A Double-blind, Multicenter, Long-term Follow-up Study to Assess Recurrence of Actinic Keratosis in Subjects Treated With Methyl Aminolevulinate Hydrochloride (MAL) 16.8% Cream (CD06809-41) or Vehicle Cream in the Treatment of Thin and Moderately Thick, Non-hyperkeratotic, Non-pigmented Actinic Keratosis of the Face and Scalp When Using Daylight Photodynamic Therapy (DL-PDT), for Subjects Achieving Complete Response of Treated Lesions at Final Visit in Study RD.06.SPR.112199
Phase: PHASE3
Conditions: Keratosis, Actinic
Sponsor: Galderma R&D

C LI NI C A L S T U D Y P R O T O C O L
A d o u ble -bli n d, m ultice nter, l o n g -ter m f oll o w-u p st u dy t o assess rec urre nce of Acti nic 
Ker at osis i n s u bjects tre ate d wit h Met hyl a mi n olev uli n ate hy dr oc hl ori de ( M A L) 1 6. 8 % cre a m 
( C D 0 6 8 0 9-4 1) or ve hicle cre a m i n t he tre at me nt of t hi n a n d m o der ately t hic k, n o n-
hy per ker at otic, n o n- pi g me nte d acti nic ker at osis of t he f ace a n d sc al p w he n usi n g d ayli g ht 
p h ot o dy n a mic t her a py ( D L- P D T), f or s u bjects ac hievi n g c o m plete res p o nse of tre ate d lesi o ns 
at Fi n al Visit i n St u dy R D. 0 6. S P R. 1 1 2 1 9 9
P r ot oc ol N u m ber: 
R D. 0 6. S P R. 1 1 5 2 3 0
E u dr a C T N u m ber:
N ot A p plica ble
:
I n vesti g ati o n al Pr o d uct:
N o ne
I N D N u m ber:
P h ase:
3
S p o ns or:
Gal der ma R esearc h & D e vel o p me nt , L LC
1 4 5 0 1 N ort h Free wa y
F ort W ort h, T X 7 6 1 7 7
C o ntr act Rese arc h Or g a niz ati o n:
Pr ot oc ol D ate :
0 7 J A N 2 0 2 1
Pr ot oc ol Versi o n :
Versi o n 3. 0 A me n d me nt 2
C O N FI D E N TI A L
T his d oc u me nt c o nt ai ns c o nfi de nti al, pr o priet ar y i nf or m ati o n, a n d m a y n ot be re pr o d uce d 
or c o m m u nic ate d t o a t hir d p art y wit h o ut t he writte n per missi o n of G al der m a R & D, L L C.
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
C CI
P P D
P P D
P P D

 
              
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 3 of 4 4
C O N FI D E N TI A L
2
S T U D Y P E R S O N N E L C O N T A C T S
G al der m a Rese arc h & Devel o p me nt, L L C Pers o n nel
Na me:
Title:
Se ni or Me dical E x pert
A d dress:
Gal der ma Researc h & De vel o p me nt, L L C
1 4 5 0 1 N ort h Free wa y
F ort W ort h, T X 7 6 1 7 7
U nite d States
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
P P D
P P D

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 4 of 4 4
C O N FI D E N TI A L
3
S Y N O P SI S
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Title: A d o u ble -bli n d, m ultice nter, l o n g -ter m f oll o w-u p st u d y t o assess rec urre nce of Acti nic Kerat osis i n s u bjects 
treate d wit h Met h yl a mi n ole v uli nate h y dr oc hl ori de ( M A L) 1 6. 8 % crea m ( C D 0 6 8 0 9-4 1) or ve hicle crea m i n t he 
treat me nt of t hi n a n d m o deratel y t hic k, n on- h y per kerat otic, n o n -pi g me nte d acti nic kerat osis of t he face a n d scal p 
w he n usi n g da yli g ht p h ot o d y na mic t hera p y ( D L -P D T), f or s u bjects ac hie vi n g c o m plete res p o nse of treate d lesi o ns at 
Fi nal Visit i n S t u d y R D. 0 6. S P R. 1 1 2 1 9 9
I n vesti g ati o n al Pr o d uct: n o ne
I N D N u m ber:
St u d y Ce nters: A p pr o xi matel y 6 0 st u d y ce nters are pla n ne d i n t he U nite d States
P h ase: 3
O bjecti ves:
Pri m ar y o bjecti ve : T he pri mar y o bjecti ve of t his st u d y is t o assess rec urre nce of  lesi o ns treate d i n R D. 0 6. S P R. 1 1 2 1 9 9
f or t h ose s u bjects w h o ac hie ve d C o m plete Res p o nse ( C R) of treate d A K lesi o ns. T h e y  will be offere d t he o p p ort u nit y 
t o partici pate i n t his 9-m o nt h l o n g -ter m f oll o w-u p st u d y (i.e., 5 2 wee ks after t he last D L - P D T), c o nti n ui n g t he d o u ble-
bli n d c o n d uct of t his st u d y .
S ec o n d ar y o bjecti ve : T he sec o n dar y o bjecti ve of t his st u d y is t o e val uate t he l o n g-ter m safet y of M A L D L -P D T a n d 
ve hicle crea m D L -P D T f or 5 2 w ee ks after t he last D L -P D T f or t h ose s u bjects w h o ac hie ve d C o m plete Res p o nse 
( C R) of treate d A K lesi o ns i n st u d y R D. 0 6. S P R. 1 1 2 1 9 9
St u d y Desi g n: T his is a d o u ble -bli n d, m ultice nter, parallel gr o u p, ve hicle -c o ntr olle d l o n g -t er m f oll o w-u p st u d y t o 
e val uate rec urre nce of A Ks i n s u bjects w h o c o m plete d st u d y R D. 0 6. S P R. 1 1 2 1 9 9. O nl y t h ose s u bjects w h o ac hie ve d 
C R of treate d A K lesi o ns at t he Fi nal Visit (1 2 w ee ks after t he last D L -P D T sessi o n) will be offere d t he o p p ort u nit y 
t o c o nti n ue t o be f oll o we d i n t he c urre nt st u d y f or 9 m o nt hs t o assess rec urre nce. After o btai ni n g i nf or me d c o nse nt 
f or t his f oll o w-u p st u d y, t he s u bjec ts will ret ur n at Wee ks 1 4 a n d 4 0, w hic h c orres p o n d t o 2 6 a n d 5 2 wee ks after t he 
last D L -P D T sessi o n, res pecti vel y t o assess t he lesi o ns treate d i n t he pre vi o us st u d y f or rec urre nce of A K.
Rec urre nce will be deter mi ne d b y rea p peara nce of t h ose lesi o ns c o m p letel y cleare d b y 2 D L-P D T sessi o ns, i.e., 
s u bjects w h ose lesi o ns are e val uate d t o be n o n-C R at t he visits i n t his st u d y will be dee me d t o ha ve rec urre nce. If t he 
perce nta ge of s u bjects mai ntai ni n g c o m plete res p o nse w o ul d be 6 0 % at Visit 3 ( 5 2 w ee ks after t he last D L -P D T), 
4 0 % of s u bjects w o ul d ha ve e x perie nce d rec urre nce (s u bject rec urre nce res p o nse). T he sa me calc ulati o n will be d o ne 
f or lesi o n c o m plete res p o nse, t o assess t he lesi o n rec urre nce. T here w ill be a tele p h o ne c hec k -i n wit h t he s u bjects b y 
t he cli nical site at Wee k 4 0 t o hel p retai n t he s u bject’s partici pati o n f or t he e ntire d urati o n of t he st u d y.
 
 
N u m ber of S u bjects: 
A p pr o xi matel y 1 1 1 s u bjects fr o m t he M A L crea m ar m a n d 1 9 s u bjects fr o m t he ve hicle crea m ar m fr o m t he pre vi o us 
st u d y are e x pecte d t o e nr oll i n t he f oll o w-u p st u d y. 
T re at me nt:
Neit her i n vesti gati o nal pr o d uct n or i nter ve nti o n will be part of t his st u d y.
St u d y D ur ati o n:
T he e x pecte d d urati o n f or eac h s u bject’s par tici pati o n i n t he st u d y will be a p pr o xi matel y 4 0 wee ks fr o m t he c o mpleti o n 
of st u d y R D. 0 6. S P R. 1 1 2 1 9 9 .
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
C CI
C CI

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 5 of 4 4
C O N FI D E N TI A L
S t u d y P o p ul ati o n:
T he st u d y p o p ulati o n will c o nsist of a d ult male a n d fe male s u bjects wit h cli nicall y c o nfir me d mil d t o m o derate acti nic 
kerat osis o n t he face a n d bal di n g scal p, w h o ha ve c o mplete d st u d y R D. 0 6. S P R. 1 1 2 1 9 9 wit h a C o m plete Res p o nse at 
Fi nal Visit of t hat st u d y, mea ni n g t h ose s u bjects, w h o se treate d A Ks were all clear e d at 1 2 we e ks after t he last D L -
P D T sessi o n.
I ncl usi o n Criteri a: T o be eli gi ble f or st u d y e ntr y, s u bjects m ust satisf y all of t he f oll o wi n g i ncl usi o n criteria :
1.
S u bjects w h o ha ve partici pate d i n st u d y R D. 0 6. S P R. 1 1 2 1 9 9 a n d ha ve ac hie ve d a c o m plete res p o nse at t he Fi nal 
Visit of t hat st u d y, defi ne d as c o m plete cleara nce of all treate d lesi o ns at 1 2 wee ks after t he last D L -P D T
2.
Writte n I nf or me d C o nse nt bef ore a n y assess me nt relate d t o t he L T F U st u d y is perf or me d
3.
Willi n g a n d ca pa ble of c o m pl yi n g wit h re q uire me nts of t he pr ot oc ol
E xcl usi o n Criteri a : S u bjects will be e xcl u de d fr o m t he st u d y if 1 or m ore of t he f oll o wi n g e xc l usi o n criteria are 
a p plica ble :
1.
S u bjects, w h o de vel o p or e x perie nce a c o n diti o n t hat m y c o m pr o mise s u bject safet y or c o m plia nce, i nterfere wit h 
e val uati o n or precl u de c o mpleti o n of t he st u d y. I n partic ular, t hese c o n diti o ns i ncl u de, b ut are n ot li mite d t o
mali g na nc y or ot her life t hreate ni n g diseases.
2.
Perti ne nt n o n -c o mplia nce wit h 
t he c o n diti o ns f or t his st u d y or i nstr ucti o ns b y  the i n vesti gat or d uri n g 
R D. 0 6. S P R. 1 1 2 1 9 9
Pri m ar y E n d p oi nt :

S u bject rec urre nce, defi ne d as t he pr o p orti o n of s u bjects wit h rec urre nce of a n y (≥1) cleare d treate d A K lesi o ns 
at Visit 3, 5 2 wee ks after t he last D L -P D T treat me nt .
Sec o n d ar y E n d p oi nt s:

S u bject rec urre nce, defi ne d as t he pr o p orti o n of s u bjects w it h rec urre nce of a n y (≥1) cleare d treate d A K lesi o ns 
at Visit 2 , 2 6 we e ks after t he last D L -P D T treat me nt ;

Lesi o n rec urre nce, defi ne d as t he perce nt rec urre nce of cleare d treate d lesi o ns at Visits 2 a n d 3, 2 6 a n d 5 2 w ee ks 
after t he last D L -P D T treat me nt .
T he rec urre nce res ults will be c o n ve ye d i n t he o p p osite se nse of cleara nce, i.e., t h ose s u bjects or lesi o ns t hat are n ot 
C R at Visits 2 a n d 3 w ill be dee me d t o ha ve rec urre nce.
S afet y Assess me nts :
T he f oll o w i n g safet y assess me nts are pla n ne d acc or di n g t o t he sc he d ule of a ssess me nts (see T a ble 1 ):

A d verse e ve nts ( A Es), Treat me nt -e mer ge nt A Es ( T E A Es) , a n d seri o us A Es ( S A Es)
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
C CI

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 6 of 4 4
C O N FI D E N TI A L
St atistic al A n al ysis :
Pri nci p al St atistic al Met h o d
P o p ul ati o ns: T he safet y p o p ulati o n will c o nsist of all e nr olle d s u bjects a n d w ill be use d f or all t he efficac y a n d safet y 
a nal yses.
P ri m ary E n d p oi nt : T he pr o p orti o n of s u bjects w it h rec urre nce of a n y (≥1) cleare d treate d A K lesi o ns at 5 2 w ee ks 
after t he last D L -P D T w ill be s u m marize d usi n g ta bles of fre q ue nc y. All s u bjects i n t he safet y p o p ula ti o n wit h 
missi n g data will be classifie d as n o n -res p o n ders re gar dless of treat me nt all ocati o n. S u m maries b y treat me nt gr o u p 
will be prese nte d f or b ot h t he i m p ute d data a n d t he o bser ve d cases .
 
Sec o n d ary E n d p oi nts: T he pr o p orti o n of s u bjects wit h rec urre nce of a n y ( ≥1) cleare d treate d A K lesi o ns at 2 6 w ee ks 
after t he last D L -P D T w ill be s u m marize d usi n g ta bles of fre q ue nc y. All s u bjects i n t he safet y p o p ulati o n wit h 
missi n g data will be classifie d as n o n -res p o n ders re gar dless of treat me nt all ocati o n. S u m maries b y treat me nt gr o u p 
will be prese nte d f or b ot h t he i m p ute d data a n d t he o bser ve d cases .
 
T he perce nt rec urre nce of cleare d treate d A K lesi o ns at 2 6 a n d 5 2 w ee ks after t he last D L -P D T treat me nt will be 
s u m marize d usi n g descri pti ve statistics. M issi n g c o u nts of cleare d treate d A K lesi o ns f or s u bjects i n t he safet y 
p o p ulati o n will be i m p ute d ass u mi n g t hat all baseli ne A K lesi o ns ha d rec urre d re gar dless of treat me nt all ocati o n.
S u m maries b y treat me nt gr o u p w ill be prese nte d f or b ot h t he i m p ute d data a n d t he o bser ve d cases.
 
