0 n m ol/ L, or 
< 3. 6 µ g/ d L).  P val ues s h o w n are f or pair e d T test, i n dicati n g si g nifica nce of t he 
c o nsiste nc y of l o n git u di nal c ha n ges of s u bjects rel ati ve t o t heir o w n i n di vi d ual baseli ne 
val ues.  Ac ute a dre n al a xis s u p pressi o n is meas ure d at 2 4 h o urs (aft er first d ose), w hereas 
c hr o nic a dre nal a xis s u p pressi o n is meas ure d after 1 4 da ys of dail y d osi n g ( 2 4 h o urs after 
last d ose).  
Fi g ure 5  
M or ni n g c ortis ol me as u res i n t he v a m or ol o ne P h ase I M A D 
v ol u n teers. * 
*  Place b o s u bj ects fr o m eac h of t he f o ur M A D c o h orts are gra p he d t o get her.   
Va m or ol o ne s h o we d little e vi de nce of eit her ac ut e ( 2 4 h o ur data), or c hr o nic ( Da y 1 5 
data) s u p pressi o n of t h e a dre nal a xis at d oses of eit her 1. 0 m g/ k g/ da y or 3. 0 m g/ k g/ da y.  
T he data s u g gest t hat va m or ol o ne i n d uces vari a ble, mil d, ac ute a n d c hr o ni c s u p pressi o n 
of t he a dre nal a xis at 9. 0 m g/ k g/ da y, a n d str o n ger e vi de nce of b ot h ac ute a n d c hr o nic 
a dre nal a xis s u p pressi o n at 2 0. 0 m g/ k g/ da y.  Pre d nis o ne t y picall y s h o ws b ot h ac ute a n d 
c hr o nic a dre nal a xis s u p pressi o n a p pr o xi matel y at 0. 1 m g/ k g/ da y, 2 5 s u g gesti n g t hat 
va m or ol o ne has a n i m pr o ve d safet y wi n d o w re gar di n g a dre nal a xis s u p pressi o n. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 5 2  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
Va m or ol o ne t h us s h o ws a p pr o xi matel y a 1 0 0-f ol d i m pr o ve me nt i n safet y wi n d o w 
c o m pare d t o pr e d nis o ne o n a m g/ k g c o m p arati ve basis.  T hese data are c o nsiste nt wit h i n 
vitr o a n d ex vi v o n o ncli nical m o use data c o m pari n g V B P 1 5/ va m or ol o ne t o pre d nis o ne f or 
a dre nal s u p pressi o n. 1 5 
I ns uli n resista n ce.  Pre d nis o ne i n d uces t he safet y si g nal of i ns uli n resista nce, w here 
gl uc ose is n ot efficie ntl y ta ke n u p fr o m t he bl o o d b y tar get tiss ues, s uc h as m uscle a n d 
li ver, lea di n g t o h y p er gl yce mia.2 5  I ns uli n resista nce ma y be a n i m p orta nt s afet y si g nal 
f or d ystr o p hic m uscle, w here t he d ysf u ncti o nal m y ofi bers ha ve bee n s h o w n t o ha ve 
i na de q uate e ner g y st or es,1 8 ,2 6 a n d i ns uli n resista nce li kel y li mits a vaila bilit y of gl yc o ge n 
s u bstrates f or gl yc ol ysis.  T he h y p er gl yce mia, i n t ur n, lea ds t o c hr o nic i n creases i n 
i ns uli n le vels ( h y peri ns uli ne mia).   
Le v els of fasti n g gl uc os e a n d i ns uli n are reas o na bl y se nsiti ve a n d relia ble m eas ures of 
i ns uli n resista nce i n n o n- dia betic i n di vi d uals.  Gl uc ose is ac utel y (si n gle d os e) a n d 
c hr o nicall y ( m ulti ple d oses) ele vate d aft er treat me nt wit h p har mac ol o gical 
gl uc o c ortic oi ds.  Gl uc ose is ele vate d 2 4 h o urs after a si n gl e a d mi nistrati o n of 
gl uc o c ortic oi ds ( 2. 0 m g/ k g). 2 7 ,2 8 
I n t he P h ase I M A D of va m or ol o ne, fasti n g ser u m gl uc ose was me as ure d at 1 0 ti me 
p oi nts d uri n g t he 2- w ee k st u d y; eac h sa m ple was ta ke n 2 4 h o urs after t he pre vi o us d ose 
of va m or ol o ne ( Fi g ure 6 ). 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 5 3  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
Fi g ure 6  
F asti n g ser u m gl uc ose d uri n g t he P h ase I M A D peri o d (t w o wee ks d ail y 
treat me nt)  
 
Gl uc ose le vels f or all va m or ol o ne d ose gr o u ps were si milar t o t h ose of t he place b o gr o u p.  
T here w as n o e vi de n ce of ele vati o ns of gl uc os e le vels at a n y ti me p oi nt or a n y d os e of 
va m or ol o ne, s u g gesti n g t hat t he si de effect of i ns uli n resista nce was n ot see n wit h 
va m or ol o ne.  T hese d ata are c o nsiste nt wit h a n o n cli nical st u d y i n a d ystr o p hi n- deficie nt 
m o use  m o del, w here c hr o nic treat me nt of pre d nis ol o ne ( 5 m g/ k g/ da y) vers us va m or ol o ne 
( 1 5 m g/ k g/ da y; 3 0 m g/ k g/ da y) s h o we d de v el o p me nt of i ns uli n resista nce wit h 
pre d nis ol o ne, b ut n ot va m or ol o ne. 2 9 
1. 3. 1. 3  
S u m m ary of P h ase I d at a 
In s u m mar y: 
 Va m or ol o ne P K data s h o w str o n g a d here nce t o d ose li nearit y a n d d ose 
pr o p orti o nalit y, wit h rel ati vel y little s u bject-s u bject variati o n ( b ot h S A D a n d 
M A D). 
 T he half-life was a b o ut 2 h o urs f or d oses 0. 1- 1. 0 m g/ k g.  D oses at 3. 0, 8. 0, a n d 
2 0. 0  m g/ k g s h o we d a n e xte n de d tail, i ncreasi n g h alf-life t o 2. 5, 3. 8, a n d 3. 8 h o urs, 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 5 4  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
res pecti vel y.  T h e P K f or t he M A D c o h orts was ver y si milar t o t he S A D c o h orts, 
s h o wi n g little if a n y dr u g acc u m ulati o n, c o nsiste nt wit h t he s h ort half-life a n d dail y 
d osi n g sc he d ul e. 
 F or t he f o o d effect gr o u p, a hi g h fat meal w as gi ve n t o a c o h ort of P has e I S A D 
v ol u nt eers wit h t he 8. 0 m g/ k g d ose of v a m or ol o ne.  T hese data were t he n c o m pare d 
t o t he faste d 8. 0 m g/ k g c o h ort data.  T he c o m paris o n s h o we d t hat a bs or pti o n was 
i ncreas e d b y 2. 5-f ol d b y t he hi g h fat meal, c o nsist e nt wit h t he li p o p hilic c haract er 
of va m or ol o ne (ster oi dal c o m p o u n d). 
 F or t he M A D c o h orts, t h ere were n o A Es precl u di n g f urt her es calati o ns i n d osi n g.  
 Re gar di n g t he pri mar y t ar get or ga n, li ver, o ne s u bject o n place b o  i n t he 1. 0 
m g/ k g/ da y c o h ort a n d o n e s u bject o n va m or ol o ne i n t he 2 0 m g/ k g/ da y c o h ort 
s h o we d mil d ele vati o ns of li ver e nz y m es, a n d dr u g d osi n g was h alte d.  N o s u bjects 
i n t he 3. 0 or 9. 0 m g/ k g/ d a y M A D c o h orts s h o w e d ele vati o ns of li ver e nz y mes. 
 Safet y P D bi o mar ker st u dies s h o we d t hat va m or ol o ne ha d a n i m pr o ve d s afet y 
wi n d o w f or a dre nal a xis s u p pressi o n ( 1 0 0-f ol d i ncrease i n t hera pe utic wi n d o w), a n d 
n o e vi de nce of i ns uli n resista nce, c o m pare d t o pre d nis o ne st u dies re p orte d i n t he 
literat ure. 
T he res ults s h o w t hat t he half-life of v a m or ol o ne is ver y si milar t o gl uc oc ortic oi ds, s uc h 
as pre d nis o ne.  D es pite t he s h ort half-life, pre d nis o ne is t y picall y gi ve n o nce per da y f or 
m ost i n dic ati o ns (i ncl u di n g D M D), a n d o nce dail y d osi n g is als o pr o p ose d f or 
va m or ol o ne.  Pre vi o us st u dies of i ncreasi n g t h e fre q ue nc y of dr u g a d mi nistrati o n of 
gl uc o c ortic oi ds ha ve s h o w n t hat t his has i ncreas e d si de effect pr ofiles wit h o ut a 
si g nifica nt gai n i n effic ac y.  T h us, t he mec ha nis m of acti o n of gl uc oc ortic oi ds ma y b e 
relate d t o t he s h ort-t er m ( p ulse d) dail y dr u g e x p os ure.  As va m or ol o n e is t h o u g ht t o s hare 
a si milar a nti-i nfla m mat or y me c ha nis m of acti o n as gl uc oc ortic oi ds ( N F- B i n hi biti o n), 
it is felt t hat t he dail y p ulse d e x p os ure i n t he P hase I M A D is m ost rele va nt t o t he pla n ne d 
clinical trials i n D M D i ncl u di n g t he P hase II M A D a n d P hase II efficac y/s afet y st u dies, 
w here d ail y d osi n g sc he d ules will be f oll o we d.  T he o pti o n of i ncreasi n g t h e d osi n g 
re gi me n i n t he P hase I M A D t o better st u d y dr u g acc u m ulati o n a n d stea d y state P D  was 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 5 5  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
c o nsi dere d, b ut t his was f elt t o be u nrelate d t o pla n ne d P hase II tri als, a n d dr u g 
mec ha nis m of acti o n. 
1. 4  
R ati o n ale f or St u d y Desi g n 
Va m or ol o ne  is u n der de v el o p me nt f or t he treat me nt of D M D.  T he first-i n- h u ma n cli nical 
assess me nt of va m or ol o n e is o n g oi n g i n t he S A D/ M A D st u d y ( V B P 1 5- 0 0 1) a n d is 
pr o vi di n g a n i nitial cli nic al assess me nt a n d ass ess me nt of t he P K c haracteristics of 
va m or ol o ne  f oll o wi n g a d mi nistrati o n of a n oral s us pe nsi o n of va m or ol o ne i n healt h y 
a d ult s u bjects.  W hile t here are li kel y t o be s o me differe n ces b et wee n a d ults a n d c hil dre n, 
a n d bet wee n healt h y a n d D M D s u bjects, t he data fr o m V B P 1 5- 0 0 1 ha v e est a blis he d t he 
2- 4 h o ur half-life of va m or ol o ne, f o o d effect, d ose pr o p orti o nalit y a n d vari a bilit y a m o n g 
s u bjects. 
A P hase IIa M ulti ple Asce n di n g D os e  st u d y ( V B P 1 5-0 0 2 ) w ill deter mi ne t he safe a n d 
t olera ble d ose(s) of va m or ol o ne  t o e na ble f ut ure st u dies wit h c hr o nic a d mi nistrati o n i n 
D M D s u bjects, a ge d 4 -7 years .  T he n arr o w a ge wi n d o w f or t his st u d y is dri ve n  b y 
se veral f act ors: 1) t h e a v era ge a ge of dia g n osis is still a p pro xi matel y 4. 8 years d ue t o lac k 
of scree ni n g pr o gra ms; 2) t he c urre nt sta n dar ds of cli nical care i n Wester n c o u ntries , 
w here gl uc o c ortic oi d  t hera p y is t y picall y i nitiate d be t wee n 5 a n d 7 years of a ge f or D M D 
patie nts; a n d 3) t he o bser vati o n t hat  pea k f u nct i o n f or D M D patie nts occ urs at ar o u n d 
7  years  of a ge  (after w hic h ti me m ost affecte d mal es wit h D M D  will be gi n t o decli ne ), all 
of w hic h res ult i n a narr o w a ge wi n d o w t o i de ntif y ster oi d -nai ve males wit h D M D.    
Ke y safet y p ara m eters i n c o nj u ncti o n wit h P K data are bei n g e val uate d d uri n g t he c o urse 
of t he P hase IIa st u d y t o assess va m or ol o ne  safet y a n d t olera bilit y.  E x pl ora t or y cli nical 
effic ac y para meters a n d P D b i o mar kers of tiss ue brea k d o w n a n d re p air are als o bei n g 
e val uate d. 
T he va m or ol o ne  d e vel o p me nt pr o gra m has ma de a d va nces i n bi o mar ker disc o ver y a n d 
de vel o p me nt i n D M D, wit h a s u bset of t hese st u dies rece ntl y p u blis he d. 3 0  A pa nel of 
bi o mar kers i n D M D pati e nt sera t hat s h o w res p o nse t o c hr o nic ( ~ 4 m o nt h) treat me nt wit h 
gl uc o c ortic oi ds has bee n i de ntifie d.  T hese c hr o nic pre d nis o ne P D bi o mar kers were 
disc o vere d t hr o u g h st u d y of ser u m sa m ples of D M D patie nts e nr olle d i n t he C o o perati ve 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 5 6  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
I nter nati o nal N e ur o m usc ular Researc h Gr o u p (CI N R G ) D uc he n n e Nat ural Hist or y St u d y  
( D N H S).  S o ma Sca n a pt a mer pa n els testi n g 1, 2 0 0 ser u m pr otei ns were use d t o disc o ver a 
ca n di date set of pre d nis o ne -res p o nsi ve bi o mar kers, wit h a s u bset of t hese vali dati n g i n a 
l o n git u di nal sa m ple set (i n di vi d ual D M D patie nts pre/ p ost ster oi d treat me nt).  T hese P D  
bi o mar kers were assi g n e d t o a safet y pa n el or effi cac y p a nel base d o n c o m paris o n t o 
n or mal c o ntr ols a n d i nf or mati o n c o ncer ni n g t he f u ncti o n of eac h pr otei n ( T a ble 4 ).  All 
safet y bi o mar kers were v ali date d i n a se parate c o h ort of pe diatric i nfl a m mat or y dise ase 
patie nts (l o n git u di nal pre/ p ost ster oi ds).  T he sa me S o ma Sca n assa y will b e use d o n t he 
c hr o nic sa m ples fr o m t he va m or ol o ne P hase IIa tri al (e ntr y, 2 wee ks treat me nt, 2 wee ks 
was h o ut), wit h i nitial data a nal yses li mite d t o t h ose vali date d bi o mar k ers s h o w n 
(T a ble  4 ). 
T a b le 4  
Bi o m ar kers pre vi o usl y defi ne d t o be res p o nsi ve t o c hr o nic d oses of 
gl uc oc ortic oi ds i n D M D b o ys 
C hr o nic s af et y  
Ass a y met h o d  
C hr o nic effic ac y  
Ass a y met h o d  
M M P -3   
S o ma Sca n  
C D 2 3  
S o ma Sca n  
Le pti n  
S o ma Sca n  
M D C  
S o ma Sca n  
I ns uli n  
S o ma Sca n  
I L-2 2 B P  
S o ma Sca n  
I G F B P-5  
S o ma Sca n  
L y m p h ot o xi n a 1/ b 2  
S o ma Sca n  
A n gi ote nsi n o ge n  
S o ma Sca n  
I G F B P-2  
S o ma Sca n  
Afa mi n  
S o ma Sca n  
I nte grin a 1 b 1; C D 4 9a  
S o ma Sca n  
1 7 -h y dr o x y pr o gester o ne  
L C -M S  
M M P -1 2  
S o ma Sca n  
C ortic oster o ne  
L C -M S  
 
 
T est oster o ne  
L C -M S  
 
 
1 1 -de o x yc ortis ol  
L C -M S  
 
 
 
A dre nal a xis s u p pressi o n is a well-d oc u me nte d s afet y si g nal wit h c hr o nic use of 
gl uc o c ortic oi ds .  As n ote d a b o ve,  n o n cli nical d ata s u g ge st t hat va m or ol o n e  ma y n ot ca use 
a dre nal a xis s u p pressi o n.  T o test w het her va m or ol o ne  treat me nt ca uses c hr o nic a dre n al 
a xis s u p pressi o n, f o ur ster oi d h or m o nes will be teste d b y L C-M S i n t he va m or ol o ne -
treate d D M D b o ys ( 1 7-h y dr o x y pr o gester o n e, c ortisc oster o ne, test oster o ne, 
1 1 -de o x yc ortis ol) ( T a ble 4 ).  All f o ur ster oi d h or m o nes s h o we d si g nifi ca nt re d ucti o ns 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 5 7  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
after gl uc o c ortic oi d treat me nt i n D M D b o ys i n t h e cr oss -s ecti o nal a n d l o n git u di nal 
CI N R G D N H S partici pa nts . 
T he c urre nt st u d y is desi g ne d t o pr o vi de l o n g -ter m safet y, efficac y, a n d P D  data f or t h e 
va m or ol o ne  d o se(s) t hat are rec o g nize d as safe a n d well -t olerate d i n Phase IIa st u d y 
V B P 1 5 -0 0 2 testi n g a n d w hic h are a ntici pate d t o be teste d i n a fut ur e  P has e II b st u d y.  
E nr oll me nt i n t he Phase IIa e xte nsi o n st u d y will be offere d t o s u bjects w h o c o m plete t he 
P hase IIa st u d y, i n or d er t o e xte n d t he treat me nt d urati o n a n d i ncrease t he p ote ntial f or 
direct be nefit of st u d y tr eat me nt t o t hese pe diatr ic D M D patie nts.   Eac h s u bject  will 
recei ve va m or ol o ne tr eat me nt i n t his P hase IIa e xte nsi o n st u d y at t he sa m e d ose le vel he 
recei v e d i n t he Phase IIa  st u d y.  It is a ntici pate d t h at s u bjects will e nr oll i n t his st u d y o n 
o ne of f o ur d os e le v els (0. 2 5 , 0. 7 5,  2. 0 , or 6 . 0 m g/ k g/ da y ) a n d c o nti n ue o n t hat d ose le vel 
f or t he d urati o n of t h e 2 4 -wee k st u d y .  E v al uati o n of u p t o f o ur d ose le vels  i n t his l o n g-
ter m st u d y will all o w c o m paris o n of t he d ose le vels f or c ha n ge fr om B as eli ne i n safet y 
para meters, m uscle stre n gt h a n d f u ncti o n effi cac y para me ters, a n d P D bi o mar ker le v els 
o ver 2 4 wee k s of treat me nt; i n partic ular, f or t he P D bi o mar kers, e val uati o n of c ha n ge 
fr o m B as eli ne o ver a l o n ger (2 4 -wee k) peri o d ma y ai d i n t he cli nical vali dati o n of 
bi o mar kers  w hic h  e x hi bi t s mall c ha n ges o ver ti me.  C o m paris o ns of  efficac y a n d s afet y 
para meters wit h hist orical nat ural hist or y ( u ntreat e d) 3 1 ,3 2 ,3 3 ,3 4 a n d pre d nis o ne-treate d 
c o ntr ol gr o u ps 3 5 will be perf or me d as pri mar y o ut c o mes of t his st u d y.  
T his tria l will be c o n d ucte d i n c o m plia nce wit h t his pr ot oc ol, G o o d Cli nical Practice 
( G CP), a p plica ble F o o d a n d Dr u g A d mi nistrati o n ( F D A) re q uir e me nts, a n d t he rece ntl y 
iss ued F D A g ui da n ce o n de vel o pi n g dr u gs f or tr eat me nt f or D uc he n n e m usc ular 
d y str o p h y a n d relate d d ystr o p hi n o pat hies. 3 6 
It is o bli gat or y t hat t he I n vesti gat or b ec o me fa miliar wit h all secti o ns of t he Va m or ol o ne 
I n v esti gat or’s Br oc h ure.2 9 
1. 5  
O ver all  Be nefit/ Ris k 
T he c urre nt st u d y is a l o n g-ter m safet y a n d efficac y st u d y i n y o u n g b o ys wit h D M D.  It is 
a ntici pate d t hat t he a d v erse effect pr ofile of t he i n vesti gati o nal pr o d u ct will be m ore 
fa v orabl e t ha n sta n dar d of care gl uc oc ortic oi ds i n t he l o n g ter m.  T he a d v erse effects of 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 5 8  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
va m or ol o ne o ver a 2 4- w ee k treat me nt peri o d are n ot c urre ntl y k n o w n.  I n t he P hase I 
S A D/ M A D st u d y i n he alt h y a d ults, n o seri o us a d v erse e v e nts were o bser ve d i n a n y 
c o h ort.  C o h orts t este d i n t he P hase I M A D st u d y were 1. 0, 3. 0, 9. 0 a n d 2 0. 0 m g/ k g/ da y 
f or 1 4 days.  I n t he P has e I M A D cli nical trial i n a d ult v ol u nteers, va m or ol o ne s h o we d 
s u p pressi o n of t he a dre nal a xis at hi g her d oses ( 9. 0 m g/ k g/ da y a n d 2 0. 0 m g/ k g/ da y i n t he 
faste d state).2 9  I nstr u cti o ns f or detecti n g a dre n al crisis a n d t he circ u msta nces i n w hic h 
stress d ose ster oi ds s h o ul d be pr o vi de d will be i ncl u de d i n t he i nf or me d c o nse nt f or m 
(I C F).   
S u bjec ts ma y or m a y n ot recei v e direct healt h be n efit fr o m partici pati n g i n t he st u d y.  
S u bjec ts will recei ve v a m or ol o ne at o ne of f o ur pla n ne d d ose le vels ( 0. 2 5 m g/ k g/ da y, 
0. 7 5 m g/ k g/ da y, 2. 0 m g/ k g/ da y, or  6. 0 m g/ k g/ da y) o ver t he c o urse of t he 2 4 - wee k tri al.  
W hile it is a ntici pate d fr o m n o ncli nical st u dies t hat t hese d ose le vels ma y b e  effi caci o us 
i n t he treat me nt of D M D, t here are n o cli nical effi cac y d ata yet a v aila ble t o vali date t his 
h y p ot hesis.  I n vie w of t h e i nitial cli nical e vi de nce of safet y a n d t h e m o nit ora ble nat ur e of 
ke y  n o n cli nical t o xic ol o gical fi n di n gs, d ata s u p p ort a n acce pta ble ris k pr ofile f or 
va m or ol o ne. 
2  
S T U D Y O B J E C TI V E S A N D  E N D P OI N T S 
2. 1  
St u d y O bjecti ves 
2. 1. 1  
Pri m ary O bjectives 
T he pri mar y o bje cti ves of t his st u d y are: 
1.  T o e val uate t he l o n g-ter m safet y a n d t olera bilit y of va m or ol o ne, a d mi nistere d 
ora ll y at dail y d os es u p t o 6. 0 m g/ k g o ver a 2 4- wee k Treat me nt Peri o d, i n b o ys 
a ges 4- 7 years wit h D M D;  
2.  T o c o m pare t h e efficac y, as meas ure d b y t he Ti me t o Sta n d Test ( T T S T A N D), of 
va m or ol o ne  a d mi nistere d orall y at dail y d os es u p t o 6. 0 m g/ k g o ver a 2 4- wee k 
Tre at me nt Peri o d vs. u ntreate d D M D hist orical c o ntr ols i n b o ys a ges 4- 7 years 
wit h D M D; a n d 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 5 9  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
3.  T o c o m pare t h e safet y, as meas ure d b y b o d y mass i n de x ( B MI) z-sc ore, of 
va m or ol o ne a d mi nistere d orall y at dail y d os es u p t o 6. 0 m g/ k g o ver a 2 4- wee k 
Tre at me nt Peri o d vs. pre d nis o ne-treate d hist orical c o ntr ols i n b o ys a ges 4- 7 years 
wit h D M D. 
2. 1. 2  
Sec o n d ary O bjectives 
T he sec o n d ar y o bjecti ves of t his st u d y are: 
1.  T o i n vesti gate t h e effects of va m or ol o ne, a d mi nistere d orall y at dail y d oses u p t o 
6. 0 m g / k g o ver a 2 4- w ee k Treat me nt Peri o d vs. pre d nis o ne-treate d hist orical 
c o ntr ols , o n ser u m p har m ac o d y na mic ( P D) bi o mar kers of safet y (i ns uli n 
resista nce, a dre n al a xis s u p pressi o n, a n d b o ne t ur n o ver);  
2.  T o i n vesti gate t h e effects of va m or ol o ne, a d mi nistere d orall y at dail y d oses u p t o 
6 . 0 m g/ k g o ver a 2 4- w ee k Treat me nt Peri o d vs. u ntreate d hist orical c o ntr ols, o n 
ser u m PD bi o mar kers of efficac y (i nfl a m mat or y pr otei n s u p pressi o n ); a n d 
3.  T o i n vesti gate t h e effects of va m or ol o ne, a d mi nistere d orall y at dail y d oses u p t o 
6 . 0 m g/ k g o ver a 2 4- w ee k Treat me nt Peri o d, o n m uscle stre n gt h, m o bilit y a n d 
f u nctio nal e x ercise ca pacit y vs. hist orical c o ntr ols as meas ure d b y Q ua ntitati ve 
M uscle Testi n g ( Q M T), Ti me t o R u n/ Wal k Test ( T T R W), N ort h Star A m b ulat or y 
Assess m e nt ( N S A A), Ti me t o Cli m b Test ( T T C LI M B), a n d 6- mi n ute Wal k Test 
( 6 M W T) i n b o ys a ges 4- 7 years wit h D M D. 
2. 1. 3  
E x pl or at ory O bjective 
T he e x pl orat or y o bj ecti v e of t his st u d y is: 
1.  T o i n vesti gate t h e effects of va m or ol o ne a d mi nistere d orall y at dail y d oses u p t o 
6. 0 m g / k g o ver a 2 4- w ee k Treat me nt Peri o d o n a n e xte n de d pa nel of P D  
bi o mar kers usi n g S o ma Sca n a pta m er arra ys, a n d pr ote o mic pr ofili n g. 
2. 1. 4  
A ncill ary St u dy  
A n o pti o nal a ncillar y st u d y title d “ Use of Micr os oft Ba n ds as a n O utc o me Meas ure i n 
B o ys wit h D M D - Parallel st u d y t o Cli nical St u d y Pr ot oc ol V B P 1 5- 0 0 3” will be 
u n derta ke n i n parallel t o t his V B P 1 5- 0 0 3 st u d y, a n d e nr olli n g partici pa nts fr o m 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 6 0  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
V B P 1 5- 0 0 3.  T he o bj ecti ves of t he a n cillar y st u d y are t o de m o nstrat e t hat 
c o m m u nit y- bas e d acti vit y m o nit ori n g t hr o u g h t he use of a Micr os oft Ba n d ( M S Ba n d) is 
feasi ble a n d relia ble; t o d eter mi ne t he relati o ns hi p of data c ollecte d t hr o u g h t he M S Ba n d 
a n d cli nical assess me nt meas ures of f u ncti o n; a n d t o deter mi ne t he a bilit y of t he M S 
Ba n d t o meas ure dail y acti vit y p atter ns a n d e x pl ore c ha n ges i n patter ns t hat occ ur o ver 
ti me.  Data c ollecte d as p art of V B P 1 5- 0 0 3 will be s hare d wit h t his st u d y f or data 
a nal ysis p ur p oses if t he s u bject’s pare nt/le gal g uar dia n c o nse nts f or his partici pati o n i n 
b ot h st u di es. 
2. 2  
St u d y E n d p oi nts 
2. 2. 1  
S afety E n d p oi nts 
2. 2. 1. 1  
Pri m ary S afety E n d p oi nt 
1.  B MI z-sc ore: C o m paris o n wit h a pre d nis o ne-tr eat e d hist orical c o ntr ol gr o u p f or 
cha n ge fr o m Baseli ne t o Wee k 2 4. 
2. 2. 1. 2  
A d diti o n al S afety E n d p oi nts 
1.  B MI z-sc ore: C ha n ge fr o m Baseli ne t o eac h of t h e sc he d ule d o n-tr eat me nt a n d 
p ost- treat me nt assess me nt ti me p oi nts. 
2.  Treat me nt- e mer ge nt a d v erse e v e nts ( T E A Es) a n d seri o us a d verse e v e nts ( S A Es) 
b y s yste m or ga n class ( S O C): O verall b y treat me nt, b y treat me nt a n d relati o ns hi p, 
a n d b y tr eat me nt a n d i nte nsit y (see Se cti o n 7. 2. 6 );  
3.  Vital si g ns [ bl o o d press ure, heart rate, res pir at or y rate, b o d y te m perat ure] : 
C ha n ge fr o m Baseli ne t o eac h of t h e sc he d ul e d o n-treat me nt a n d p ost-tr eat me nt 
assess me nt ti me p oi nts;   
4.  B o d y wei g ht: C ha n ge fr o m Baseli ne t o eac h of t h e sc he d ule d o n-tr eat me nt a n d 
p ost -treat me nt assess me nt ti me p oi nts; 
5.  Cli nical la b orat or y val ues ( he mat ol o g y a n d bi oc he mistr y ): C ha n ge fr o m Baseli ne 
t o eac h of t he s c he d ule d o n-treat me nt a n d p ost-tr eat me nt assess me nt ti me p oi nts; 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 6 1  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
6.  Li pi d pr ofile (tri gl yceri d es, t otal c h olester ol, l o w de nsit y li p o pr otei n [ L D L], hi g h 
de nsit y li p o pr otei n [ H D L]): C ha n ge fr o m Bas eli ne t o eac h of t he s c he d ule d o n-
treat me nt a n d p ost-tr eat me nt assess me nt ti me p oi nts; 
7.  Uri nal ysis b y di pstic k a n d micr osc o pic a n al ysis : C ha n ge fr o m Baseli ne t o eac h of 
t he sc hed ule d o n-tr eat me nt a n d p ost-treat me nt ass ess me nt ti me p oi nts;  
8.  1 2 -lea d ele ctr ocar di o gra m ( E C G): C ha n ge fr o m Baseli ne t o eac h of t he sc he d ule d 
o n-treat me nt a n d p ost-tr eat me nt assess me nt ti me p oi nts; 
Data f or t h e f oll o wi n g a d diti o nal safet y o ut c o mes will be liste d o nl y: 
1.  P h ysical e x a mi nati o n fi n di n gs at Pretr eat me nt a n d Wee k 2 4. 
2. 2. 2  
Cli nic al Effic acy E n d p oi nts 
2. 2. 2. 1  
Pri m ary Cli nic al Effic acy E n d p oi nt 
1.  Ti me t o Sta n d Test ( T T S T A N D) vel o cit y (rise/sec o n d) : C o m paris o n wit h a 
hist orical nat ural hist or y ( u ntreate d) c o ntr ol gr o u p f or c ha n ge fr o m Bas eli ne t o 
We e k 2 4. 
2. 2. 2. 2  
Sec o n d ary Effic acy E n d p oi nt s 
1.  Ti me t o Sta n d Test ( T T S T A N D) vel o cit y (rise/sec o n d): C ha n ge fr o m Baseli ne t o 
eac h of t h e sc he d ul e d o n-treat me nt a n d p ost-tr eat me nt assess me nt ti me p oi nts; 
2.  Ti me t o Cli m b ( 4 Ste ps ) Test ( T T C LI M B): C ha n ge fr o m Baseli ne t o eac h of t he 
sc he d ule d o n-tr eat me nt a n d p ost-treat me nt assess me nt ti me p oi nts; 
3.  
N ort h Star A m b ulat or y Assess me nt ( N S A A): C h a n ge i n ti me d assess me nts a n d 
t otal sc ore fr o m Bas eli ne t o eac h of t he s c he d ule d o n-treat me nt a n d p ost-
treat me nt assess me nt ti me p oi nts;  
4.  
Q ua ntitati ve M uscle Testi n g ( Q M T): C ha n ge fr o m Baseli ne t o eac h of t he 
sche d ule d o n-tr eat me nt a n d p ost-treat me nt assess me nt ti me p oi nts;  
5.  
T otal dista nce tra v ele d, i n meters, i n c o m pleti n g t he Si x- mi n ute Wal k Test 
( 6 M W T): C ha n ge fr o m Baseli ne t o eac h of t he sc he d ule d o n-treat me nt a n d p ost-
treat me nt assess me nt ti me p oi nts; a n d 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 6 2  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
6.  
Ti me t o R u n/ W al k Test ( T T R W) : C ha n ge fr o m Baseli ne t o eac h of t he sc he d ule d 
o n-treat me nt a n d p ost-tr eat me nt assess me nt ti me p oi nts. 
2. 2. 3  
P h ar m ac o dy n a mic E n d p oi nts 
1.  C o nce ntrati o ns of ser u m P D bi o mar kers: oste ocal ci n, A C T H, i ns uli n, gl uc ose, 
1 7- h y dr o x y pr o gester o ne, car b o x y-t er mi nal tel o pe pti de ( C T X), ser u m 
ami n oter mi nal pr o pe pti de of t y p e I c olla ge n ( P 1 N P), c ortis ol, test oster o ne, 
c ortic oster o ne, 1 1- de o x yc ortis ol, a n d he m o gl o bi n A 1c ( H b A 1 c).  
2. 2. 4  
E x pl or at ory E n d p oi nts 
1.  Le v els of a n e xte n de d pa nel of P D  bi o mar kers usi n g S o ma Sca n a pta mer arra ys 
a n d prote o mic pr ofili n g. 
2. 2. 5  
E n d p oi nts f or S u bject Re p orte d O utc o m es 
Sa fet y e n d p oi nts base d o n s u bject re p orts of A Es are liste d i n Se cti o n 2. 2. 1. 2 .  S u bjects 
will be as ke d t o assess acce pta bilit y of v a m or ol o n e b y a 5- p oi nt he d o nic s cale (see 
Se cti o n 7. 2. 7 ).  A d diti o nall y, s u bjects’ p are nts/le gal g u ar dia ns will be as k e d t o c o m plete 
t he Pe diatric O utc o mes Data C ollecti o n I nstr u me nt (see Secti o n 7. 3. 8 ).  N o ot her s u bject-
re p orte d o utc o m es are pla n ne d.   
3  
S T U D Y D E SI G N 
3. 1  
O ver all  St u d y Desi g n 
T his P hase IIa e xte nsi o n st u d y is a n o pe n-la bel, m ulti ple- d ose st u d y t o e val uate t he 
l o n g-ter m safet y, t olera bilit y, effi cac y a n d P D of v a m or ol o ne a d mi nistere d o nce dail y b y 
li q uid oral s us pe nsi o n o ver a Treat me nt Peri o d of 2 4 wee ks t o b o ys a ges 4- 7 years wit h 
D M D.   
O nl y  s u bjects w h o ha ve c o m plete d P hase IIa c ore st u d y V B P 1 5- 0 0 2 Wee k 4 F oll o w- u p 
Visit asse ss me nts will be eli gi ble f or partici pati o n i n t his o pe n-la bel e xte nsi o n st u d y.  
Partici pati o n i n t his e xte nsi o n st u d y will be disc usse d wit h t he s u bject’s pare nt or 
g uar dia n pri or t o t he V B P 1 5- 0 0 2 Wee k 4 Visit.  Sta n dar d of care treat me nt 
( gl uc o cortic oi ds) f or D M D ma y b e offere d t o t he s u bje ct f oll o wi n g c o m pleti o n of t he 
P hase IIa V B P 1 5- 0 0 2 st u d y, if t he s u bject’s pare nt or g u ar dia n d o es n ot wis h t o e nr oll t he 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 6 3  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
s u bject i n t he e xte nsi o n st u d y a n d/ or t he I n vesti gat or feels it t o be i n t he best i nterest of 
t he s u bject.  A t otal of u p t o a p pr o xi matel y 4 8 s u bj ects will be e nr olle d i nt o t his 
e x te nsi o n st u d y. 
T he pare nts or le gal g uar dia ns of s u bjects w h o c h o ose t o e nr oll i n t his e xte nsi o n st u d y 
will gi ve writte n i nf or m e d c o nse nt f or t he e xte nsi o n st u d y at t he V B P 1 5- 0 0 3 Baseli ne 
Da y  - 1 Visit.  T he Baseli ne Da y - 1 Visit, i ncl u di n g si g ni n g of t he I C F, ma y occ ur at t he 
c o ncl usi o n of t he V B P 1 5- 0 0 2 Wee k 4 Visit f oll o wi n g c o m pleti o n of all Wee k 4 
assess me nts; alter nati vel y, t he Bas eli ne Da y - 1 Visit a n d V B P 1 5- 0 0 3-s pecific I C F 
si g ni ng ma y occ ur u p t o 8 wee ks after t he fi nal V B P 1 5- 0 0 2 Wee k 4 Visit, at t he 
c o n venie nce of t he s u bject’s pare nt or le gal g uar dia n a n d discreti o n of t he I n v esti gat or.  
S u bjects are c o nsi dere d t o be e nr olle d i n t he V B P 1 5- 0 0 3 e xte nsi o n st u d y after t he pare nt 
or g u ar dia n h as si g n e d t he V B P 1 5- 0 0 3-s pecifi c I C F at t he Baseli ne Da y - 1 Visit.  Eac h 
s u bject will retai n t he st u d y i de ntificati o n n u m ber assi g ne d t o hi m at t he start of t he 
P hase IIa c ore st u d y. 
F or  s u bjects w h o e nr oll i n t he V B P 1 5- 0 0 3 e xte nsi o n st u d y wit hi n 2 8 da ys after 
c o m pleti o n of all fi nal V B P 1 5- 0 0 2 Wee k 4 assess me nts, ma n y of t h e safet y, efficac y, a n d 
P D  assess me nts perf or m e d f or t he V B P 1 5- 0 0 2 st u d y at t he fi nal Wee k 4 Visit will be 
use d t o dete r mi ne e xte nsi o n st u d y eli gi bilit y or t o pr o vi de baseli ne st u d y data f or t he 
e x te nsi o n st u d y a n d d o n ot nee d t o be re p eat e d at t he V B P 1 5- 0 0 3 Baseli ne Da y - 1 Visit 
(see T a ble 6 ).  F or t hese s u bjects, a d diti o nal e xte nsi o n st u d y pr oce d ures will still be 
perf or me d at t he Baseli n e Da y - 1 Visit, wit hi n 2 4 h o urs pri or t o a d mi nistrati o n of t he first 
d ose of  st u d y dr u g i n t he e xte nsi o n st u d y.  S u bjects w h o e nr oll i n t he V B P 1 5- 0 0 3 
e x te nsi o n st u d y > 2 8 d a ys after t he date of t he fi nal V B P 1 5- 0 0 2 Wee k 4 Visit m ust ha ve 
all Baseli ne Da y - 1 assess me nts perf or me d, acc or di n g t o t he sc he d ul e i n T a b le 6. 
S u bjec ts will be gi n d osi n g i n t his st u d y o n St u d y Da y 1 at t he sa me v a m or ol o ne d ose 
le vel the y recei ve d i n t he P hase IIa c ore st u d y.  S u bjects will c o nti n ue t o recei ve 
va m or ol o ne at t he d ose recei ve d i n t he P has e IIa c ore st u d y f or t he d urati o n of t he 
2 4- wee k Treat me nt Peri o d, u nless ne w safet y d ata i n dicate t he d ose le vel s h o ul d be 
de- escalate d. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 6 4  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
T he pla n ne d d ose l e vels are 0. 2 5  m g/ k g ( D os e Le vel Gr o u p 1), 0. 7 5 m g/ k g ( D ose Le v el 
Gr o u p  2), 2. 0 m g/ k g ( D ose Le vel Gr ou p  3), a n d 6 . 0 m g/ k g ( D ose Le vel Gr o u p 4) (see 
T a b le 5).  A p pr o xi matel y 1 2 s u bjects ma y b e eli gi ble f or e xte nsi o n st u d y d osi n g at eac h 
of t he d ose  le vels t olerate d i n t he P hase IIa st u d y.   
T a b le 5  
Pl a n ne d D ose Le vel C o m p ositi o n 
Pl a n ne d D ose L e vel 
G r o u p 
N o. S u bjects 
i n D ose 
L e vel G r o u p  
V a m or ol o ne  
D ose  Le vel  
1  
1 2  
0. 2 5 m g/ k g  
2  
1 2  
0. 7 5 m g/ k g  
3  
1 2  
2. 0 m g. k g  
4  
1 2  
6. 0 m g/ k g  
If d ose li miti n g t o xicities are i de ntifie d i n t he P has e IIa c ore st u d y w hi c h precl u de 
c o nfirmati o n of safet y of all f o ur pla n ne d d ose l e v els, t he d ose le vels i n t his e xte nsi o n 
st u d y will be m o difie d, as nee de d. 
I n t he e ve nt a n y cli nical o bser vati o n s u g gests a n i nt olera bilit y f or a n i n di vi d ual s u bject t o 
t he st u d y me dicati o n, i n t he o pi ni o n of t he I n vesti gat or, t h e s u bject’s d ose l e vel ma y be 
decrease d t o t he n e xt l o wer d ose le vel (e. g., a s u bj ect ta ki n g 6. 0 m g/ k g/ da y decrease d t o 
2. 0 m g/ k g/ da y) a n d m ai ntai ne d at t hat l o wer d ose le vel t hr o u g h o ut t he d urati o n of t he 
Tre at me nt Peri o d.  I n t h e e ve nt t he ne xt l o wer d ose le vel is als o n ot t olerate d a n d is 
c o nsidere d a safet y ris k t o t he s u bject, i n t he o pi ni o n of t he I n vesti gat or, St u d y C hair, a n d 
Me dical M o nit or, t he s u bject s h o ul d be wit h dra w n fr o m t he st u d y.  Details of d ose 
i nterr u pti o n, de-es calati o n, a n d disc o nti n uati o n are prese nt e d i n Secti o n 5. 6 . 
S u bjec ts will be assesse d f or safet y a n d t olera bilit y, cli nical efficac y, a n d P D at 
sc he d ule d visits t hr o u g h o ut t he 2 4- wee k Treat me nt P eri o d (see Secti o n 6  f or a sc he d ul e 
of st u d y ass ess me nts).  Treat me nt Peri o d st u d y visits will occ ur at Wee k 2, Wee k 4, a n d 
e ver y 4 w ee ks t hereafter t hr o u g h Wee k 2 4 (T a ble 6 ).  A d verse e ve nts, i ncl u di n g S A Es, 
a n d co nc o mita nt me dicati o ns will be rec or de d t hr o u g h o ut t he st u d y.   
O nce dail y Treat me nt Peri o d st u d y dr u g d osi n g will occ ur fr o m Da y 1 u ntil t he Wee k 2 4 
Visit  (Secti o n 5. 3 ).  St u d y dr u g d osi n g will occ ur at h o me o n all da ys e xce pt t he da ys of 
t he Wee k 1 2 a n d Wee k 2 4 Visits, w he n d osi n g will occ ur at t he st u d y site.   

