Clinical trial NCT02448381
Conditions: Cutaneous T-Cell Lymphoma
Keywords: CTCL Mycosis fungoides Hypericin SGX301 MF
Sponsor: Soligenix
Start date: 2015-12-01; Completion date: 2020-11-01
Enrollment: 169 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To evaluate the use of SGX301, a topical photosensitizing agent, to treat patients with patch/plaque phase cutaneous T-cell lymphoma (mycosis fungoides).

Detailed description:

Arms: arm 1: Three treatment cycles, each six (6) weeks followed by a two (2) week rest period. Treatment uses 0.25% SGX301 in USP Hydrophilic Ointment (or placebo) applied twice per week followed by fluorescent light therapy.

Cycle 1: Patients randomized 2:1 to active/placebo will have three (3) index lesions treated and evaluated.

Cycle 2: All patients will have three (3) index lesions treated and evaluated with active SGX301 ointment.

Cycle 3: All patients will be given the opportunity to enter an open-label cycle of active SGX301 ointment treatment for all lesions (index and non-index). arm 2: Placebo ointment is indistinguishable from ointment containing active SGX301 and is only used in Cycle 1. Treatment paradigm (ointment application and fluorescent light therapy) is identical.
Interventions: intervention 1: SGX301 (synthetic hypericin) intervention 2: Placebo
Intervention descriptions: intervention 1: 0.25% SGX301 in USP Hydrophilic Ointment applied twice per week, covered by opaque bandage for 12-24 hours, then treated with an initial dose of 5 J/cm\^2 fluorescent light. intervention 2: USP Hydrophilic Ointment applied twice per week, covered by opaque bandage for 12-24 hours, then treated with an initial dose of 5 J/cm\^2 fluorescent light.

Protocol documents:
Prot_000.pdf: 
Pr ot oc ol H P N- C T C L - 0 1 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 1 of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8
S G X 3 0 1, S Y N T H E TI C H Y P E RI CI N 
H P N- C T C L -0 1  
A P h ase 3 M ultice nter , R a n d o mize d, D o u ble-Bli n d,  Pl ace b o -C o ntr olle d St u dy t o Deter mi ne 
t he Effic acy of T o pi c al S G X 3 0 1 ( Sy nt hetic Hy perici n) a n d Fl u oresce nt B ul b -Li g ht Irr a di ati o n 
f or t he Tre at m e nt of C ut a ne o us T-Cell Ly m p h o m a  
S p o ns or:  
S oli ge ni x , Inc. 
2 9 E m m o ns Dri ve 
S uite B- 1 0 
Pri ncet o n, NJ  0 8 5 4 0 
( 6 0 9) 5 3 8- 8 2 0 0
D oc u me nt D at e : 
Ori gi n al  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1  
N o ve m ber 1 8, 2 0 1 4  
A me n d me nt 2  
J ul y 3 1, 2 0 1 5 
A me n d me nt 3  
Dece m b er 7 , 2 0 1 6 
A me n d me nt 4  
J u ne 5, 2 0 1 7 
A me n d me nt 5 
N o ve m ber 3 0, 2 0 1 8 
U S I N D N u m ber:  
 
Me dic al M o nit or  
Ri c har d Stra u be, M D 
C O N FI D E N TI A LI T Y S T A T E M E N T  
T he i nf or mati o n i n t his d oc u me nt c o ntai ns tra d e secrets a n d c o m mercial i nf or mati o n t hat are 
pri vile ge d or c o nfi d e ntial a n d ma y n ot be discl ose d u nless s uc h discl os ure is re q uire d b y fe deral 
or state la w or re g ulati o ns . I n a n y e ve nt, p ers o ns t o w h o m t he i nf or mati o n is discl ose d m ust be 
i nf or me d t hat t he i nf or m ati o n is pri vile ge d or c o nfi de ntial a n d ma y n ot be f urt her discl ose d b y 
t he m. T hese restri cti o ns o n discl os ure will a p pl y e q uall y t o all f ut ure i nf or mati o n s u p plie d t o 
y o u, w hic h is i n dicat e d as pri vile ge d or c o nfi d e ntial. 
N C T 0 2 4 4 8 3 8 1








Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 5 of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
•  
≥1 8 years  of a ge . 
•  
S u bj ects m ust  ha ve  a  cli nical  dia g n osis  of  c uta ne o us  T -cell  l y m p h o ma  ( C T C L,  m yc osis  
f u n g oi des), Sta ge I A, Sta ge IB, or Sta ge II A.  
•  
S u bj ects wit h  a mi ni m u m of t hree ( 3) e val ua ble, discrete lesi o ns . 
•  
S u bj ects willi n g t o f oll o w t he cli nical pr ot oc ol a n d v ol u ntaril y gi ve t heir writte n i nf or me d 
c o nse nt.  
•  
Fe male s u bjects n ot pre g na nt or n ursi n g a n d willi n g t o u n der g o a pre g na nc y test wit hi n 3 0 da ys 
pri or t o  treat me nt i nitiati o n. 
•  
S u bj ects m ust be willi n g t o refrai n fr o m s u n bat hi n g f or t he d urati o n of t he st u d y. 
 
E xcl usi o n Criteri a  
Patie nt s wit h a n y of t he f oll o wi n g criteria are N O T  eli gi ble f or e nr oll me nt: 
•  
Hist or y of s u n h y perse nsiti vit y a n d p h ot ose nsiti ve der mat oses i ncl u di n g p or p h yria, s yste mic 
l u p us  er yt he mat os us,  Sj ö gre n’s  s y n dr o me,  xer o der ma  pi g me nt os u m, p ol y m or p h o us  li g ht  
er u pti o ns, or ra diati o n t hera p y wit hi n 3 0 da ys of e nr olli n g. 
•  
Hist or y of aller g y or h y perse nsiti vit y t o a n y of t he c o m p o ne nts of S G X 3 0 1. 
•  
Pre g na nc y or m ot hers w h o are breast -fee di n g. 
•  
M ales a n d fe males n ot willi n g t o  use effecti ve c o ntrace pti o n.  
•  
U n heale d  s u n b ur n. 
•  
S u bj ects recei vi n g t o pical ster oi ds or ot her t o pical treat me nts (e. g., nitr o ge n m ustar d) o n i n de x 
lesi o ns f or C T C L wit hi n 2 wee ks. 
•  
S u bj ects recei vi n g s yste mi c ster oi ds, ps orale n U V A ra diati o n t hera p y ( P U V A), n arr o w ba n d 
U V B li g ht t hera p y ( N B -U V B)  or car m usti ne ( B C N U) or ot her s yste mic t hera pies f or C T C L 
wit hi n 3 wee ks of e nr oll me nt.  
•  
S u bj ects  w h o  ha ve  recei ve d  electr o n  bea m  irra diati o n  wit hi n  t he  p o te ntial  treat me nt  fiel d  
wit hi n 3 m o nt hs of e nr oll me nt. 
•  
S u bj ects wit h a hist or y of si g nifica nt s yste mic i m m u n os u p pressi o n.  
•  
S u bj ects ta ki n g ot her i n vesti gati o nal dr u gs or dr u gs of a b use wit hi n 3 0 da ys of e ntr y i nt o t his 
st u d y.  
•  
S u bj ects w h ose c o n diti o n is s p o nta ne o usl y i m pr o vi n g. 
•  
S u bj ects wit h t u m or sta ge or er yt hr o der mic C T C L (sta ges II B -I V). 
•  
S u bj ect has a n y c o n diti o n t hat, i n t he j u d g me nt of t he pri nci pal i n vesti gat or ( PI ), is li kel y t o 
i nterfere wit h partici pati o n i n t he st u d y.  
•  
Pr i or partici pati o n i n t he c urre nt st u d y . 
I n vesti g ati o n al Pr o d uct, D os a ge a n d M o de of A d mi nistr ati o n:  
S G X 3 0 1 will be s u p plie d i n plastic scre w-t o p j ars c o ntai ni n g 2 5 gra ms of  S G X 3 0 1 (0. 2 5 % s y nt hetic 
h y perici n, 2. 5 m g/ gra m) . Oi nt me nt will be a p plie d t wice wee kl y a n d c o ver e d usi n g o pa q ue ba n da gi n g 
a p pr o ve d/ pr o vi de d b y S oli ge ni x f or a peri o d of 1 8  t o 2 4 h o urs pri or t o li g ht treat me nt. Li g ht treat me nts  
will be gi ve n usi n g a ba n k of 1 2 c o ol w hite visi ble fl u oresce nt b ul bs f or a pe ri o d calc ulate d usi n g 
d osi meter rea di n gs a n d ta bles t o deter mi ne t he d urati o n of t hera p y ( a p pr o xi matel y 1 mi n ute /J o ule wit h 
t he i nitial d ose of 5  Jo ules /c m2) a n d t he patie nt’s p ositi o n mar ke d t o ass ure c o nsiste nt p ositi o ni n g 








Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 9 of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
a nal ysis are deli neate d i n t he Statistical A nal ysis  Pla n.  
I nteri m A n al ysis: 
T he Data M o nit ori n g C o m mittee ( D M C) will c o n d uct o ne ( 1) i nteri m a nal ysis w he n a p pr o xi matel y 
6 0 % ( n = 8 0) of t he t otal s u bj ects ha ve c o m plete d t he C ycle 1 Wee k 8 e val uati o n (i.e., t he pri mar y 
e n d p oi nt e val uati o n). S oli ge ni x, I nc.,  partici pati n g cli nical i n vesti gat ors, a n d a n y pers o n nel i n v ol ve d i n 
trial c o n d uct will re mai n bli n de d t o st u d y treat me nt. T he pri mar y efficac y e n d p oi nt a n d t he ke y safet y 
e n d p oi nts  will  be  a nal yze d.  A  sa m ple  size  recalc ulati o n  ma y  be  perf or me d  after  e xa mi ni n g  t he  
ass u m pti o ns. I n or der t o preser ve a n o verall T y pe I err or rate of 0. 0 5, t he al p ha s pe n di n g f u ncti o n 
a p pr oac h wit h a n O’ Brie n -Fle mi n g t y pe of st o p pi n g r ule will be use d wit h a 2 si de d si g nifica nce le vel 
of α  = 0. 0 0 1 f or t he i nteri m a nal ysis a n d a 2  si de d si g nifica nce le vel of α  = 0. 0 4 9 f or t he fi nal a nal ysis. 
S pecific g ui deli nes c o ncer ni n g rec o m me n dati o ns f or resizi n g t he st u d y, i ncl u di n g ter mi nati n g t he st u d y 
earl y f or reas o ns of safet y or o ver w hel mi n g efficac y, are o utli ne d i n t he D M C c harter.  T he  I nteri m 
a nal ysis  was  perf or me d  a n d  t he  D M C  rec o m me n de d  t hat  e nr oll me nt  c o nti n ue  t o  1 6 0  e val ua ble  
patie nts.  
 
Fi n al A n al ysis :  
U p o n c o m pleti o n of e nr oll me nt, t he st u d y data base is t o be l oc ke d, release d, a n d a nal yze d i n  t w o parts, 
t he first bei n g a n a nal ysis of data t hr o u g h C ycle 1 W ee k 8, a n d t he sec o n d fi nal a nal ysis of  all data 
t hr o u g h l o n g-ter m f oll o w- u p. 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 1 0  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
3.  
T A B L E O F C O N T E N T S, LI S T O F T A B L E S, A N D LI S T O F 
FI G U R E S  
3. 1.  
T a ble of C o nte nts  
2.  
S Y N O P SI S  ................................................................................................................... 3 
3.  
T A B L E O F C O N T E N T S, L I S T O F T A B L E S, A N D LI S T O F FI G U R E S ............... 1 0 
3. 1.  
Ta ble of C o nte nts ........................................................................................................ 1 0  
3. 2.  
List of Ta bl es  .............................................................................................................. 1 4 
3. 3.  
List of Fi g ures  ............................................................................................................. 1 5 
4.  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F  T E R M S ............................. 1 6 
5.  
I N T R O D U C TI O N ...................................................................................................... 1 9 
5. 1.  
Bac k gr o u n d I ntr o d u cti o n  ............................................................................................ 1 9 
5. 1. 1  
Nat ural Hist or y a n d Treat me nt of C uta ne o us T- cell L y m p h o ma  ............................... 1 9 
5. 2.  
Rati o nale  ..................................................................................................................... 2 1 
5. 3.  
C he mistr y  .................................................................................................................... 2 2 
5. 4.  
Precli nical Data  ........................................................................................................... 2 2 
5. 4. 1  
A nti viral Acti vit y  ........................................................................................................ 2 2 
5. 4. 2  
A nti pr oliferati ve Effects o n L y m p h oi d Cells  ............................................................. 2 3 
5. 4. 3  
T o xic ol o g y .................................................................................................................. 2 4  
5. 4. 4  
P har mac o ki netics  ........................................................................................................ 2 5 
5. 5.  
Pri or Cli nical Trials  .................................................................................................... 2 5 
5. 5. 1  
S yste mic H y perici n  ..................................................................................................... 2 5 
5. 5. 2  
T o pical H y peri ci n  ....................................................................................................... 2 7 
5. 6.  
C urre nt Trial  ............................................................................................................... 2 8 
6.  
T RI A L O BJ E C TI V E S A N D  P U R P O S E  .................................................................... 2 9 
6. 1.  
Pri mar y o bjecti ve  ........................................................................................................ 2 9 
6. 2.  
Sec o n dar y o bjecti ves .................................................................................................. 2 9  
7.  
I N VE S TI G A TI O N A L P L A N  ..................................................................................... 3 1 
7. 1.  
O verall St u d y Desi g n a n d Pla n: Descri pti o n  .............................................................. 3 1 
7. 2.  
S pecific Assess me nts  .................................................................................................. 3 9 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 1 1  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
7. 2. 1  
La b orat or y Ass ess me nts  ............................................................................................. 3 9 
7. 2. 1. 1.  
Scree ni n g Tests  ........................................................................................................... 3 9 
7. 2. 1. 2.  
He mat ol o g y T ests  ....................................................................................................... 3 9 
7. 2. 1. 3.  
Cli nical C he mistr y La b or at or y Tests  .......................................................................... 3 9 
7. 2. 1. 4.  
S ki n p u nc h bi o ps y....................................................................................................... 4 0  
7. 2. 1. 5.  
S G X 3 0 1 Plas ma C o nce ntrati o n Sa m ples .................................................................... 4 0  
7. 2. 2  
Ot her Assess me nts  ...................................................................................................... 4 0 
7. 2. 2. 1.  
Me dical Hist or y  .......................................................................................................... 4 0 
7. 2. 2. 2.  
P h ysical E x a mi nati o n a n d Vis ual Lesi o n I ns pecti o n .................................................. 4 1  
7. 2. 2. 3.  
Vital Si g ns  .................................................................................................................. 4 1 
7. 2. 2. 4.  
C o m p osite Assess me nt of I n de x Lesi o ns Se v erit y ( C AI L S) Sc ore ............................ 4 1  
7. 2. 2. 5.  
T he P h ysicia n Gl o bal Assess me nt ( P G A)  .................................................................. 4 3 
7. 2. 2. 6.  
M o difie d Se verit y Wei g hte d Assess me nt T o ol ( m S W A T) ........................................ 4 4  
7. 2. 2. 7.  
S ki n Reacti o n Safet y Gra di n g .................................................................................... 4 4  
7. 3.  
Visit Sc he d ule  ............................................................................................................. 4 5 
7. 3. 1  
Scree ni n g  .................................................................................................................... 4 5 
7. 3. 2  
C ycle 1  ........................................................................................................................ 4 5 
7. 3. 2. 1.  
Baseli ne Da y  ............................................................................................................... 4 5 
7. 3. 2. 2.  
Li g ht Treat me nt # 1  ..................................................................................................... 4 6 
7. 3. 2. 3.  
A p plicati o n Da y 2 ....................................................................................................... 4 6  
7. 3. 2. 4.  
Li g ht Treat me nt # 2  ..................................................................................................... 4 7 
7. 3. 2. 5.  
A p plicati o n Da ys 3- 1 2 ................................................................................................ 4 7  
7. 3. 2. 6.  
Li g ht Treat me nts # 3 - 1 2 .............................................................................................. 4 7 
7. 3. 2. 7.  
C ycle 1 Assess me nt  .................................................................................................... 4 8 
7. 3. 3  
C ycle 2  ........................................................................................................................ 4 9 
7. 3. 3. 1.  
A p plicati o n Da ys 1 3- 2 4 .............................................................................................. 4 9  
7. 3. 3. 2.  
Li g ht Treat me nts # 1 3- 2 4 ............................................................................................ 4 9  
7. 3. 3. 3.  
C ycle 2 Assess me nt  .................................................................................................... 4 9 
7. 3. 4  
C ycle 3  ........................................................................................................................ 5 0 
7. 3. 4. 1.  
A p plicati o n Da ys 2 5- 3 6 .............................................................................................. 5 0  
7. 3. 4. 2.  
Li g ht Treat me nts # 2 5- 3 6 ............................................................................................ 5 0  


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 1 2  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
7. 3. 4. 3.  
C ycle 3 Assess me nt  .................................................................................................... 5 1 
7. 3. 5  
F oll o w- u p visits .......................................................................................................... 5 1  
8.  
S E L E C TI O N A N D WI T H D R A W A L O F S U BJ E C T S  .............................................. 5 3 
8. 1.  
S u bject I n cl usi o n Criteria  ........................................................................................... 5 3 
8. 2.  
S u bject E x cl usi o n Criteria  .......................................................................................... 5 3 
8. 3.  
Patie nt Wit h dra wal Criteria  ........................................................................................ 5 4 
8. 4.  
Treat me nt I nterr u pti o n i n t he E ve nt of P h ot ot o xicit y ................................................. 5 4  
8. 5.  
Ter mi nati o n of t he St u d y ............................................................................................ 5 4  
9.  
T R E A T M E N T O F S U BJ E C T S .................................................................................. 5 6  
9. 1.  
Descri pti o n of St u d y Dr u g .......................................................................................... 5 6  
9. 2.  
C o nc o mita nt Me dicati o ns ........................................................................................... 5 6  
9. 3.  
Treat me nt C o m plia nce  ................................................................................................ 5 8 
9. 4.  
Ra n d o mizati o n a n d Bli n di n g ...................................................................................... 5 8  
1 0.  
S T U D Y D R U G M A T E RI A L S  A N D M A N A G E M E N T  ........................................... 5 9 
1 0. 1.  
St u d y Dr u g  .................................................................................................................. 5 9 
 
 
 
 
 
 
1 0. 5.  
A d mi nistrati o n  ............................................................................................................ 5 9 
1 0. 6.  
St u d y Dr u g A cc o u nta bilit y ......................................................................................... 6 0  
1 0. 7.  
St u d y Dr u g H a n dli n g a n d Dis p osal ............................................................................ 6 0  
1 1.  
A S S E S S M E N T O F E F FI C A C Y  ................................................................................ 6 1 
1 1. 1.  
Disease Assess me nt  .................................................................................................... 6 1 
1 1. 1. 1  
C o m p osite Assess me nt of I n de x Lesi o n Se v erit y  ( C AI L S) ...................................... 6 1  
1 1. 1. 2  
S ki n Reacti o n Safet y Gra di n g .................................................................................... 6 1  
1 1. 1. 3  
Classificati o n of Treat e d S ki n Lesi o n Res p o nse ........................................................ 6 1  
1 1. 1. 4  
M o difie d Se verit y Wei g hte d Assess me nt T o ol ( m S W A T) ........................................ 6 2  
1 1. 1. 5  
P h ysicia n Gl o bal Ass ess me nt ( P G A)  ......................................................................... 6 2 
1 1. 1. 6  
Di gital P h ot o gr a p h y  .................................................................................................... 6 2 
1 1. 1. 7  
Bi o ps y ......................................................................................................................... 6 2  
1 1. 2.  
E n d p oi nts .................................................................................................................... 6 3  


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 1 3  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
1 1. 2. 1  
Pri mar y Efficac y E n d p oi nt ......................................................................................... 6 3  
1 1. 2. 2  
Sec o n dar y Efficac y E n d p oi nts .................................................................................... 6 3  
1 1. 2. 2. 1.  
C ycle 1 Sec o n dar y E n d p oi nts ..................................................................................... 6 3  
1 1. 2. 2. 2.  
C ycle 2 Sec o n dar y E n d p oi nts ..................................................................................... 6 4  
1 1. 2. 2. 3.  
C ycle 3 Sec o n dar y E n d p oi nts ..................................................................................... 6 5  
 
 
1 2.  
A S S E S S M E N T O F S A F E T Y  ..................................................................................... 6 6 
1 2. 1.  
Defi niti o ns  .................................................................................................................. 6 6 
1 2. 1. 1  
A d verse E x perie n ce ( A E)  ........................................................................................... 6 6 
1 2. 1. 2  
Seri o us A d verse E x perie nce ( S A E)  ............................................................................ 6 6 
1 2. 1. 3  
P ote ntiall y Seri o us A d verse E x perie nce ..................................................................... 6 6  
1 2. 2.  
Relati o ns hi p t o St u d y Dr u g ........................................................................................ 6 7  
1 2. 3.  
Se verit y of A d verse E ve nt .......................................................................................... 6 7  
1 2. 4.  
Rec or di n g A d verse E ve nts ......................................................................................... 6 7  
1 2. 5.  
Re p orti n g A d v erse E v e nts .......................................................................................... 6 7  
1 2. 5. 1  
A d verse E v e nts  ........................................................................................................... 6 7 
1 2. 5. 2  
Seri o us A d verse E v e nts .............................................................................................. 6 8  
1 2. 6.  
Data M o nit ori n g C o m mittee  ....................................................................................... 6 9 
1 3.  
S T A TI S TI C S  .............................................................................................................. 7 0 
1 3. 1.  
Sa m ple Size Calc ulati o n  ............................................................................................. 7 0 
 
 
 
 
 
 
 
 
 
 
1 3. 3.  
Statistical A nal ysis  ...................................................................................................... 7 1 
1 3. 3. 1  
Pri mar y E n d p oi nt ........................................................................................................ 7 1  
1 3. 3. 2  
Sec o n dar y E n d p oi nts .................................................................................................. 7 2  
 
 
1 3. 3. 4  
I nteri m A nal ysis .......................................................................................................... 7 2 
 
 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 1 4  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
1 4.  
Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E  ......................................... 7 4 
1 4. 1.  
St u d y M o nit ori n g ........................................................................................................ 7 4  
1 4. 1. 1  
Pre -st u d y E v al uati o n ................................................................................................... 7 4 
1 4. 1. 2  
Site I nitiati o n Visit  ...................................................................................................... 7 4 
1 4. 1. 3  
M o nit ori n g Visits  ........................................................................................................ 7 4 
1 4. 1. 4  
Cl ose- o ut Visit  ............................................................................................................ 7 5 
1 4. 2.  
A u dits a n d I ns p ecti o ns ................................................................................................ 7 5  
1 5.  
E T HI C S  ...................................................................................................................... 7 6 
1 5. 1.  
I nstit uti o nal Re vie w B oar d ......................................................................................... 7 6 
1 5. 2.  
Et hical C o n d uct of t he St u d y ...................................................................................... 7 6  
1 5. 3.  
Writte n I nf or m e d C o nse nt .......................................................................................... 7 6  
1 5. 4.  
S u bject data pr otecti o n  ............................................................................................... 7 6 
1 5. 5.  
Fi na ncial Discl os ur e  ................................................................................................... 7 6 
1 6.  
D A T A H A N D LI N G A N D R E C O R D K E E PI N G  ....................................................... 7 8 
1 6. 1.  
I ns p ecti o n of Rec or ds ................................................................................................. 7 8 
1 6. 1. 1  
M o nit ori n g .................................................................................................................. 7 8  
1 6. 1. 2  
A u dits .......................................................................................................................... 7 8  
1 6. 2.  
Rete nti o n of Rec or ds .................................................................................................. 7 8  
1 7.  
I N V E S TI G A T O R A G R E E M E N T ............................................................................. 7 9 
1 8.  
A P P E N DI C E S  ............................................................................................................ 8 0 
A p pe n di x 1 8. 1.  Li g ht Treat me nt D ur ati o n Base d o n Li g ht Met er Rea di n g at t he Lesi o n 
P ositi o n  ....................................................................................................................... 8 0 
A p pe n di x 1 8. 2.  Lesi o n L o cati o n Ma p  ......................................................................................... 8 1 
A p pe n di x 1 8. 3.  Patie nt I nstr ucti o ns/ Treat me nt L o g  ................................................................... 8 2 
A p pe n di x 1 8. 4.  Bi o ps y Pr o cessi n g  ............................................................................................. 8 5 
1 9.  
R E F E R E N C E S  ........................................................................................................... 8 6 
 
3. 2.  
List of T a bles  
Ta ble 1: E mer ge n c y C o ntact I nf or mati o n ........................................................................................ 2 
Ta ble 2: A b bre vi ati o ns a n d s pecialist ter ms .................................................................................. 1 6  
Ta ble 3: S ki n P h ot ot o xicit y Gra di n g ............................................................................................. 3 2  


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 1 5  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
Ta ble 4:  St u d y Assess m e nts:  C ycle 1 - Wee k 1 R a n d o mize d Dr u g t o I n dex Lesi o ns  .................. 3 4 
Ta ble 5:  St u d y Assess m e nts:  C ycle 1 - A p plicati o n a n d Li g ht Treat me nt # 3- 1 2 
R a n d o mize d Dr u g t o I n d ex Lesi o ns  ............................................................................ 3 5 
Ta ble 6:  C ycl e 1 - Wee ks 7 a n d 8 Tre at me nt Ev al u ati o n  ............................................................. 3 5 
Ta ble 7:  C ycl e 2 - Li g ht Treat me nt # 1 3- 2 4 All P atie nts S G X 3 0 1 Oi nt me nt t o I n dex 
Lesi o ns  ........................................................................................................................ 3 6 
Ta ble 8:  C ycl e 2 - Assess me nt  ...................................................................................................... 3 6 
Ta ble 9:  O pti o nal C ycl e 3 - Wee k 1 7 t hr o u g h 2 2 All P atie nts 0. 2 5 % S G X 3 0 1 Oi nt me nt 
t o All Tre ate d Lesi o ns ................................................................................................. 3 7 
Ta ble 1 0:  C ycl e 3: Assess me nt - Cycle 3 Ev al u ati o n  ................................................................... 3 7 
Ta ble 1 1:  Wee ks 2 5- 4 8 - L o n g- ter m F oll o w- u p ........................................................................... 3 8 
Ta ble 1 2:  C o m p osite Assess me nt of I n de x Lesi o n Se verit y ........................................................ 4 2  
Ta ble 1 3:  P h ysicia n’s Gl o bal Assess me nt  .................................................................................... 4 3 
Ta ble 1 4:  M o difie d Se verit y Wei g ht e d Assess me nt T o ol ( m S W A T) .......................................... 4 4  
Ta ble 1 5: Cli nical Res p o nse Defi niti o ns ....................................................................................... 6 1  
Ta ble 1 6:  Gra di n g of Bi o ps y......................................................................................................... 6 3  
 
3. 3.  
List of Fi g ures  
Fi g ure 1:  St u d y Sc h e ma  ................................................................................................................ 3 3 
 
 
 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 1 6  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
4.  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F  T E R M S 
T a ble 2 : A b bre vi ati o ns a n d s peci alist ter ms  
A b bre vi ati o n or s peci alist ter m  
E x pl a n ati o n 
A E  
A d verse e ve nt  
A L T  
Ala ni ne a mi n otra nsferase  
A S T  
As partate a mi n otra nsferase  
A N O V A  
A nal ysis of Varia nce  
B C N U  
Bis -c hl or oet h yl nitr os o urea ( Car m usti ne) 
B S A  
B o d y S urface Area 
B U N  
Bl o o d urea nitr o ge n 
B V D V  
B o vi ne diarr hea vir us  
C AI L S  
C o m p osite Assess me nt of I n de x Lesi o n Se verit y  
C D #  
C l uster of differe ntiati o n # 
C F R  
C o de of Fe deral Re g ulati o ns 
C L L  
C hr o nic l y m p h oc ytic le u ke mia 
C O 2 
Car b o n di o xi de 
C R  
C o m plete res p o nse 
C T C L  
C uta ne o us T -cell L y m p h o ma 
D C F  
De o x yc of or m yci n 
D M C  
Data M o nit ori n g C o m mittee  
E C P  
E xtrac or p oreal P h ot o p heresis 
e C R F 
Electr o nic Case Re p ort F or m  
F D A  
U nite d States F o o d a n d Dr u g A d mi nistrati o n  
F V  
Frie n d Le u ke mia Vir us  
G C P  
G o o d Cli nical Practice  
G M P  
G o o d Ma n ufact uri n g Practice 
H C V  
He patitis C Vir us   
H C G  
H u ma n c h ori o nic g o na d otr o pi n 
H C L  
H air y cell le u ke mia  
HI V  
H u ma n I m m u n o deficie nc y Vir us 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 1 7  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
A b bre vi ati o n or s peci alist ter m  
E x pl a n ati o n 
I C F 
I nf or me d C o nse nt F or m 
I C H 
I nter nati o nal C o nfere nce o n Har m o nizati o n 
I D B 
I n vesti gat or’s Dr u g Br oc h ure 
I F N 
I nterfer o n 
I F N-α  
I nterfer o n-al p ha 
I N D 
I n vesti gati o nal Ne w Dr u g A p plicati o n 
I R B 
I nstit uti o nal Re vie w B oar d 
I T T 
I nte nt-t o- Treat p o p ulati o n 
J 
J o ules 
L N  
L y m p h N o des 
M C H  
Mea n c or p usc ular he m o gl o bi n  
M C H C  
Mea n c or p usc ular he m o gl o bi n c o nce ntrati o n  
M C V  
Mea n c or p usc ular v ol u me  
M F  
M yc osis F u n g oi des 
M P D  
Mi ni m u m P h ot ot o xic D ose 
m S W A T  
M o difie d Se verit y Wei g hte d Assess me nt T o ol  
N B -U V B  
Narr o w ba n d Ultra vi olet- B li g ht ra diati o n  
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 G A  
P h ysicia n Gl o bal Assess me nt  
PI  
Pri nci pal I n vesti gat or  
P K  
P har mac o ki netic  
P P  
Per - pr ot oc ol P o p ulati o n 
P U V A  
Ps orale n Ultra vi olet -A treat me nt  
R B C  
Re d bl o o d cell 
S A E  
Seri o us a d verse e ve nt  
S S  
Sézar y S y n dr o me  
U S P  
U nite d States P har mac o peia  
U V  
Ultra vi olet  
U V A  
Ultra vi olet -A li g ht ra diati o n  