S a m ple Size : T here is n o f or mal h y p ot hesis t o be teste d. T he n u m ber of 1 0 0 c o m pleters i n t he M A L crea m ar m is 
dee me d s ufficie nt f or t he descri pti ve p ur p oses of t his st u d y.
F i g ure 1 : St u d y Sc he m a ( S y n o psis)
T C =tele p h o ne c all
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
C CI
C CI
C CI

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 7 of 4 4
C O N FI D E N TI A L
4
T A B L E O F C O N T E N T S
1
P R O T O C O L A P P R O V A L SI G N A T U R E S .............................................................. 2
2
S T U D Y P E R S O N N E L C O N T A C T S ......................................................................... 3
3
S Y N O P SI S .................................................................................................................... 4
4
T A B L E O F C O N T E N T S ............................................................................................ 7
T A B L E O F FI G U R E S ................................................................................................................... 9
T A B L E O F T A B L E S ..................................................................................................................... 9
5 
LI S T O F A B B R E VI A TI O N S................................................................................... 1 0
6
I N T R O D U C TI O N ..................................................................................................... 1 1
6. 1
B ac k gr o u n d & R ati o n ale .......................................................................................... 1 1
7
S T U D Y O B J E C TI V E S & E N D P OI N T S ................................................................. 1 4
7. 1
Pri m ar y O bjecti ve ..................................................................................................... 1 4
7. 2
Sec o n d ar y O bjecti ve .................................................................................................. 1 4
7. 3
Pri m ar y E n d p oi nt ...................................................................................................... 1 4
7. 4
Sec o n d ar y E n d p oi nts ................................................................................................. 1 4
7. 5
S afet y Assess me nts ..................................................................................................... 1 4
7. 6
Ot her Assess me nts ..................................................................................................... 1 4
8
I N V E S TI G A TI O N A L P L A N ................................................................................... 1 5
8. 1
O ver all St u d y Desi g n a n d Pl a n ................................................................................. 1 5
St u d y  Sc he ma .............................................................................................................. 1 6
Sc he d ule of Assess me nts ........................................................................................... 1 7
8. 2  
Disc ussi o n of St u d y Desi g n ....................................................................................... 2 0
St u d y  Desi g n................................................................................................................ 2 0
8. 3
Selecti o n of t he St u d y P o p ul ati o n ............................................................................. 2 0
N u m ber of Pla n ne d S u bjects ....................................................................................... 2 0
I ncl usi o n Criteria......................................................................................................... 2 0
E x cl usi o n Criteria........................................................................................................ 2 1
Re m o val of S u bjects Fr o m Assess me nts..................................................................... 2 1
Met h o d of C o nti n ui n g alrea d y Ra n d o mize d S u bject fr o m Pre vi o us st u d y ................. 2 2
Bli n di n g....................................................................................................................... 2 2
Pri or a n d C o nc o mita nt T hera p y................................................................................... 2 2
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 8 of 4 4
C O N FI D E N TI A L
8. 4
D ur ati o n of S u bject P artici p ati o n............................................................................ 2 4
Earl y Ter mi nati o n Visit ............................................................................................... 2 4
8. 5
U nsc he d ule d Visit ...................................................................................................... 2 4
9
S T U D Y A S S E S S M E N T S .......................................................................................... 2 5
9. 1
Effic ac y Assess me nts ................................................................................................. 2 5
Lesi o n Res p o nse.......................................................................................................... 2 5
9. 2
S afet y Assess me nts ..................................................................................................... 2 6
9. 2. 1. 1
Seri o us A d verse E ve nts ............................................................................................... 2 8
9. 2. 1. 2
A d verse E ve nts of S pecial I nterest ( A E SIs) ................................................................ 2 9
9. 2. 1. 3
Pr oce d ure f or Re p orti n g a Seri o us A d verse E ve nt ...................................................... 2 9
9. 2. 1. 4
Pr oce d ure f or Re p orti n g Pre g na ncies .......................................................................... 3 0
9. 2. 1. 5  
U ne x pecte d A d verse Reacti o ns................................................................................... 3 1
Pre ga nc y  Testi n g ......................................................................................................... 3 1
............................................................................... 3 2
1 0 
S T A TI S TI C A L M E T H O D S..................................................................................... 3 3
1 0. 1
St atistic al a n d A n al ytic al Pl a ns ................................................................................ 3 3
Data sets or P o p ulati o ns A nal y ze d .............................................................................. 3 3
1 0. 1. 1. 1
I nte nt-t o-Treat P o p ulati o n ........................................................................................... 3 3
1 0. 1. 1. 2
Safet y  P o p ulati o n......................................................................................................... 3 3
1 0. 1. 1. 3
Per Pr ot oc ol P o p ulati o n ............................................................................................... 3 3
De m o gra p hic a n d Ot her Baseli ne C haracteristics .......................................................3 3
Efficac y  A nalys is......................................................................................................... 3 3
1 0. 1. 3. 1
Pri mar y  E n d p oi nt A nalys is.......................................................................................... 3 3
1 0. 1. 3. 2
Pri mar y  E n d p oi nt Se nsiti vit y A nalys is........................................................................ 3 4
1 0. 1. 3. 3
Sec o n dar y  E n d p oi nts A nal ysis .................................................................................... 3 4
1 0. 1. 3. 4
S u b gr o u p A nal y sis ....................................................................................................... 3 4
Safet y A nal ys is............................................................................................................ 3 4
1 0. 1. 4. 1  
A d verse E ve nts ............................................................................................................ 3 4
I nteri m A nalys es .......................................................................................................... 3 4
Ha n dli n g of Missi n g Data............................................................................................ 3 5
1 0. 2
Deter mi n ati o n of S a m ple Size................................................................................... 3 6
1 0. 3 
Pr ot oc ol De vi ati o ns.................................................................................................... 3 6
1 1
Q U A LI T Y A S S U R A N C E A N D Q U A LI T Y C O N T R O L ....................................... 3 7
1 1. 1
A u dit a n d I ns pecti o n ................................................................................................. 3 7
1 1. 2
M o n it ori n g.................................................................................................................. 3 7
1 1. 3
Pers o n nel Tr ai ni n g .................................................................................................... 3 7
1 1. 4
D at a M a n a ge me nt ...................................................................................................... 3 7
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
C CI

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 9 of 4 4
C O N FI D E N TI A L
1 1. 5
Cli nic a l St u d y C o n d uct ............................................................................................. 3 8
1 1. 6
A m e n d me nts ............................................................................................................... 3 8
1 1. 7
Q u alit y M a n a ge me nt a n d Ris k E v al u ati o n ............................................................. 3 8
1 2
E T HI C S ...................................................................................................................... 3 9
1 2. 1
I n de pe n de nt Et hics C o m mittee or I nstit uti o n al Re vie w B o ar d............................ 3 9
1 2. 2
Re g ul at or y A ut h orities .............................................................................................. 3 9
1 2. 3
Et hic al C o n d uct of t he St u d y .................................................................................... 3 9
1 2. 4
I nf or me d C o nse nt ...................................................................................................... 3 9
1 2. 5
S u bject C o nfi de nti alit y .............................................................................................. 4 0
1 3
R E P O R TI N G A N D P U B LI C A TI O N, I N C L U DI N G A R C HI VI N G .................... 4 1
1 4
R E F E R E N C E S .......................................................................................................... 4 2
I N V E S TI G A T O R SI G N A T UR E P A G E .................................................................................... 4 4
T A B L E O F FI G U R E S
Fi g ure 1: St u d y  Sc he ma ( S yn o psis) ................................................................................................. 6
Fi g ure 2: St u d y  Sc he ma.................................................................................................................. 1 6
T A B L E O F T A B L E S
Ta ble 1: Sc he d ule of Assess me nts .................................................................................................. 1 7
Ta ble 2: F or bi d de n Treat me nts i n Treat me nt Area........................................................................ 2 3
Ta ble 3: Lesi o n Se verit y Gra de Scale ............................................................................................ 2 5
Ta ble 4: Lesi o n Res p o nse ............................................................................................................... 2 5
................................................................................................... 3 6
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
C CI

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 1 0 of 4 4
C O N FI D E N TI A L
5
LI S T O F A B B R E VI A TI O N S
A E
A d ve rse E ve nt
A K
Acti nic kerat osis
B C C
Basal cell carci n o ma
B L
Baseli ne
CI
C o nfi de nce i nter val
C R
C o m plete res p o nse
C R O
C o ntract researc h or ga nizati o n
C S
Cli nicall y si g nifica nt
c-P D T
C o n ve nti o nal P D T
D L
Da yli g ht
e CR F
Electr o nic C ase R e p ort F or m
E D C
Electr o nic data ca pt ure
E T
Earl y ter mi nati o n
F D A
F o o d a n d Dr u g A d mi nistrati o n
F S T
Fitz patric k S ki n T y pe
G C P
G o o d Cli nical Practice
HI P A A
Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act 
I B
I nvesti gat or’s Br oc h ure
I C
I nf or me d C o nse nt
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 u ncil f or Har m o nisati o n of Tec h nical Re q uire me nts f or P har mace uticals 
f or H u ma n Use
I E C
In de pe n de nt E t hics C o m mittee
I R B
Instit uti o nal R e vie w B oar d
L T F U
L o n g -ter m f oll o w- u p
M A L
Met h yl a mi n ole vi n ulate h y dr oc hl ori de
Me d D R A
Me dical Dicti o nar y f or Re g ulat or y Acti vities
N D A
Ne w dr u g a p plicati o n
P D T
P h ot o d y na mic T hera p y
P pI X
Pr ot o p or p h yri n I X
S A E
S eri o us a d verse e ve nt
S A P
S tatistical anal ysis p la n
S C C
S q ua m o us cell car ni n o ma
SI N 
S u bject i de ntificati o n n u m ber
S O C
S yste m Or ga n Class
S U S A R
S us pecte d u ne x pecte d seri o us a d verse reacti o n
T A
Treat me nt area
T E A E
T reat me nt-e mer ge nt ad verse eve nt
T M F
Trial Master File
U P T
U ri ne p re g na nc y test
U S
U nite d States
U V
Ultra vi olet
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 1 1 of 4 4
C O N FI D E N TI A L
6
I N T R O D U C TI O N
6. 1 
B ac k gr o u n d & R ati o n ale
Acti nic kerat osis ( A K) is a c o m m o n e pit helial n o n- i nfiltrati ve lesi o n ca use d b y pr ol o n ge d 
e x p os ure t o ultra vi olet ( U V) ra diati o n, w hic h da ma ges cell c y cle re g ulat ors a n d lea ds t o t he 
pr oliferati o n of e pi der mal kerati n oc y tes. A cti nic kerat oses are pre mali g na nt s ki n lesi o ns t hat are 
c haracteristicall y distri b ute d o n s u n -e x p ose d areas s uc h as face, bal d scal p, nec k, c hest, bac k of 
t he ha n ds, a n d f orear ms. I n di vi d uals ofte n prese nt wit h m ulti ple a cti nic kerat osis.
A cti nic kerat os is is a gl o bal c o n diti o n a n d it is t he sec o n d m ost fre q ue nt dia g n osis ma de b y 
der mat ol o gists i n t he U S ( U hle n ha ke 2 0 1 3 ) wit h pre vale nce bet wee n 1 1 % a n d 2 6 % 
(Salasc he 2 0 0 0 ). A cti nic kerat oses t he msel ves are dee me d n ot seri o us, b ut t he y  are ver y c o m m o n, 
hi g hl y wi des prea d , a n d rec urre nt. A cti nic kerat osis is c o nsi dere d t he earliest, cli nicall y 
rec o g niza ble ma nifestati o n of s q ua m o us cell carci n o ma ( S C C) t hat is ca pa ble of tra nsf or mi n g 
i nt o S C C (in sit u a n d i n vasi ve) ( Fel d ma n 2 0 1 1 p 2 0 1 ). Bet wee n 6 0-8 0 % of S C C cases be gi n as 
A K ( Fel d ma n 2 0 1 1 ). T he rate of pr o gressi o n of A K t o i n vasi ve S C C has bee n esti mate d t o be 
fr o m less t ha n 0. 0 2 5 % to 1 6 % per y ear (Wer ner 2 0 1 3 ). H o we ver, t here is n o relia ble wa y t o 
meas ure t his rate a n d pre dict w hic h lesi o ns will tra nsf or m, mea ni n g t hat it is necessar y  t o treat 
A K lesi o ns t o a v oi d pr o gressi o n.
T he eti ol o g y  of A K is m ultifact orial, a n d ris k fact ors i ncl u de i ncrease d a ge, male ge n der, a fair 
s ki n Fitz patric k s ki n t y pe, a n d e xte nsi ve o ut d o or acti vities (G ol d ber g 2 0 1 0 ). M ore o ver, A K is a n 
i n dicat or of c hr o nic ultra vi olet ( U V ) da ma ge a n d t h us , of i ncrease d ris k f or U V -relate d s ki n 
ca ncer. A re vie w of e pi de mi ol o gical st u dies s h o we d t hat t he pre vale nce a n d i nci de nce of A K are
hi g hl y varia ble acc or di n g t o t he p o p ulati o n st u die d, w orl d l ocati o n, a ge, a n d ge n der ( Fr ost 1 9 9 4 ). 
F or e xa m ple, pre vale nce rates near 6 0 % ha ve bee n re p orte d i n A ustralia, a n d e ve n u p t o 6 4 % i n 
w o me n a n d 8 3 % i n me n a ge d 6 0 t o 6 9 y ears ( Fr ost 1 9 9 8 ; Fr ost 2 0 0 0 ), i n c o ntrast t o t he 
pre vale nce rate re p orte d i n E n gla n d i n 2 0 0 0 of 1 5. 4 % i n me n a n d 5. 9 % i n w o me n ol der t ha n 4 0 
ye ars (Me m o n 2 0 0 0 ). T hese rates i ncrease d t o 3 4. 1 % a n d 1 8. 2 %, res pecti vel y, at 7 0 years of a ge, 
w he n pre vale nce wa s m ost str o n gly relate d t o 2 o bjecti ve si g ns of s u n e x p os ure, s olar elast osis 
a n d le nti gi nes. T he S o ut h Wales S ki n Ca ncer St u d y re p orte d a n A K pre vale nce of 2 3 % 
(Har ve y 1 9 9 6 ). St u dies i n t he U nite d States ha ve re p orte d pre vale nce rates of 5 5 % i n i n di vi d uals 
a ge d 6 5 t o 7 5 y ears wit h hi g h s u n e x p os ure, b ut o nl y  1 2 % t o 1 9 % i n t h ose wit h l o w s u n e x p os ure 
(E n gel 1 9 8 8 ).
Vari o us treat me nt o pti o ns are a vaila ble f or A K lesi o ns, i ncl u di n g destr ucti ve t hera pies s uc h as 
cr y os ur ger y  or e xcisi o nal s ur ger y, t o pical t hera pies s uc h as 5-fl u or o uracil, i mi q ui m o d, 
dicl ofe nac, i n ge n ol me b utate, a n d n o n- a p pr o ve d t o pical or or al reti n oi ds (G ol d 2 0 0 6 ; 
Fe ns ke 2 0 1 0 ). H o we ver, patie nt satisfacti o n wit h ma n y of t hese treat me nts, es pecially t he 
destr ucti ve t hera pies, ca n be affecte d b y c o nsi dera ble treat me nt disc o mf ort a n d resi d ual scarri n g. 
P h ot o d y na mic t hera p y  ( P D T) is a hi g hl y efficaci o us t hera p y rec o m me n de d as a first-li ne 
treat me nt f or i n di vi d ual, or m ulti ple a n d/ or c o nfl ue nt A K lesi o ns (de Ber ker 2 0 0 7 ; 
Braat he n 2 0 0 7 ). P h ot o d y na mic t hera p y has bee n ass ociate d wit h a better c os metic o utc o me t ha n 
ot h er treat me nts, a n d it ca n als o be use d t o treat m ulti ple A K le si o ns o ver lar ge areas 
(Le h ma n n 2 0 0 7 ; Si d or off 2 0 1 0 ).
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 1 2 of 4 4
C O N FI D E N TI A L
Met vi xia ® crea m 1 6 8 m g/ g ( met h yl  a mi n ole v uli nate) was a p pr o ve d i n t he U S A i n 2 0 0 8 ( N D A
0 2 1 4 1 5) i n c o m bi nati o n wit h L E D re d li g ht ill u mi nati o n usi n g t he A ktilite ® C L 1 2 8 la m p f or t he 
treat me nt of t hi n a n d m o derately t hic k, n o n -h y per kerat otic , a n d n o n -pi g me nte d A K of t he face 
a n d scal p (it was i nitiall y a p pr o ve d i n 2 0 0 4 wit h t he C u reli g ht la m p), a n d was mar kete d f or m ore 
t ha n 4 years u ntil it was wit h dra w n i n t he U nite d States i n 2 0 1 2 f or c o m mercial reas o ns. T he 
pr o d uct, use d i n c o m bi nati o n wit h re d li g ht ill u mi nati o n, is als o na me d Met vi x or Met vi xi a i n 
ot her c o u ntries w orl d wi de.
Gal der ma has de ve l o pe d a ne w treat me nt re gi me n f or t he face a n d scal p, i n w hic h nat ural 
da y li g ht ( D L) ma y re place t he pre vi o usly-a p pr o ve d re d li g ht as t he mea ns of acti vati n g t he P pI X 
f or me d after a p plicati o n of t he crea m d uri n g P D T.
Gi ve n t hat t he area t o be treate d is n o l o n ger li mite d b y  t he size or c o nfi g urati o n of t he la m p, t he 
D L - P D T pr oce d ure is si m plifie d c o m pare d t o c o n ve nti o nal P D T ( c-P D T ). In a d diti o n, 
si g nifica ntly less pai n is e x perie nce d d uri n g ill u mi nati o n as s h o w n i n 2 ra n d o mize d, P hase 3 
cli nical st u dies rece ntl y c o n d ucte d b y Gal der ma. T hese st u dies, perf or me d i n A ustralia ( N = 1 0 0) 
a n d E ur o pe ( N = 1 0 8), c o nfir me d t hat m et h yl  a mi n ole v uli nate h y dr oc hl ori de (M A L ) D L -P D T has 
si milar efficac y as M A L wit h c - P D T, lea ds t o fe wer relate d a d verse e ve nts, is nearl y pai nless ,
a n d m ore c o n ve nie nt f or s u bjects ( R u bel 2 0 1 4 , Lac o ur 2 0 1 5 ). It is k n o w n t hat t he use of t he re d 
la m p res ults i n disc o mf ort a n d pai n f or s u bjects, as all pr o d uce d P pI X is p h ot o bleac he d i n a s h ort 
peri o d of ti me. Wit h 2 h o urs of D L e x p os ure, P pI X will be c o nti n u o usl y  pr o d uce d at a ver y l o w 
le vel a n d i m me diately p h ot o blea c he d wit h n o or al m ost n o pai n.
T he use of D L -P D T , as o p p ose d t o t he use of bl ue or re d li g ht s o urces c-P D T , has ma n y be nefits. 
I n partic ular, t he use of D L will treat w h ole fiel ds of ca ncerizati o n t o tar get visi ble a n d 
s u bcli nical A K lesi o ns, a n d is n ot li mit e d t o cli nicall y a p pare nt lesi o ns. I n 2 0 1 5, a n E ur o pea n 
c o nse ns us o n D L-P D T ( M ort o n 2 0 1 5 p 1 ) rec o m me n de d D L-P D T as a first -li ne treat me nt o pti o n 
f or i m m u n oc o m pete nt patie nts wit h Gra de I (t hi n) or II ( m o deratel y t hic k) A Ks or fiel ds of 
acti nic da ma ge o n t he face a n d scal p, d ue t o its efficac y , t olera bilit y, a n d si m plicit y. M ore 
rece ntly, a str uct ure d E x pert C o nse ns us o n Acti nic Kerat osis has c o nfir me d D L -P D T as a 
val ua ble o pti o n f or s u bjects wit h m ulti ple A Ks i n s mall or lar ge fiel ds ( Calza vara -Pi nt o n, 2 0 1 7 ).
Met h y l a mi n ole v uli nate h y dr oc hl ori de is mar kete d u n der vari o us tra de na mes: Met vi x / Met vi xia 
/ Me x vi via 1 6 0 m g/ g or 1 6 8 m g/ g. T he pr o d ucts are i de ntical b ut are la belle d differe ntl y ,
de pe n di n g o n t he vari o us c o u ntr y  s pecific a p pr o vals. As of 3 0 J u ne 2 0 19 , t he pr o d uct is a p pr o ve d 
i n 3 9 c o u ntries f or t he treat me nt of A K, basal cell carci n o ma (B C C ), a n d B o we n’s disease 
(i n di vi d ual c o u ntr y a p pr o vals var y) wit h a re d la m p. As of 3 0 J u ne 2 0 1 9 , Met vi x® Crea m wit h 
D L  acti vati o n f or t he treat me nt of A K has bee n a p pr o ve d as a variati o n to t he c urre nt Met vi x 
A ktilite a ut h oriz ati o n i n E ur o pe a n d o utsi de E ur o pe ( Ar ge nti na, A ustralia, Ne w Zeala n d, 
Si n ga p ore, S witzerla n d, R ussia n Fe derati o n, C ol o m bia, Me xic o, Brazil, C osta Rica, Ve nez uela, 
C hile , a n d Ca na da). I n a d diti o n, Lu xera, L u xer m , a n d Lu me xia are ot her c o m mercial na mes f or 
t he sa me pr o d uct, w hic h is a p pr o ve d f or t he treat me nt of A Ks wit h da y li g ht o nl y, a p pr o ve d i n 
A ustria, Ger ma n y, Ital y, P ort u gal, S pai n, a n d S we de n.
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 1 3 of 4 4
C O N FI D E N TI A L
Gal der ma is de vel o pi n g M A L  D L-P D T i n t he U nite d S tates f or lesi o n treat me nt, b ut ma y  
c o nsi der fiel d treat me nt as a sec o n dar y  i n dicati o n f or life c ycle ma na ge me nt. T his st u d y  ser ves as 
a f oll o w-u p st u d y  t o R D. 0 6. S P R. 1 1 2 1 9 9 t o e val uate rec urre nces of lesi o ns t hat ac hie ve d C R i n 
b ot h M A L crea m D L-P D T a n d ve hicle crea m D L-P D T treate d gr o u ps.
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 1 4 of 4 4
C O N FI D E N TI A L
7
S T U D Y O B J E C TI V E S & E N D P OI N T S
7. 1
Pri m ar y O bjecti ve
T he pri mar y  objecti ve of t his st u d y is t o assess rec urre nce of A Ks treate d i n R D. 0 6. S P R. 1 1 2 1 9 9 
f or t h ose s u bjects w h o ac hie ve d C o m plete Res p o nse ( C R) of treate d A K lesi o ns. T he y  will be 
offere d t he o p p ort u nit y  to partici pate i n t his 9- m o nt h l o n g-ter m f oll o w-u p st u d y (i.e., 5 2 wee ks 
after t he last D L-P D T), c o nti n ui n g t he d o u ble- bli n d c o n d uct of t his st u d y . 
7. 2
Sec o n d ar y O bjecti ve
T he sec o n dar y  o bjecti ve of t his st u d y is t o e val uate t he l o n g-ter m safety of M A L  D L-P D T a n d 
ve hicle crea m D L -P D T f or 5 2 wee ks after t he last D L-P D T f or t h ose s u bjects w h o ac hie ve d 
C o m plete Res p o nse ( C R) of treate d A K lesi o ns i n st u d y  R D. 0 6. S P R. 1 1 2 1 9 9.
7. 3
Pri m ar y E n d p oi nt
•
T he pri mar y  efficac y e n d p oi nt is t he s u bject rec urre nce, defi ne d as t he pr o p orti o n of s u bjects 
wit h rec urre nce of a n y ( ≥1) cleare d treate d A K lesi o ns at Visit 3, 5 2 wee ks after t he last D L -
P D T treat me nt .
7. 4
Sec o n d ar y E n d p oi nts
•
Lesi o n rec urre nce, defi ne d as t h e perce nt rec urre nce of cleare d treate d lesi o ns at Visits 2 a n d 
3, 2 6 a n d 5 2 wee ks after t he last D L -P D T treat me nt .
•
S u bject rec urre nce, defi ne d as t he pr o p orti o n of s u bjects wit h rec urre nce of a n y  (≥1) cleare d 
treate d A K lesi o ns at Visit 2, 2 6 wee ks after t he last D L -P D T treat me nt .
7. 5 
S afet y Assess me nts
•
Assess safety, i ncl u di n g a d verse e ve nts ( A Es), Treat me nt -e mer ge nt A Es ( T E A Es), relate d t o 
t he st u d y dr u g a d mi nistered i n st u d y R D. 0 6. S P R. 1 1 2 1 9 9 a n d seri o us A Es ( S A Es)
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
C CI