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 6 5  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
S u bject diaries will be dis pe nse d at Baseli ne Da y - 1 a n d at eac h m o nt hl y st u d y visit t o 
rec or d A Es a n d c o n c o mita nt me dicati o ns ta ke n d uri n g t he st u d y. 
All s u bjects will ret ur n t o t he cli nical site f or Wee k 2 4 assess me nts.  F oll o wi n g 
c o m pleti o n of t he 2 4- wee k Treat me nt Peri o d, s u bjects ma y b e offere d f urt her e xte n de d 
treat me nt wit h va m or ol o ne i n a se parate e xte nsi o n st u d y, or s witc h t o sta n dar d of care 
treat me nt (e. g., gl u c oc ortic oi ds) f or D M D, as dee me d a p pr o priat e f or eac h s u bject.  
Alter na ti vel y, s u bjects m a y c h o ose t o disc o nti n ue va m or ol o ne a n d n ot be gi n 
gl uc o c ortic oi d treat me nt f or D M D.  S u bjects w h o s witc h t o sta n dar d of care 
gl uc o c ortic oi ds f or D M D or w h o disc o nti n ue treat me nt will partici pate i n a 
D ose- ta peri n g Peri o d of 2- 5 wee ks i n d urati o n, f oll o wi n g t he e n d of t h e Treat me nt Peri o d 
a n d pri or t o disc har ge fr o m t he st u d y (see Secti o n 6. 3. 4 ); s u bjects w h o elect t o recei ve 
f urt her va m or ol o ne treat me nt will be disc har ge d fr o m t he V B P- 0 0 3 st u d y after 
c o m pleti o n of fi nal V B P- 0 0 3 st u d y assess me nts at t he Wee k 2 4 Visit, pri or t o e nr oll me nt 
i n a s u bse q uent e xte nsi o n stu d y.  S u bjects will be disc har ge d fr o m t he st u d y f oll o wi n g 
c o m pl eti o n of all fi nal Wee k 2 4 or D os e-ta p eri n g Peri o d assess me nts, as a p pr o priate.   
I n t he e ve nt t hat a n y cli nical or la b orat or y para met ers re mai n a b n or mal at t h e ti me of 
disc har ge fr o m t he st u d y, t he s u bject will be f oll o we d me dicall y as cli nicall y i n dicate d.  
A n y s u bject w h o disc o nti n ues t he st u d y pri or t o t he Wee k 2 4 Visit s h o ul d ret ur n t o t he 
st u d y u nit f or fi nal Wee k 2 4 safet y a n d efficac y assess me nts at t he ti me of earl y 
disc o nti n ua ti o n. 
I n vie w of t he ti me sc he d ule f or i nter nati o nal, n ati o nal a n d l ocal a p pr o vals, t his P hase IIa 
e xte nsi o n st u d y pr ot oc ol a n d relate d d o c u me ntati o n will be s u b mitte d f or re g ulat or y 
a p pr o val c o n c urre nt wit h P hase IIa c ore st u d y V B P 1 5- 0 0 2 .  
3. 2  
St u d y S u m m ar y 
T his P has e IIa e xte nsi o n st u d y is a n o pe n-la bel, m ultice nter st u d y t o e val uate t he 
l o n g-ter m safet y, t olera bilit y, cli nical efficac y, a n d P D  of va m or ol o ne at d ose le vels u p t o 
6. 0 m g/ k g a d mi nistere d d ail y b y li q ui d oral s us pe nsi o n o ver a Treat me nt Peri o d of 
2 4 wee ks t o b o ys a ges 4- 7 years wit h D M D.  

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 6 6  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
T he st u d y is c o m prise d of a Pretreat me nt Baseli ne Peri o d of u p t o 2 4 h o urs i n d urati o n, 
w hic h be gi ns at t he si g ni n g of t he e xte nsi o n st u d y-s pecific i nf or me d c o ns e nt, a 2 4- wee k 
Tre at me nt Peri o d, a n d a 2- t o 5- wee k D ose- tap e ri n g Peri o d f or s u bjects w h o elect t o 
tra nsiti o n off va m or ol o ne treat me nt at t he e n d of t he st u d y. 
4  
S E L E C TI O N A N D WI T H D R A W A L O F S T U D Y S U B J E C T S 
4. 1  
S u bject Scree ni n g, E nr oll me nt, a n d I de ntific ati o n L o g 
All s u bjec ts w h o c o m plete t he Wee k 4 F oll o w- u p assess me nts i n t he V B P 1 5- 0 0 2 c ore 
st u d y will be eli gi ble f or e nr oll me nt i n t his V B P 1 5- 0 0 3 e xte nsi o n st u d y, pr o vi de d t he y 
meet all V B P 1 5- 0 0 3 st u d y e ntr y criteri a.  Li mite d data will be c ollecte d f or s u bjec ts w h o 
d o n ot q ualif y  f or e nr oll me nt i nt o t he e xte nsi o n st u d y, or w h o are n ot i ntereste d i n 
partici pa ti n g i n t he st u d y, i ncl u di n g date of birt h a n d reas o n f or e x cl usi o n fr o m t he st u d y.  
S u bjec ts are c o nsi dere d t o be e nr olle d i n t he V B P 1 5- 0 0 3 e xte nsi o n st u d y after t he pare nt 
or g u ar dia n h as si g n e d t he V B P 1 5- 0 0 3-s pecifi c I C F at t he Baseli ne Da y - 1 Visit.  T he 
Ba seli ne Da y - 1 Visit, i ncl u di n g si g ni n g of t he I C F, ma y occ ur at t he c o ncl usi o n of t he 
V B P 1 5- 0 0 2 Wee k 4 Visit f oll o wi n g c o m pleti o n of all Wee k 4 assess me nts; alter nati vel y, 
t he Bas eli ne Da y - 1 Visit a n d V B P 1 5- 0 0 3-s pecifi c I C F si g ni n g ma y o cc ur u p t o 8 wee ks 
after t he fi nal V B P 1 5- 0 0 2 Wee k 4 Visit, at t he c o n ve nie nce of t he s u bject’s pare nt or 
le gal g u ar dia n a n d discreti o n of t he I n v esti gat or. 
S u bject e nr oll me nt a n d i de ntificati o n l o gs will be mai ntai ne d f or all s u bje ct s e nr olle d i n 
t he st u d y.  T hes e l o gs will be re vie we d d uri n g r o uti ne m o nit ori n g calls a n d/ or visits. 
4. 2  
I ncl usi o n Criteri a 
T o q ua lif y f or e nr oll me nt i n t his e xte nsi o n st u d y, t he s u bject m ust satisf y t h e f oll o wi n g 
i ncl usi o n criteria: 
1.  S u bject’s pare nt or l e gal g uar dia n has pr o vi de d writte n i nf or me d c o nse nt/ HI P A A 
a ut h orizati o n pri or t o a n y e xte nsi o n st u d y-s p ecific pr oce d ures; 
2.  S u bject has pre vi o usl y c o m plete d st u d y V B P 1 5- 0 0 2 u p t o a n d i ncl u di n g t h e 
Wee k 4 F oll o w- u p ass ess me nts wit hi n 8 wee ks pri or t o e nr oll me nt; a n d 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 6 7  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
3.  S u bject a n d pare nt/ g uar dia n are willi n g a n d a bl e t o c o m pl y wit h sc he d ul e d visits, 
st u d y dr u g a d mi nistrati o n pla n, a n d st u d y pr oce d ures. 
4. 3  
E xcl usi o n Criteri a 
A s u bject will be e x cl u de d fr o m e nr oll me nt i n t his e xte nsi o n st u d y if he m eets a n y of t he 
f oll o wi n g e x cl usi o n criteria: 
1.  S u bject ha d a seri o us or s e vere a d verse e v e nt i n st u d y V B P 1 5- 0 0 2 t hat, i n t he 
o pi ni o n of t he I n v esti gat or, was pr o ba bl y or defi nitel y rel ate d t o va m or ol o ne use 
a n d precl u d es safe use of va m or ol o ne f or t he s u bj ect i n t his st u d y; 
2.  S u bject has c urre nt or hist or y of m aj or re n al or he patic i m pair me nt, dia betes 
melli t us or i m m u n os u p pressi o n;  
3.  S u bject has c urre nt or hist or y of c hr o nic s yste mic f u n gal or viral i nfecti o ns; 
4.  S u bject has use d mi neral oc ortic oi d rece pt or a ge nts, s uc h as s pir o n olact o ne, 
eplere n o n e, ca nre n o n e (ca nre n oat e p otassi u m), pr ore n o ne ( pr ore n o ate p otassi u m), 
me xre n o ne ( me xre n oate p otassi u m) wit hi n 4 wee ks pri or t o t he first d ose of st u d y 
me dica ti o n; 
5.  S u bject has e vi de nce of s y m pt o matic car di o m y o p at h y.  [ N ote: As y m pt o matic 
car diac a b n or m alit y o n i n vesti gati o n w o ul d n ot b e e x cl usi o nar y]; 
6.  S u bject is c urre ntl y bei n g treate d or h as recei ve d pre vi o us treat me nt wit h oral 
g l uc o c ortic oi ds or ot her i m m u n os u p pressi ve a ge nts.  [ N otes: Past tra nsie nt use of 
oral gl u c oc ortic oi ds or ot her oral i m m u n os u p pressi ve a ge nts f or n o l o n ger t ha n 3 
m o nt hs c u m ulati ve, wit h last use at least 3 m o nt hs pri or t o first d ose of st u d y 
me dicati o n, will be c o nsi dere d f or eli gi bilit y o n a case- b y -cas e basis.  I n hal e d 
a n d/ or t o pi cal c ortic oster oi ds prescri be d f or a n i n dicati o n ot her t ha n D M D are 
per mitt e d b ut m ust be a d mi nistere d at sta ble d ose f or at least 3 m o nt hs pri or t o 
st u d y dr u g a d mi nistrati o n]; 
7.  S u bject has use d i de be n o ne wit hi n 4 wee ks pri or t o t he first d ose of st u d y 
me dic ati o n; 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 6 8  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
8.  S u bject has a n a ller g y or h y perse nsiti vit y t o t he st u d y me dicati o n or t o a n y of its 
c o nstit ue nts;  
9.  S u bject has se vere be ha vi oral or c o g niti ve pr o ble ms t hat precl u de partici pati o n i n 
t he st u dy, i n t he o pi ni o n of t he I n vesti gat or; 
1 0.  S u bject has pre vi o us or o n g oi n g me dical c o n diti o n, me dical hist or y, p h ysic al 
fi n di n gs or la b orat or y a b n or malities t hat c o ul d affect safet y, m a ke it u nli kel y t hat 
treat me nt a n d f oll o w- u p will be c orrectl y c o m plete d or i m pair t he ass ess me nt of 
st u d y res ults, i n t he o pi ni o n of t he I n vesti gat or; or 
1 1.  S u bject is c urre ntl y ta ki n g a n y i n v esti gati o nal dr u g, or has ta ke n a n y 
i n vesti gati o nal dr u g ot her t ha n va m or ol o ne wi t hi n 3 m o nt hs pri or t o t he start of 
st u dy treat me nt. 
N ote : S u bjects ma y be re- e val u ate d if i neli gi ble d u e t o a tra nsie nt c o n diti o n w hic h 
w o ul d pre ve nt t he s u bje ct fr o m partici pati n g. 
4. 4  
Wit h d r a w al of S u bjec ts fr o m St u d y 
A s u bject ma y wit h dra w fr o m t he st u d y, or ma y b e wit h dra w n b y his pare nt or g uar dia n 
at a n y ti me wit h o ut t h e nee d t o j ustif y t h e decisi o n. 
T h e  I n v esti gat or has t h e ri g ht t o ter mi n at e partici pati o n of a s u bj ect i n t h e st u d y f or a n y 
of t h e f oll o wi n g reas o ns:  
 T h e s u bje ct’s p are nt/le gal g u ar dia n is u n c o o p erati ve/ n o nc o m pli a nt a n d d o es n ot 
ad here t o st u d y res p o nsi biliti es, i n cl u di n g fail ure t o a p pear at st u d y visits; 
 Diffi c ult y i n o bt ai ni n g bl o o d s a m pl es fr o m t h e s u bject f or safet y m o nit ori n g; 
 T h e s u bje ct e x peri e n ces a n u n ma n a gea bl e or n o n-t ol era bl e A E/ S A E w hi c h is 
co nsi dere d t o b e p ossi bl y, pr o b a bl y, or d efi nit el y rel at e d t o st u d y dr u g, i n t he 
o pi ni o n of t h e I n v esti gat or; 
 T h e S p o ns or ter mi n at es t he st u d y ; 
 A n y ot h er reas o n relati n g t o s u bj ect s afet y or i nte grit y of t he st u d y d at a.   

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 6 9  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
I n t he e ve nt a s u bj ect is wit h dra w n fr o m t he st u d y, t he S p o ns or or d esi g n ee (e. g., 
C o or di nati n g Ce nter) will be i nf or me d wit hi n o ne b usi ness da y.  If t here is a me dical 
reas o n f or wit h dra w al, t he s u bject will re mai n u n d er t he s u per visi o n of t he I n v esti gat or 
u ntil res ol uti o n of t he e ve nt. 
All s u bjects w h o wit h dra w fr o m t he st u d y pri or t o t he Wee k 2 4 Visit s h o ul d ret ur n t o 
t he st u d y site f or Wee k 2 4  assess me nts at t he ti me of earl y wit h dr a wal, ass u mi n g t he 
s u bject has n ot wit h dra w n c o nse nt.  I n t he e v e nt a s u bject wit h dra ws i nf or m e d 
c o nse nt, n o f urt her st u d y pr oce d ures s h o ul d be perf or me d a n d n o a d diti o nal data 
s h o ul d be c ollecte d.  A n y data c ollecte d u p t o t he p oi nt of wit h dra wal of i nf or me d 
c o nse nt ma y be use d b y t he S p o ns or. 
4. 5  
Re pl ace me nt of Wit h dr a w n S u bjec ts 
O nl y s u bje cts w h o ha ve c o m plete d t he P hase IIa st u d y are eli gi ble t o e nr oll i n t his 
e xte nsi o n st u d y.  S u bjects pre mat urel y disc o nti n u e d fr o m t he V B P 1 5- 0 0 3 e xte nsi o n 
st u d y will n ot be re pla ce d.  
4. 6  
Ter mi n ati o n of St u d y 
T his s t u d y ma y be pre mat urel y ter mi nate d if, i n t h e o pi ni o n of t he S p o ns or, t here is 
s ufficient reas o na ble ca use.  A n e x a m ple of a cir c u msta nce t hat ma y warra nt ter mi nati o n 
is deter minati o n of u ne x pecte d, si g nifica nt, or u n acce pta ble ris ks t o partici pa nts.   
If t he st u d y is pre mat urel y ter mi nat e d or s us pe n d e d, t he S p o ns or will pr o m ptl y i nf or m t he 
site I n v esti gat ors a n d t he re g ulat or y a ut h orit y(i es) of t he ter mi nati o n or s us pe nsi o n a n d 
t he reas o n(s) f or t h e ter mi nati o n or s us pe nsi o n.  T he I nstit uti o nal Re vie w B oar d(s) 
(IR B[s])/I n de p e n de nt Et hics C o m mittee(s) (I E C[s ]) will als o be i nf or me d pr o m ptl y b y 
t he I n v esti gat or/i nstit uti o n or t he S p o ns or a n d pr o vi de d t he reas o n(s) f or t he ter mi nati o n 
or s us pe nsi o n . 
S u bjec t e nr oll me nt at a gi ve n site ma y b e ter mi nat e d b y t h e S p o ns or.  P ossi ble reas o ns 
f or ter mi nati o n of t he st u d y at a gi ve n site i ncl u de, b ut are n ot li mite d t o: 
1.  U nsatisfact or y e nr oll me nt wit h res pect t o q ua ntit y or q ualit y 
2.  I n acc urate or i nc o m plete data c ollecti o n 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 7 0  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
3.  Falsificati o n of rec or ds 
4.  Fail ure t o a d h ere t o t he pr ot oc ol.  
5  
T R E A T M E N T O F S T U D Y S U B J E C T S  
5. 1  
St u d y Me dic ati o n A d mi nistere d 
V a m or ol o ne will be a d mi nistere d t o all s u bjects as a n oral li q ui d s us pe nsi o n. 
Pla n ne d va m or ol o ne d os e le vels: 0. 2 5 m g/ k g, 0. 7 5 m g/ k g/ da y, 2. 0 m g/ k g, a n d 6. 0 m g/ k g.   
Va m or ol o ne will be a d mi nistere d t o all s u bjects o nce dail y f or 2 4 wee ks, fr o m St u d y 
Da y  1 u ntil t he Wee k 2 4 Visit.  At t he e n d of t he 2 4- wee k Treat me nt Peri o d, a s u bset of 
s u bjects ma y recei ve a d diti o nal va m or ol o ne treat me nt i n a d ose-ta peri n g ma n ner d uri n g a 
2- t o 5- wee k D ose-ta p eri n g Peri o d, pri or t o disc har ge fr o m t he st u d y (see S ecti o n 6. 3. 4 ). 
5. 2  
I de ntit y of I n vesti g ati o n al Pr o d uct 
R e vera G e n Bi o P har ma, I nc. will s u p pl y t he f oll o wi n g i n vesti gati o nal st u d y me dicati o n: 
Na me : 
 
Va m or ol o ne 
Acti ve S u bsta nce:  
V B P 1 5 
Stre n gt h:  
 4 % b y wei g ht 
D osa ge F or m:  
 
Oral s us pe nsi o n 
Ma n ufact ur er:  
 