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 1 8  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
A b bre vi ati o n or s peci alist ter m  
E x pl a n ati o n 
U V B  
Ultra vi olet -B li g ht ra diati o n  
W B C  
W hite bl o o d cell  
 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 1 9  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
5.  
I N T R O D U C TI O N 
5. 1.  
B ac k gr o u n d I ntr o d ucti o n  
T his secti o n c o ntai ns a brief descri pti o n of t he rati o nale a n d a v aila ble i nf or mati o n c o ncer ni n g t he 
c he mistr y, n o n-cli nical p har mac ol o g y a n d t o xic ol o g y, p har mac o ki netics ( P K), a n d pre vi o us 
cli nical e x perie nce wit h S G X 3 0 1 . Please refer t o t he I n v esti gat or's Dr u g Br oc h ure (I D B) f or 
a d diti o nal details a n d i nf or mati o n. 
5. 1. 1  
N at ur al Hist or y a n d Tre at me nt of C ut a ne o us T- cell L y m p h o m a  
C uta ne o us T- cell l y m p h o ma ( C T C L), of w hic h t he m ost c om m o n earl y sta ges are als o k n o w n as 
m yc osis f u n g oi des ( M F), is t he m ost c o m m o n t y p e of T- cell l y m p h o ma. C T C L affects 
a p pr o xi matel y 2 5, 0 0 0 t o 5 0, 0 0 0 i n di vi d uals i n t he US [ 1]. M F m ost c o m m o nl y pres e nts wit h 
s ki n i n v ol ve me nt o nl y, m a nifeste d as s cal y, er yt h e mat o us patc hes. As MF pr o gresses , p atie nts 
de vel o p t hic ker s ki n lesi o ns ( pla q ues), s ki n t u m ors, l y m p h n o de ( L N) i n v ol ve me nt, bl o o d 
i n v ol ve me nt ( Sézar y s y n dr o me), a n d visceral or ga n i n v ol ve me nt. A fe w patie nts will prese nt 
wit h m ore a d va nce d sta ges of C T C L re q uiri n g s yste mic t hera p y fr o m t he ti me of dia g n osis [ 2]. 
A d va nce d dis ease wit h diff use L N a n d vis ceral or ga n i n v ol ve m e nt is us uall y ass oci ate d wit h a 
p o orer r es p o nse r ate t o sta n dar d t hera pies a n d t h e patie nt’s s ur vi val ca n ofte n be meas ure d i n 
m o nt hs [ 3]. A s u b - gr o u p of C T C L patie nts prese nt wit h e xte nsi ve s ki n i n v ol ve me nt ( ge neralize d 
er yt hr oder m a) a n d circ ul ati n g mali g na nt cere brif or m T -cells t hat is c o m m o nl y desi g nate d Sézar y 
s y n dr o me ( S S) [ 4, 5]. 
M F has s u bsta ntial m or bi dit y a n d p ote ntial m ortalit y. M ortalit y is relate d t o sta ge of diseas e [ 6]. 
Me dia n s ur vi val f or sta ge T 1 (c uta n e o us patc h es or pla q ues < 1 0 % b o d y s urface area ( B S A)) or 
T 2 ( patc hes or pla q ues > 1 0 % B S A) e x cee ds 1 2 years; T 1 or T 2 patie nts wit h l y m p h n o de or 
bl o o d i n v ol ve me nt a n d T 3 ( o ne or m or e c uta ne o us t u m ors) or T 4 patie nts (er yt hr o d er ma) ha ve a 
5 year me dia n s ur vi val; t h ose wit h visceral i n v ol v e me nt or l y m p h n o d e efface me nt b y t u m or 
ha ve o nl y a 2. 5 year me dia n s ur vi val.  
T he dia g n osis of C T C L is c o nfir me d b y s ki n bi o ps y w hic h c haracteristicall y de m o nstrates t he 
pat h o g n o m o nic e pi der mal i nfiltrati o n ( Pa utrier’s micr o -a bscesses) of  h y p erc hr o m atic  T-cells 
t hat are i m m u n o hist oc he micall y p ositi ve f or t he C D 4 mar ker i d e ntif yi n g t h e “ hel per” T-cell 
s u bset a n d ofte n f ail t o e x press C D 7 [ 7, 8]. Bl o o d i n v ol ve me nt ca n be i n vesti gate d t hr o u g h fl o w 
c yt o metr y, Sézar y c o u nt a n d/ or ge ne rearra n ge me nt st u dies t o deter mi ne t he prese n ce of a 
circ ulati n g cl o ne [ 6, 9]. M ore a d va n ce d s ki n disease pr o d uces vertical gr o wt h res ulti n g i n t u m ors 
or ulcers a n d is fre q u e ntl y ass o ciate d wit h re gi o n al L N i n v ol ve me nt t hat ca n be detect e d via 
p h ysical e x a mi nati o n a n d ra di ol o gical i ma gi n g .  
Treat me nt of M F i n v ol ves s ki n directe d t hera pies, bi ol o gic res p o ns e m o dif yi n g t hera pies ai me d 
at pr o m oti n g a h ost r es p o nse t o t u m or, ra diati o n t hera p y ( directe d at i n di vi d ual t u m ors or t otal 
b o d y el ectr o n bea m irra diati o n), a n d i n s o me i nsta nces m ulti -a ge nt c h e m ot hera pe utic m o d alities. 
M ost patie nts ha ve recei ve d s h ort c o urses of t o pical c ortic oster oi ds pri or t o t he dia g n osis of M F 
[ 1 0]. T he mali g na nc y-s p ecific t o pical treat me nts i ncl u de mec hl oret ha mi ne [ 1 1-1 3]  ( nitr o ge n 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 2 0  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
m ustar d or M ustar ge n ®) a d mi nistere d i n a ta p w ater s ol uti o n or as a n oi nt me nt, a n d car m usti ne 
( B C N U) [ 1 4]. B ot h treat me nts ha ve si g nifi ca nt res p o nse rates i n earl y sta ge M F diseas e, b ut 
ha ve virt uall y n o effect o n e xtra c uta ne o us diseas e or t he circ ul ati n g mali g n a nt T -cells i n S S 
patie nts [ 1 3].  
M ost c urre ntl y use d M F treat me nts ar e n ot a p pr o v e d b y t h e U nite d States F o o d a n d Dr u g 
A d mi nistrati o n ( F D A ) a n d m ust still be c o nsi dere d i n vesti gati o nal a ge nts [ 1 5, 1 6]. Oral 5 - or 8 -
met h o x y ps or ale n ( Ps oral e n) gi ve n wit h ultra vi olet A li g ht ( P U V A) [ 1 7- 1 9]  is c o m m o nl y us e d i n 
t he treat me nt of pla q u e sta ge a n d c uta ne o us t u m ors. T he d ura ble efficac y of P U V A is lar gel y 
li mite d t o patie nts wit h earl y st a ge diseas e ( Sta ge I A, I B a n d II A). Patie nts wit h Sta ge II B 
(t u m ors pl us a de n o pat h y) a n d Sta ge III ( ge n eralize d er yt hr o der m a pl us a de n o pat h y) h a ve a 
c o m plete res p o nse ( C R) rate i n less t ha n 5 0 % of cases [ 1 9]. T he C R rate is n ot as hi g h as s ee n i n 
earlier sta ge patie nts . T h e maj orit y of t hese patie nts will rela pse after P U V A a n d are e ve nt u all y 
refr act or y t o t his treat me nt [ 1 8]. A variati o n of P U V A calle d e xtrac or p oreal p h ot o p heresis ( E C P) 
is o ne of t he fe w s yst e mic treat me nts c urre ntl y a p pr o ve d b y t he F D A f or t he treat me nt of C T C L 
patie nts (t he ot hers bei n g Be x ar ote ne a n d De nile u ki n Diftit o x, disc usse d bel o w). Wit h E C P, t he 
peri p her al bl o o d of a pati e nt is di verte d t hr o u g h a le u k o p h oresis mac hi ne (t he E C P circ uit) a n d 
e x p ose d t o U V A wa vele n gt h  li g ht i n t he prese n ce of Ps orale n. I n ad diti o n t o t he direct 
destr ucti o n of t he mali g n a nt T- cells, a n i m m u ne res p o nse t o war d ot h er n o n-U V A  e x p ose d 
mali g na nt T- cells has bee n p ost ulate d [ 1 7]. P h ot o p heresis has de m o nstrate d efficac y n ot o nl y f or 
M F patie nts b ut, i n partic ular, is als o effecti ve i n t he treat me nt of S S patie nts [ 1 9]. Ultra vi olet B 
le n gt h li g ht has als o bee n use d t o treat M F p atie nts . T his treat me nt ca n b e gi ve n at h o me a n d 
d oes n ot re q uire pretreat me nt wit h Ps orale n. Alt h o u g h U V B treat me nt has a p preci a ble res p o nse 
rates i n earl y st a ge diseas e [ 2 0], it has n ot gai ne d wi de p o p ularit y f or t he treat me nt of m ore 
a d va nce d M F p atie nts.  
Patie nts wit h a d va nce d c uta ne o us lesi o ns or disease refract or y t o t o pical t hera pies h a ve recei v e d 
c o n ve nti o nal c o m bi nati o n c he m ot hera p e utic l y m p h o ma re gi me ns wit h u ni m pressi ve l o n g-ter m 
res ults [ 2 1, 2 2]. Rece ntl y, t he n ucle osi de a n al o gs Fl u dara bi n e ®, de o x yc of or m yci n ( D C F) a n d 2-
c hl or o de o x y a d e n osi ne ( 2- C D A), w hic h h a ve si g nifica nt acti vit y i n ot her l y m p h oc ytic 
mali g na n cies s uc h as c hr o nic l y m p h oc ytic le u k e mia ( C L L) a n d hair y cell le u ke mia ( H C L), ha v e 
bee n i ntr o d uce d i nt o cli nical trials f or M F a n d S S patie nts [ 2 3-2 6] . Earl y res ults s u g gest  acti vit y 
a n d a d diti o nal trials are u n der wa y or i n t he pla n ni n g sta ge.  
Se veral bi ol o gi c a ge nts h a ve bee n teste d i n patie nts wit h M F or S S [ 2 7- 3 5] . I nterfer o n-al p h a 
(I F N-α ) tr eat me nt has bee n teste d i n M F a n d S S p atie nts i n a variet y of d osi n g re gi me ns [ 1 6, 2 7, 
2 8] . T he res ults fr o m t hese trials ha ve de m o nstrate d great v ariati o ns i n res p o nse rates wit h s o me 
s u g gesti o n of d ose relate d i m pr o ve me nts i n s ustai ne d effi cac y [ 2 9]. T he t o xicities of hi g her d ose 
a n d t he c u m ulati ve t o xicities wit h c hr o nic a d mi nistrati o n ha ve te m pere d t he earl y e nt h usias m f or 
t he pr o mise of I F N-α  i n M F ( 2 9), b ut I F N-α  re mai ns a mai nsta y of treat me nt f or M F a n d S S, 
a n d ma y re prese nt o ne of t he m ost acti ve bi ol o gical a ge nts f or C T C L. Alt h o u g h res ults fr o m 
ot her t y p es of I F Ns [ 3 1, 3 2] a n d bi ol o gical res p o nse m o difiers [ 3 3, 3 4] ha ve bee n less 
e nc o ura gi n g, s e ver al rece nt re p orts of efficac y wit h c o m bi ne d I F N- α  a n d n ucle osi de 
c he m ot hera p e utics ha v e le d t o re ne w e d a p praisal of I F N i n t his setti n g [ 3 5]. F urt her m ore, rece nt 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 2 1  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
o bser vati o ns s u p p ort t he c o m bi ne d use of I F N wit h p h ot o p heresis f or t he treat me nt of S S [ 3 6, 
3 7] . 
5. 2.  
R ati o n ale  
H y p erici n is a k n o w n p h ot o d y na mic a ge nt wit h p ote ntia l t o treat a vari et y of i nfla m mat or y 
der mat ol o gi cal diseas es ass ociate d wit h l y m p h oc ytic i nfiltrates, i ncl u di n g C T C L .  
T he m ost c o m m o nl y use d re gi me n, P U V A li g ht treat me nt, is a f or m of p h ot o d y na mic t hera p y 
( P D T) si nce o x y ge n c o ns u mi n g p h ot oreacti o ns ma y be i n v ol ve d i n t his p h ot ot hera p y [ 3 8]. 
Si milar t o ot her k n o w n p h ot ose nsitizi n g a ge nts, si n glet o x y ge n is t he pri nci pal pr o d uct i n t he 
p h ot ose nsitizati o n of h y p erici n. I n t he prese n ce of li g ht irra diati o n, h y perici n e x cites o x y ge n t o 
its si n glet state a n d is ca p a ble of ge n erati n g s u per o xi de ra dicals t hat ca n lea d t o o xi dati o n of 
tr y pt o p ha n i mi daz ole gr o u ps i n pr otei ns a n d t o o xi dati o n of fatt y aci ds i n bi ol o gical s yste ms . 
H y p erici n is ma xi mall y acti vate d b y li g ht of a b o ut 5 9 0- 6 5 0 n m wa vele n gt h ( i.e., i n t he yell o w 
re gi o n) [ 3 9-4 1] . H y perici n bi n ds t o p h os p h oli pi ds s uc h as p h os p hati d yl c h oli nei of cell 
me m bra nes a n d it bi n ds t o retr o viral particles, pr o ba bl y b y ass ociati n g wit h t he me m bra ne 
deri ve d li pi d e n vel o pe ( 4 2). 
E mer gi n g e vi de nce i n dicates t hat h y p erici n bi n ds t o heat s h oc k pr otei n 9 0 l ea di n g t o its 
e n ha nce d u bi q uiti n ylati o n. T his disr u pts se veral critical gr o wt h pat h wa ys ulti matel y l ea di n g t o 
cell deat h [ 4 2]. 
H y p erici n is re p orte d t o be e q ual i n p h ot o d y na mi c p ote nc y t o ot her p h ot os e nsitizi n g p or p h yri ns, 
c hl or o p h yll a n d r ose be n ga 1 [ 4 3]. Se veral st u dies ha ve s h o w n t hat be ni g n h y p er pr oliferati ve a n d 
h y per vasc ul ar c o n diti o ns s uc h as ps oriasis ca n b e i m pr o ve d b y p h ot ose nsiti zati o n wit h 
p or p h yri ns. Sel ecti ve se nsitizati o n of ps oriasis usi n g p or p h yri ns h as bee n d e m o nstrate d as a n 
effecti ve treat me nt a n d ma y b e relat e d t o t he i ncrease d vas c ularit y of ps ori atic pla q ues [ 4 4]. 
A n ot her re p ort usi n g s yst e mic ti n - pr ot o p or p h yri n i n c o m bi nati o n wit h l o n g wa vele n gt h 
ultra vi olet li g ht s u g gests a meli orati o n of ps oriasis i n ps oriatic patie nts [ 4 5]. 
H y p erici n has s e ver al attri b utes t hat ma ke it attracti ve f or i n vesti gati n g its cli nical use i n s ki n 
dis or ders wit h p ote ntial a d va nta ges o ver p h o t ot hera p y wit h P U V A . H y peri ci n has bee n s h o w n t o 
be n o n- m uta ge nic; it d oes n ot i ntercalate i nt o D N A . H y p erici n is ma xi mall y acti vate d b y visi ble 
li g ht at wa v ele n gt hs pr o d uce d b y fl u oresce nt li g ht t hat ma y si g nifica ntl y re d uce t he si de effects 
ass ociate d wit h U V irra diati o n  a n d all o ws f or dee per s ki n pe netrati o n. H y p erici n has a relati vel y 
l o n g half -life ( 2 0- 2 4 h o urs) w hic h all o ws f or re p eate d li g ht acti vati o n wit h si n gle d oses. 
H y p erici n has b ee n de m o nstrate d t o be pres e nt i n s ki n after s yste mic a d mi nistr ati o n a n d it has 
bee n s h o w n t o be a b o ut 2 0 % bi oa vaila ble after oral a d mi nistrati o n. T he mec ha nis m of 
p h ot oreacti o ns (si n glet o x y ge n pr o d ucti o n) is t he sa me as ot her p h ot ot hera pe utic a ge nts t hat ha v e 
bee n s h o w n t o be b e neficial i n t he treat me nt of ps oriasis.  
A P hase 1 c li nical st u d y i n healt h y s u bjects deter mi ni n g t he p h ot ose nsiti ve c o nce ntrati o ns of 
t o picall y- a p plie d h y perici n a n d t he mi ni m u m p h ot ot o xic d ose ( M P D) of li g ht re q uire d t o ca use 
p h ot ose nsiti vit y w as c o m plete d [ 4 6]. Data deri ve d fr o m t his cli nical trial i n dicate t hat h y peri ci n 
c o nce ntr ati o ns of 0. 1 % a n d 0. 5 % i n H y dr o p hilic Oi nt me nt U S P ca use c uta ne o us p h ot ose nsiti vit y 
w he n t o picall y a p plie d f or 2 4 h o urs a n d acti vate d b y visi ble li g ht. T h e M P D was f o u n d t o be 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 2 2  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
4 J o ules/ c m 2, w hereas 8 J o ules/c m 2 was deter mi ne d t o be a ver y effecti ve li g ht d ose yiel di n g 
bris k p h ot ot o xic reacti o ns. 
F urt her m ore, r ece nt r esearc h i n dicat es t hat p h ot oacti vate d h y perici n p osses ses si g nifica nt 
a nti pr oliferati ve eff ects o n acti vate d n or mal h u ma n l y m p h oi d cells a n d mali g na nt T- cells 
p urifie d fr o m t he bl o o d of patie nts wit h S S, t he le u ke mic p hase of C T C L . T he mec ha nis m of t he 
a nti pr oliferati ve acti vit y ma y b e relat e d t o t he hi g h rat e of a p o pt otic deat h i n t hese l y m p h oi d 
cells [ 4 7]. 
T he i n vitr o data ge n erat e d usi n g acti vate d l y m p h oc yt es a n d mali g na nt T -cells le d t o t he 
i nitiati o n of a P hase 2 , m ultice nter, place b o-c o ntr olle d cli nical trial usi n g t o pical S G X 3 0 1  
f oll o we d b y li g ht acti vati o n t o treat earl y sta ge patie nts wit h C T C L as well as pla q ue ps oriasis. 
Differ e nt s ki n lesi o ns were treate d wit h o ne of t w o differe nt stre n gt hs of t o pical S G X 3 0 1  or 
place b o . A t otal o f 1 2 p atie nts wit h C T C L w ere e ntere d. A hi g h rate of cli ni cal res p o nse was 
o bser ve d a m o n g t h ose lesi o ns treate d wit h t he p h ot oacti ve S G X 3 0 1 , w hic h was statisticall y 
si g nifica nt as c o m par e d t o lesi o ns treate d wit h place b o [ 4 8].  
T hese la b or at or y data i n dicati n g i n hi biti o n of cell pr oliferati o n a n d a p o pt otic deat h b y li g ht-
acti vate d S G X 3 0 1  i n l y m p h oi d cells, ta ke n t o get her wit h t he P hase 1 a n d P h ase 2 cli nical res ults 
de m o nstrati n g c uta ne o us p h ot ose nsiti vit y reacti o ns t o t o picall y-a p plie d, li g ht- acti vate d S G X 3 0 1 , 
a n d cleari n g of acti ve s ki n lesi o ns of C T C L patie nts ser ve as t he b asis f or c o n d ucti n g t he 
pr o p ose d P hase 3 cli nical trial i n C T C L . 
5. 3.  
C he mistr y  
H y p erici n is a nat ur al c o m p o u n d f o u n d i n ste ms a n d petals of 
pla nts of t he ge n us Hy p eric u m . Wit hi n t his ge n us are 8 fa milies 
a n d 4 3 s pecies, i ncl u di n g t he c o m m o n St. J o h n's w ort pla nt, 
Hy peric u m p erf or at u m . T he c he mical na me is 4, 5, 7, 4', 5', 7' -
di met h yl - mes o na p ht h o dia nt hr o ne, a c o m p o u n d c o m p ose d of ei g ht 
c o nj u gate d ri n gs c o ntai ni n g si x h y dr o x yl gr o u ps, t w o car b o n yl a n d 
t w o met h yl gr o u ps i n a s y m metric p atter n w h e n i n verte d a b o ut a 
ce ntral a xis . W he n diss ol ve d i n et ha n ol s ol uti o ns it pr o d uces a 
bri g ht f 1 u oresce nt c o m p o u n d. H y p erici n t o be us e d i n t his cli nical 
trial is c he micall y s y nt h esize d a n d n ot e xtracte d fr o m pla nts. 
5. 4.  
Precli nic al D at a  
5. 4. 1  
A nti vir al Acti vit y  
H y p erici n is a n effecti ve vir uci dal a ge nt t hat  directl y i nacti vates a br oa d ra n ge of vir uses a n d 
retr o vir uses. Affecte d vir uses i ncl u de t he m uri ne Frie n d [ 4 0] a n d Ra usc her vir uses [ 4 9], e q ui ne 
i nfecti o us a ne mia vir us [ 5 0], m uri ne i m m u n o deficie nc y vir us [ 3 9], m uri ne c yt o me gal o vir us ( 5 1), 
i nfl ue nza [ 4 9], vesic ul ost o matitis vir us [ 5 1], Se n dai [ 5 1], her pes [ 4 9], a n d d uc k he patitis B vir us 
[ 5 2]. 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 2 3  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
I n vitr o e x peri me nts ha ve de m o nstrate d t hat h y p erici n i n hi bits t he a bilit y of HI V t o esta blis h 
pr o d ucti ve i nfecti o n i n acti vate d m o n o n uclear cells i n a c o nce ntrati o n de pe n de nt ma n ner. I n 
a d diti o n, t he pr o d ucti o n of HI V b y cells pre- i nfecte d b y relati vel y l o w a m o u nts of HI V was als o 
i n hi bite d t o a lesser e xte nt. 
Rece ntl y, i nfecti o us vir us titers of b o vi ne diarr h ea vir us ( B V D V) w ere c o m pletel y i nacti vate d b y 
h y perici n i n vitr o i n t he prese nce of li g ht ( Pri nce et al. u n p u blis he d). B V D V is a pesti vir us t hat 
s hares cl ose si milarities a n d si g nifica nt h o m ol o g y wit h he patitis C vir us ( H C V) i n t he 5' 
u ntra nslate d re gi o n s e q ue nc e, i n sec o n d ar y str uct ures a n d i n t he or ga nizati o n of ge nes e n c o di n g 
t he p ol y pr otei n [ 5 3]. T hese st u dies s u g gest t hat h y perici n ma y ha v e p ote ntial efficac y a gai nst 
H C V . St u dies b y Ta n g et al. [ 4 9] s u g gest t hat li pi d e n vel o pe d vir uses as a gr o u p are i n acti vate d 
b y h y perici n, w hereas n o n-e n vel o pe d vir us es s uc h as a de n o vir us a n d p oli o vir us are u naffecte d. 
H y p erici n a p p ears t o bec o me ass ociate d wit h t he li pi d e n vel o pe of t he vir us a n d ge nerates si n glet 
o x y ge n t h at cr oss -li n ks viral ca psi d pr otei ns a n d pre ve nts vir us u nc o ati n g d uri n g i nfecti o n [ 4 1, 
5 4, 5 5] . T he mec ha nis m of a cti o n d oes n ot a p p ear t o all o w f or t he de v el o p me nt of dr u g resista nt 
m uta nts i n vitr o. 
Se veral li nes of e vi d e nce s u g gest t hat t he a ntiretr o viral acti vit y of h y perici n res ults fr o m its 
a bilit y t o i ncrease ri gi dit y of t he retr o viral ca psi d . Ca psi d ri gi dit y ma y t h e n i n hi bit vir us 
i nfecti vit y a n d pre v e nt release of r e verse tra ns cri ptase e nz y me. I nteracti o ns wit h t he ca psi d 
pr otei ns ma y als o acc o u nt f or electr o n micr osc o pi c e vi de nce t hat  s h o ws a diff use d, i m pr o perl y 
f or me d ca psi d i n viri o ns b u d di n g fr o m h y p erici n-treate d cells. A p pare ntl y, t he acti o n of 
h y perici n o n t he ca psi d ca n occ ur w he ne v er t he dr u g c o m es i n c o ntact wit h t he vir us, w het her 
t he vir us is i n s ol uti o n or i nfecti n g or b u d di n g fr o m a cell w h ose me m bra n e c o ntai ns h y peri ci n. 
I n viv o st u dies ha ve d e mo nstrate d t hat h y perici n pr o d uces c o m plet e i n hi biti o n of s ple n o me gal y 
at 1 0 da ys i n B A L B/c mi ce i nfecte d wit h Frie n d le u ke mia vir us ( F V) w he n t he d ose ( 5 0 
µ g/ m o use) is a d mi nistere d si m ulta ne o usl y wit h t he viral i n oc ul u m . W he n c o-a d mi nistere d wit h 
t he vir us, h y p erici n i n hi bite d s ple n o me gal y i n a d ose- de pe n d e nt fas hi o n acr oss t he d osa ge r a n ge 
fr o m 0. 1 n g t o 5 0 µ g ( p er m o use) . T he de gree of i n hi biti o n ra n ges fr o m a p pr o xi matel y 2 0 % at 
0. 1 µ g / m o use t o 1 0 0 % at 5 0 µ g/ m o use. Ass u mi n g a 2 5 g m o us e, t hese d oses w o ul d ra n ge fr o m 
4 µ g/ k g t o 2  m g/ k g . At t h e hi g h est d ose, h y perici n was als o s h o w n t o pre v e nt vire mia as 
meas ure d b y r e verse tra nscri ptase acti vit y i n t he s er u m , a n d s plee ns of treate d a ni mals were free 
of bi ol o gicall y acti ve  F V . W he n t he d ose ( 5 0 µ g/ m o use) was a d mi nistere d o n t he sa me da y, b ut 
f oll o wi n g i n oc ulati o n wit h t he vir us, F V-i n d u ce d s ple n o me gal y was o nl y re d uce d b y 
a p pr o xi matel y 7 0 %. I n a d diti o n t o t he st u dies i n F V, i n vitr o m uri ne st u dies ha ve als o s h o w n 
h y perici n t o be acti ve a gai nst ra diati o n le u ke mia vir us a n d c hr o nic L P- B M 5 i nfecti o n ( m uri ne 
AI D S).  
5. 4. 2  
A nti pr olif er ati ve Eff ects o n L y m p h oi d Cells  
Data fr o m t he l a b orat or y of Dr. Alai n R o o k of t he U ni versit y of Pe n ns yl v a nia ha ve de m o nstrate d 
a si g nifica nt a nti pr olifer ati ve effect of h y perici n o n acti v ate d n or mal h u ma n l y m p h oi d cells w he n 
t he h y p erici n-tr eate d cells are e x p ose d t o visi ble li g ht [ 4 7]. At c o nce ntrati o ns of h y p erici n 
ra n gi n g b et wee n 0. 1 a n d 0. 5 µ M, a 2 0-mi n ute  e x p os ure of n or mal l y m p h oi d cells t o fl u oresce nt 
li g ht pr o d uce d c o m plete i n hi biti o n of pr oliferati ve res p o nses t o t he p ote nt mit o ge ns P H A a n d 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 2 4  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
C o n A. Si milarl y, mali g n a nt T -cells p urifie d fr o m t he bl o o d of patie nts wit h S S , t he le u ke mic 
p hase of C T C L , ha d t heir a bilit y t o gr o w i n res p o nse t o T-cell gr o wt h fact ors mar ke dl y i n hi bite d 
b y 0. 3 µ M of h y perici n a n d 2 0- mi n ute  e x p os ure t o fl u oresce nt li g ht. W hile t he precise 
mec ha nis m of i n hi biti o n of pr olifer ati o n is u nclear, it a p p ears t hat h y perici n has t he ca p acit y t o 
i n d uce a hi g h rat e of a p o pt otic deat h i n b ot h n or mal a n d mali g n a nt l y m p h oi d cells [ 4 7]. T he 
i m plicati o ns of t hese fi n di n gs f or t h e use of t o pical h y perici n t o treat C T C L , w hic h is 
c haracterize d b y mali g na nt l y m p h o c ytic i nfiltrates i n t he s ki n, are si g nifica nt, a n d ser ve as t he 
basis f or t he pr o gr a m .  
5. 4. 3  
T o xic ol o g y 
T o date, a ni mal t o xic ol o g y st u dies ha v e bee n p erf or me d i n m o n ke ys f oll o wi n g i ntra v e n o us (I V) 
a d mi nistrati o n of h y perici n a n d i n rats a n d m o n ke ys f oll o wi n g oral a d mi nistrati o n. 
F oll o wi n g a d mi nistrati o n of a n I V b ol us d ose of 3 0 m g/ k g t o c y n o m ol g us m o n ke ys, p u pil 
dilati o n, e mesis, r hi n orr hea, sali vati o n, pr ostrati o n, ata xia, a n d tre m ors were o b ser ve d. T he 
effects wer e o bser v e d s h ortl y after a d mi nistrati o n of t he d ose a n d w ere re p orte d t o last f or 1 0 t o 
2 0 mi n utes. T hese eff ects were pre ve nt e d or re d uce d i n i nte nsit y a n d fre q ue nc y b y i nf usi n g t he 
d ose o ver a 2 0- mi n ute peri o d. Wit h t he e x ce pti o n of a tra nsie nt i ncreas e i n S G O T, n o ot her 
a b n or malities wer e re p orte d i n t he cli nical c he mistr y para met ers . Pat h ol o gi c e val uati o ns re veale d 
a d ose-r elate d r eacti o n at t he site of i njecti o n, c haracterize d b y ple ocell ular i nfiltrates, fi bri n, or 
or ga nizi n g t hr o m bi. At hi g her d oses, t he se v erit y pr o gresse d t o i ncl u de aca nt h osis, e pi der mal 
necr osis, a n d v asc ulitis. Fi bri n t hr o m bi were als o o bser ve d i n t he l u n g a n d m y ocar di u m, a n d 
were b elie ve d t o be a res ult of t he reacti o n at t he i njecti o n site ( platelet c o u nts  a n d c oa g ulati o n 
i n dices were re p orte d t o be wit hi n n or mal li mits).  
T we nt y -ei g ht da y, r e peate d - d ose or al t o xicit y st u dies ha ve bee n c o n d uct e d i n rats at d oses of 2 0, 
4 0, a n d 8 0 m g/ k g/ da y, a n d i n r hes us m o n ke ys at d oses of 3, l 0, a n d 3 0 m g/ k g/ da y (i n c o m paris o n 
t o place b o). I n precli nical a ni mal safet y st u dies, n o detecta ble e vi de nce of s yste mic t o xicit y was 
o bser ve d i n rats recei vi n g or al d oses u p t o 8 0 m g/ k g/ da y f or 2 8 da ys. I n c y n o m ol g us m o n ke ys, 
oral d oses of 3 m g/ k g/ da y f or 2 8 da ys s h o we d n o si g ns of s yste mic t o xicit y; h o we ver, si g ns of 
p h ot ot o xicit y wer e o bser ve d wit h 1 0 a n d 3 0 m g/ k g/ da y. I n b ot h a n A mes t est a n d a n i n vitr o 
c yt o ge nic assa y, h y p erici n has bee n s h o w n t o be n o n- m uta ge nic. I n t he m o n ke y st u d y, s ki n 
reacti o ns i ncl u di n g b ullae, er yt he ma, a n d scratc hi n g w ere o bs er ve d i n a ni mals recei vi n g 1 0 a n d 
3 0 m g/ k g/ da y . T his reacti o n is t h o u g ht t o re pres e nt t he k n o w n p h ot ot o xic effects of h y p erici n. 
T he a vera ge pl as ma c o nce ntrati o ns i n t his st u d y h a ve bee n re p orte d t o be 0. 5 µ g/ m L at 3  
m g/ k g/ da y, 3. 3 µ g/ m L at 1 0  m g/ k g/ da y, a n d 1 5 µ g/ ml at 3 0 m g/ k g/ da y . N o ot her t o xic effects 
were re p orte d (see I D B).  
I n a d diti o n t o s yste mic t o xicit y st u dies descri be d a b o ve, a 2 8-da y der mal t o xicit y st u d y w as 
u n derta ke n i n r a b bits wit h h y perici n c o m bi ne d wit h fl u oresce nt li g ht treat me nt (see I D B). T he 
p ur p ose of t his st u d y w as t o deter mi ne t he t o xicit y p ote ntial of h y p erici n a d mi nistere d t wice -
wee kl y t o t he d orsal area of ra b bits at d oses of 1 0, 2 0 a n d 1 0 0 µ g/ d ose i n H y dr o p hilic Oi nt me nt 
U S P f oll o we d b y fl u or es ce nt li g ht treat me nt 2 4 h o urs later. A d ose-rel ate d res p o nse w as 
o bser ve d i n t he i nci de n ce of er yt he ma, e de ma a n d des q ua mati o n a m o n g a ni mals recei vi n g 1 0, 2 0 
or 1 0 0 µ g/ d ose of h y p eri ci n a n d li g ht treat me nt c o m pare d t o a ni mals recei vi n g t he place b o 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 2 5  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
ve hicle a n d li g ht treat me nt. At o nia was see n o nl y at 2 0 a n d 1 0 0 µ g/ d ose; fiss uri n g w as o bser ve d 
at o nl y 1 0 0 µ g/ d os e b ut esc har f or mati o n was n ot o bser ve d i n a n y gr o u p. T he o nl y fi n di n g i n t he 
gr o u p recei vi n g t h e place b o ve hicle a n d li g ht treat me nt was ver y sli g ht er yt he ma, w hic h w as 
see n i nter mitte ntl y i n all a ni mals i n t his gr o u p. T h e der mal effects o bser v e d wit h h y perici n 
oi nt me nt i n t his gr o u p were n ot se v ere a n d see m e d t o res ol ve wit h ti me.  
Der mal a p plicati o n of h y perici n ha d n o a p p are nt effects o n cli nical pat h ol o g y res ults. T here were 
test material-rel ate d fi n di n gs u p o n a n at o mical pat h ol o g y e x a mi nati o n of t he s ki n. 
M acr osc o picall y, o n e of t hree or t w o of t hree a ni m als fr o m t he gr o u p a d mi nistere d 2 0 a n d 1 0 0 
µ g/ d ose , res p ecti vel y, ha d o bser vati o ns i n t he treate d s ki n. Micr osc o picall y, treate d s ki n ha d 
e pit helial h y p er plasia a n d i ncreas e i n i nfla m mat or y cells . A ni mals a d mi nistere d 1 0 0  µ g/ d ose ha d 
t he m ost se vere c h a n ges a n d fe males were m ore s e verely affecte d t ha n m ales. Mi ni mal 
h y per plasia a n d i n crease d i nfla m mat or y cells c o ul d be attri b ute d t o li g ht treat me nt  of sites 
treate d wit h place b o ve hi cle al o ne. Uri nar y bla d d er calc uli were m ore c o m m o n at t he hi g her 
d ose gr o u ps es peciall y i n males treate d wit h 1 0 0 µ g/ d ose. W het her t h e i ncrease i n calc uli was a 
test-material -r elate d eff ect is u ncertai n. 
5. 4. 4  
P h ar m a c o ki netics  
T he P K  of h y peri ci n f oll o wi n g I V b ol us a d mi nistrati o n has  bee n i n v esti gat e d i n mice ( 4. 5  
m g/ m 2), r hes us m o n ke ys ( 2. 5 m g/ k g), a n d c y n o m ol g us m o n ke ys ( 2 mg/ k g) . T he a vera ge 
eli mi nati o n half-life was re p orte d t o be 3 6. 7 h o urs i n t he c y n o m ol g us m o n k e y, 4 0. 3 h o urs i n t he 
m o use, a n d 5 5. 8 h o urs i n t he r hes us m o n ke y. 
5. 5.  
Pri or Cli nic al Tri als  
5. 5. 1  
S yste mic H y perici n  
T o date, si x ( 6) cli nical trials ha ve bee n c o n d ucte d a n d / or i nitiate d wit h orall y a n d i ntra v e n o usl y 
a d mi nistere d h y perici n. T hese trials i ncl u de :  
( 1) A bi oa vaila bilit y st u d y i n 1 0 healt h y s u bjects,  
( 2 & 3) T w o trials ( A C T G 1 5 0 a n d A C T G 2 5 8) s p o ns ore d b y t he Nati o nal I nstit ute of Aller g y 
a n d I nfecti o us Disease 
  