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 1 5 of 4 4
C O N FI D E N TI A L
8
I N V E S TI G A TI O N A L P L A N
8. 1
O ver all St u d y Desi g n a n d Pl a n
T his is a d o u ble -bli n d, ve hicle -c o ntr olle d, m ultice nter, parallel- gr o u p l o n g-ter m f oll o w- u p st u d y to 
e val uate rec urre nce of A Ks i n s u bjects w h o c o m plete d st u d y RD. 0 6. S P R. 1 1 2 1 9 9.
O nl y  th ose 
s u bjects w h o ac hie ve d C R of treate d A K lesi o ns at t he Fi nal Visit of t hat st u d y  will be offere d t he 
o p p ort u nit y  t o c o nti n ue t o be f oll o we d i n t he c urre nt st u d y f or 9 m o nt hs t o assess rec urre nce.
I n this st u d y, t he res ults of D L-P D T wit h M A L  1 6.8 % crea m or a ve hicle crea m will be c o m pare d ; 
n o i nter ve nti o n occ urs i n t his st u d y . 
All s u bjects will pr o vi de writte n i nf or me d c o nse nt pri or t o a n y st u d y -relate d pr oce d ure.
A t otal of a p pr o xi matel y 1 3 0 s u bjects will
c o nti n ue fr o m t he st u d y RD. 0 6. S P R. 1 1 2 1 9 9 t o be 
f oll o we d f or a n ot her 4 0 wee ks , w hic h c orres p o n ds t o 5 2 wee ks after t he last D L -P D T. It is 
a ntici pate d t hat a p pr o xi matel y 1 1 1 s u bjects will c o nti n ue fr o m t he M A L  crea m ar m, a n d 1 9 
s u bjects will c o nti n ue fr o m t he ve hicle crea m arm. Bli n di n g will be mai ntai ne d t hr o u g h t his st u d y.
S u bjects will ha ve a c o m bi ne d visit w hic h i ncl u des t he fi nal visit f or t he R D. 0 6. S P R. 1 1 2 1 9 9 st u d y  
a n d t he i nitial visit f or t his st u d y. Data fr o m t he pre vi o us st u d y will be p ulle d i nt o t he data base f or 
t his st u d y. S u bjects will ret ur n t o t he st u d y ce nter f or a n ot her visit at Visit 2 ( Wee k 1 4, 2 6 wee ks 
after t he last D L -P D T treat me nt) f or efficac y an d safet y assess me nts. T he i n vesti gati ve site staff 
will c o ntact t he s u bject via tele p h o ne at Wee k 2 6 ( 3 8 wee ks after t he last D L -P D T treat me nt) t o 
deter mi ne if t he s u bject is e x perie nci n g a n y  treat me nt-relate d safety iss ues.
T he pri mar y  e n d p oi nt of t his st u d y occ urs at Visit 3; Fi nal V isit, Wee k 4 0 ( 5 2 wee ks after t he last 
D L -P D T visit ).
T he 4 pla n ne d i nteracti o ns are:
Visit 1
R oll o ver visit fr o m st u d y R D. 0 6. S P R. 1 1 2 1 9 9 ; c orres p o n ds t o Visit 6 i n t hat 
st u d y. O nly t h ose s u bjects w h o ac hie ve C R will be gi ve n t he o p p ort u nit y t o 
c o nti n ue i n t his l o n g-ter m f oll o w-u p st u d y . All assess me nts ca pt ure d are 
tra nsferre d t o t his st u d y 
Visit 2
Wee k 1 4 ( 2 6 wee ks after t he last D L -P D T treat me nt) - Efficac y a n d safet y 
assess me nts ; 
 
Tele p h o ne 
c hec k i n 
Wee k 2 6
( 3 8 wee ks after t he last D L -P D T treat me nt ) - Safet y assess me nts
Visit 3
Wee k
4 0 Fi nal Visit (5 2 wee ks after t he last D L -P D T treat me nt) - Efficac y 
a n d safety assess me nts; 
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
C CI
C CI

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 1 6 of 4 4
C O N FI D E N TI A L
St u d y Sc he m a
Fi g ure 2: St u d y Sc he m a
T C =tele p h o ne c all
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 1 7 of 4 4
C O N FI D E N TI A L
Sc he d ule of Assess me nts
T a ble 1 : Sc he d ule of Assess me nts
Vi sit
1
2
2 b a, b
3
4
4 b a, b
5 a, b
6 a, b
1 
2 ( 7)
T C
3 ( 8)
P ur p o s e
M e di c al 
hi st or y  
a n d l a b s
Fir st
D L -P D T
s e s si o n
If
r e q uir e d
F oll o w -u p
1 w e e k aft er
1 st D L -P D T
S e c o n d D L -
P D T
s e s si o n
If
r e q uir e
d
F oll o w -u p
1 w e e k aft er
2 n d D L -P D T
Fi n al
1 2 w e e k s 
aft er
l a st D L -P D T
Vi sit 6 i s 
Vi sit 1 of 
L T F U 
st u d y
2 6 w e e k s 
aft er l a st
D L -P D T
T el e p h o n e 
c all t o 
c h e c k o n 
s u bj e ct
Fi n al
5 2 w e e k s 
aft er l a st 
D L -P D T
W e e k
S cr e e ni n g
B a s eli n e
W e e k 2
W e e k 3
W e e k 1 4/ E T f
W e e k
1 4
W e e k 2 8
W e e k
2 6
W e e k 4 0
W e e k
4 0 / E T
W e e k 5 4
Vi sit wi n d o w
-1 4 t o -5
d a y s
0 t o + 1 4
d a y s
0 t o + 1 4
d a y s
-2 t o + 1 4
d a y s
-2 t o + 2 8
d a y s
+/ - 5 d a y s
+/ - 5 d a y s
+/ - 5 d a y s
L O N G -T E R M F O L L O W -U P S T U D Y
I nf or m e d C o n s e nt 
 
X
X
D e m o gr a p hi c s 
(i n cl u di n g F S T)
X
X
M e di c al Hi st or y
X
X
Pr e vi o u s 
T h er a pi e s/ Pr o c e d ur e s 
X
X
Vit al Si g n s/ P h y si c al 
E x a mi n ati o n
X
X
g →
X
I n cl u si o n/ E x cl u si o n 
Crit eri a
X
X
X →
X
H e m at ol o g y/ Bl o o d 
C h e mi str y/ U A/ E C G
X
X
Pr e g n a n c y T e st c
X
X
X
X
X
X →
X 
X
X
W e at h er a s s e s s m e nt
X
X
X
X
A K m a p pi n g + c o u nti n g 
+ gr a di n g d
X
X
X
X
X →
X 
X
X
S u n s cr e e n a p pli c ati o n
X
X
X
X
R D. 0 6. S P R. 1 1 5 2 3 0
R D. 0 6. S P R. 1 1 2 1 9 9
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
C CI
C CI