Velesc o P har m a 
5. 3  
D os a ge Sc he d ule a n d A d mi nistr ati o n of St u d y Me dic ati o n 
S u bjects w h o ha ve c o m plete d t he P hase IIa V B P 1 5- 0 0 2 c ore st u d y a n d w h o meet all 
ot her eli gi bilit y criteri a (see Secti o n 4. 2  a n d Secti o n 4. 3 ) will be e nr olle d i nt o t his 
exte nsi o n st u d y o n Baseli ne Da y - 1, f oll o wi n g si g ni n g of t he e xte nsi o n-st u d y-s p ecific 
I CF.  S u bjects will retai n t he e nr oll me nt n u m bers assi g ne d t o t he m f or t he P hase IIa 
V B P 1 5- 0 0 2 c ore st u d y.   
S u bjec ts will recei ve v a m or ol o ne 0. 2 5  m g/ k g, 0. 7 5 m g/ k g/ da y, 2. 0 m g/ k g, or 6. 0  m g/ k g, 
a d mi nistere d orall y o nce dail y fr o m St u d y Da y 1 t o Wee k 2 4.  A s u bset of s u bjects ma y 
als o recei ve va m or ol o ne f or a n a d diti o nal 1- 4 wee ks acc or di n g t o a d os e-ta peri n g 
pr ot oc ol f oll o wi n g t he e n d of t he Treat me nt Peri o d (see Secti o n 6. 3. 4 ). 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 7 1  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
T he site p har macist or desi g nate d site st u d y staff will dis pe nse st u d y me di cati o n i n 
1 0 0 m L b ottles t o eac h s u bject e nr olle d i n t he st u d y (see Secti o n 5. 8. 1  a n d A p pe n di x  
1 4. 1 ).  All s u bjects will recei ve v a m or ol o ne 4 % oral s us pe nsi o n.  B ottles will be fitte d 
wit h a da pt ors b y t he site p har macist or desi g n ate d site st u d y staff pri or t o dis pe nsi n g.   
St u d y m e dicati o n s uffici e nt f or 1 2 wee ks of d osi n g ( pl us o vera ge) will be dis pe nse d b y 
trai ne d st u dy staff o n St u d y D a y - 1 a n d at t he Wee k 1 2 Visit.  S u bjects w h o partici pate i n 
t he D ose-ta p eri n g Peri o d will be dis pe nse d st u d y me dicati o n at t he Wee k 2 4 Visit 
s ufficie nt f or t he 4- wee k D ose-ta peri n g Peri o d.  E ac h s u bject’s d os e (i n m g) will be 
calc ulate d b ase d o n t he wei g ht of t he s u bject (i n k g) rec or de d at t he dis p e nsi n g visit (see 
A p pe n di x 1 4. 1  f or a d ose calc ul ati o n w or ks heet).   
E nr olle d s u bjects will recei ve a ll d oses of va m or ol o ne u n der t he s u p er visi o n of pare nt or 
le gal g u ar dia n or trai ne d st u d y staff.  T he d oses a d mi nistere d o n t he dates of t he Wee k 1 2 
a n d W ee k 2 4 Visits will be a d mi nistere d at t he st u d y site; all ot her d oses, i n cl u di n g t he 
first d ose a d mi nistere d o n St u d y Da y 1, will be a d mi nistere d at h o me.  St u d y dr u g will be 
a d ministere d b y m o ut h usi n g a v ol u metric s yri n ge s u p plie d b y t he site.  F oll o wi n g 
a d ministrati o n of t he d ose of st u d y dr u g, t he s yri n ge will be fille d o nce wit h water a n d 
t he water will be a d mi nistere d b y m o ut h usi n g t he v ol u metric s yri n ge.  T he s u bject will 
t he n dri n k a p pro xi matel y 5 0 m L of water t o e ns ure t he f ull d ose has bee n i n geste d.  
S u bjec ts s h o ul d recei ve eac h d ose of st u d y me dicati o n at a p pr o xi matel y t h e sa me ti me of 
da y .   
T he dail y d os e of st u d y me dicati o n s h o ul d be ta ke n wit h 8 o u nces of w h ol e mil k ( or 
e q ui vale nt hi g h fat f o o d p orti o n).  At t he Wee k 1 2 a n d Wee k 2 4 Visits, t he s u bject will 
be a s ke d t o c o ns u me a n 8- o u nce glass of w h ole mil k ( or e q ui vale nt hi g h fat f o o d p orti o n) 
a n d 1 c u p of cereal at t he st u d y site wit hi n a p pr o xi matel y 3 0 mi n utes pri or t o 
a d mi nistrati o n of t he d ose of st u d y m e dicati o n.  T here are n o ot her f o o d or dri n k 
restricti o ns bef ore or after d osi n g d uri n g t he st u d y. 
T he dis pe nse d st u d y me dicati o n b ottle( s) will be ret ur ne d t o t he st u d y site at eac h 
s u bse q ue nt sc hed ule d m o nt hl y visit.   St u d y me di cati o n ret ur ne d at t he Wee ks 4, 8, 1 6, 
a n d 2 0 Visits will be re dis pe nse d t o s u bjects at t he e n d of eac h visit, after i nteri m 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 7 2  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
c o m plia nce m o nit ori n g, f or c o nti n ue d d osi n g t hr o u g h t he re mai n der of t he 1 2- wee k 
dis pe nsi n g i nter val.  Dr u g pr o d u ct ret ur n e d at t he Wee ks 1 2 a n d 2 4 Visits, a n d e n d of t he 
D ose - Ta p eri n g Peri o d, if a p plica ble, will be retai n e d at t he cli nical st u d y site f or 
i n vesti gati o nal dr u g acc o u nta bilit y m o nit ori n g. 
5. 4  
R ati o n ale f or D ose Selecti o n 
D ose  le vels were c h ose n f or t his st u d y t o e ns ure t he safet y of s u bj ects e nr oll e d i n t he 
st u d y, t o all o w de m o nstr ati o n of efficac y a n d P D  effects, a n d t o e ns ure a de q uate safet y i n 
f ut ure cli nical st u dies a n d i n t he patie nt p o p ulati o n after F D A re g ulat or y a p pr o val.  All 
d osi n g  will be d o ne i n t h e m or ni n g wit h a gl ass of w h ole mil k ( 8 o u nces or 2 3 0 m L) or 
si milar fat e q ui vale nt me al (a p pr o xi matel y 8 gra ms fat). 
Eac h s u bject will e nr oll i n t his e xte nsi o n st u d y t o recei v e t he sa me d os e t hat he recei ve d 
d uri n g t he V B P 1 5- 0 0 2 c ore st u d y.  T he pla n ne d d ose le vels i n t his st u d y are 0. 2 5 m g/ k g, 
0. 7 5 m g/ k g, 2. 0 m g/ k g, a n d 6. 0 m g/ k g.  If d ose-li miti n g t o xicities are o bser ve d i n t he 
P ha se 2a c ore st u d y at d oses bei n g us e d i n t his st u d y, d ose l e vel(s) will be de-escalate d, 
as a p pr o priat e. 
T he rati o nale f or t he l o w est d ose of 0. 2 5 m g/ k g/ d a y, a d mi nistere d wit h a glass of w h ole  
mil k is as f oll o ws:  As P hase II d osi n g i n 4- 7 y ear ol d D M D c hil dre n will be d o ne at 
h o me i n t he m or ni n g, c h alle n ges were c o nsi dere d wit h s u bject a n d pare nt c o m plia nce 
wit h eit her f asti n g i n t he m or ni n g ( pri or t o sc h o ol or ot her acti vities), or a ri gi d pres cri be d 
diet of k n o w n fat c o nt e nt.  T o bala nce c o m plia nce wit h a p pr o priate assess me nts of 
bi oa vaila bilit y a n d m o nit ori n g of safet y, it was d eci de d t o a d mi nister m or ni n g d oses at 
h o me wit h a gl ass of w h ole mil k ( ~ 8 gra ms of fat) or si milar fat c o nte nt m eal.  
Fr o m t he P hase I st u d y i n a d ult v ol u nteers, a hi g h fat diet ( 4 0 gra ms) i n crease d 
bi oa vail a bilit y of va m or ol o ne ( 8 . 0 m g/ k g/ da y) b y 2 5 0 % c o m pare d t o t he faste d c o h ort at 
t his d ose.  As a f or mal f o o d effect st u d y h as n ot bee n d o ne, we m ust ass u me t hat a n y fat 
i ntake wit h dr u g d eli ver y has t he p ote ntial t o ha ve a 2 5 0 % i ncrease i n bi oa v aila bilit y vs. 
t he faste d state.  T h us, a c o nser vati ve a p pr o xi mati o n of va m or ol o ne dr u g e x p os ure i n 
D M D c hil dre n w h e n ta ke n wit h a glass of w h ole mil k is 2 5 0 % of t he faste d 
bi oa va ila bilit y.  A starti n g d ose of 0. 2 5 m g/ k g/ da y wit h a glass of mil k w o ul d be 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 7 3  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
e q ui vale nt t o 0. 6 2 5 m g/ k g/ da y fast e d, a n d t his starti n g d ose is 3. 1 % of t he hi g hest safe 
d ose teste d i n a d ults ( 2 0. 0 m g/ k g/ da y fast e d). 
T he hi g h est d ose t o be a d mi nistere d, 6. 0 m g/ k g/ da y, will si milarl y b e a d mi nistere d wit h a 
glass of  mil k, wit h a n e x pecte d i ncreas e d bi oa vail a bilit y of 2 5 0 %, or e q ui v ale nt t o 1 5. 0 
m g/ k g/ da y fast e d.  As 2 0. 0 m g/ k g/ da y fast e d i n a d ult v ol u nteers was s h o w n t o be safe i n 
t he P hase I a d ult v ol u nteer st u d y, t h e pr o p ose d hi g hest d ose i n 4- 7 yea r ol d c hildre n is 
a p pr o xi matel y 7 5 % of t h e safe hi g h est a d ult d ose.  Base d o n t h e P hase I P D  bi o mar ker 
safet y data prese nt e d i n Secti o n 1. 3 , safet y si g nals reflecti ve of i ns uli n resista nce are n ot 
a ntici pate d at a n y of t he pla n ne d P hase 2a e xte nsi o n d ose le vels.  Als o bas e d o n t he 
P hase I data, re gar di n g t h e s afet y si g nal of s u p pressi o n of t he a dre n al a xis, n o e vi de nce of 
a dre nal s u p pressi o n is a ntici pate d at t he pla n ne d 0. 2 5 m g/ k g/ da y, 0. 7 5 m g/ k g/ da y a n d 
2. 0 m g/ k g/ da y d ose le v els i n t he P hase IIa e xte nsi o n st u d y; s u p pressi o n of t he a dre n al 
a x is ma y b e o bser ve d at 6. 0 m g/ k g/ da y.   
5. 5  
Tre at me nt C o m pli a nce 
S u bject c o m plia nce wit h t he d osi n g sc he d ule will be assesse d b y site mai nt e na nce of 
acc urate st u d y dr u g dis pe nsi n g a n d ret ur n rec or ds.  T he I n vesti gat or is r es p o nsi ble f or 
e ns uri n g t h at d osi n g is a d mi nistere d i n c o m plia nce wit h t he pr ot oc ol.  T he I n vesti gat or or 
desi g nee will i nstr uct t he s u bject’s pare nt or g uar dia n wit h re gar d t o pr o p er d osi n g of 
st u d y me dicati o n, a n d will rei nf orce t h e i m p orta nce of ta ki n g all st u d y m e dicati o n per 
pr ot oc ol i nstr ucti o ns.  T he v ol u me of u n use d st u d y me dicati o n re mai ni n g i n eac h b ottle 
ret ur ne d will be d o c u me nte d i n t he s o urce d o c u me nts a n d o n t he a p pr o priate electr o nic 
case re p ort f or m (e C R F).  
5. 6  
St u d y Dr u g D ose I nterr u pti o n, De-esc al ati o n, or Disc o nti n u ati o n 
A d mi nistra ti o n of st u d y dr u g t o i n di vi d ual s u bjects s h o ul d be i nterr u pte d, a n d t he cas e 
disc usse d wit h t he St u d y C hair a n d Me dical M o nit or wit hi n 2 4 h o urs, i n t he e ve nt a n y 
clinical o bser vati o n s u g gests a n i nt olera bilit y of a n i n di vi d ual s u bject t o t he st u d y 
me dica ti o n, i n t he o pi ni o n of t he I n vesti gat or.  I n s uc h a n e ve nt, t he s u bj ect’s d ose le vel 
ma y  b e decreas e d t o t he ne xt l o wer d ose le vel (e. g., a s u bj ect ta ki n g 6. 0  m g/ k g/ da y 
dec rease d t o 2. 0 m g/ k g/ da y) a n d mai ntai ne d at t hat l o wer d ose le vel t hr o u g h o ut t he 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 7 4  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
d urati o n of t he st u d y.  I n t he e ve nt t he ne xt l o wer d ose le vel is als o n ot t olerate d a n d is 
c o nsi dere d a safet y ris k t o t he s u bject, i n t he o pi ni o n of t he I n vesti gat or, St u d y C hair a n d 
Me dical M o nit or, t he s u bject s h o ul d be wit h dra w n fr o m t he st u d y.   
I n t he eve nt t hat d ose-li miti n g t o xicities are o bser ve d i n t he V B P 1 5- 0 0 2 P hase IIa st u d y 
t hat req uire d e-es calati o n of d ose i n t he e xte nsi o n st u d y, s u bjects will be de-escal ate d as 
dictate d b y safet y res ults i n t he V B P 1 5- 0 0 2 st u d y. 
5. 7  
Pri o r a n d C o nc o mit a nt Me dic ati o ns a n d T her a pies 
5. 7. 1  
Pri or T her a py 
A n y c ha n ges i n n o n-st u d y me dicati o n/t hera p y, i ncl u di n g a d mi nistrati o n of ne w 
me dicati o n(s), c h a n ge of d ose, or disc o nti n uati o n of me dicati o n, t hat occ ur after 
c o m pl eti o n of t he V B P 1 5- 0 0 2 c ore st u d y Wee k 4 assess me nts a n d pri or t o a d mi nistrati o n 
of t he first d ose of st u d y me dicati o n i n t he e xte nsi o n st u d y will be ca pt ure d as pri or 
me dica ti o ns ( Me dicati o n Hist or y) i n t he e xte nsi o n st u d y e C R F. 
5. 7. 2  
C o nc o mit a nt T her a py 
A n y me di cati o ns t hat are starte d after a d mi nistrati o n of t he first d ose of st u d y me dicati o n 
i n t he e xte nsi o n st u d y will be rec or d e d as c o nc o mita nt me dicati o ns o n t he a p pr o priate 
e C R F.  S u bject diaries will be pr o vi de d t o s u bjects t o rec or d a n y c o nc o mit a nt me dicati o n 
c han ges d uri n g t he st u d y (see Se cti o n 8. 4 ).  
A ll me dicati o ns ( prescri pti o n a n d o ver-t he-c o u nter [ O T C]) ta ke n d uri n g t he st u d y m ust 
be  rec or de d i n t he s o ur ce d oc u me nts a n d i n t he e C R F, i ncl u di n g t he na me of t he 
me dica ti o n ( or de vi ce or pr oce d ure), d osa ge a n d re gi me n, reas o n f or t hera p y, a n d 
treat me nt start a n d st o p d ates.  F urt h er m ore, eac h c ha n ge i n c o nc o mita nt me dicati o n 
(e.g., ne w treat me nt, disc o nti n uati o n of treat me nt, or c ha n ge i n d os a ge/re gi me n) d uri n g 
t he st u d y m ust be d oc u m e nte d i n t he sa me ma n ner.  Details of a n y n o n- p h ar mac ol o gi cal 
t herapies (e. g., de vic es, pr oce d ures), i ncl u di n g na me, reas o n f or t hera p y, a n d dates of 
t hera p y, will als o be rec or de d.  Site pers o n nel will re vie w t he i nf or mati o n wit h t he 
s u bject a n d/ or his pare nt or g u ar dia n, if a p plica ble, f or c o m plete ness a n d acc urac y at eac h 
st u d y visit. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 7 5  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
5. 7. 3  
Pr o hi bite d T her a pies 
S u bjects m ust disc o nti n ue use of t he f oll o wi n g me dicati o ns pri or t o partici p ati o n i n t he 
st u d y, as i n dicat e d, a n d refrai n fr o m usi n g t hes e me dicati o ns t hr o u g h o ut t he d urati o n of 
t he st u d y: 
 Mi neral oc ortic oi d r ece pt or a ge nts, s uc h as s pir o n olact o ne, e plere n o ne, ca nre n o ne 
(ca nre n oate p ot assi u m), pr ore n o ne ( pr ore n oate p otassi u m), me xre n o ne 
( me xre n oate p otassi u m); use m ust be disc o nti n ue d at least 4 wee ks pri or t o t he 
first d ose of st u d y m e dicati o n; 
 Oral gl uc oc ortic oi ds or ot he r oral i m m u n os u p pressi ve a ge nts.  S u bjects w h o ha ve 
recei v e d m ore t ha n 3 m o nt hs c u m ulati ve treat me nt wit h oral i m m u n os u p pressi ve 
a ge nts or last treat me nt wit hi n 3 m o nt hs pri or t o first d ose of st u d y m e dicati o n are 
i neli gi ble f or st u d y e ntr y.  [ N ote: I n hale d a n d/ or t o pical c ortic oster oi ds pres cri be d 
f or a n i n dicati o n ot her t h a n D M D are per mitte d b ut m ust be a d mi nistere d at sta ble 
d ose f or at least 3 m o nt hs pri or t o st u d y dr u g a d mi nistrati o n]; 
 I d e be n o ne ( use m ust be disc o nti n ue d at least 4 wee ks pri or t o first d ose of st u d y 
me dic ati o n); 
 Li ve atte n uate d v acci n es ( use m ust be a v oi de d f or t he d urati o n of partici p ati o n i n 
t he st u dy); 
 A n y i n vesti gati o nal me di cati o ns ot her t ha n va m or ol o ne ( use m ust be disc o nti n ue d 
at least 3 m o nt hs pri or t o t he first d ose of st u d y me dicati o n). 
T he I n vesti gat or s h o ul d c o ntact t he St u d y C hair c o ncer ni n g i n di vi d ual me dicati o ns or 
t herapies n ot liste d t hat ma y b e of c o n cer n. 
5. 7. 4  
Per mitte d T her a pies 
E ver y eff ort s h o ul d be m a de N O T t o ta k e a n y pres cri pti o n or O T C me dicati o ns d uri n g 
t he st u dy.  C o nc o mita nt me dicati o ns s h o ul d be mai ntai ne d o n t he sa me d ose a n d re gi me n 
t hr o u g h o ut the st u d y w he ne ver p ossi ble.  H o we ver, all ot her me dicati o ns ot her t ha n t h ose 
s pecificall y pr o hi bite d a b o ve ma y be ta ke n d uri n g t he st u d y, if cli nicall y i n dicate d, 
pr o vi de d t he y are rec or d e d i n t he s o urce d o c u me nts a n d i n t he e C R F.   

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 7 6  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
5. 8  
St u d y Me dic ati o n M a n a ge me nt 
5. 8. 1  
P ac k a gi n g a n d L a beli n g of St u dy Me dic ati o n 
T he site p har macist or desi g nate d st u d y staff will r ecei ve cli nical trial m aterial ( C T M) 
w he n all re g ulat or y re q uire me nts ha ve b ee n c o m plete d b y t he site.  A d diti o nal C T M will 
be a vaila ble u p o n re q uest.  Re vera Ge n Bi o P har ma, I n c. or desi g n ee will pr o vi de C T M i n 
b ul k q ua ntities s uf ficie nt t o satisf y t he pr ot o c ol re q uire me nt.  Cli nical trial material will 
be s hi p pe d i n b ul k t o t he st u d y site’s re gistere d p h ar macist or desi g n ate d st u d y staff i n 
s uita bl y la bele d st u d y cart o ns.  Cart o ns will c o ntai n st u d y me dicati o n pac ka ge d i n sterile 
1 0 0 m L glass b ottles; eac h b ottle will c o ntai n 4 gra ms of va m or ol o ne as a 4 % s us pe nsi o n 
i n sterile water.  B ul k dr u g s u p plies will be la bel e d wit h t he na me of S p o ns or, pr ot oc ol 
n u m ber, l ot  n u m ber, e x pirati o n or retest d ate, a n d ot her a p pr o pri ate st u d y i nf or mati o n.  
B ott le la bels will i ncl u de t he f oll o wi n g state m e nt: “ Ca uti o n: Ne w Dr u g – Li mite d b y 
Fe deral La w t o I n vesti gati o nal Use” or c o m p ara bl e state me nt, as re q uire d b y e x- U S 
re gulat or y a ut h orities.   
1 0 0 m L  b ottles of 4 % v a m or ol o ne oral s us pe nsi o n will be dis pe nse d t o t he s u bject’s 
pare nt or le gal g uar dia n at t he Baseli ne Da y - 1 Visit a n d at 1 2- wee k i nter vals (see 
A p pe n di x 1 4. 1  f or i nstr ucti o ns o n calc ulati n g t he n u m ber of va m or ol o ne b ottles t o be 
dis pe nse d a t eac h visit); dis pe nse d b ottle(s) of st u d y me dicati o n will be ret ur ne d at e ac h 
s u bse q ue nt m o nt hl y visit f or i nteri m c o m plia nce m o nit ori n g ( Wee ks 4, 8, 1 6, a n d 2 0) or 
pri or t o di s pe nsi n g b ottle(s) f or t he ne xt d osi n g i nter val ( Wee ks 1 2 a n d 2 4).  B ottles will 
be fitte d wit h a da pt ors b y t he site p har macist or desi g nate d site st u d y staff pri or t o 
dis pe nsi n g.   Eac h va m or ol o ne st u d y me dicati o n b ottle ma y be us e d f or a si n gle s u bject 
o nl y .  T he v ol u me p er d ose t o be a d mi nistere d t o eac h s u bject de p e n ds o n t he s u bject 
wei g ht calc ulate d at t he dis pe nsi n g visit; see A p pe n di x 1 4. 1  f or c o m plete i nstr ucti o ns o n 
calc ulati n g d ose v ol u me.  Cli nical s u p plies dis pe nse d b y t h e st u d y site staff a n d rea d y f or 
a d ministrati o n t o s u bjects will be la bele d wit h t he dis pe nse date, pr ot oc ol n u m ber, 
va m or ol o ne d ose le v el, a n d v ol u me t o be a d mi nistere d per d ose.   

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 7 7  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
5. 8. 2  
St or a ge of St u dy Me dic ati o n 
All C T M f or use i n t he trial m ust be st ore d i n a l oc ke d c o ntai n er/ca bi n et free fr o m 
e n vir o n me ntal e xtre mes, u n der t he res p o nsi bilit y of t he i nstit uti o nal p har macist or 
Pri nci pal I n v esti gat or.  B ul k st u d y me dicati o n s h o ul d be st ore d at refri gerat e d 
te m perat ur e ( 2oC – 8 oC; 3 6 oF – 4 6 oF) .  E x c ursi o ns t o a m bie nt te m perat ure are all o we d.  
Acc ess t o st u d y me dicati o n st ore d at t he st u d y site m ust be li mite d t o a ut h orize d cli nic 
pers o n ne l. 
5. 8. 3  
St u dy Me dic ati o n S hi p pi n g a n d H a n dli n g 
Cli nical trial material will be s hi p pe d t o t he st u d y sites o nl y after recei pt of re q uire d 
d oc u me nts i n acc or da nce wit h a p plica ble re g ul at or y re q uire m e nts a n d S p o ns or 
pr oce d ures.   
Cli nical trial material will o nl y be dis pe nse d o n ce a s u bject has ( 1) a si g ne d I C F/ HI P A A 
a ut h oriz ati o n o n file, a n d has bee n e nr olle d i n t he e xte nsi o n st u d y; ( 2) m et all eli gi bilit y 
criteria f or e ntr y i nt o t he e xte nsi o n st u d y, ( 3) c o m plete d all Pretreat me nt re q uire me nts.   
It is esse ntial t o t his st u d y t hat all C T M be acc o u nte d f or d uri n g t he st u d y p eri o d.  All 
u n use d st u d y me dicati o n will be retai ne d at t he st u d y site f or rec o nciliati o n a n d c ollecti o n 
b y  t he S p o ns or's st u d y m o nit ors ( or desi g nees) d uri n g r o uti ne m o nit ori n g visits.  St u d y 
site pers o n nel s h o ul d n ot dis p ose of a n y C T M.  Fi nal dis p ositi o n of all u n use d C T M will 
be c o or di nate d b y t h e S p o ns or's st u d y m o nit ors ( or desi g n ees) at t he e n d of t he st u d y (s ee 
Sec ti o n 5. 8. 4 ).   
Cli nical trial material m ust be dis pe nse d a n d a d mi nistere d acc or di n g t o t he pr oce d ures 
desc ri be d i n t his pr ot oc ol.  O nl y s u bjects e nr olle d i n t he st u d y ma y recei v e st u d y 
me dicati o n, i n acc or da nce wit h all a p plica ble re g ulat or y re q uire m e nts.  O nl y a ut h orize d 
st u d y pers o n n el ma y s u p pl y C T M.  A ut h orize d st u d y pers o n nel r efers t o t he I n vesti gat or 
( or desi g nee), i n acc or da nce wit h all a p plica ble re g ulat or y re q uire m e nts a n d t he Site 
Si g nat ure L o g/ D ele gati o n of A ut h orit y.  O nl y a ut h orize d st u d y pers o n nel or t he s u bject’s 
pare nt or le gal g uar dia n ma y a d mi nister C T M. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 7 8  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
5. 8. 4  
St u dy Me dic ati o n Acc o u nt a bility 
T he I n vesti gat or is r es p o nsi ble f or t he c o ntr ol of dr u gs u n d er i n vesti gati o n.  A de q uate 
recor ds of t he recei pt (e. g., Dr u g Recei pt Rec or d) a n d dis p ositi o n (e. g., Dr u g Dis pe nsi n g 
L o g) of t he st u d y dr u g m ust be mai ntai ne d.  T he Dr u g Dis pe nsi n g L o g m ust be ke pt 
c urre nt a n d s h o ul d c o ntai n t he f oll o wi n g i nf or m ati o n: 
 T he i de ntificati o n of t he s u bject t o w h o m t he st u d y dr u g was dis pe nse d 
 T he date(s) a n d q ua ntit y of t he st u d y dr u g dis pe ns e d t o t he s u bject 
 T he date(s) a n d q ua ntit y of t he st u d y dr u g ret ur n e d b y t he s u bject. 
All rec or ds a n d dr u g s u p plies m ust be a vaila ble f or i ns pecti o n b y t h e St u d y M o nit or at 
e ver y m o nit ori n g visit.  U n use d me dicati o n will be ret ur n e d t o Re vera Ge n or its desi g nee 
at the e n d of t he st u d y.  T he c o m plete d Dr u g Dis pe nsi n g L o g a n d Dr u g Ret ur n Rec or d(s) 
will be  ret ur ne d t o Re vera Ge n or its desi g nee.  T h e I n vesti gat or’s c o p y of t he Dr u g 
Re t ur n Rec or d(s) m ust acc urat el y d o c u me nt t he ret ur n of all st u d y dr u g s u p plies t o 
Re vera G e n or its desi g nee. 
5. 9  
Pr o ce d ures f or Assi g ni n g S u bject St u d y N u m b ers 
T his is a n o pe n-la bel st u d y.  S u bjects e nr olle d i n t his e xte nsi o n st u d y will retai n t he 
e nroll me nt n u m bers assi g ne d t o t he m at t he start of t he V B P 1 5- 0 0 2 c ore st u d y.  All data 
f or all s u bjects w h ose p are nt or g u ar dia n si g ns t he I C F f or t he e xte nsi o n st u d y will be 
i de ntifie d usin g t he u ni q ue s u bject i de ntificati o n n u m ber.  S u bjects are c o nsi dere d t o be 
e nrolle d i n t his e xte nsi o n st u d y w he n t h e pare nt or g uar dia n si g ns t he e xte nsi o n 
st u d y-s pecific I C F at t he Baseli ne Da y - 1 Visit.  T he Site I n v esti gat or will kee p a rec or d 
relati n g t h e na mes of t h e s u bjects t o t heir e nr oll me nt n u m bers ( S u bject I de ntificati o n 
L o g) t o p er mit effici e nt verificati o n of d ata s u bject files, w he n re q uire d.  T his rec or d will 
als o i ncl u de t he dates of s u bject e nr oll me nt a n d c o m pleti o n/ter mi nati o n.   

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 7 9  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
6  
S T U D Y S C H E D U L E 
6. 1  
Ti me a n d E ve nts Sc he d ule 
T he  st u d y pr oce d ures t o be c o n d ucte d f or eac h s u bject are di vi de d i nt o t he f oll o wi n g 
st u d y peri o ds:  
 Pretre at me nt B aseli ne Peri o d:   T he 2 4- h o ur peri o d i m me diatel y pri or t o 
a d ministrati o n of t he first d ose of st u d y m e dicati o n ( St u d y Da y - 1), w hic h 
i ncl u des si g ni n g of t he e xte nsi o n st u d y-s pecific I C F a n d e nr oll me nt i nt o t he 
e x te nsi o n st u d y.  T he Baseli ne Da y - 1 Visit ma y c oi nci de wit h t he fi nal Wee k 4 
F oll o w- u p Visit i n t he V B P 1 5- 0 0 2 c ore st u d y.  Alter nati vel y, s u bjects ma y ret ur n 
t o t he st u d y site u p t o 8 wee ks after c o m pleti o n of t he V B P 1 5- 0 0 2 Wee k 4 
assess me nts  f or Baseli ne Da y - 1 I C F si g ni n g a n d c o m pleti o n of Baseli ne 
assess m e nts. 
 Tre at me nt Peri o d:   T he 2 4- wee k i nter val starti n g wit h a d mi nistrati o n of t he first 
d ose of  st u d y m e dicati o n o n St u d y Da y 1a n d c o nti n ui n g t hr o u g h t he ti me of t he 
We e k 2 4 Visit a n d a d mi nistrati o n of t he fi nal d ose of Treat me nt Peri o d st u d y 
me dicati o n.  S u bjects electi n g t o c o nti n ue va m or ol o ne t hera p y u n der a s u bs e q ue nt 
e x te nsi o n pr ot oc ol will be disc har ge d fr o m t he V B P 1 5- 0 0 3 st u d y f oll o wi n g 
c o m pleti o n of all Wee k 2 4 safet y, efficac y, a n d P D assess me nts. 
 D ose-t a peri n g Peri o d:  T he 2- t o 5- wee k i nter val f oll o wi n g t he e n d of t he 
2 4- wee k Treat me nt Peri o d d uri n g w hi c h s u bjects w h o elect t o eit her s witc h t o 
sta n dar d of care gl uc oc ortic oi ds f or D M D, or disc o nti n ue va m or ol o ne a n d n ot 
be g i n sta n d ar d of care gl uc oc ortic oi d treat me nt, at t he e n d of t he st u d y will ha ve 
t heir vam or ol o ne d ose ta pere d t o 0 m g/ k g/ d a y.  T he le n gt h of ti me re q uir e d f or 
t his ta peri n g will de p e n d u p o n t he d ose recei ve d d uri n g t he Treat me nt Peri o d (see 
Secti o n 6. 3. 4 ).  S u bjects w h ose d ose is ta pere d d uri n g t he D ose-ta p eri n g Peri o d 
will be disc har ge d fr o m t he st u d y f oll o wi n g c o m pleti o n of all fi nal D ose-ta peri n g 
Peri o d assess me nts.   

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d  Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 8 0  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
T he pr oce d ures t o be c o m plete d d uri n g eac h st u d y peri o d are pres e nte d i n t he Sc he d ule 
of  St u d y Assess me nts i n T a ble 6  a n d i n t he secti o ns t hat f oll o w.  Detaile d descri pti o ns of 
t he assess me nts an d t he d efi niti o ns of st u d y e n d p oi nts are pr o vi de d i n Se cti o n 7  a n d 
Se cti o n 2. 2 .  A n y d e viati o n fr o m st u d y pr oce d ures s h o ul d be n ote d i n t he s o urce 
d oc u me nts a n d i n t he e C R F, a n d si g nifica nt de viati o ns s h o ul d be re p orte d i m me diatel y t o 
t he S p o ns or.   
O vera ll, a p pr o xi matel y 2 4 - 2 9 wee ks are all ocate d f or ea c h s u bject t o c o m pl ete t he st u d y, 
i ncl u di n g a 1- d a y Pretr eat me nt Baseli ne Peri o d a n d a 2 4- wee k Treat me nt Peri o d f or all 
s u bjects.  F or s u bjects w h o elect t o eit her s witc h t o sta n dar d of care gl uc oc oc ortic oi ds f or 
D M D, or d isc o nti n ue va m or ol o ne a n d n ot be gi n gl uc oc ortic oi d treat me nt at t he e n d of t he 
st u d y, a n a d diti o nal 2- 5 wee ks are all ocate d f or va m or ol o ne d ose ta peri n g. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
P a ge 8 1  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
T a ble 6   
Sc he d ule of St u d y Acti vities 
 
Pr etr e at m e nt 
P eri o d  
Tr e at m e nt P eri o d  
D o s e -
t a p eri n g 
P eri o d  
B a s eli n e  
 
D a y  
W e e k  
St u d y D a y or 
W e e k/ Vi sit  
-1 a  
 
1 b  
 
2  
(1 d)  
4  
(2 d)  
8  
(5 d)  
1 2  
(1 w)  
1 6  
(1 w)  
2 0  
(1 w)  
2 4 c  
(1 w)  
2 6 -2 9 d  
(1 w)  
I n cl u si o n/ E x cl u si o n 
Crit eri a  
X  
 
 
 
 
 
 
 
 
 
I nf or m e d C o n s e nt 
X e  
 
 
 
 
 
 
 
 
 
E nr oll m e nt  
X  
 
 
 
 
 
 
 
 
 
I nt eri m M e di c al 
Hi st or y  
X f 
 
 
 
 
 
 
 
 
 
M e di c at i o n Hi st or y 
X g  
 
 
 
 
 
 
 
 
 
P h y si c al E x a mi n ati o n  
X h  
 
 
 
 
 
 
 
X  
 
H ei g ht  
X  
 
 
 
 
X  
 
 
X  
 
W ei g ht  
X  
 
 
X  
X  
X  
X  
X  
X  
 
Vit al Si g n s i 
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
Bl o o d f or Cli ni c al L a b s j 
X h  
 
 
X  
X  
 
X  
 
X  
X  
Uri n al y si s k 
X h  
 
 
X  
X  
 
X  
 
X  
 
Bl o o d f or S er u m P D 
Bi o m ar k er P a n el l 
X h  
 
 
 
X  
 
X  
 
X  
X  
F a sti n g bl o o d f or 
i n s uli n, gl u c o s em  
 
 
 
 
 
X  
 
 
X  
 
1 2 -l e a d E C Gn  
X h  
 
 
 
 
X  
 
 
X  
 
Di s p e n s e St u d y 
M e di c ati o n  
X  
 
 
 
 
X  
 
 
X o  
 
R et ur n St u d y 
M e di c ati o n/ 
C o m pli a n c e 
M o nit ori n g  
 
 
 
X  
X  
X  
X  
X  
X  
X  
St u d y M e di c ati o n 
D o si n g p  
 
X  
 
 
 
 
 
 
X  
 
V a m or ol o n e d o s e 
t a p eri n gq  
 
 
 
 
 
 
 
 
 
X  
Ti m e t o St a n d T e st 
( T T S T A N D) 
X h  
 
 
 
 
X  
 
 
X  
 
Ti m e t o Cli m b T e st 
( T T C LI M B) 
X h  
 
 
 
 
X  
 
 
X  
 
Ti m e t o R u n/ W al k 
T e st ( T T R W)  
X h  
 
 
 
 
X  
 
 
X  
 
N S A A r 
X h  
 
 
 
 
X  
 
 
X  
 
Q u a ntit ati v e M u s cl e 
T e sti n g ( Q M T)  
X h  
 
 
 
 
X  
 
 
X  
 
Si x -mi n ut e W al k T e st  
( 6 M W T) 
X h  
 
 
 
 
X  
 
 
X  
 
P e di atri c O ut c o m e s 
D at a C oll e cti o n 
I n str u m e nt 
X  
 
 
 
 
X  
 
 
X  
 
St u d y M e d i c ati o n 
A c c e pt a bilit y 
A s s e s s m e nt s 
 
 
 
 
 
X  
 
 
X  
 
Di s p e n s e S u bj e ct 
Di ari e s t 
X  
 
 
X  
X  
X  
X  
X  
X p  
 
R et ur n S u bj e ct Di ari e s  
 
 
X  
X  
X  
X  
X  
X  
X  
X  
A E/ S A E R e c or di n g u 
X  
 
 
 
 
 
 
 
X  
X  
C o n c o mit a nt 
M e di c a ti o n s 
 
X  
 
 
 
 
 
 
X  
X  
Di s c h ar g e fr o m St u d y  
 
 
 
 
 
 
 
 
X v 
X w  
d = da y(s); w = wee k.  

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 8 2  of 1 3 7 
Re v era Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
a. 
Baseli ne Da y - 1, wit hi n 2 4 h o urs pri or t o a d mi nistrati o n of t h e first d ose of st u d y dr u g.   T he Baseli ne Visit 
f or St u d y V B P 1 5- 0 0 3 ca n c oi nci de wit h t h e fi n al Wee k 4 F oll o w- u p Visit f or St u d y V B P 1 5- 0 0 2 or occ ur u p 
t o 8 wee ks after t he date of t h e V B P 1 5- 0 0 2 Wee k 4 Visit. 
b.  
Treat me nt Da y 1 be gi ns at t he ti me of a d mi nistrati o n of t h e first d ose of V B P 1 5- 0 0 3 st u d y me dicati o n at 
h o me.  N o sc he d ule d st u d y visit will occ ur o n Da y 1. 
c. 
S u bjects w h o pre mat urel y disc o nti n ue fr o m t h e st u d y pri or t o Wee k 2 4 s h o ul d c o m plete t h e Wee k 2 4 
assess me nts at t h e ti me of earl y disc o nti n uati o n. 
d.  
All s u bjects E X C E P T t h ose w h o elect t o c o nti n ue va m or ol o ne t h era p y i n a f urt h er e xte nsi o n st u d y m ust 
c o nti n ue i n t he D ose-ta peri n g P eri o d a n d ha ve t h eir va m or ol o ne d ose ta pere d at wee kl y i nter vals o ver a 1- 4 
we e k peri o d pri or t o disc har ge fr o m t his st u d y.  S u bjects partici p ati n g i n t he D ose-ta peri n g P eri o d will ha ve 
o ne st u d y site visit d uri n g t his peri o d, at t h e e n d of d ose ta peri n g ( Wee ks 2 5- 2 9)  (see Secti o n 6. 3. 4 ).  
e. 
I nf or me d C o nse nt f or t his e xte nsi o n st u d y ma y be o btai ne d at t h e St u d y V B P 1 5- 0 0 2 Wee k 4 F oll o w- u p Visit, 
after c o m pleti o n of all fi n al V B P 1 5- 0 0 2 st u d y assess me nts a n d pri or t o a n y e xte nsi o n st u d y-s pecific 
pr oce d ures. 
f. 
I nteri m Me dical Hist or y will be c ollecte d o n Baseli ne Da y -1 f or all s u bjects, a n d will i n cl u de a n y A Es t h at 
occ urre d d uri n g t h e V B P 1 5- 0 0 2 c ore st u d y a n d are o n g oi n g at t he ti me of e ntr y i nt o V B P 1 5- 0 0 3 (see 
Secti o n 7. 2. 1 ). 
g.  
A n y c ha n ges i n me dicati o n/t hera p y i n cl u di n g a d mi nistrati o n of ne w me dicati o n(s), c ha n ge of d ose, or 
disc o nti n uati o n of me dicati o n aft er c o m pleti o n of t h e V B P 1 5- 0 0 2 c ore st u d y a n d pri or t o a d mi nistrati o n of 
t h e first d ose of st u d y me dicati o n i n V B P 1 5- 0 0 3 will be ca pt ure d as Pri or Me dicati o ns.  
h.  
If t h e Baseli ne Da y - 1 Visit occ urs ≤ 2 8 da ys after t he date of t h e fi n al V B P 1 5- 0 0 2 c ore st u d y Wee k 4 Visit, 
t h ese assess me nts d o n ot nee d t o be re peate d f or t h e V B P 1 5- 0 0 3 st u d y.  Cli nical la b orat or y a n d uri nal ysis test 
res ults fr o m t h e V B P 1 5- 0 0 2 Wee k 2 or Wee k 4 Visit ( w hic he ver is a vaila ble a n d later) ma y be use d a n d 
s h o ul d be re vie we d b y t h e Site I n vesti gat or t o deter mi n e eli gi bilit y f or Baseli ne Da y - 1 e nr oll me nt i nt o t he 
e xte nsi o n st u d y. 
i. 
S u pi ne bl o o d press ure, oral te m perat ure, res pirat or y rate, a n d he art rate. 
j. 
Bl o o d f or he mat ol o g y , c he mistr y, a n d li pi ds. 
k.  
Uri n al ysis b y di pstic k a n d micr osc o pic a nal ysis. 
l. 
Bl o o d c ollecte d f or c ortis ol, P 1 N P, oste ocalci n, 1 7- h y dr o x y pr o gester o ne, test oster o ne, c ortic oster o ne, 
1 1- de o x yc ortis ol, C T X, A C T H, H b A 1c ( n ot c ollecte d at Baseli ne), S o ma Sca n, a n d pr ote o mic testi n g. 
m.  Bl o o d will be c ollecte d f or i ns uli n a n d gl u c ose deter mi n ati o n i n t he m or ni n g after s u bjects ha ve fast e d f or ≥ 6 
h o urs, pri or t o t he dail y d ose of st u d y me dicati o n. 
n.  
E C G rec or de d after s u bject has reste d q uietl y i n a s u pi ne p ositi o n f or at l east 5 mi n utes. 
o.  
O nl y f or s u bjects w h o will partici pate i n t he D ose-ta peri n g P eri o d. 
p.  
T he d ose of st u d y me dicati o n o n t he da ys of t h e We e k 1 2 a n d Wee k 2 4 Visits will be a d mi nistere d after 1) a 
fasti n g bl o o d dra w f or i ns uli n a n d gl u c ose; a n d 2) brea kfast pr o vi d e d b y t h e st u d y site.  All ot h er d oses will 
be ta ke n at h o me. 
q.  
S u bjects w h o elect t o s witc h t o sta n dar d of care gl u c oc ortic oi ds, or disc o nti n ue va m or ol o ne a n d n ot be gi n 
gl u c oc ortic oi d treat me nt f or D M D at t h e e n d of t h e st u d y will ha ve t h eir va m or ol o ne d ose ta pere d at wee kl y 
i nter vals t o a d ose of 0 m g/ k g/ d a y pri or t o fi n al st u d y assess me nts (see Secti o n 6. 3. 4 ). 
r. 
N ort h Star A m b ulat or y Assess me nt; i ncl u des t h e Ti me t o Sta n d Test ( T T S T A N D). 
s. 
St u d y me dicati o n acce pta bilit y assesse d i m me diatel y bef ore (s mell) a n d after (taste) d osi n g at t he Wee k 1 2 a n d 
Wee k 2 4 Visits. 
t. 
S u bject diaries use d t o rec or d a n y c o nc o mita nt me dicati o ns ta ke n a n d a n y A Es e x perie nce d d uri n g t he st u d y. 
u.  
All A Es a n d S A Es m ust b e c ollecte d i n t h e s o urce d oc u me nts a n d e C R F fr o m t h e date of t h e s u bject’s writte n 
i nfor me d c o nse nt u ntil t he Wee k 2 4 Visit or t h e s u bject’s partici pati o n i n t he st u d y is c o m plete d.  O n g oi n g A Es 
will be f oll o we d t o res ol uti o n, sta bilizati o n, or u ntil s uc h ti me t h e I n vesti gat or a grees f oll o w- u p is n ot necessar y. 
v.  
S u bjects w h o elect t o c o nti n ue va m or ol o ne t h era p y i n a s u bse q ue nt e xte nsi o n st u d y ma y be disc har ge d fr o m 
t h e st u d y f oll o wi n g c o m pleti o n of all fi n al Wee k 2 4 pr oce d ures. 
w.  S u bjects w h o partici p ate i n t h e D ose-ta peri n g P eri o d ma y be disc har ge d fr o m t h e st u d y f oll o wi n g c o m pleti o n 
of all fi n al D ose-ta peri n g Visit assess me nts (see Secti o n 6. 3. 4 ). 
 