( 4) A d ose d eter mi ni n g st u d y after d ail y oral a d mi nistrati o n f or 2 8 da ys i n HI V- i nfecte d patie nts 
t o deter mi ne t he ma xi m u m t olerated d ose ( M T D),  
( 5) A trial f or he patitis C patie nts t o deter mi ne t he a nti-H C V acti vit y after 2 m o nt hs of oral 
h y perici n, a n d  
( 6) A cli nical trial f or patie nts wit h mali g na nt brai n gli o mas treate d f or t hree m o nt hs wit h oral 
h y perici n. 
A si n gle - d os e bi oa vaila bilit y st u d y w as c o n d uct e d i n 1 0 healt h y s u bjects. Fi ve ( 5) s u bjects 
recei v e d 1. 2 5 m g/ k g orall y a n d 0. 2 5 m g/ k g i ntra v e n o usl y w hile t he ot h er fi ve ( 5) s u bjects 
recei v e d 2. 0 m g/ k g orall y a n d 0. 3 7 5 m g/ k g i ntra v e n o usl y. E ac h s u bject recei ve d o ne ( 1) I V d ose, 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 2 6  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
o ne ( 1) or al d ose u n der f asti n g c o n diti o ns, a n d o n e ( 1) oral d ose f oll o wi n g a sta n dar d fatt y 
brea kf ast . T he d oses w er e a d mi nistere d i n ra n d o m or der, a n d eac h d ose w as se parate d b y a 1-
wee k w as h o ut peri o d. S o me i n di vi d uals w h o recei ve d oral h y perici n i n t h e first wee k de v el o pe d 
c o nsi dera ble c uta ne o us disc o mf ort wit hi n h o urs of bei n g e x p ose d t o li g ht. A fe w of t h ese 
i n di vi d uals de vel o pe d t his reacti o n after o nl y a fe w mi n utes of s u n e x p os ure. After t his 
e x perie nce, s u bjects t o o k a p pr o priate preca uti o ns t o mi ni mize s u nli g ht e x p os ure a n d, as a res ult, 
e x perie nce d less s y m pt o mat ol o g y.  
I n A C T G 1 5 0, I V h y peri ci n was a d mi nistere d t o 2 7 HI V-i nfecte d patie nts at t hree ( 3) d os e le vels 
( 0. 2 5 m g/ k g t w o ti mes w ee kl y, 0. 5 m g/ k g t w o ti m es wee kl y, a n d 0. 2 5 m g/ k g t hree ti mes  
wee kl y) . D os e -li miti n g t o xicit y i ncl u di n g pai nf ul parest hesia, c uta ne o us disc o mf ort, a n d 
er yt h e ma d ue t o p h ot ose nsitizati o n was o bser ve d at 0. 5 m g/ k g t wice wee kl y . Si milar s y m pt o ms 
were o bs er ve d at 0. 2 5 m g/ k g t wice wee kl y, b ut t h e y were mil der a n d ge nerall y di d n ot re q uire 
disc o nti n uati o n of treat me nt. N o si g nifica nt c ha n ges were o bser v e d i n he m at ol o g y or s er u m 
c he mistr y p a nels f or p atie nts treate d wit h h y perici n wit h t he e x ce pti o n of o ne  ( 1) patie nt w h o 
de vel o pe d a b n or mal li ver f u ncti o n test res ults f oll o wi n g t he i nitial d ose a n d a gai n o n re-
c halle n ge. St u d y A C T G 2 5 8 was i nitiate d as a c o nce ntrati o n -c o ntr olle d st u d y of escal ati n g oral 
d oses of h y perici n i n HI V- i nfect e d patie nts. T he i nitial treat me nt gr o u p st arte d at a d osa ge of 0. 5 
m g/ k g o nce d ail y wit h t he o bjecti ve of pr o d uci n g a tr o u g h h y perici n c o nce ntrati o n i n t he ra n ge 
of 0. 4 t o 0. 7 µ g/ m L . After e nr olli n g t hree  ( 3) s u bjects i nt o t he first d osa ge le vel ( 0. 5 m g/ k g/ d a y), 
t he st u d y w as place d o n cli nical h ol d after all t hree ( 3) patie nts de v el o pe d p h ot oto xic reacti o n s 
after 6 - 8 d a ys of tr eat m e nt. T he p h ot ose nsiti vit y reacti o ns w ere c haracterize d b y er yt h e ma, 
b ur ni n g se ns ati o n a n d ti n gli n g a n d w ere m ost pr o mi ne nt o n t he face a n d h a n ds, partic ularl y 
w he n e x p ose d t o t he s u n. S y m pt o ms a b ate d after 4 - 5 da ys. I b u pr ofe n w as re p orte d t o pr o vi de 
s o me be nefit. 
I n a d diti o n t o t hese trials, a cli nical trial has bee n u n derta ke n i n 2 7 patie nts t o deter mi ne t he d ose 
se parati o n bet w ee n a nti- HI V acti vit y a n d c ut a ne o us p h ot ose nsiti vit y. T he d ose -res p o ns e st u d y 
was carrie d o ut i n HI V- i nfecte d p atie nts after d ail y oral a d mi nistrati o n of h y p erici n f or 2 8 d a ys. 
T his trial was c o n d ucte d at t he Vacci ne Trial Ce ntre at Ma hi d ol U ni versit y, Ba n g k o k, T h aila n d. 
T he oral d ose of 0. 0 5 m g/ k g was well t olerate d a n d 0. 1 m g/ k g a p pears t o b e t he ma xi m u m 
t olerate d d ose i n t hese HI V i nfecte d p atie nts. Bi oa vaila bilit y of h y perici n w as f urt her d eter mi ne d 
i n t his trial. D ose pr o p orti o nalit y i n ter ms of tr o u g h ( Cmi n ) a n d pea k ( Cma x ) c o nce ntrati o ns a n d 
area u n d er t he s er u m c o n ce ntrati o n -ti me c ur ves w as ma nifeste d wit h t he 0. 0 5 a n d 0. 1 0 m g/ k g 
d oses. T he mea n bi ol o gic half- life of h y p erici n i n t he HI V-i nfecte d p atie nts was a b o ut 2 0 h o urs. 
All s u bjects b ut o ne w h o recei v e d t he 0. 0 5 m g/ k g d ose c o m plete d 2 8 da ys of d osi n g. F o ur ( 4) of 
ele ve n ( 1 1) w h o r ecei ve d 0. 0 5 m g/ k g d osa ge c o m plai ne d of mil d b ur ni n g s e nsati o n. T w o ( 2) 
patie nts w h o recei ve d 0. 1 6 m g/ k g were wit h dra w n fr o m t he st u d y d u e t o se vere b ur ni n g 
se nsati o n; o ne ( 1) of t hes e t w o ( 2) de v el o pe d er yt he ma w hic h disa p peare d wit hi n 7 da ys of 
st o p pi n g t he dr u g. Ni ne  ( 9) of t wel ve ( 1 2) patie nts w h o recei ve d 0. 1 0 m g/ k g ha d mil d 
p h ot ose nsiti vit y s y m pt o ms a n d fi ve ( 5) of t wel ve (1 2) ha d mil d h y p erest h esia o n e x p os ure t o 
r o o m te m perat ur e water. 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 2 7  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
A d diti o nall y, a cli nical trial was u n derta k e n wit h h y perici n i n f ort y- t w o (4 2 ) patie nts wit h 
mali g na nt brai n gli o mas usi n g oral d os es of h y perici n ( 0. 0 5 t o 0. 5 0 m g/ k g) a d mi nistere d o nce 
dail y f or u p t o t hree ( 3) m o nt hs. T here were te n  ( 1 0) patie nts w h o were dee me d “res p o n ders ” 
a n d t hese patie nts w ere c o nti n ue d o n dr u g t hera p y u n der ‘c o m p assi o nate us e”. Of t he t e n ( 1 0) 
res p o n ders, f o ur ( 4) p atie nts c o nti n ue d o n t he dr u g be y o n d 1 7. 5 m o nt hs u p t o 4 5 m o nt hs. A 
s u m mar y of t he A d verse E ve nts ( A E) ca n be f o u n d i n t he I n v esti gat or’s Dr u g  Br oc h ure  (I D B). 
P h ot ot o xicit y ass o ciate d wit h mil d urticaria, er yt h e ma, itc hi n g a n d re d n ess o n face a n d ha n ds 
were t he m aj orit y of s y m pt o ms . Heat e x ha usti o n a n d facial s u n b ur n were d efi nitel y ass ociate d 
wit h h y perici n t hera p y . Ele vate d L D H, s eiz ure a n d bl o o d cl ot t o ri g ht le g w ere o bser ve d i n 
se parat e patie nts a n d dee me d “ p ossi bl y relate d t o dr u g”. 
A n ot her cli nical st u d y has bee n c o m plete d i n patie nts i nfecte d wit h he patitis C vir us at 0. 0 5 
m g/ k g a n d 0. 1 m g/ k g f or u p t o t w o ( 2) m o nt hs of dail y d osi n g wit h h y p erici n. T wel ve  ( 1 2) 
s u bjects c o nsisti n g of te n ( 1 0) me n a n d t w o ( 2) w o me n ra n gi n g i n a ge fr o m 3 6 t o 6 6 years were 
e ntere d i nt o t he 0. 0 5 m g/ k g d ose l e vel; se ve n ( 7) s u bjects c o nsisti n g of fi v e ( 5) me n a n d t w o ( 2) 
w o me n ra n gi n g i n a ge fr o m 4 0 t o 5 3 years were e ntere d i n t he 0. 1 0 m g/ k g d ose le vel. At t he 0. 0 5 
m g/ k g d osa ge le v el, ei g ht  ( 8) of t wel ve ( 1 2) s u bjects treate d a n d at t he 0. 1 0 m g/ k g d osa ge le v el, 
all se ve n ( 7) s u bjects e x perie nce d at least o ne ( 1) A E  w hic h was a p h ot ose nsiti vit y reacti o n. 
T here w er e f o ur ( 4) differe nt t y p es of p h ot ose nsiti vit y reacti o ns - na mel y, p arest hesias, 
der matitis, dar ke ne d c ol orati o n of e x p ose d s ki n a n d pr uritic n o d ules. O ne ( 1) s u bject e x perie nce d 
slee pi ness w hic h w as dee me d “ p ossi bl y relate d” t o dr u g t hera p y.  
Serial bl o o d a n d uri ne s p eci me ns were o btai ne d d uri n g t he st u d y t o m o nit or t he s u bjects f or 
la b orat or y a b n or malities. F or m ost s u bjects, la b orat or y v al ues re mai ne d fairl y sta ble o v er t he 
c o urse of t he st u d y. T h er e wer e n o la b orat or y -relate d Gra de 3 (se vere) A E s f or eit her d os a ge 
gr o u p a n d n o s u bject ha d t o wit h dra w beca use of l a b orat or y a b n or malities. Fi ve  ( 5) s u bj ects 
c o m plai ne d of c hr o nic fati g ue. F o ur ( 4) s u bjects (t w o p er d osa ge gr o u p ) h a d i nter mitte nt u p per 
q ua dra nt a b d o mi nal pai n . All b ut t w o  ( 2) s u bjects ha d mil d-t o- m o derate ele vati o ns of ser u m 
ala ni ne a mi n otra nsf eras e at baseli ne ( me dia n 7 0 U/ L; ra n ge 3 0 t o 1 5 8 U/ L). T here w ere n o 
si g nifica nt c ha n ges i n t hese val ues wit h h y perici n d osa ges. 
5. 5. 2  
T o pic al H y perici n  
I n a P hase 1 trial of t o pical S G X 3 0 1  (s y nt h etic h y perici n), 1 5 healt h y s u bjects ha d S G X 3 0 1  
a p plie d t o t he s ki n i n c o nce ntrati o ns of 0. 0 2 % t o 0. 5 % s y nt hetic h y p erici n i n h y dr o p hilic 
oi nt me nt u n der occl usi o n f or 2 t o 2 4 h o urs f oll o we d b y e x p os ure t o 2 0- w att fl u oresce nt li g hts 
yi el di n g a t otal e x p os ure ra n gi n g fr o m 4 t o 8 J o ules/ c m 2. Dela ye d er yt he ma was o bser v e d i n o ne-
t hir d of s u bjects usi n g 0. 1 % S G X 3 0 1  u n der occl usi o n f or 2 4 h o urs f oll o wi n g e x p os ure t o 4 
J o ules/c m 2 of li g ht, w hile b ot h i m me diate a n d dela ye d er yt he ma o cc urre d i n all s u bjects wit h 
0. 1 % S G X 3 0 1  u n der occl usi o n f or 2 4 h o urs f oll o we d b y a d mi nistrati o n of 8 J o ules/c m 2 of li g ht. 
N o er yt he ma was o bser v e d usi n g 0. 0 2 % S G X 3 0 1. 
I n a P hase 2 trial of t o pical S G X 3 0 1  f or C T C L a n d pla q ue ps oriasis, a t otal of 1 2 patie nts wit h 
earl y sta ge C T C L a n d 1 2 patie nts wit h pla q ue ps oriasis ha d t hree ( 3) differe nt lesi o ns treate d 
wit h eit her place b o or t w o  ( 2) differe nt stre n gt hs of S G X 3 0 1  oi nt me nt ( 0. 1 0 % a n d 0. 2 5 % 
s y nt hetic h y perici n) f oll o we d t he ne xt da y b y e x p os ure t o visi ble li g ht i n t he f or m of c o ol w hite 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 2 8  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
fl u oresce nt t u bes. F oll o wi n g si x  ( 6) wee ks of t wi ce -wee kl y t h era p y of 1 2 l o w d ose treat e d 
lesi o ns, 5 ( 4 1. 7 %) res p o n de d t o S G X 3 0 1  treat me nt. Of 1 1  hi g h - d os e treate d lesi o ns, 6 ( 5 4. 5 %) 
res p o n de d t o S G X 3 0 1  treat me nt. Of 1 2 place b o oi nt me nt treate d lesi ons, 1 ( 8. 3 %) res ol ve d wit h 
o nl y place b o treat me nt, a n d t he differ e nce i n res p o nse was statisticall y si g nifica nt ( p < 0. 0 4) . 
A m o n g ps oriasis patie nts, 5 of 1 2 ( 4 1. 7 %) t otal l o w d ose treat e d lesi o ns res p o n de d t o S G X 3 0 1  
treat me nt; 5 of 1 2 ( 4 1. 7 %) t otal hi g h d ose treat e d lesi o ns res p o n de d t o S G X 3 0 1  treat me nt; a n d 0 
of 1 2 ( 0 %) place b o oi nt me nt treate d lesi o ns res ol ve d wit h o nl y place b o treat me nt, a n d t he 
differe n ce i n r es p o nse w as statisticall y si g nifica nt ( p < 0. 0 2) . Fi n di n gs wit h b ot h t he C T C L 
patie nts a n d ps ori asis patie nts i n dicate a n acti ve treat me nt effect of S G X 3 0 1  [ 4 8]. 
T he res ults of t his st u d y s u p p ort t he c o ncl usi o n t hat:  
(a) S G X 3 0 1  t o pical p h ot ot hera p y has a be neficial treat me nt effect o n C T C L a n d ps oriasis, a n d  
( b) T he  be n efit a p p ears t o be ma xi mize d o ver a certai n c o nce ntrati o n -treat me nt ti me ra n ge.  
I m p ort a ntl y, n o dr u g relate d or p ote ntiall y dr u g rel ate d A E s were re p orte d f or t hese patie nts 
ot her t ha n mil d p h ot ot o xicit y at t he tr eat me nt site. T his A E  ra pi dl y res ol ve d u p o n l o weri n g t he 
ti me f or li g ht e x p os ure or s ki p pi n g of a n a p plicati o n a n d li g ht treat me nt e pis o de.  
Base d o n t h e saf et y  pr ofile o btai ne d i n t he P hase 1 trial wit h t o pical S G X 3 0 1  a n d li g ht treat me nt 
c o u ple d wit h t he d ose r elate d, statisticall y si g nifica nt cli nical res ults i n t he treat me nt of C T C L, 
a n d t he de m o nstrate d s af et y fr o m t he P hase 2 trial, a pi v otal P hase 3 trial wit h t o pical S G X 3 0 1  
a n d p h ot ot hera p y is warr a nte d as des cri be d i n t his pr ot oc ol t o dete r mi ne cli nical effi cac y a n d 
safet y i n C T C L p atie nts. T he c o nce ntrati o n of S G X 3 0 1 a n d t he d ose of li g ht are bas e d u p o n t he 
res ults o btai ne d fr o m t he P hase 1 trial i n n or mal s u bjects a n d fr o m t he P has e 2 trial i n patie nts 
wit h C T C L.  
5. 6.  
C urre nt Tri al  
T his st u d y will e val uate t he eff ect of S G X 3 0 1 ( 0. 2 5 % s y nt hetic h y p erici n) ass ociate d wit h 
fl u oresce nt-li g ht b ul b visi ble li g ht o n s ki n lesi o ns i n patie nts wit h earl y m yc osis f u n g oi d es 
(C T C L  Sta ges I A, I B, a n d II A). T his st u d y will be c o n d ucte d i n c o m plia nce wit h t he pr ot oc ol 
a p pr o ve d b y t he I nstit uti o nal Re vie w B o ar d (I R B), a n d acc or di n g t o G o o d Cli nical Practice 
sta n dar ds. N o de vi ati o n fr o m t he pr ot oc ol will be i m ple me nte d wit h o ut t he pri or re vie w a n d 
a p pr o val of t he I R B e x ce pt w here it ma y be n ecessar y t o eli mi nate  a n i m me diate hazar d t o a 
researc h s u bject. I n s uc h case, t he d e viati o n will be re p ort e d t o t he I R B as s o o n as p ossi ble. 
T his st u d y will be c o n d u cte d i n c o m plia nce wit h t he pr ot oc ol, I nter n ati o nal C o nfere nce o n 
Har m o nisati o n G o o d Cli nical Practice E 6 (I C H - G C P) a n d t he a p plica ble re g ulat or y re q uire m e nts 
as s pecifie d i n t he U. S. C o de of Fe der al Re g ulati o ns a p plica ble t o cli nical st u dies ( 4 5 C F R 4 6 
a n d 2 1 C F R i ncl u di n g p arts 5 0 a n d 5 6 c o ncer ni n g i nf or me d c o nse nt a n d I R B re g ul ati o ns i n 2 1 
C F R 3 1 2). 




Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 3 0  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
baseli ne t o t he 1 6- w ee k E val uati o n Visit w he n c o m pare d t o patie nts recei vi n g place b o  a n d 
visi ble li g ht . 
 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 3 1  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
7.  
I N V E S TI G A TI O N A L P L A N 
7. 1.  
O ver all St u d y Desi g n a n d Pl a n: Descri pti o n  
A p pr o xi matel y 1 8 0 s u bj ects will be e nr olle d i nt o t his P hase 3, place b o -c o ntr olle d, d o u ble bli n d, 
m ultice nter st u d y (i n or d er t o fi nis h wit h 1 6 0 e val ua ble patie nts) t o e v al uate t he efficac y a n d 
safet y of t o pical p h ot ot hera p y wit h S G X 3 0 1  (s y nt hetic h y p erici n) at a c o n ce ntrati o n of 0. 2 5 %. 
T he pri mar y e n d p oi nt of t his st u d y is t he n u m ber of patie nts ac hie vi n g a t reat me nt res p o nse of  3 
treate d lesi o ns (Partial or C o m plete Res p o nse defi ne d as a ≥5 0 % re d ucti o n i n t he C AI L S sc ore 
s u m me d o ver t he 3 i n de x lesi o ns w he n t he 8-w ee k assess me nt is c o m pare d t o t he baseli ne val ue ) 
after u n d er g oi n g a 6 -wee k c ycle of t wice per wee k st u d y o i nt me nt f oll o we d 1 8- 2 4 h o urs later b y 
fl u oresce nt b ul b visi ble li g ht treat me nt. 
Patie nts ma y u n der g o 3 C ycles of t hera p y: 
Cycle 1:  Patie nts will be ra n d o mize d 2: 1 S G X 3 0 1 : place b o f or treat me nt of t he 3 i n de x 
lesi o ns selecte d b y t he i n vesti gat or. T h e res ults of t his c ycle will be t he basis of t he pri mar y 
efficac y a n al ysis.  
Cycle 2:  All patie nts will recei v e S G X 3 0 1 treat me nt of t he 3 i n de x lesi o ns u nless a lesi o n 
ha d ac hie v e d a C R f oll o wi n g C ycle 1 t hera p y. 
O pti o n al Cycle 3:  All patie nts will recei ve S G X 3 0 1 treat me nt of all of t heir lesi o ns  c h ose n 
b y t he p h ysicia n a n d pati e nt. 
F or eac h c ycle, st u d y oi nt me nt will be a p plie d t wice wee kl y f or 6 w ee ks a n d o pa q ue ba n d a ge 
a p plie d for 1 8- 2 4 h o urs f oll o we d b y t he a d mi nistrati o n of visi ble li g ht u p t o a d ose of 1 2 
J o ules/c m 2. T he li g ht treat me nt  will be perf or me d  3-4 cale n d ar da ys a part  ( ± 1 da y) eac h wee k 
(e. g., M o n da y/ T h urs d a y, M o n da y/ Fri da y, or T ues da y/ Fri da y). 
Pri or t o ra n d o mizati o n, eac h patie nt will ha ve 3 lesi o ns i de ntifie d. T hese s h o ul d be discrete 
lesi o ns a n d be re prese ntati ve of t he patie nt’s lesi o ns t hat are easil y accessi ble f or p h otot hera p y . 
T hese lesi o ns will ser ve as t he i n de x lesi o ns  f or treat me nt a n d e v al uati o n. C ycle 1 p atie nts will 
recei v e eit her S G X 3 0 1 or place b o oi nt me nt ap plie d t o t heir 3 i n de x lesi o ns; i n C ycle 2 all 
patie nts will ha ve S G X 3 0 1 a p plie d t o t he i n de x lesi o ns t hat di d n ot ac hie ve a C R  after C ycle 1 
t hera p y; a n d i n o pti o nal C ycle 3, all patie nts will ha ve S G X 3 0 1 a p plie d t o all of t he lesi o ns 
c h ose n b y t he p h ysicia n a n d patie nt. T he treat me nt e val uati o n  f or eac h c ycl e will be perf or me d  
after a 2- wee k  r est peri o d ( Wee k 8, 1 6 a n d 2 4) i n or der t o per mit a n y lig ht i n d uce d er yt h e ma t o 
s u bsi de.  
F oll o wi n g e val uati o n f or safet y a n d efficac y at t he e n d of C ycle 2 ( Wee k 1 6), all patie nts will be 
gi ve n t he o p p ort u nit y t o e nter a n o p e n- la b el treat me nt c ycle ( C ycle 3) i n w hic h all selecte d 
lesi o ns (i n de x a n d n o n-i n de x) will be treate d f or a n a d diti o nal 6 wee ks wit h S G X 3 0 1  oi nt me nt. 
E val uati o n of saf et y a n d efficac y d uri n g t he o p e n- la bel c ycle will ta ke place at W ee k 2 4. 
All patie nts will be f oll o we d f or 6 m o nt hs f oll o wi n g t he last ass ess me nt visit ( Wee k 4 8 f or t h ose 
part ici pati n g i n C ycle 3 a n d Wee k 4 0 f or t h ose n ot partici pati n g i n C ycle 3). 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 3 2  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
S G X 3 0 1  will be a p plie d t o defi ne d patc h es or pla q ues o n t he s ki n of s u bjects at a c o nce ntrati o n 
of 0. 2 5 % s y nt hetic h y perici n. T he a m o u nt of s y nt hetic h y p erici n i n eac h t o pical a p plicati o n is as 
f oll o ws: 0. 2 5 % = 0. 0 2 5 m g/c m 2 ( 2. 5 m g s y nt heti c h y p erici n i n 1 gra m of S G X 3 0 1  oi nt me nt) . 
T he act ual d os e will be d e pe n de nt o n t he e xte nt of t he lesi o ns u n der g oi n g treat me nt. 
St u d y oi nt me nt will be a p plie d t wice wee kl y  wit h a n y e x cess oi nt me nt o n healt h y s ki n wi pe d off 
a n d t he n pr otect e d fr o m li g ht f or a peri o d of 1 8- 2 4 h o urs pri or t o t he li g ht treat me nt. Eac h 
a p plicati o n site will be c o vere d b y o pa q ue ba n d a gi n g t hat has bee n a p pr o ve d/ pr o vi de d b y 
S oli ge ni x . 
Treat me nt  wit h visi ble li g ht will be u n dert a ke n usi n g t he s u p plie d 
 fl u oresce nt li g ht 
pa nel c o nsisti n g of a ba n k of 1 2 c o ol w hite fl u oresce nt b ul bs ( 5 9 0- 6 5 0 n m ; G E ®  c o ol w hite 
fl u oresce nt b ul bs, 6 0- watt fl u oresce nt t u bes h o use d i n t he s u p plie d reflecti n g ba n k). Lesi o ns will 
be p ositi o ne d as cl ose as practical t o t he li g ht pa nel a n d t he d urati o n of li g ht treat me nt will be  
calc ulate d fr o m d osi metr y meas ure me nt b ase d o n p ositi o ni n g of t he lesi o n relati ve t o t he li g ht 
s o urce (s ee visi ble li g ht treat me nt ma n ual f or details) wit h t he i nitial d ose of 5 J o ules/ c m 2. T he 
li g ht d ose will be a d mi nistere d t wice wee kl y se p arate d b y 3-4 cale n d ar da ys  (e. g., 
M o n da y/ We d nes d a y, M o n da y/ T h urs da y, M o n da y/ Fri da y) a n d will be assesse d usi n g a 
ra di o meter t o pr ecisel y d eter mi ne t he e missi o n of visi ble li g ht fr o m t he b ul bs at t he p ositi o n of 
t he lesi o n fart hest fr o m t he li g ht pa n el. 
T he li g ht d ose ma y b e i n creas e d b y 1 J o ule/c m2 eac h visit  u ntil s y m pt o ms or si g ns of mil d 
p h ot ot o xicit y a p pear  as d efi ne d i n Ta ble 3  t o a ma xi m u m li g ht d ose of 1 2 J o ules/ c m 2. At t hat 
p oi nt, t he d ose ca n be eit her mai ntai ne d or re d uce d b y 1 J o ule /c m2 if p h ot ot o xicit y is pr o n o u nce d 
(s ki n er yt he ma of > Gr a d e I)  u ntil s y m pt o ms  a n d si g ns s u bsi de or t he d os e is at 5 J o ules/c m 2.  
T a ble 3: S ki n P h ot ot o xi cit y Gr a di n g 
T o xicit y
 Gr a de : 
Er yt he m a  
a n d/ or e de m a  
Se verit y  
Gra de  0 
N o a p pare nt reacti o n 
Gra de I  
Mil d  
Gra de II  
M o derate 
Gra de III  
Se vere wit h e de ma  
Gra de I V  
Life -threate ni n g wit h vesic ulati o n  
S ki n reacti o ns will be e v al uate d bef ore a n d after eac h li g ht treat me nt . T he sites of treat me nt  s hall 
be e x a mi ne d a n d a n y c h a n ges i n er yt he ma, e de ma, des q ua mati o n, a n d s hall be rec or de d.  
T he st u d y o v erall st u d y d esi g n is s u m marize d i n Fi g ure 1  a n d t he sc h e d ule of pr oce d ures is 
prese nte d i n  Ta bl e  4 t hr o u g h Ta bl e 1 1 . T hese s c he d ules ass u me a T ues d a y/ Fri da y sc h e d ule b ut  
ot her da y c o m bi nati o ns, e. g., a M o n da y/ T h urs d a y or M o n da y/ Fri d a y sc he d ule are acce pta ble 
o nce t he St u d y Staff is c o mf orta ble t hat t he patie nt is ca pa ble of relia bl y a p pl yi n g  st u d y oi nt me nt 
a n d i nstr ucte d t o a p pl y t h e dr u g o n S u n da y.  
 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 3 3  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6  
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
Fi g ure 1:  St u d y Sc he m a  
 
Patie nts Scree ne d  
3 Re prese ntati ve I n de x  
Lesi o ns Selecte d  
~ 1 0 7 Patie nts Ra n d o mize d 
t o S G X 3 0 1 Oi nt me nt  
Treat me nt t o 3 I n de x 
Lesi o ns f or 6 Wee ks 
~ 5 3 Patie nts Ra n d o mize d 
t o Place b o Oi nt me nt  
Treat me nt t o 3 I n de x 
Lesi o ns f or 6 W ee ks  
Assess 3 I n de x Lesi o ns  
After 2 Wee k Rest  
Assess 3 I n de x Lesi o ns  
After 2 Wee k Rest  
All Patie nts ( 1 6 0)  
S G X 3 0 1 Oi nt me nt  
Treat me nt t o 3 I n de x Lesi o ns 
f or 6 Wee ks 
Assess 3 I n de x Lesi o ns  
After 2 Wee k Rest  
All Patie nts ( 1 6 0)  
S G X 3 0 1 Oi nt me nt  
Treat me nt t o All Lesi o ns  
f or 6 Wee ks 
Assess All Treate d Lesi o ns  
After 2 Wee k Rest  
C y cl e 1  
C y cl e  2  
O pti o n al 
C y cl e  3 


Pr ot oc ol H P N - C T C L - 0 1 
 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 3 4  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
T a ble 4 :  St u d y Assess me nts :  C ycl e 1 - Wee k 1  R a n d o mize d Dr u g t o I n de x Lesi o ns  
E v al u ati o n  
Scree ni n g  
D a y -2 1 t o -1  
M o n d a y  
B aseli ne -D a y 1  
T ues d a y  
D a y 2  
We d nes d a y  
D a y 3  
T h urs d a y  
D a y 4  
F ri d a y  
D a y 5  
Cli nic visit  
X  
X  
X  
 
X  
X  
E ntr y criteria  
X  
X  
 
 
 
 
I nf or me d c o nse nt 
X  
 
 
 
 
 
Me dical hist or y  
X  
 
 
 
 
 
I nteri m me dical hist or y/A Es  
 
X  
X  
 
X  
X  
Vital si g ns  
X  
X  
X  
 
X  
X  
P h ysical e xa m  
X  
X  
 
 
 
 
Vis ual lesi o n ins pecti o n  
 
 
X  
 
 
X  
Ser u m H C G  (fe males o nl y) 
X  
 
 
 
 
 
He mat ol o g y  
 
X  
 
 
 
 
C he mistr y  
 
X  
 
 
 
 
I de ntif y i n de x lesi o ns 
 
X  
 
 
 
 
3 m m p u nc h bi o ps y  
 
X  
 
 
 
 
C AI L S  
 
X  
 
 
 
 
P G A  
 
X  
 
 
 
 
m S W A T  
 
X  
 
 
 
 
Di gital p h ot o gra p h y  
 
X  
 
 
 
 
Distri b ute dr u g  
 
X  
 
 
 
 
Trai ni n g o n dr u g a p plicati o n  
 
X  
 
 
X  
 
A p pl y dr u g/ o pa q ue  ba n da ge  
 
X  
 
 
X  
 
Li g ht Treat me nt  
 
 
X  
 
 
X  
Safet y gra di n g  
 
 
I m me diatel y 
pri or a n d after 
ra diati o n 
 
 
I m me diatel y pri or 
a n d after 
ra diati o n 
 
 


Pr ot oc ol H P N - C T C L - 0 1 
 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 3 5  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
T a ble 5 :  St u d y A ssess me nts:  C ycl e 1  - A p plic ati o n a n d Li g ht Tre at me nt  # 3- 1 2 R a n d o mize d Dr u g t o I n de x Lesi o ns  
E v al u ati o n  
A p plic ati o n D a y  
Tre at me nt D a y  
Cli nic visit  
X 1 
X  
I nteri m me dical hist or y/A Es  
 
X  
Vital si g ns  
 
X  
Vis ual lesi o n ins pecti o n  
 
X  
A p pl y dr u g /o pa q ue  ba n da ge  
X  
 
Li g ht treat me nt 
 
X  
Safet y gra di n g  
 
I m me diatel y pri or 
a n d after ra diati o n 
1 P atie nt  will c o me t o cli nic f or me dicati o n a p plicati o n u ntil st u d y pers o n nel c o mf orta ble wit h t heir a bilit y t o a p pl y  a p pr o priatel y 
 
T a ble 6 :  C ycle 1  - Wee k s 7 a n d 8 Tre at m e nt Ev al u ati o n  
E v al u ati o n 
Wee k 7  
Rest P eri o d  
1 4 ( ± 2) D a ys After 
L ast  Tre at me nt  
Cli nic visit  
 