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 1 8 of 4 4
C O N FI D E N TI A L
Vi sit
1
2
2 b a, b
3
4
4 b a, b
5 a, b
6 a, b
1 
2 ( 7)
T C
3 ( 8)
P ur p o s e
M e di c al 
hi st or y  
a n d l a b s
Fir st
D L -P D T 
s e s si o n
If
r e q uir e d
F oll o w -u p
1 w e e k aft er
1 st D L -P D T
S e c o n d D L -
P D T
s e s si o n
If
r e q uir e
d
F oll o w -u p
1 w e e k aft er
2 n d D L -P D T
Fi n al
1 2 w e e k s 
aft er
l a st D L -P D T
Vi sit 6 i s 
Vi sit 1 of 
L T F U 
st u d y
2 6 w e e k s 
aft er l a st
D L -P D T
T el e p h o n e 
c all t o 
c h e c k o n 
s u bj e ct
Fi n al
5 2 w e e k s 
aft er l a st 
D L -P D T
W e e k
S cr e e ni n g
B a s eli n e
W e e k 2
W e e k 3
W e e k 1 4/ E T f
W e e k
1 4
W e e k 2 8
W e e k
2 6
W e e k 4 0
W e e k
4 0 / E T
W e e k 5 4
Vi sit wi n d o w
-1 4 t o -5 
d a y s
0 t o + 1 4
d a y s
0 t o + 1 4
d a y s
-2 t o + 1 4
d a y s
-2 t o + 2 8 
d a y s
+/ - 5 d a y s
+/ - 5 d a y s
+/ - 5 d a y s
L O N G -T E R M F O L L O W -U P S T U D Y
L e si o n d é bri d e m e nt 
a n d tr e at m e nt 
a p pli c ati o n
X
X
X
X
G e ol o c ali z e d S at ellit e 
d at a a n d e x p o s ur e ti m e 
X
X
X
X
St u d y dr u g( s) 
Di s p e n si n g ( D) a n d 
A c c o u nt a bilit y ( A)
X
X
X
X
S u bj e ct A s s e s s m e nt of 
P ai n
X
X
X
X
S u bj e ct S ki n A s p e ct 
A s s e s s m e nt d
X
S u bj e ct s ati sf a cti o n 
q u e sti o n n air e d
X
X
X d
S af et y Vi sit Q u e sti o n
X
X
A d v er s e E v e nt s e
X
X
X
X
X
X
X
X →
X
X
X
X
C o n c o mit a nt 
T h er a pi e s/ Pr o c e d ur e s d
X
X
X
X
X
X
X →
X 
X 
X 
X
S u bj e ct s wit h C o m pl et e 
R e s p o n s e e v al u ati o n 
a n d I C f or c o nti n u ati o n 
i nt o l o n g-t er m f oll o w-u p 
st u d y
X
E x it f or mf
X
X
Vi sit s 2 a n d 4 m a y b e d el a y e d f or u p t o 2 w e e k s i n c a s e of u n s uit a bl e w e at h er c o n diti o n s at r a n d o mi z ati o n/tr e at m e nt o ut s et; t h e s e vi sit s wil l b e Vi sit s 2 b a n d 4 b . 
T h e s e p o st p o n e m e nt s will b e a ut o m ati c all y a d d e d t o t h e ti m e of s c h e d ul e d Vi sit s 5 a n d 6
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 1 9 of 4 4
C O N FI D E N TI A L
If s u bj e ct s e x p eri en c e r ai n d uri n g t h e 2 h o ur s of d a yli g ht e x p o s ur e of eit h er D L -P D T vi sit, t h e y will b e i n str u ct e d t o g o i n d o or s at t h e i n v e sti g ati v e sit e a n d t h e st u d y 
dr u g will b e w a s h e d off. T h e tr e at m e nt will b e c o n si d er e d i n c o m pl et e a n d s h o ul d b e r e p e at e d at a mi ni m u m i nt er v al of 2 w e e k s. T h er e will b e o nl y  on e att e m pt at 
r etr e at m e nt of a n i n c o m pl et e tr e at m e nt. T h e s e vi sit s will b e Vi sit s 2 b a n d 4 b. If t h e att e m pt at r etr e at m e nt i s al s o i n c o m pl et e, t h e s u bj e ct will n ot b e e x cl u d e d fr o m 
t h e st u d y. Li k e wi s e, t h e s e r e p e at vi sit s will b e a d d e d t o t h e ti m e of s c h e d ul e d Vi sit s 5 a n d 6 . If a s u bj e ct h a s t w o i n c o m pl et e vi sit s i n a r o w, t h er s u bj e ct will c o nti n u e 
wit h a s s e s s m e nt i n t hi s st u d y. 
a)
O nl y f or f e m al e s of c hil d b e ari n g p ot e nti al, U P T at Vi sit s 1, 2, a n d 3 of t hi s st u d y 
b)
S h o ul d b e p erf or m e d e arli er if s u bj e ct di s c o nti n u e s b ef or e Vi sit 3 of t hi s st u d y
c)
A d v er s e E v e nt s h a v e t o b e c oll e ct e d fr o m t h e ti m e of t h e I nf or m e d C o n s e nt si g n at ur e
d)
E x it f or m s h o ul d b e c o m pl et e d aft er s u bj e ct d at a c oll e cti o n h a s b e e n c o m pl et e d f or s u bj e ct s i n t h e st u d y; F S T = Fit z p atri c k S ki n T y p e
e)
R e d arr o w s si g nif y t h at p erti n e nt d at a o bt ai n e d at Vi sit 6 of R D. 0 6. S P R. 1 1 2 1 9 9 will b e tr a n s cri b e d a s t hi s vi sit a s Vi sit 1 of R D. 0 6. S P R. 1 1 5 2 3 0
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 2 0 of 4 4
C O N FI D E N TI A L
8. 2
Disc ussi o n of St u d y Desi g n
St u d y Desi g n
T his st u d y will e val uate rec urre nce of A Ks treate d i n st u d y R D. 0 6. S P R. 1 1 2 1 9 9. I n t his st u d y, 
in vesti gat ors will re vie w t he c o n diti o n of lesi o ns map pe d a n d treate d i n t hat st u d y, o ver a 9-m o nt h 
f oll o w-u p. O nl y t h ose s u bjects w h o ac hie ve a C o m plete Res p o nse at t he Fi nal Visit fr o m t he 
ve hicle a n d acti ve crea m gr o u ps i n t hat st u d y, are eli gi ble t o c o nti n ue i n t his l o n g-ter m f oll o w- u p 
st u d y.
I n st u d y RD. 0 6. S P R. 1 1 2 1 9 9, a p pr o xi matel y 5 7 0 s u bjects wit h mil d t o m o derate acti nic kerat oses 
of t he face a n d scal p, meeti n g s pecific criteria, will recei ve 2 sessi o ns of D L -P D T, ra n d o mize d t o 
recei ve eit her M A L 1 6. 8 % crea m ( C D 0 6 8 0 9-4 1) or ve hicle crea m i n a 
 rati o. It is esti mate d t hat 
3 8 0 s u bjects w o ul d recei ve M A L  D L-P T a n d 1 9 0 s u bjects w o ul d recei ve ve hicle crea m D L -P D T 
at 2 treat me nt sessi o ns 2 t o 4 wee ks a part. T he e n d p oi nt of st u d y RD. 0 6. S P R. 1 1 2 1 9 9 occ urs at 
Visit 6, 1 2 wee ks after t he last D L -P D T treat me nt, w he n t he treate d A K lesi o ns are assesse d f or 
c o m plete res p o nse. T he s u bject c o m plete res p o nse, defi ne d as t he pr o p orti o n of s u bjects wit h 
c o m plete cleara nce of all A K lesi o ns treate d, will c o m pare M A L crea m wit h ve hicle crea m. I n t he 
p o weri n g of t he st u d y, t he ass u m pti o ns of a 4 5 % s u bject c o m plete res p o nse f or M A L  16. 8 % crea m 
( C D 0 6 8 0 9-4 1) a n d 1 5 % s u bject c o m plete res p o nse f or ve hicle crea m were use d. Beca use t here will 
be s u bjects e nr olli n g i n t he l o n g-ter m f oll o w- u p st u d y fr o m b ot h treat me nt ar ms, it is esse ntial t o 
kee p t he s u bjects a n d t he site pers o n nel bli n de d t o t he treat me nt, i n or der t o n ot bias t he e val uati o ns 
of rec urre nce sc he d ule d at Visits 2 a n d 3 of t his st u d y, occ urri n g 2 6 a n d 5 2 wee ks after t he last 
D L -P D T .
A p pr o xi matel y  1 3 0 s u bjects w h o c o m plete d t he st u d y RD. 0 6. S P R. 1 1 2 1 9 9 a n d ac hie ve c o m plete 
res p o nse of all treate d lesi o ns (esti mate d t o be 1 1 1 ra n d o mize d t o M A L  DL- P D T a n d 1 9
ra n d o mize d t o Ve hicle D L-P D T) will be e nr olle d i n t his st u d y  i n or der t o ha ve a p pr o xi matel y 1 0 0 
s u bjects ra n d o mize d t o M A L D L-P D T w h o c o m plete t he l o n g -ter m f oll o w- u p.
8. 3
Selecti o n of t he St u d y P o p ul ati o n
N u m ber of Pl a n ne d S u bjects
A p pr o xi matel y 1 3 0 s u bjects. 
Refer t o Secti o n 1 0. 2 f or t he statistical c o nsi derati o ns o n w hic h t he sa m ple size is base d .
I ncl usi o n C riteri a
T o be eli gi ble f or st u d y e ntr y , s u bjects m ust satisf y all of t he f oll o wi n g i ncl usi o n criteria:
1.
S u bjects w h o ha ve partici pate d i n st u d y  R D. 0 6. S P R. 1 1 2 1 9 9 a n d ha ve ac hie ve d a c o m plete 
res p o nse at Fi nal Visit of t hat st u d y, c o m plete cleara nce of treate d lesi o ns at 1 2 wee ks after 
t he last D L -P D T .
2.
Writte n I nf or me d C o nse nt bef ore a n y  assess me nt relate d t o t he L T F U st u d y is perf or me d.
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
C CI

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 2 1 of 4 4
C O N FI D E N TI A L
3.
S u bject is willi n g a n d a ble t o c o m pl y wit h all of t he ti me c o m mit me nts a n d pr oce d ur al 
re q uire me nts of t he cli nical st u d y pr ot oc ol.
E xcl usi o n C riteri a
S u bjects will be e xcl u de d fr o m t he st u d y  if 1 or m ore of t he f oll o wi n g criteria are a p plica ble :
1.
S u bjects, w h o de vel o p or e x perie nce a c o n diti o n t hat ma y c o m pr o mise s u bject safet y or 
c o m plia nce, i nterfere wit h e val uati o n or precl u de c o m pleti o n of t he st u d y . I n partic ular, t hese 
c o n diti o ns i ncl u de, b ut are n ot li mite d t o mali g na nc y or ot her life t hreate ni n g diseases.
2.
Perti ne nt n o n- c o m plia nce wit h t he c o n diti o ns f or t his st u d y or i nstr ucti o ns b y t he i n vesti gat or 
d uri n g R D. 0 6. S P R. 1 1 2 1 9 9.
Re m o v al of S u bjects F r o m A ssess me nts
Alt h o u g h t he i m p orta nce of c o m pleti n g t he e ntire cli nical st u d y will be e x plai ne d t o t he s u bjects, 
a n y s u bject is free t o disc o nti n ue his/ her partici pati o n i n t he stu d y  at a n y ti me a n d f or w hate ver 
reas o n, s pecifie d or u ns pecifie d, a n d wit h o ut a n y prej u dice. N o c o nstrai nts are t o be i m p ose d o n 
t he s u bject, a n d w he n a p pr o priate, a s u bject ma y be treate d wit h ot her c o n ve nti o nal t hera p y w he n 
cli nicall y i n dicate d. I n vestigat ors or t he S p o ns or ca n als o wit h dra w s u bjects fr o m t he cli nical 
st u d y if dee me d t o be necessar y. Data c ollecte d u p t o t he ti me of s u bject re m o val will be use d.
Reas o ns f or disc o nti n ui n g t he st u d y i ncl u de:

WI T H D R A W A L B Y S U BJ E C T
S u bject re q uest (i.e., c o nse nt wit h dra wal)

P R O T O C O L  VI O L A TI O N
U se of no n- per mitte d c o nc urre nt t hera p y ( u nless disc usse d a n d a gree d u p o n wit h t he 
In vesti gat or a n d m e dical m o nit or) see Secti o n 8. 3. 7

N O N -C O M P LI A N C E WI T H S T U D Y S C H E D U L E

L O S T T O F O L L O W -U P

A D V E R S E E V E N T
Occ urre nce of A Es n ot c o m pati ble wit h t he c o nti n uati o n of s u bject partici pati o n i n t he st u d y, 
i n t he I n vesti gat or’s o pi ni o n, or u nacce pta ble t o t he s u bject t o c o nti n ue 

P H Y SI CI A N D E CI SI O N 

O T H E R
T he reas o n(s) f or wit h dra wal will be d oc u me nte d i n t he e C R F.
S u bjects w h o pre mat urel y disc o nti n u e t he st u d y will be e nc o ura ge d t o c o m plete t he 
Fi nal/ E T st u d y visit .
Reas o na ble eff orts will be ma de t o c o ntact s u bjects w h o are l ost t o f oll o w - u p. T hese eff orts m ust 
be d oc u me nte d i n t he s u bject’s file . 
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 2 2 of 4 4
C O N FI D E N TI A L
T he sp o ns or has t he ri g ht t o ter mi nate t he st u d y  at a n y ti me i n case of S A Es or if s pecial 
circ u msta nces c o ncer ni n g t he t he c o m pa n y itself occ ur . I n t his e ve nt, t he In vesti gat or(s) will be 
i nf or me d of t he reas o n f or st u d y ter mi nati o n.
Met h o d of C o nti n ui n g alre a d y R a n d o mize d S u bject fr o m Pre vi o us st u d y
O nce a SI N has bee n assi g ne d, t hat n u m ber m ust n ot be use d a gai n f or a n y ot her s u bject (e. g., 
w he n a s u bject is wit h dra w n fr o m t he st u d y, t hat s u bject’s SI N m ust n ot be re use d f or a n y ot her 
s u bject). S ee S ecti o n 9.
Bli n di n g
Al l atte m pts will be ma de t o kee p t he i n vesti gati ve site staff a n d s u bjects bli n de d t o t he st u d y 
treat me nt fr o m st u dy R D. 0 6. S P R. 1 1 2 1 9 9 t hr o u g h o ut t he st u d y. Me m bers of t he st u d y ce nter 
staff, i ncl u di n g t he pr oce d ure o perat or, will n ot ha ve access t o t he ra n d o mize d treat me nt 
assi g n me nt of s u bjects i n R D. 0 6. S P R. 1 1 2 1 9 9 . It w o ul d be e xtre mel y u nli kel y f or a sit uati o n t o 
occ ur i n w hic h t he bli n d w o ul d nee d t o be br o ke n d uri n g t his st u d y .  The In vesti gat or or s u b-
i n vesti gat or s h o ul d c o ns ult wit h t he me dical m o nit or a n d t he S p o ns or i n cases w here it be 
re q uire d t o brea k t he bli n d.  
W he n t he bli n di n g c o de is br o ke n, t he reas o n m ust be f ull y  d oc u me nte d. If t he c o de is br o ke n b y 
t he In vesti gat or, t he s u bject m ust be wit h dra w n fr o m t he st u d y. T he re p orti n g re q uire me nts f or 
u n bli n di n g are t he sa me f or re p orti n g a n S A E. See als o Secti o n 9. 2. 1. 3
T he ra n d o mizati o n c o de will re mai n bli n de d t o all st u d y  sites a n d st u d y tea m me m bers u ntil 
c o m pleti o n of t he st u d y a n d after t he st u d y data base has bee n l oc ke d. Initial treat me nt peri o d 
res ults will be a nalyz e d after all s u bjects ha ve eit her c o m plete d Visit 6 , or ha ve wit h dra w n or 
bee n disc o nti n ue d fr o m t he st u d y  bef ore Visit 6. H o we ver , pers o n nel fr o m s p o ns or, C R O, a n d 
i n vesti gati o nal sites directl y i n v ol ve d wit h t he o n g oi n g c o n d uct of t he st u d y will n ot ha ve access 
t o a n y i nf or mati o n t hat ma y lea d t o u n bli n di n g f or t he o n g oi n g rec urre nce e val uati o n d uri n g t he 
f oll o w- u p st u d y.
Pri or a n d C o nc o mit a nt T her a p y
C o nc o mita nt t hera pies / me dicati o ns are defi ne d as f oll o ws:

A n y  e xisti n g t hera pies o n g oi n g at t he ti me of t he scree ni n g visit,

A n y  c ha n ges t o e xisti n g t hera pies (s uc h as c ha n ges i n d ose, f or m ulati o n, or a p plicati o n 
fre q ue nc y) d uri n g t he c o urse of t he st u d y, or

A n y  ne w t hera pies recei ve d b y t he s u bject si nce t he scree ni n g visit 
T he f oll o wi n g 2 cate g ories are t o be c o nsi dere d f or pri or a n d c o nc o mita nt t hera pies: 

Dr u gs/ T hera pies i ncl u de b ut are n ot li mite d t o prescri pti o n, o ver-t he-c o u nter, birt h c o ntr ol 
pills/ patc hes/ h or m o nal de vices, vita mi ns, m oist urizers, s u n scree ns, her bal 
me dici nes/s u p ple me nts, a n d h o me o pat hic pre parati o ns.