V B P 1 5 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3 
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 8 3  of 1 3 7 
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
6. 2  
I nf or me d C o nse nt/ HI P A A A ut h oriz ati o n 
T he pare nts or g uar dia ns of s u bjects w h o c h o ose t o e nr oll i n t his e xte nsi o n st u d y will 
gi ve writte n i nf or me d c o nse nt f or t his st u d y at t he Baseli ne Da y - 1 Visit.  If t he Baseli ne 
Da y  - 1 Visit c oi nci des wit h t he V B P 1 5- 0 0 2 Wee k 4 Visit, t he pare nts or g u ar dia ns of 
s u bjects will gi ve writte n i nf or me d c o nse nt f or t his st u d y at t he P hase IIa V B P 1 5- 0 0 2 
We e k 4 Visit, f oll o wi n g c o m pleti o n of all V B P 1 5- 0 0 2 Wee k 4 assess me nts.  T he 
I n vesti gat or ( or d esi g n ate d staff) will o btai n t he writte n i nf or me d c o nse nt a n d HI P A A 
a ut h orizati o n, if a p plica ble, fr o m t he s u bject’s p are nt or g u ar dia n pri or t o a n y e xte nsi o n 
st u d y-s pecific pr oce d ures.  Eac h s u bject’s p a re nt or g u ar dia n will recei ve a n e x pla nati o n 
of t he na t ure a n d p ur p oses of t he st u d y fr o m t he I n vesti gat or or desi g nee.  T he 
I n vesti gat or or desi g nee will e ns ure t he st u d y is a p pr o priate f or t he s u bject.  Reas o ns f or 
e x cl usi o n will be d oc u me nte d f or s u bjects f o u n d i neli gi ble d uri n g t he Pr etr eat me nt 
Peri o d.  T he s u bject’s pare nt or g uar di a n will be as ke d if s/he u n de rsta n ds t hat t he st u d y 
is f or researc h p ur p oses o nl y a n d t hat it ma y n ot pr o vi de a n y t hera p e utic be nefit t o t he 
s u bject.  Eac h s u bject’s p are nt or g u ar dia n will be as ke d if s/ he u n dersta n ds t hat t he 
s u bject is free t o wit h dra w fr o m t he st u d y at a n y ti me wit h o ut prej u dice.  T he I n vesti gat or 
or de si g n ee will re vi e w t he ele me nts of t he HI P A A a n d Pr otecte d Healt h I nf or mati o n 
( P HI) wit h eac h s u bject’s pare nt or g u ar dia n a n d eac h s u bject’s p are nt or g uar dia n will be 
as ke d if s/ he u n dersta n ds HI P A A a ut h orizati o n a n d P HI.  E ac h s u bject’s parent or 
g ua r dia n will be re q uire d t o si g n a st u d y I C F (a n d HI P A A a ut h orizati o n, if a p plica ble) 
bef or e a n y pr oce d ures are perf or me d f or t h e e xte nsi o n st u d y.  T he writte n asse nt of 
c hildre n will be o btai ne d per i n di vi d ual site g ui deli nes. 
T he I n vesti gat or or d esi g nee will o btai n writte n i nf or me d c o nse nt fr o m eac h s u bject’s 
pare nt or g u ar dia n pri or t o s u bject’s partici pati o n i n t he e xte nsi o n st u d y o n I nf or me d 
C o nse nt F or ms a p pr o ve d b y t he a p pr o priat e I R B/I E C at eac h site.  C o nse nt m ust be 
o btai ne d i n acc or da nce wit h t he pri nci ples o utli ne d i n t he c urre nt v ersi o n of t he 
De clar ati o n of Helsi n ki.  I nf or me d C o nse nt F or ms m ust be date d a n d si g ne d b y t he 
I n vesti gat or or desi g nee a n d t he s u bject’s le gal re prese ntati ve a n d t he ori gi nal si g ne d 
c o nse nt f or m m ust be ke pt b y t he I n v esti gat or i n t he st u d y s u bject’s file.  “ Le gal 
re pres e ntati ve” me a ns a n i n di vi d ual w h o m a j u dicial or ot her b o d y a ut h orize d u n der 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 8 4  of 1 3 7 
Re v era Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
a p plica ble la w t o c o nse nt o n be half of a pr os pecti ve st u d y s u bject t o t he s u bjec t’s 
partici pati o n i n t he pr oce d ure(s) i n v ol ve d i n t he researc h.  T h e St u d y M o nit or will e ns ure 
t hat t he I C F has bee n si g ne d b y t h e s u bject’s le gal re pres e ntati ve.  T he st u d y s u bject’s 
legal re prese ntati ve will recei ve a c o p y of t h e si g n e d c o nse nt f or m. 
6. 3  
Visit Sc he d ule a n d Pr oce d ures 
D uri n g t h e st u d y, t here will be a t otal of u p t o 9 st u d y site visits : Pretreat m e nt Bas eli ne 
Visit ( Da y - 1); Tr eat me nt Peri o d Wee ks 2, 4, 8, 1 2, 1 6, 2 0, a n d 2 4; a n d a fi nal D ose-
ta peri n g Peri o d Visit f or s u bjects w h ose va m or ol o ne d ose is ta pere d at t he e n d of t he 
Treat me nt Peri o d.  E ac h s u bject will recei v e t he i n vesti gati o nal pr o d u ct at sta ble d ose f or 
a peri o d of 2 4 w ee ks.  S u bjects w h o partici pat e i n t he D ose-ta peri n g Peri o d will recei ve 
a d diti o nal va m or ol o ne at decreasi n g d ose o ver a 1- t o 4- wee k i nter val, a n d will ret ur n t o 
t he st u d y site f or fi nal st u d y ass ess me nts at t he e n d of t he 2- t o 5- wee k D ose-ta peri n g 
Pe ri o d.  T he Baseli ne D a y - 1 Visit ma y ta ke place o n t he sa me da y as t h e fi nal P hase IIa 
V B P 1 5- 0 0 2 Wee k 4 Visit.  I n t his cas e, Baseli ne Da y - 1 pr o ce d ures s ho ul d be perf or me d 
after c o m pleti o n of all fi nal V B P 1 5- 0 0 2 Wee k 4 assess me nts.  See Secti o n 7  f or a 
detaile d descri pti o n of t he safet y, cli nical effi cac y, a n d P D assess me nts t o be perf or me d 
i n t his st u d y. 
6. 3. 1  
B aseli ne Peri o d ( D ay - 1) 
F or  all s u bjects, t he Bas eli ne Da y - 1 Visit will occ ur after c o m pleti o n of all V B P 1 5- 0 0 2 
Wee k 4 pr oce d ures a n d wit hi n 2 4 h o urs pri or t o a d mi nistrati o n of t he first d ose of st u d y 
me dicati o n i n t he V B P 1 5- 0 0 3 e xte nsi o n st u d y.   
Pare nts or g uar di a ns of s u bjects w h o ha ve c o m plete d all V B P 1 5- 0 0 2 st u d y assess me nts 
will si g n t he I C F f or t he V B P 1 5- 0 0 3 e xte nsi o n st u d y at t he Bas eli ne Da y - 1 Visit.  If t he 
V B P 1 5- 0 0 2 Wee k 4 Visit will ser ve as t he Baseli ne Visit f or V B P 1 5- 0 0 3 , t he 
V B P 1 5- 0 0 3-s pecific I C F m ust be si g ne d after c o m pleti o n of all fi nal V B P 1 5- 0 0 2 Wee k 4 
assess me nts  a n d pri or t o t he perf or m a nce of a n y e xte nsi o n st u d y-s pecific pr oce d ures 
(Se cti o n 6. 2 ).   
S u bjec ts w h ose V B P 1 5- 0 0 3 Baseli ne Da y - 1 Visit occ urs ≤ 2 8 da ys after t h e fi nal 
V B P 1 5- 0 0 2 Wee k 4 Visit d o n ot nee d t o re peat, at t he Bas eli ne Da y - 1 Visit,  t he p h ysical 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 8 5  of 1 3 7 
Re v era Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
e x a mi nati o n, cli nical la b orat or y tests, P D bi o mar ker bl o o d dra w, 1 2-lea d E C G, a n d 
clinical efficac y assess m e nts perf or m e d at t he V B P 1 5- 0 0 2 Wee k 4 Visit.  
V B P 1 5- 0 0 2 Wee k 2 or Wee k 4 ( w hic he v er is a v aila ble a n d later) cli nical la b orat or y 
bl o o d ( he mat ol o g y, c he mistr y, a n d li pi ds) a n d uri nal ysis test res ults s h o ul d be recei ve d 
b y  t he site a n d re vie we d b y t he I n vesti gat or t o det er mi ne eli gi bilit y f or Bas eli ne Da y - 1 
e nroll me nt i nt o t he e xte nsi o n st u d y.   
S u bjects will retai n t he s u bject i de ntificati o n n u m ber assi g ne d f or t he P has e IIa 
V B P 1 5- 0 0 2 c ore st u d y. 
A n y  n e w me dic ati o ns ta ke n fr o m t he ti me of c o m pleti o n of t he V B P 1 5- 0 0 2 st u d y t o 
a d ministrati o n of t he first d ose of st u d y m e dicati o n i n t he V B P 1 5- 0 0 3 st u d y, or a n y 
c ha n ges t o me dic ati o ns ta ke n d uri n g t he c ore st u d y, will be rec or d e d as Pri or Me dicati o ns 
o n t he a p pr o priat e e C R F.  See Secti o n 7  f or d etaile d descri pti o ns a n d i nstr ucti o ns f or 
c o m pl eti o n of eac h s afet y, efficac y, a n d P D assess me nt. 
T he f oll o wi n g pr oce d ures will be perf or me d at t he Bas eli ne Da y - 1 Visit (see T a ble 6 ): 
 
Re vie w of I ncl usi o n a n d E x cl usi o n Criteria (see Secti o n 4. 2  a n d Secti o n 4. 3 )  
 
Writte n i nf or me d c o nse nt f or e xte nsi o n st u d y (see Secti o n 6. 2 ) 
 
E nr oll me nt (see Secti o n 5. 9 ) 
 
Re c or di n g of I nteri m Me dical Hist or y (see Secti o n 7. 2. 1 ) 
 
Re c or di n g of Me dic ati o n Hist or y (s ee Secti o n 5. 7. 1 ) 
 
Re c or di n g of A Es a n d S A Es be gi n ni n g at t he ti me writte n i nf or me d c o nse nt is 
o btai ne d (se e Secti o n 7. 2. 6 ) 
 
C o m plete p h ysical e x a mi nati o n ( n ot t o be re pe ate d if B aseli ne D a y - 1 is 
≤ 2 8 d a ys after t he V B P 1 5- 0 0 2 Wee k 4 Visit ass ess me nt d ate)  (see Secti o n 
7. 2. 2 ). 
 
Meas ure me nt of hei g ht a n d wei g ht (see Secti o n 7. 2. 2 ) 
 
Re c or di n g of vital si g ns (s u pi ne bl o o d press ure, h eart rate, oral te m perat ure, 
res pirat or y rate) (see Secti o n 7. 2. 3 ) 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 8 6  of 1 3 7 
Re v era Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
 
Cli nical la b orat or y e val u ati o n i ncl u di n g he mat ol o g y, cli nical c he mistr y, li pi ds, 
a n d uri nal ysis tests ( n ot t o be re pe ate d if B aseli ne D a y - 1 is ≤ 2 8 d a ys after t he 
V B P 1 5- 0 0 2 W ee k 4 Visit assess me nt d ate)  (see Secti o n 7. 2. 4 )  
 
Bl o o d s a m ples f or P D bi o mar kers i ncl u di n g A C T H, oste ocalci n, 
1 7- h y dr o x y pr o gester o ne, C T X, P 1 N P, c ortis ol, test oster o ne, c ortic oster o ne, a n d 
1 1- de o x yc ortis ol.  Bl o o d will als o be c ollecte d a n d st ore d f or f ut ur e pr ote o mics 
pr of ili n g a n d S o ma Sc a n st u dies.  ( N ot t o be re pe ate d if B aseli ne D a y - 1 is ≤ 2 8 
d a ys af ter t he V B P 1 5- 0 0 2 Wee k 4 Visit assess me nt d ate.)  (see Secti o n 7. 3. 7 )  
 
1 2-lea d E C G ( n ot t o be re pe ate d if B aseli ne D a y - 1 is ≤ 2 8 d a ys after t he 
V B P 1 5- 0 0 2 W ee k 4 Visit assess me nt d ate)  (see Secti o n 7. 2. 5 ) 
 
Q ua nti tati ve M uscle Testi n g ( Q M T) ( n ot t o be re pe ate d if B aseli ne D a y - 1 is 
≤ 2 8 d a ys after t he V B P 1 5- 0 0 2 Wee k 4 Visit ass ess me nt d ate)  (see 
Secti o n 7. 3. 1 ) 
 
Ti me t o R u n/ W al k Test ( T T R W) ( n ot t o be re pe ate d if B aseli ne D a y - 1 is 
≤ 2 8 d a ys after t he V B P 1 5- 0 0 2 Wee k 4 Visit ass ess me nt d ate)  (see 
Secti o n 7. 3. 4 ) 
 
Ti me t o S ta n d Test ( T T S T A N D) ( n ot t o be re pe ate d if B aseli ne D a y - 1 is 
≤ 2 8 d a ys after t he V B P 1 5- 0 0 2 Wee k 4 Visit ass ess me nt d ate)  (see 
Secti o n 7. 3. 2 )  
 
Ti me t o Cli m b Test ( T T C LI M B) ( n ot t o be re pe ate d if B aseli ne D a y - 1 is 
≤ 2 8 d a ys after t he V B P 1 5- 0 0 2 Wee k 4 Visit ass ess me nt d ate)  (see 
Secti o n 7. 3. 3 ) 
 
N or t h Star A m b ulat or y Assess me nt ( N S A A) ( n ot t o be re pe ate d if B aseli ne 
D a y - 1 is ≤ 2 8 d a ys after t he V B P 1 5- 0 0 2 Wee k 4 Visit assess me nt d ate)  (see 
Se cti o n 7. 3. 5 ) 
 
Si x- mi n ute Wal k Test ( 6 M W T) ( n ot t o be re pe ate d if B aseli ne D a y - 1 is 
≤ 2 8  d a ys after t he V B P 1 5- 0 0 2 Wee k 4 Visit ass ess me nt d ate)  (see 
Secti o n 7. 3. 6 ) 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 8 7  of 1 3 7 
Re v era Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
 
Pe diatric O utc o mes Data C ollecti o n I nstr u me nt c o m plete d b y p are nt/le gal 
g uar dia n (see Secti o n 7. 3. 8 ). 
 
Dis pe ns i n g of st u d y me dicati o n a n d s u bject diaries (see Secti o n 5. 3  a n d 
Se cti o n 8. 4 ) 
6. 3. 2  
Tre at m e nt Peri o d D ay 1 
Treat me nt Peri o d Da y 1 be gi ns wit h a d mi nistrati o n of t he first d ose of st u d y me dicati o n.  
T here  is n o sc he d ule d cli nic visit o n Da y 1.   
S u bjects will ta ke t he first d ose of st u d y me dicati o n at h o me o n t he m or ni n g of t he d a y 
after t he Da y - 1 Visit, o n St u d y Da y 1, u n der t he s u per visi o n of a pare nt or g uar dia n 
(Se cti o n 5. 3 ).   
6. 3. 3  
Tre at m e nt Peri o d Wee ks 2- 2 4  
S u bjec ts will ret ur n t o t he st u d y site f or safet y, efficac y, a n d P D assess me nts be gi n ni n g at 
We e k 2 a n d c o nti n ui n g t hr o u g h Wee k 2 4, acc or di n g t o t he sc h e d ule of visits i n T a b le 6.   
S u bjec ts will c o nti n ue t o recei v e dail y oral a d mi nistrati o n of va m or ol o ne t hr o u g h o ut t he 
2 4- wee k Treat me nt Peri o d, ta ke n f oll o wi n g i n gesti o n of 8 o u nces of w h ole mil k.  If 
w h ole mi l k is n ot t olera ble t o t he s u bject, a ser vi n g of a n ot her hi g h fat f o o d ma y b e 
s u bstitute d.   
D osi n g is t o occ ur at h o me t hr o u g h o ut t he 2 4- wee k Treat me nt Peri o d, e x ce pt at t he 
Wee k 1 2 a n d Wee k 2 4 Visits w he n d osi n g will occ ur at t he st u d y site.  S u bjects m ust 
ha ve  fast e d ≥ 6 h o urs pri or t o arri val at t he st u d y site f or Wee k 1 2 a n d Wee k 2 4 
pr oc e d ures a n d ass ess me nts.  T he pre- d os e bl o o d dra ws f or P D (i ns uli n a n d gl uc ose o nl y ) 
deter mi nati o n m ust be c ollecte d after s u bjects ha v e faste d f or ≥ 6 h o urs.  Brea kfast (a n 
8- o u nce glass of w h ole mil k [ or e q ui vale nt hi g h fat f o o d p orti o n] a n d 1 c u p of cereal) 
will be  ser ve d at t he st u d y site after t he bl o o d dr a w f or i ns uli n a n d gl uc ose, a n d wit hi n 
a p pr o x i matel y 3 0 mi n utes pri or t o a d mi nistrati o n of t he d ose of st u d y me di cati o n.  St u d y 
me dica ti o n acce pta bilit y will be assesse d b y a 5- p oi nt he d o nic scale i m me diatel y b ef ore 
(s mell) a n d aft er (taste) a d mi nistrati o n of t he dail y d ose of st u d y m e dicati o n at t he 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 8 8  of 1 3 7 
Re v era Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
Wee k 1 2 a n d Wee k 2 4 Visits.  All ot her Wee k 1 2 a n d Wee k 2 4 assess me nts s h o ul d be 
perf or me d after a d mi nistrati o n of t he fi nal d ose of st u d y me dicati o n.   
Cli nical efficac y assess m e nts ( Q M T, T T S T A N D, T T R W, T T C LI M B, N S A A, a n d 
6 M W T) a n d t he Pe diatric O utc o mes D ata C ollecti o n I nstr u me nt will be c o n d ucte d at 
1 2- wee k i nter vals ( Wee ks 1 2 a n d 2 4 ).  Wei g ht will be rec or de d e v er y 4 wee ks a n d hei g ht 
will be  meas ure d at 1 2- w ee k i nter vals.  Vital si g ns will be rec or d e d at eac h st u d y visit.  A 
p h ysical e x a mi nati o n will be perf or m e d at Wee k 2 4.  A 1 2-lea d E C G will b e rec or de d at 
We e ks 1 2 a n d 2 4.  Bl o o d a n d uri ne sa m ples f or cli nical la b orat or y tests a n d bl o o d f or t he 
ser u m PD bi o mar ker pa n el i ncl u di n g S o masca n a n d pr ote o mics pr ofili n g will be 
c ollecte d at sc h e d ule d visits t hr o u g h o ut t he st u d y (see  T a ble 6 ).  A d verse e ve nts, 
i ncl u di n g SA Es, a n d c o n c o mita nt me dicati o ns will be assesse d at eac h st u d y visit a n d 
rec or d e d t hr o u g h o ut t he st u d y.   
St u d y m e dicati o n will be dis pe nse d at 1 2- wee k i nter vals a n d ret ur ne d f or d osi n g 
c o m plia nce m o nit ori n g at 1- m o nt h i nter vals f or all s u bjects.  St u d y m e dicati o n ret ur ne d 
at the Wee k 4, 8, 1 6, a n d 2 0 Visits will be re dis pe nse d t o t he s u bject at t he e n d of eac h 
visit , after i nteri m c o m plia nce m o nit ori n g, f or c o nti n ue d d osi n g t hr o u g h t he e n d of t he 
1 2- wee k dis pe nsi n g i nter val.  S u bjects will recei v e s u bject diaries at eac h 1- m o nt h 
i nter val visit a n d ret ur n t he diaries at eac h s u bs e q ue nt visit.  Diaries will be re vie we d 
wit h t he  s u bject’s pare nt or g u ar dia n b y t he st u d y staff t o assess A Es a n d c ha n ges t o 
c o nco mita nt me dicati o ns/t hera pies.  
Li mite d safet y assess me nts a n d re vie w of t he s u bject diar y are c o n d ucte d at t he Wee k 2 
Visit.  
S u bjects w h o will n ot partici pate i n t he D ose-ta peri n g Peri o d (s ee Secti o n 6. 3. 4 ) will be 
disc har ge d fr o m t he st u d y f oll o wi n g c o m pleti o n of all Wee k 2 4 assess me nts.  S u bjects 
w h o d o partici pa te i n t he D ose-ta peri n g Peri o d will be dis pe nse d va m or ol o ne (a n d 
sta n dar d of care gl uc oc ortic oi d at t he discreti o n of t he I n v esti gat or f or s u bj ects w h o elect 
t o transiti o n t o sta n dar d of care gl uc oc ortic oi d treat me nt) at t he Wee k 2 4 Visit, as well as 
i nstr ucti o ns f or ta peri n g t he d ose of va m or ol o ne d uri n g t he D ose-ta peri n g Peri o d.   

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 8 9  of 1 3 7 
Re v era Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
6. 3. 4  
D ose T a peri n g Peri o d ( Wee ks 2 5- 2 9) 
S u bjects w h o elect t o tra nsiti o n t o sta n dar d of care gl u c oc ortic oi d treat me nt f or D M D, or 
disc o nti n ue va m or ol o ne a n d n ot be gi n sta n dar d of care gl u c oc ortic oi d tr eat me nt f or 
D M D at t he e n d of t h e st u d y will ha ve t h eir va m or ol o ne d ose ta pere d pri or t o disc har ge 
fr o m t he st u d y.  S u bjects w h o disc o nti n ue st u d y m e dicati o n pri or t o c o m pleti o n of Wee k 
2 4 assess me nts will als o partici pate i n t he D os e-ta peri n g Peri o d if p ossi ble a n d if, i n t he 
o pi ni o n of t he I n v esti gat or, it is safe t o d o s o.  D ose ta peri n g will be perf or me d i n a 
ste p wise man ner, acc or di n g t o t he s u bject’s va m or ol o ne d ose d uri n g t he 2 4- wee k 
Treat me nt Peri o d, as o utli ne d i n T a ble 7 .  S u bjects w h o elect t o tra nsiti o n t o a sta n dar d 
of c are gl uc oc ortic oi d will ha ve t heir va m or ol o ne d ose ta pere d as i n T a ble 7 , a n d will 
be g i n treat me nt wit h a st a n dar d of care gl uc oc ortic oi d o n t he da y d ose ta peri n g be gi ns.  
T hese  s u bjects will c o nti n ue t o recei ve sta n dar d of care gl uc oc ortic oi d treat me nt, wit h 
dr u g  a n d d ose at t he discreti o n of t he I n vesti gat or, t hr o u g h o ut t he d urati o n of t he 
D ose- ta peri n g Peri o d a n d after disc h ar ge fr o m t he st u d y. 
T he s u bject’s w ei g ht r ec or de d at t he Wee k 2 4 Visit will be use d t o calc ulat e d ose v ol u me 
f or all d ose de-escalati o ns d uri n g t he D os e-ta peri n g Peri o d (see A p pe n di x 1 4. 1 ) 
T a b le 7  
V a m or ol o ne D ose T a peri n g 
Tre at me nt Peri o d 
V a m or ol o ne D ose 
Le v el  
Wee k 2 5 D ose 
Le v el  
Wee k 2 6 D ose 
Le vel  
Wee k 2 7 D ose 
Le vel  
Wee k 2 8 D ose 
Le vel  
Wee k 2 9 
D ose Le v el  
0. 2 5 m g/ k g/ d a y  
0. 1 2 5  m g/ k g/ d a y  
0  m g/ k g/ d a y  
 
 
 
0. 7 5 m g/ k g/ d a y  
0. 3 7 5  m g/ k g/ d a y  0. 1 2 5  m g/ k g/ d a y  
0 m g/ k g/ d a y  
 
 
2. 0 m g/ k g/ d a y  
1 m g/ k g/ d a y  
0. 5 m g/ k g/ d a y  
0. 2 5 m g/ k g/ d a y  
0 m g/ k g/ d a y  
 
6. 0 m g/ k g/ d a y  
3 m g/ k g/ d a y  
1. 5 m g/ k g/ d a y  
0. 7 5 m g/ k g/ d a y  
0. 2 5 m g/ k g/ d a y  
0 m g/ k g/ d a y  
 
All s u bjects partici pati n g i n t he D ose-ta peri n g Peri o d will ret ur n t o t he st u d y site f or fi nal 
st u d y assess me nts a p pr o xi matel y o ne wee k after t he fi nal d ose de-escalati o n (i.e., 
a p pr o x i matel y o ne w ee k after t he s u bject has recei ve d his last d ose of va m or ol o ne).  T he 
d urati o n of t he D ose-ta peri n g Peri o d will t heref ore var y de pe n di n g u p o n t he va m or ol o ne 
d ose recei ve d b y t he s u bj ect d uri n g t he Treat me nt Peri o d, fr o m a t otal d urati o n of t w o 
wee ks (f or s u bjects r ecei vi n g 0. 2 5 m g/ k g/ d a y va m or ol o ne; fi nal st u d y visit at W ee k 2 6) 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 9 0  of 1 3 7 
Re v era Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
t o fi ve wee ks (f or s u bjects recei vi n g va m or ol o n e 6. 0 m g/ k g/ da y; fi nal st u d y visit at Wee k 
2 9). 
At t he f i nal st u d y visit, s u bjects partici pati n g i n t he D ose-ta peri n g Peri o d will ha ve vital 
si g ns rec or de d, a n d bl o o d c ollecte d f or cli nical la b orat or y tests a n d P D bi o mar ker pa nel.  
St u d y m e dicati o n will be ret ur ne d f or c o m plia nce m o nit ori n g.  A d verse e ve nts, i ncl u di n g 
S A Es, a n d c o nc o mita nt me dicati o ns will be assesse d.  S u bject diaries will be ret ur n e d 
a n d re vie we d wit h site staff.   
S u bjects will be disc har ge d fr o m t he st u d y f oll o wi n g c o m pleti o n of all fi nal D ose-
ta peri ng Peri o d assess me nts. 
6. 4  
S u bject Disc o nti n u ati o n 
In t he e ve nt t hat a s u bj ect wit h dra ws earl y fr o m t he st u d y pri or t o t he Wee k 2 4 Visit, t he 
reas o n f or disc o nti n uati o n m ust be f ull y d oc u me nt e d i n t he s o urce d o c u me nts a n d t he 
e C R F.  F or s u bjects w h o wit h dra w earl y, fi nal Wee k 2 4 assess me nts s h o ul d be perf or me d 
at the ti me of earl y disc o nti n uati o n (s ee Secti o n 6. 3. 3 ).  Site pers o n nel will d oc u me nt all 
assess me nts, i ncl u di n g a n y A Es, i n t he s o urce d o c u me nts a n d e C R F.  S u bj ects w h o 
disc o nti n ue  st u d y me dicati o n s h o ul d f oll o w va m or ol o ne d ose ta peri n g pr oce d ures 
desc ri be d i n Secti o n 6. 3. 4  a n d detaile d i n t he Ma n ual of O perati o ns. 
6. 5  
St u d y C o m pleti o n 
A c o m plete d s u bject is d efi ne d as a s u bject w h o h as c o m plete d t he 2 4- wee k Treat me nt 
Pe ri o d a n d D ose-t a peri n g Peri o d, if a p plica ble, a n d has n ot pre mat urel y wit h dra w n fr o m 
t he st u d y f or a n y reas o n. 
7  
S T U D Y A S S E S S M E N T S A N D M E A S U R E M E N T S 
7. 1  
De m o gr a p hic Assess me nts 
D e m o gra p hic i nf or mati o n ( birt h date, race, a n d et h nicit y) c ollecte d d uri n g t he 
V B P 1 5- 0 0 2 st u d y will be use d f or t his st u d y; c ollecti o n of data will n ot be re peate d 
d uri n g t hi s st u d y.   

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 9 1  of 1 3 7 
Re v era Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
7. 2  
S afet y a n d T oler a bilit y Assess me nts 
7. 2. 1  
I nteri m Me dic al Hist ory 
At t he Bas eli ne Da y - 1 Visit, i nteri m me dical hist or y will be rec or de d f or eac h s u bject, 
i ncl u di n g me dical hist or y mi grate d fr o m t he V B P 1 5- 0 0 2 c ore st u d y a n d a n y me dical 
hist or y t hat occ urre d i n t he peri o d bet w ee n c o m pl eti o n of V B P 1 5- 0 0 2 a n d e nr oll me nt 
i nt o t he VB P 1 5- 0 0 3 e xte nsi o n st u d y.  Mi grate d m e dical hist or y will i ncl u de a n y 
c o n diti o n t hat was rec or de d as me dical hist or y f or t he V B P 1 5- 0 0 2 c ore st u d y.  Me dical 
hist or y occ urri n g bet w ee n c o m pleti o n of V B P 1 5- 0 0 2 a n d V B P 1 5- 0 0 3 e nr oll me nt will 
i ncl u de s urgical hist or y a n d c o nc urre nt diseases, i ncl u di n g a n y c ha n ges fr o m t he c ore 
st u d y.  All A Es t hat are rec or de d d uri n g t he V B P 1 5- 0 0 2 c ore st u d y a n d are o n g oi n g at 
t he ti me of e nr oll me nt i nt o t he V B P 1 5- 0 0 3 st u d y will be rec or d e d as me di cal hist or y i n 
t he V BP 1 5- 0 0 3 st u d y. 
I nteri m me dical hist or y will be rec or d e d i n t he s o urce d oc u m e nts a n d i n t he e C R F. 
7. 2. 2  
P hysic al E x a mi n ati o n,  Wei g ht, a n d Hei g ht 
A c o m plete p h ysical e x a mi nati o n will be perf or m e d at t he Baseli ne Da y - 1 a n d Wee k 2 4 
Visit s, a n d will i ncl u d e e x a mi n ati o n of t h e f oll o wi n g: h e a d, e yes, ears, n ose, a n d t hr oat, 
nec k (i ncl u di n g a n e x a mi n ati o n of t he t hyr oi d), heart, l u n gs, a b d o me n (i ncl u di n g a n 
ex a mi n ati o n of t he liver a n d s plee n),  l y m p h n o d es, e xtre mities, ner v o us s yste m, a n d s ki n.  
If t he Baseli ne D a y - 1 Visit occ urs ≤ 2 8 da ys aft er t he date of t he fi nal V B P 1 5- 0 0 2 c ore 
st u d y Wee k 4 Visit, t he Baseli ne Da y - 1 p h ysic al e x a mi nati o n d oes n ot nee d t o be 
re peat e d (res ults fr o m t he V B P 1 5- 0 0 2 Wee k 4 Visit will be use d).  
A d diti o na l u nsc he d ule d s y m pt o m- directe d p h ysical e xa mi nati o ns ma y b e c o n d ucte d at 
a n y ti me at t he I n vesti gat or’s discreti o n.   
Hei g ht (i n c m) will be rec or de d at Bas eli ne Da y - 1, a n d Wee ks 1 2 a n d 2 4.  Wei g ht 
(i n k g) will be rec or de d at Baseli ne Da y - 1, Wee k 4, a n d eac h sc he d ule d m o nt hl y visit 
t hereafter t hr o u g h Wee k 2 4.  Wei g ht rec or de d at eac h m o nt hl y visit will be use d t o 
calc ulate t he v a m or ol o ne d ose v ol u me f or eac h s u bse q ue nt m o nt h’s d osi n g (see 
A p pe n di x 1 4. 1 ).   