X  
I nteri m me dical hist or y/A Es  
 
X  
Vital si g ns  
 
X  
P h ysical e xa m  
 
X  
Ser u m H C G  
 
Fe males o nl y  
He mat ol o g y  
 
X  
C he mistr y  
 
X  
3 m m p u nc h bi o ps y  
 
Sa me i n de x lesi o n  
C AI L S  
 
X  
P G A  
 
X  
Di gital p h ot o gra p h y  
 
X  
Distri b ute C ycle 2 dr u g  
 
X  
 


Pr ot oc ol H P N - C T C L - 0 1 
 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 3 6  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
T a ble 7 :  C ycle 2  - Li g ht Tre at me nt # 1 3 - 2 4 All P atie nts S G X 3 0 1 Oi nt me nt t o I n de x Lesi o ns  
E v al u ati o n  
A p plic ati o n D a y  
Tre at me nt D a y  
Cli nic visit  
 
X  
Vital si g ns  
 
X  
I nteri m me dical hist or y/A Es  
 
X  
Vis ual lesi o n i ns pecti o n 
 
X  
A p pl y dr u g /o pa q ue  ba n da ge  
X  
 
Li g ht treat me nt 
 
X  
Safet y gra di n g  
 
I m me diatel y pri or 
a n d after ra diati o n 
C AI L S  
 
X 1 
P G A  
 
X 1 
Di gital p h ot o gra p h y  
 
X 1 
1 I n de x lesi o ns will be e val uat e d i n W ee k 1 0 o nl y f or t h ose l esi o ns t hat were a c o m plete res p o nse after C ycle 1.  
T a ble 8 :  C ycle 2  - Assess me nt  
E v al u ati o n 
Wee k 1 5  
Rest P eri o d  
1 4 ( ± 2) D a ys After 
L ast  Tre at me nt  
Cli nic visit  
 
X  
I nteri m me dical hist or y/A Es  
 
X  
Vital si g ns  
 
X  
P h ysical e xa m  
 
X  
He mat ol o g y  
 
X  
C he mistr y  
 
X  
C AI L S  
 
X  
m S W A T  
 
X  
P G A  
 
X  
Di gital p h ot o gra p h y  
 
X  
Distri b uti o n of C ycle 3 dr u g  
 
X  
 


Pr ot oc ol H P N - C T C L - 0 1 
 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 3 7  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
T a ble 9 :  O pti o n al C ycle 3  - Wee k 1 7 t hr o u g h 2 2 All P atie nts 0. 2 5 % S G X 3 0 1 Oi nt m e nt t o All Tre ate d Lesi o ns  
E v al u ati o n  
A p plic ati o n D a y  
Tre at me nt D a y  
Cli nic visit  
 
X  
Vital si g ns  
 
X  
I nteri m me dical hist or y/A Es  
 
X  
Vis ual lesi o n i ns pecti o n 
 
X  
A p pl y dr u g /o pa q ue  ba n da ge  
X  
 
Li g ht treat me nt 
 
X  
P K bl o o d  
 
X 1 
Safet y gra di n g  
 
I m me diatel y pri or 
a n d after ra diati o n 
  
  
  
  
  
  
  
 
1 D uri n g t he 4 treat me nt sessi o n s i n last 2 wee ks of C ycle 3 ( W ee ks 2 1 a n d 2 2 a n d A d mi nistrati o n 3 3 – 3 6)  
 
T a ble 1 0 :  C ycle 3: Assess me nt  - Cycle 3 E v al u ati o n  
E v al u ati o n 
Wee k 2 3  
Rest P eri o d  
1 4 ( ± 2) D a ys After 
L ast  Tre at me nt  
Cli nic visit  
 
X  
I nteri m me dical hist or y/A Es  
 
X  
Vital si g ns  
 
X  
P h ysical e xa m  
 
X  
He mat ol o g y  
 
X  
C he mistr y  
 
X  
C AI L S  
 
X  
m S W A T  
 
X  
P G A  
 
X  
Di gital p h ot o gra p h y  
 
X  
 


Pr ot oc ol H P N - C T C L - 0 1 
 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 3 8  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
T a ble 1 1 :  Wee ks 2 5- 4 8 - L o n g -ter m F oll o w-u p  
E v al u ati o n  
Wee k 2 8  
Wee k 3 2  
Wee k 3 6  
Wee k 4 0  
Wee k 4 4  
Wee k 4 8  
Cli nic visit  
X  
X  
X  
X  
X  
X  
I nteri m me dical hist or y/A Es  
X  
X  
X  
X  
X  
X  
Vital si g ns  
X  
X  
X  
X  
X  
X  
P h ysical e xa m  
X  
X  
X  
X  
X  
X  
C AI L S  
X  
X  
X  
X  
X  
X  
m S W A T  
X  
X  
X  
X  
X  
X  
P G A  
X  
X  
X  
X  
X  
X  
Di gital p h ot o gra p h y  
X  
X  
X  
X  
X  
X  
Ne w lesi o n i de ntificati o n  
X  
X  
X  
X  
X  
X  
 
 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 3 9  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
7. 2.  
S pecific Assess me nts  
7. 2. 1  
L a b or at or y Assess me nts 
7. 2. 1. 1.  
Scree ni n g Tests  
If necessar y, a bl o o d sa m ple will be o btai ne d at t he scree ni n g visit t hat will occ ur  wit hi n 3 wee ks 
of starti n g t he st u d y me di cati o n . La b orat or y tests will be perf or me d b y t h e l ocal la b orat or y. 
R es ults of t hese tests m ust be  re vie w e d pri or t o starti n g t he p atie nt o n st u d y me dicati o n .  
•  Ser u m pre g na n c y test  ( h u ma n c h ori o nic g o na d otr o pi n [ HC G])  f or all w o me n 
7. 2. 1. 2.  
He m at ol o g y Tests 
T he he mat ol o g y pa nel will be perf or me d at t he Ce ntral La b orat or y o n sa m ples c ollecte d at 
Baseli ne ( Da y 1), Wee k 8,  Wee k 1 6, a n d Wee k 2 4 ( pr o vi de d t he patie nt elects t o c o nti n ue i nt o 
C ycle 3 ). T he pa n el will c o nsist of t he f oll o wi n g t ests: 
•  Re d bl o o d cell c o u nt ( R B C) 
•  He mat ocrit  
•  He m o gl o bi n 
•  Mea n c or p us c ular v ol u m e ( M C V) 
•  Mea n c or p us c ular h e m o gl o bi n ( M C H) 
•  Mea n c or p us c ular h e m o gl o bi n c o nce ntrati o n ( M C H C) 
•  Platelet c o u nt 
•  W hite bl o o d cell c o u nt ( W B C) 
•  Perce nt a n d a bs ol ute ne utr o p hil c o u nt 
•  Perce nt a n d a bs ol ute i m mat ure gra n ul o c yt e c o u nt 
•  Perce nt a n d a bs ol ute l y m p h oc yt e c o u nt 
•  Perce nt a n d a bs ol ute m o n oc yt e c o u nt 
•  Perce nt a n d a bs ol ute e osi n o p hil c o u nt 
•  Perce nt a n d a bs ol ute bas o p hil c o u nt 
7. 2. 1. 3.  
Cli nic al C he mistr y L a b or at or y Tests 
T he cli nical c h e mistr y p a nel will be perf or m e d at t he Ce ntral La b orat or y o n sa m ples c ollecte d at 
Baseli ne ( Da y 1) , Wee k 8, Wee k 1 6, a n d Wee k 2 4 ( pr o vi de d t he patie nt elects t o c o nti n ue i nt o 
C ycle 3 ). T he pa n el will c o nsist of t he f oll o wi n g t ests:  
•  Ser u m s o di u m 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 4 0  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
•  Ser u m p otassi u m 
•  Ser u m c hl ori de 
•  Ser u m bicar b o nat e ( C O 2) 
•  Ala ni ne a mi n otra nsf eras e  ( A L T)  
•  As partate a mi n otra nsferase ( A S T)  
•  T otal bilir u bi n  
•  T otal pr otei n  
•  Ser u m creati ni ne  
•  Bl o o d urea nitr o ge n ( B U N) 
•  Al kali n e p h os p hatase 
7. 2. 1. 4.  
S ki n p u nc h bi o ps y  
Eac h st u d y partici pa nt will ha ve a si n gl e i n de x lesi o n selecte d f or bi o ps y at st u d y e ntr y. T his 
lesi o n s h o ul d be re pres e ntati ve of t he patie nt’s  lesi o ns a n d t he sa me lesi o n will be re- bi o psie d at 
t he c o ncl usi o n of C ycle 1 t o deter mi ne t he nat ure of cleari n g of t he mali g n a nt i nfiltrate. Eac h 
bi o ps y s h o ul d be ta ke n fr o m a re pr ese ntati ve p orti o n of t he lesi o n a n d t he s ec o n d bi o ps y 
o btai ne d at least 1 c m f or t he ori gi nal bi o ps y site. Eac h bi o ps y will c o nsist of a 3 m m p u nc h 
bi o ps y t hat  will be f or mali n -fi x e d, paraffi n e m be d de d , secti o ne d a n d st ai ne d at t he site as 
descri be d i n A p p e n di x 1 8. 4.    o n pa ge 8 5 . T he st ai ne d a n d u nstai ne d sli des will  be se nt t o t he 
Ce ntral Pat h ol o g y La b or at or y f or gr a di n g  a n d f urt her a nal ysis . 
7. 2. 1. 5.  
S G X 3 0 1 Pl as m a C o nce ntr ati o n S a m ples  
D uri n g t h e c o urs e of t he C ycle 3  ( o pti o nal o pe n la bel), plas ma sa m ples s hall be o btai ne d i n 
patie nts wit hi n 3 0 mi n utes of c o m pleti n g eac h of t he t w o li g ht treat me nt sessi o ns d uri n g Wee k 
2 1 a n d Wee k 2 2 (i.e., Tr eat me nts 3 3, 3 4, 3 5, a n d 3 6) t o deter mi ne t he c o nce ntrati o n of S G X 3 0 1 
in t he circ ulati o n f oll o wi n g t o pical a p plicati o n of S G X 3 0 1 t o all lesi o ns. Sa m ples will be 
o btai ne d i n t he i nitial 2 5 patie nts a n d s h o ul d all sa m ples ha ve u n detecta ble h y perici n le vels, as 
e x pecte d, testi n g o n s u bs e q ue nt patie nts will n ot be d o ne. 
7. 2. 2  
Ot her Assess me nts  
7. 2. 2. 1.  
Me dic al Hist or y  
De m o gra p hic i nf or mati o n will be c ollecte d at scree ni n g a n d i ncl u de t he f oll o wi n g i nf or m ati o n 
t hat will be rec or d e d i n t he Electr o nic Cas e Re p ort F or m ( e C R F ): 
•  Birt h date  
•  A ge (calc ulate d fr o m t he date of I C F si g n at ure mi n us t he birt h date) 
•  Se x  


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 4 1  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
•  Race  
•  Et h nic gr o u p 
C o m plete me dical hist or y will be o btai ne d at t he scree ni n g visit. Details of t he dia g n osis of 
C T C L will be c ollecte d i ncl u di n g:  
•  Date of dia g n osis of C T C L  
•  N u m ber of r ela pses  
•  Treat me nts r ecei ve d  - t y pe, d urati o n, dates  
•  Date of last r ela pse  
•  Date of last t her a p y  
•  Sta gi n g of C T C L   
At eac h cli nical visit, i nter val me dical hist or y will be o btai ne d a n d rec or d e d.  
7. 2. 2. 2.  
P h ysic al E x a mi n ati o n a n d Vis u al Lesi o n I ns pecti o n  
At scree ni n g, t he tr eat me nt e val uati o n visits ( Wee ks 8, 1 6, a n d 2 4), a n d e v er y m o nt h d uri n g t h e 
6- m o nt h f oll o w- u p visits a c o m plete p h ysical e x a mi nati o n will be perf or m e d a n d all 
a b n or malities n ote d i n t he e C R F wit h partic ular atte nti o n f or e vi de nce of visceral or ga n 
i n v ol ve me nt of t he C T C L. I nt er val vis ual lesi o n i ns pecti o ns will be perf or me d  b y q u alifie d 
pers o n nel at eac h cli nic visit t o assess all s ki n lesi o ns t hat will be c harte d o n a “ B o d y M a p” a n d 
ne w lesi o ns n ote d i n t he e C R F. 
7. 2. 2. 3.  
Vit al Si g ns  
Vital si g ns will be c ollect e d at eac h cli nic visit. B M I will be calc ulat e d at base li ne o nl y. Vital 
si g ns will i ncl u de t he f oll o wi n g meas ure me nts: 
•  Heart r ate  
•  Res pirat or y rate  
•  Te m perat ur e  
•  Bl o o d  press ur e (sitti n g) 
•  Hei g ht ( Baseli ne o nl y) 
•  Wei g ht  
7. 2. 2. 4.  
C o m p osite Assess me nt of I n de x Lesi o ns Se verit y ( C AI L S) Sc ore  
C AI L S sc ore will be calc ulate d b y assessi n g t he er yt he ma, s cali n g, pla q ue ele vati o n a n d 
i n v ol ve d s urface ar ea usi n g t he gr a di n g scal e s h o w n i n Ta ble 1 2  f or eac h of t he 3 i n de x lesi o ns. 
Eac h of t he assess me nts a n d t he t otal sc ore f or eac h e val uat e d lesi o n will be rec or de d i n t he 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 4 2  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
e C R F. T he t otal C AI L S s c ore will be calc ulate d b y a d di n g t he s c ores of all e val uate d  lesi o ns 
t o get her - t he 3 i n de x lesi o ns f or C ycl es 1 a n d 2 a n d all treate d lesi o ns i n C ycle 3. 
 
T a ble 1 2:  C o m p osite Assess me nt of I n de x Lesi o n Se verit y  
E R Y T H E M A  
Sc ore  
Descri pti o n  
0  
N o e vi de nce of er yt h e ma, p ossi ble br o w n h y p er pi g me ntati o n  
1  
*  
2  
Mil d: Li g ht r e d lesi o n  
3  
*  
4  
M o derate: Re d lesi o n  
5  
*  
6  
Se vere: Ver y re d l esi o n  
7  
*  
8  
Ver y se v ere: E xtre mel y re d lesi o n  
S C A LI N G  
Sc ore  
Descri pti o n  
0  
N o e vi de nce of scali n g o n lesi o n  
1  
*  
2  
Mil d: Mai nl y fi n e scal es: lesi o n partiall y c o vere d  
3  
*  
4  
M o derate: S o me w hat c oarser scales: lesi o n partiall y c o v ere d 
5  
*  
6  
Se vere: C oars e, t hic k scales; virt uall y all of t he lesi o n c o vere d; r o u g h 
s urface 
7  
*  
8  
Ver y se v ere:  C oarse, ver y t hic k scales; all of t he l esi o n c o vere d ver y 
r o u g h s urface 
P L A Q U E E L E V A TI O N  
Sc ore  
Descri pti o n  
0  
0 m m: N o e vi de nce of pl a q ue a b o v e n or mal s ki n le vel  
1  
Mil d ele vati o n  
2  
M o derate ele vati o n  
3  
Mar ke d el e vati o n  
S U R F A C E A R E A  
L o n gest dia m eter a n d t h e l o n gest dia meter per p e n dic ular t o t his dia meter 
of eac h i n d e x lesi o n will meas ure d t o t he n earest milli meter . T he lesi o n 
area will be t he pr o d uct of t hese t w o dia meters  
Sc ore  
Area  
0  
0  c m 2 
1  
> 0 a n d ≤4  c m 2 
2  
> 4 a n d ≤1 0 c m 2 
3  
> 1 0 a n d ≤1 6 c m 2 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 4 3  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
T a ble 1 2:  C o m p osite Assess me nt of I n de x Lesi o n Se verit y  
4  
> 1 6 a n d ≤2 5 c m 2 
5  
> 2 5 a n d ≤3 5 c m 2 
6  
> 3 5 a n d ≤4 5 c m 2 
7  
> 4 5 a n d ≤5 5 c m 2 
8  
> 5 5 a n d ≤7 0 c m 2 
9  
> 7 0 a n d ≤9 0  c m 2 
1 0  
> 9 0 a n d ≤1 1 0 c m 2 
1 1  
> 1 1 0 a n d ≤1 3 0 c m 2 
1 2  
> 1 3 0 a n d ≤1 5 5 c m 2 
1 3  
> 1 5 5 a n d ≤1 8 0 c m 2 
1 4  
> 1 8 0 a n d ≤2 1 0 c m 2 
1 5  
> 2 1 0 a n d ≤2 4 0 c m 2 
1 6  
> 2 4 0 a n d ≤2 7 0 c m 2 
1 7  
> 2 7 0 a n d ≤3 0 0 c m 2 
1 8  
> 3 0 0 c m 2 
* I nter me diate i nter vals 1, 3, 5, a n d 7 are t o ser ve as mi d -p oi nts bet wee n t he defi ne d gra des 0, 2, 4, 6, a n d 8  
7. 2. 2. 5.  
T he P h ysici a n Gl o b al Assess me nt ( P G A)  
T he P G A re prese nts t he i n vesti gat or's assess me nt of t he o verall e xte nt of i m pr o ve me nt or 
w orse ni n g of t he p atie nt's c uta ne o us diseas e c o m pare d wit h bas eli ne as s h o w n i n Ta ble 1 3 . T his 
assess me nt is desi g n e d t o c o nsi der all c ut a ne o us lesi o ns , i ncl u di n g b ot h i n de x a n d n o n-i n de x 
lesi o ns.  
T a ble 1 3 :  P h ysici a n’s Gl o b al Assess me nt   
Gr a de  
Descri pti o n  
0  c o m pletel y clear  
N o e vi de nce of disease; 1 0 0 % i m pr o ve me nt 
1  al m ost clear  
Ver y o b vi o us i m pr o ve me nt ( ≥9 0 % t o < 1 0 0 %);  
o nl y traces of disease re mai n  
2  mar ke d i m pr o ve me nt 
Si g nifica nt i m pr o ve me nt ( ≥5 0 t o < 9 0 % clear);  
s o me e vi de nce of disease re mai ns 
3  m o derate i m pr o ve me nt 
I nter me diate bet wee n mar ke d a n d mil d ( ≥2 5 % t o < 5 0 %)  
4  sli g ht i m pr o ve me nt 
≥1 0 % t o < 2 5 %; si g nifica nt e vi de nce of disease re mai ns  
5  n o c ha n ge 
Disease has n ot c ha n ge d si g nifica ntl y fr o m baseli ne  
( 1 0 t o - 2 5 %) 
6  c o n diti o n w orse 
Disease is w orse t ha n baseli ne b y ≥2 5 %  
 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 4 4  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
7. 2. 2. 6.  
M o difie d Se verit y Wei g hte d Assess me nt T o ol ( m S W A T)  
T he m S W A T  is desi g ne d t o q ua ntif y t he disease b ur de n ass ociat e d wit h C T C L a n d is bas e d o n 
a n esti mate of t he p erce nt t otal area of s ki n i n v ol v e d base d o n t he b o d y s urface area ( B S A). T h e 
t y pes of l esi o ns are wei g hte d b y t he l esi o n c haract eristic ( patc h, pla q u e, or t u m or) as s h o w n i n 
Ta ble 1 4 . 
 
T a ble 1 4 :  M o difie d Se verit y Wei g hte d Assess me nt T o ol  ( m S W A T) 
B o d y Re gi o n 
% B S A
1  i n B o d y 
 
Assess me nt of I n v ol ve me nt i n P atie nt’s S ki n  
 
 
Re gi o n 
P atc h 2 
Pl a q ue 3 
T u m or 4 
Hea d  
7 % 
 
 
 
Nec k  
2 % 
 
 
 
A nteri or tr u n k 
1 3 % 
 
 
 
Ar ms  
8 % 
 
 
 
F orear ms  
6 % 
 
 
 
Ha n ds 
5 % 
 
 
 
P osteri or tr u n k  
1 3 % 
 
 
 
B utt oc ks  
5 % 
 
 
 
T hi g hs  
1 9 % 
 
 
 
Le gs  
1 4 % 
 
 
 
Feet  
7 % 
 
 
 
Gr oi n  
1 % 
 
 
 
Wei g hti n g Fact or  
 
x 1 
x 2 
x 4 
S u bt ot al lesi o n B S A x w ei g hti n g f act or  
 
 
 
 
1 B S A =  b o d y s urface area  
2 A n y size lesi o n wit h o ut i n d urati o n or si g nifica nt ele vati o n a b o ve t he s urr o u n di n g  u ni n v ol ve d s ki n; p oi kil o der ma 
ma y be prese nt.  
3 A n y size lesi o n t hat is ele vat e d or i n d urate d; cr usti n g, ulcerati o n, or  p oi kil o der ma ma y b e prese nt.  
4 A n y s oli d or n o d ular lesi o n > 1 c m i n dia meter wit h e vi de nc e of dee p  i nfiltrati o n i n t he s ki n a n d/ or vertical gr o wt h. 
 
7. 2. 2. 7.  
S ki n Re acti o n S af et y Gr a di n g  
S ki n r eacti o ns will be e v al uate d bef ore a n d after eac h li g ht treat me nt. Eac h site of treat me nt  s hall 
be e x a mi ne d a n d assesse d d uri n g t he visit b ut at least 5 mi n utes after c o m pleti o n of t he li g ht 
treat me nt usi n g t h e scale i n Ta ble 3  o n pa ge 3 2 . 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 4 5  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
7. 3.  
Visit Sc he d ule  
7. 3. 1  
Scree ni n g  
T he scree ni n g visit m ust be d o ne wit hi n 2 1 da ys pri or t o t he start of t he Bas eli ne visit . Pri or t o 
starti n g t he st u d y me dicati o n, t he res ults of all tests m ust be re vie we d t o ass ure t hat t he patie nt 
meets all e ntr y criteria . Pr oce d ur es t o be d o ne at t his visit are:  
•  O btai n I nf or me d C o nse nt F or m (I C F) si g nat ure 
•  Assess me nt of e ntr y criteria  
•  C o m plete Me dical Hist or y  
•  C o m plete P h ysi cal E x a mi nati o n  
•  Vital Si g ns  
•  La b orat or y T ests  
o  Ser u m H C G pre g na n c y t est ( w o me n o nl y) 
7. 3. 2  
C ycle 1  
7. 3. 2. 1.  
B aseli ne  D a y  
Patie nt will be see n i n t he cli nic o n t he first da y of treat me nt. T he e ntr y criteria will be re vie we d 
a n d a n i nteri m me dical hist or y ta k e n t o ass ure t hat t he patie nt meets all e ntr y criteria. If t he 
patie nt q ualifies,  t he y will u n der g o t he f oll o wi n g pr oce d ures: 
•  T he 3 i n de x lesi o ns wi ll be i de ntifie d, la bele d “ 1”, “ 2”, a n d “ 3”, a n d t h eir l ocati o n 
rec or d e d o n t he “I n de x B o d y Ma p ”, see A p pe n di x 1 8. 2.    o n pa ge 8 1 . Eac h lesi o n 
will be d oc u me nte d as t o w het her t he y are p atc h or pla q ue.  
•  A 3 m m p u nc h bi o ps y will be perf or me d o n a re prese ntati ve area of  t he m ost 
re pres e ntati ve of t he 3 i n de x lesi o ns 
•  I nterim Me dical Hist or y  
•  Vital Si g ns  
•  P h ysical E x a mi nati o n  
•  Lesi o n Ass ess me nt  
o  Di gital p h ot o gra p h y of eac h of t he 3 i n de x lesi o ns ( o ver vie w a n d cl ose- u p) a n d 
c o pies se nt t o t he Ce ntral P h ot o gra p h y La b orat or y  
 
o  C AI L S sc ori n g of t he 3 i n de x lesi o ns 
o  P G A assess me nt  
o  m S W A T assess me nt  


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 4 6  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
•  La b orat or y T ests  
o  He mat ol o g y p a nel  
o  Cli nical C he mistr y p a nel  
•  Trai ni n g o n dr u g a p plicati o n/ ba n da gi n g 
•  A p plicati o n of st u d y oi nt me nt 
•  A p plicati o n of o pa q ue b a n da gi n g 
•  Distri b uti o n of bli n de d st u d y oi nt me nt jars a n d p atie nt i nf or mati o n s heet (see 
A p pe n di x 1 8. 3.   o n pa ge 8 2 )  
7. 3. 2. 2.  
Li g ht Tre at me nt # 1 
Patie nts will ret ur n t o t he cli nic 1 8- 2 4 h o urs aft er t he st u d y d r u g was a p plie d. Patie nts will 
u n der g o t he f oll o wi n g pr oce d ures a n d t he det ails e ntere d i nt o t he e C R F : 
•  I nteri m me dical hist or y i ncl u di n g a n y AEs  
•  Vis ual Lesi o n I ns pecti o n 
•  Vital Si g ns  
•  Safet y gra di n g of t he l esi o ns  
•  Ra di o meter use d t o deter mi ne precise fl u oresce nt li g ht-pa nel  e missi o n o ut p ut 
•  Patie nts are t o be p ositi o ne d s o t hat t he lesi o ns are e q ui dista nt fr o m t he li g ht pa nel 
a n d as cl ose t o t he fr o nt of t he li g ht-p a nel as is c o m f orta ble. The d urati o n of treat me nt 
is calc ulated fr o m t he d osi metr y rea di n g at t he p ositi o n of t he treate d lesi o n (see t he 
“ Visi ble Li g ht Tr eat me nt  Ma n ual” f or details  a n d A p pe n di x 1 8. 1.    o n pa ge 8 0  f or 
calc ulati o n of d ur ati o n of treat me nt base d o n t h e li g ht o ut p ut meas ure d at t h e p osi ti o n 
of t he lesi o n fart h est fr o m t he li g ht pa nel wit h t he s u p plie d li g ht meter ). T he patie nt 
s h o ul d be p ositi o ne d as c o nsiste ntl y as p ossi ble. 
•  D uri n g t h e cli nic visit , b ut at least 5 mi n utes after c o m pleti o n of t he li g ht treat me nt 
t hera p y, t he lesi o ns will a gai n u n der g o s afet y gra di n g  
7. 3. 2. 3.  
A p plic ati o n D a y 2 
If t he site pers o n n el deter mi ne t hat a d diti o nal patie nt trai ni n g is nee d e d, pati e nts will ret ur n t o 
t he cli nic 2 cale n d ar da ys after li g ht Treat me nt  # 1. Patie nts will u n der g o t he f oll o wi n g 
pr oce d ur es: 
•  I nterim me dical hist or y i ncl u di n g a n y A Es  
•  Vital Si g ns  
•  Trai ni n g o n dr u g a p plicati o n/ ba n da gi n g 
•  A p plicati o n of st u d y oi nt me nt 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 4 7  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
•  A p plicati o n of o pa q ue b a n da gi n g 
7. 3. 2. 4.  
Li g ht Tre at me nt  # 2 
Patie nts will ret ur n t o t he cli nic 1 8- 2 4 h o urs aft er t he st u d y dr u g was a p plie d. Patie nts will 
u n der g o t he f oll o wi n g pr oce d ures a n d t he det ails e ntere d i nt o t he e C R F. 
•  I nteri m me dical hist or y i ncl u di n g a n y A Es  
•  Vis ual Lesi o n I ns pecti o n  
•  Vital Si g ns  
•  Safet y gra di n g of t he l esi o ns  
•  Patie nts are t o be p ositi o ne d s o t hat t he lesi o ns are e q ui dista nt fr o m t he li g ht pa nel 
a n d as cl ose t o t he fr o nt of t he li g ht- p a nel as is c o mf orta ble . T he d urati o n of treat me nt 
is calc ulate d fr o m t he d osi metr y rea di n g at  t he p ositi o n of t he treate d lesi o n (see t he 
“ Visi ble Li g ht Tr eat me nt Ma n ual” f or details a n d A p pe n di x 1 8. 1.    o n pa ge 8 0  f or 
calc ulati o n of d ur ati o n of treat me nt base d o n t h e li g ht o ut p ut meas ure d at t h e p ositi o n 
of t he lesi o n fart h est fr o m t he li g ht pa nel wit h t he s u p plie d li g ht meter). T he patie nt 
s h o ul d be p ositi o ne d as c o nsiste ntl y as p ossi ble.  
•  D uri n g t h e c li nic visit, b ut at least 5 mi n utes after c o m pleti o n of t he li g ht treat me nt 
t hera p y, t he lesi o ns will a gai n u n der g o s afet y gra di n g  
7. 3. 2. 5.  
A p plic ati o n D a ys 3- 1 2 
Patie nts will ret ur n t o t he cli nic f or st u d y dr u g a p plicati o n u ntil t he St u d y Staff are c o mf orta ble 
t hat t he patie nt will c o nsiste ntl y a n d r elia bl y a p pl y t he st u d y me dicati o n. At t hat ti me, t he y will 
be i nstr ucte d t o a p pl y t he st u d y dr u g t o t he i n de x lesi o ns 1 8- 2 4 h o urs pri or t o t heir sc he d ule d 
li g ht treat me nts. T he y will be i nstr ucte d t o rec or d t he ti me of t he self-a d mi nistrati o n  of t he 
oi nt me nt.  W he n see n i n t he cli nic, patie nts will u n der g o t he f oll o wi n g pr oce d ures a n d t h e details 
e ntere d i nt o t he e C R F:  
•  I nteri m me dical hist or y i ncl u di n g a n y A Es  
•  Vital Si g ns  
•  Trai ni n g o n dr u g a p plicati o n/ ba n da gi n g 
•  A p plicati o n of st u d y oi nt me nt 
•  A p plicati o n of o pa q ue b a n da gi n g 
7. 3. 2. 6.  
Li g ht Tre at me nts # 3 - 1 2 
Patie nts will recei ve t heir li g ht treat me nt 1 8- 2 4 h o urs after t h e st u d y dr u g w as a p plie d. At t he 
discreti o n of t he PI, t he li g ht d ose ma y b e i ncrease d b y 1 J o ule /c m2 eac h visit pr o vi de d t he S ki n 
Er yt h e ma T o xicit y gra d e is ≤1 , or ma y be h el d at t he sa me d ose . If t he S ki n Er yt h e ma T o xicit y 
gr a de  is > 1, t he li g ht d os e s h o ul d be re d u ce d b y 1 J o ule/c m2 or ca n be hel d at t he c urre nt d ose at 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 4 8  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
t he PIs discr eti o n. At eac h  li g ht treat me nt, patie nts will u n der g o t he f oll o wi n g pr o ce d ures a n d t he 
details e ntere d i nt o t he e C R F:  
•  I nteri m me dical hist or y i ncl u di n g a n y A Es  
•  Vis ual lesi o n i ns pecti o n  
•  Vital Si g ns  
•  Safet y gra di n g of t he l esi o ns  
•  Patie nts are t o be p ositi o ne d s o t hat t he lesi o ns are e q ui dista nt fr o m t he li g ht pa nel 
a n d as cl ose t o t he fr o nt of t he li g ht- p a nel as is c o mf orta ble . T he d urati o n of treat me nt 
is calc ulate d fr o m t he d osi metr y rea di n g at t he p ositi o n of t he treate d lesi o n (see t he 
“ Visi ble Li g ht Tr eat me nt Ma n ual” f or details a n d A p pe n di x 1 8. 1.    o n pa ge 8 0  f or 
calc ulati o n of d ur ati o n of treat me nt base d o n t h e li g ht o ut p ut meas ure d at t h e p ositi o n 
of t he lesi o n fart h est fr o m t he li g ht pa nel wit h t he s u p plie d li g ht meter). T he patie nt 
s h o ul d be p ositi o ne d as c o nsiste ntl y as p ossi ble. 
•  D uri n g t h e cli nic visit , b ut at least 5 mi n utes after c o m pleti o n of t he li g ht treat me nt 
t hera p y, t he lesi o ns will a gai n u n der g o s afet y gra di n g.  
7. 3. 2. 7.  
C ycle 1 Assess me nt  
T he i n de x lesi o ns will be assesse d 1 4 ± 2 da ys after t he last li g ht treat me nt ( Treat me nt  # 1 2). 
Patie nts will ha ve t he f oll o wi n g pr o ce d ures: 
•  A 3 m m p u nc h bi o ps y will be perf or me d fr o m a re prese ntati ve area of t he s a me i n de x 
lesi o n t hat was bi o psie d at baseli ne t hat is at least 1 c m fr o m t he ori gi nal bi o ps y site.  
•  I nteri m Me dical Hist or y i ncl u di n g a n y A E s 
•  Vital Si g ns  
•  P h ysical E x a mi nati o n  
•  Lesi o n Ass ess me nt  
o  Di gital p h ot o gra p h y of eac h of t he 3 i n de x lesi o ns ( o ver vie w a n d cl ose- u p) a n d 
c o pies se nt t o t he Ce ntral P h ot o gra p h y La b orat or y 
  