Me dical a n d s ur gical pr oce d ures
(e. g., p h ot ot hera p y, e x o d o ntia). Pr oce d ures w h ose s ole 
p ur p ose is dia g n osis ( n o n -t hera pe utic) are n ot i ncl u de d.
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 2 3 of 4 4
C O N FI D E N TI A L
Pri or a n d c o nc o mita nt t hera pies f or dr u gs/t hera pies or f or me dical/s ur gical pr oce d ures are t o be 
rec or de d i n t he a p pr o priate e C R F. 
C o nc o mita nt t hera pies are t o be rec or de d, re vie we d, a n d u p date d at eac h visit. 
A n y  ne w c o nc o mita nt t hera p y or m o dificati o n of a n e xisti n g t hera p y ma y be li n ke d t o a n A E. I n 
s uc h cases, a c orres p o n di n g A E f or m s h o ul d be c o m plete d t o acc o u nt f or t he ne w t hera p y or 
c ha n ge i n t hera p y, i n w hic h case t he me dicati o n will be li n ke d t o a n ite m i n t he s u bject’s me dical 
hist or y .
T he t hera pies liste d i n Ta ble 2 are c o nsi dere d pr o hi bite d i n t he treat me nt areas beca use t he y  m a y 
i nterfere wit h t he lesi o n assess me nt s.
T a ble 2 : F or bi d de n Tre at me nts i n Tre at me nt Are a
Tre at me nt(s)
T o pical: 5 -fl u or o uracil, dicl ofe nac, i mi q ui m o d, reti n oi ds, al p ha-h y dr o x y  aci d, salic ylic aci d 
oi nt me nt, i n ge n ol me b utate
S ur gical: elli ptical e xcisi o n, e xcisi o n a n d rec o nstr ucti ve s ur ger y , M o hs’ micr o gra p hic s ur ger y, 
c he mical peels/c he m os ur ger y , cr yos ur ger y , der ma brasi o n
P h ot o d y na mic t hera p y
Electr oc oa g ulati o n t hera p y
Ra di ot hera p y of t he s ki n
Laser t hera p y
I n vesti gati ve t hera pies f or acti nic kerat osis
S y ste mic reti n oi ds
I m m u n os u p pressi ve a ge nts s uc h as gl uc oc ortic oi ds, c yt ostatic a ge nts, a nti b o dies, dr u gs acti n g 
o n i m m u n o p hili ns, i nterfer o n, T N F bi n di n g pr otei ns, m y c o p he n olate m ofetil, or bi ol o gics 
I n case t he s u bject is usi n g t o pical t hera py liste d i n Ta ble 2 o n ot her area s t ha n o n t he 
d oc u me nte d lesi o ns, t he I nvesti gat or will re mi n d hi m/ her t o pa y strict atte nti o n t o n ot a p pl y a ny 
of t hese t hera pies o n t he treat me nt areas.
If pr o hi bite d t hera pies bec o me a necessar y treat me nt f or t he safety or best i nterest of t he s u bject,
t he me dical m o nit or s h o ul d be n otifie d t o disc uss p ossi ble alter nati ves pri or t o a d mi nistrati o n of a 
pr o hi bite d t hera p y. It is als o p ossi ble t hat t he use of pr o hi bite d thera pies ma y  res ult i n early 
ter mi nati o n of a s u bject.
If a s u bject recei ves pr o hi bite d t hera py d uri n g t he cli nical st u d y, t he me dical m o nit or s h o ul d be 
n otifie d t o disc uss t he si g nifica nce a n d t he m o dalities t o be use d f or t he su bject t o c o nti n ue i n t he 
cli nical st u d y.
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 2 4 of 4 4
C O N FI D E N TI A L
8. 4  
D ur ati o n of S u bject P artici p ati o n
T he e x pecte d d urati o n f or eac h s u bject’s partici pati o n i n t he st u d y will be a p pr o xi matel y 4 0 wee ks.
E arl y Ter mi n ati o n Visit
S u bjects ma y  disc o nti n ue fr o m t he st u d y at a n y ti me.
S u bjects w h o pre mat urel y disc o nti n ue fr o m t he st u d y  s h o ul d u n der g o fi nal st u d y assess me nts.
8. 5
U nsc he d ule d Visit
T he s u bject s h o ul d be re mi n de d t o a d here t o t he st u d y sc he d ule. U nsc he d ule d visits are defi ne d 
as visits occ urri n g o utsi de of t he visit wi n d o w.
Assess me nts t o be c o n d ucte d at t he u nsc he d ule d visit will de pe n d o n t he reas o n f or t he visit a n d 
will be c o n d ucte d at t he discreti o n of t he pri nci pal i n ves ti gat or. A n y of t he 
pr oce d ures/assess me nts liste d i n Secti o n 8. 1. 2 ma y be c o n d ucte d, b ut n ot all are re q uire d.
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 2 5 of 4 4
C O N FI D E N TI A L
9
S T U D Y A S S E S S M E N T S
A writte n , si g ne d Inf or me d C o nse nt F or m (I C F) , a n d Healt h I ns ura nce P orta bilit y  a n d 
Acc o u nta bil it y Act ( HI PA A) a ut h orizati o n is re q uire d bef ore a n y st u d y- relate d pr oce d ures are 
perf or me d.
U p o n pr o visi o n of t he si g ne d I C F, eac h s u bject will be assi g ne d a u ni q ue differe nt SI N fr o m t he 
SI N i n pr ot oc ol R D. 0 6. S P R. 1 1 2 1 9 9 . F or t he d urati o n of t he cli nical st u d y, t he s u bject will be 
i de ntifie d usi n g t he ne w SI N i n all d oc u me ntati o n a n d disc ussi o n f or t his pr ot oc ol.
9. 1
Effic ac y Assess me nts
E val uati o ns are t o be perf or me d b y t he sa me I n vesti gat or f or a gi ve n s u bject t hr o u g h o ut the 
st u d y, w he ne ver p ossi ble. T he I n vesti gat or is t o re mai n bli n de d t o t he st u d y treat me nt fr o m st u dy 
R D. 0 6. S P R. 1 1 2 1 9 9 . 
Lesi o n Res p o nse
T he lesi o ns treate d i n t he pi v otal trial will be e val uate d f or re occ urre nce.  A n y lesi o ns t hat ha ve 
rec urre d will be e val uate d f or se verit y acc or di n g t o t he gra di n g scale i n Ta ble 3
T a ble 3: Lesi o n S e verit y G r a de S c ale
Gr a de
Se verit y
Descri pti o n
Gra de 1
Mil d
S li g htl y pal pa ble, better felt t ha n see n
Gra de 2
M o derate
M o deratel y t hic k, easil y felt a n d see n
Gra de 3
Se vere
V er y t hic k a n d/ or o b vi o us acti nic kerat oses
T he In vesti gat or will be as ke d at Visit s 2 a n d 3 / E T t o i de ntif y eac h lesi o n treate d pre vi o usl y, a n d 
t he lesi o n res p o nse as a C R or a n o n -C R, as descri be d i n Ta ble 4 .
T a ble 4 : Lesi o n R es p o nse
Res p o nse
Sc ore
Descri pti o n
C o m plete res p o nse ( C R)
1
C o m plete disa p peara nce of t he lesi o n, vis uall y  
a n d b y pal pati o n
N o n c o m plete re p o nse (n o n -C R)
0
N o n -c o m plete disa p peara nce of t he lesi o n
If all of t he treate d lesi o ns i n t he treat me nt area are assesse d t o be C R at Visits 2 a n d 3 of t his 
st u d y ( 26 a n d 5 2 wee ks after t he last D L -P D T sessi o n), t he s u bject will be assesse d a s a s u bject 
C R a n d will be dee me d t o ha ve n o rec urre nce. If a n y of t he treate d lesi o ns i n t he treat me nt area 
are assesse d t o be n o n-C R, t h ose lesi ons are rec urre nces; t he s u bject will be assesse d as a n o n -
c o m plete res p o n der or dee me d as a s u bject rec urre nce . 
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 2 6 of 4 4
C O N FI D E N TI A L
9. 2
S afet y Assess me nts
Safet y  assess me nts will be c o n d ucte d f or all s u bjects at Visit 1 ( u p o n si g ni n g of t he I C F) a n d at 
e ver y s u bse q ue nt visit.
A d verse e ve nts ( A Es), Treat me nt -e mer ge nt A Es ( T E A Es), relate d t o t he st u d y treat me nt i n st u d y 
R D. 0 6. S P R. 1 1 2 1 9 9 . a n d seri o us A Es ( S A Es) will be rec or de d d uri n g eac h visit, s h o ul d t he y 
occ ur.
A d verse E ve nt Defi niti o n
A n A E is defi ne d as a n y u nt o war d me dical occ urre nce i n a cli nical st u d y , i n w hic h a s u bject is 
a d mi nistere d a me dici nal pr o d uct t hat d oes n ot necessaril y ha ve a ca usal relati o ns hi p wit h t his 
treat me nt. A n A E ca n t heref ore be a n y u nfa v ora ble a n d u ni nte n de d si g n (i ncl u di n g a n a b n or mal 
la b orat or y fi n di n g), sy m pt o m, or disease te m p orall y  ass ociate d wit h t he use of a me dici nal  
pr o d uct, w het her or n ot it is relate d t o t he me dici nal pr o d uct . T his i ncl u des a n e xacer bati o n of 
pre -e xisti n g c o n diti o ns or e ve nts, i nterc urre nt ill nesses, dr u g i nteracti o n, or t he si g nifica nt 
w orse ni n g of t he i n dicati o n u n der i n vesti gati o n, t hat is n ot rec or de d else w here i n t he eC R F u n der 
s pecific efficac y assess me nts. 
N ote(s): 

A n y  ne w si g n or sy m pt o m re p orte d b y t he s u b ject t hat a p pears after acci de ntal or 
i nte nti o nal o ver d ose or mis use s h o ul d be re p orte d as a n A E.

W he ne ver p ossi ble, a dia g n osis s h o ul d be re p orte d o n t he A E f or m, i nstea d of si g ns, 
s ym pt o ms , or a b n or mal la b orat or y  val ues. 
Pre g na nc y  is n ot t o be c o nsi dered a n A E 

Eac h ne w e pis o de of a c hr o nic disease (e . g., ha y fe ver, aller g y) fr o m t he ti me t he I C F is 
si g ne d s h o ul d be re p orte d as a ne w A E.
T he In vesti gat or or desi g nee will re p ort all A Es t hat occ ur fr o m t he ti me t he I C F is si g ne d u ntil 
t he e n d of t he st u dy. T he s p o ns or/ C R O s h o ul d be i nf or me d if t he I n vesti gat or bec o mes a ware of 
a n y safety i nf or mati o n t hat a p pears t o be relate d t o t he st u d y treat me nt of st u d y 
R D. 0 6. S P R. 1 1 2 1 9 9 , e ve n after t he s u bject has c o m plete d t he cli nical st u d y.
At eac h p ost -e nr oll me nt visit, t he In vesti gat or ( or s u b-i n vesti gat or) will q uesti o n t he s u bject 
a b o ut hi s/ her e x perie nci n g of A Es , usi n g a n o pe n n o n -pers uasi ve q uesti o n t o elicit re p orti n g of 
A Es (f or e xa m ple, “ Ha ve yo u n otice d a n y  c ha n ge i n yo ur healt h si nce t he last visit?” ). Directe d 
q uesti o ni n g a n d e xa mi nati o n will t he n be perf or me d as a p pr o priate. 
A n y  A E occ urri n g d uri n g t he A E re p orti n g peri o d will be rec or de d i m me diatel y  i n t he s o urce 
d oc u me nt a n d descri be d o n t he A d verse E ve nt F or m (“ A E F or m”) al o n g wit h t he da te of o nset, 
seri o us ness, se verit y, relate d ness or ca usalit y a n d o utc o me, wit h o ut o mitti n g a n y re q ueste d a n d 
k n o w n i nf or mati o n. A d diti o nal i nf or mati o n will be re q ueste d u n der certai n circ u msta nces.
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 2 7 of 4 4
C O N FI D E N TI A L
A d verse e ve nts assesse d as relate d t o t he st u d y treat me nt fr o m t he pre vi o us st u d y will be 
m o nit ore d u ntil t he y  ha ve res ol ve d or reac he d a sta ble c o n diti o n. Ot her A Es will be m o nit ore d 
u ntil t he last visit if t he y  ha ve n ot res ol ve d or reac he d a sta ble c o n diti o n. If n ot res ol ve d at ti me of 
L T F U st u d y c o m pleti o n, sites will c o nti n ue t o c o ntact patie nt o n a re g ular basis u ntil res ol ve d or 
sta ble.
T he In vesti gat or will o btai n a n d mai ntai n all perti ne nt me dical rec or ds i n t he s u bject’s files, 
i nf or mati o n a n d me dical j u d g me nt fr o m c ollea g ues w h o assiste d i n t he s u bject’s o versi g ht. If 
necessar y , t he In vesti gat or will c o ntact t he s u bject’s pers o nal p h ys icia n or h os pital staff t o o btai n 
f urt her details.
Assess me nt of Se verit y
Eac h A E will be assi g ne d a cate g or y  b y t he In vesti gat or as f oll o ws:
Mil d :  
An A E t hat is easil y  t olerate d b y t he s u bject, ca uses mi ni mal disc o mf ort, a n d d oes 
n ot i nterfere wit h e ver y d a y  acti vities.
M o derate :  
An A E t hat is s ufficie ntl y  disc o mf orti n g t o i nterfere wit h n or mal e ver yd a y  
acti vities; i nter ve nti o n ma y be nee de d.
Se vere :  
A n A E t hat pre ve nts n or mal e ver y d a y  acti vities; treat me nt or ot her i nter ve nti o n 
us uall y  nee de d.
If t here is a c ha n ge i n se verit y of a n A E, it m ust be rec or de d as a se parate e ve nt.
Assess me nt of C a us alit y
T he In vesti gat or will ha ve deter mi ne d t hat t here is a reas o na ble ca usal relati o ns hi p bet wee n t he 
occ urre nce of t he A E, a n d e x p os ure t o t he st u d y dr u g (i .e.,
M A L crea m or ve hicle crea m ) a n d/ or 
st u d y pr oce d ure (e. g., ill u mi nati o n, bl o o d sa m ple c ollecti o n) i n st u d y R D. 0 6.S P R. 1 1 2 1 9 9.
F or A Es arisi n g d u ri n g t his st u d y, me dical j u d g me nt s h o ul d be use d t o deter mi ne t he relati o ns hi p, 
c o nsi deri n g all rele va nt fact ors i ncl u di n g t he patter n of t he reacti o n, te m p oral relati o ns hi ps, 
rele va nt me dical hist or y, a n d c o nf o u n di n g fact ors s uc h as c o-me dicati o n or c o nc u rre nt diseases.
T he e x pressi o n “reas o na ble ca usal relati o ns hi p” is mea nt t o c o n ve y  i n ge neral t hat t here are facts 
or ar g u me nts t o s u g gest a ca usal relati o ns hi p (I C H E 2 A, Secti o n III A 1).
T he relati o ns hi p assess me nt f or a n A E is t o be c o m plete d usi n g t he f oll o wi n g defi niti o ns as a 
g ui deli ne f or all A Es occ urri n g d uri n g t his cli nical st u d y:
Re as o n a ble p ossi bilit y:
Acc or di n g t o t he re p orti n g In vesti gat or, t here is a reas o na ble p ossi bilit y  (i. e., s u g gesti ve e vi de nce 
or ar g u me nts) t hat t here is a ca usal relati o ns hi p irres pecti ve of t he d ose a d mi nistere d:

Bet wee n t he st u d y dr u g ( met h y l a mi n ole vi n ulate h ydr oc h oli de 1 6. 8 % crea m or ve hicle 
crea m) a n d t he A E, a n d/ or
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 2 8 of 4 4
C O N FI D E N TI A L

Bet wee n t he cli nical st u d y pr ot oc ol p r oce d ure (e. g., t o pical bac k gr o u n d t hera py , bl o o d 
sa m ple c ollecti o n) a n d t he A E
N o Re as o n a ble P ossi bilit y:
N o s u g gesti ve e vi de nce or ar g u me nts ca n be i de ntifie d re gar di n g a ca usal relati o ns hi p bet wee n 
t he st u d y dr u g or t he cli nical st u d y pr ot oc ol pr oce d ure a n d t he A E.
F oll o w -u p of A d verse E ve nts
All In vesti gat ors s h o ul d f oll o w - u p wit h s u bjects wit h relate d A Es u ntil t he e ve nt is res ol ve d or 
u ntil, i n t he o pi ni o n of t he I n vesti gat or, t he e ve nt is sta bilize d or deter mi ne d t o be c hr o nic. 
Details of A E res ol uti o n m ust be d oc u me nte d i n t he e C R F.
D oc u me nt ati o n a n d Re p orti n g of A d verse E ve nts
A d verse e ve nts s h o ul d be re p orte d a n d d oc u me nte d i n acc or da nce wit h t he pr oce d ures o utli ne d 
bel o w . All A Es occ urri n g d uri n g t he st u d y m ust be d oc u me nte d o n t he rele va nt e C R F pa ges . T he 
f oll o wi n g data s h o ul d be d oc u me nte d f or eac h A E:

D escri pti o n of t he s y m pt o m /e ve nt

Classificati o n of “seri o us” or “n ot seri o us ”

Se verit y

Date of first occ urre nce a n d dat e of res ol uti o n (if a p plica ble)

Ot her acti o n ta ke n

Ca usal relati o ns hi p

O utc o m e of e ve nt ( u n k n o w n, rec o vere d, n ot yet rec o vere d, rec o vere d wit h se q uelae, deat h 
[ wit h date a n d ca use re p orte d])
9. 2. 1. 1
Seri o u s A d verse E ve nts
A n S A E is a n y  u nt o war d me dical occ urre nce or effect t hat, at a n y d ose,

Res ults i n deat h.

Is life-t hreate ni n g (a n A E is life-t hreate ni n g if t he s u bject was at i m me diate ris k of deat h fr o m 
t he e ve nt as it occ urre d, i.e., it i ncl u des a reacti o n t hat mi g ht ha ve ca use d deat h if it ha d 
o cc urre d i n a m ore seri o us f or m).