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 9 2  of 1 3 7 
Re v era Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
Res ults will be rec or de d i n t he s o urce d o c u me nts a n d o n t he a p pr o priat e e C R F. 
7. 2. 3  
Vit al Si g ns 
Vital si g ns (s u pi ne bl o o d press ure, h eart rate, res pirati o n rate, a n d oral te m perat ur e ) will 
be  rec or de d at Bas eli ne Da y - 1, Wee k 2, Wee k 4, a n d eac h sc he d ule d m o nt hl y visit 
t hereafter t hr o u g h Wee k 2 4 , a n d at t he fi nal Wee k 2 6- 2 9 st u d y visit f or s u bjects w h ose 
d ose is ta pere d d uri n g t h e D ose-ta peri n g Peri o d.  Vital si g ns s h o ul d be rec or de d aft er t he 
s u bject has bee n resti n g f or at least 5 mi n utes.   
Re s ults will be rec or de d i n t he s o urce d o c u me nts a n d o n t he a p pr o priat e e C R F. 
If vital si g ns ass ess me nt is perf or me d at t he sa me st u d y visit as bl o o d sa m pli n g a n d E C G 
rec or di n g, t he f oll o wi n g se q ue nce s h o ul d b e f oll o we d: 1) E C G rec or di n g; 2) vital si g ns 
assess me nt; a n d 3) bl o o d sa m pli n g.  
7. 2. 4  
Cli nic al L a b or at ory Tests 
Eac h s u bject will ha v e bl o o d dra w n a n d uri ne c oll ecte d f or t he he mat ol o g y, c he mistr y, 
li pi ds, a n d uri nal ysis cli nical la b orat or y tests liste d i n T a ble 8  a n d T a ble 9 , bel o w, at t he 
B aseli ne Da y - 1, a n d Wee k 4, 8, 1 6, a n d 2 4 Visits.  S u bjects w h ose d ose is ta pere d will 
als o ha ve cli nical la b orat or y tests p erf or m e d at t he fi nal Wee k 2 6- 2 9 Visit at t he e n d of 
t he D ose-ta p eri n g Peri o d.  If t he Baseli ne Da y - 1 Visit occ urs ≤ 2 8 da ys after t he date of 
t he fi nal V BP 1 5- 0 0 2 c ore st u d y Wee k 4 Visit, cli nical la b orat or y tests d o n ot nee d t o be 
re peat e d o n Baseli ne D a y - 1 f or t he V B P 1 5- 0 0 3 st u d y (res ults fr o m t he V B P 1 5- 0 0 2 c ore 
st u d y will be use d as b as eli ne meas ure me nts f or t he V B P 1 5- 0 0 3 st u d y).   
F or  all s u bjects, t he cli nical la b orat or y test res ults o btai ne d at t he V B P 1 5- 0 0 2 Wee k 2 
Visit wil l be use d t o assess e xte nsi o n st u d y eli gi bilit y, u nl ess V B P 1 5- 0 0 2 Wee k 4 Visit 
cli nical la b orat or y test r es ults are a vaila ble: if t he V B P 1 5- 0 0 2 Wee k 4 Visit cli nical 
la b orat or y test r es ults are a vaila ble pri or t o V B P 1 5- 0 0 3 e nr oll me nt, V B P 1 5- 0 0 2 Wee k 4 
res ults will be use d t o assess e xte nsi o n st u d y eli gi bilit y.  Re vie w of V B P 1 5- 0 0 2 Wee k 2 
res ults ( or V B P 1 5- 0 0 2 Wee k 4 res ults if a vaila bl e) is re q uir e d pri or t o e nr oll me nt of t he 
s u bject i nt o t his e xte nsi o n st u d y. 
All bl o o d a n d uri ne sa m ples will be se nt t o t he desi g nate d ce ntr al la b orat or y f or testi n g. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 9 3  of 1 3 7 
Re v era Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
F or t he h e mat ol o g y,  c he mistr y, a n d li pi ds la b orat or y tests, bl o o d will be c ollecte d b y 
direct ve ni p u nct ur e of peri p heral vei ns.  A p pr o xi matel y 4. 5 m L ( 7 m L at n o n- U S sites) of 
bl o o d will be o bta i ne d f or cli nical la b orat or y tests at eac h s c he d ule d visit.  A t otal of 
a p pr o xi matel y 1 8- 2 7 m L ( 2 8- 4 2 m L at n o n- U S sites) of bl o o d will be c ollecte d o ver t he 
c o urse of t his st u d y f or cli nical la b orat or y e val uati o n (see Secti o n 7. 4  f or d etails of bl o o d 
v ol u me s t o be c ollecte d).   
If bl o o d sa m pli n g is perf or me d at t he sa me st u d y visit as vital si g ns assess me nt a n d E C G 
rec or di n g, t he f oll o wi n g se q ue nce s h o ul d b e f oll o we d: 1) E C G rec or di n g; 2) vital si g ns 
assess me nt; a n d 3) bl o o d sa m pli n g.  
A n y a b n or mal he mat ol o g y, c h e mistr y, li pi d, or uri nal ysis test res ult dee me d cli nicall y 
si g nifica nt b y t he I n vesti gat or or me di call y q u alifie d s u b-i n vesti gat or ma y be re peate d, 
i ncl u di n g test res ults o bt ai ne d o n t he fi nal st u d y d a y.   
A n y  tr eat me nt- e mer ge nt a b n or mal la b orat or y test res ult t hat is cli nicall y si g nifica nt, i.e., 
meeti n g o n e or m ore of t he f oll o wi n g c o n diti o ns, s h o ul d be rec or de d as a si n gle dia g n osis 
o n t he A E se cti o n of t he e C R F: 
 Acc o m pa nie d b y cli nical s y m pt o ms  
 Re q uiri n g a c ha n ge i n c o nc o mita nt t hera p y (e. g. , a d diti o n of, i nterr u pti o n of, 
disc o nti n uati o n of, or a n y ot her c ha n ge i n a c o n c o mita nt me dicati o n, t hera p y, or 
treat me nt)  
 Is ot her wise c o nsi d ere d cli nicall y si g nifica nt b y t h e I n vesti gat or 
A n y cli nicall y si g nifica nt test a b n or malit y as defi n e d a b o ve s h o ul d be rec or de d as a n A E 
( u nless it was c o nsi dere d s p uri o us), a n d re p eat a nal ysis perf or me d u ntil res ol uti o n or 
u ntil t he I n vesti gat or or me dicall y q u alifie d s u b-i n vesti gat or d eter mi nes t h at res ol uti o n of 
t he a b n or malit y is n ot e x pecte d.   

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 9 4  of 1 3 7 
Re v era Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
T a ble 8   
He m at ol o g y, C he mist r y, a n d Li pi ds Cli nic al L a b or at or y Tests 
He m at ol o g y  
Re d Bl o o d Cells ( R B C ) 
N u merical platelet c o u nt (esti mate n ot acce pta ble)  
He m o gl o bi n  
W hite Bl o o d Cells ( W B C ) wit h differe ntial ( perce nt)  
He mat ocrit  
 
 
 
C he mistr y  
S o di u m  
T otal Bilir u bi n a 
P otassi u m  
Uric Aci d  
C hl ori de  
Gl uc ose  
Calci u m  
Al kali ne p h os p hatase ( A L P)  
I n or ga nic P hos p h or us  
Ga m ma Gl uta m yl Tra nsferase ( G G T)  
Bl o o d Urea Nitr o ge n ( B U N ) 
As partate a mi n otra nsferase  ( A S T) 
Creati ni ne  
Ala ni ne a mi n otra nsferase  ( A L T) 
T otal Pr otei n  
Creati ne ki nase ( C K)  
Al b u mi n  
Li pase  
Bicar b o nate  
A m ylase  
Lactate De h y dr o ge nase ( L D H)  
 
 
 
Li pi ds  
Tri gl yceri des  
L o w De nsit y Li p o pr otei n ( L D L)  
T otal c h olester ol  
Hi g h de nsit y Li p o pr otei n ( H D L)  
a. If o utsi de n or mal ra n ge, direct bilir u bi n will be meas ure d a n d re p orte d. 
Uri ne will be c ollect e d f or r o uti ne a nal ysis, b y di pstic k a n d micr osc o pic a n al ysis, f or t h e 
tests descri bed i n T a ble 9 .  Uri ne will be a nal yze d b y di pstic k a n d micr osc o pic a nal ysis 
b y  t he ce ntral la b orat or y at all assess me nt ti me p oi nts. 
T a ble 9  
Uri n al ysis Cli nic al L a b or at or y Tests 
Uri n al ysis (i ncl u di n g micr osc o pic e x a mi n ati o n) 
Di pstic k a 
Micr osc o pic A n al ysis  
Pr otei n  
W B C/ h pf  
Gl uc ose  
R B C/ h pf  
Ket o nes  
Casts  
p H  
Bacteria  
Le u k oc yte esterase  
 
Bl o o d  
 
aA mi dstrea m clea n -catc h uri ne s peci me n will be c ollecte d f or di pstic k a nal ysis.   
Cli nical la b orat or y tests will be perf or me d b y a ce ntral la b orat or y; res ults will be re p orte d 
t o t he st u d y site a n d tra nsferre d electr o nicall y i nt o t he cli nical st u d y d ata bas e. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 9 5  of 1 3 7 
Re v era Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
T he pr oce d ures f or t he c ollecti o n, ha n dli n g, a n d s hi p pi n g of la b orat or y sa m ples will be 
s pecifie d i n t he La b orat or y M a n ual(s) pr o vi de d t o t he cli nical ce nter. 
7. 2. 4. 1  
F oll o w- u p of A b n or m al L a b or at ory Test Res ults 
In t he e ve nt of a me dicall y si g nifica nt, u n e x plai ne d, or a b n or mal cli nical la b orat or y test 
val ue, t he test(s) ma y b e re peat e d, e val u ate d b y t h e I n vesti gat or f or s ustai na bilit y a n d 
re pro d uci bilit y t o d eter mi ne if t he a b n or malit y re prese nts a n A E, a n d f oll o we d- u p u ntil 
t he res ults ha ve ret ur ne d t o t he n or mal ra n ge, sta bilize d, a n d/ or a n a de q uat e e x pla nati o n 
f or t he a b n or m alit y is f o u n d.  If a cl ear e x pla nati o n is esta blis he d, it s h o ul d be rec or de d i n 
t he s o urce d o c u me nts a n d e C R F.  T he cli nical la b orat or y will clearl y m ar k all la b orat or y 
test val ues t hat are o utsi d e t he n or mal ra n ge a n d t h e I n vesti gat or will i n dicate w hic h of 
t hese de viati o ns are cli nicall y si g nifica nt.  T hese cli nicall y si g nifica nt d e viati n g 
la b orat or y res ults will t he n be f urt h er des cri be d as A Es, a n d t he rel ati o ns hi p t o t he 
treat me nt, i n t he I n vesti gat or’s o pi ni o n, will be i n dicate d (see Se cti o n 7. 2. 6 ).  
7. 2. 5  
1 2 - Le a d E C G 
1 2-lea d E C Gs will be c ollecte d at t he Ba seli ne Da y - 1, Wee k 1 2, a n d Wee k 2 4 Visits.  If 
t he Bas eli ne Da y -1 Visit occ urs ≤ 2 8 da ys after t h e date of t he fi nal V B P 1 5- 0 0 2 c ore 
st u d y Wee k 4 Visit, t he Baseli ne Da y - 1 1 2-lea d E C G d oes n ot nee d t o be re peat e d 
(res ults fr o m t he V B P 1 5- 0 0 2 Wee k 4 Visit will be use d).  All E C G rec or di n gs m ust be 
perf or me d usi n g a sta n dar d hi g h- q u alit y, hi g h-fi delit y m ac hi ne e q ui p pe d wit h c o m p uter-
base d i nter val meas ure m e nts.  Di gital E C G rec or di n g is rec o m me n de d.  A ut o mate d E C G 
i nter vals ( Q R S d urati o n, P R [ PQ] i nter val, R R i nter val [i nter beat i nter v al], Q T i nter val, 
Q Tc , a n d heart rate) will be ca pt ur e d or calc ulate d.   
1 2-lea d E C Gs will be o bt ai ne d o ver a 3- t o 5- mi n ute peri o d aft er t he s u bject has bee n 
restin g q uietl y i n a s u pi n e p ositi o n f or at least 5 mi n utes.  
If bl o o d sa m pli n g, vital si g ns assess me nt, a n d E C G rec or di n gs are s c he d ul e d at t he sa me 
st u d y visits, t he f oll o wi n g se q ue nce s h o ul d b e f oll o we d: 1) E C G rec or di n g; 2) vital si g ns 
assess me nt; a n d 3) bl o o d sa m pli n g. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 9 6  of 1 3 7 
Re v era Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
E C G  res ults will be rea d l ocall y.  Res ults m ust be i nter prete d a n d rec or de d o n t he 
a p pr o priate e C R F. 
7. 2. 6  
A dverse Eve nts a n d Seri o us A dverse Eve nts 
T he c o n diti o n of t he s u bjects will be m o nit ore d t hr o u g h o ut t he d urati o n of t he st u d y b y 
t he clinical site st u d y te a m a n d b y rec or di n g of A Es i n s u bject diaries.  A n A E is a n y 
u nt o war d me dical o cc urre nce i n a s u bject w hic h d oes n ot necess aril y h a ve t o ha ve a 
ca usal relati o ns hi p wit h t he i nter ve nti o n.  A n A E ca n t heref ore be a n y u nfa v or a ble a n d 
u ni nte n de d si g n (i n cl u di n g a n a b n or mal la b orat or y fi n di n g, f or e x a m ple), s y m pt o m, or 
disease te m p orall y ass o ciate d wit h t he use of a n i n vesti gati o nal pr o d u ct, w h et her or n ot 
c o nsi dere d relate d t o t he pr o d uct.  Pre-e xisti n g c o n diti o ns t hat w orse n d uri n g a st u d y are 
t o be re p orte d as A Es. 
A d verse e ve nts will be rec or de d fr o m t he date of i nf or me d c o ns e nt a n d t hr o u g h t he ti me 
of t he s u bject’s last st u d y visit (st u d y c o m pleti o n or earl y disc o nti n uati o n).  Seri o us 
a d verse e ve nts will be rec or de d fr o m t he date of i nf or me d c o ns e nt, t hr o u g h o ut t he 
clinical trial, a n d f or u p t o 3 0 da ys after t he fi nal a d mi nistrati o n of st u d y dr u g.  S u bjects 
w h o e nr oll i n t he V B P 1 5- 0 0 3 e xte nsi o n st u d y will ha ve a n y A Es w hic h i nitiate d d uri n g 
V B P 1 5- 0 0 2 partici pati o n a n d w hic h are o n g oi n g at t he ti me of e nr oll me nt i nt o 
V B P 1 5- 0 0 3 rec or d e d i n t he V B P 1 5- 0 0 3 e C R F a n d f oll o we d d uri n g V B P 1 5- 0 0 3 
partici pati o n.  I n a d diti o n, s u bjects (a n d t heir p are nt or le gal g u ar dia n) will be q uesti o ne d 
b y st u d y staff at eac h st u d y visit f or a n y n e w si g ns or s y m pt o ms or c h a n ges i n e xisti n g 
si g ns or s y m pt o ms. 
All A Es a n d S A Es t hat are s p o nta ne o usl y re p orte d, i de ntifie d d uri n g q u esti o ni n g, or are 
a p pare nt fr o m a partici pa nt’s p h ysic al a p peara n ce will be rec or d e d i n t he s o urce 
d oc u me nts a n d i n t he s u bject’s e C R F.  T he d ate a n d ti me of o nset will be rec or de d.  A n y 
la b orat or y a b n or malit y t h at is o utsi de t he n or mal r a n ge a n d is c o nsi dere d a n A E (see 
Secti o n 7. 2. 4 ) s h o ul d be rec or d e d as a n A E o n t he a p pr o priate e C R F.  T he details 
recor d e d s hall i ncl u de t h e nat ure, d ate of o nset, fi nal o utc o me a n d its date, i nte nsit y 
assess me nt ( C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts [ C T C A E] gra de), a n d a 
deter mi nati o n of t he relati o ns hi p of t he e ve nt t o a d mi nistrati o n of t he st u d y dr u g (i.e., 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 9 7  of 1 3 7 
Re v era Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
ca usalit y).  All A Es will be gra de d b y C T C A E, Versi o n 4. 0 3.  Details of a n y me dicati o ns 
gi ve n t o t he s u bject t o a b ate t he A E s h o ul d be rec or de d i n t he a p pr o priate e C R F. 
I nte nsit y 
All cli nical A Es e nc o u nt ere d d uri n g t he cli nical st u d y will be rec or d e d i n t he e C R F.  
I nte nsit y of A Es will be gra de d usi n g t he m ost c urre nt versi o n of t he C o m m o n 
Ter mi n ol o g y Criteri a f or A d verse E v e nts ( C T C A E), versi o n 4. 0 3, 5- p oi nt s cale, a n d 
re p orte d i n det ail as i n dicate d o n t he e C R F.  A des cri pti o n of t he i nte nsit y s cales ca n be 
f o u n d bel o w: 
Mil d ( Gra de 1):  As y m pt o matic or mil d s y m pt o ms: cli nical or dia g n ostic o bser vati o ns 
o nl y; i nter ve nti o n n ot i n dicate d. 
M o derate ( Gra d e 2) :  Mi ni mal, l ocal, or n o ni n vasi ve i nter ve nti o n i n dicate d; li miti n g 
a ge-a p pr o priate i nstr u me ntal acti vities of dail y li vi n g ( A D L). 
Se vere ( Gra d e 3):  Se vere or me dicall y si g nifica nt b ut n ot i m me diatel y life-
t hreate ni n g: h os pitalizati o n or pr ol o n gati o n of h os pitalizati o n i n dicate d; disa bli n g; 
li miti n g self-care A D L; i nca pacitati n g wit h i na bilit y t o w or k or p erf or m n or mal dail y 
acti vit y. 
Lif e- T hreate ni n g ( Gra d e 4):  Ur ge nt i nter ve nti o n i n dicate d. 
Deat h ( Gra de 5):  Deat h relate d t o A E. 
Rel ati o ns hi p 
Relati o ns hi p t o st u d y dr u g will be gra de d o n a 5- p oi nt scale ( defi nite, pr o ba ble, p ossi ble, 
re m ote, or u nrelate d).  A descri pti o n of t he relati o ns hi p scale ca n b e f o u n d bel o w: 
Defi nite:  T his cate g or y a p plies t o a n A E t hat meets at least criteria 1, 2, a n d 4 of t he 
“ Pr o ba ble‟ cate g or y. 
Pr o ba ble:  T his cate g or y a p plies t o t h ose A Es t hat are c o nsi d ere d, wit h a hi g h de gree 
of cert ai nt y, t o be relate d t o t he st u d y dr u g.  A n A E ma y b e c o nsi dere d pr o ba ble, if 
( m ust i ncl u de first 3): 
1.  It f oll o ws a reas o na ble te m p oral se q ue nce fr o m a d mi nistrati o n of t he st u d y 
dr u g. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 9 8  of 1 3 7 
Re v era Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
2.  It c a n n ot be reas o na bl y e x plai ne d b y t h e k n o w n c haract eristics of t he 
s u bject’s cli nical state, e n vir o n me ntal or t o xic fact ors, or ot her m o des of 
t hera p y a d mi nistere d t o t he s u bject. 
3.  It disa p p ears or decreas es after d osi n g is c o m plete.  ( T here are i m p orta nt 
ex ce pti o ns w he n a n A E d oes n ot disa p pear u p o n disc o nti n uati o n of st u d y 
dr u g, yet dr u g relate d ness clearl y e xists, e. g., [ 1] b o ne marr o w d e pressi o n 
a n d [ 2] tar di ve d ys ki nesia.)  
4.  It f oll o ws a k n o w n patter n of res p o nse t o t he s us p ecte d st u d y dr u g. 
P ossi ble:  T his cate g or y a p plies t o t h ose A Es f or w hic h t he c o n necti o n wit h st u d y 
dr u g a d mi nistrati o n a p pears u nli kel y b ut ca n n ot b e r ule d o ut wit h certai nt y.  A n A E 
ma y b e c o nsi dere d p ossi bl y rel ate d t o st u d y dr u g if or w he n ( m ust i ncl u de first 2): 
1.  It f oll o ws a reas o na ble te m p oral se q ue nce fr o m a d mi nistrati o n of t he st u d y 
dr u g. 
2.  It ma y h a ve bee n pr o d u ce d b y t h e s u bject’s cli nical state, e n vir o n me ntal or 
t o xic fact ors, or ot her m o des of t hera p y a d mi nistere d t o t he s u bject. 
3.  It f oll o ws a k n o w n patter n of res p o nse t o t he s us p ecte d st u d y dr u g. 
Re m ote: I n ge neral, t his cate g or y is a p plica ble t o a n A E t hat meets t he f oll o wi n g 
criteria ( m ust i ncl u de t he first 2): 
1.  It d oes n ot f oll o w a reas o na ble te m p oral se q u e nce fr o m a d mi nistrati o n of 
t he st u d y dr u g. 
2.  It ma y rea dil y ha v e bee n pr o d uce d b y t he s u bject’s cli nical state, 
en vir o n me ntal or t o xic fact ors, or ot her m o des of t hera p y a d mi nistere d t o 
t he s u bject. 
3.  It d oes n ot f oll o w a k n o w n patter n of res p o nse t o t he s us pecte d st u d y dr u g. 
U nrelate d: T his c ate g or y is a p plica ble t o t h ose A Es w hic h are j u d ge d t o be clearl y 
a n d i nc o ntr o verti bl y d ue o nl y t o e xtra ne o us ca uses ( disease, e n vir o n me nt, etc.) a n d 
d o n ot meet t he criteria f or st u d y dr u g relati o ns hi p liste d u n der re m ote, p ossi ble, or 
pr o ba ble. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 9 9  of 1 3 7 
Re v era Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
Cli nic al L a b or at or y Test A b n or m alities 
Cli nical la b orat or y test res ults will be rec or de d i n t he desi g n ate d e C R F.  T h e i nte nsit y of 
a b n or mal cli nical la b orat or y test res ults t hat are A Es will als o be gra de d usi n g t he m ost 
c urre nt v ersi o n of t he C T C A E, versi o n 4. 0 3, 5- p oi nt scale a n d re p orte d i n d etail as 
i n dicate d i n t he e C R F.  A descri pti o n of t he i nte nsit y scal e ca n b e f o u n d a b o ve. 
A n y tr eat me nt- e mer ge nt a b n or mal cli nical la b orat or y test res ult t hat is cli nicall y 
si g nifica nt, i.e., m eeti n g o ne or m ore of t he f oll o wi n g c o n diti o ns, s h o ul d be rec or de d as a 
si n gle diag n osis o n t he A E secti o n of t he e C R F: 
 Acc o m pa nie d b y cli nical s y m pt o ms 
 Re q uiri n g a c ha n ge i n c o nc o mita nt t hera p y (e. g., a d diti o n of, i nterr u pti o n of, 
disc o nti n uati o n of, or a n y ot her c ha n ge i n a c o n c o mita nt me dicati o n, t hera p y, or 
treat me nt) 
 Is ot her wise c o nsi d ere d cli nicall y si g nifica nt b y t h e I n vesti gat or 
T his a p plies t o a n y pr ot oc ol a n d n o n- pr ot oc ol-s p ecifie d safet y la b orat or y res ult fr o m 
tests perf orme d after t h e first d ose of st u d y dr u g, w hic h falls o utsi de t he la b orat or y 
refere nce ra n ge a n d m eets t he cli nical si g nifica nce criteria per I n v esti gat or sta n dar d 
o perati n g pr oce d ures ( S O Ps). 
T his d oes n ot a p pl y t o a n y a b n or mal la b orat or y res ult t hat falls o utsi de t he la b orat or y 
refere nce ra n ge, b ut d oes n ot meet t he cli nical si g nifica nce criteri a ( w hic h will be 
a nal yze d a n d re p orte d as la b orat or y a b n or malities); t h ose t hat are c o nsi dere d A Es of t he 
t y pe e x plicitl y e x e m pte d b y t he pr ot oc ol; or t h ose t hat are t he res ult of a n A E w hic h h as 
alrea d y b ee n re p orte d. 
Ple as e N ote : a n y cli nical la b orat or y a b n or malit y f ulfilli n g t he criteri a f or a n S A E s h o ul d 
be re p ort e d as s uc h, i n a d diti o n t o bei n g rec or de d as a n A E i n t he e C R F. 
F oll o w- U p of A d verse E ve nts 
A d verse e ve nts will be f oll o we d u ntil t he y ha v e ret ur ne d t o baseli ne stat us, sta bilize d, or 
t he I n v esti gat or, St u d y C hair, Me dical M o nit or a n d S p o ns or a gree t h at f oll o w- u p is n o 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 0 0  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
l o n ger nee d e d.  If a cle ar e x pla nati o n of ca use is esta blis he d, it s h o ul d be rec or de d i n t he 
s o urce d oc u m e nts a n d e C R F.  I n t h e e ve nt of u n e x plai ne d a b n or mal la b orat or y test 
val ues, t he te sts ma y be re peate d as s o o n as p ossi ble a n d f oll o we d u p u ntil t he y h a ve 
ret ur ne d t o t he n or m al ra n ge or baseli ne v al ue a n d/ or a n a de q u ate e x pla nati o n of t he 
a b n or malit y is f o u n d.  I n case of o n g oi n g A Es at t he ti me of data bas e cl os ure, t he data 
o btai ne d at t he ti me of data base cl os ur e will be use d i n t he statistical a nal ysis.  T he 
f oll o w- u p of A Es will be d oc u me nte d i n t he s o urce d oc u me nts a n d will be descri be d i n 
t he fi nal re p ort o nl y if c o nsi dere d rel e va nt b y t he I n vesti gat or, t h e St u d y C h air, t he 
Me dical M o nit or a n d/ or t he S p o ns or. 
I n a d diti o n, t he Me dical M o nit or ma y re q uest a d diti o nal bl o o d tests, dia g n ostic i ma gi n g 
st u dies, or s pecialist p h ysicia n c o ns ultati o ns i n or der t o f urt her e val u ate a n y A E or test 
a b n or malit y c o nsi dere d t o be cli nicall y si g nifica nt b y t he St u d y S p o ns or. 
D osi n g Err or 
F or t he p ur p os es of t his st u d y, a d osi n g err or is defi ne d as a d os e e x cee di n g or less t ha n 
t he sc he d ule d d ose of 0. 2 5 m g/ k g, 0. 7 5 m g/ k g, 2. 0 m g/ k g, or 6. 0 m g/ k g s pecifie d f or 
eac h d ose l e vel gr o u p.  S uc h occ urre n ces s h o ul d b e re p ort e d a n d rec or d e d i n t he d osi n g 
pa ge  of t he eC R F  a n d as f oll o ws: 
 Use of st u d y me dicati o n i n d oses i n e x cess of t hat s pecifie d i n t he pr ot oc ol s h o ul d 
n ot be r ec or de d as a n A E u nless t here are ass o ciat e d si g ns or s y m pt o ms. 
 A d osi n g err or wit h ass o ciate d n o n-seri o us A Es s h o ul d be rec or de d as A Es o n t he 
rele va nt A E f or ms i n t he e C R F. 
 A d osi n g err or wit h a n ass ociate d S A E s h o ul d be rec or de d as a n S A E. 
 Details of all d osi n g err ors, i ncl u di n g act ual d ose a d mi nistere d, s h o ul d be 
d oc u me nte d i n t he s o urce d oc u me nts a n d rec or d e d o n t he Pr ot oc ol De viati o ns 
e CR F. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 0 1  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
7. 2. 6. 1  
Seri o us A dverse Eve nts  
F or  treat me nt-eli gi ble s u bjects, S A Es will be c ollecte d a n d re p ort e d d uri n g t he st u d y 
fr o m t he ti me i nf or me d c o nse nt is o btai ne d t hr o u g h 3 0 da ys after t he fi nal d ose of st u d y 
me dicati o n, acc or di n g t o t he pr ot oc ol a n d a p plica ble re g ulati o ns. 
All S A Es, i nc l u di n g t h ose t hat c o nti n ue be y o n d t h e n or mal A E c ollecti o n peri o d (i.e., are 
o n g oi n g at t he s u bject’s last st u d y visit), will be f oll o we d u ntil res ol uti o n or u ntil 
sta bilize d wit h o ut se q uelae.  Seri o us a d v erse e ve nts t hat be gi n after t he s u bject’s 
partici pati o n i n t he st u d y is c o m plete b ut t hat t he I n vesti gat or c o nsi ders t o be relate d t o 
st u d y dr u g will be re p ort e d t o t he S p o ns or wit hi n 2 4 h o urs or disc o ver y b y t he 
I n v esti gat or. 
D uri n g t h e S A E c ollecti o n peri o d, t he I n vesti gat or or cli nical site pers o n nel s h o ul d n otif y 
t he P R A safet y ma na ge m e nt tea m of all S A Es, re gar dless of relati o ns hi p t o t he 
i n vesti gati o nal dr u g, wit hi n 2 4 h o urs of cli nical staff bec o mi n g a ware of t h e e ve nt; 
n otificati o n t o t he P R A safet y ma na ge me nt tea m will tri g ger alerts t o t he C o or di nati n g 
Ce nter, St u d y C hair, t he S p o ns or, a n d t he Me dical M o nit or.  T he I n vesti gat or will 
pr o vi de t he i nitial n otificati o n b y c o m pleti n g t he S A E e C R F i n t he electr o nic data ca pt ure 
( E D C), whic h m ust i ncl u de t he I n vesti gat or’s assess me nt of t he relati o ns hi p of t he e ve nt 
t o i n vesti gati o nal dr u g.  I n t he u nli kel y e v e nt t hat t he electr o ni c st u d y d ata base is 
i naccessi ble a n d t he I n vesti gat or is u na ble t o c o m plete t he S A E e C R F wit hi n 2 4 h o urs, 
t he S A E N otificati o n F or m ( p df) s h o ul d be c o m pl ete d a n d e m aile d or pri nt e d/fa x e d t o t he 
P R A safet y m a na ge me nt tea m. 
I n a d diti o n, n otificati o n is se nt b y t he I n vesti gat or t o t he I R B a n d t he s u bject’s Pri mar y 
Care P h ysi cia n. 
F oll o w- u p i nf or mati o n, or ne w i nf or mati o n r e gar di n g a n o n g oi n g S A E, m ust be pr o vi de d 
pr o m ptl y t o t he P R A safet y ma na ge me nt tea m wit hi n 2 4 h o urs of k n o wle d ge of t he ne w 
or f oll o w- u p i nf or mati o n, w hic h will f or war d t he i nf or mati o n t o t he C o or di nati n g Ce nter, 
St u d y C h air, t he S p o ns or, a n d t he Me dical M o nit or. 
All S A E re p orts s h o ul d be c o m plete d wit hi n t he E D C. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 0 2  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
T he Data a n d Safet y M o nit ori n g B o ar d ( D S M B) will re vie w S A Es a n d ot her perti ne nt 
safet y data at re g ular i nter vals d uri n g t he st u d y. 
A n A E or s us pect e d a d verse reacti o n is c o nsi dere d seri o us if, i n t he vie w of eit her t he 
I n v esti gat or or S p o ns or, it res ults i n a n y of t h e f oll o wi n g o utc o mes: 
 Is fatal (res ults i n t he o utc o me of deat h) 
 Is life-t hreate ni n g  
 Re q uires i n- patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n 
 Res ults i n persiste nt or si g nifica nt i nca pacit y or s u bsta ntial disr u pti o n of t he 
a bilit y t o c o n d uct n or mal life f u ncti o ns 
 Is a c o n ge nital a n o mal y or birt h defect 
 Is a n i m p orta nt me dical e ve nt t hat ma y j e o par dize t he s u bject a n d ma y re q uire 
me dic al or s ur gic al i nter ve nti o n t o pre ve nt o ne of t he o utc o mes liste d a b o v e. 
T he ter m “s u d de n d eat h” s h o ul d o nl y be use d w he n t he ca use is of a car diac ori gi n as pe r 
sta n dar d defi niti o n. 
T he ter ms deat h a n d s u d de n deat h are cl earl y disti nct a n d m ust n ot be use d 
i nterc ha n gea bl y. 
A n y A E or cli nicall y si g nifica nt a b n or mal la b orat or y test v al ue, as det er mi ne d b y t h e 
I n v esti gat or, t hat is seri o us a n d w hic h occ urs d uri n g t he c o urse of t he st u d y (as defi ne d 
a b o ve) m ust be re p orte d t o t he P R A safet y ma na ge me nt tea m, w h o will n otif y t he 
C o or di nati n g Ce nter, St u d y C hair, t he S p o ns or, a n d t he Me dical M o nit or wit hi n 2 4 h o urs 
of t he I n vesti gat or b ec o mi n g a ware of t he e v e nt.  A d diti o nal i nf or mati o n t hat bec o mes 
a vaila ble f or a n S A E after t he i nitial re p ort is s u b mitte d will be re p orte d t o t he P R A 
safet y ma na ge me nt tea m, w h o will n otif y t he C o or di nati n g Ce nter, St u d y C hair, t he 
S p o ns or, a n d t he Me dical M o nit or wit hi n 2 4 h o urs of t he I n vesti gat or b ec o mi n g a ware of 
t he ne w i nf or mati o n. 
Re late d S A Es M U S T be c ollecte d a n d re p orte d re gar dless of t he ti me el a pse d fr o m t he 
last a d mi nistrati o n of st u d y dr u g, e ve n if t he st u d y has bee n cl os e d.  U nrelate d S A Es 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 0 3  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
m ust be c ollecte d a n d re p orte d d uri n g t he st u d y fr o m t he ti me of i nf or me d c o nse nt 
t hr o u g h 3 0 d a ys after t he fi nal d ose of st u d y me di cati o n. 
If, at a n y ti me d uri n g t he st u d y, a s u bject e x perie n ces a n S A E, a p pr o priate care s h o ul d b e 
i nstit ute d. 
I n t he e ve nt of a n S A E, t he I n vesti g at or will c o m plete t he S A E e C R F wit hi n 2 4 
h o urs of first a w are ness of t he e ve nt.  I n t he u nli kel y e ve nt t h at t he electr o nic st u d y 
d at a b ase is i n accessi ble a n d t he I n vesti g at or is u n a ble t o c o m plete t he S A E e C R F 
wit hi n 2 4 h o urs, t he S A E N otific ati o n F or m ( p df) s h o ul d be c o m plete d a n d e m aile d 
or pri nte d/f a xe d t o t he P R A s afet y m a n a ge me nt te a m wit hi n 2 4 h o urs, usi n g t he 
c o nt act i nf or m ati o n bel o w : 
E m ail C H O S afet y @ pr a hs.c o m 
Dr u g S afet y F a x: 1- 8 8 8- 7 7 2- 6 9 1 9 or 1- 4 3 4- 9 5 1- 3 4 8 2 
 
S A E Q uesti o ns: Dr u g S afet y H otli ne: 1- 8 0 0- 7 7 2- 2 2 1 5 or 1- 4 3 4- 9 5 1- 3 4 8 9 
Se ri o us A d verse E v e nts will be rec or d e d fr o m t he ti me t he s u bject’s writte n i nf or me d 
c o nse nt is o btai ne d.  Seri o us a d verse e ve nts t hat o cc ur wit hi n 3 0 da ys of st u d y dr u g 
d osi n g m ust c o nti n ue t o be rec or de d a n d re p orte d t o t he St u d y S p o ns or or its desi g nee.  
S h o ul d t here be a n S A E t hat occ urs t hat s u g gests a n i ncreas e d ris k t o t he partici pa nts, t he 
f oll o wi n g ste ps will be c o nsi dere d, de p e n di n g o n t he n u m ber a n d se v erit y of t he S A E(s): 
m o dificati o n of t he pr ot o c ol, i n vesti gati o n of t he relati o ns hi p of t he S A E(s) t o st u d y dr u g, 
s us pe nsi o n of t he st u d y, a n d/ or disc o nti n uati o n of t he st u d y. 
7. 2. 7  
St u dy Me dic ati o n Acce pt a bility Assess m e nt 
Acce pt a bilit y of t he st u d y me dicati o n will be assesse d usi n g a 5- p oi nt he d o nic scale 
i m me diatel y bef ore (s mell) a n d after (taste) d osi n g at t he Wee k 1 2 a n d Wee k 2 4 Visits.  
T he assess me nts will be a d mi nistere d b y trai ne d st u d y staff.  Res ults will be rec or de d i n 
t he s o urce d o c u me nts a n d e C R F.  