o  C AI L S  sc ori n g of t he 3 i n de x lesi o ns 
o  P G A assess me nt  
•  La b orat or y T ests  
o  He mat ol o g y p a nel  
o  Cli nical C he mistr y p a nel  
o  H C G pre g na n c y test (f e males o nl y)  
•  Distri b uti o n of u n bli n de d S G X 3 0 1 oi nt me nt jars f or C ycl e 2 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 4 9  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
7. 3. 3  
C ycle 2  
Lesi o ns t h at h ave a c o m plete res p o nse at t he e n d of Cycle 1 are N O T  tre ate d i n Cycle 2. 
7. 3. 3. 1.  
A p plic ati o n D a ys 1 3- 2 4 
C ycle 2 is t o start t he w ee k after t he C ycle 1 Wee k 8 visit. Patie nts will be i nstr ucte d t o a p pl y t h e 
st u d y dr u g t o t he i n de x lesi o ns 1 8- 2 4 h o urs pri or t o t heir sc he d ule d li g ht treat me nts.  
7. 3. 3. 2.  
Li g ht Tre at me nts # 1 3 -2 4  
Patie nts will recei ve t heir li g ht treat me nt 1 8- 2 4 h o urs after t h e st u d y dr u g is a p plie d. T he li g ht 
d os a ge f or C ycle 2 will st art at 5 J o ules/c m 2 re g ar dless of w here t he p atie nts li g ht d ose w as 
at t he c o m pleti o n of C ycle 1 . At t he discreti o n of t he PI, t he li g ht d ose ma y be i n crease d b y 1 
J o ule/c m2 per visit pr o vi de d t he S ki n Er yt h e ma T o xicit y gra d e is ≤1 or ma y be h el d at t he sa me 
d ose. If t he S ki n Er yt he ma T o xicit y gr a de is > 1, t he li g ht d ose s h o ul d be re d uce d b y 1 J o ule/c m 2 
or ca n be h el d at t he c urr e nt d ose at t he PIs discreti o n . At eac h  li g ht treat me nt, patie nts will 
u n der g o t he f oll o wi n g pr oce d ures a n d t he det ails e ntere d i nt o t he e C R F: 
•  I nteri m me dical hist or y i ncl u di n g a n y AEs 
•  Vis ual lesi o n i ns pecti o n  
•  Vital Si g ns  
•  Safet y gra di n g of t he l esi o ns  
•  Patie nts are t o be p ositi o ne d s o t hat t he lesi o ns are e q ui dista nt fr o m t he li g ht pa nel 
a n d as cl ose t o t he fr o nt of t he li g ht- p a nel as is c o mf orta ble . T he d urati o n of treat me nt 
is calc ulat e d fr o m t he d osi metr y rea di n g at t he p ositi o n of t he treate d lesi o n (see t he 
“ Visi ble Li g ht Tr eat me nt Ma n ual” f or details a n d A p pe n di x 1 8. 1.    o n pa ge 8 0  f or 
calc ulati o n of d ur ati o n of treat me nt base d o n t h e li g ht o ut p ut meas ure d at t h e p ositi o n 
of t he lesi o n fart h est fr o m t he li g ht pa nel wit h t he s u p plie d li g ht meter). T he patie nt 
s h o ul d be p ositi o ne d as c o nsiste ntl y as p ossi ble. 
•  D uri n g t h e cli nic visit , b ut at least 5 mi n utes after c o m pleti o n of t he li g ht treat me nt 
t hera p y, t he lesi o ns will a gai n u n der g o s afet y gra di n g.  
•  If patie nts elect t o c o nti n ue partici pati o n i nt o C ycl e 3, all treat me nts a p plie d t o t he 
n o n-i n de x lesi o ns nee d t o be st o p pe d at least 2 w ee ks pri or t o t he start of C ycle 3. 
•  At Wee k 1 0 ( 2 wee ks i nt o C ycle 2), a n y i n de x lesi o n wit h a c o m plete res p o nse at 8 
wee ks  will be sc ore d usi n g t he C AI L S scale a n d di gital p h ot o gra p hs ta k e n.  Lesi o ns 
t hat ha ve a co m plete res p o nse at t he e n d of C ycl e  1 are N O T treat e d i n C ycle 2.  
7. 3. 3. 3.  
C ycle 2 Assess me nt  
T he i n de x lesi o ns will be assesse d 1 4 ± 2 da ys after t he last li g ht treat me nt ( Treat me nt  # 2 4). 
Patie nts wi ll ha ve t he f oll o wi n g pr o ce d ures: 
•  I nteri m Me dical Hist or y i ncl u di n g a n y A E s 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 5 0  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
•  Vital Si g ns  
•  P h ysical E x a mi nati o n  
•  Lesi o n Ass ess me nt  
o  Di gital p h ot o gra p h y of eac h of t he 3 i n de x lesi o ns ( o ver vie w a n d cl ose- u p) a n d 
c o pies se nt t o t he Ce ntral P h ot o gra p h y La b orat or y  
 
o  C AI L S sc ori n g of t he 3 i n de x lesi o ns 
o  P G A assess me nt  
o  m S W A T assess me nt of t he e xte nt of disease  
•  La b orat or y T ests  
o  He mat ol o g y p a nel  
o  Cli nical C he mistr y p a nel  
•  Distri b uti o n of u n bli n de d S G X 3 0 1 oi nt me nt jars f or C ycl e 3 t o patie nts electi n g t o 
c o nti n ue t o C ycle 3 
7. 3. 4  
C ycle 3  
7. 3. 4. 1.  
A p plic ati o n D a ys 2 5- 3 6 
C ycle 3 visits will start t he wee k f oll o wi n g t he C ycl e 2 Wee k 8 visit. Patie nts will be i nstr ucte d 
t o a p pl y t he st u d y dr u g t o all treate d lesi o ns 1 8-2 4  h o urs pri or t o t heir sc h e d ule d li g ht treat me nts.  
7. 3. 4. 2.  
Li g ht Tre at me nts # 2 5 -3 6  
Patie nts will recei ve t heir li g ht treat me nt 1 8- 2 4 h o urs after t h e st u d y dr u g is a p plie d. T he starti n g 
d ose of t he li g ht t hera p y s h o ul d be t he ma xi m u m well t olerate d d ose s ee n d uri n g C ycle 2. At t he 
discreti o n of t he PI, t he li g ht d ose ma y b e i ncrease d b y 1 J o ule/c m2 per visit pr o vi de d t he S ki n 
Er yt h e ma T o xicit y gra d e is ≤1  or ca n be hel d at t he c urre nt d ose at t he PIs discreti o n . If t he S ki n 
Er yt h e ma T o xicit y gra d e  is > 1, t he li g ht d ose s h o ul d be re d uce d b y 1 J o ule/c m2. At eac h  li g ht 
treat me nt, patie nts will u n der g o t he f oll o wi n g pr o ce d ures a n d t he det ails e ntere d i nt o t he e C R F: 
•  I nteri m me dical hist or y i ncl u di n g a n y A E s 
•  Vis ual lesi o n i ns pecti o n  
•  Vital Si g ns  
•  Safet y gra di n g of t he l esi o ns  
•  Patie nts are t o be p ositi o ne d s o t hat t he lesi o ns are e q ui dista nt fr o m t he li g ht pa nel 
a n d as cl ose t o t he fr o nt of t he li g ht- p a nel as is c o mf orta ble . T he d urati o n of treat me nt 
is calc ulate d fr o m t he d osi metr y rea di n g at  t he p ositi o n of t he treate d lesi o n (see t he 
“ Visi ble Li g ht Tr eat me nt Ma n ual” f or details a n d A p pe n di x 1 8. 1.   o n pa ge 8 0  f or 
calc ulati o n of d ur ati o n of treat me nt base d o n t h e li g ht o ut p ut meas ure d at t h e p ositi o n 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 5 1  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
of t he lesi o n fart h est fr o m t he li g ht pa nel wit h t he s u p plie d li g ht meter). T he patie nt 
s h o ul d be p ositi o ne d as c o nsiste ntl y as p ossi ble. 
•  D uri n g t h e cli nic visit , b ut at least 5 mi n utes  after c o m pleti o n of t he li g ht treat me nt 
t hera p y, t he lesi o ns will a gai n u n der g o s afet y gra di n g.  
7. 3. 4. 3.  
C ycle 3 Assess me nt  
L esi o ns will be ass esse d 1 4 ± 2 da ys after t h e last li g ht treat me nt ( Treat me nt  # 3 6). Patie nts will 
ha ve t he f oll o wi n g pr o ce d ures: 
•  I nteri m Me dical Hist or y i ncl u di n g a n y A E s 
•  Vital Si g ns  
•  P h ysical E x a mi nati o n  
•  Lesi o n Ass ess me nt  
o  Di gital p h ot o gra p h y of eac h of t he lesi o ns ( o v er vi e w a n d cl ose- u p) a n d c o pies 
se nt t o t he Ce ntral P h ot o gra p h y La b orat or y  
 
o  C AI L S sc ori n g of all i n de x lesi o ns  
o  P G A assess me nt  
o  m S W A T assess me nt of t he e xte nt of disease  
•  La b orat or y T ests  
o  He mat ol o g y p a nel  
o  Cli nical C he mistr y p a nel  
•  S G X 3 0 1 Bl o o d le vels 
o  Plas ma le vels of S G X 3 0 1 will be o btai ne d 3 0 mi n utes after t he li g ht treat me nt at 
eac h of t h e 4 treat me n t sessi o n i n t he last 2 wee ks of Cycl e  3 ( Wee ks 2 1 a n d 2 2 
d uri n g A d mi nistrati o n 3 3 – 3 6) 
7. 3. 5  
F oll o w- u p visits  
Patie nts will be see n i n cli nic e ver y 4 w ee ks ± 5 da ys f or 6 m o nt hs after t he last assess me nt 
(eit her C ycle 2 or C ycl e 3). At eac h visit t he f oll o w pr oce d ures will be d o n e: 
•  I nteri m Me dical Hist or y i ncl u di n g a n y A E s 
•  Vital si g ns  
•  P h ysical E x a mi nati o n  
•  Lesi o n Ass ess me nt  
o  Di gital p h ot o gra p h y of eac h of t he 3 i n de x lesi o ns ( o ver vie w a n d cl ose- u p) a n d 
c o pies se nt t o t he Ce ntral P h ot o gra p h y La b orat or y  
 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 5 2  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
o  C AI L S sc ori n g of t he 3 i n de x lesi o ns 
o  P G A assess me nt  
o  m S W A T assess me nt of t he e xte nt of disease  
o  I d e ntificati o n of t he n u m ber of ne w lesi o ns si nce t he last cli nic visit 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 5 3  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
8.  
S E L E C TI O N A N D WI T H D R A W A L O F S U B J E C T S  
8. 1.  
S u bject I ncl usi o n Criteri a  
Patie nts e nr olle d i nt o t his trial m ust meet all  of t he f oll o wi n g criteria:  
1.  ≥1 8 years of a ge . 
2.  S u bjects m ust ha ve a cli nical dia g n osis of c uta ne o us T -cell l y m p h o ma ( C T C L, 
m yc osis f u n g oi des), Sta ge I A, Sta ge I B, or Sta ge II A. 
3.  S u bjects wit h a mi ni m u m of t hree ( 3) e val u a ble, discrete lesi o ns.  
4.  S u bjects willi n g t o f oll o w t he cli nical pr ot oc ol a n d v ol u ntaril y gi ve t heir writte n 
i nf or me d c o nse nt.  
5.  Fe male s u bjects n ot pre g na nt n or n ursi n g a n d willi n g t o u n der g o a pre g n a n c y t est 
wit hi n 3 0 da ys pri or t o  tr eat me nt i nitiati o n. 
6.  S u bjects m ust be willi n g  t o refrai n fr o m s u n bat hi n g f or t he d urati o n of t h e st u d y. 
 
8. 2.  
S u bject E xcl usi o n Criteri a  
Patie nt wit h a n y of t he f oll o wi n g criteria c a n n ot b e e nr olle d i nt o t he trial:  
1.  Hist or y of s u n h y p erse nsiti vit y a n d p h ot ose nsiti ve der mat oses i ncl u di n g p or p h yri a, 
s yste mic l u p us er yt h e mat os us, Sj ö gre n’s s y n dr o m e, x er o der ma pi g me nt os u m, 
p ol y m or p h o us li g ht er u pti o ns, or ra diati o n t hera p y wit hi n 3 0 da ys of e nr olli n g. 
2.  Hist or y of aller g y or h y p erse nsiti vit y t o a n y of t h e c o m p o ne nts of S G X 3 0 1. 
3.  Pre g n a nc y or m ot hers w h o are breast -fee di n g. 
4.  M ales a n d fe m ales n ot willi n g t o  use effecti ve c o ntrace pti o n.  
5.  U n heale d  s u n b ur n. 
6.  S u bjects recei vi n g t o pical ster oi ds or ot her t o pical treat me nts  (e. g., nitr o ge n m ustar d) 
o n i n de x lesi o ns f or C T C L wit hi n 2 wee ks. 
7.  S u bjects recei vi n g s yste mic ster oi ds, ps ora le n U V A ra diati o n t hera p y ( P U V A),  
narr o w b a n d U V B li g ht t hera p y ( N B- U V B) or car m usti ne ( B C N U) or ot h er s yste mic 
t hera pies f or C T C L wit hi n 3 wee ks of e nr oll me nt. 
8.  S u bjects w h o ha ve r ecei v e d electr o n b ea m irra diati o n wit hi n t he p ote ntial treat me nt 
fiel d wit hi n 3 m o nt hs of e nr oll me nt. 
9.  S u bjects wit h a hist or y of si g nifica nt s yste mic i m m u n os u p pressi o n.  
1 0.  S u bjects ta ki n g ot her i n v esti gati o nal dr u gs or dr u gs of a b use wit hi n 3 0 da ys of e ntr y 
i nt o t his st u d y.  


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 5 4  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
1 1.  S u bjects w h ose c o n diti o n is s p o nta ne o usl y i m pr o vi n g. 
1 2.  S u bj ects wit h t u m or sta ge or er yt hr o d er mic C T C L (sta ges II B -I V). 
1 3.  S u bject has a n y c o n diti o n t hat , i n t he j u d g me nt of t he PI, is li kel y t o i nterfere wit h 
partici pati o n i n t he st u d y . 
1 4.  Pri or partici pati o n i n t he c urre nt st u d y. 
8. 3.  
P atie nt  Wit h dr a w al Criteri a  
Patie nts ha ve t he ri g ht t o wit h dra w fr o m t his trial at a n y ti me (as descri be d i n t he i nf or me d 
c o nse nt d oc u me nt) wit h o ut prej u dice t o f urt her care. A n i n vesti gat or ma y wit h dra w a patie nt 
fr o m t he st u d y at a n y ti me f or a n y of t he f oll o wi n g reas o ns:  
•  T he patie nt  wit h dra ws his/ her c o nse nt or ref us es f oll o w- u p e val uati o ns.  
•  T he patie nt  is l ost t o f oll o w- u p a n d will n ot atte n d f urt her st u d y visits. 
•  T he i n vesti gat or deter mi nes t hat f urt her p artici pati o n w o ul d be detri me ntal t o t he 
patie nt’s healt h or w ell -b ei n g.  
•  T he patie nt  fails t o c o m pl y wit h t he st u d y re q uire me nts s o as t o ca use har m t o self or 
seri o usl y i nterfer e wit h t he vali dit y of t he st u d y res ults. 
•  T he fe mal e patie nt  bec o mes pre g na nt d uri n g t he treat me nt peri o d. I n t his case, 
treat me nt s h o ul d be halte d a n d t he patie nt f oll o we d u ntil t he e n d of t he pre g na n c y. If 
a c hil d is b or n, t he i nfa nt s h o ul d be f oll o we d t hr o u g h at least 6 m o nt hs of a ge. 
•  At t he discreti o n of t he site  i n vesti gat or if h e/s he feels t hat it is i n t he best me dical 
i nterest of t he patie nt . 
Patie nt s wit h dra w n fr o m t he st u d y will ha ve as ma n y of t he trial assess me nts c o m plete d as t he 
patie nt per mits i ncl u di n g bl o o d tests a n d lesi o n e val uati o ns. 
Patie nts wit h dra w n fr o m t he trial will n ot be re place d b ut it is a ntici pate d t hat i ncl usi o n of 1 8 0 
patie nts will pr o vi de a mi ni m u m of e val ua ble 1 6 0 patie nts.  
8. 4.  
Tre at me nt I nterr u pti o n i n t he E ve nt of P h ot ot o xicit y  
F or patie nts e x perie n ci n g p h ot ot o xicit y , d efi ne d b y a n er yt he ma s c ore (Ta ble 3: S ki n 
P h ot ot o xicit y Gr a di n g   o n  pa ge 3 2 ) of Gra d e 3 or 4, t hera p y will be disc o nti n ue d f or o ne w ee k, 
or u ntil t he p h ot ot o xic reacti o n has s u bsi de d ( Gra de 1 or better), f oll o we d b y res u m pti o n of 
t hera p y. If t h e p h ot ot o xic reacti o n has n ot s u bsi de d b y t w o w ee ks, t he p atie nt m ay  be re m o v e d 
fr o m t he st u d y at t he discreti o n of t he i n vesti gat or.  
8. 5.  
Ter mi n ati o n of t he St u d y  
T h e st u d y ma y b e ter mi n ate d earl y f or a n y of t he f oll o wi n g reas o ns:  


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 5 5  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
•  T he U S F o o d & Dr u g A d mi nistrati o n ( F D A) or D ata M o nit ori n g C o m mittee  ( DM C ) 
re q uests ter mi nati o n of t he st u d y. 
•  It has b ee n d eter mi ne d t h at t he ris k le vel ass oci ate d wit h t he e x peri me ntal dr u g is 
si g nifica nt a n d warra nts t er mi nati o n of t he st u d y.  
•  T he S p o ns or, f or r eas o ns ot her t ha n safet y, m a y ter mi nate t he st u d y at a n y ti me b y 
writte n n otice of i nte n de d ter mi nati o n pr o vi de d at least t hirt y ( 3 0) da ys pri or t o 
ter mi nati o n. 
•  T he i n vesti gat or or I R B, f or reas o ns ot her t ha n s afet y, ma y t er mi nate partici pati o n of 
t his site i n t he st u d y b y writte n n otice of i nte n de d t er mi nati o n pr o vi de d at least t hirt y 
( 3 0) da ys pri or t o ter mi nati o n. 
•  A n y ot her cla us e descri be d i n t he i n di vi d ual site St u d y A gree me nt (e. g., if G o o d 
Cli nical Practices or ot her re g ulat or y pr oce d ures are n ot f oll o we d; if e nr oll me nt rate 
is n ot s ufficie nt t o meet st u d y g oals). 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 5 6  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
9.  
T R E A T M E N T O F S U B J E C T S 
9. 1.  
Descri pti o n of St u d y Dr u g  
D uri n g C ycl e 1, patie nts will be ra n d o mize d 2: 1 t o eit her S G X 3 0 1 ( 0. 2 5 % s y nt hetic h y perici n) 
oi nt me nt or a n i de nticall y a p p eari n g place b o oi nt me nt. Patie nts will a p pl y t he oi nt me nt t wice a 
wee k t o t he 3 i n de x lesi o ns , mi ni mizi n g a p plicati o n t o ot her s ki n areas, a n d c o ver t he area wit h 
o pa q ue ba n d a gi n g. Trai ni n g f or c orr ect  a p plicati o n a n d ba n da gi n g will be gi ve n d uri n g t he first 
wee k  a n d c o nti n ue u ntil t he site staff is c o nfi d e nt t hat t he patie nt ca n a n d will a p pr o priatel y 
a d mi nister t he dr u g t he msel ves . T he lesi o ns will t he n be e x p ose d t o fl u ores ce nt li g ht treat me nt 
1 8- 2 4 h o urs later. T h ese pr oce d ur es will be c o nti n ue d f or 6 w ee ks ( 1 2 treat me nts) a n d, after a 2-
wee k r est peri o d , t he r es p o nse t o treat me nt will be assesse d. It is i m p orta nt t o n ote t hat t he mai n 
p ur p ose of c o v eri n g t he l esi o ns is t o pre ve nt e x p os ure t o li g ht. T heref ore, a n y met h o d of 
c o veri n g t he lesi o ns s uc h as ba n da ges, wra ps, cl ot hi n g, etc. is acce pta ble if it creates a n o pa q ue 
barrier o v er t he tr eate d ar ea a n d is ke pt i n place u ntil it is ti me f or t he li g ht t hera p y.  S oli ge ni x 
will pr o vi de a n u m ber of differe nt o pti o ns f or c o veri n g t he lesi o ns t o t he sit es d uri n g st art u p. 
Beca use t he b o d y h a bit us a n d lesi o n l ocati o n is differe nt f or eac h patie nt, t h e best met h o d of 
c o veri n g t he lesi o ns ma y differ fr o m patie nt t o patie nt.     
D uri n g C ycl e 2, all patie nts will be treate d wit h S G X 3 0 1. Patie nts will a p pl y t he oi nt me nt t wice 
a wee k t o t he i n de x lesi o ns t h at di d N O T ac hie ve a c o m plete res p o nse f oll o wi n g C ycle 1 
t her a p y, mi ni mizi n g a p plicati o n t o ot her s ki n areas, a n d c o ver t h e area wit h o pa q ue ba n d a gi n g. 
T he lesi o ns will t he n be e x p ose d t o fl u oresce nt li g ht treat me nt 1 8- 2 4 h o urs later. T hese 
pr oce d ur es will be c o nti n ue d f or 6 w ee ks ( 1 2 treat me nts) a n d t he res p o ns e t o treat me nt will be 
assesse d after a 2- wee k r est peri o d. 
D uri n g t h e o pti o nal C ycl e 3, all patie nts wi ll be treate d wit h S G X 3 0 1. Patie nts will a p pl y t he 
oi nt me nt t wice a wee k t o  all lesi o n s selecte d b y t he p h ysici a n a n d p atie nt, mi ni mizi n g 
a p plicati o n t o ot her s ki n areas, a n d c o v er t he area wit h o pa q ue ba n da gi n g. T he lesi o ns will t he n 
be e x p ose d t o fl u ores ce nt li g ht treat me nt 1 8- 2 4 h o urs later. T hes e pr oce d ures will be c o nti n ue d 
f or 6 wee ks ( 1 2 treat me nts) a n d t he res p o ns e t o treat me nt will be assesse d after a 2- wee k rest 
peri o d. 
Patie nts will be f oll o we d e ver y 4 w ee ks f or Weeks 2 4 t o 4 8 b ut n o st u d y m e dicati o n gi ve n 
d uri n g t his peri o d. 
9. 2.  
C o nc o mit a nt Me dic ati o ns  
Pri or me dicati o ns , g oi n g bac k 3 wee ks  fr o m t he s cree ni n g date (s yste mic a n d t o pical), will be 
c ollecte d at t he s cree ni n g visit . C o nc o mita nt me dicati o ns (s yst e mic a n d t o pical) will be c ollect e d 
at eac h cli nic visit.  
T o pical ster oi ds ca n b e a p plie d t o a n y n o n- i n de x lesi o n if t he y are at least 1 c m a wa y fr o m all 
i n de x lesi o ns d uri n g C ycles 1 a n d 2. Treat me nts a p plie d t o n o n-i n de x lesi o ns nee d t o be halte d a 
mi ni m u m of 2 wee ks pri or t he start of C ycle 3 , if t he patie nt i nte n ds t o partici pate i n C ycl e 3. 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 5 7  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
T he f oll o wi n g dr u gs ar e n ot all o w e d o n i n de x lesi o ns  wit hi n 2  w ee ks  of e nr oll me nt or d uri n g 
t he st u d y:  
•  T o pical ster oi ds (i ncl u di n g 1 % h y dr oc ortis o ne crea m or oi nt me nt) of t he 3 i n de x 
lesi o ns. 
•  T o pical N itr o ge n m ustar d  of t he 3 i n de x lesi o ns 
T he f oll o wi n g dr u gs ar e n ot all o w e d wit hi n 3 w ee ks  of e nr oll me nt or d uri n g t he st u d y: 
•  S yste mic ster oi ds  
•  P s orale n U V A r a diati o n t hera p y ( P U V A) 
•  Narr o w b a n d -U V B  
•  C ar m usti ne ( B C N U)  
•  O t her s yste mic t her a pies f or C T C L 
T he f oll o wi n g dr u gs ar e n ot all o w e d wit h i n 3 0 d a ys of e nr oll me nt or d uri n g t he st u d y: 
•  I n v esti gati o nal dr u gs 
•  Dr u gs of a b use 
•  A ge nts k n o w n t o ca use p h ot ose nsitizati o n 
o  T he f oll o wi n g dr u gs ca n n ot be gi ve n wit hi n 3 0 da ys of e nr oll me nt: 
 5-fl u or o uracil 
 V i n blasti ne 
 Dac ar bazi ne 
 A L A or 5 -a mi n ole v uli nic aci d  
 Met h yl - 5-a mi n ole v uli nic aci d  
o  T he f oll o wi n g dr u gs ca n o nl y be us e d if t here h a v e bee n n o p h ot ot o xic reacti o ns 
t o t he sta ble d ose of t he dr u g after a mi ni m u m of 1 4 da ys of treat me nt: 
 Q ui n ol o ne a nti bi otic 
 Tetrac ycli ne  
 S ulf o na mi de  
 Di p he n h y dra mi ne 
 Q ui ni ne  
 C hl or o q ui ne  
 H y dr o x yc hl or o q ui ne   
 A mi o dar o ne 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 5 8  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
 S yste mic nife di pi ne 
 Q ui ni di ne 
 D iltiaze m 
 F ur ose mi de  
 T hiazi des  
 S ulf o n yl ureas  
 Is otr eti n oi n  
 A citreti n 
 P he n ot hiazi nes 
 T ric yclic a nti de pressa nts 
9. 3.  
Tre at me nt C o m pli a nce  
Patie nts will be trai ne d i n t he pr o per a p plicati o n of t he st u d y dr u g. T his i nitial a p plicati o ns will 
be d o ne u n der s u per visi o n of st u d y pers o n nel a n d c o nti n ue u ntil t he y are c o mf orta ble t hat t he 
patie nt ca n a p pr o priatel y a p pl y t he oi nt me nt. Patie nts will be q uesti o ne d pri or t o t he li g ht 
treat me nt t o ass ure t h at t he dr u g was a p plie d a n d it was a p plie d 18- 2 4 h o urs earlier. 
9. 4.  
R a n d o miz ati o n a n d Bli n di n g  
F or C ycle 1, p atie nts will be ra n d o mize d 2: 1 t o S G X 3 0 1: place b o usi n g a ra n d o mizati o n c o de 
ge n erat e d b y a n i n de p e n de nt statisticia n. Ra n d o mizati o n will be perf or me d usi n g a n I nt eracti ve 
We b Res p o nse S yste m i n a d o u ble- bli n d fas hi o n. B ot h S G X 3 0 1 a n d t he i d e nticall y a p peari n g 
place b o oi nt me nts will be pac k e d i n t he sa me plastic scre w-t o p jars a n d la b ele d i de ntical l y wit h a 
u ni q ue jar i de ntificati o n n u m ber.  
Patie nt s will be stratifie d at ra n d o mizati o n b y C T C L Sta ge  (I A, I B, a n d II A) a n d site. 




Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 6 0  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
1 0. 6.  
St u d y Dr u g Acc o u nt a bilit y  
T he PI  m ust e ns ure t hat all dr u g s u p plies are ke pt u n der l oc k a n d k e y wit h access li mite d t o t h ose 
a ut h orize d b y t he i n vesti gat or. T he PI  m ust mai ntai n acc urate rec or ds of t h e recei pt of all st u d y 
me dicati o n s hi p pe d b y t h e S p o ns or, i ncl u di n g dat e recei v e d, l ot n u m ber, e x pirati o n/re- test date, 
a m o u nt recei v e d a n d dis p ositi o n of all st u d y me di cati o n. C urre nt dis pe nsi n g rec or ds will be 
mai ntai ne d a n d i ncl u de d ate a n d a m o u nt of me di cati o n dis pe nse d, i nitials of s u bjects recei vi n g 
t he me dicati o n, a n d a n y a m o u nt of me dicati o n n ot use d or ret ur n e d ( or l ost) b y t he s u bj ect. All 
re mai ni n g m e dicati o n n ot re q uire d b y re g ulati o n t o be hel d b y t he cli nical facilit y, m ust be 
destr o ye d f oll o wi n g all a p pr o priate r e g ulat or y g ui deli nes or ret ur n e d t o t he S p o ns or i m me diatel y 
after t he st u d y is c o m plet e d. A n y l ost, s pille d or missi n g dr u g m ust be d oc u me nte d. 
1 0. 7.  
St u d y  Dr u g H a n dli n g a n d Dis p os al  
Dis p osa ble gl o v es s h o ul d be use d w he n a p pl yi n g t he dr u g t o s ki n lesi o ns a n d after a p pl yi n g t he 
oi nt me nt, ha n ds a n d a n y areas recei vi n g ot h er u ni nte n de d oi nt me nt s h o ul d be was he d wit h s oa p 
a n d water.  


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 6 1  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
1 1.  
A S S E S S M E N T O F E F FI C A C Y  
1 1. 1.  
Dise ase Assess me nt  
1 1. 1. 1  
C o m p osite As sess me nt of I n de x Lesi o n Se verit y   ( C AI L S) 
T he c o m plete C AI L S ass ess me nt sc ori n g s yst e m is prese nte d i n  Ta bl e 1 2  o n pa ge 4 2 . All 
patie nts will ha ve 3 i n de x lesi o ns i de ntifie d pri or t o ra n d o mizati o n. T hese lesi o ns will be 
assesse d at bas eli ne a n d t he n at t he e n d of C ycl e 1 a n d C ycl e 2 ( Wee ks 8 a n d 1 6) . All lesi o ns 
t hat are sc h e d ule d t o be treate d will be e va l uate d pri or t o C ycle 3 ( Wee k 1 6) a n d t he n a gai n at 
t he e n d of C ycle 3 ( Wee k 2 4). Eac h lesi o n will be sc ore d usi n g criteria s h o w n i n Ta ble 1 2 .  
T he t otal C AI L S sc ore will be calc ulate d b y a d di n g t he sc ores of eac h t he e val uate d lesi o n 
t o get her (t he sa m e 3 lesi o ns i n C ycles 1 a n d 2, a n d all of t he lesi o ns at t he baseli ne a n d e n d of 
C ycle 3). T he c h a n ge i n C AI L S sc ore will be calc ulate d b y t h e rati o of t he C AI L S sc ore at t he 
e n d of t he c ycl e t o t he C AI L S s c ore at t he be gi n ni n g of t he c ycle. 
1 1. 1. 2  
S ki n Re acti o n S af et y Gr a di n g  
S ki n reacti o ns will be e v al uate d bef ore a n d after eac h li g ht treat me nt. Eac h site of li g ht treat me nt 
s hall be e x a mi ne d a n d assesse d at least 5 mi n utes after c o m pleti o n of t he li g ht treat me nt a n d 
gr a de d usi n g t he scale s h o w n i n Ta ble 3  o n pa ge 3 2 .  
1 1. 1. 3  
Cl assific ati o n of Tre ate d S ki n Lesi o n Res p o nse  
Base d o n t h e I S C L/ U S C L/ E O R T C criteria [ 5 6], t he cli nical cat e g orizati o n will be as gi ve n i n 
Ta ble 1 5  usi n g t h e C AI L S sc ore rati o as t he m eas ure of s ki n res p o ns e. 
 