Re q uires or pr ol o n gs i n patie nt h os pitalizati o n. ( C o m plicati o ns occ urri n g d uri n g 
h os pitalizati o n are A Es a n d S A Es , if t he y ca use pr ol o n gati o n of t he c urre nt h os pitalizati o n. 
I n patie nt h os pitalizati o n is c o nsi dere d t o ha ve occ urre d if t he s u bject has ha d t o sta y f or a 
ni g ht at t he h os pital. T he criteri o n f or pr ol o n ga ti o n of h os pitalizati o n is als o defi ne d as a n 
e xtra ni g ht at t he h os pital. H os pitalizati o n ma y  n ot c o nstit ute s ufficie nt gr o u n ds t o be 
c o nsi dere d as a n S A E , if it is s olel y f or t he p ur p ose of dia g n ostic tests [e ve n if relate d t o a n 
A E], electi ve h os pitaliz ati o n f or a n i nter ve nti o n t hat was alrea d y pla n ne d bef ore s u bject 
e nr oll me nt i n t he cli nical st u d y, a d missi o n t o a da y care facilit y, s ocial a d missi o n [e.g. , if t he 
s u bject has n o place t o slee p], or a d mi nistrati ve a d missi o n [e.g. , f or a ye arl y e xa mi nati o n]. 
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 2 9 of 4 4
C O N FI D E N TI A L
T he details of s uc h h os pitalizati o ns m ust be rec or de d o n t he me dical hist or y or p h ys ical 
e xa mi nati o n eC R F .)

Res ults i n persiste nt or si g nifica nt disa bilit y /i nca pacit y. ( A n A E is i nca pacitati n g or disa bli n g 
if it res ults i n a s u bsta ntial a n d/ or per ma ne nt disr u pti o n of t he s u bject’s a bilit y  t o carry o ut 
n or mal life f u ncti o ns .)

Res ul ts i n a c o n ge nital a n o mal y/ birt h defect.

A n i m p orta nt me dical e ve nt t hat ma y  n ot res ult i n deat h, be life-t hreate ni n g, or re q uire 
h os pitalizati o n, ma y  be c o nsi dere d a n S A E w he n, base d u p o n a p pr o priate me dical j u d g me nt, 
t he e ve nt ma y je o par dize t he safety of t he s u bject, a n d ma y  re q uire me dical or s ur gical 
i nter ve nti o n t o pre ve nt 1 of t he o utc o mes liste d a b o ve i n t his defi niti o n. E xa m ples of s uc h 
e ve nts are i nte nsi ve treat me nt i n a n e mer ge nc y r o o m or at h o me f or aller gic br o nc h os pas m, 
bl o o d d y scrasia, or c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n.
9. 2. 1. 2
A d verse E ve nts of S peci al I nterest ( A E SIs)
T here are n o A E SI s i n t his st u d y as t here is n o treat me nt or i nter ve nti o n.
9. 2. 1. 3
Pr oce d ure f or Re p orti n g a Seri o us A d verse E ve nt
F or a n y S A E occ urri n g d uri n g t he cli nical st u d y, re gar dless of w het her or n ot relate d t o t he st u d y 
dr u g a n d/ or pr oce d ure, t he In vesti gat or m ust:
1.
Ta ke pr o m pt a n d a p pr o priate me dical acti o n, if necessar y . T he safety of t he s u bject is t he 
first pri orit y.
2.
E ns ure t hat t he e ve nt is e val uate d as a n S A E. I mme diatel y n otif y ( wit hi n 2 4 h o urs of 
recei pt of t he e ve nt ) t he 
 Safety a n d P har mac o vi gila nce gr o u p of a n S A E 
re p ort, by e mail or fa x:
F a x N u m ber : 
S afet y e m ail: 
N ote : Im me diate S A E re p orti n g is re q uire d b y  t he In vesti gat or if it occ urs d uri n g t he cli nical 
st u d y, w het her or n ot t he e ve nt is c o nsi dere d t o be relate d t o t he i n vesti gati o nal pr o d uct.
T he de m o gra p hics, me dical hist or y , dr u gs/t hera pies, a n d me dical a n d s ur gical pr oce d ures f or ms 
m ust als o be a vaila ble f or re vie w i n t he eC R F, at t hat ti me.
3.
Se n d a n y  rele va nt i nf or mati o n or a n o n ymize d me dical rec or ds t o t he 
 Safety 
a n d P har mac o vi gila nce gr o u p (see c o ntact details a b o ve), wit hi n 2 4 h o urs of recei pt of t his 
rele va nt i nf or mati o n.
4.  
M o nit or a n d rec or d t he pr o gress of t he e ve nt u ntil it res ol ves or reac hes a sta ble c o n diti o n, 
wit h or wit h o ut se q uelae. F or all a d diti o nal f oll o w -u p e val uati o ns, c o m plete a n u p date d 
S A E re p ort wit hi n 2 4 h o urs of recei pt of t he u p date d i nf or mati o n.
5.  
O btai n a n d mai ntai n i n t he s u bject files all perti ne nt me dical rec or ds, i nf or mati o n, a n d 
me dical j u d g me nts fr o m c ollea g ues w h o partici pate i n t he treat m e nt a n d f oll o w -u p of t he 
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
P P D
P P D
P P D
P P D

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 3 0 of 4 4
C O N FI D E N TI A L
s u bject. If necessar y, c o ntact t he s u bject’s pers o nal p h ysicia n or h os pital staff t o o btai n 
f urt her details.
6.
W he n t he o utc o me of t he e ve nt is k n o w n, c o m plete a n u p date d S A E re p ort, if a p pr o priate.
7.
Pr o m pt n otificati o n of S A Es b y  the In vesti gat or is esse ntial s o t hat le gal o bli gati o ns a n d 
et hical res p o nsi bilities t o war d t he safet y of s u bjects are met. T he S p o ns or has a le gal 
res p o nsi bilit y t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d ot her re g ulat or y a ge ncies 
a b o ut t he safet y of a pr o d uct u n der cli nical i n vesti gati o n. T he S p o ns or or its dele gate (i . e., 
t he C R O) will c o m pl y wit h c o u ntr y-s pecific re g ulat or y re q uire me nts relati n g t o safety 
re p orti n g t o re g ulat or y a ut h orities, Instit uti o nal Re vie w B oar d (I R B)/I n de pe n de nt Et hics 
C o m mittee (I E C) a n d In vesti gat ors. I n vesti gat or safety re p orts are pre pare d f or S U S A Rs 
acc or di n g t o l ocal re g ulat or y re q uire me nts, a n d are f or war de d t o In vesti gat ors as necessar y.
A n In vesti gat or w h o recei ves a n In vesti gat or safet y  re p ort descri bi n g an S A E(s) or ot her s pecific 
safety i nf or mati o n (e . g., s u m mar y or listi n g of S A Es) fr o m t he S p o ns or or its dele gate (i .e., 
t he C R O) will file it acc or di n gl y (i .e., wit hi n t he Trial Master File [ T M F]), a n d will n otif y 
t he IR B/I E C, if a p pr o priate acc or di n g t o l ocal re q uire me nts.
8.
C o m pl y  wit h t he a p plica ble re g ulat or y re q uire me nt(s) relate d t o t he re p orti n g of S A Es t o 
t he IR B/I E C.
9. 2. 1. 4
Pr oce d ure f or Re p ort i n g Pre g n a ncies
A pre g na nc y  occ urri n g d uri n g t his cli nical st u d y, w here t he fet us w o ul d n ot ha ve bee n e x p ose d t o 
t he st u d y dr u g beca use of t he te m p oral ga p fr o m st u d y dr u g e x p os ure t o t he be gi n ni n g of t his 
st u d y ( 1 2 wee ks a n d > 7 half lifes) will be m o nit ore d n o net heless , i n or der t o e ns ure t he c o m plete 
c ollecti o n of safet y data. If a s u bject bec o mes pre g na nt, t he i n vesti gat or m ust:
1.
C o nti n ue t o f oll o w t he s u bject i n t he cli nical st u d y. T he s u bject will n ot be recei vi n g a n y 
i nter ve nti o n i n t his st u d y. 
2.
C o m plete as f ull y as p ossi ble t he Pre g na nc y  S ur veilla nce F or m – Part I : Hist or y a n d Start 
of Pre g na nc y . Se n d b y e mail or fa x al o n g wit h t he e xit f or m wit hi n 2 4 h o urs of recei pt of 
t he i nf or mati o n, t o t he 
 Safet y a n d P har mac o vi gila nce gr o u p. Refer t o 
Secti o n 9. 2. 1. 3 .
N ote: I mme diate pre g na nc y  re p orti n g is re q uire d b y t he In vesti gat or if it occ urs d uri n g t he 
cli nical st u d y.
3.
M o nit or a n d rec or d t he pr o gress of t he pre g na nc y  u ntil its o utc o me. C o ntact t he s u bject’s 
re g ular p hys icia n ( ge neral practiti o ner or g ynec ol o gist) or h os pital staff t o o btai n f urt her 
details , a n d as k f or re g ular f oll o w -u p i nf or mati o n.
4.
Pr o vi de tri -m o nt hl y  u p dates u ntil t he fi nal o utc o me of t he pre g na nc y , b y c o m pleti n g t he 
Pre g na nc y  S ur veilla nce F or m – Part II: C o urse a n d O utc o me of Pre g na nc y . F or all 
a d diti o nal f oll o w -u p e val uati o ns, se n d t he f or m b y e mail or fa x t o t he 
 Safety 
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
P P D
P P D

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 3 1 of 4 4
C O N FI D E N TI A L
a n d P har mac o vi gi la nce gr o u p wit hi n 2 4 h o urs of recei pt of t he i nf or mati o n. If t he s u bject 
ca n n o l o n ger be reac he d (i .e., l ost t o f oll o w-u p), d oc u me ntati o n of t he 
n o n- res p o nse/c o ntact wit h 2 p h o ne calls a n d a letter (certifie d wit h ret ur n recei pt) is 
re q uire d.
5.
At t he o utc o me of t he pre g na nc y , c o m plete as f ull y as p ossi ble t he Pre g na nc y S ur veilla nce 
F or m – Part II: C o urse a n d O utc o me of Pre g na nc y . Pri nt a n d se n d t he f or m b y e mail or fa x 
t o t he 
 Safet y a n d P har mac o vi gila nce gr o u p wit hi n 2 4 h o urs of re cei pt of t he 
i nf or mati o n.
6.
If t he pre g na nc y lea ds t o a n a b orti o n (i.e., v ol u ntar y a b orti o n, s p o nta ne o us a b orti o n, or 
t hera pe utic a b orti o n), i n uter o deat h , or c o n ge nital a n o mal y , f oll o w t he pr oce d ure f or 
declarati o n of /re p orti n g a n S A E (see Secti o n 9. 2. 1. 3 ).
9. 2. 1. 5
U ne x pecte d A d verse Re acti o ns
A n u ne x pecte d a d verse reacti o n is a n y u nt o war d a n d u ni nte n de d res p o nse t hat is relate d t o t he 
a d mi nistrati o n of t he st u d y  dr u g at a n y d ose, t he nat ure or se verity of w hic h is n ot c o nsiste nt wit h 
t he a p plica ble pr o d uct i nf or mati o n (e. g., refere nce safety i nf or mati o n i n t he I B f or M A L 1 6. 8 % 
crea m , st u d y pr ot oc ol ).
T he S p o ns or or its dele gate ( i.e.,
) will c o m pl y wit h c o u ntr y-s pecific re g ulat or y 
re q uire me nts relati n g t o safet y re p orti n g t o re g ulat or y a ut h orities, I R B/I E C , a n d In vesti gat ors. 
I n vesti gat or safet y re p orts are pre pare d f or S U S A Rs acc or di n g t o l ocal re g ulat or y re q uire me nts 
a n d s p o ns or p olic y , a n d are f or war de d t o In vesti gat ors as necessar y .
A n In vesti gat or w h o r ecei ves a n In vesti gat or safet y  re p ort descri bi n g an S A E(s) or ot her s pecific 
safety i nf or mati o n (e . g., s u m mar y or listi n g of S A Es) fr o m t he S p o ns or or its dele gate ( i.e., 
) will file it acc or di n gl y (i.e., wit h t he T M F), a n d will n otif y t he IR B /IE C, if 
ap pr o priate , acc or di n g t o l ocal re q uire me nts.
Pre g a nc y Testi n g
All w o me n of c hil d beari n g p ote ntial will ha ve a uri ne pre g na nc y  test at V isit 1 a n d U P Ts at 
s u bse q ue nt visits at Visits 2 a n d 3, acc or di n g t o Secti o n 8. 1. 2 .
If t he res ult of a U P T is p ositi ve, it m ust be c o nfir me d wit h a ser u m pre g na nc y  test.
S u bjects wit h a p ositi ve ser u m pre g na nc y  test res ult at Visit 1 will be f oll o we d i n t his st u d y .
U ri ne pre g na nc y tests wit h a se nsiti vit y  < 2 5 I U/ L will be pr o vi ded t o t he st u d y ce nters f or use i n 
t he st u d y.
U ri ne pre g na nc y  tests will be perf or me d at t he st u d y ce nters, a n d all ot her sa m ples will be se nt t o 
t he ce ntral la b orat or y f or a nalys is.
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
P P D
P P D
P P D

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 3 2 of 4 4
C O N FI D E N TI A L
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
C CI

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 3 3 of 4 4
C O N FI D E N TI A L
1 0
S T A TI S TI C A L M E T H O D S
A statistical anal y sis p la n ( S A P) will be de vel o pe d as a se parate d oc u me nt. T he S A P will c o ntai n 
detaile d a n d tec h nical descri pti o n s of s pecific data c o n ve nti o ns, calc ulati o ns , a n d statistical 
pr oce d ures f or e xec uti n g t he a nal yses t hat are s pecifie d i n t his S ecti o n 1 0 of t he cli nical st u d y 
pr ot oc ol .
1 0. 1
St atistic al a n d A n al ytic al P l a ns
D at a sets or P o p ul ati o ns A n al y ze d
1 0. 1. 1. 1
I nte nt-t o-Tre at P o p ul ati o n
N ot a p plica ble.
1 0. 1. 1. 2
S afet y P o p ul ati o n
T he safet y p o p ulati o n will c o nsist of all e nr olle d s u bjects a n d will be use d f or all t he effica c y a n d 
safety a nal yses.
1 0. 1. 1. 3
Per Pr ot oc ol P o p ul ati o n
N ot a p plica ble.
De m o gr a p hic a n d Ot her B aseli ne C h ar acteristics
S u bject dis p ositi o n, de m o gra p hics, baseli ne c haracteristics, pre vi o us t h era pies, a n d c o nc o mita nt 
t hera pies b y  treat me nt will be s u m marize d b y descri pti ve statistics.
Effic ac y A n al ysis
B ot h pri mar y  a n d sec o n dar y e n d p oi nts will be e val uate d f or t he safety p o p ulati o n.
All efficac y  varia bles will be s u m marize d b y treat me nt at eac h visit.
T he cate g orical varia bles will be s u m marize d b y  fre q ue nc y an d perce nta ge f or eac h res p o nse 
cate g or y ( N, %). T he c o nti n u o us varia bles will be s u m marize d usi n g descri pti ve statistics 
( n u m ber of o bser vati o ns, mea n, me dia n, mi ni m u m, ma xi m u m, a n d sta n dar d de viati o n ) f or t he 
data c ollecte d at eac h visit.
F urt her details o n efficac y  a n al yses will be pr o vi de d i n t he S A P.
1 0. 1. 3. 1
Pri m ar y E n d p oi nt A n al ysis
T he pr o p orti o n of s u bjects wit h rec urre nce of a n y (≥1) cleare d treate d A K lesi o ns at 5 2 wee ks 
after t he last D L -P D T will be s u m marize d usi n g ta bles of fre q ue nc y . All s u bjects i n t he safet y 
p o p ulati o n wit h missi n g data will be classifie d as n o n -res p o n ders re gar dless of treat me nt 
all ocati o n. S u m maries b y treat me nt gr o u p will be prese nte d f or b ot h t he i m p ute d data a n d t he 
o bser ve d cases .
 
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
C CI

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 3 4 of 4 4
C O N FI D E N TI A L
 
1 0. 1. 3. 2
Pri m ar y E n d p oi nt Se nsiti vit y A n al ysis
N o se nsiti vit y  a nalys is is pla n ne d.
1 0. 1. 3. 3
Sec o n d ar y E n d p oi nts A n al ysis
T he pr o p orti o n of s u bjects wit h rec urre nce of a n y (≥1) cleare d treate d A K lesi o ns at 2 6 wee ks 
after t he last D L -P D T will be s u m marize d usi n g ta bles of fre q ue nc y . All s u bjects i n t he safety 
p o p ulati o n wit h missi n g data will be classifie d as n o n-res p o n ders re gar dless of treat me nt 
all ocati o n. S u m maries b y treat me nt gr o u p will be prese nte d f or b ot h t he i m p ute d data a n d t he 
o bser ve d cases .
 