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 0 4  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
7. 3  
Cli nic al Effic ac y a n d P h ar m a c o d y n a mic Assess me nts  
7. 3. 1  
Q u a ntit ative M uscle Testi n g ( Q M T) 
Q ua ntitati ve M uscle Testi n g ( Q M T) will be a d mi nistere d t o s u bjects at t he Baseli ne 
Da y - 1, Wee k 1 2, a n d Wee k 2 4 Visits  usi n g t he CI N R G Q ua ntitati ve Meas ure me nt 
S y ste m ( C Q M S).3 7  If t h e Bas eli ne Da y -1 Visit occ urs ≤ 2 8 da ys after t h e date of t he 
fi nal V BP 1 5- 0 0 2 c ore st u d y Wee k 4 Visit, t he Baseli ne Da y - 1 Q M T d oes n ot nee d t o be 
re peat e d (res ults fr o m t he V B P 1 5- 0 0 2 Wee k 4 Visit will be use d). 
T he Q M T meas ures u nilateral stre n gt h of f o ur m uscle gr o u ps : el b o w fle xi o n/e xte nsi o n, 
a n d k nee fl e xi o n/e xte nsi o n. 3 7  C o m plete i nstr ucti o ns f or a d mi nisteri n g t h e Q M T are 
gi ve n i n t he st u d y  ma n ual t o be s u p plie d t o t he sites pri or t o st u d y start. 
Res ults will be c ollecte d usi n g t he C Q M S 3 s oft ware a n d tr a nsferre d i n t o t h e e C R F. 
7. 3. 2  
Ti m e t o St a n d Test ( T T S T A N D) 
T he Ti me t o Sta n d Test ( T T S T A N D) will be a d mi nistere d t o s u bjects at t he Baseli ne 
Da y  - 1, Wee k 1 2, a n d Wee k 2 4 Visits.  If t he Bas eli ne Da y -1 Visit occ urs ≤ 2 8 da ys 
after t he d ate of t he fi nal V B P 1 5- 0 0 2 c ore st u d y Wee k 4 Visit, t he Baseli ne Da y - 1 
T T S T A N D d oe s n ot nee d t o be re peate d (res ults fr o m t he V B P 1 5- 0 0 2 Wee k 4 Visit will 
be use d). 
T he T T S T A N D me as ures t he s pee d ( m/s; vel ocit y) wit h w hic h t he c hil d ca n sta n d t o a n 
erect p ositi o n fr o m s u pi n e (fl o or), a n d is a d mi nistere d as p art of t he N S A A (see 
Secti o n 7. 3. 5 ).  C o m plete i nstr ucti o ns f or a d mi nisteri n g a n d sc ori n g t he T T S T A N D are 
g i ve n i n t he st u d y ma n ual t o be s u p plie d t o t he sites pri or t o st u d y start. 
Res ults will be rec or de d i n t he s o urce d o c u me nts a n d i n t he e C R F. 
7. 3. 3  
Ti m e t o Cli m b Test ( T T C LI M B) 
T he Ti me t o Cli m b Test ( T T C LI M B) will be a d mi nistere d t o s u bjects at t he Bas eli ne 
Da y  - 1, Wee k 1 2, a n d Wee k 2 4 Visits.  If t he Bas eli ne Da y -1 Visit occ urs ≤ 2 8 da ys 
after t he d ate of t he fi nal V B P 1 5- 0 0 2 c ore st u d y Wee k 4 Visit, t he Baseli ne Da y - 1 
T T C L I M B d oes n ot nee d t o be re peate d (res ults fr o m t he V B P 1 5- 0 0 2 Wee k 4 Visit will 
be use d). 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 0 5  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
T he T T C LI M B m eas ur es t he ti me (i n sec o n ds) re q uire d f or t he s u bject t o cli m b 
4 sta n dar d stairs, be gi n ni n g a n d e n di n g i n a sta n di n g p ositi o n wit h ar ms at t he si des .3 8  
C o m pl ete i nstr ucti o ns f or a d mi nisteri n g t he T T C LI M B are gi ve n i n t he st u d y ma n ual t o 
be s u p plie d t o t he sites pri or t o st u d y start.  
Res ults will be rec or de d i n t he s o urce d o c u me nts a n d i n t he e C R F. 
7. 3. 4  
Ti m e t o R u n/ W al k Test ( T T R W) 
T he T T R W will be a d mi nistere d t o s u bjects at t he Baseli ne Da y - 1, Wee k 1 2, a n d 
We e k 2 4 Visits .  If t he Baseli ne Da y -1 Visi t occ urs ≤ 2 8 da ys after t he dat e of t he fi nal 
V B P 1 5- 0 0 2 c ore st u d y Wee k 4 Visit, t he Baseli ne Da y - 1 T T R W d oes n ot nee d t o be 
re peat e d (res ults fr o m t he V B P 1 5- 0 0 2 Wee k 4 Visit will be use d).   
T he Ti me t o R u n/ W al k Test ( T T R W) meas ures t h e ti me (i n sec o n ds) t hat it ta kes a 
s u bject t o r u n or wal k 1 0 meters a n d is a d mi nistere d as part of t he N S A A (s ee 
Se cti o n 7. 3. 5 .  C o m plete i nstr ucti o ns f or a d mi nisteri n g a n d sc ori n g t he T T R W are gi ve n 
i n t he st u d y ma n ual t o be s u p plie d t o sites pri or t o st u d y start. 
Re s ults will be rec or de d i n t he s o urce d o c u me nts a n d i n t he e C R F. 
7. 3. 5  
N ort h St ar A m b ul at ory Assess m e nt ( N S A A) 
T he N ort h Star A m b ulat or y Assess me nt ( N S A A) is a cli nical assess me nt s cale 
s pecificall y desi g ne d t o meas ure f u n cti o nal a bilit y i n a m b ula nt b o ys wit h D M D.3 9  T he 
N S A A c o nsists of 1 7 sc ore d ite ms a n d 2 ti me d tests, i ncl u di n g t he T T R W a n d t he 
T T S T A N D (see Secti o n 7. 3. 2 ).  T he N S A A will b e c o n d ucte d at t he Baseli ne Da y - 1, 
We e k 1 2, a n d Wee k 2 4 Visits.  If t he Bas eli ne Da y - 1 Visit occ urs ≤ 2 8 d a ys after t h e 
date of  t he fi n al V B P 1 5- 0 0 2 c ore st u d y Wee k 4 Visit, t he Baseli ne Da y - 1 N S A A d oes 
n ot nee d t o be re p eate d (res ults fr o m t he V B P 1 5- 0 0 2 Wee k 4 Visit will be use d).  
S u bjects s h o ul d be baref o ot a n d wear c o mf orta bl e cl ot hi n g. C o m plete i nstr ucti o ns f or 
a d mi nisteri n g a n d s c ori n g t he N S A A are gi ve n i n t he st u d y ma n ual t o be s u p plie d t o t he 
sites pri or t o st u d y start. 
T he N S A A s h o ul d be a d mi nistere d B E F O R E t he 6 M W T at st u d y visits w h ere b ot h tests 
are a d mi nistere d.    

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 0 6  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
Res ults will be r ec or de d i n t he s o urce d o c u me nts a n d i n t he e C R F. 
7. 3. 6  
Si x- mi n ute W al k Test ( 6 M W T) 
F u ncti o nal e x ercise ca p acit y a n d m o bilit y will be assesse d i n all s u bjects b y mea ns of t he 
Si x- mi n ute Wal k Test ( 6 M W T) at t he Baseli ne Da y - 1, Wee k 1 2, a n d Wee k 2 4 Visits.  If 
t he Bas eli ne Da y -1 Visi t occ urs ≤ 2 8 da ys after t h e date of t he fi nal V B P 1 5- 0 0 2 c ore 
st u d y Wee k 4 Visit, t he Baseli ne Da y - 1 6 M W T d oes n ot nee d t o be re peate d (res ults 
fr o m t he V B P 1 5- 0 0 2 Wee k 4 Visit will be use d). 
T his e val uati o n is a m o difie d versi o n of t he 6 M W T, a da pte d f or use i n D M D patie nts. 4 0 
T he t otal dista nce tra v ele d, i n meters, s h o ul d be rec or de d al o n g wit h t he vali dit y of t he 
test as assesse d b y t he test a d mi nistrat or i n t he s o urce d oc u m e nts a n d i n t he e C R F.  If a 
s u bject ca n n ot c o m plete 6 mi n utes of wal ki n g, t he t otal meters a n d t he ti me u ntil 
disc o nti n ua ti o n of t he test s h o ul d be rec or d e d.  C o m plete i nstr ucti o ns f or a d mi nisteri n g 
t he 6 M W T are gi ve n i n t he st u d y ma n ual t o be s u p plie d t o t he sites pri or t o st u d y start. 
T he 6 M W T s h o ul d be a d mi nistere d A F T E R t he N S A A at st u d y visits w here b ot h tests 
are a d mi nistere d.   
Res ults will be rec or de d i n t he s o urce d o c u me nts a n d i n t he e C R F. 
7. 3. 7  
P h ar m ac o dy n a mic Bi o m ar ker P a nel 
Bl o o d s a m ples will be c ollecte d t o e x pl ore t he effect of va m or ol o ne o n bi o mar kers of 
m uscle c ell ular pat h ol o g y, bi o mar kers ass o ciate d wit h c hr o nic gl uc oc ortic oi d treat me nt, 
a n d bi o mar kers ass ociate d wit h i ns uli n resista nce, a dre nal s u p pressi o n, a n d b o ne 
t ur n o ver, as liste d i n T a ble 1 0 .  Bl o o d sa m ples will be c ollecte d at t he Baseli ne Da y - 1 
a n d W ee ks 8, 1 6, a n d 2 4 Visits, a n d at t he fi nal D ose-ta peri n g Peri o d Visit f or s u bjects 
w h ose va m or ol o ne d os e is ta pere d at t he e n d of t h e st u d y.  If t he Baseli ne Da y - 1 Visit 
occ urs ≤ 2 8 da ys after t h e date of t he fi nal V B P 1 5- 0 0 2 c ore st u d y Wee k 4 Visit, t he 
Ba seli ne Da y - 1 bl o o d dr a w f or t he P D bi o mar ker pa nel d oes n ot nee d t o b e re peat e d 
(res ults fr o m t he V B P 1 5- 0 0 2 Wee k 4 Visit will be use d).  T he bi o mar ker a nal ysis 
i ncl u des A C T H, oste ocal ci n, 1 7- h y dr o x y pr o gester o ne, C T X, P 1 N P, c ortis ol, H b A 1c 
(e xce pt Bas eli ne), test ost er o ne, c ortic oster o ne, a n d 1 1- de o x yc ortis ol.  Bl o o d will als o be 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 0 7  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
c ollecte d at eac h of t hese ti me p oi nts a n d st ore d f or f ut ure pr ot e o mics pr ofili n g a n d 
S o ma Sca n st u dies .   
Bl o o d  sa m ples will be c ollecte d at t he Wee ks 1 2 a n d 2 4 Visits f or meas ure me nt of 
gl uc ose  a n d i ns uli n, after t he s u bject has fast e d f or ≥ 6 h o urs a n d pri or t o a d mi nistrati o n 
of t he da il y d os e of st u d y me dicati o n.   
A t otal of 6 1- 9 3 m L  ( 58 - 89 m L at n o n- U S sites) of bl o o d will be c ollecte d f or P D  
bi o mar kers, i ncl u di n g bl o o d c ollecte d f or fasti n g gl uc ose a n d i ns uli n, o ver t he c o urse of 
t he 2 4-wee k t o 2 9- wee k st u d y (see Secti o n 7. 4 ).   
T a b le 1 0  
P h ar m a c o d y n a mi c Bi o m a r kers 
A dre n al S u p pressi o n  
C ortis ol  
1 7 - h y dr o x y pr o gester o ne  
A C T H  
T est oster o ne  
C ortic oster o ne  
1 1 - De o x yc ortis ol  
I ns uli n Resist a nce 
Gl uc ose  
I ns uli n 
H b A 1c  
B o ne T ur n o ver  
Oste o calci n  
P 1 N P  
C T X  
E x pl or at or y Bi o m ar kers  
S o ma Sca n a n d Pr ote o mics Pr ofili n g  
 
7. 3. 8  
Pe di atric O utc o m es D at a C ollecti o n I nstr u m e nt 
Q ualit y of lif e will be ass esse d b y c o m pleti o n of t he Pe diatri c O utc o mes Data C ollecti o n 
I nstr u me nt.  T he s u bject pare nt/le gal g uar dia ns will be as ke d t o c o m plete t his i nstr u me nt 
at the Bas eli ne Da y - 1, Wee k 1 2, a n d Wee k 2 4 Visits.   
Res ults will be rec or de d i n t he e C R F. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 0 8  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
7. 4  
T ot al Bl o o d V ol u me Re q uire d 
T he n u m ber a n d v ol u me of bl o o d sa m ples a n d t otal v ol u me of bl o o d t o be c ollecte d fr o m 
eac h s u bject t hr o u g h o ut t he d urati o n of t he 2 4- wee k t o 2 9- wee k st u d y are s u m marize d i n 
T a b le 1 1.  A t otal of 7 9- 1 2 0 m L ( 8 6- 1 3 1 m L at n o n- U S sites) of bl o o d will be c ollecte d 
fr o m eac h s u bject o ver t he c o urse of t he u p t o 2 9- wee k st u d y.   
T a ble 1 1  
Bl o o d S a m ple N u m ber a n d V ol u me 
 
T ot al m L of Bl o o d  
Test  
D a y -1 a Wee k 
4  
Wee k 
8  
Wee k 
1 2  
Wee k 
1 6  
Wee k 
2 4  
Wee k 2 6 -2 9 
( E n d of 
D ose -
t a per)b  
T ot al 
V ol u me  
Cli nical Safet y La bs c 
4. 5   
( 7. 0)d 
4. 5  
( 7. 0)d 
4. 5  
( 7. 0)d 
 
4. 5  
( 7. 0)d 
4. 5  
( 7. 0)d 
4. 5   
( 7. 0)d 
1 8 -2 7  
( 2 8-4 2) d 
P D Bi o mar ker Pa nel  
1 5 e 
 
1 7 f 
( 1 6)f, d 
 
1 7 f 
( 1 6)f, d 
1 7 f 
( 1 6)f, d 
1 7 f  
( 1 6)f, d 
5 1 -8 3  
(4 8 -7 9) d 
P D I ns uli n/ Gl uc ose  
 
 
 
5 g 
 
5 g 
 
1 0  
T otal V o l u me b y Visit 
( m L) 
1 9. 5  
( 2 2)d 
4. 5  
( 7. 0)d 
2 1. 5  
( 2 3)d 
5  
2 1. 5  
( 2 3)d 
2 6. 5  
( 2 8)d 
2 1. 5  
( 2 3)d 
7 9 -1 2 0  
( 8 6-1 3 1) d 
T ot al V ol u me:  7 9 -1 2 0  m L  ( 8 6-1 3 1 m L) d  
a Da y -1 bl o o d dra ws f or cli nical la bs a n d P D bi o mar kers will n ot be re peate d f or s u bjects w h ose Da y -1 Visit c oi nci d es 
wit h t h e fi n al V B P 1 5 -0 0 2 Wee k 4 Visit a n d w h o ha d bl o o d dra w n f or cli nical la bs a n d P D bi o mar kers f or t h e 
V B P 1 5 -0 0 2 Wee k 4 Visit.  
b O nl y s u bjects w h o partici p ate i n t h e D ose -ta peri n g P eri o d will ha ve bl o o ds dra w n. 
c He mat ol o g y, C he mistr y, Li pi ds . 
d Bl o o d  v ol u me t o be c ollecte d at n o n -U S sites.  
e c ortis ol, P 1 N P, oste ocalci n, 1 7 - h y dr o x y pr o gester o ne, test oster o ne, c ortic oster o ne, 1 1 -de o x yc ortis ol, C T X, A C T H, 
S o ma Sca n, a n d pr ote o mics testi n g .  
f c ortis ol, P 1 N P, oste ocalci n, 1 7 - h y dr o x y pr o gester o ne, test oster o ne, c ortic oster o ne, 1 1 -de o x yc ortis ol, C T X, A C T H, 
H b A 1c, S o ma Sca n, a n d pr ote o mics testi n g . 
g  S u bjects m ust h a ve faste d ≥ 6 h o urs pri or t o bl o o d dra ws.   Bl o o d will be dra w n pri or t o a d mi nistrati o n of t h e d ose of 
st u d y me dicati o n.   
 
8  
D A T A C O L L E C TI O N 
8. 1  
S o urce D oc u me nts 
S o urce d oc u me nts are defi ne d as ori gi nal d oc u me nts, data, a n d rec or ds.  T hese 
d oc u me nts ma y i n cl u de h os pital rec or ds, cli nical a n d office c harts, la b orat or y 
data/i nf or mati o n, s u bjects’ diaries or e val uati o n c hec klists, p har mac y dis p e nsi n g a n d 
ot her r ec or ds, rec or d e d d ata fr o m a ut o mate d i nstr u me nts, micr ofil m or ma g netic m e dia, 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 0 9  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
a n d/ or x-ra ys.  Data c ollecte d d uri n g t his st u d y m ust be rec or d e d o n t he a p pr o priate 
s o urce d oc u m e nts. 
A s u bjec t e nr oll me nt l o g is t o be c o m plete d at eac h st u d y site.  Data rec or de d o n t he 
e nroll me nt l o g are t o i ncl u de a s u bject i de ntifier, t he date of e nr oll me nt, a n d t he reas o n 
t he s u bject was n ot e ntere d (if a p plica ble).  All s u bjects i nitiall y c o nsi dere d f or 
e nr oll me nt are t o b e rec or de d i n t his l o g.  
T he i n vesti gat or(s)/i nstit uti o n(s) will per mit st u d y-relate d m o nit ori n g, a u dits, I R B/I E C 
re vie w, a n d re g ulat or y i ns pecti o n(s), pr o vi di n g dir ect access t o s o urce data d oc u me nts. 
8. 2  
Electr o nic C ase Re p ort F or m C o m pleti o n 
S u bject data will be c ollecte d i n t his st u d y usi n g a n E D C s yste m.  T he E D C a n d data base 
s yste m will be O pe n Cli nica b y A kaza Res earc h, L L C.  O pe n Cli nica is a we b- base d 
(htt ps:/ / w w w. o pe ncli nica.c o m) data e ntr y s yst e m utilizi n g a hi g h sec urit y e n vir o n me nt.  
T he u n derl yi n g st ora ge facilit y will be P ost gre S Q L, w h os e str uct ur e per mits t he li n ki n g 
of s u bject i nf or mati o n acr oss all ta bles i n relati o nal data bases.  O pe n Cli nica uses sec ure 
s oc ket la yers ( S S L) a n d i n its E nter prise versi o n use d i n t his st u d y is 2 1 C o de of Fe deral 
Re g ulati o ns ( C F R) Part 1 1 c o m plia nt.  O nce a n e C R F is create d i n t he data base, a dat a 
dicti o nar y  e xists a n d t he data tea m creat es c o m pati ble pa per s o urce d oc u m e ntati o n.  
T he C o or di nati n g Ce nt er will desi g n a n el ectr o nic data base i n O p e n Cli nica f or t his st u d y.  
Access ri g hts t o t he E D C s yste m f or t h e st u d y site tea m me m bers will nee d t o be 
re q ueste d.  E v er y user of t he s yste m will be ma d e a ware of t he fact t hat user na me a n d 
pass w or d s h o ul d ne ver be s hare d a n d t heir el ectr o nic si g nat ur e c o nstit utes t he le gall y 
bi n di n g e q ui vale nt of a h a n d- writte n si g nat ur e.  O nl y trai ne d pers o n nel certifie d b y t he 
C o or di nati n g Ce nter will recei v e a user na me a n d pass w or d. 
All data will be directl y e ntere d or c ollecte d o n a s o urce d oc u m e nt a n d t he n e ntere d i nt o 
O pe n Cl i nica or tra nsf erre d electr o nicall y t o t he st u d y dat a base (e. g., cli nical la b orat or y 
res ults, q ua ntitati ve m uscle testi n g).   
T he C o or di nati n g Ce nt er data ma na ge me nt tea m will m o nit or t he e C R Fs f or 
c o m pl ete ness a n d acce pt a bilit y t hr o u g h o ut t he c o urse of t he st u d y.  Re vera Ge n pers o n nel 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 1 0  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
( or t heir re pres e ntati ves) will be all o we d access t o all s o urce d oc u m e nts i n or der t o verif y 
e C R F e ntries. 
8. 3  
D at a Pr ocessi n g 
A cli nical st u d y d ata bas e will be c o nstr ucte d fr o m t he eC R F s a n d a n y d ata mer ge d 
electr o nicall y, a n d t he data will be vali date d b ot h ma n uall y a n d electr o nicall y.  
Clar ificati o n of data will be re q uest e d fr o m t he st u d y site as re q uire d.  T h e data base will 
be q ualit y ass ure d i n a cc or da nce t o t he d ata ma n a ge m e nt pla n a n d will be a vaila ble f or 
statistical a nal ysis acc or di n g t o t he met h o ds o utli ne d i n Secti o n 9. 7  a n d t he Statistical 
A nal ysis Pla n ( S A P).  
8. 4  
S u bject Di aries 
T he  pare nt or le gal g uar dia n of eac h s u bject will b e gi v e n a s u bject diar y at t he Bas eli ne 
Da y  - 1 Visit i n w hic h t o rec or d a n y ne w c o nc o mit a nt me dicati o ns a n d a n y c ha n ges t o 
e x isti n g c o nc o mita nt me dicati o ns ta ke n d uri n g t h e st u d y, as well as a n y A Es e x perie nce d 
b y t he s u bject d uri n g t he st u d y.  Pare nts/le gal g u a r dia ns will be i nstr ucte d i n h o w t o 
recor d i nf or mati o n i n t he diar y a n d will be i nstr ucte d t o bri n g t he diar y wit h t he m t o eac h 
st u d y visit f or re vie w b y st u d y staff f or c o m plet e n ess a n d acc urac y.  A ne w diar y will be 
dis pe nse d at eac h m o nt hl y visit f or use t hr o u g h t h e ti me of t he ne xt sc he d ule d m o nt hl y 
visit.  C ollecti o n of fi nal diaries will occ ur at t he Wee k 2 4 Visit, or at t he e n d of t he 
D ose- ta perin g Peri o d f or s u bjects w h ose va m or ol o ne d ose is ta pere d at t he e n d of t he 
st u d y.  T he i nf or mati o n rec or de d i n t he di ar y will be c o nsi dere d s o urce d oc u me ntati o n, 
a n d an y i nf or mati o n r ec or de d i n t he diar y s h o ul d be tra nscri b e d b y st u d y st aff t o t he 
a p pr o priate e C R F. 
9  
S T A TI S TI C A L M E T H O D S A N D P L A N N E D A N A L Y S E S 
9. 1  
S a m ple Size D eter mi n ati o n 
Eli g i ble s u bjects are t h os e w h o e nr olle d i n t he V B P 1 5- 0 0 2 st u d y a n d ha v e c o m plete d u p 
t o a n d i ncl u di n g t he F oll o w- u p Wee k 4 st u d y assess me nts, u p t o a p pr o xi matel y 
4 8 s u bjects ( n = 1 2 per va m or ol o ne d ose gr o u p).   

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 1 1  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
T his is a n o pe n-la bel e xte nsi o n st u d y wit h n o place b o c o ntr ol.  Hist orical c o ntr ol data are 
a vaila ble f or t he sa me a ge ra n ge ( 4- 7 y ears), at lar gel y t he s a me st u d y sites, wit h t he 
sa me o utco me meas ures.  U ntreate d nat ural hist or y c o ntr ol p o p ulati o n dat a is fr o m t he 
o n g oi n g CI N R G D N H S st u d y of ~ 4 0 0 D M D b o ys. 3 1 ,3 2 ,3 3 ,3 4  Pre d nis o ne-treate d hist orical 
c o ntr ol data is fr o m a cli nical trial of pre d nis o n e carrie d o ut b y t he CI N R G gr o u p. 3 5  T he 
va m or ol o ne  P hase IIa e xte nsi o n trial is carrie d o ut wit h dail y d osi n g.  T o m ore acc uratel y 
deter mi ne sa m ple size n u m bers t o detect a gl u c oc ortic oi d effect o n efficac y, sa m ple size 
calc ulati o ns were li mite d t o t he dail y pre d nis o ne treat me nt ar m of t he CI N R G 
gl uc o c ortic oi d cli nical tri al ( n = 1 1- 1 3), at 6 or 1 2 m o nt hs, f or t hree gr oss m ot or milest o ne 
o utc o mes ( T T S T A N D, T T R W, T T C LI M B) ( T a ble 1 2 ).  Sa m ple siz e was als o calc ulate d 
ass u m i n g t he o bser ve d effect of v a m or ol o ne was 1 0 0 %, 8 0 % or 6 0 % of t hat o bser ve d 
wit h dail y  gl uc oc ortic oi ds (T a ble 1 2 ).  
T he pri ma r y p har mac ol o gic al safet y o utc o m e pr o p ose d i n t he P hase IIa e xte nsi o n trial is 
c ha n ge i n B MI z-sc ore.  Dail y gl uc oc ortic oi ds s h o w a relati vel y ra pi d i ncrease i n B MI 
z-sc ore ( 6 m o nt h c ha n ge i n n o n-treate d = - 0. 1 4; 6 m o nt h c ha n ge i n 
pre d nis o ne-tr eate d = + 0. 5 4) ( T a ble 1 2 ).  Va m or ol o ne is n ot a ntici pate d t o s h o w a n 
i ncreas e i n B MI. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 1 2  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
T a ble 1 2   
6- m o nt h a n d 1 2- m o nt h C h a n ges i n O utc o mes i n 4- < 8 ye ar- ol d D M D 
B o ys  
 
N otes: a) All patie nts a re 4-< 8 years of a ge at st u d y start.  
b) D ata fr o m u ntreate d s u bjects i n t h e CI N R G D M D Nat ural hist or y st u d y;3 1 ,3 2 ,3 3 ,3 4 d ata fr o m tre ate d 
s u bjects i n t h e CI N R G Pre d nis o ne trial.3 5   
c) C o m pares all o nl y dail y d ose pre d nis o ne -treate d patie nts t o u ntreate d patie nts. 
d) All calc ulati o ns as s u me a re peate d me as ures A N O V A m o del wit h o ne pre - a n d o ne p ost -meas ure me nt .  
C orrelati o n bet wee n re peate d me as ures use d as f oll o ws:  0. 7 5 f or hei g ht c ha n ges, 0. 7 0 f or 6 m o nt h B MI 
c ha n ges, a n d 0. 6 5 f or 1 2 m o nt h B MI c ha n ges, a n d 0. 5 7 5 f or 6 a n d 1 2 m o nt h vel ocit y c ha n ges.  
P o wer  =  0. 8 0  a n d al p ha  =  0. 0 2 5 f or all calc ulati o ns t o acc o u nt f or m ulti ple gr o u p c o m paris o ns (i.e. t w o 
va m or ol o ne  d oses, eac h c o m pare d t o pre d nis o ne f or safet y a n d place b o f or efficac y).  
^  C o nser vati ve c ha n ge esti mates wer e defi n e d as f ol l o ws: F or B MI, t h e e x pecte d c ha n ge i n va m or ol o ne  was set t o 
0. 0 rat h er t ha n t he o bser ve d decrease.  F or ti me d tests, t h e e x pecte d c ha n ge i n va m or ol o ne  was set t o 8 0 % of t h e 
o bser ve d c ha n ge i n t he pre d nis o ne gr o u p.   
^ ^ C o nser vati ve c ha n ge esti mates were de fi n e d as f oll o ws: F or ti me d tests, t h e e x pecte d c ha n ge i n va m or ol o ne  
was set t o 6 0 % of t h e o bser ve d c ha n ge i n t h e pre d nis o ne gr o u p ( wit h S D at 8 0 %).  
 