T a ble 1 5 : Cli nic al Res p o nse Defi niti o ns 
Res p o nse  
Defi niti o n  
C o m plete Res p o nse  
1 0 0 % cleari n g of s ki n lesi o ns ( C AI L S rati o 0 %) 
Partial Res p o nse  
5 0- 9 9 % cleara nce of disease ( C AI L S rati o 1 % t o 5 0 %)  
N o ne w ≥1 c m dia meter t u m or defi ne d as a s oli d or n o d ular lesi o n wit h e vi de nce 
of de pt h a n d/ or vertical gr o wt h  
Sta ble Disease  
2 5 % i ncrease t o 5 0 % cleara nce of s ki n disease ( C AI L S  rati o of 1 2 5 % t o 4 9 %) 
N o ne w ≥1 c m dia meter t u m or defi ne d as a s oli d or n o d ular lesi o n wit h e vi de nce 
of de pt h a n d/ or vertical gr o wt h  
Pr o gressi ve disease  
> 2 5 % i ncrease of s ki n disease ( C AI L S rati o  of > 1 2 5 % ) O R 1 or m ore  ne w ≥1 
c m dia meter t u m or defi ne d as a s oli d or n o d ular lesi o n wit h e vi de nce of de pt h 
a n d/ or vertical gr o wt h O R l oss of partial or c o m plete res p o nse defi ne d as a n 
i ncrease of C AI L S > s u m of t he na dir pl us 5 0 % of t he baseli ne sc ore 
Rela pse  
A n y disease rec urre nce i n t h ose wit h c o m plete res p o nse  


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 6 2  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
Lesi o ns d eter mi ne d t o ha ve a C o m plete Res p o nse will n ot be treate d d uri n g t he ne xt C ycl e of 
t hera p y.  
T o be cate g orize d as a Partial Res p o nse ( C AI L S Rati o ≤5 0 %), t he patie nt m ust als o ha ve n o ne w 
cli nicall y a b n or mal l y m p h n o des, n o c uta ne o us t u m ors, a n d n o ne w pat h ol o gicall y p ositi ve 
l y m p h n o de or visceral disease i n a n area pre vi o usl y d oc u m e nte d t o be ne gati ve i n or der t o 
mai ntai n t he sc ori n g as a Partial Res p o nse.  
1 1. 1. 4  
M o difie d Se verit y Wei g hte d Assess me nt T o ol ( m S W A T)  
T he m S W A T  is desi g ne d t o q ua ntif y t he disease b ur de n ass ociat e d wit h C T C L a n d is bas e d o n 
a n esti mate of t he p erce nt t otal area of s ki n i n v ol v e d base d o n t he b o d y s urface area ( B S A). T h e 
t y pes of l esi o ns are wei g hte d b y t he l esi o n c haract eristic ( patc h, pla q u e, or t u m or) as s h o w n i n 
Ta ble 1 4  o n pa ge 4 4 . 
1 1. 1. 5  
P h ysici a n Gl o b al A ssess me nt ( P G A) 
T he P G A re prese nts t he i n vesti gat or's assess me nt of t he o verall e xte nt of i m pr o ve me nt or 
w orse ni n g of t he p atie nt's c uta ne o us diseas e c o m pare d wit h bas eli ne as s h o w n i n Ta ble 1 3  o n 
pa ge 4 3 . T his assess me nt is desi g ne d t o c o nsi der all c uta ne o us lesi o ns, i ncl u di n g b ot h i n de x a n d 
n o n-i n de x lesi o ns.  
1 1. 1. 6  
Di git al P h ot o gr a p h y 
All i n vesti gat ors will be caref ull y tr ai ne d pri or t o e nr olli n g patie nts s o t hat hi g h q ualit y a n d 
u nif or m di gital p h ot o gra p hs will be o btai ne d t hr o u g h o ut t he e ntire st u d y. At t he start of eac h 
treat me nt c ycl e a n d at t h e 8- wee k  e val u ati o n p oi nt, o ver vie w p h ot o gra p hs will be o btai ne d a n d 
all treate d lesi o ns will be e val uate d b y cl ose - u p di gital p h ot o gra p h y. Pri or t o C ycle 2 a n d at 
W ee k 1 6 all treate d lesi o ns will be e val uate d b y o ver vie w a n d cl ose - u p di gital p h ot o gra p h y. 
Pri or t o C ycle 3 a n d at Wee k 8 of C ycle 3, cl ose - u p a n d o ver vie w p h ot o gra p hs will als o be 
o btai ne d f or e v al uati o n of t he treat me nt. 
1 1. 1. 7  
Bi o ps y 
Eac h st u d y partici pa nt will ha ve a si n gl e i n de x lesi o n selecte d f or bi o ps y at st u d y e ntr y. T his 
lesi o n s h o ul d be re pres e ntati ve of t he patie nt’s lesi o ns a n d t he sa me lesi o n will be re- bi o psie d at 
t he c o ncl usi o n of Cycle 1 t o deter mi ne t he nat ure of cleari n g of t he mali g n a nt i nfiltrate. Eac h 
bi o ps y s h o ul d be ta ke n fr o m a re pr ese ntati ve p orti o n of t he lesi o n a n d t he s ec o n d bi o ps y 
o btai ne d at least 1 c m f or t he ori gi nal bi o ps y site. Eac h bi o ps y will c o nsist of a 3 m m p u nc h 
bi o ps y t hat will be f or mali n -fi x e d, paraffi n e m be d de d, secti o ne d a n d st ai ne d at t he site as 
descri be d i n  A p p e n di x 1 8. 4.    o n pa ge 8 5 . T he st ai ne d a n d  u nstai ne d sli des will be se nt t o t he 
Ce ntral Pat h ol o g y La b or at or y f or gr a di n g a n d f urt her a nal ysis.  
All bi o psies will be rea d b y a si n gle , st u d y-wi de  p at h ol o gist i n a bli n de d ma n ner. T h e de gree of 
i nfiltrate will be c har acterize d at eac h ti me peri o d (i.e., at baseli ne a n d at t h e e n d of C ycle  1) o n a 
0 t o 3 + scale  as s h o w n i n Ta ble 1 6 . 
 








Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 6 6  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
1 2.  
A S S E S S M E N T O F S A F E T Y  
Ti mel y, acc ur ate a n d c o m plete re p orti n g a n d a nal ysis of safet y i nf or mati o n fr o m trials is cr ucial 
f or t he pr otecti o n of s u bjects, i n vesti gat ors a n d t h e S p o ns or, a n d is ma n dat e d b y re g ulat or y 
a ge ncies w orl d wi de. S oli ge ni x has esta blis he d sta n dar d o perati n g pr oce d ures ( S O Ps) i n 
c o nf or mit y wit h re g ulat or y re q uire m e nts t o e ns ure a p pr o priate re p orti n g of safet y i nf or mati o n. 
All trials t hat are t he r es p o nsi bilit y of S oli ge ni x m ust be c o n d ucte d i n acc or da nce wit h t he 
pr oce d ur es as pr o vi d e d b el o w. 
1 2. 1.  
Defi niti o ns  
1 2. 1. 1  
A d verse E x perie nce ( A E ) 
A n y n o xi o us or u ni nte n de d e ve nt t hat occ urs i n ass ociati o n wit h t he use of a n i n vesti gati o nal 
a ge nt i n h u ma ns , w het her c o nsi dere d rel ate d t o t he i nvesti g ati o n al a ge nt or n ot. T his defi niti o n 
e nc o m passes s y m pt o ms or si g ns r e p orte d b y t he s u bject or detecte d b y t he i n vesti gat or or o t h er 
c o m pete nt o bser v er, as w ell as me dicall y i m p orta nt de viati o ns fr o m n or malit y i n t he res ults of 
a ncillar y i n vesti gati o ns. If prese nt at ti me of first d ose of st u d y dr u g, s uc h A Es m ust be rec or d e d 
as part of t he me di cal hist or y.  
Tre at me nt -E mer ge nt A E : A n A E t hat is ne w i n o nset or a g gra vate d i n se verit y or fre q ue nc y 
f oll o wi n g e ntr y i nt o t he st u d y. I n a d diti o n, a n y p at h ol o gical fi n di n g o n p h ysical e x a mi nati o n or 
dia g n ostic pr o ce d ur e t hat is ne w i n occ urre nce or e x acer bate d i n c o m paris o n wit h t he s u bject's 
stat us at st u d y e ntr y is c o nsi dere d a tr eat me nt-e m er ge nt A E if it re q uires a n y me dical or s ur gical 
i nter ve nti o n w hats oe ver (i ncl u di n g, b ut n ot li mite d t o, a d diti o nal dia g n ostic pr oce d ures or 
alterati o n of pr escri be d t hera p y).  
1 2. 1. 2  
Seri o us A d verse E x peri e nce ( S A E)  
A n y A E occ urri n g at a n y d ose t hat res ults i n a n y of t he f oll o wi n g o ut c o mes: 
•  D eat h  
•  A life-t hreate ni n g A E 
•  Pr ol o n gati o n of e xisti n g h os pitalizati o n or s u bse q ue nt nee d f or h os pitalizati o n 
•  A persiste nt or si g nifica nt disa bilit y/i nca p acit y  
•  A c o n ge nital a n o mal y/ birt h defect  
•  A me dical or s ur gical i nter ve nt i o n t o pre v e nt o ne of t he a b o ve 
1 2. 1. 3  
P ot e nti all y Seri o us A d verse E x perie nce  
A n y A E t hat is s ufficie ntl y se vere or alar mi n g as t o re q uire a n y f or m of si g nifica nt me dical 
i nter ve nti o n. N ote: I m p orta nt me dical ev e nts t hat ma y n ot res ult i n deat h, b e life t hreate ni n g, or 
re q uire h os pitalizati o n ma y b e c o nsi dere d a n S A E w he n, base d u p o n a p pr o priate me dical 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 6 7  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
j u d g me nt, t he y ma y je o p ar dize t he s u bject a n d re q uire me dical or s ur gical i nter ve nti o n t o pre ve nt 
o ne of t he o utc o mes liste d i n t he S A E defi niti o n.  
1 2. 2.  
Rel ati o ns hi p t o St u d y Dr u g  
T he relati o ns hi p of a n A E t o t he assi g ne d st u d y dr u g is ass esse d usi n g t he f oll o wi n g defi niti o ns: 
•  N ot Rel at e d : T he dr u g e x perie nce is clearl y relat e d t o ot her fact ors s uc h as t he 
patie nt’s/s u bject’s cli nical state, t hera pe utic i nter v e nti o ns or c o nc o mita nt dr u gs.  
•  P ossi bl y Rel ate d:  T h e dr u g e x perie nce f oll o ws a reas o na bl e se q ue n ce fr o m t he ti me 
of dr u g a d mi nistrati o n a n d/ or f oll o ws a k n o w n res p o nse patter n t o t he st u d y dr u g, b ut 
c o ul d ha ve bee n pr o d uce d b y ot her fact ors s uc h as t he patie nt’s/s u bject’s cli nical 
state, t hera p e utic i nter ve nti o ns or c o nc o mita nt dr u gs. 
•  Rel ate d:  T he dr u g e x perie nce f oll o ws a reas o n a bl e te m p oral se q u e nce fr o m t he ti me 
of dr u g a d mi nistrati o n a n d f oll o ws a k n o w n res p o nse patter n t o t he st u d y dr u g, a n d 
ca n n ot be r eas o na bl y e x plai ne d b y ot h er fact ors s u c h as t he patie nt’s/s u bject’s cli nical 
state, t hera p e utic i nter ve nti o ns or c o nc o mita nt dr u gs. 
1 2. 3.  
Se verit y of A d verse E ve nt  
A cli nical deter mi nati o n of t he i nte nsit y of a n A E  s h o ul d be d o ne f or all re p orte d A Es. T he 
se verit y assess me nt f or s h o ul d be c o m plete d usi n g t he f oll o wi n g defi niti o ns as g ui deli nes: 
•  Mil d:  A ware n ess of si g n or s y m pt o m, b ut easil y t olerate d. 
•  M o der ate:  Disc o mf ort e n o u g h t o ca use i nterfere n ce wit h us ual acti vit y.  
•  Se vere:  I nca pacitati n g wit h i na bilit y t o w or k or d o us ual acti vit y. 
•  N ot a p plic a ble:   I n s o me cases, a n A E  ma y be a n “all or n ot hi n g” fi n di n g, w hic h 
ca n n ot be gr a de d. 
1 2. 4.  
Rec or di n g A d verse E ve nts  
All A Es, w het her j u d ge d t o be relate d or n ot t o t he st u d y d r u g, s h o ul d be rec or de d i n b ot h t he 
me dical rec or d a n d t he e C R F. T he start a n d res ol uti o n dates, t he j u d g me nt of t he se verit y of t h e 
A E, t he j u d g me nt of t he r elati o ns hi p of t he A E t o t he st u d y dr u g, t h e acti o n ta ke n f or s u bse q u e nt 
d ose of st u d y dr u g, a n d t he o utc o me s h o ul d be n ote d. 
1 2. 5.  
Re p orti n g A d verse E ve nts  
1 2. 5. 1  
A d verse E ve nts  
All A E s s h o ul d be n ote d i n t he e C R F wit hi n 3 da ys of bei n g rec o g nize d. A n y A E  t h at is eit her a 
S A E or p ote ntial S A E s h o ul d be ha n dle d wit hi n t he ti mefra mes gi ve n i n s ecti o n 1 2. 5. 2 , bel o w. 
T he res ol uti o n date f or all rec or d e d A Es s h o ul d be e ntere d wit hi n 3 da ys of deter mi nati o n t hat 




Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 6 9  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
1 2. 6.  
D at a M o nit ori n g C o m mittee  
A n i n de pe n de nt D ata M o nit ori n g C o m mittee ( D M C ) c o nsisti n g of o ne Bi ostatisticia n (c hair) a n d 
t w o cli nicia ns, i ncl u di n g at least o ne Der mat ol o gist wit h e x pertise i n C T C L will be f or me d t o 
m o nit or t he safet y a n d c o n d uct of t he st u d y o n a n o n g oi n g b asis. Para meters t o be e val uate d will 
i ncl u de A E s (cli nical a n d la b orat or y), n u m ber of dr o p o uts o verall, t h ose wit h dra wals s pecificall y 
d ue t o w orse ni n g of disease, a n d t h ose wit h dra wals d ue t o fail ure t o i m pr o ve i n a ti mel y fas hi o n. 
Data will be re vi e we d  f or safet y i n a se mi- bli n de d fas hi o n wit h t he data prese nte d as treat me nt A 
a n d B. H o we ver, t he D M C, as part of its c hart er t o e val uate a n d e ns ure t he safet y of s u bjects 
partici pati n g i n t he tri al, has t he a ut h orit y t o u n bli n d t he data as a p pr o priat e. 
T he D M C ma y re q u est a n y safet y data i n cl u di n g, b ut n ot li mite d t o, S A Es, A Es, a n d la b orat or y 
val ues. T he D M C ma y als o re q uest a n y efficac y d ata i ncl u di n g, b ut n ot li mite d t o t he pri mar y 
a n d sec o n dar y o utc o mes i n or der t o e val u ate be n efit t o ris k. A d diti o nall y, t h e D M C will  c o n d uct 
o ne ( 1) i nteri m a n al ysis w he n a p pr o xi matel y 6 0 % ( n = 8 0) of t he ori gi nall y pla n ne d t otal n u m ber 
of e val ua ble s u bj ects ( n = 1 2 0) ha v e c o m plete d t h e C ycl e 1 W ee k 8 e v al uati o n (i.e., t he pri mar y 
e n d p oi nt e val uati o n). S oli ge ni x, I n c., par tici p ati n g cli nical i n vesti gat ors a n d a n y p ers o n nel 
i n v ol ve d i n trial c o n d uct will re mai n bli n de d t o st u d y treat me nt. T he pri mar y efficac y e n d p oi nt 
a n d t he ke y safet y e n d p oi nts will be c o m pare d bet wee n treat me nts i n a n u n bli n de d ma n ner as 
descri be d i n t he Statistical Secti o n 1 3. 3. 4 .  
 
 










Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 7 4  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
1 4.  
Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E  
1 4. 1.  
St u d y M o nit ori n g  
It is t he r es p o nsi bilit y of t he PI a n d site pers o n nel t o ass ure t hat t he data rec or de d i n t he Case 
Re p ort F or ms is acc urat e, c o m plete a n d ca n be v erifie d fr o m t he me dical rec or ds.  
I n acc or da n ce wit h t he G ui deli nes f or t he M o nit ori n g of Cli nical I n vesti gati o ns prese nte d i n t he 
I C H G ui d a nce o n G o o d Cli nical Practices ( E 6), S oli ge ni x will select, eit her directl y or t hr o u g h 
s u bc o ntract, q ualifie d i n di vi d uals t o m o nit or t he pr o gress of t he st u d y a n d a d here nce t o pr ot oc ol 
b y t he i n di vi d ual cli nical sites.  
1 4. 1. 1  
Pre -stu d y E v al u ati o n 
T his i nitial e nc o u nter wit h t he site will esta blis h t hat t he site has all of t he n ecessar y ele me nts t o 
s uccessf ull y partici pate i n t he pr o p ose d pr ot oc ol i ncl u di n g a d e q uate trai ne d staff, a de q u ate free 
ti me of t he staff, a d e q uat e facilities for s afe a n d pr o per trial c o n d u ct, e vi de n ce f or p ot e ntial 
e nr oll me nt of s uita ble patie nts, a de q uate researc h p har mac y s u p p ort, t he prese nce of a n I R B 
meeti n g t he l o cal a n d F D A re q uire m e nts, a n d a c o m mit me nt f or trai ni n g of all i n v ol ve d staff o n 
t he pr ot oc ol. 
1 4. 1. 2  
Site I niti ati o n Visit  
O nce all r e q uire d trials d oc u me nts ha ve bee n pr o cesse d,  t he Me dical M o nit or ( or trai n e d 
desi g nee) will i nitiat e t he st u d y aft er o n- site trai ni n g of t he partici pati n g staff at t he i nstit uti o n. 
T o pics c o ver e d will i ncl u de trai ni n g o n: 
•  T he i n vesti gati o nal stat us of t he st u d y dr u g a n d t he re q uire me nts f or its 
acc o u nta bilit y.  
•  Bac k gr o u n d o n t he st u d y dr u g. 
•  Details of t he pr ot oc ol i n cl u di n g patie nt sel ecti o n, st u d y dr u g a d mi nistrati o n , 
pr oce d ur es t o be perf or m e d, a n d visit sc he d ules. 
•  Critic al nat ure of o btai ni n g i nf or m e d c o nse nt i n acc or da n ce wit h t he D eclarati o n of 
Helsi n ki a n d I C H G ui da nce o n G C Ps ( E 6) bef ore e nr olli n g eac h s u bject i n t he st u d y. 
•  T he o bli gati o n t o e ns ur e I R B re vi e w a n d a p pr o val f or t he st u d y, i ncl u di n g t he 
pr ot oc ol, a me n d me nts, I C F a n d a n y a d vertise me nts,  is o btai ne d pri or t o its i nitiati o n 
at his/ her cli nical site, t o e ns ure c o nti n ui n g re vi e w of t he st u d y b y t he I R B, a n d t o 
kee p S oli ge ni x i nf or me d of s uc h a p pr o v al a n d s u bse q ue nt acti o ns c o n cer ni n g t he 
st u d y. 
1 4. 1. 3  
M o nit ori n g Vis its 
S oli ge ni x or t heir trai ne d desi g nee will perf or m o n -site m o nit ori n g visits as fre q ue ntl y as it 
dee ms necessar y. At t hes e visits, t he site m o nit or will c o m pare t he dat a e nt ere d i nt o t he eC R Fs 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 7 5  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
wit h t he s o urce d oc u m e nts a n d c hec k f or pr ot oc ol c o m plia nce i ncl u di n g a rec or d of i nf or me d 
c o nse nt, e nr oll me nt criteria, all s u bject assess me nts, all A E s a n d all c o nc o mita nt me dicati o ns. I n 
a d diti o n, st u d y dr u g a n d s u p p orti n g r ec or ds will b e re vie w e d. A d diti o nall y, t he y ass ure t hat all 
seri o us, life-t hreate ni n g or fatal A E s are b ei n g re p orte d i m me diatel y [a n d i n n o case later t ha n 
t we nt y-f o ur ( 2 4) h o urs after t he e ve nt] t o t he Me di cal M o nit or or desi g nee at S oli ge ni x. 
Fi n di n gs fr o m t hese r e vie ws will be disc usse d wit h t he i n vesti gat or a n d staff. C o m plete d pa ges 
of t h e eC R Fs will be e v al uate d at eac h visit. T he d ates of t he m o nit ori n g visits will be rec or de d 
i n a si g n-i n l o g t hat will be ke pt at t he site. T he st u d y c o or di nat or a n d i n v esti gat or are e x pecte d 
t o be a vaila ble f or q uesti o ns, t he s o urce d o c u me ntati o n rea dil y a vaila bl e, a n d a s uita ble 
e n vir o n me nt pr o vi de d f or re vie w of st u d y- rel ate d d oc u me nts. 
1 4. 1. 4  
Cl ose -o ut Visit  
T he cli nical res ear c h m o nit or(s) will perf or m a n e n d of trial visit t o e ns ure t hat:  
•  All dr u g r ec o n ciliati o n f or ms are acc urate a n d c o m plete.  
•  All u n use d st u d y dr u g is ret ur ne d t o t he a p pr o priat e l ocati o n. 
•  All data iss ues are res ol v e d a n d eC R Fs are c o m plete d a n d verifie d.  
•  T he I R B h as bee n n otifie d t hat t he st u d y has b ee n c o m plete d. 
•  T he i n vesti gat or at eac h site is a ware t h at t he st u d y has bee n c o m plet e d a n d n o f urt her 
s u bjects are e nr olle d. 
1 4. 2.  
A u dits a n d I ns pecti o ns  
Healt h A ut h orities (e. g., F D A), i n t he p ers o n of a trai ne d a n d pr o p erl y a ut h orize d e m pl o yee, ma y 
re q uest access t o all st u d y r ec or ds, i ncl u di n g s o urce d oc u me nts, f or i ns pecti o n a n d c o p yi n g. T h e 
i n vesti gat or will i m me diatel y n otif y S oli ge ni x of a n y u p c o mi n g i ns pecti o ns.  
Peri o dic a u diti n g i ns pecti o ns ma y als o be c o n d uct e d b y a re prese nt ati ve of t he Q ualit y 
Ass ura nce De p art me nt of S oli ge ni x or its desi g nee(s). 
 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 7 6  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
1 5.  
E T HI C S 
1 5. 1.  
I nstit uti o n al Re vie w B o ar d 
T he fi nal st u d y pr ot oc ol, i ncl u di n g t he fi nal v ersi o n of t he S u bject I nf or m ati o n a n d C o nse nt 
F or ms, m ust be a p pr o v e d i n writi n g b y a n I nstit uti o nal Re vie w B o ar d (I R B) t hat meets t he 
mi ni m u m F D A sta n dar ds bef ore e nr ol me nt of a n y s u bject i nt o t he st u d y. T h e PI o r t heir desi g nee 
is res p o nsi ble f or i nf or mi n g t he I R B of a n y S A E a n d a me n d me nt(s) t o t he pr ot oc ol as per 
re g ulat or y r e q uire me nts. 
1 5. 2.  
Et hic al C o n d uct of t he St u d y  
T he st u d y will be p erf or me d i n acc or d a nce wit h t he et hical pri nci ples i n t h e Decl arati o n of 
Helsi n ki, G o o d Cli nical Practice s a n d a p plica ble re g ulat or y re q uire me nts.  
1 5. 3.  
Writte n I nf or me d C o nse nt  
T he I n vesti gat or will e ns ure t hat t he s u bject or a l e gall y a ut h orize d re prese ntati ve of t he s u bject  
are gi ve n f ull a n d a de q u ate oral a n d writte n i nf or mati o n a b o ut t he nat ure, p ur p ose, p ossi ble ris k 
a n d be nefit of t h e st u d y. S u bjects m ust als o be n otifie d t hat t he y are free t o disc o nti n ue fr o m t he 
st u d y at a n y ti me. T h e s u bject s h o ul d be gi v e n t he o p p ort u nit y t o as k q uesti o ns a n d all o we d ti me 
t o c o nsi der t he i nf or mati o n pr o vi de d. T he s u bject’s si g ne d a n d d ate d i nf or m e d c o nse nt m ust be 
o bt ai ne d bef ore c o n d ucti n g a ny st u dy s pecific pr oce d ure . T he c o nse nt f or m t hat is use d m ust 
meet t he re q uir e me nts as o utli ne d i n t he I C H G ui d a nce o n G C Ps ( E 6) a n d m ust be a p pr o ve d b y 
b ot h t he re vie wi n g I R B a n d b y S oli ge ni x. 
1 5. 4.  
S u bject d at a pr otecti o n  
 
T he S u bject I nf or m ati o n a n d C o nse nt F or m will e x plai n t hat st u d y data will be st ore d i n a 
c o m p uter data b ase, mai ntai ni n g c o nfi d e n tialit y. S u bjects i n t his data base will be i de ntifie d  b y 
i nitials or e nr ol me nt c o de/s u bject n u m ber o nl y. A ut h orize d re prese nt ati ve of a re g ul at or y 
a ut h orit y ( e. g., M C C) ma y r e q uire dir ect access t o parts of t he trial site rec or ds rele va nt t o t he 
st u d y, i ncl u di n g s u bj ects’ me dical hist or y f or d ata verificati o n p ur p os es. 
1 5. 5.  
Fi n a nci al Discl os ure  
T he F D A has iss ue d r e g ulati o ns ( 2 1 C F R Part 5 4) t hat re q uire S p o ns ors (i n t his case S oli ge ni x) 
t o s u b mit c o m plete a n d acc urat e certificati o n or discl os ure state me nts t o certif y t he a bse nce of 
certai n fi n a ncial i nter ests of cli nical i n vesti gat ors a n d/ or discl ose t h ose fi na ncial i nterests, as 
re q uire d, w h e n cli nical st u dies are s u b mitte d t o t he F D A i n s u p p ort of mar keti n g a p pr o val of a 
ne w dr u g a p plicati o n ( N D A). T hes e re g ulati o ns are i nte n de d t o e ns ure t hat fi na ncial i nterests a n d 
arra n ge me nts of cli nical i n vesti gat ors, t hat c o ul d affect relia bilit y of d ata s u b mitte d t o t he F D A 
i n s u p p ort of mar keti n g a p pr o val, ar e i de ntifie d a n d discl ose d b y t he S p o ns or. 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 7 7  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
Cli nical i n vesti gat ors s hall be as ke d t o discl ose pr o prietar y (e. g., pate nt, lice nsi n g a gree me nt) 
a n d fi na ncial (e. g., st oc k o pti o ns, r o yalt y) i nterests as t he y p ertai n t o S oli ge ni x, pri or t o 
partici pati n g i n t he st u d y . I n a d diti o n, cli nical i n vesti gat ors will be re q uire d t o c o ns ult wit h 
S oli ge ni x bef ore ac q uiri n g a n y fi na ncial i nterest i n t he c o m pa n y a n d m ust discl ose a n y c ha n ge i n 
t heir pr o prietar y or fi na n cial i nterests if it occ urs d uri n g t he c o urse of t he st u d y a n d f or o ne year 
f oll o wi n g st u d y c o m pleti o n. Cli nical I n vesti gat or is defi ne d u n der Title 2 1 C F R Part 5 4 as a n 
i n vesti gat or or s u b-i n vesti gat or liste d o n t he F D A F or m 1 5 7 2 t hat is directl y i n v ol ve d i n t he 
treat me nt or e v al uati o n of researc h s u bjects. T he re q uire me nt f or pr o prietar y a n d fi na ncial 
discl os ure als o i ncl u des a n y o w n ers hi p b y t he s p o use or a n y de p e n de nt c hil d of t he i n vesti gat or. 
If t he F D A deter mi nes t hat t he fi na ncial i nterests of a n y cli nical i n vesti gat or raise seri o us 
q uesti o n a b o ut t he i nte grit y of t he d ata, t he F D A will ta ke a n y acti o n it dee ms nece ssar y t o 
e ns ure t he r elia bilit y of t he data , i ncl u di n g: 
•  Initiati n g a ge n c y a u dits of t he data deri ve d fr o m t he cli nical i n vesti gat or i n q uesti o n;  
•  Re q uesti n g t hat t he S p o ns or s u b mit f urt her a nal ys es of data, e. g., t o e val uat e t he effect of 
t he cli nical i n vesti gat or’s data o n o verall st u d y o ut c o me; 
•  Re q uesti n g t hat t he a p plica nt c o n d uct a d diti o nal i n de pe n de nt st u dies t o c o nfir m t he 
res ults of t he q uesti o ne d st u d y; a n d/ or 
•  R ef usi n g t o treat t he c o v ere d cli nical st u d y as pr o vi di n g data t hat ca n be t h e basis f or a n  
a ge nc y acti o n.  
If t he S p o ns or d oes n ot i ncl u de certificati o n or discl os ure, or b ot h, if re q uire d, or d oes n ot certif y 
t hat it was n ot p ossi ble t o o btai n t he i nf or mati o n, t he F D A m a y ref use t o fil e t he N D A. 
 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 7 8  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
1 6.  
D A T A H A N D LI N G A N D R E C O R D K E E PI N G  
1 6. 1.  
I ns pecti o n of Rec or ds 
1 6. 1. 1  
M o nit ori n g  
I n acc or da n ce wit h t he G ui deli nes f or t he M o nit ori n g of Cli nical I n vesti gati o ns prese nte d i n t he 
I C H G ui d a nce o n G o o d Cli nical Practices ( E 6), t he f oll o wi n g will be o bser ve d: 
S oli ge ni x will select, eit her directl y or t hr o u g h s u bc o ntract , q ualifie d i n di vi d uals t o m o nit or t he 
pr o gress of t he st u d y a n d a d here n ce t o pr ot o c ol b y t he i n di vi d ual cli nical sites. 
It is t he r es p o nsi bilit y of t he PI t o ass ure t hat, at m ut uall y a gree d u p o n ti mes, t he cli nical m o nit or 
has a p pr o priat e access t o all me d ical rec or ds, st u d y materials, st u d y a n d re g ulat or y bi n ders, 
la b orat or y a n d ra di o gr a p hic res ults, st u d y pers o n n el, t heir ti me t o all o w a de q uate assess me nt as 
t o t he q ualit y, c o m plete n ess a n d a d here nce t o all as pects of t he pr ot oc ol. 
1 6. 1. 2  
A u dits  
Healt h A ut h orities (e. g., F D A , et c.), i n t he pers o n of a trai ne d a n d pr o perl y a ut h orize d e m pl o yee, 
ma y r e q uest access t o all st u d y rec or ds, i ncl u di n g s o urce d oc u m e nts, f or i ns pecti o n a n d c o p yi n g. 
T he i n vesti gat or will i m me diatel y n otif y S oli ge ni x of a n y u pc o mi n g i ns pecti o ns. Peri o dic 
a u diti n g i ns pecti o ns ma y als o be c o n d ucte d b y a re prese nt ati ve of t he Q u alit y Ass ura n ce 
De part me nt of S oli ge ni x or its desi g nee(s). 
1 6. 2.  
Rete nti o n of Rec or ds  
C o pies of e C R Fs s h o ul d be retai ne d b y sites al o n g wit h all ori gi nal s o urce d oc u me nts (e. g., 
i nf or me d c o nse nt f or ms, la b orat or y r e p orts, pr o gress n otes, me dical hist ories, p h ysical a n d 
dia g n ostic fi n di n gs, dia g n oses a n d dates of t h era p y pri or t o a n d d uri n g t his st u d y, dr u g 
dis pe nsi n g/ dis p ositi o n rec or ds) t hat s u p p ort e C R Fs of eac h s u bj e ct m ust be retai ne d i n t he files 
of t he res p o nsi ble i n vesti gat or or i n h os pital rec or ds f or a mi ni m u m of t w o ( 2) years f oll o wi n g 
n otificati o n b y S oli ge ni x t hat all i n vesti gati o ns ha ve bee n disc o nti n ue d or t hat t he last a p pr o val 
of a mar k eti n g a p plicati o n h as bee n o btai ne d. 
If t he res p o nsi ble i n vesti gat or retires, rel ocates, or f or ot her reas o n wit h dra ws fr o m t he 
res p o nsi bilit y of kee pi n g t he st u d y r ec or ds, c ust o d y m ust be tra nsferre d t o a pers o n w h o will 
acce pt t he res p o nsi bilit y. S oli ge ni x m ust be n otifie d  i n writi n g of t he n a me a n d a d dress of t he 
ne w c ust o dia n. 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 7 9  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3:  Dece m b er 7, 2 0 1 6   
A me n d me nt 4:  J u n e 5, 2 0 1 7 
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
1 7.  
I N V E S TI G A T O R A G R E E M EN T  
 
I h a ve r ea d t he f ore g oi n g pr ot oc ol t hat i ncl u des A me n d me nt 5 a n d a gree t h at it c o ntai ns all 
necessar y details f or carr yi n g o ut t his st u d y. I will c o n d uct t he st u d y as o utli ne d herei n, i n 
acc or d a nce wit h l ocal a n d fe der al re g ulati o ns, G o o d Cli nical Practices a n d will c o m plete t he 
st u d y wit hi n t he ti me desi g nate d. 
 
I will pr o vi de c o pies of t he pr ot oc ol a n d all perti ne nt i nf or mati o n t o all i n di vi d uals res p o nsi ble t o 
me w h o assist  i n t he c o n d uct of t his st u d y. I will disc uss t his material wit h t he m t o e ns ure t he y 
are f ull y i nf or m e d re gar di n g t he st u d y dr u gs a n d t he c o n d uct of t he st u d y. 
 
I will use o nl y t he i nf or me d c o nse nt f or m a p pr o ve d b y t he I nstit uti o nal Re vie w B oar d/ Et hics 
C o m mittee a n d S oli ge ni x a n d will f ulfill all res p o nsi bilities f or s u b mitti n g perti ne nt i nf or mati o n 
t o t he I nstit uti o nal Re vie w B oar d/ Et hics C o m mittee res p o nsi ble f or t his st u d y. 
 
I f urt her a gree t hat t he H ealt h A ut h orities, S oli ge ni x, or t heir desi g nee(s) s hall ha ve access t o a n y 
s o urce d oc u m e nt fr o m w hic h case re p ort f or m i nf or mati o n ma y h a ve bee n ge n erat e d. 
 
I a gree t hat I a n d all i n vesti gat ors liste d o n t he F D A F or m 1 5 7 2 s hall i nf or m S oli ge ni x of a n y 
e q uit y i nter est i n t he c o m pa n y pri or t o a n d d uri n g partic i pati o n i n t his trial. I f urt her a gree t hat I 
a n d all liste d i n vesti gat ors will c o ns ult wit h S oli ge ni x bef ore ac q uiri n g a n y fi na ncial i nterest i n 
t he c o m pa n y d uri n g t he st u d y a n d f or o ne year aft er t he st u d y’s c o m pleti o n. 
 