 
T he perce nt rec urre nce of cleare d treate d A K lesi o ns at 2 6 a n d 5 2 wee ks after t he last D L -P D T 
treat me nt will be s u m marize d u si n g descri pti ve statistics. M issi n g c o u nts of cleare d treate d A K 
lesi o ns f or s u bjects i n t he safet y p o p ulati o n will be i m p ute d ass u mi n g t hat all baseli ne A K lesi o ns 
ha d rec urre d re gar dless of treat me nt all ocati o n. S u m maries b y  treat me nt gr o u p will be pres e nte d 
f or b ot h t he i m p ute d data a n d t he o bser ve d cases.
 
1 0. 1. 3. 4
S u b gr o u p A n al ysis
N o s u b gr o u p a nal ys is is pla n ne d.
S afet y A n al ysis
All safet y a nal ys es will be base d o n t he safet y p o p ulati o n.
S u m ma ries of all sa fety e n d p oi nts will be prese nte d.
1 0. 1. 4. 1
A d verse E ve nts
Treat me nt -e mer ge nt A Es , defi ne d as t h ose A Es occ urri n g after t he first a d mi nistrati o n of st u d y 
treat me nt u ntil t he last st u d y visit, fr o m st u d y RD. 0 6. S P R. 1 1 2 1 9 9 will be ta b ulate d i n fre q ue nc y 
ta bles b y  s yste m or ga n class a n d preferre d ter m base d o n t he Me dical Dicti o nar y  for Re g ulat or y 
Acti vities f or eac h st u d y p hase. A d diti o nal s u m mar y ta bles will be pr o vi de d f or S A Es, A Es relate d 
t o t he st u d y dr u g(s) (defi ne d as t he o nes wit h a reas o na ble p ossi bilit y  of ca usal relati o ns hi p wit h 
t he st u d y dr u g ), A Es relate d t o t he st u d y pr oce d ures ( defi ne d as t he o nes wit h a reas o na ble 
p ossi bilit y  of ca usal relati o ns hi p wit h t he st u d y pr oce d ures) , a n d A Es lea di n g t o treat me nt 
disc o nti n uati o n a n d st u d y wit h dra wal . F or a gi ve n A E, a s u bject will be c o u nte d o nce e ve n if he/s he 
has e x perie nce d m ulti ple e pis o des of t hat partic ular A E. 
I nteri m A n al yses
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
C CI
C CI
C CI

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 3 5 of 4 4
C O N FI D E N TI A L
A n i nteri m a nalys is is pla n ne d of all a vaila ble data fr o m t his st u d y , R D. 0 6. S P R. 1 1 5 2 3 0, at t he 
ti me of re g ulat or y s u b missi o n f or mar keti n g a p pr o val f or M A L crea m. 
H a n dli n g of Missi n g D at a
F or t he pr o p orti o n of s u bjects wit h rec urre nce at 2 6 a n d 5 2 wee ks after t he last D L -P D T 
treat me nt, all s u bjects i n t he safety p o p ulati o n wit h missi n g data will be classifie d as n o n -
res p o n ders re gar dless of treat me nt all ocati o n.
F or t he rec urre nce of cleare d treat e d A K lesi o ns at 2 6 a n d 5 2 wee ks after t he last D L -P D T 
treat me nt, missi n g c o u nts of cleare d treate d A K lesi o ns f or s u bjects i n t he safety p o p ulati o n will 
be i m p ute d ass u mi n g t hat all baseli ne A K lesi o ns ha d rec urre d re gar dless of treat me nt all ocati o n.
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 3 6 of 4 4
C O N FI D E N TI A L
1 0. 2
Dete r mi n ati o n of S a m ple S ize
T his l o n g-ter m f oll o w u p st u d y is pla n ne d t o gat her data a b o ut rec urre nces at ar o u n d t he 1 ye ar 
ti me p oi nt after t he D L-P D T treat me nts.
S u bjects w h o ac hie ve a c o m plete re s p o nse at Fi nal Visit of st u d y  R D. 0 6. S P R. 1 1 2 1 9 9 , 1 2 wee k s 
after t he last D L -P D T treat me nt, will be offere d t he o p p ort u nit y  t o be f oll o we d i n t his 9- m o nt h 
l o n g-ter m f oll o w-u p st u d y  t o ha ve treate d lesi o ns assesse d f or rec urre nce. T he sa m ple size 
calc ulati o n of st u d y  R D. 0 6. S P R. 1 1 2 1 9 9 was base d o n pr o vi di n g e n o u g h s u bjects t o e na ble t he 
detecti o n of a treat me nt differe nce i n t he pri mar y  e n d p oi nt of t hat st u d y a n d e ns uri n g 
a p pr o xi matel y 1 0 0 s u bjects ra n d o mize d t o M A L D L-P D T c o m plete t he l o n g -ter m f oll o w-u p 
st u d y.
A p pr o xi matel y  6 7 5 s u bjects are scree ne d f or a t otal of 5 7 0 s u bjects t o be ra n d o mize d ( 3 8 0 i n t he 
M A L  D L-P D T ar m a n d 1 9 0 i n t he ve hicle crea m D L -P D T ar m usi n g a  
 ra n d o mizati o n rati o)
i n t he st u d y R D. 0 6. S P R. 1 1 2 1 9 9 t o ha ve a p pr o xi matel y 1 0 0 s u bjects ra n d o mize d t o M A L  D L-
P D T c o m plete t his l o n g-ter m f oll o w-u p st u d y.
 
 
 
1 0. 3
Pr ot oc ol De vi ati o ns
Maj or de viati o ns are cate g orize d i nt o t he f oll o wi n g cate g ories:

Eli gi bilit y  de viati o ns (incl usi o n/ e xcl usi o n criteria)

N o nc o m plia nce wit h st u d y  pr oce d ures if t he c o nse q ue nce of n o nc o m plia nce w o ul d 
c o m pr o mise eit her t he s u bject’s safet y  a n d/ or t he st u d y i ntegrit y, pri mar y e n d p oi nt, a n d/ or is 
n ot i n li ne wit h G o o d Cli nical Practice (G C P )/IC H g ui deli nes

Use of p r o hi bite d c o nc o mita nt t hera pies
All pr ot oc ol de viati o ns will be i de ntifie d, e val uate d, a n d cl ose d bef ore t he res pecti ve data base 
l oc k (fi nal a nal ysis) a n d will be descri be d i n t he fi nal S A P a n d cli nical st u d y re p ort.
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0
C CI
C CI
C CI