9. 2  
St atistic al a n d A n al ytic al Pl a n ( S A P) 
T he secti o ns bel o w s u m mariz e t he i nte n de d statistical met h o ds a n d a nal ys es f or t he 
e xte nsi o n st u d y.  A m ore detaile d S A P will be writte n a n d fi nalize d pri or t o fi nalizati o n 
of t he cli nical st u d y data base.  T he S A P will gi ve a detaile d des cri pti o n of t he s u m maries 
a n d a nal yses t hat will be perf or me d a n d will clearl y des cri be w he n t hese a n al yses will 
ta ke place.  A n y c h a n ges t o t he pla n ne d met h o ds a n d a nal ys es will be descri be d a n d 
j ustifie d i n t he S A P a n d/ or i n t he fi nal cli nical st u d y re p ort, as a p pr o priate.  
9. 2. 1  
Devi ati o ns fr o m t he St atistic al A n alysis Pl a n 
A n S A P will be writte n a n d fi nalize d pri or t o a n y l oc k of t he st u d y data base.  T he S A P 
will gi ve a d etaile d descri pti o n of t he s u m maries a n d a nal ys es t hat will be perf or me d a n d 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 1 3  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
will clearl y descri be w he n t hese a nal yses will ta ke place.  A n y d e viati o n(s) fr o m t he 
ori gi nal S A P will be descri be d a n d j ustifie d i n t he cli nical st u d y re p ort. 
9. 3  
A n al ysis  P o p ul ati o ns 
All a nal ys es will be base d o n t he act ual treat me nt eac h s u bject recei ve d.  F o ur 
p o p ulati o ns will be defi ne d f or dat a a nal ysis.   
9. 3. 1  
S afety P o p ul ati o n  
All s u bjec ts w h o recei ve at least o ne d ose of v a m or ol o ne st u d y me di cati o n i n t he 
e x te nsi o n st u d y will be i ncl u de d i n t he Safet y P o p ulati o n.  T he Safet y P o p ulati o n is t he 
pri m ar y a nal ysis p o p ulati o n f or safet y assess me nts.  T his is als o t he m o difie d I nte nti o n t o 
Tre at ( mI T T) p o p ulati o n. 
9. 3. 2  
F ull A n alysis Set ( F A S) 
All s u bjects w h o recei ve at least o ne d ose of v a m or ol o ne st u d y me di cati o n i n t he 
e x te nsi o n st u d y a n d h a ve at least o ne p ost- bas eli ne assess me nt will be i ncl u de d i n t he 
F A S.  T he F A S is t he pri mar y a nal ysis p o p ulati o n f or efficac y a n d P D assess me nts.  T his 
is t he mI T T p o p ulati o n, wit h t he a d diti o nal re q uir e me nt t o ha ve at least o ne p ost- baseli ne 
assess me nt.  S u bjects w h o recei v e at least o ne d ose of va m or ol o ne b ut n e ver ha ve p ost-
base li ne assess me nts will be e x cl u de d.   
9. 3. 3  
C o ntr o l P o p ul ati o n D N H S St u dy 
T he c o ntr ol p o p ulati o n fr o m t he D N H S st u d y will i ncl u de all st u d y s u bjects w h o were 
o bser ve d as p art of t he st u d y i n a ges ≥ 4 years a n d < 7 years of a ge at a start of a n i nter val 
of o bse r vati o n a n d o bs er ve d f or at least o ne year.  F urt her, t h e s u bjects nee d t o ha ve ha d 
at least t w o visits i n a ti me i nter val of n o m ore t ha n 1 5 m o nt hs (e. g., M o nt h 2 4 a n d 
M o nt h 3 6 of o bser vati o n f or a s u bject w h o e ntere d at a ge 2 or 3).  T he s u bject s h o ul d 
ha ve  bee n a ble t o w al k i n de pe n de ntl y wit h o ut assisti ve de vices at t he start of t he i nter val 
a n d s h o ul d ha ve bee n a bl e t o c o m plete t he T T S T A N D.  T h e s u bject s h o ul d n ot ha ve ha d 
a n y hist or y of disease or i m pair me nt or me dicati o ns t hat w o ul d ha ve ma de hi m i neli gi ble 
t o recei ve t h e va m or ol o n e i nter ve nti o n as defi ne d b y t he P has e IIa st u d y e x cl usi o n 
criteria.  T h e s u bject s h o ul d ha ve bee n gl u c oc orti c oi d- naï ve f or t he e ntire i nter val 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 1 4  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
c o nsi dere d i n t he c o ntr ol p o p ulati o n f or t his st u d y a n d s h o ul d n ot ha ve be g u n a n y 
i n vesti gati o nal treat me nt f or t he i nter val c o nsi dere d f or t he c o ntr ol c o m p aris o n.  Fi nall y, 
t he c o ntr ol inter vals t o be c o nsi dere d s h o ul d ha v e t he st u d y o utc o mes of T T S T A N D, 
T T C LI M B, T T R W, N S A A, 6 M W T a n d Q M T meas ure d.  It is acce pt a ble if t he 
partici pa nt ha d pr o gressi ve disease a n d c o ul d n ot perf or m a m eas ure me nt at a later p oi nt 
i n t he i nter val; t his will be a vel ocit y zer o. 
9. 3. 4  
C o ntr ol P o p ul ati o n Pre d nis o ne St u dy 
T he c o ntr ol p o p ulati o n fr o m t he pre d nis o ne st u d y will i ncl u de all s u bjects w h o were 
y o u n ger t ha n 7 years ol d at e ntr y a n d w h o were ra n d o mize d t o t he dail y pre d nis o ne ar m. 
9. 4  
Me as ures T a ke n t o A v oi d/ Mi ni mize Bi as 
N ot a p plica ble. 
9. 5  
I nteri m A n al ysis 
N o i nteri m statistical a nal yses are pla n ne d. 
9. 6  
Missi n g, U n use d, a n d S p uri o us D at a 
T he  p ossi bilit y of bias fr o m missi n g data of s u bjects w h o pre mat urel y dis c o nti n ue will be 
a d dresse d i n t he cli nical st u d y re p ort.  Missi n g val ues f or safet y a n d e x pl orat or y 
o utc o mes will be treate d as missi n g; w hile t h ose f or efficac y meas ure m e nts will be 
i m p ute d usi n g met h o d ol o g y as d escri be d i n t he S A P.  
9. 7  
St atistic al A n al ysis 
9. 7. 1  
Ge ner al C o nsi der ati o ns 
Statistical a nal yses will b e perf or me d usi n g S A S ® . 
All meas ure me nts will be a nal yz e d base d u p o n t h e t y p e of distri b uti o n, a n d descri pti ve 
statistics will be prese nte d b y treat me nt gr o u p a n d assess me nt ti me p oi nt, as a p pr o priate.  
Descri pti ve statistics f or c o nti n u o us varia bles ( n u m ber [ N], mea n, me dia n, sta n dar d 
de viati o n [ S D], mi ni m u m, a n d ma xi m u m), descri pti ve statistics f or cate g orical vari a bles 
( N a n d perce nt a ge), a n d i n di vi d ual s u bject pr ofiles will be prese nte d, as a p pr o priate.   

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 1 5  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
Baseli ne m eas ur e me nt is defi ne d as t he l ast n o n- missi n g val ue pri or t o t he first d ose of 
st u d y dr u g i n t he e xte nsi o n st u d y.  
9. 7. 2  
S u bject Dis p ositi o n, De m o gr a p hics, a n d B aseli ne C h ar acteristics 
S u bjec t dis p ositi o n will be s u m marize d b y  a nal ysis p o p ulati o n.  T he n u m ber of s u bjects 
e nr olle d, t he n u m ber i n eac h p o p ulati o n, a n d t he reas o n f or disc o nti n uati o n fr o m t he 
st u d y will be s u m mariz e d. 
S u bjec t de m o gra p hics ( e. g., a ge, race, a n d et h nicit y ) a n d baseli ne c haracteristics (e. g., 
hei g ht, w ei g ht, a n d m o nt hs/ years si nce D M D dia g n osis ) will be  s u m marize d 
descri pti vel y b y  a nal ysis p o p ulati o n.  Listi n gs of i n di vi d ual s u bject data s orte d b y d ose 
gr o u p will be re vie we d f or a n y differe n ces a m o n g t he d ose gr o u ps. 
9. 7. 3  
S afety A n alyses 
All s u bjects w h o recei ve d at least o ne d ose of v a m or ol o ne ( Safet y P o p ulati o n) will be 
i ncl u de d i n the safet y a nal yses.  I n ge neral, descri pti ve st atistics f or eac h s afet y e n d p oi nt 
will be prese nte d b y d o se le vel, w hile i n di vi d ual s u bject listi n gs of safet y e n d p oi nts, 
s orte d by d os e gr o u p, will be re vie we d f or a n y e vi de nce of d os e-relate d differe n ces or 
tre n ds i n t he safet y pr ofile of va m or ol o ne. 
All safet y data will be liste d. 
Ba seli ne m eas ur e me nt is defi ne d as t he n o n- missi n g val u e of t he c ore st u d y V B P 1 5- 0 0 2 
F oll o w- u p Wee k 4 or last n o n- missi n g val ue pri or t o first a d mi nistrati o n of st u d y dr u g i n 
t he e xte nsi o n st u d y. 
All e val uati o ns of cli nical safet y will be liste d wit h descri pti ve statistics prese nte d b y 
treat me nt gr o u p.  T he pri mar y s afet y v aria ble will be B MI z-sc ore a n d will be assesse d 
usi n g t he sa me t y p e of st atistical m o dels use d f or efficac y.  A d diti o nal sec o n dar y safet y 
data will i ncl u de hei g ht z-sc ore, bl o o d pr ess ure, a n d E C G res ults.  As n o c ha n ge i n bl o o d 
pre ss ure or car diac res ults is e x pecte d, t hese data will be a nal yze d usi n g a n a nal ysis of 
c o varia n ce ( A N C O V A) a p pr oac h w hic h i ncl u des t he baseli ne val u e f or eac h 
meas ure me nt as a c o v ari ate.  C ha n ges i n hei g ht z-sc ores, f or w hic h a n o bs er ve d c ha n ge is 
e x pecte d, will be m o delle d usi n g a li near mi x e d effects m o del.  C o nti n u o us, q ua ntitati ve 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 1 6  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
la b orat or y val u es will be a nal yze d si milar t o B MI z-sc ores.  Cate g orize d la b orat or y 
val ues a n d prese nce or a bse nce of A Es will be c o m pare d usi n g a n e x act c hi-s q uare test.   
A d verse e ve nts will be c o de d usi n g t he M e dical Dicti o nar y f or Re g ul at or y Acti vities 
( Me d D R A).  T h e i nci de n ce of A Es will be s u m marize d o verall a n d b y d ose le vel, S O C 
a n d preferre d ter m; d ose le vel, S O C, preferre d ter m, a n d i nte nsit y ( C T C A E gra de); a n d 
d ose le ve l, S O C, preferre d ter m, a n d rel ati o ns hi p t o st u d y dr u g.  A d diti o nal A E a nal yses 
will be  at t he s u bject le vel: t he n u m ber of s u bjects w h o ha d a n y A E, t h e distri b uti o n of 
n u m ber of A Es per s u bject wit hi n a d ose le vel, w orst i nte nsit y i n a s u bject wit hi n a d ose 
le vel, hig h est le vel of relati o ns hi p t o st u d y tr eat m e nt f or eac h s u bject wit hi n a d ose le vel. 
A d diti o nal h y p ot heses of safet y will i ncl u de si milar li near m o d elli n g wit h t he sec o n dar y 
a n d e x pl orat or y o ut c o mes.   
P h ysical e x a mi nati o n res ults will be liste d o nl y.   
9. 7. 4  
Cli nic al Effic acy a n d P h ar m ac o dy n a mic A n alyse s  
T he e val uati o ns of cli nical efficac y a n d P D  will be perf or me d usi n g t he F A S P o p ulati o n. 
T he pri mar y effic ac y o ut c o me is t he ti me t o sta n d fr o m s u pi ne vel ocit y ( T T S T A N D).  
Sec o n dar y effic ac y o utc o mes are t he N S A A assess me nt, ti me t o cli m b f o ur stairs 
( T T C LI M B), ti me t o r u n/ wal k 1 0 meters ( T T R W), Q ua ntitati ve M uscle Testi n g ( Q M T), 
a n d t he dista nce w al ke d i n 6 mi n utes ( 6 M W T) .  T he pri mar y o utc o me will be c o m pare d 
bet we e n v a m or ol o ne a n d hist orical u ntreate d c o ntr ols usi n g a mi x e d-effects li near m o del 
wit h trea t me nt gr o u p.  A ge at st u d y e ntr y will be i ncl u de d as a c o vari ate.  T he i nitial 
m o del will c o m bi ne va m or ol o ne d oses a n d a s u bse q ue nt sec o n d ar y m o del will l o o k at 
eac h d ose i n c o m paris o n t o u ntreate d nat ur al hist or y c o ntr ols.  T his will all o w t he testi n g 
of w het her v a m or ol o ne i n ge n eral a n d va m or ol o n e at i n di vi d ual d oses ha v e si g nifica nt 
effects o n t he sl o pe of t h e vel ocit y.  A d diti o nal h y p ot heses of efficac y will i ncl u de 
si milar li near m o delli n g wit h t he sec o n dar y o ut c o mes.  T he y will als o i ncl u de differi n g 
c o m paris o n gr o u ps i ncl u di n g u ntreate d nat ur al hist or y c o ntr ols.  
Ser u m P D bi o mar kers of a dre nal a xis s u p pressi o n, i ns uli n resista nce, a n d b o ne t ur n o ver 
will be assesse d.  L o n git u di nal a nal ysis of P D bi o mar kers will be st u die d as a f u ncti o n of 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 1 7  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
treat me nt, wit h c o m paris o n t o pre d nis o ne-treate d a n d u ntreate d hist orical c o ntr ols, as 
a p pr o priate.   
I n di vi d ual cli nical effi cac y a n d P D  data will be liste d.   
9. 7. 5  
C o nc urre nt Me dic ati o ns 
A s u m mar y of all c o nc o mita nt me dicati o ns ta ke n d uri n g t he c o urse of t he st u d y will be 
prese nte d i n ta b ular f or m b y t hera pe utic dr u g class a n d ge neri c dr u g na m e usi n g t he 
W orl d Healt h Or ga niz ati o n ( W H O) Dr u g cl assificati o n ( Versi o n 4. 3).  All c o nc o mita nt 
me dica ti o ns will be detaile d i n t he s u bject data listi n gs.   
1 0  
S T U D Y M A N A G E M E N T A N D E T HI C A L A N D R E G U L A T O R Y 
R E Q UI R E M E N T S 
1 0. 1  
Re g ul at or y A p pr o v al a n d G o o d Cli nic al Pr acti ce 
T his s t u d y will be c o n d u cte d i n acc or da n ce wit h t he pri nci ples of t he 1 8t h W orl d Me dical 
Asse m bl y ( Helsi n ki, J u ne 1 9 6 4), a n d a m e n d me nts of t he 2 9 t h ( T o k y o, 1 9 7 5), 3 5t h 
( Venice, 1 9 8 3), 4 1 st ( H o n g K o n g, 1 9 8 9), 4 8t h ( S o merset West, 1 9 9 6), 5 2n d ( Edi n b ur g h, 
2 0 0 0), 5 3 r d ( Was hi n gt o n, 2 0 0 2), 5 5t h ( T o k y o, 2 0 0 4), 5 9t h ( Se o ul, 2 0 0 8), a n d 6 4t h 
( F ortal eza, 2 0 1 3) W orl d Me dical Asse m blies. 
F urt her, t h e trial will be c o n d ucte d i n acc or da n ce wit h: 
 I nter nati o nal C o nfere nce o n Har m o nisati o n (I C H) E 6 G ui deli ne f or G o o d Cli nical 
Practice ( G C P) 
 T he U nite d States ( U S) F D A C o de of Fe deral Re g ulati o ns, Title 2 1 C F R Part 3 1 2 
– I n v esti gati o nal Ne w Dr u g A p plicati o n, Part 5 0 – Pr otecti o n of H u ma n Patie nts 
wit h parti c ular f o c us i n S u b Part D, a n d/ or Part 5 6 – I nstit uti o nal Re vie w B oar ds 
 U S Healt h I ns ura n ce P orta bilit y a n d Acc o u nta bilit y Act of 1 9 9 6 ( HI P A A). 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 1 8  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
1 0. 2  
I n vesti g at or Res p o nsi bilities 
1 0. 2. 1  
S u bject I nf or m ati o n a n d I nf or m e d C o nse nt 
Bef ore bei n g a d mitte d t o t he e xte nsi o n st u d y, a pare nt/ g uar dia n m ust c o nse nt i n writi n g 
f or t he s u bject t o partici pate.  Writte n or ver bal asse nt will als o be o btai ne d fr o m eac h 
s u bject as re q uir e d per re g ulati o ns.  A n  a p pr o ve d I C F will be gi ve n t o eac h 
pare nt/ g uar di a n w hic h will c o ntai n all U S  fe derall y re q uire d ele me nts, all I C H-re q uire d 
ele me nts, a n d HI P A A a ut h orizati o n i nf or mati o n, if a p plica ble, i n la n g u a ge t hat is 
u n dersta n da ble t o t he p are nt/ g uar dia n.  T he c o nse nt s h o ul d n ote t hat t he I n vesti gat or is 
recei vi n g c o m p e nsati o n f or t he e x pe nses of c o n d u cti n g t he st u d y. 
T he pr ocess of o btai ni n g t he i nf or me d c o nse 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 uir e me nts, a n d l ocal la ws. 
T he I n vesti gat or or d esi g nee will re vie w t h e st u d y wit h t he pare nt/ g uar di a n of eac h 
s u bject.  T he re vi e 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 ue nces of t he s u bj ec t’s partici p ati o n i n t he st u d y.  T he c o nse nt, asse nt, a n d re vie w 
m ust be i n a f or m u n dersta n da ble t o t he pare nt/ g u ar dia n of t he s u bject.  T h e I n vesti gat or 
or de si g n ee a n d t he pare nt/ g uar dia n of t he s u bject m ust b ot h si g n a n d date t he I C F after 
re vie w a n d b ef ore t he s u bject ca n p artici pate i n t h e st u d y.  T h e pare nt/ g u ar dia n of t he 
s u bject will recei v e a c o p y of t he si g n e d a n d dat e d f or m, a n d t he ori gi nal will be retai ne d 
i n t he site st u d y files.  T h e I n vesti gat or or d esi g n ee m ust e m p hasize t o t he 
pare nt/ g uar di a n of t he s u bject 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 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 ntitle d. 
If t he I C 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 all ne w s u bj ects a n d re peat t he c o nse nt pr ocess wit h 
t he a me n de d I C F f or a n y o n g oi n g s u bjects. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 1 9  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
1 0. 2. 2  
I nstit uti o n al Revie w B o ar d/I n de pe n de nt Et hics C o m mittee A p pr ov al a n d 
Ot her I nstit uti o n al Re q uire m e nts 
Bef ore t he start of t he st u d y, t he st u d y pr ot oc ol, I C F, a n d a n y ot h er a p pr o pri ate 
d oc u me nts will be s u b mitte d t o t he I R B/I E C f or re vie w a n d a p pr o val.  Per i nstit uti o nal 
re q uireme nts, t he st u d y pr ot oc ol a n d a n y ot her a p pr o priate d oc u m e nts will be s u b mitte d 
t o scie ntific c o m mittees f or a p pr o val. 
T he I n vesti gat or will f or war d t o t he S p o ns or, or d esi g nee ( C o or di nati n g Ce nter), a c o p y 
of t he I R B/I E C’s a p pr o val of t his pr ot oc ol, a me n d me nts, I C F a n d a n y c ha n ges t o t he I C F, 
base d o n t he F D A re g ulati o ns set f ort h i n Part 5 6 of Title 2 1 of t he C F R.  T he 
I n vesti gat or will als o kee p d oc u me ntati o n of st u d y a p pr o val b y i nter nal scie ntific 
c o m mittees per i nstit uti o nal re q uire m e nts.  
St u d y m e dicati o n ca n o nl y be s u p plie d t o t he I n vesti gat or after d oc u me ntati o n of all 
et hical a n d le gal re q uire me nts f or starti n g t h e st u d y has b ee n recei ve d b y t he S p o ns or or 
desi g nee ( C o or di nati n g Ce nter).  T his d oc u me ntati o n m ust als o i ncl u de a n I R B/I E C 
me m bers hi p list t hat c o ntai ns me m bers’ occ u pati o ns a n d q ualificati o ns.  If t he I R B/I E C 
wi ll n ot discl ose t he na mes of t he c o m mittee me m bers, it s h o ul d be as ke d t o iss ue a 
state me nt c o nfir mi n g t hat t he c o m p ositi o n of t he c o m mittee is i n acc or d a nce wit h G C P.  
T he I R B Ass ura nce N u m ber ma y be acce pte d as a s u bstit ute f or t he I R B me m bers hi p list.  
T he I n vesti gat or will ke e p t he I R B/I E C i nf or me d re gar di n g t he pr o gress of t he st u d y, per 
i nstit uti o nal re q uire me nts.  N o c ha n ges will be m a de i n t he st u d y wit h o ut I R B/I E C 
a p pr o val, e x ce pt w he n re q uire d t o eli mi nate a p pare nt i m me diate hazar ds t o t he s u bject s. 
W hile t he st u d y is o n g oi n g a n d at st u d y c o m pleti o n/ disc o nti n uati o n, t he I n vesti gat or m ust 
s u b mit t o t he I R B/I E C t h e f oll o wi n g i nf or mati o n i n acc or d a nce wit h U S Fe deral 
re g ulat or y re q uire me nts: 
1.  I nf or mati o n o n seri o us or u ne x pecte d A Es, s h o wi n g d ue dili ge n ce i n pr o vi di n g 
t his i nf or mati o n as s o o n as p ossi ble 
2.  Peri o dic re p orts o n t he pr o gress of t he st u d y 
3.  Fi nal St u d y S u m mar y u p o n st u d y c o m pleti o n or cl os ure. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 2 0  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
N otificati o n of t he e n d of t he trial will be se nt t o t he I R B/I E C wit hi n 3 0 da ys after 
c o m pleti o n of t he st u d y cl ose- o ut visit.  I n case t he st u d y is e n de d pre mat urel y, t he 
I R B/I E C will be n otifie d wit hi n 1 5 da ys, i ncl u di n g t he reas o ns f or t he pre mat ure 
ter mi nati o n.  T he e n d of t he trial is defi ne d as t h e date of fi nal a nal ysis of t he st u d y d ata 
acc or di n g t o t he S A P. 
1 0. 2. 3  
St u dy D oc u m e nt ati o n 
1 0. 2. 3. 1  
Bef ore t he St art of t he St u dy 
T he f oll o wi n g st u d y d o c u me ntati o n will be i n place at t he st u d y site pri or t o t he first 
a d mi nistrati o n of st u d y dr u g: 
 
F ull y si g ne d pr ot oc ol a n d pr ot oc ol-s u p p orti n g m a n uals 
 
I n v esti gat or’s Br oc h ure2 9 
 
Pr ot oc ol Acce pta n ce f or m si g ne d b y t he I n v esti gat or 
 
I R B/I E C-a p pr o ve d c o p y of t he I C F 
 
C urric ul u m vitae of t he I n vesti gat or a n d all s u b-i n vesti gat ors liste d o n t he F D A 
F or m 1 5 7 2 
 
A letter of I R B/I E C a p pr o val f or pr ot oc ol 
 
A list of me m bers of t he I R B/I E C a n d t heir affiliati o ns 
 
A c o p y of t he I n v esti gat or-si g n e d F D A 1 5 7 2 f or m 
 
A n I n vesti gat or-si g ne d fi na ncial discl os ure f or m. 
1 0. 2. 3. 2  
D uri n g t he St u dy 
T he f oll o wi n g d o c u me nt ati o n s h o ul d be a d de d t o t he site st u d y file d uri n g st u d y c o n d u ct: 
 
A n y p a per s o urce f or ms c o m plete d a n d s u bse q ue ntl y e ntere d i nt o t he st u d y 
data base.  A n e x pla nati o n s h o ul d be gi ve n f or all missi n g data a n d a n y pr ot oc ol 
de viati o ns d oc u me nte d i n t he site st u d y file 
 
A n y c ha n ges t o t he d o c u me ntati o n i de ntifie d a b o ve i n Secti o n 1 0. 2. 3. 1  

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 2 1  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
 
S hi p pi n g d oc u me nts relati n g t o s hi p me nt of me dicati o n ( dr u g acc o u nta bilit y) a n d 
bi oa nal ytical sa m ples 
 