 
 
 
 
 
I n v esti gat or's Si g nat ure 
Date  
 
 
 
 
Na me of I n v esti gat or ( T y pe d or Pri nte d) 
 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 8 0  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3: Dece m b er 7, 2 0 1 6   
A me n d me nt 4: J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
 
1 8.  
A P P E N DI C E S  
A p pe n di x 1 8. 1.    Li g ht Tre at me nt D ur ati o n B ase d  o n Li g ht Meter Re a di n g at t he  Lesi o n P ositi o n  
 
T R E A T M E N T TI M E S B A S E D O N P R E S C RI B E D D O S E A N D LI G H T O U T P U T  
  
  
 
LI G H T M E T E R  R E A DI N G A T L E SI O N P O SI TI O N I N W / M
2 
 
 
1 0 0  
1 0 5  
1 1 0  
1 1 5  
1 2 0  
1 2 5  
1 3 0  
1 3 5  
1 4 0  
1 4 5  
1 5 0  
5  
8: 1 8  
7: 5 7  
7: 3 6  
7: 1 4  
6: 5 4  
6: 3 9  
6: 2 4  
6: 1 2  
6: 0 0  
5: 4 8  
5: 3 6  
6  
1 0: 0 0  
9: 3 3  
9: 0 6  
8: 4 2  
8: 1 8  
8: 0 0  
7: 4 2  
7: 2 4  
7: 0 6  
6: 5 4  
6: 4 2  
7  
1 1: 4 2  
1 1: 0 9  
1 0: 3 6  
1 0: 0 9  
9: 4 2  
9: 2 1  
9: 0 0  
8: 3 9  
8: 1 8  
8: 0 3  
7: 4 8  
8  
1 3: 1 8  
1 2: 4 2  
1 2: 0 6  
1 1: 3 6  
1 1: 0 6  
1 0: 3 9  
1 0: 1 2  
9: 5 1  
9: 3 0  
9: 1 2  
8: 5 4  
9  
1 5: 0 0  
1 4: 1 8  
1 3: 3 6  
1 3: 0 3  
1 2: 3 0  
1 2: 0 0  
1 1: 3 0  
1 1: 0 6  
1 0: 4 2  
1 0: 2 1  
1 0: 0 0  
1 0  
1 6: 4 2  
1 5: 5 7  
1 5: 1 2  
1 4: 3 3  
1 3: 5 4  
1 3: 2 1  
1 2: 4 8  
1 2: 2 1  
1 1: 5 4  
1 1: 3 0  
1 1: 0 6  
1 1  
1 8: 2 4  
1 7: 2 8  
1 6: 4 0  
1 5: 5 7  
1 5: 1 7  
1 4: 4 0  
1 4: 0 7  
1 3: 3 5  
1 3: 0 6  
1 2: 3 9  
1 2: 1 3  
1 2  
2 0: 0 0  
1 9: 0 3  
1 8: 1 1  
1 7: 2 4  
1 6: 4 0  
1 6: 0 0  
1 5: 2 3  
1 4: 4 9  
1 4: 1 7  
1 3: 4 8  
1 3: 2 0  
 
 
 
1 5 5  
1 6 0  
1 6 5  
1 7 0  
1 7 5  
1 8 0  
1 8 5  
1 9 0  
1 9 5  
2 0 0  
5  
5: 2 4  
5: 1 2  
5: 0 3  
4: 5 4  
4: 4 5  
4: 3 6  
4: 3 0  
4: 2 4  
4: 1 8  
4: 1 2  
6  
6: 2 7  
6: 1 2  
6: 0 3  
5: 5 4  
5: 4 2  
5: 3 0  
5: 2 1  
5: 1 2  
5: 0 6  
5: 0 0  
7  
7: 3 3  
7: 1 8  
7: 0 6  
6: 5 4  
6: 3 9  
6: 2 4  
6: 1 5  
6: 0 6  
5: 5 7  
5: 4 8  
8  
8: 3 6  
8: 1 8  
8: 0 3  
7: 4 8  
7: 3 6  
7: 2 4  
7: 1 2  
7: 0 0  
6: 4 8  
6: 3 6  
9  
9: 4 2  
9: 2 4  
9: 0 6  
8: 4 8  
8: 3 5  
8: 1 8  
8: 0 3  
7: 4 8  
7: 3 9  
7: 3 0  
1 0  
1 0: 4 5  
1 0: 2 4  
1 0: 0 6  
9: 4 8  
9: 3 0  
9: 1 2  
8: 5 7  
8: 4 2  
8: 3 0  
8: 1 8  
1 1  
1 1: 5 0  
1 1: 2 8  
1 1: 0 7  
1 0: 4 7  
1 0: 2 9  
1 0: 1 1  
9: 5 5  
9: 3 9  
9: 2 4  
9: 1 0  
1 2  
1 2: 5 5  
1 2: 3 0  
1 2: 0 7  
1 1: 4 6  
1 1: 2 6  
1 1: 0 7  
1 0: 4 9  
1 0: 3 2  
1 0: 1 6  
1 0: 0 0  
D O S E I N J o ules/c m 2 


Pr ot oc ol H P N- C T C L - 0 1 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 8 1  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3: Dece m b er 7, 2 0 1 6   
A me n d me nt 4: J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
 
A p pe n di x 1 8. 2.    Lesi o n L oc ati o n M a p  
B O D Y  L E SI O N  DI A G R A M : S O LI G E NI X  / S G X 3 0 1  
 
Pl e as e  i d e ntif y t h e i n d e x l esi o ns l o c ati o n usi n g  s u p pli e d w hit e  r ef ere n c e l a b els wit h  t h e 
a p pr o pri at e  n u m b eri n g  ( E x. 1,  2 or 3)  writt e n  o n t h e m. 
 
 
 


Pr ot oc ol H P N- C T C L - 0 1 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 8 2  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3: Dece m b er 7, 2 0 1 6   
A me n d me nt 4: J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
 
 
A p pe n di x 1 8. 3.    P atie nt I nstr ucti o ns/ Tre at me nt L o g  
 
F L A S H  ( Fl u oresce nt Li g ht Acti vate d S y nt hetic H y peri ci n)   
A P hase 3 cli nical st u d y f or t he treat me nt of C uta ne o us T- Cell L y m p h o ma 
 
Oi nt me nt A p plic ati o n I nstr ucti o ns  
 
T he ni g ht bef ore y o ur h os pital visit f or li g ht treat me nt, y o u will a p pl y t he st u d y dr u g oi nt me nt t o 
y o ur s ki n lesi o ns t hat were i de ntifie d as t he t hree i n de x lesi o ns b y y o ur d oct or. F or C ycles 1 a n d 
2, y o u will o nl y a p pl y t he oi nt me nt t o t hese 3. F or C ycle 3, y o u will a p pl y t he oi nt me nt t o all 
lesi o ns. Eac h ti me y o u a p pl y t he oi nt me nt, write d o w n t he date a n d ti me of a p plicati o n i n t he 
a p pr o priate sl ot bel o w. 
 
Bef ore a p pl yi n g t he st u d y dr u g oi nt me nt t o y o ur s ki n lesi o ns, y o u or t he pers o n hel pi n g y o u 
s h o ul d p ut o n dis p osa ble gl o ves. T h e oi nt me nt s h o ul d be a p plie d t hi nl y a n d e ve nl y o ver t he 
e ntire s urf ace of eac h le si o n. T he u naffecte d s ki n ar o u n d t he lesi o n s h o ul d be a v oi de d as m uc h as 
p ossi ble a n d a n y oi nt me nt o n t he u naffecte d s ki n s h o ul d be wi pe d a w a y. After a p plicati o n, eac h 
lesi o n s h o ul d be c o vere d wit h t he ba n da ge a n d ta p e pr o vi de d t o y o u b y t he h os pital. T his will 
e ns ure t hat t he s ki n lesi o n is pr otecte d fr o m li g ht u ntil y o ur h os pital visit a n d f or 2 4 h o urs after 
t he li g ht treat me nt. Ma k e s ure t hat t he jar t o p is ti g htl y cl ose d after usi n g. Fi nall y, after a p pl yi n g 
t he oi nt me nt, y o u or t he pers o n hel pi n g y o u s h o ul d was h t heir ha n ds wit h s oa p a n d wat er. 
 
 


Pr ot oc ol H P N- C T C L - 0 1 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 8 3  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3: Dece m b er 7, 2 0 1 6   
A me n d me nt 4: J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
 
C ycle 1 - Wee k 1, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 1 - Wee k 2, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 1 - Wee k 3, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 1 - Wee k 4, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 1 - Wee k 5, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 1 - Wee k 6, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 2 - Wee k 1, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 2 - Wee k 2, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 2 - Wee k 3, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 2 - Wee k 4, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 2 - Wee k 5, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
 
C ycle 1 - Wee k 1, A p plic ati o n 2 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 1 - Wee k 2, A p plic ati o n 2 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 1 - Wee k 3, A p plic ati o n 2 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 1 - Wee k 4, A p plic ati o n 2 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 1 - Wee k 5, A p plic ati o n 2 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 1 - Wee k 6, A p plic ati o n 2 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 2 - Wee k 1, A p plic ati o n 2 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 2 - Wee k 2, A p plic ati o n 2 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 2 - Wee k 3, A p plic ati o n 2 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 2 - Wee k 4, A p plic ati o n 2 
Dat e _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p pl icati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 2 - Wee k 5, A p plic ati o n 2 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
 


Pr ot oc ol H P N- C T C L - 0 1 
 
Ori gi nal:  
Ma y 2 7, 2 0 1 4  
A me n d me nt 1:  N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 8 4  of 8 9  
A me n d me nt 2:  J ul y 3 1, 2 0 1 5 
A me n d me nt 3: Dece m b er 7, 2 0 1 6   
A me n d me nt 4: J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
 
 
C ycle 2 - Wee k 6, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
 
C ycle 3 - Wee k 1, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 3 - Wee k 2, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 3 - Wee k 3, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 3 - Wee k 4, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 3 - Wee k 5, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 3 - Wee k 6, A p plic ati o n 1 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
 
C ycle 2 - Wee k 6, A p plic ati o n 2 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
 
C ycle 3 - Wee k 1, A p plic ati o n 2 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 3 - Wee k 2, A p plic ati o n 2 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 3 - Wee k 3, A p plic ati o n 2 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 3 - Wee k 4, A p plic ati o n 2 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 3 - Wee k 5, A p plic ati o n 2 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
C ycle 3 - Wee k 6, A p plic ati o n 2 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Ti me of a p plicati o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
 
 




Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:              Ma y 2 7, 2 0 1 4  
A me n d me nt 1:    N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 8 6  of 8 9  
A me n d me nt 2:    J ul y 3 1, 2 0 1 5 
A me n d me nt 3:    Dece m b er 7, 2 0 1 6   
A me n d me nt 4:    J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
 
1 9.  
R E F E R E N C E S  
1.  
Crisci o ne, V. D. a n d M. A. Wei nst oc k, I nci de nce of c ut a ne o us T-cell ly m p h o m a i n t he 
U nite d St ates, 1 9 7 3- 2 0 0 2.  Arc h D er mat ol, 2 0 0 7. 1 4 3 ( 7): p. 8 5 4- 9. 
2.  
B u n n, P. A., Jr., et al., Syste mic t her a py of c ut a ne o us T-cell ly m p h o m as ( m yc osis 
f u n g oi des a n d t he Sez ary sy n dr o me). A n n I nter n Me d, 1 9 9 4. 1 2 1 ( 8): p. 5 9 2- 6 0 2. 
3.  
Bi gl er, R. D., et al., A ut ol o g o us b o ne m arr o w tr a ns pl a nt ati o n f or a dv a nce d st a ge 
myc osis f u n g oi des.  B o n e Marr o w Tra ns pla nt, 1 9 9 1. 7 ( 2): p. 1 3 3- 7. 
4.  
Gra ha m, S.J., et al., Pr o g n ostic i m plic ati o ns of a b o ne m arr o w hist o p at h ol o gic 
cl assific ati o n syste m i n myc osis f u n g oi des a n d t he Sez ary sy n dr o m e.  Ca ncer, 1 9 9 3. 
7 2 ( 3): p. 7 2 6- 3 4. 
5.  
Br o der, S., et al., T he Sez ary sy n dr o me: a m ali g n a nt pr olifer ati o n of hel per T cells.  J 
Cli n I n vest, 1 9 7 6. 5 8 ( 6): p. 1 2 9 7- 3 0 6. 
6.  
B u n n, P. A., Jr. a n d S.I. La m ber g, Re p ort of t he C o m mittee o n St a gi n g a n d 
Cl assific ati o n of C ut a ne o us T- Cell Ly m p h o m as.  Ca ncer Treat Re p, 1 9 7 9. 6 3 ( 4): p. 7 2 5-
8. 
7. 
Ha y nes, B. F., et al., P he n oty pic c h ar acteriz ati o n of c ut a ne o us T-cell ly m p h o m a. Use of 
m o n ocl o n al a nti b o dies t o c o m p are wit h ot her m ali g n a nt T cells.  N E n gl J Me d, 1 9 8 1. 
3 0 4 ( 2 2): p. 1 3 1 9- 2 3. 
8.  
Ber ger, C. L., et al., C ut a ne o us T-cell ly m p h o m a: ne o pl as m of T cells wit h hel per 
activity.  Bl o o d, 1 9 7 9. 5 3 ( 4): p. 6 4 2- 5 1. 
9.  
K uli n, P. A., et al., Di a g n ostic i m a gi n g i n t he i niti al st a gi n g of myc osis f u n g oi des a n d 
Sez ary sy n dr o me.  Arc h Der mat ol, 1 9 9 0. 1 2 6 ( 7): p. 9 1 4- 8. 
1 0.  
E va ns, L. T., S. L. M ac ke y, a n d D. A. Vi d mar, A n asy m pt o m atic sc aly pl a q ue. 
U nilesi o n al myc osis f u n g oi des ( M F).  Arc h D er mat ol, 1 9 9 7. 1 3 3 ( 2): p. 2 3 1, 2 3 4. 
1 1.  
Bre n e ma n, D. L., et al., T o pic al mec hl oret h a mi ne i n t he tre at me nt of myc osis f u n g oi des. 
U nif or mity of a p plic ati o n a n d p ote nti al f or e nvir o n me nt al c o nt a mi n ati o n.  J A m Aca d 
Der mat ol, 1 9 9 1. 2 5 ( 6 Pt 1): p. 1 0 5 9- 6 4. 
1 2.  
Ki m, Y. H., et al., Cli nic al st a ge I A (li mite d p atc h a n d pl a q ue) myc osis f u n g oi des. A 
l o n g-ter m o utc o me a n alysis. Arc h Der m at ol, 1 9 9 6. 1 3 2 ( 1 1): p. 1 3 0 9- 1 3. 
1 3.  
V o n der hei d, E. C., et al., L o n g-ter m effic acy, c ur ative p ote nti al, a n d c arci n o ge nicity of 
t o pic al mec hl oret h a mi ne c he m ot her a py i n c ut a ne o us T cell ly m p h o m a. J A m Aca d 
Der mat ol, 1 9 8 9. 2 0 ( 3): p. 4 1 6- 2 8. 
1 4.  
Zac k hei m, H. S., E. H. E pstei n, Jr., a n d W. R. Crai n, T o pic al c ar m usti ne ( B C N U) f or 
c ut a ne o us T cell ly m p h o m a: a 1 5-ye ar ex p erie nce i n 1 4 3 p atie nts.  J A m Aca d 
Der mat ol, 1 9 9 0. 2 2 ( 5 Pt 1): p. 8 0 2- 1 0. 
1 5.  
A bel, E. A., et al., P U V A tre at me nt of eryt hr o der mic a n d pl a q ue- ty pe m yc osis 
f u n g oi des. Te n-year f oll o w- u p st u dy.  Arc h D er mat ol, 1 9 8 7. 1 2 3 ( 7): p. 8 9 7- 9 0 1. 
1 6.  
Dall ot, A., et al. I nterfer o n tre at me nt i n c ut a ne o us ly m p h o m as. i n I nt S oc H e m at ol 
Pr oc . 1 9 8 8. 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:              Ma y 2 7, 2 0 1 4  
A me n d me nt 1:    N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 8 7  of 8 9  
A me n d me nt 2:    J ul y 3 1, 2 0 1 5 
A me n d me nt 3:    Dece m b er 7, 2 0 1 6   
A me n d me nt 4:    J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
 
1 7.  
Mar ks, D.I., et al., Mec h a nis ms of ly m p h ocyt ot oxi city i n d uce d by extr ac or p ore al 
p h ot oc he m ot her a py f or c ut a ne o us T cell ly m p h o m a.  J Cli n I n vest, 1 9 9 0. 8 6 ( 6): p. 2 0 8 0-
5. 
1 8.  
E dels o n, R., et al., Tre at me nt of c ut a ne o us T-cell ly m p h o m a by extr ac or p ore al 
p h ot oc he m ot her a py. Pr eli mi n ary res ults.  N E n gl J Me d, 1 9 8 7. 3 1 6 ( 6): p. 2 9 7- 3 0 3. 
1 9. 
Zic, J., et al ., Extr ac or p ore al p h ot o p heresis f or t he tre at me nt of c ut a ne o us T- cell 
ly m p h o m a. J A m Aca d D er mat ol, 1 9 9 2. 2 7 ( 5 Pt 1): p. 7 2 9- 3 6. 
2 0.  
Ra msa y, D. L., et al., Ultr avi olet - B p h ot ot her a py f or e arly-st a ge c ut a ne o us T-cell 
ly m p h o m a. Ar c h Der m at ol, 1 9 9 2. 1 2 8 ( 7): p. 9 3 1- 3. 
2 1.  
Ka ye, F.J., et al., A r a n d o mize d tri al c o m p ari n g c o m bi n ati o n electr o n- be a m r a di ati o n 
a n d c he m ot her a p y wit h t o pic al t her a py i n t he i niti al tre at me nt of myc osis f u n g oi des.  N 
E n gl J Me d, 1 9 8 9. 3 2 1 ( 2 6): p. 1 7 8 4- 9 0. 
2 2.  
Wils o n, L. D., et al., Syste mi c c he m ot h er a py a n d extr ac or p ore al p h ot oc he m ot her a py f or 
T 3 a n d T 4 c ut a ne o us T-cell ly m p h o m a p atie nts w h o h ave ac hieve d a c o m plete res p o nse 
t o t ot al ski n electr o n be a m t her a py. I nt J Ra diat O nc ol Bi ol P h ys, 1 9 9 5. 3 2 ( 4): p. 9 8 7-
9 5. 
2 3.  
Dear d e n, C., E. Mat utes, a n d D. Cat o vs k y, De oxyc of or myci n i n t he tre at me nt of m at ure 
T- cell le uk ae mi as.  Br J Ca ncer, 1 9 9 1. 6 4 ( 5): p. 9 0 3- 6. 
2 4.  
Gre ver, M. R., et al., A n i nvesti g ati o n of 2'- de oxyc of or myci n i n t he tre at me nt of 
c ut a ne o us T- cell ly m p h o m a.  Bl o o d, 1 9 8 3. 6 1 ( 2): p. 2 7 9- 8 2. 
2 5.  
Lee, E., et al. P h ase II tri al of 2-c hl or o de oxy a d e n osi ne f or t he tre at me nt of c ut a ne o us 
T- cell ly m p h o m a . i n Pr oc 3 5t h A n n Meeti n g A m S oc He m at ol . 1 9 9 3. Bl o o d. 
2 6.  
V o n H off, D. D., et al., A ctivity of fl u d ar a bi ne m o n o p h os p h ate i n p atie nts wit h 
a dv a nce d m yc osis f u n g oi des: a S o ut h west O nc ol o gy Gr o u p st u dy.  J Natl Ca ncer I nst, 
1 9 9 0. 8 2 ( 1 6): p. 1 3 5 3- 5. 
2 7.  
B u n n, P. A., Jr., et al., Rec o m bi n a nt le uk ocyte A i nterfer o n: a n active a g e nt i n a dv a nce d 
c ut a ne o us T- cell ly m p h o m as.  A n n I nter n Me d, 1 9 8 4. 1 0 1 ( 4): p. 4 8 4- 7. 
2 8.  
Dre n o, B., et al., L o w- d ose rec o m bi n a nt i nterfer o n- al p h a i n t he tre at me nt of c ut a ne o us 
T-cell ly m p h o m as.  Br J Der mat ol, 1 9 8 9. 1 2 1 ( 4): p. 5 4 3- 4. 
2 9.  
Estrac h, T., et al., Tre at me nt of c ut a ne o us T-cell ly m p h o m a wit h rec o m bi n a nt alf a 2 B 
i nterfer o n. J I n v est Der m at ol, 1 9 8 9. 9 3 : p. 4 5 9. 
3 0.  
Fi gli n, R. A. a n d L. M. Itri, A nti -i nterfer o n a nti b o dies: a pers pective. Se mi n He mat ol, 
1 9 8 8. 2 5 ( 3 S u p pl 3): p. 9- 1 5. 
3 1.  
Czar niec ki, C. W., et al., Sy ner gistic a ntivir al a n d a nti pr olifer ative activities of 
Esc heric hi a  c oli- derive d h u m a n al p h a, bet a, a n d g a m m a i nterfer o ns. J Vir ol, 1 9 8 4. 
4 9 ( 2): p. 4 9 0- 6. 
3 2.  
K urzr oc k, R., et al., P h as e I st u dy of m ulti ple d ose i ntr a m usc ul arly a d mi nistere d 
rec o m bi n a nt g a m m a i nterfer o n. J Cli n O nc ol, 1 9 8 6. 4 ( 7): p. 1 1 0 1- 9. 
3 3.  
Miller, R. A. a n d R. Le v y, Res p o nse of c ut a ne o us T cell ly m p h o m a t o t her a py wit h 
hy bri d o m a m o n ocl o n al a nti b o dy.  La n cet, 1 9 8 1. 2 ( 8 2 4 0): p. 2 2 6- 3 0. 
3 4.  
K n o x, S., et al., Tre at me nt of c ut a ne o us T- cell ly m p h o m a wit h c hi meric a nti -C D 4 
m o n ocl o n al a nti b o dy.  Bl o o d, 1 9 9 6. 8 7 ( 3): p. 8 9 3- 9. 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:              Ma y 2 7, 2 0 1 4  
A me n d me nt 1:    N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 8 8  of 8 9  
A me n d me nt 2:    J ul y 3 1, 2 0 1 5 
A me n d me nt 3:    Dece m b er 7, 2 0 1 6   
A me n d me nt 4:    J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
 
3 5.  
F oss, F. M., et al., P h ase II st u dy of pe nt ost ati n a n d i nter mitte nt hi g h- d ose rec o m bi n a nt 
i nterfer o n alf a- 2 a i n a dv a nce d myc osis f u n g oi des/ Sez ary sy n dr o me. J Cli n O nc ol, 1 9 9 2. 
1 0 ( 1 2): p. 1 9 0 7- 1 3. 
3 6.  
Ric har ds o n, S. K., et al., Ext r ac or p ore al p h ot o p heresis a n d m ulti m o d ality 
i m m u n o m o d ul at ory t her a py i n t he tre at me nt of c ut a ne o us T-cell ly m p h o m a. J C uta n 
Me d S ur g, 2 0 0 3. 7 ( 4 S u p pl): p. 8- 1 2. 
3 7.  
B u d gi n, J. B., et al., Bi ol o gic al effects of bex ar ote n e i n c ut a ne o us T-cell ly m p h o m a.  
Arc h D er mat ol, 2 0 0 5. 1 4 1 ( 3): p. 3 1 5- 2 1. 
3 8.  
Parris h, J. A., et al., P h ot oc he m ot her a p y of ps ori asis wit h or al met h oxs ale n a n d 
l o n g w ave ultr avi olet li g ht. N E n gl J Me d, 1 9 7 4. 2 9 1 ( 2 3): p. 1 2 0 7- 1 1. 
3 9.  
T h o mas, C., et al., P h ot o activ ati o n of hy perici n ge ner ates si n gle t oxy g e n i n 
mit oc h o n dri a a n d i n hi bits s ucci n oxi d ase.  P h ot oc h e m P h ot o bi ol, 1 9 9 2. 5 5 ( 1): p. 4 7- 5 3. 
4 0.  
Mer uel o, D., G. La vie, a n d D. La vie, T her a pe utic a ge nts wit h dr a m atic a ntiretr ovir al 
activity a n d little t oxicity at effective d oses: ar o m atic p olycyclic d i o nes h y p erici n a n d 
pse u d o hy perici n.  Pr oc N atl Aca d Sci U S A, 1 9 8 8. 8 5 ( 1 4): p. 5 2 3 0- 4. 
4 1.  
La vi e, G., et al., St u dies of t he mec h a nis ms of acti o n of t he a ntiretr ovir al a ge nts 
hy perici n a n d pse u d o hy p erici n.  Pr oc Natl Aca d Sci U S A, 1 9 8 9. 8 6 ( 1 5): p. 5 9 6 3- 7. 
4 2.  
Bla n k, M., et al., E n h a n ce d u bi q uiti nyl ati o n of he at s h ock pr otei n 9 0 as a p ote nti al 
mec h a nis m f or mit otic cell de at h i n c a ncer cells i n d uce d wit h hy perici n.  Ca ncer Res, 
2 0 0 3. 6 3 ( 2 3): p. 8 2 4 1- 7. 
4 3.  
D ura n, N. a n d P. S. S o n g, Hy perici n a n d its p h ot o dy n a mic acti o n.  P h ot oc he m 
P h ot o bi ol, 1 9 8 6. 4 3 ( 6): p. 6 7 7- 8 0. 
4 4.  
Ber ns, M. W., et al., Res p o nse of ps ori asis t o re d l aser li g ht ( 6 3 0 n m) f oll o wi n g 
syste mic i njecti o n of he m at o p or p hyri n deriv ative. Las ers S ur g Me d, 1 9 8 4. 4 ( 1): p. 7 3- 7. 
4 5. 
E mtesta m, L., et al.,  Ti n - pr ot o p or p hyri n a n d l o n g w ave le n gt h ultr avi olet li g ht i n 
tre at me nt of ps ori asis. La ncet, 1 9 8 9. 1 ( 8 6 4 9): p. 1 2 3 1- 3. 
4 6.  
S R S, I. C., A n O p e n L a bel P h ase I/II St u dy t o Det er mi ne t he S afety a n d Effic acy of 
Hy perici n After T o pic al A p plic ati o n a n d Li g ht Irr a di ati o n f or I nfl a m m at ory Ski n 
Dise ases a n d W arts:  Ev al u ati o n of P h ot o dy n a mic T her a py.  Cli nical St u d y Re p ort, 
2 0 0 1. 
4 7.  
F o x, F. E., et al., P h ot o activ ate d hy perici n is a n a nti- pr olifer ative a ge nt t h at i n d uces a 
hi g h r ate of a p o pt otic de at h of n or m al, tr a nsf or me d, a n d m ali g n a nt T ly m p h ocytes: 
i m plic ati o ns f or t he tre at me nt of c ut a ne o us ly m p h o pr olifer ative a n d i nfl a m m at ory 
dis or ders.  J I n vest D er m at ol, 1 9 9 8. 1 1 1 ( 2): p. 3 2 7- 3 2. 
4 8.  
R o o k, A. H., et al., A p h ase II pl ace b o-c o ntr olle d st u dy of p h ot o dy n a mic t her a py wit h 
t o pic al hy perici n a n d visi ble li g ht irr a di ati o n i n t he tre at me nt of c ut a ne o us T-cell 
ly m p h o m a a n d ps ori asis. J A m Aca d Der mat ol, 2 0 1 0. 6 3 ( 6): p. 9 8 4- 9 0. 
4 9.  
Ta n g, J., et al., Vir uci d al activity of hy perici n a g ai nst e nvel o pe d a n d n o n-e nvel o pe d 
D N A a n d R N A vir uses.  A nti viral Res, 1 9 9 0. 1 3 ( 6): p. 3 1 3- 2 5. 
5 0.  
Kra us, G. A., et al., A ntiretr ovir al activity of sy nt hetic hy perici n a n d rel ate d a n al o gs.  
Bi oc he m Bi o p h ys R es C o m m u n, 1 9 9 0. 1 7 2 ( 1): p. 1 4 9- 5 3. 
5 1.  
Le n ar d, J., A. Ra bs o n, a n d R. Va n der oef, P h ot o dy n a mic i n activ ati o n of i nfectivity of 
h u m a n i m m u n o deficie ncy vir us a n d ot her e nvel o pe d vir uses usi n g hy perici n a n d r ose 


Pr ot oc ol H P N- C T C L - 0 1 
 
 
Ori gi nal:              Ma y 2 7, 2 0 1 4  
A me n d me nt 1:    N o ve m b er 1 8, 2 0 1 4  
C o nfi de nti al  
P a ge 8 9  of 8 9  
A me n d me nt 2:    J ul y 3 1, 2 0 1 5 
A me n d me nt 3:    Dece m b er 7, 2 0 1 6   
A me n d me nt 4:    J u n e 5, 2 0 1 7  
A me n d me nt 5:  N o ve m b er 3 0, 2 0 1 8  
 
be n g al: i n hi biti o n of f usi o n a n d sy ncyti a f or m ati o n.  Pr oc Natl Aca d Sci U S A, 1 9 9 3. 
9 0 ( 1): p. 1 5 8- 6 2. 
5 2.  
M orale da, G., et al., I n hi biti o n of d uck he p atitis B vir us re plic ati o n by hy perici n. 
A nti viral Res, 1 9 9 3. 2 0 ( 3): p. 2 3 5- 4 7. 
5 3.  
C h o o, Q. L., et al., Ge neti c or g a niz ati o n a n d diversity of t he he p atitis C vir us.  Pr oc Natl 
Aca d Sci U S A, 1 9 9 1. 8 8 ( 6): p. 2 4 5 1- 5. 
5 4.  
De gar, S., et al., I n activ atio n of t he h u m a n i m m u n o deficie ncy vir us by hy p erici n: 
evi de nce f or p h ot oc he mi c al alter ati o ns of p 2 4 a n d a bl ock i n u nc o ati n g.  AI D S Res 
H u m Retr o vir uses, 1 9 9 2. 8 ( 1 1): p. 1 9 2 9- 3 6. 
5 5.  
De gar, S., G. La vie, a n d D. Mer uel o, P h ot o dy n a mic i n activ ati o n of r a di ati o n le uke mi a 
vir us pr o d uce d fr o m hy p erici n- tre ate d cells. Vir ol o g y, 1 9 9 3. 1 9 7 ( 2): p. 7 9 6- 8 0 0. 
5 6.  
Olse n, E. A., et al., Cli nic al e n d p oi nts a n d res p o nse criteri a i n myc osis f u n g oi des a n d 
Sez ary sy n dr o me: a c o ns e ns us st ate me nt of t he I nt er n ati o n al S ociety f or C ut a ne o us 
Ly m p h o m as, t he U nite d St ates C ut a ne o us Ly m p h o m a C o ns orti u m, a n d t he C ut a ne o us 
Ly m p h o m a T ask F orce of t he E ur o pe a n Or g a nis ati o n f or Rese arc h a n d Tre at me nt of 
C a ncer.  J Cli n O nc ol, 2 0 1 1. 2 9 ( 1 8): p. 2 5 9 8- 6 0 7. 
5 7.  
Me hta, C. R. a n d S.J. P oc oc k, A d a ptiv e i ncre as e i n s a m ple size w he n i nteri m res ults are 
pr o misi n g: a pr actic al g ui de wit h ex a m ples.  Stat Me d, 2 0 1 1. 3 0 ( 2 8): p. 3 2 6 7- 8 4. 
 