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 3 7 of 4 4
C O N FI D E N TI A L
1 1
Q U A LI T Y A S S U R A N C E A N D Q U A LI T Y C O N T R O L
1 1. 1
A u dit a n d I ns pecti o n
St u d y  ce nters a n d st u d y d oc u me ntati o n ma y  be s u bject t o Q ualit y Ass ura nce a u dit d uri n g t he 
c o urse of t he st u dy b y t he sp o ns or or i ts n o mi nate d re prese ntati ve. I n a d diti o n, i ns pecti o ns ma y 
be c o n d ucte d b y re g ulat or y a ut h orities at t heir discreti o n.
1 1. 2
M o nit ori n g
Data f or eac h s u bject will be rec or de d o n eC R F s. Data c ollecti o n m ust be c o m plete d f or eac h 
s u bject w h o si g ns a n I C F a n d is a d mi nistere d st u d y dr u g.
I n acc or da nce wit h curre nt G C P a n d I C H g ui deli nes, t he st u d y  m o nit or will carr y o ut s o urce 
d oc u me nt verificati o n at re g ular i nter vals t o e ns ure t hat t he data c ollecte d i n t he eC R F are 
acc urate a n d relia ble. 
T he In vesti gat or m ust per m it t he m o nit or, t he IE C /IR B , t he S p o ns or’s i nter nal a u dit ors, a n d 
re prese ntati ves fr o m re g ulat or y a ut h orities direct access t o all st u d y-relate d d oc u me nts a n d 
perti ne nt h os pital or me dical rec or ds f or c o nfir mati o n of data c o ntai ne d wit hi n t he e C R Fs.
1 1. 3
Pers o n nel Tr ai ni n g
St u d y  m o nit ors a n d all rele va nt pers o n nel will be trai ne d bef ore st u d y i nitiati o n o n t he sta n dar d 
o perati n g pr oce d ures t o be use d i n t his cli nical st u d y, t he pr ot oc ol, a n d all st u d y-s pecific 
pr oce d ures. Tea m or ga nizati o n, c o m m u nicati o n, a n d o perati o nal iss ues will als o be disc usse d a n d 
a gree d u p o n.
I n vesti gat ors, e val uat ors, a n d st u d y c o or di nat ors will be trai ne d at t he Site I nitiati o n Visit b y  t he 
site cli nical researc h ass ociate.
It is t he pri nci pal i n vesti gat or’s res p o nsi bilit y t o e nsure t hat a ll pers o n nel i n v ol ve d i n t he st u d y 
c o n d uct recei ve trai ni n g bef ore partici pati n g i n a n y  pr oce d ure a n d/ or e val uati o n. Eac h st u d y 
ce nter will ha ve a trai ni n g rec or d as part of t he site file a n d T M F .
1 1. 4
D at a M a n a ge me nt
T he desi g nate d C R O will be res p o n si ble f or acti vities ass ociate d wit h t he data ma na ge me nt of 
t his st u d y. T his will i ncl u de , b ut is n ot li mite d t o, setti n g u p a rele va nt data base a n d data tra nsfer 
mec ha nis ms, al o n g wit h a p pr o priate vali dati o n of data a n d res ol uti o n of q ueries . All data 
ma n a ge me nt acti vities will be detaile d i n t he data ma na ge me nt pla n. 
St u d y  ce nters will rec or d all st u d y i nf or mati o n i n a n a p pr o priate s o urce d oc u me nt. T he data wi ll 
t he n be e ntere d directl y  i nt o a n electr o nic data ca pt ure ( E D C) s yste m b y c o m pleti n g t he e C R F via 
a sec ure i nter net c o n necti o n. Data e ntere d i nt o t he eC R F m ust be verifia ble a gai nst s o urce 
d oc u me nts at t he st u d y  ce nter. A n y c ha n ges t o t he data e ntere d i nt o t he E D C s yste m will be 
rec or de d i n t he a u dit trail.
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 3 8 of 4 4
C O N FI D E N TI A L
1 1. 5
Cli nic al St u d y C o n d uct
Wit h t he e xce pti o n
of a v oi di n g a n i m me diate ris k t o a s u bject, t he In vesti gat or s h o ul d n ot de viate 
fr o m t he cli nical st u d y pr ot oc ol or i m ple me nt a n y  c ha n ges wit h o ut writte n a p pr o val fr o m t he 
s p o ns or a n d pri or re vie w a n d d oc u me nte d a p pr o val/fa v ora ble o pi ni o n fr o m t he IR B/I E C of a 
pr ot oc ol a me n d me nt.
T he in vesti gat or s h o ul d d oc u me nt a n d e x plai n a n y de viati o n fr o m t he cli nical st u d y pr ot oc ol.
1 1. 6
A m e n d me nts
T he sp o ns or ma y  m o dif y t he cli nical st u d y pr ot oc ol at a n y  ti me f or et hical, me dical, or scie ntific 
reas o ns. A ny a me n d me nts will be ha n dle d acc or di n g t o a p plica ble l ocal re g ulati o ns.
1 1. 7
Q u alit y M a n a ge me nt a n d Ris k E v al u ati o n
Details will be pr o vi de d i n a se parate I nte grate d Q ualit y Ris k Ma na ge me nt Pla n.
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 3 9 of 4 4
C O N FI D E N TI A L
1 2
E T HI C S
1 2. 1 
I n de pe n de nt Et hics C o m mittee or I nstit uti o n al Re vie w B o ar d
Bef ore i nitiati o n of t he st u d y  at eac h st u d y ce nter, t he pr ot oc ol, t he I C F, ot her writte n material 
gi ve n t o t he s u bjects, a n d a n y  ot her rele va nt st u d y d oc u me ntati o n will be s u b mitte d t o t he 
a p pr o priate I E C/I RB. Writte n a p pr o val of t he st u d y  a n d all rele va nt st u d y i nf or mati o n m ust be 
o btai ne d bef ore t he st u d y ce nter ca n be i nitiate d . A n y  necessar y e xte nsi o ns or re ne wals of 
I E C/I R B a p pr o val m ust be o btai ne d f or c ha n ges t o t he st u d y s uc h as a me n d me nts t o t he pr ot oc ol, 
t he IC F or ot her st u d y  d oc u me ntati o n. T he writte n a p pr o val of t he I E C/IR B t o get her wit h t he 
a p pr o ve d I C F m ust be file d i n t he st u d y  files.
T he in vesti gat or will re p ort pr o m ptl y  t o t he I E C/I R B a n y ne w i nf or mati o n t hat ma y a d versel y 
affect t he safet y of t he s u bjects or t he c o n d uct of t he st u d y . T he n vesti gat or will s u b mit writte n 
s u m maries of t he st u d y stat us t o t he IE C/I R B as re q uire d . O n c o m pleti o n of t he st u d y , t he 
I E C/I R B will be n otifie d t hat t he st u d y has e n de d.
1 2. 2
Re g ul at or y A ut h orities
R ele va nt st u d y d oc u me ntati o n will be s u b mitte d t o t he re g ulat or y aut h orities of t he partici pati n g 
c o u ntries, acc or di n g t o l ocal/ nati o nal re q uire me nts, f or re vie w a n d a p pr o val bef ore t he be gi n ni n g 
of t he st u d y . O n c o m pleti o n of t he st u d y , t he re g ulat or y aut h orities will be n ot ifie d t hat t he st u d y 
has e n de d.
1 2. 3
Et hic al C o n d uct of t he St u d y
T he in vesti gat or(s) a n d all parties i n v ol ve d i n t his st u d y  s h o ul d c o n d uct t he st u d y i n a d here nce t o 
t he et hical pri nci ples base d o n t he Declarati o n of Helsi n ki, G C P, IC H g ui deli nes, a n d t he 
a p plica ble nati o nal a n d l ocal la ws a n d re g ula t or y re q uire me nts.
1 2. 4
I nf or me d C o nse nt
T he pr ocess of o btai ni n g i nf or me d c o nse nt m ust be i n acc or da nce wit h a p plica ble re g ulat or y  
re q uire me nt(s) a n d m ust a d here t o G C P.
T he In vesti gat or is res p o nsi ble f or e ns uri n g t hat n o s u bject u n der g oes a n y  st u d y-relate d 
e xa mi nati o n or acti vit y bef ore t hat s u bject has gi ve n writte n i nf or me d c o nse nt t o partici pate i n 
t he st u d y.
T he In vesti gat or or desi g nate d pers o n nel will i nf or m t he s u bject of t he o bjecti ves, met h o ds, 
a ntici pate d be nefits a n d p ote ntial ris ks , a n d i nc o n ve ni e nces of t he st u d y. T he s u bject s h o ul d be 
gi ve n e ver y  o p p ort u nit y t o as k f or clarificati o n of a n y p oi nts s he/he d oes n ot u n dersta n d a n d, if 
necessar y , as k f or m ore i nf or mati o n. At t he e n d of t he i nter vie w, t he s u bject will be gi ve n a m ple 
ti me t o c o nsi der the st u d y . S u bjects will be re q uire d t o si g n a n d date t he I C F . After si g nat ures are 
o btai ne d, t he I C F will be ke pt a n d arc hi ve d b y t he in vesti gat or i n t he In vesti gat or’s st u d y  file. A 
si g ne d a n d date d c o py of t he s u bject I C F will be pr o vi de d t o t he s u bject or his/ her a ut h orize d 
re prese ntati ve.
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 4 0 of 4 4
C O N FI D E N TI A L
It s h o ul d be e m p hasized t hat t he s u bject m a y ref use t o e nter t he st u d y or t o wit h dra w fr o m t he 
st u d y at a ny ti me, wit h o ut c o nse q ue nces f or t heir f urt her care or pe nalt y or l oss of be nefits , t o 
w hic h t he s u bject is ot he r wise e ntitle d. S u bjects w h o ref use t o gi ve or w h o wit h dra w writte n 
i nf or me d c o nse nt s h o ul d n ot be i ncl u de d or c o nti n ue i n t he st u d y.
If ne w i nf or mati o n bec o mes a vaila ble t hat ma y be rele va nt t o t he s u bject’s willi n g ness t o 
c o nti n ue partici pati o n i n t he st u d y , a ne w I C F will be a p pr o ve d b y t he I E C(s)/IR B(s) (a n d 
re g ulat or y aut h orities , if re q uire d). T he st u d y s u bjects will be i nf or me d a b o ut t his ne w 
i nf or mati o n a n d rec o nse nt will be o btai ne d.
1 2. 5
S u bject C o nfi de nti alit y
M o nit ors, a u dit ors, a n d ot her a ut h orize d age nts of t he S p o ns or a n d/ or its desi g nee, t he 
I E C(s)/IR B(s) a p pr o vi n g t his researc h, a n d t he U S F D A , as well as t hat of a n y ot her a p plica ble 
a ge nc y(ies), will be gra nte d direct access t o t he st u d y s u bjects’ ori gi nal me dical rec or ds f or 
verificati o n of cli nical st u d y pr oce d ures a n d/ or data, wit h o ut vi olati n g t he c o nfi de ntialit y  of t he 
s u bjects t o t he e xte nt per mitte d b y t he la w a n d re g ulati o ns. I n a ny prese ntati o ns of t he res ults of 
t his st u d y or i n p u blicati o ns, t he s u bjects’ i de ntities will re mai n c o nfi de ntial.
All pers o nal data c ollecte d a n d pr ocesse d f or t he p ur p oses of t his st u d y  s h o ul d be ma na ge d b y t he 
In vesti gat or a n d his/ her staff wit h a de q uate preca uti o ns t o e ns ure c o nfi de ntialit y  of t h ose data, 
a n d i n acc or da nce wit h t he a p plica ble nati o nal a n d/ or l ocal la ws a n d re g ulati o ns ( HI P A A f or t he 
U ni te d S tates) o n per s o nal data pr otecti o n.
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 4 1 of 4 4
C O N FI D E N TI A L
1 3  
R E P O R TI N G A N D P U B LI C A TI O N, I N C L U DI N G A R C HI VI N G
Esse ntial d oc u me nts are t h ose d oc u me nts t hat i n di vi d uall y  a n d c ollecti vely per mit e val uati o n of 
t he st u d y a n d q ualit y of t he data pr o d uce d. After c o m pleti o n of t he st u d y (e n d of st u d y defi ne d as 
t he date of t he last visit of t he last s u bject), all d oc u me nts a n d data relati n g t o t he st u d y will be 
ke pt i n a n or derl y ma n ner b y  t he in vesti gat or i n a sec ure st u d y  file. T his file will be a vaila ble f or 
i ns pecti o n b y t he S p o ns or or its re prese ntati ves. Esse ntial d oc u me nts s h o ul d be retai ne d f or 
2 ye ars after t he fi nal mar keti n g a p pr o val i n a n I CH re gi o n or f or at least 2 ye ars si nce t he 
disc o nti n uati o n of cli nical de vel o p me nt of t he i n vesti gati o nal pr o d uct. It is t he res p o nsi bilit y of 
t he S p o ns or t o i nf or m t he st u d y ce nter w he n t hese d oc u me nts n o l o n ger nee d t o be retai ne d . T he 
In vesti gat or m ust c o ntact t he s p o ns or bef ore destr o yi n g a ny st u d y- relate d d oc u me ntati o n. I n 
a d diti o n, all s u bject me dical rec or ds a n d ot her s o urce d oc u me ntati o n will be ke pt f or t he 
ma xi m u m ti me per mitte d b y t he h os pital, i nstit uti o n , or me dical practice.
T he S p o ns or m ust re vie w a n d a p pr o ve a n y res ults of t he st u d y or a bstracts f or pr ofessi o nal 
meeti n gs pre pare d b y t he In vesti gat or(s) . P u blis he d data m ust n ot c o m pr o mise t he o bjecti ves of 
t he st u d y. Data fr o m i n di vi d ual st u d y ce nters i n m ulti ce nter st u dies m ust n ot be p u blis he d 
se paratel y.
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 4 2 of 4 4
C O N FI D E N TI A L
1 4  
R E F E R E N C E S
Braat he n L, Szei mies R- M, Basset -Se g ui n N, Biss o n nette R, F ole y  P, Pariser D et al. G ui deli nes 
o n t he use of p h ot o d y na mic t hera p y f or n o n mela n o ma s ki n ca ncer: A n i nter nati o nal c o nse ns us. J 
A m Ac a d Der m at ol . 2 0 0 7; 5 6: 1 2 5 - 4 3.
Braat he n L R. Da y li g ht p h ot o d yna mic t hera p y i n pri vate practice i n S witzerla n d: gai n wit h o ut 
pai n. Act a Der m Ve nere ol . 2 0 1 2; 9 2( 6): 6 5 2 - 3.
Calza vara -Pi nt o n P G et al. Str uct ure d E x pert C o nse ns us o n Acti nic Kerat osis: Treat me nt 
Al g orit h m F oc usi n g o n Da y li g ht P D T. J C ut a n Me d S ur g 2 0 1 7; 2 1: 3 S - 1 6 S.
De Ber ker D, Mc Gre g or J M, H u g hes B R. G ui deli nes f or t he ma na ge me nt of acti nic kerat osis. Br 
J Der m at ol . 20 0 7 ; 1 5 6: 2 2 2 – 2 3 0.
E n gel et al . Healt h Effects of S u nli g ht E x p os ure i n t he U nite d States. Arc h Der m at o l. 1 9 8 8; 1 2 4: 
7 2 - 7 9.
Fel d ma n S R, Fleisc her A B Jr. P r o gressi o n of acti nic kerat osis t o s q ua m o us cell carci n o ma 
re visite d: cli nical a n d treat me nt i m plicati o ns. C utis . 2 0 1 1; 8 7( 4): 2 0 1 - 2 0 7.
Fe ns ke N A. Acti nic Kerat oses: Past, Prese nt a n d F ut ure . J Dr u gs Der m at ol . 2 0 1 0; 9( 5):s 4 5- s 4 9.
Fr ost C A . E pi de mi ol o g y  of solar kerat oses . Br J Der m at ol . 1 9 9 4; 1 3 1: 4 5 5 - 4 6 4.
Fr ost C A . T he pre vale nce a n d deter mi na nts of s olar kerat oses at a s u btr o pical latit u de 
( Q uee nsla n d, A ustralia). Br J Der m at ol . 1 9 9 8; 1 3 9: 1 0 3 3 - 1 0 3 9.
Fr ost C A et al. Hi g h I nci de nce a n d Re gressi o n Rates of S olar Kerat oses i n a Q uee nsla n d 
C o m m u nit y . J Invest Der m at ol . 2 0 0 0; 1 1 5( 8): 2 7 3 - 2 7 7.
G ol d M H . C urre nt treat me nts of acti nic kerat osis . J Dr u gs Der m at ol . 2 0 0 6; 5( 2): s 1 7 -s 2 5.
G ol d ber g D. Re vie w of acti nic kerat osis. Part I: eti ol o g y , e pi de mi ol o g y a n d cli nical prese ntati o n. 
J Dr u gs Der m at ol . 2 0 1 0; 9( 9): 1 1 2 5 - 3 2.
Har ve y  I. N o n - mela n o ma s ki n ca ncer a n d s olar kerat oses. I. Met h o ds a n d descri pti ve res ults of 
t he S o ut h Wales s ki n ca ncer st u dy. Br J C a ncer . 1 9 9 6; 7 4: 1 3 0 2 - 1 3 0 7.
Lac o ur J P, Ulric h C, Gila berte Y, V o n Fel bert V , Basset -Se g ui n N , Dre n o B, Girar d C, Re d o n d o 
P, Serra -G uille n C, S y n nersta d I, Tarste dt M, Tsia na kas A, Ve ne ma A W, Kelle ners- S meets N, 
A da ms ki H, Perez -Garcia B, Gerritse n MJ, Leclerc S, Kerr o uc he N, Szei mies R M. Da y li g ht 
p h ot o d y na mic t hera p y wit h met h y l ami n ole v uli nate crea m is effecti ve a n d nearl y pai nless i n 
treati n g acti nic kerat oses: a ra n d o mise d, i n vesti gat or-bli n de d, c o ntr olle d, p hase III st u d y  
t hr o u g h o ut E ur o pe. J E ur Ac a d Der m at ol Ve nere ol . 2 0 1 5; 2 9( 1 2): 2 3 4 2 - 8.
Le h ma n n P . Met h y l a mi n ole v uli nate- p hot o d y na mic t hera p y:  a re vie w of cli nical trials i n t he 
treat me nt of acti nic kerat oses a n d n o n mela n o ma s ki n ca ncer. Br J Der m at ol . 2 0 0 7; 1 5 6: 7 9 3 - 8 0 1.
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 4 3 of 4 4
C O N FI D E N TI A L
Me m o n A A . Pre vale nce of s olar da ma ge a n d acti nic kerat osis i n a Merse ysi de p o p ulati o n. Br J 
Der m at ol . 2 0 0 0 ; 1 4 2: 1 1 5 4- 1 1 5 9.
M ort o n C, W ulf H C, Szei mies R M, Gila berte Y, Basset- Se g ui n N, S ortiri o u et al. Practical 
a p pr oac h t o t he use of da yli g ht p h ot o d y na mic t hera p y  wit h t o pical met h yl a mi n ole v uli nate f or 
acti nic kerat osis: a E ur o pea n c o nse ns us. J E ur Aca d Der mat ol Ve nere ol. 2 0 1 5 Se p; 2 9( 9): 1 7 1 8 -
2 3 .
Salasc he S. E pi de mi ol o g y  of acti nic kerat osis a n d s q ua m o us cell carci n o ma. J A m A c a d 
Der m at ol . 2 0 0 0; 4 2: 4 - 7.
R u bel D M, S pel ma n L, M urrell D F, See J A, He witt D, F ole y  P, B osc C, Ker o b D, Kerr o uc he N, 
W ulf H C, S h u mac k S. Da y li g ht p h ot o d yna mic t hera p y wit h met h yl a mi n ole v uli nate crea m as a 
c o n ve nie nt, si milarl y effecti ve, nearly pai nless alter nati ve t o c o n ve nti o nal p h ot o d y na mic t hera p y 
i n acti nic kerat osis treat me nt: a ra n d o mize d c o ntr olle d trial. Br J Der m at ol. 2 0 1 4; 1 7 1( 5): 
1 1 6 4 - 7 1.
Si d or off A . Ta ki n g treat me nt decisi o ns i n n o n-mela n o ma s ki n ca ncer -t he place f or t o pical 
p h ot o d y na mic t hera p y ( P D T) . P h ot o di a g a n d P h o t o dy n T her. 2 0 1 0; 7: 2 4 - 3 2.
S pie wa k R . Patc h testi n g f or c o ntact aller g y a n d aller gic c o ntact der matitis . T he O pe n Aller gy
J o ur n al . 2 0 0 8; 1: 4 2 - 5 1.
U hle n ha ke E. O pti mal treat me nt of acti nic kerat osis. Cli n I nterv A gi n g . 2 0 1 3; 8: 2 9 - 3 5.
U S De part me nt of Healt h a n d H u ma n Ser vices. Healt h i ns ura nce p orta bilit y  a n d acc o u nta bilit y 
act of 1 9 9 6 ( P. L. 1 0 4-1 9 1) [ HI P A A]. htt p://as pe. h hs. g o v/a d m nsi m p/ pl 1 0 4 1 9 1. ht m . Effecti ve 
A u g ust 2 1, 1 9 9 6.
Wer ner R N . T he nat ural hist or y  of acti nic kerat osis: a s yste matic re vie w. Br J Der m at ol . 2 0 1 3; 
1 6 9: 5 0 2 - 5 1 8.
Wie gell S R, Hae ders dal M, P hili pse n P A, Eri kse n P, E n k C D, W ulf H C . C o nti n u o us acti vati o n 
of P pI X b y da y li g ht is effecti ve as a n d less pai nf ull t ha n c o n ve nti o nal p h ot o d yna mic t hera p y f or 
acti nic kerat osis; a ra n d o mize d, c o ntr olle d, si n gle-bli n de d st u d y . Br J Der m at ol . 2 0 0 8; 1 5 8: 7 4 0 -
7 4 6 .
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0

G al der m a R & D 
 
0 7 J A N 2 0 2 1
Pr ot oc ol N u m ber: R D. 0 6. S P R. 1 1 5 2 3 0
Versi o n 3. 0
P a ge 4 4 of 4 4
C O N FI D E N TI A L
I n vesti g at or Si g n at ure P a ge
Pr ot oc ol Title:
A 
d o u ble -bli n d, m ultice nter, 
l o n g-ter m f oll o w-u p st u d y to assess 
rec urre nce of Acti nic 
Kerat osis 
i n s u bjects treate d wit h 
Met h y l 
a mi n ole v uli nate h y dr oc hl ori de ( M A L) 1 6. 8 % crea m ( C D 0 6 8 0 9-4 1) or 
ve hicle crea m i n t he treat me nt of t hi n a n d 
m o deratel y t hic k, n o n-
h y per kerat otic, n o n- pi g me nte d acti nic kerat osis of t he face a n d scal p w he n 
usi n g d a y li g ht p h ot o d y na mic t hera p y (D L -P D T), f or s u bjects ac hie vi n g 
c o m plete 
res p o nse of 
treate d lesi o ns at 
Fi nal 
Visit i n 
S t u d y 
R D. 0 6. S P R. 1 1 2 1 9 9
Pr ot oc ol N u m ber:
R D. 0 6. S P R. 1 1 5 2 3 0
C o nfi de nti alit y a n d C urre nt G C P C o m pli a nce St ate me nt
I, t he u n dersi g ne d, ha ve re vie we d t his pr ot oc ol (a n d a me n d me nts), i ncl u di n g a p pe n dices, a n d I 
will c o n d uct t he st u d y  as descri be d i n c o m plia nce wit h t his pr ot oc ol (a n d a me n d me nts), G C P, 
a n d rele va nt I CH g ui deli nes.
O nce t he pr ot oc ol has bee n a p pr o ve d b y t he I E C/I R B, I will n ot m o dif y t his pr ot oc ol wit h o ut 
o btai ni n g pri or a p pr o val of Gal der ma Researc h & De vel o p me nt, L L C a n d of t he I E C/I RB. I will 
s u b mit t he pr ot oc ol a me n d me nts a n d/ or a n y I C F m o dificati o ns t o Gal der ma Researc h & 
De vel o p me nt, L L C a n d t he I E C/IR B, a n d a p pr o val will be o btai ne d bef ore a n y  a me n d me nt s are 
i m ple me nte d.
I u n dersta n d t hat all i nf or mati o n o btai ne d d uri n g t he c o n d uct of t he st u dy wit h re gar d t o t he 
s u bjects’ state of healt h will be re gar de d as c o nfi de ntial . N o s u bjects’ na mes will be discl ose d . 
All s u bjects will be i de ntifie d b y assi g ne d n u m bers o n all eC R F s, la b orat or y sa m ples, or s o urce 
d oc u me nts f or war de d t o t he s p o ns or. Cli nical i nf or mati o n ma y  be re vie we d b y t he s p o ns or or its 
a ge nts or re g ulat or y a ge ncies. A gree me nt m ust be o btai ne d fr o m t he s u bject bef ore discl os ure of 
s u bject i nf or mati o n t o a t hir d party.
I nf or mati o n de vel o pe d i n t his cli nical st u d y ma y be discl ose d b y Gal der ma Researc h & 
De vel o p me nt, L L C t o ot her cli nical i n vesti gat ors, re g ulat or y a ge ncies, or ot her healt h a ut h ority 
or g o ver n me nt a ge ncies as re q uire d.
I n vesti gat or Si g nat ure
Date
Pri nte d Na me
Title
I nstit uti o n
St u d y  Ce nter N u m ber
 
1 5- J a n- 2 0 2 1 0 0: 0 0: 0 0
R D. 0 6. S P R. 1 1 5 2 3 0 A m e n d m e nt 2 Pr ot o c ol V 3. 0 0 7 J A N 2 0 2 1 e U S
A p pr o v e d
1. 0