C o pies of rele va nt c orres p o n de nce s uc h as letters, e mails, meeti n g n otes, a n d 
telep h o ne calls. 
1 0. 2. 3. 3  
After t he St u dy 
After c o m pleti o n or pre mat ure ter mi nati o n of t he trial, all of t he d oc u me nts i de ntifie d 
s h o ul d be i n t he file, t o get her wit h t he f oll o wi n g: 
 St u d y dr u g acc o u nta bilit y d oc u m e nts 
 A u dit certificates (if a p plica ble) 
 I n v esti gat or dele gati o n of res p o nsi bilities l o g 
 Site si g nat ure l o g 
 S u bject e nr oll me nt l o g 
 S u bsta nti ve c orres p o n de nce wit h t he S p o ns or a n d I R B/I E C 
 N otificati o n of t he e n d of t he trial t o t he I R B/I E C. 
1 0. 2. 4  
Dele g ati o n of I nvesti g at or Res p o nsi bilities 
T he I n vesti gat or m ust (a) e ns ure t hat a n y i n di vi d u al t o w h o m a tas k is dele gat e d is 
q uali fie d b y e d ucati o n, trai ni n g, a n d e x perie nce (a n d lice ns ure, if rele va nt) t o perf or m t he 
tas k; a n d ( b) pr o vi de a de q uate s u per visi o n.  T he I n vesti gat or s h o ul d mai nt ai n a list of 
s u b-i n vesti gat ors a n d ot her a p pr o priatel y q ualifie d pers o ns t o w h o m he or s he has 
dele gate d si g nifica nt st u d y-relate d d uties. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 2 2  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
1 0. 3  
Pr ot oc ol D e vi ati o ns a n d Vi ol ati o ns 
1 0. 3. 1  
Pr ot oc ol Devi ati o n a n d Vi ol ati o n Defi niti o ns 
1 0. 3. 1. 1  
Pr ot oc ol De vi ati o n 
A pr ot oc ol de viati o n is a n y c h a n ge, di ver ge nce, or d e part ure fr o m t he st u d y desi g n or 
pr oce d ures of a researc h pr ot oc ol t hat is u n der t he I n v esti gat or’s c o ntr ol a n d t hat has n ot 
bee n a p pr o ve d b y t he I R B/I E C. 
C ha n ges or alterati o ns i n t he c o n d uct of t he tri al w hic h d o n ot ha ve a maj or i m pact o n t he 
s u bject's ri g hts, safet y or well- bei n g, or t he c o m plete ness, acc urac y a n d reli a bilit y of t he 
st u d y data are c o nsi dere d mi n or pr ot oc ol de viati o ns. 
1 0. 3. 1. 2  
Pr ot oc ol  Vi ol ati o n 
A pr ot oc ol vi olati o n is a de viati o n fr o m t he I R B/I E C-a p pr o ve d pr ot oc ol t hat ma y affect 
t he s u bject's ri g hts, s afet y, or well- bei n g a n d/ or t h e c o m plete ness, acc urac y a n d relia bilit y 
of t he st u d y d ata. T his i ncl u des e x a m ples s uc h as i na p pr o priate c o nse nt, err ors i n dr u g 
d osi n g , or la c k of re p orti n g of safet y d ata. 
1 0. 3. 2  
Re p orti n g Devi ati o ns/ Vi ol ati o ns 
U p o n disc o ver y of a maj or pr ot oc ol de viati o n or vi olati o n, t he I n vesti gat or is res p o nsi ble 
f or re p orti n g pr ot oc ol de viati o ns or vi olati o ns t o t he I R B/I E C a n d S p o ns or or desi g n ee 
( C o or di nati n g Ce nter) wit hi n 2 4 h o urs of disc o ver y. 
All ot her de viati o ns m ust be re p ort e d i n writi n g wit hi n 7 da ys of t he e ve nt or its 
disc o ver y. 
1 0. 4  
St u d y Rec or ds Rete nti o n a n d Direct Access t o S o urce D oc u me nts 
F e deral r e g ulati o ns re q uire t hat, f oll o wi n g c o m pleti o n of a cli nical st u d y, a c o p y of all 
rec or ds of t hat st u d y b e mai ntai ne d b y t h e I n v esti gat or f or at least t he s h orter of t he 
f oll o wi n g t w o ti me peri o ds: 
 T w o years after F D A a p pr o val of t he dr u g f or t he i n dicati o n f or w hic h it was 
i n vestigate d, or 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 2 3  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
 I n sit uati o ns w here n o a p plicati o n is t o be s u b mitte d or a n a p plicati o n is n ot 
ap pr o ve d f or s uc h i n dicati o n, 2 years aft er t he I n v esti gati o nal Ne w Dr u g (I N D) 
A p plicati o n is disc o nti n ue d a n d t he F D A is n otifie d. 
T he I n vesti gat or m ust mai ntai n a c o p y of all data c ollecte d f or eac h s u bject treate d 
(i ncl u di n g e C R Fs a n d s o urce dat a).  I n or der t o ass ure t he acc urac y of data c ollecte d i n 
t he e C R F, it is ma n dat or y t hat re pres e ntati ves of t he S p o ns or, or desi g nee, as well as 
re pres e ntati ves of t he F D A or ot her healt h a ut h orities ha ve direct access t o ori gi nal 
s o urce d oc u m e nts (e. g., s u bject rec or ds, s u bject c harts, a n d la b orat or y re p orts).  D uri n g 
t he re vie w of t hese d oc u me nts, t he a n o n y mit y of t he s u bject will be res pecte d wit h strict 
a d here n ce t o pr ofessi o nal sta n dar ds of c o nfi de ntialit y. 
T he S p o ns or reser ves t he ri g ht t o ter mi nate t he st u d y f or ref usal of t he I n vesti gat or t o 
s u p pl y s o urce d oc u me ntati o n of w or k perf or me d i n t his cli nical st u d y. 
T he f oll o wi n g i n cl u des, b ut is n ot li mite d t o, t he rec or ds t hat m ust be retai ne d b y t h e 
I n v esti gat or: 
1.  Si g ne d i nf or me d c o nse nt d oc u me nts f or all s u bjects 
2.  S u bject e nr oll me nt l o g 
3.  Rec or d of all rele va nt c o m m u nicati o ns bet wee n t he I n vesti gat or a n d t h e I R B/I E C 
4.  C o m p ositi o n of t he I R B/I E C 
5.  Rec or d of all rele va nt c o m m u nicati o ns bet wee n t he I n vesti gat or a n d t h e S p o ns or 
( or desi g nee) 
6.  List of s u b-i n vesti gat ors a n d ot her a p pr o pri atel y q ualifie d pers o ns t o w h o m t he 
In v esti gat or has del e gate d si g nifica nt st u d y-relate d d uties, t o get her wit h t heir 
r oles i n t he st u d y a n d t h eir si g nat ur es 
7.  Dr u g acc o u nta bilit y rec or ds (see S ecti o n 5. 8. 4 ) 
8.  Rec or d of a n y b o d y fl ui ds or tiss ue sa m ples retai n e d 
9.  All ot her s o urce d o c u me nts (s u bject rec or ds, h os pital rec or ds, la b orat or y rec or ds, 
etc.) 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 2 4  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
1 0.  All ot her d oc u me nts as liste d i n Secti o n 8 of t he I C H c o ns oli date d g ui d eli ne o n 
G C P ( Esse ntial D oc u me nts f or t he C o n d uct of a Cli nical Trial). 
1 0. 5  
St u d y M o nit ori n g 
In acc or da n ce wit h a p pli ca ble re g ulati o ns, G C P, a n d t he pr oce d ures of t he S p o ns or or its 
desi g nees, t he St u d y M o nit or will peri o dicall y c o ntact t he site a n d c o n d u ct o n-site visits.  
T he e xte nt, nat ure, a n d fre q ue nc y of o n-site visits will be base d o n e nr oll m e nt rate a n d 
data q ualit y at t he site.  T hr o u g h fre q u e nt c o m m u nicati o ns (e. g., letter, e- mail, a n d 
tele p h o ne), t he St u d y M o nit or will e ns ure t hat t he i n vesti gati o n is c o n d ucte d acc or di n g t o 
pr ot oc ol a n d re g ul at or y re q uire me nts. 
D uri n g t h ese c o nta cts, t he m o nit ori n g acti vities will i ncl u de: 
1.  C hec ki n g a n d assessi n g t he pr o gress of t he st u d y 
2.  Re vie wi n g st u d y dat a c ollecte d t o date f or c o m plet e ness a n d acc urac y 
3.  Re vie wi n g c o m plia nce wit h pr ot oc ol assess me nts 
4.  C o n d ucti n g s o urce d oc u me nt verificati o n b y re vie wi n g e C R F data base dat a 
agai nst s o urce d o c u me nts w he n a vaila ble (e. g., m e dical rec or ds, s u bject diaries, 
I C F [a n d asse nt, if a p plica ble], la b orat or y res ult re p orts, ra w dat a c ollecti o n 
f or ms) 
5.  I d e ntif yi n g a n y iss ues a n d a d dressi n g res ol uti o ns. 
T he se acti vities will be d o ne i n or der t o verif y t hat t he: 
1.  Data are a ut he ntic, acc urate, a n d c o m plete 
2.  Safet y a n d ri g hts of t he s u bjects are b ei n g pr otect e d 
3.  St u d y is c o n d ucte d i n acc or da nce wit h t he c urre ntl y a p pr o ve d pr ot o c ol (a n d a n y 
a me n d me nts), G C P, a n d all a p plica ble re g ulat or y re q uire me nts. 
T he I n vesti gat or will all o w t he St u d y M o nit or direct access t o all rele va nt d oc u me nts, 
a n d all ocate his/ her ti me a n d t he ti me of his/ her st aff t o t he St u d y M o nit or t o disc uss 
fi n di n gs a n d a n y rele v a nt iss ues. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 2 5  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
I n a d diti o n t o c o ntacts d uri n g t he st u d y, t he St u d y M o nit or will c o ntact t he site pri or t o 
t he start of t he st u d y t o disc uss t he pr ot oc ol a n d data c ollecti o n pr oce d ures wit h site 
pers o n nel. 
At st u d y cl os ur e, St u d y M o nit ors will c o n d uct all a cti vities as i n dicate d i n Secti o n 1 0. 7 . 
1 0. 6  
Q u alit y Ass ur a nce 
At it s discreti o n, t he S p o ns or or its desi g n ee ma y c o n d uct a q ualit y ass ur a n ce a u dit of t his 
st u d y.  A u diti n g pr oce d ures of t he S p o ns or a n d/ or its desi g n ee will be f oll o we d i n or der 
t o c o m pl y wit h G C P g ui deli nes a n d e ns ure acce pt a bilit y of t he st u d y data f or re gistrati o n 
p ur p oses.  If s uc h a n a u dit occ urs, t he I n v esti gat or will gi ve t he a u dit or dir ect access t o 
all rele va nt d oc u m e nts, a n d will all ocate his/ her ti me a n d t he ti me of his/ her staff t o t he 
a u dit or as ma y be re q uire d t o disc uss fi n di n gs a n d a n y rele va nt iss ues. 
I n a d diti o n, re g ulat or y a ut h orities a n d/ or t he I R B/I E C ma y c o n d u ct a n i ns pecti o n of t his 
st u d y.  If s u c h a n i ns pecti o n occ urs, t he I n vesti gat or will all o w t he i ns pect or direct access 
t o all s o urce d oc u me nts, e C R Fs, a n d ot her st u d y d oc u me ntati o n f or s o urce data c hec k 
a n d/ or o n-site a u dit i ns pe cti o n.  T he I n vesti gat or m ust all ocate his/ her ti me a n d t he ti me 
of his/ her staff t o t he i ns pect or t o disc uss fi n di n gs of a n y rel e va nt iss ues. 
A n e x pla nati o n will be gi ve n f or all missi n g, u n use d, a n d s p uri o us d ata i n t he rele va nt 
secti o n of t he st u d y re p ort. 
1 0. 7  
St u d y Ter mi n ati o n a n d Site Cl os ure 
U p o n c o m pleti o n of t he st u d y, t he f oll o wi n g acti vities, w he n a p plica ble, m ust be 
c o n d ucte d b y t he St u d y M o nit or i n c o nj u ncti o n wit h t he I n v esti gat or, as a p pr o priate: 
1.  Pr o visi o n of all st u d y d at a t o t he S p o ns or 
2.  Data clarificati o ns a n d/ or res ol uti o ns 
3.  Acc o u nti n g, rec o nciliati o n, a n d fi nal dis p ositi o n of use d a n d u n use d st u d y 
me dicati o n 
4.  Re vie w of site st u d y rec or ds f or c o m plete ness. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 2 6  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
I n a d diti o n, t he S p o ns or reser ves t he ri g ht t o te m p oraril y s us pe n d or pre mat urel y 
ter mi nate t his st u d y f or a n y reas o n. 
If t he st u d y is s us pe n de d or ter mi nate d f or safet y reas o n(s), t he S p o ns or will pr o m ptl y 
i nf or m the I n vesti gat or, a n d will als o i nf or m t he re g ulat or y a ut h orities of t h e s us pe nsi o n 
or ter mi nati o n of t he st u d y a n d t h e reas o n(s) f or t h e acti o n.  T he I n vesti gat or is 
res p o nsi ble f or pr o m ptl y i nf or mi n g t he I R B/I E C, a n d pr o vi di n g t he r eas o n(s) f or t he 
s us pe nsi o n or ter mi nati o n of t he st u d y. 
If t he st u d y is pre mat urel y ter mi nat e d, all st u d y d ata m ust be ret ur ne d t o t he S p o ns or.  I n 
a d diti o n, t he site m ust c o n d uct fi nal dis p ositi o n of all u n use d st u d y me dicati o ns i n 
acc or d a nce wit h t he S p o ns or pr oce d ures f or t he st u d y. 
1 0. 8  
Site Ter mi n ati o n 
T he  S p o ns or ma y at a n y ti me, at its s ole discreti o n, ter mi nate t he st u d y site f or vari o us 
reas o ns, i ncl u di n g, wit h o ut li mitati o n, t he f oll o wi n g: 
1.  Fail ure of t he I n vesti gat or t o e nr oll s u bjects i nt o t he st u d y at a reas o na ble rate 
2.  Fail ure of t he I n vesti gat or t o c o m pl y wit h a p plica ble la ws a n d/ or perti ne nt F D A 
reg ulati o ns 
3.  S u b missi o n of k n o wi n gl y false i nf or mati o n fr o m t he researc h facilit y t o t h e 
S p o ns or, St u d y M o nit or, F D A, or ot h er re g ulat or y a ut h orities 
4.  I ns ufficie nt a d h ere n ce t o pr ot oc ol re q uire m e nts. 
If partici pati o n of a st u d y site is ter mi nate d, t he S p o ns or an d St u d y C hair will iss ue a 
writte n n otice t o t he I n vesti gat or.  T he writte n n otice will c o ntai n t he reas o ns f or ta ki n g 
s uc h acti o n.  If t he st u d y site is ter mi nate d f or n o n c o m plia nce, a p pr o priate re g ulat or y 
a ut h orities will als o be n otifie d b y t he S p o ns or. 
St u d y t er mi nati o n a n d f oll o w- u p will be perf or m e d i n c o m plia nce wit h t he c o n diti o ns set 
f ort h i n 2 1 C F R 3 1 2. 5 0 a n d 2 1 C F R 3 1 2. 5 6. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 2 7  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
1 0. 9  
Disc o nti n u ati o n of St u d y 
T he S p o ns or reser ves t he ri g ht t o disc o nti n ue t he st u d y f or a n y reas o n at a n y ti me.  I n 
a d diti o n, t he st u d y ma y b e st o p pe d at a n y ti me if, i n t he o pi ni o n of t he S p o ns or a n d 
Me dical M o nit or, safet y data s u g gest t hat t he me dical safet y of s u bj ects is bei n g or m a y 
bec o me c o m pr o mise d. 
1 1  
DI S C L O S U R E O F D A T A 
1 1. 1  
C o nfi de nti alit y 
T he  ri g hts a n d pri va c y of partici pa nts i n t his st u d y will be pr otecte d at all ti mes.  All 
pers o nal details of s u bjects will be treate d as c o nfi de ntial b y t he I n vesti gat or a n d 
ha n dli n g of pers o nal dat a will be i n c o m plia nce wit h HI P A A.  All a p plica bl e data 
pr otecti o n la ws i n t he rel e va nt c o u ntries will be a d here d t o at all ti mes. 
S u bject na mes will re mai n c o nfi de ntial a n d will n ot be i ncl u de d i n t he data base.  O nl y 
e nr oll me nt n u m ber, a n d birt h date will be rec or de d o n t he e C R F.  If t he s u bject’s na me 
a p pears o n a n y ot her d o c u me nt c ollecte d (e. g., h os pital disc har ge s u m mar y), t he na me 
m ust be  o bliterate d bef ore t he d oc u me nt is tra ns mitte d t o t he S p o ns or or its desi g nee.  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’ pare nts or g u ar dia ns 
will gi ve 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/I E C t o i ns pect t he s u bjects’ me dical r ec or ds t o verif y t he i nf or mati o n 
c ollecte d.  T he s u bj ects’ pare nts or g uar dia ns will be i nf or me d t hat all pers o nal 
i nf or mati o n ma de a v aila ble 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 d a nce wit h all state, l ocal, a n d fe deral data pr otecti o n/ pri vac y la ws, i ncl u di n g, 
wit h o ut li mitati o n, t he HI P A A, as a p plica ble. 
T he pare nts or g uar dia ns of all partici pa nts i n t he U nite d States will pr o vi de writte n 
a ut h oriz ati o n t o discl ose pri vate healt h i nf or m ati o n eit her 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 2 1 C F R 5 0, a n d will c o ntai n a wai v er of s u bject access t o st u d y-relate d 
pri vate  healt h i nf or m ati o n u ntil t he c o ncl usi o n of t he cli nical st u d y.  T h e 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 h e e x pirati o n of 
2 years after t he st u d y m e dicati o n is a p pr o ve d f or t he i n dicati o n bei n g st u di e d, or ( 2) t he 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 2 8  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
e x pirati o n of 2 years aft er t he researc h pr o gra m is disc o nti n ue d.  I n di vi d ual s u bjec t 
me dical i nf or mati o n o btai ne 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 
parties ( 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 be pr o vi de d t o t he s u bj ect’s pers o n al 
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 uire 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 welfare. 
T he st u d y I n vesti gat or will mai ntai n a s u bject i de ntificati o n l o g ( e nr oll me nt n u m bers a n d 
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 de ntifie d. 
St u d y d ata will be s hare d wit h t he st u d y ‘ Us e of Micr os oft Ba n ds as a n O utc o me 
Meas ure i n B o ys wit h D M D  - Parallel st u d y t o Cli nical St u d y Pr ot oc ol V B P 1 5- 0 0 3’ if 
t he s u bject’s pare nt/le gal g uar dia n c o ns e nts f or his partici pati o n i n b ot h st u dies. 
1 1. 2  
P u blic ati o n 
R e vera G e n Bi o P har ma, I nc. retai ns t he o w ners hi p of all data a n d res ults c ollecte d d uri n g 
t his st u d y.  T h eref ore, t h e S p o ns or reser ves t he ri g ht t o use t he dat a fr o m t his prese nt 
st u d y, eit her i n t he f or m of e C R Fs ( or c o pies of t h ese), or i n t he f or m of a re p ort, wit h or 
wit h o ut c o m me nts a n d a nal ysis i n or der t o s u b mit t he m t o t he U S F D A or t he Healt h 
A ut h orities of a n y c o u ntr y. 
F urt her m ore, i n t he e v e nt t hat t he cli nical researc h lea ds t o pate nta ble res ults, t he 
I n v esti gat or ( or e ntit y acti n g o n his/ her be h alf acc or di n g t o l ocal re q uire m e nts) s hall 
refrai n fr o m fili n g pate nt a p plicati o n(s).  Pate nt a p plicati o ns will be file d b y Re vera Ge n 
Bi o P har ma, I n c. or a n ot h er e ntit y d ele gat e d b y Re vera Ge n Bi o P har ma, I nc. 
All i nf or mati o n c o ncer ni n g t he pr o d uct as well as a n y i nf or mati o n s uc h as cli nical 
i n dicati o ns f or t he dr u g, its f or m ula, met h o ds of ma n ufact ure a n d ot h er scie ntific data 
relati n g t o it, t hat ha v e bee n pr o vi de d b y t he S p o ns or or desi g nee, a n d are u n p u blis he d, 
are c o nfi de ntial a n d m ust re mai n t he s ole pr o p ert y of t he S p o ns or.  T he I n v esti gat or will 
a gree t o us e t he i nf or mati o n o nl y f or t h e p ur p oses of carr yi n g o ut t his st u d y a n d f or n o 
ot her p ur p ose u nless pri or writte n per missi o n fr o m t he S p o ns or is o btai ne d.  T he S p o ns or 
has f ull o w ners hi p of t he e C R Fs c o m plete d as p art of t he st u d y. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 2 9  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
B y si g ni n g t he st u d y pr ot oc ol, t he I n vesti gat or a grees t hat t he res ults of t he st u d y ma y be 
use d f or t he p ur p os es of nati o nal a n d i nter nati o nal re gistrati o n, p u blicati o n, a n d 
i nf or mati o n f or me dic al a n d p har mace utical pr ofessi o nals b y t he S p o ns or.  If necessar y, 
t he a ut h orities will be n otifie d of t he I n vesti gat or's na me, a d dress, q ualificati o ns, a n d 
e xte nt of i n v ol ve me nt. 
T he S p o ns or or desi g nee will pre pare a fi nal re p ort o n t he st u d y.  T h e I n vesti gat or ma y 
n ot p u blis h or prese nt a n y i nf or m ati o n o n t his st u d y wit h o ut t he e x press writte n a p pr o val 
of t he S p o ns or.  A d diti o nall y, t he S p o ns or, ma y, f or a n y reas o n, wit h h ol d a p pr o val f or 
p u blicati o n or prese ntati o n. 
1 2  
I N V E S TI G A T O R’ S P R O T O C O L A G R E E M EN T  
T he  I n vesti gat or's Pr ot oc ol A gree me nt at t he fr o nt of t his d oc u me nt m ust be si g ne d b y 
t he st u d y site Pri nci pal I n vesti gat or.  T he ori gi nal or a c o py  m ust be ke pt o n file b y  t he 
S p o ns or a n d t he I n vesti gat or m ust retai n t he ori gi nal or a c o py .  T he Pr ot o c ol A gree m e nt 
si g nifies r e vie w a n d acce pta nce of t he pr ot oc ol b y t he Pri nci pal I n vesti gat or pri or t o 
i nitiati o n of t he st u d y. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 3 0  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
1 3  
R E F E R E N C E S 
1.  Ma h J K, K or n g ut L, D y k e ma n J, Da y L, Pri n gs hei m T, J ette N. A s yst e mic 
revie w a n d m eta- a nal ysis o n t he e pi de mi ol o g y of D uc he n ne a n d Bec k er 
m usc ular d ystr o p h y. Ne ur o m usc ul Dis or d . 2 0 1 4; 2 4( 6): 4 8 2 - 9 1. 
2.  H off ma n E P, Br o w n R H a n d K u n kel L M. D ystr o p hi n: t he pr otei n pr o d uct of 
t he D uche n n e m usc ular d ystr o p h y l oc us. Cell . 1 9 8 7; 5 1: 9 1 9- 2 8. 
3.  E va ns N P, Mis ya k S A, R o berts o n J L, Bassa g an ya -Riera J, Gra n ge R W. 
I m m u ne me di ate d mec h a nis ms p ote ntiall y re g ulat e t he disease ti me c o urse of 
D uc he n ne m us c ular d ystr o p h y a n d pr o vi de tar gets f or t hera p e utic 
i nter ve nti o n. P M R . 2 0 0 9; 1( 8): 7 5 5-6 8.  
4.  K u mar A a n d  B ori e k A M. Mec ha nical stress acti vates t he n uclear fact or-
ka p pa B pat h wa y i n s kel etal m uscle fi bers: a p ossi ble r ole i n D uc he n n e 
m usc ular d ystr o p h y. F A S E B J . 2 0 0 3; 1 7( 3): 3 8 6- 9 6. 
5.  Ac har y ya S, Villalta S A, Ba k kar N, et al. Inter pla y of I K K/ N F -ka p p a B 
si g nali n g i n macr o p ha ges a n d m y ofi bers pr o m otes m uscle cell de ge n erati o n i n 
D uc he n ne m us c ular d ystr o p h y. J Cli n I nvest . 2 0 0 7; 1 1 7( 4): 8 8 9-9 0 1.  
6.  D o gra C, C ha n g otra H, Wer ge d al J E, K u mar A. Re g ulati o n of 
p h os p ha ti d yli n osit ol- 3- ki nase ( PI 3 K)/ A kt a n d n uclear fact or- k a p pa B 
si g nali n g pat h wa ys i n d ystr o p hi n- deficie nt s kelet al m uscle i n res p o nse t o 
mec ha nic al stretc h. J Cell P hysi ol . 2 0 0 6; 2 0 8( 3): 5 7 5- 8 5. 
7.  Pa hl H L. A cti vat ors a n d tar get ge nes of Rel/ N F- k a p pa B tra nscri pti o n fact ors. 
O nc o ge ne . 1 9 9 9; 1 8( 4 9): 6 8 5 3- 6 6. 
8.  S pe ncer MJ, M o nteci n o- R o dri g uez E, D ors h ki n d K, Ti d ball J G. Hel per 
( C D 4( +)) a n d c yt ot o xic ( C D 8( +)) T cells pr o m ote t he pat h ol o g y of 
d ystr o p hi n- d eficie nt m us cle. Cli n I m m u n ol . 2 0 0 1; 9 8( 2): 2 3 5- 4 3. 
9.  S pe ncer MJ a n d Ti d ball J G. D o i m m u ne cells pr o m ote t he pat h ol o g y of 
d ystr o p hi n- d eficie nt m y o pat hies? Ne ur o m usc ul Dis or d . 2 0 0 1; 1 1( 6- 7): 
5 5 6- 6 4. 
1 0.  Mali k V, R o di n o - Kla pac L a n d M e n dell J R. E mer gi n g dr u g f or D uc h e n ne 
m usc ular d ystr o p h y. Ex p ert O pi n E mer g Dr u gs . 2 0 1 2; 1 7( 2): 2 6 1- 7 7. 
1 1.  Ree ves E K, H off ma n E P, Na garaj u K, Da ms ker J M, Mc Call J M. V B P 1 5: 
p recli nical c h aracterizati o n of a n o vel a nti-i nfla m mat or y d elta 9, 1 1 ster oi d. 
Bi o or g Me d C he m . 2 0 1 3; 2 1( 8): 2 2 4 1- 9. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 3 1  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
1 2.  B us h b y K, Fi n k el R, Bir n kra nt DJ, et al. Dia g n osis a n d ma na ge me nt of 
D uc he n ne m us c 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 o cial ma na ge me nt. L a ncet Ne ur ol . 2 0 1 0; 9( 1): 7 7- 9 3. 
1 3.  Pa ne M, Mazz o ne E S, Si v o S, et al. L o n g ter m nat ural hist or y d ata i n 
a m b ula nt B o ys wit h D uc he n ne m usc ular d ystr o p h y: 3 6 -m o nt h c ha n ges. 
Pl os O ne . 2 0 1 4; 1 0: 1 3 7 1/j o ur nal. p o ne. 0 1 0 8 2 0 5.  
1 4.  Ma nz ur A Y, K u ntzer T, Pi ke M, S wa n A V. Gl uc oc ortic oi d c ortic oster oi ds f or 
D uc he n ne m us c ular d ystr o p h y.  C oc hr a ne D at a b ase Syst Rev. 2 0 0 8; ( 1): 
C D 0 0 3 7 2 5.  
1 5.  Heier C R, Da ms ker J M, Y u Q, et al. V B P 1 5, a n o vel a nti -i nfla m mat or y a n d 
me m bra ne -sta biliz er i m pr o ves m usc ular d ystr o p h y wit h o ut si de effects. 
E M B O M ol M e d . 2 0 1 3; 5( 1 0): 1 5 6 9-8 5.  
1 6.  Da ms ker J M, Dilli n g ha m B C, R ose M C, et al. V B P 1 5, a gl uc oc ortic oi d 
anal o g ue, is effecti ve at r e d uci n g aller gic l u n g i nfl a m mati o n i n mice. Pl os 
O ne . 2 0 1 3; 8( 5): e 6 3 8 7 1. 
1 7.  Dilli n g ha m B C, K n o blac h S M, Ma n y G M, et al. V B P 1 5, a n o vel a nti-
i nfla m mat or y, is effecti ve at re d u ci n g t h e se verit y of m uri ne e x peri me ntal 
a ut oi m m u ne e nce p h al o m yelitis. Cell M ol Ne ur o bi ol.  2 0 1 5; 3 5( 3): 3 7 7- 8 7. 
1 8.  Da d gar S, Wa n g Z, J o h nst o n H, et al. As y n c hr o n o us re m o deli n g is a dri ver of 
faile d re ge nerati o n i n D uc he n ne m usc ular d ystr o p h y. J Cell Bi ol . 2 0 1 4; 
2 0 7( 1): 1 3 9- 5 8.   
1 9.  Ra ma n S V, H or K N, Maz ur W, Hal n o n NJ, Kissel J T, He X, Tra n T, S mart S, 
Mc Ca rt h y B, T a yl or M D, J efferies J L, Rafael- F ort ne y J A, L o we J, R o ble S L, 
Cri pe L H. E plere n o n e f or earl y car di o m y o p at h y i n D uc he n ne m us c 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. L a ncet 
Ne ur ol.  2 0 1 5; 1 4( 2): 1 5 3- 6 1. 
2 0.  A vi oli L V. Gl uc o c ortic oi d effects o n stat ural gr o wt h. Br J  R he u m at ol. 1 9 9 3;  
3 2 S u p pl 2: 2 7- 3 0. 
2 1.  W olt hers O D a n d Pe derse n S. S h ort ter m li near gr o wt h i n ast h matic c hil dre n 
d uri n g tr eat me nt wit h pre d nis ol o ne. B MJ . 1 9 9 0; 3 0 1( 6 7 4 4): 1 4 5- 8. 
2 2.  Birca n Z, S ora n M, Yil diri m I, et al. T he effect of alter nate- da y l o w d ose 
pr e d nis ol o ne o n b o ne a ge i n c hil dre n wit h ster oi d de pe n de nt ne p hr otic 
s y n dr o me. I nt Ur ol Ne p hr ol. 1 9 9 7; 2 9( 3): 3 5 7- 6 1. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 3 2  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
2 3.  Ma n ola gas S C, Wei nstei n R S. Ne w de vel o p me nts i n t he pat h o ge nesis a n d 
treat me nt of ster oi d-i n d u ce d oste o p or osis. J B o n e Mi ner Res . 1 9 9 9; 1 4( 7): 
1 0 6 1- 6.  
2 4.  Sali A, G uerr o n A D, G or dis h- Dress ma n H, et al. Gl uc oc ortic oi d -tr eate d mice 
are a n i n a p pr o priat e p ositi ve c o ntr ol f or l o n g-ter m precli nical st u dies i n t he 
m d x m o use.  Pl os O ne. 2 0 1 2; 7( 4): e 3 4 2 0 4. 8 
2 5.  Ka u h E, Mi xs o n L, M alice M- P, Mese ns S, Ra mael S, B ur ke J, Re y n d ers T, 
Va n D yc k K, Beals C, R ose n ber g E, a n d R u d d y M. Pre d nis o ne affects 
i nfla m mati o n, gl uc ose t olera nce, a n d b o ne t ur n o ver wit hi n h o urs of tr eat me nt 
i n healt h y i n di vi d uals. E ur o pe a n J E n d ocri n ol.  2 0 1 2; 1 6 6: 4 5 9 – 6 7. 
2 6.  We hli n g- He nric ks M, Olt ma n n M, Ri nal di C, M y u n g K H, a n d Ti d ball J G. 
L oss of p ositi ve all osteri c i nteracti o ns bet w ee n n e ur o nal nitric o xi de s y nt hase 
a n d p h os p h ofr uct o ki nas e c o ntri b utes t o defects i n gl yc ol ysis a n d i ncreas e d 
fati ga bilit y i n m usc ular d ystr o p h y. H u m M ol Ge n et . 2 0 0 9; 1 8( 1 8): 3 4 3 9- 5 1. 
2 7.  Y o u nes M, Neffati F, T o uzi M, Hasse n- Zr o ur S, Fe n dri Y, Bejia I, Be n A m or 
A, Be r ga o ui N, a n d Najjar M F. S yst e mic effects of e pi d ural a n d i ntraartic ul ar 
gl uc o c ortic oi d i njecti o ns i n dia betic a n d n o n- dia betic patie nts. J oi nt B o ne 
S pi ne . 2 0 0 7; 7 4( 5): 4 7 2- 6. 
2 8.  M o o n HJ, C h oi K H, Lee SI, Lee OJ, S hi n J W, a n d Ki m T W. C ha n ges i n 
bl o o d gl uc ose a n d c ortis ol le vels after e pi d ural or s h o ul der i ntra-artic ular 
gl uc o c ortic oi d i njecti o ns i n dia betic or n o n dia betic patie nts. A m J P hys Me d 
Re h a bil . 2 0 1 4; 9 3( 5): 3 7 2- 8. 
2 9.  I n v esti gat or’s Br oc h ure, Versi o n 3, Va m or ol o n e ( 1 7 α, 2 1- di h y dr o x y- 1 6 α-
met h yl- pre g na- 1, 4, 9( 1 1)-trie ne- 3, 2 0- di o ne) 4 % Oral S us pe nsi o n,  Re vera Ge n 
Bi o P ha r ma, I n c., J a n uar y 2 3, 2 0 1 6. 
3 0.  Hat h o ut Y, Br o d y E, Cle me ns P R, et al. L ar ge-s cale ser u m pr otei n bi o mar ker 
disc o ver y i n D uc h e n ne m usc ular d ystr o p h y. Pr o c N atl Ac a d Sci U S A.  2 0 1 5; 
1 1 2( 2 3): 7 1 5 3 -8.  
3 1.  Bell o L, Kes ari A, G or dis h- Dress ma n H, et al. Ge netic m o difiers of 
am b ulati o n i n t he C o o perati ve I nter n ati o nal Ne ur o m usc ular Researc h Gr o u p 
D uc he n ne n at ural hist or y st u d y. A n n Ne ur ol . 2 0 1 5; 7 7( 4): 6 8 4- 6 9 6. 
3 2.  S p ur ne y C, S hi miz u R, M or ge nr ot h L P, et al. C o o perati ve I nt er nati o nal 
Ne ur o m usc ular Researc h Gr o u p D uc h e n ne Nat ural Hist or y St u d y 
de m o nstrates i ns ufficie nt dia g n osis a n d tr eat me nt of car di o m y o pat h y i n 
D uc he n ne m us c ular d ystr o p h y. M us cle Nerve . 2 0 1 4; A u g; 5 0( 2): 2 5 0- 2 5 6.  

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 3 3  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
3 3.  Mc D o nal d C M, He nrics o n E K, A bres c h R T, et al. T he C o o perati ve 
I nter nati o nal N e ur o m usc ular Researc h Gr o u p D uc he n ne nat ur al hist or y st u d y 
–  a l o n git u di nal i n vesti gati o n i n t he era of gl uc oc ortic oi d t hera p y: desi g n of 
pr ot oc ol a n d t he met h o ds use d. M uscle Ner ve.  2 0 1 3; 4 8( 1): 3 2- 5 4.  
3 4.  He nrics o n E K, A bres c h R T, C naa n A, et al. T he C o o perati ve I nter nati o nal 
Ne ur o m usc ular Researc h Gr o u p D uc h e n ne nat ur al hist or y st u d y: 
gl uc o c ortic oi d treat me nt preser ves cli nicall y mea ni n gf ul f u n cti o n milest o nes 
a n d re d uces rat e of disease pr o gressi o n as meas ure d b y m a n ual m uscle testi n g 
a n d ot her c o m m o nl y use d cli nical trial o utc o me meas ures. M us cle Nerve.  
2 0 1 3; 4 8( 1): 5 5- 6 7. 
3 5.  Esc olar D M, Hac he L P, Cle me ns P R, et al. Ra n d o mize d, bli n de d trial of 
we e ke n d vs. d ail y pre d nis o ne i n D uc he n n e m usc ular d ystr o p h y. Ne ur ol o gy.  
2 0 1 1; 7 7( 5): 4 4 4- 4 5 2. 
3 6.  F D A Draft G ui da n ce f or I n d ustr y: D u c he n n e m usc ular d ystr o p h y a n d relat e d 
d ystr o p hi n o pat hies: de v el o pi n g dr u gs f or treat me nt. J u ne 2 0 1 5. 
3 7.  Ma y h e w J E, Fl ore nce J M, Ma y h e w T P, et al. Relia ble s urr o gate o utc o m e 
meas ures i n m ultice nter cli nical trials of D uc h e n n e m usc ular d ystr o p h y. 
M uscle Nerve.  2 0 0 7; 3 5( 1): 3 6- 4 2. 
3 8.  Br o o ke M H, Gri g gs R C, Me n dell J R, et al. Cli nical trial i n D uc he n ne 
d ystr o p h y. I. T h e desi g n of t he pr ot oc ol. M uscl e & N erve.  1 9 8 1; 4( 3): 1 8 6- 9 7. 
3 9.  Mazz o ne E S, Messi na S, Vasc o G, et al. Relia bilit y of t he N ort h Star 
A m b ulat or y Assess me nt i n a m ultice ntric setti n g. Ne ur o m usc ul Dis or d . 2 0 0 9; 
1 9( 7): 4 5 8- 6 1. 
4 0.  Mc D o nal d C M, He nrics o n E K, Ha n JJ, et al. T he 6- mi n ute Wal k Test as a 
ne w o utc o me meas ure i n D uc he n ne m us c ular d ystr o p h y. M us cle Nerve.  2 0 1 0; 
4 1( 4):  5 0 0- 1 0. 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 3 4  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
1 4  
A P P E N DI C E S 
 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 3 5  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
A p pe n di x 1 4. 1  
V a m or ol o ne D ose C al c ul ati o n W or ks heet a n d B ul k Dis pe nsi n g 
G ui de 
Va m or ol o ne is a d mi nistere d o nce d ail y as a 4 % oral s us pe nsi o n.  T he v ol u me per d ose is 
deter mi ne d b y t he s u bject’s d osi n g le vel a n d b o d y wei g ht (i n k g) at eac h st u d y 
me dica ti o n dis pe nsi n g visit, as s h o w n b y E q uati o n 1: 
E q u ati o n 1  
S u bject Wei g ht ( k g) x D ose Le vel ( m g/ k g)  
= S u bject D ose (i n m L)  
4 0 m g/ m L  
S u bject wei g ht (i n k g) s h o ul d be r o u n de d t o t he nearest w h ole i nte ger f or t h e calc ul ati o n 
of v ol u me per d ose.  
Calc ulate d d ose v ol u me will be r o u n de d t o t he nearest 0. 0 1 m L ( 1 m L s yri n ge), 0. 1 m L 
( 3 m L s yri n ge), or 0. 2 m L ( 5 m L s yri n ge), de p e n di n g u p o n t he t otal d ose v ol u me a n d 
cali brati o n of t he v ol u metric s yri n ge t o be use d f or a d mi nistrati o n of d ose, as s h o w n i n 
t he e xa m ples bel o w: 
E x a m ple 1:  D ose v ol u me calc ulati o n f or a s u bject recei vi n g 0. 2 5 m g/ k g/ da y wit h a b o d y 
wei g ht of 2 7 k g:  
S u bject Wei g ht ( 2 7 k g) x  D ose Level (0. 2 5  m g/ k g)  
=  0. 1 6 9  m L  
4 0 m g/ m L  
T he s u bject will r ecei ve a d ose v ol u me of 0. 1 6 9 m L per d ose t hr o u g h o ut t he f oll o wi n g 
1 2 wee ks.  D ose will be a d mi nistere d usi n g a 1 m L v ol u metric s yri n ge r o u n de d t o t he 
nearest 0. 0 1 m L, or 0. 1 7 m L dail y. 
E x a m ple 2:  D ose v ol u me calc ulati o n f or a s u bject recei vi n g 6. 0 m g/ k g/ d a y wit h a b o d y 
wei g ht of 2 3 k g:  
S u bject Wei g ht ( 2 3 k g) x D ose Level ( 6 .0 m g/ k g)  
= 3. 4 5  m L  
4 0 m g/ m L  
T he s u bject will recei ve a d ose v ol u me of 3. 4 5 m L per d ose t hr o u g h o ut t he  f oll o wi n g 
1 2 wee ks.  D ose will be a d mi nistere d usi n g a 5 m L v ol u metric s yri n ge r o u n de d t o t he 
nearest 0. 2 m L, or 3. 4 m L dail y. 
 
V a m or ol o ne 4 % S us pe nsi o n Dis pe nsi n g G ui de 
Eac h s u bject e nr olle d i n t he st u d y will be dis pe nse d 1 0 0 ml b ottle(s) of va m or ol o ne 4 % 
s us pe nsi o n at t he Bas eli ne Da y - 1 Visit, s ufficie nt f or d osi n g t hr o u g h t h e ti m e of t he 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 3 6  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
Wee k 1 2  Visit.  A d diti o nal s u p plies will be dis pe nse d at Wee k 1 2, s uffici e nt f or d osi n g 
t hr o u g h Wee k 2 4.  S u bje cts w h ose va m or ol o ne d ose is ta pere d d uri n g t h e D ose-ta peri n g 
Pe ri o d will be dis pe nse d a d diti o nal va m or ol o ne 4 % s us pe nsi o n at t he Wee k 2 4 Visit, 
s ufficie nt f or d os e ta peri n g t o 0 m g/ k g/ d a y (see Se cti o n 6. 3. 4 ). 
T he n u m ber  of b ottles t o be dis pe nse d at eac h dis p e nsi n g visit f or t he f oll o wi n g 1 2- wee k 
d osi n g  peri o d is c alc ulate d b y m ulti pl yi n g t he s u bj ect’s dail y d ose (i n m L/ d a y) (as 
calc ulate d b y E q u ati o n 1) b y 9 1 d a ys ( 8 4 da ys i n t he d osi n g p eri o d + 7 da ys o vera ge) a n d 
di vi di n g  b y 1 0 0 m L, t he n u m ber of m L per b ottle, as s h o w n i n E q uati o n 2, bel o w: 
E q u ati o n 2  
D ail y D ose ( m L/ d a y)  x 9 1 D a ys  
= # B ottle s t o be Dis pe nse d 
1 0 0 m L  
 
E x a m ple 3 : Calc ulati o n of n u m ber of b ottles t o be dis pe nse d f or a s u bject ta ki n g a dail y 
d ose of 0. 1 7 m L (fr o m E xa m ple 1 a b o ve):  
D ail y D ose (0. 1 7  m L / d a y) x 9 1 D a ys  
= 0. 1 5 B ottles  
1 0 0 m L  
T he n u m ber of b ottles dis pe nse d is r ou n de d t o t he nearest w h ole i nte ger, or 1 b ottle t o be 
dis pe nse d. 
E x a m ple 4 : Calc ulati o n of n u m ber of b ottles t o be dis pe nse d f or a s u bject ta ki n g a dail y 
d ose of 3. 4 m L (fr o m E xa m ple 2 a b o ve):  
D ail y D ose ( 3. 4 m L/ d a y) x 9 1  D a ys  
=   3. 0 9 B ottles  
1 0 0 m L  
T h e n u m ber of b ottles dis pe nse d is r o u n de d t o t he nearest w h ole i nte ger, or 4 b ottles t o 
be dis pe nse d. 
Eac h b ul k b ottle s h o ul d be use d f or o n e s u bject o nl y.  Eac h b ottle dis pe nse d t o t he 
s u bject a n d rea d y f or a d mi nistrati o n t o s u bjects will be la bele d wit h s u bject n u m ber, 
dis pe nse date, pr ot oc ol n u m ber, d ose le vel, a n d v ol u me t o be a d mi nistere d per d ose.   
A n y u n us e d or partiall y use d dr u g pr o d uct s h o ul d be ret ur n e d at eac h m o nt hl y visit 
t hr o u g h Wee k 2 4 a n d at t he e n d of t he D ose-ta peri n g Peri o d, if a p plica bl e.  Dr u g pr o d uct 
ret ur ned at t he Wee ks 4, 8, 1 6, a n d 2 0 Visits will be re dis pe nse d t o s u bjects at t he e n d of 
t he visit, after i nteri m c o m plia nce m o nit ori n g; dr u g pr o d u ct ret ur n e d at t he Wee ks 1 2 a n d 

Va m or ol o ne 
2 2 Fe br uar y 2 0 1 7 
Re v ise d Cli nical Pr ot oc ol # 2 
D oc u me nt N o. V B P 1 5- 0 0 3 - R 2 
Pr ot oc ol N o. V B P 1 5- 0 0 3  
I N D 1 1 8, 9 4 2 
 
 
 
P a ge 1 3 7  of 1 3 7  
Re vera Ge n Bi o P har ma, I nc. – C O N FI D E N TI A L 
2 4 Visits, a n d e n d of t he D ose- Ta p eri n g Peri o d, if a p plica ble, will be retai n e d at t he 
clinical st u d y site f or i n vesti gati o nal dr u g acc o u nta bilit y m o nit ori n g.