SAP_001.pdf: 
S G X 3 0 1, S Y N T H E TI C H Y P E RI CI N  
H P N -C T C L -0 1  
A P h ase 3 M ultice nter, R a n d o mize d, D o u ble -Bli n d, Pl ace b o C o ntr olle d St u dy t o 
Deter mi ne t he Effic acy of T o pic al S G X 3 0 1 ( Sy nt hetic Hy perici n) a n d Fl u oresce nt B ul b -
Li g ht Irr a di ati o n f or t he Tre at me nt of C ut a ne o us T -Cell Ly m p h o m a  
S T A TI S TI C A L A N A L Y SI S P L A N  
Versi o n:   
4. 0  
Rele ase D ate:  
1 9  M a y  2 0 2 0  
C o nfi de nti ality St ate m e nt  
T he i nf or mati o n i n t his d oc u me nt c o ntai ns tra de secrets a n d c o m mercial i nf or mati o n t hat are  
pri vile ge d or c o nfi de ntial a n d ma y n ot be discl ose d u nless  s uc h discl os ure is re q uire d b y 
fe deral or state la w or re g ulati o ns. I n a n y e ve nt, pers o ns t o w h o m t he i nf or mati o n is discl ose d 
m ust be i nf or me d t hat t he i nf or mati o n is pri vile ge d or c o nfi de ntial a n d ma y n ot be f urt her 
discl ose d b y t he m. T hese restricti o ns o n discl os ure will a p pl y e q uall y t o all f ut ure  
i nf or mati o n s u p plie d t o y o u w hic h is i n dicate d as pri vile ge d or c o nfi de ntial. 
N C T 0 2 4 4 8 3 8 1






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S O LI G E NI X  
 C o nfi de nti al a n d Pr o priet ary                                P a ge 4  of 4 8  
 
T a ble of C o nte nts  
LI S T O F A B B R E VI A TI O NS ........................................................................................................................... 7  
I N T R O D U C TI O N ........................................................................................................................................ 8  
2.  
S T U D Y O BJ E C TI V E S  .......................................................................................................................... 9  
2. 1.  
P RI M A R Y O BJ E C TI V E S  ......................................................................................................................... 9  
2. 2.  
S E C O N D A R Y O BJ E C TI V E S  ..................................................................................................................... 9  
3.  
S T U D Y D E SI G N  .............................................................................................................................. 1 0  
4.  
S T U D Y E N D P OI N T S A N D D E FI NI TI O N  ............................................................................................ 1 3  
4. 1.  
P RI M A R Y E FFI C A C Y E N D P OI N T  ........................................................................................................... 1 3  
4. 2.  
S E C O N D A R Y E F FI C A C Y E N D P OI N TS  ...................................................................................................... 1 3  
4. 2. 1  
Cycl e 1 S ec o n d ary E n d p oi nts  ................................................................................................. 1 3  
4. 2. 2  
Cycl e 2 S ec o n d ary E n d p oi nts  ................................................................................................. 1 4  
4. 2. 3  
Cycl e 3 S ec o n d ary E n d p oi nts  ................................................................................................. 1 4  
 
 
 
 
4. 3.  
S A F E T Y E N D P OI N TS  .......................................................................................................................... 1 6  
4. 4.  
S T U D Y E N D P OI N T D EFI NI TI O N ............................................................................................................ 1 6  
4. 4. 1  
C o m p osit e Ass ess m e nt of L esi o ns S ev erity ( C AIL S) Sc or e  ...................................................... 1 6  
4. 4. 2  
T h e P hysici a n Gl o b al Ass ess m e nt ( P G A)  ................................................................................ 1 8  
4. 4. 3  
M o difi e d S ev erity W ei g ht e d Ass ess m e nt T o ol ( m S W A T)  ....................................................... 1 8  
4. 4. 4  
S ki n R e acti o n S af ety Gr a di n g  ................................................................................................. 1 9  
4. 4. 5  
Bi o psy  .................................................................................................................................... 1 9  
4. 4. 6  
D ur ati o n of P arti al a n d/ or C o m pl et e R es p o ns e i n t h e i n d ex l esi o ns  ..................................... 2 0  
4. 4. 7  
Ti m e t o r el a ps e i n t h e i n d ex l esi o ns  ....................................................................................... 2 0  
4. 4. 8  
Cl assific ati o n of tr e at e d s ki n l esi o n r es p o ns e  ........................................................................ 2 0  
5.  
S T A TI S TI C AL C O N SI D E R A TI O N S  ..................................................................................................... 2 2  
5. 1.  
S A M PL E S I Z E C AL C UL A TI O N  ............................................................................................................... 2 2  
5. 2.  
A N AL Y SIS P O P UL A TI O N S  ................................................................................................................... 2 2  
5. 2. 1  
I nt e nt-t o-tr e at (I T T) P o p ul ati o n ............................................................................................. 2 2  
5. 2. 2  
P er Pr ot oc ol ( P P) P o p ul ati o n .................................................................................................. 2 2  
5. 2. 3  
S af ety P o p ul ati o n  .................................................................................................................. 2 2  
5. 3.  
M E T H O D OL O G Y A N D C O N V E N TI O N S  ................................................................................................... 2 3  
5. 4.  
A D DI TI O N AL D A T A H A N DLI N G R UL ES A N D P R E S E N T A TI O N S P E CIFI C A TI O N S  ................................................. 2 3  
5. 5.  
S U BJ E C T D I S P O SI TI O N ...................................................................................................................... 2 4  
5. 6.  
D E M O G R A P HI C S A N D O T H E R B A S ELI N E C H A R A C T E RIS TI C S  ....................................................................... 2 5  
5. 7.  
M E DI C AL H IS T O R Y ........................................................................................................................... 2 5  
5. 8.  
P RI O R A N D C O N C O MI T A N T M E DI C A TI O N S  ........................................................................................... 2 6  
6.  
I N T E RI M A N AL Y SI S ........................................................................................................................ 2 7  
6. 1.  
A S S E SS M E N T O F O V E R W H EL MI N G S U P E RI O RI T Y O F O N E D O S E G R O U P  ...................................................... 2 7  
6. 2.  
C O N DI TI O N AL P O W E R P R O C E D U R E A N D , IF N E C ES S A R Y , S A M PL E S I Z E R E -E S TI M A TI O N ................................. 2 8  


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S O LI G E NI X  
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7.  
E F FI C A C Y A N AL Y S E S  ...................................................................................................................... 3 0  
7. 1.  
A N AL Y SIS O F P RI M A R Y E N D P OI N T  ....................................................................................................... 3 0  
7. 2.  
A N AL Y SIS O F S E C O N D A R Y E N D P OI N TS  .................................................................................................. 3 0  
 
 
 
 
 
8.  
S A F E T Y A N AL Y S E S  ......................................................................................................................... 3 6  
8. 1.  
A D V E R S E E V E N TS  ............................................................................................................................ 3 6  
8. 2.  
C LI NI C AL L A B O R A T O R Y P A R A M E T E RS  .................................................................................................. 3 7  
8. 3.  
V I T AL S I G N S ................................................................................................................................... 3 7  
8. 4.  
E X T E N T O F E X P OS U R E  ...................................................................................................................... 3 8  
A P P E N DI X 1:  D A T A H A N DLI N G C O N V E N TI O N S  ...................................................................................... 3 9  
1.  
M I S SI N G S E V E RI T Y A S S E S S M E N T F O R A D V E R S E E V E N T S  ................................................................ 3 9  
2.  
M I S SI N G R E L A TI O N S HI P T O S T U D Y D R U G F O R A D V E R S E E V E N T S  ................................................... 3 9  
3.  
M I S SI N G D A T E IN F O R M A TI O N F O R A D V E R S E E V E N T S  ..................................................................... 3 9  
4.  
M I S SI N G D A T E IN F O R M A TI O N F O R P RI O R O R C O N C O MI T A N T M E DI C A TI O N S  ................................... 4 0  
5.  
C LI NI C A L L A B O R A T O R Y P A R A M E T E R S  ............................................................................................ 4 1  
A P P E N DI X 2: S C H E D UL E  O F P R O C E D U R E S  .............................................................................................. 4 4  
 
 
 


H P N -C T C L -0 1  
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S O LI G E NI X  
 C o nfi de nti al a n d Pr o priet ary                                P a ge 6  of 4 8  
 
List of Fi g ures  
Fi g ure 1: St u d y Sc he ma  ................................................................................................................................ 1 2  
List of T a bles  
T a ble 1: S ki n P h ot ot o xicit y Gra di n g  ............................................................................................................. 1 1  
T a ble 2:  C o m p osite Assess me nt of I n de x Lesi o n Se verit y  .......................................................................... 1 6  
T a ble 3: P h ysicia n Gl o bal Ass ess me nt  .......................................................................................................... 1 8  
T a ble 4: M o difie d Se verit y W ei g hte d Assess me nt T o ol ( m S W A T)  ............................................................. 1 8  
T a ble 5 : P h ot ot o xicit y/ Er yt he ma Sc ore ......................................................................................................... 1 9  
T a ble 6:  Gra di n g of Bi o ps y  .......................................................................................................................... 2 0  
T a ble 7 : Cli nical Res p o nse Defi niti o ns ......................................................................................................... 2 0  
T a ble 8. Vital Si g ns Cli nicall y Si g nifica nt Val ue  ......................................................................................... 3 8  
T a ble 9: E xa m ple f or C o di n g of S pecial C haracter Val ues f or Cli nical La b orat or y P ara met ers  .................. 4 2  
T a ble 1 0: Ra n ges of P ote ntiall y Cli nicall y Si g nifica nt La b V al ues  .............................................................. 4 3  
T a ble 1 1: St u d y Assess me nts: C ycle 1 –  Wee k 1 Ra n d o mize d Dr u g t o I n de x Lesi o ns  ................................ 4 4  
T a ble 1 2: St u d y assess me nts: C ycle 1 - A p plicati o n a n d Irra diati o n # 3 -1 2 Ra n d o mize d Dr u g t o I n de x 
Lesi o ns  .............................................................................................................................. 4 5  
T a ble 1 3: C ycle 1 -W ee ks 7 a n d 8 Treat me nt E val uati o n  .............................................................................. 4 5  
T a ble 1 4: C ycle 2 - Irra diati o n Treat me nt # 1 3-2 4 All P atie nts 0. 2 5 % S G X 3 0 1 Oi nt me nt t o I n de x 
Lesi o ns  .............................................................................................................................. 4 6  
T a ble 1 5: C ycle 2 - Assess me nt  ..................................................................................................................... 4 6  
T a ble 1 6: O pti o nal C ycle 3 - W ee k 1 7 t hr o u g h 2 2 All P atie nts 0. 2 5 % S G X 3 0 1 Oi nt me nt t o All Lesi o ns  ... 4 7  
T a ble 1 7: C ycle 3: Assess me nt - C ycle 3 E val uati o n  ..................................................................................... 4 7  
T a ble 1 8: W ee ks 2 5 -4 8 - L o n g -ter m F oll o w-u p  ............................................................................................. 4 8  
 


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S O LI G E NI X  
 C o nfi de nti al a n d Pr o priet ary                                P a ge 7  of 4 8  
 
LI S T O F A B B R E VI A TI O N S  
 
A E  
A d verse E ve nt  
A N C O V A  
A nal ysis of C o varia nce  
A N O V A  
A nal ysis of Varia nce  
A T C  
A nat o mical T hera pe utic C he mical  
B S A  
B o d y S urface Area  
C AI L S  
C o m p osite Assess me nt of I n de x Lesi o n Disease Se verit y  
C T C L  
C uta ne o us T -cell L y m p h o ma  
e C R F  
Electr o nic Case Re p ort F or m  
E O R T C  
E ur o pea n Or ga nisati o n f or Researc h a n d Treat me nt of Ca ncer  
I S C L 
I nter nati o nal S ociet y f or C uta neo us L y m p h o mas  
I T T  
I nte nt-t o-Treat p o p ulati o n  
Me d D R A  
Me dical Dicti o nar y of Re g ulat or y Acti vities  
m S W A T  
M o difie d Se verit y Wei g hte d Assess me nt T o ol  
P G A  
P h ysicia n Gl o bal Assess me nt  
P P  
Per -P r ot oc ol P o p ulati o n  
S A E  
Seri o us A d verse E ve nt  
S A P  
Statistical A nal ysis Pla n  
S O C  
S yste m Or ga n Class  
U S C L C  
U nite d States C uta ne o us L y m p h o ma C o ns orti u m  
W H O  
W orl d Healt h Or ga nizati o n Dr u g Dicti o nar y  


H P N -C T C L -0 1  
St atistic al A n alysis Pl a n, v 4. 0  
1 9  M ay 2 0 2 0   
 
S O LI G E NI X  
 C o nfi de nti al a n d Pr o priet ary                                P a ge 8  of 4 8  
 
I N T R O D U C TI O N 
T his statistical a nal ysis pl a n ( S A P) pr o vi des a m ore tec h nical a n d detaile d ela b orati o n of t he 
statistical a nal yses of efficac y a n d safet y as o utli ne d a n d/ or s pecifie d i n A me n d me nt 5  of t he fi nal 
st u d y pr ot oc ol date d N o ve m ber 3 0, 2 0 1 8 . S pecificati o ns of ta bles, fi g ures, a n d data listi n gs are 
c o ntai ne d i n a se parate d oc u me nt  ( Ta ble s hells).  
 


H P N -C T C L -0 1  
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S O LI G E NI X  
 C o nfi de nti al a n d Pr o priet ary                                P a ge 9  of 4 8  
 
2.  
S T U D Y O B J E C TI V E S  
2. 1.  
P ri m ar y O bjecti ves  
 
Cycle 1 : T he pri mar y o bjecti ve of t his P hase 3 st u d y is t o e val uate t he a bilit y of t he i nitial 6 -wee k 
c o urse of S G X 3 0 1 a n d visi bl e li g ht ( C ycle 1) i n patie nts wit h patc h/ pla q ue p hase c uta ne o us 
T -cell l y m p h o ma ( C T C L) t o i n d uce a treat me nt res p o nse i n 3 i n de x lesi o ns t hat is defi ne d t o 
be a ≥5 0 % i m pr o ve me nt i n t he C o m p osite Assess me nt of I n de x Lesi o n Se verit y ( C AI L S) 
sc ore fr o m baseline t o t he Wee k 8 E val uati o n Visit w he n c o m pare d t o patie nts recei vi n g 
place b o a n d visi ble li g ht.  
 
Cycle 2 : T his c ycle is desi g ne d t o e val uate, as sec o n dar y e n d p oi nts, t he utilit y of a sec o n d c o urse of 
treat me nt o n i n de x lesi o ns wit h less t ha n c o m plete res po nse wit h t he i nitial t hera p y (t he 
C ycle 1 S G X 3 0 1 patie nts) a n d t o e xte n d t he data o n t he res p o nse rate of S G X 3 0 1 i n 
u ntreate d lesi o ns (t he C ycle 1 place b o patie nts).  
 
Cycle 3 : I n t his o pti o nal, o pe n-la bel p orti o n of t he st u d y, t he o bjecti ve is t o deter mi ne t he i m pact of 
S G X 3 0 1 treat me nt o n t he patie nt’s e xte nt of disease rat her t ha n i n di vi d ual lesi o ns.  
2. 2.  
S ec o n d ar y  o bjecti ves  
 
 
  
 
 
 
 
T o e val uate t he a bilit y of t o pical S G X 3 0 1 a n d visi ble li g ht i n patie nts wit h patc h / pla q ue p hase 
C T C L t o i n d uce P artial a n d/ or C o m plete R es p o nse after C ycles 2 a n d 3.  
 
T o e val uate t he de gree of i m pr o ve me nt of t he i n de x lesi o ns meas ure d b y C AI L S sc ore i n d uce d 
b y t o pical S G X 3 0 1 a n d visi ble li g ht i n patie nts wit h patc h/ pla q ue p hase C T C L d uri n g C ycles 1 
a n d 2. 
 
 
 
 
 
 
 
Assess t he safet y of t o pical S G X 3 0 1 a n d visi ble li g ht i n patie nts wit h patc h/ pla q ue p hase C T C L.  


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3.  
S T U D Y D E SI G N  
T his is a P hase 3 m ultice nter, ra n d o mize d, d o u ble -bli n d , place b o-c o ntr olle d st u d y t o deter mi ne t he 
efficac y of t o pical S G X 3 0 1 (s y nt hetic h y perici n) a n d fl u oresce nt b ul b -li g ht irra diati o n f or t he 
treat me nt of C T C L .  
A p pr o xi matel y 1 8 0  s u bjects will be ra n d o mize d i nt o t his P hase 3, place b o-c o ntr olle d, d o u ble -bli n d, 
m ultice nter st u d y (i n or der t o ass ure 1 6 0  e val ua ble patie nts) t o e val uate t he efficac y a n d safet y of 
t o pical p h ot ot hera p y wit h S G X 3 0 1 (s y nt hetic h y perici n) at a c o nce ntrati o n of 0. 2 5 % oi nt me nt. 
Patie nts will be stratifie d b y site a n d t u m or sta ge (I A, I B , a n d II A) at ra n d o mizati o n. Pri or t o 
ra n d o mizati o n eac h patie nt will ha ve 3 discrete lesi o ns j u d ge d b y t he PI t o be re prese ntati ve of t heir 
disease, a n d if b ot h pla q ue a n d patc h lesi o ns are prese nt, at least o ne of eac h t y pe will be selecte d as 
i n de x lesio ns t hat will be treate d d uri n g C ycle 1 a n d 2.  
Patie nts ma y u n der g o t hree c ycles of t hera p y:  
Cycle 1 : Patie nts will be ra n d o mize d 2: 1 S G X 3 0 1: P lace b o f or treat me nt of t he 3 i n de x lesi o ns 
selecte d b y t he i n vesti gat or. T he res ults of t his c ycle will be t he basis of t he pri mar y efficac y 
a nal ysis.  
Cycle 2 : All patie nts will recei ve S G X 3 0 1 treat me nt of t he 3  i n de x lesi o ns. 
O pti o n al Cycle 3 : All patie nts will recei ve S G X 3 0 1 treat me nt of u p t o all of t heir lesi o ns.  
F or eac h c ycle, st u d y oi nt me nt will be a p plie d t wice wee kl y f or 6 wee ks a n d o pa q ue  ba n da ge a p plie d 
f or 1 8 -2 4 h o urs f oll o we d b y t he a d mi nistrati o n of visi ble li g ht u p t o a d ose of 1 2  Jo ule /c m2. T he li g ht 
treat me nt will be perf or me d 3 -4 cale n dar da ys  ( ± 1 d a y) a part eac h wee k (e. g., M o n da y/ T h urs da y, 
M o n da y/ Fri da y, or T ues da y/ Fri da y).  
Pri or t o ra n d o mizati o n, eac h patie nt will ha ve t hree lesi o ns i de ntifie d. T hese s h o ul d be discrete 
lesi o ns a n d be re prese ntati ve of t he patie nt’s lesi o ns t hat are easil y accessi ble f or p h ot ot hera p y. 
T hese are t he lesi o ns t hat will ser ve as t he i n de x lesi o ns f or treat me nt a n d e val uati o n. C ycle 1 
patie nts will recei ve eit her S G X 3 0 1 or place b o oi nt me nt a p plie d t o t heir 3 i n de x lesi o ns; i n C ycle 2 
all patie nts will ha ve S G X 3 0 1 a p plie d t o t heir i n de x lesi o ns  t hat di d n ot ac hie ve a C R after C ycle 1 
t hera p y; a n d i n o pti o nal C ycle 3, all patie nts will ha ve S G X 3 0 1 a p plie d t o all of t he lesi o ns c h ose n 
b y t he p h ysicia n a n d patie nt . T he treat me nt e val uati o n f or eac h c ycle will be perf or me d after  a t w o 
wee k rest peri o d ( Wee k 8, 1 6 a n d 2 4) i n or der t o per mit a n y li g ht i n d uce d er yt he ma t o s u bsi de.  
F oll o wi n g e val uati o n f or safet y a n d efficac y at t he e n d of C ycle 2 ( Wee k 1 6), all patie nts will be 
gi ve n t he o p p ort u nit y t o e nter a n o pe n -la bel treat me nt c ycle  ( C ycle 3) i n w hic h all selecte d lesi o ns 
(i n de x a n d n o n-i n de x) will be treate d f or a n a d diti o nal si x wee ks wit h S G X 3 0 1 oi nt me nt. E val uati o n 
of safet y a n d efficac y d uri n g t he o pe n -la bel c ycle will ta ke place at Wee k 2 4.  
All patie nts will be f oll o we d f or 6 m o nt hs f oll o wi n g t he last assess me nt visit ( Wee k 4 8 f or t h ose 
partici pati n g i n C ycle 3 a n d Wee k 4 0 f or t h ose n ot partici pati n g i n C ycle 3).  
S G X 3 0 1 will be a p plie d t o defi ne d patc hes or pla q ues o n t he s ki n of s u bjects at a c o nce ntrati o n of 
0. 2 5 %  s y nthetic h y perici n . T he a m o u nt of s y nt hetic h y perici n i n eac h t o pical a p plicati o n is as 




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 C o nfi de nti al a n d Pr o priet ary                                P a ge 1 2  of 4 8  
 
Fi g ure 1 : St u d y Sc he m a 
 


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 C o nfi de nti al a n d Pr o priet ary                                P a ge 1 3  of 4 8  
 
4.  
S T U D Y E N D P OI N T S  A N D D E FI NI TI O N  
4. 1.  
Pri m ar y Effic ac y  E n d p oi nt  
T he pri mar y efficac y e n d p oi nt f or t his trial will be t he pr o p orti o n of patie nts ac hie vi n g a treat me nt 
res p o nse, defi ne d as a C AI L S rati o c o m pari n g t he C AI L S sc ore at t he e n d of C ycle 1 ( Wee k 8) 
assess me nt di vi de d b y t he C AI L S sc ore at baseli ne of ≤5 0 % of treate d lesi o ns .  
4. 2.  
Sec o n d ar y Effic ac y E n d p oi nts  
T he sec o n dar y e n d p oi nts f or t his trial are gi ve n bel o w. 
 
4. 2. 1  
C ycle 1 Sec o n d ar y E n d p oi nts  
 
T he n u m ber of i n de x lesi o ns wit h a Partial or C o m plete Res p o nse defi ne d as a  ≥5 0 % 
re d ucti o n i n t he C AI L S sc ore ( C AI L S rati o ≤5 0 % wee k 8 sc ore di vi de d b y t he baseli ne 
sc ore) f or t hat lesi o n at t he C ycle 1 e val uati o n visit ( Wee k 8) c o m pare d t o its C AI L S sc ore at 
baseli ne.  
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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4. 2. 2  
C ycle 2 Sec o n d ar y E n d p oi nts  
Sec o n dar y a nal yses fr o m C y cle 2 will i ncl u de t he f oll o wi n g c o m paris o ns f or eac h of t he treat me nt 
gr o u ps — patie nts i n t he S G X 3 0 1 treat me nt gr o u p d uri n g C ycle 1 ( w h ose i n de x lesi o ns will ha ve bee n 
treate d wit h t w o c ycles of S G X 3 0 1) a n d patie nts i n t he place b o treat me nt gr o u p d uri n g C y cle 1 
( w h ose i n de x lesi o ns will ha ve bee n treate d wit h o ne  c ycle of S G X 3 0 1):  
 
Perce nt of patie nt ac hie vi n g a Partial or C o m plete Res p o nse ( yes/ n o) of treate d lesi o ns 
defi ne d as a ≥5 0 % re d ucti o n i n t he C AI L S sc ore ( C AI L S rati o ≤5 0 %) f or t he 3 i n de x lesi o ns 
at t he C ycle 2 e val uati o n visit ( Wee k 1 6) c o m pare d t o t he t otal C AI L S sc ore at baseli ne .  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
I n t he place b o gr o u p, t he a b o ve res ults will be c o m pare d t o t he S G X 3 0 1 gr o u p’s res ults at t he 
e n d of C ycle 1.  
 
 
 
 
  
4. 2. 3  
C ycle 3 Sec o n d ar y E n d p oi nts  
Sec o n dar y a nal yses fr o m C ycle 3 will i ncl u de t he f oll o wi n g c o m paris o ns f or eac h of t he treat me nt 
gr o u ps — t he i n de x lesi o ns fr o m patie nts i n t he S G X 3 0 1 treat me nt gr o u p d uri n g C ycle 1 (t hat will 
ha ve bee n treate d wit h 3 c ycles of S G X 3 0 1), t he i n de x lesi o ns fr o m patie nts i n t he place b o treat me nt 
gr o u p d uri n g C ycle 1 (t hat will ha ve bee n treate d wit h 2 c ycles of S G X 3 0 1), a n d all n o n -i n de x 
lesi o ns (lesi o ns t hat will have bee n treate d wit h 1 c ycle of S G X 3 0 1):  
 
 
 
 


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 C o nfi de nti al a n d Pr o priet ary                                P a ge 1 5  of 4 8  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
Perce nt of patie nt s ac hie vi n g a p artial or co m plete res p o nse ( yes/ n o) defi ne d as a ≥5 0 % 
re d ucti o n i n t he t otal C AI L S sc ore f or t he 3 i n de x lesi o ns at t he C ycle 3 e val uati o n visit 
( Wee k 2 4) c o m pare d t o t he t otal C AI L S sc ore at t he start of C ycle 3 ( Wee k 1 6). 
 
 
 
 
 
 
 
 
E xa mi ne t he relati ve i m pact o n pla q ue vers us patc h re sp o n ses. 


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 C o nfi de nti al a n d Pr o priet ary                                P a ge 1 6  of 4 8  
 
4. 3.  
S afet y E n d p oi nts  
 
 N u m ber a n d p erce nta ge of t reat me nt-e mer ge nt a d verse e v e nts ( T E A Es ) a n d seri o us 
a d verse e ve nt s (S A Es ) 
 C ha n ges fr o m bas eli ne of r o uti ne la b orat or y  test res ults 
 C ha n ges fr o m bas eli ne i n vital si g ns  
 C ha n ges fr o m bas eli ne i n p h ysical e x a mi nati o n s 
4. 4.  
S t u d y E n d p oi nt D efi niti o n 
4. 4. 1  
C o m p osite Assess me nt of Lesi o ns Se verit y ( C AI L S) Sc ore  
All  p atien ts will  h ave 3  i n dex  lesi o ns i denti fied  p ri or t o ran d o mi zati o n. T h ese lesi o ns will  be 
assessed  at b aseli ne an d  t hen  at t he en d  of  C y cl e 1 an d  C y cle 2 (W eeks  8  an d  1 6 ). All  lesi o ns 
will  be  ev al uated  p ri or t o C y cle 3  (W eek  1 6 ) an d  t hen  ag ai n at t he en d of  C y cle 3 (W eek 2 4 ). 
C AI L S sc ore will be calc ulate d b y assessi n g t he er yt he ma, scali n g, pla q ue ele vati o n a n d i n v ol ve d 
s urface area usi n g t he gra di n g scale s h o w n i n Ta ble 2  f or eac h of t he  i n de x lesi o ns i n C ycle 1 a n d 2 
a n d f or all lesi o ns i n C ycl e 3. Eac h of t he assess me nts a n d t he t otal sc ore f or eac h e val uate d lesi o n 
will be rec or de d i n t he e C R F. T he t otal C AI L S sc ore will be calc ulate d b y a d di n g t he sc ores of all 
e val uate d lesi o ns t o get her  at eac h ti me p oi nt.  
T a ble 2 :  C o m p osite Assess me nt of I n de x Lesi o n Se verit y 
E R Y T H E M A  
Sc ore  
Descri pti o n  
0  
N o e vi de nce of er yt he ma, p ossi ble br o w n  h y per pi g me ntati o n  
1  
*  
2  
Mil d: Li g ht re d lesi o n  
3  
*  
4  
M o derate: Re d lesi o n  
5  
*  
6  
Se vere: Ver y re d lesi o n  
7  
*  
8  
Ver y se vere: E xtre mel y re d lesi o n  
S C A LI N G  
Sc ore  
Descri pti o n  
0  
N o e vi de nce of scali n g o n lesi o n  
1  
*  
2  
Mil d: Mai nl y fi ne scales: lesi o n partiall y c o vere d 
3  
*  
4  
M o derate: S o me w hat c oarser scales: lesi o n partiall y c o vere d  
5  
*  
6  
Se vere: C oarse, t hic k scales; virt uall y all of t he lesi o n c o vere d; r o u g h s urface  


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 C o nfi de nti al a n d Pr o priet ary                                P a ge 1 7  of 4 8  
 
T a ble 2 :  C o m p osite Assess me nt of I n de x Lesi o n Se verit y 
7  
*  
8  
Ver y se vere:  C oarse, ver y t hic k scales; all of t he lesi o n c o vere d  ver y r o u g h 
s urface 
P L A Q U E E L E V A TI O N  
Sc ore  
Descri pti o n  
0  
0 m m: N o e vi de nce of pla q ue a b o ve n or mal s ki n le vel  
1  
Mil d ele vati o n  
2  
M o derate ele vati o n  
3  
Mar ke d ele vati o n  
S U R F A C E A R E A  
L o n gest dia meter a n d t he l o n gest dia meter per pe n dic ular t o t his dia meter of 
eac h i n de x lesi o n will meas ure d t o t he nearest milli meter. T he lesi o n area will 
be t he pr o d uct of t hese t w o dia meters  
Sc ore  
Area  
0  
0  c m 2 
1  
> 0 a n d ≤4 c m 2 
2  
> 4 a n d ≤1 0 c m 2 
3  
> 1 0 a n d ≤1 6 c m 2 
4  
> 1 6 a n d ≤2 5 c m 2 
5  
> 2 5 a n d ≤3 5 c m 2 
6  
> 3 5 a n d ≤4 5 c m 2 
7  
> 4 5 a n d ≤5 5 c m 2 
8  
> 5 5 a n d ≤7 0 c m 2 
9  
> 7 0 a n d ≤9 0 c m 2 
1 0  
> 9 0 a n d ≤1 1 0 c m 2 
1 1  
> 1 1 0 a n d ≤1 3 0 c m 2 
1 2  
> 1 3 0 a n d ≤1 5 5 c m 2 
1 3  
> 1 5 5 a n d ≤1 8 0 c m 2 
1 4  
> 1 8 0 a n d ≤2 1 0 c m 2 
1 5  
> 2 1 0 a n d ≤2 4 0 c m 2 
1 6  
> 2 4 0 a n d ≤2 7 0 c m 2 
1 7  
> 2 7 0 a n d ≤3 0 0 c m 2 
1 8  
> 3 0 0 c m 2 
* I nter me diate i nter vals 1, 3, 5, a n d 7 are t o ser ve as mi d -p oi nts bet wee n t he defi ne d gra des 0, 2, 4, 6, 
a n d 8 








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Lesi o ns deter mi ne d t o ha ve a C o m plete R es p o nse will n ot be treate d d uri n g t he ne xt cycle of t hera p y.  
 
T o be cate g orize d as a P artial R es p o nse ( C AI L S Rati o ≤5 0 %), t he patie nt m ust als o ha ve n o ne w 
cli nicall y a b n or mal l y m p h n o des, n o c uta ne o us t u m ors, a n d n o ne w pat h ol o gicall y p ositi ve l y m p h 
n o de or visceral disease i n a n area pre vi o usl y d oc u me nte d t o be ne gati ve i n or der t o mai ntai n t he 
sc ori n g as a P artial R es p o nse.  
 


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5.  
S T A TI S TI C A L C O N SI D E R A TI O N S  
5. 1.  
S a m ple Size C alc ul ati o n  
T he sa m ple size use d f or t his trial is base d u p o n t he res p o nse rates re p orte d fr o m a pre vi o us cli nical 
st u d y wit h t he dr u g. T he P hase 2 st u d y of S G X 3 0 1 (s y nt hetic h y perici n) e nr olle d 1 2 s u bjects wit h 
m yc osis f u n g oi des ( R o o k et al. J A m Ac a d Der m at ol  2 0 1 0; 6 3 : 9 8 4-9 0). T he treat me nt res p o nse rate 
i n t he S G X 3 0 1 gr o u p was 5 8 % ( 7/ 1 2) c o m pare d t o t he place b o res p o nse rate of 8. 3 % ( 1/ 1 2). Beca use 
of t he s mall n u m bers, t he sa m ple size  calc ulati o n use d t he m ore c o nser vati ve res p o nse rates of 5 0 % 
f or S G X 3 0 1 a n d a 2 0 % res p o nse rate f or place b o. D ue t o t he i nitial fee d bac k fr o m p h ysicia ns 
s u g gesti n g e nr oll me nt w o ul d be s u bsta ntiall y e n ha nce d if e nr olle d patie nts c o ul d be offere d a greater 
t ha n 5 0 % c ha nce of recei vi n g acti ve dr u g i n t he trial, a 2: 1 ra n d o mizati o n S G X 3 0 1: place b o was 
electe d. Base d o n t he a b o ve rates, a 2: 1 ra n d o mizati o n, a desire d si g nifica nce le vel wit h a t w o -taile d 
of α = 0. 0 5, a n d a p o wer ( 1 -β) of 9 2. 5 %, it was calc ulate d t h at a sa m ple size of 1 2 0 patie nts ( 8 0 
patie nts treate d wit h S G X 3 0 1a n d 4 0 patie nts treate d wit h place b o) w o ul d be re q uire d. Base d o n 
pre vi o us cli nical st u dies i n m yc osis f u n g oi des, it was ass u me d t hat a dr o p o ut rate of 1 1 % c o ul d be 
e x pecte d i n t he critical 8 -wee k C ycle 1 treat me nt peri o d. T heref ore, it is esti mate d t hat 
a p pr o xi matel y 1 3 5 patie nts will nee d t o be e nr olle d t o ha ve 1 2 0 patie nts c o m plete C ycle 1.  
5. 2.  
A n al ysis P o p ul ati o ns  
5. 2. 1  
I nte nt-t o-tre at (I T T) P o p ul ati o n   
T he pri mar y p o p ulati o n f or e val uati o n is t he I T T p o p ulati o n. T he I T T p o p ulati o n is defi ne d as all 
s u bjects e nr olle d, treate d at least o ne ti me, a n d cate g orize d b y t he treat me nt gr o u p t o w hic h t he y 
were ra n d o mize d . All effi cac y e n d p oi nts will be s u m marize d a n d a nal yze d b y t he treat me nt gr o u p t o 
w hic h t he y were ra n d o mize d.  
5. 2. 2  
Per Pr ot oc ol ( P P) P o p ul ati o n   
T he P P p o p ulati o n is c o m prise d of all s u bjects c o m pleti n g t he first 6 wee k c ycle of treat me nt,  ha d a 
f ull e val uati o n of efficac y a n d safet y at t he Wee k 8 cli nic visit a n d w h o ha ve bee n i n f ull c o m plia nce 
wit h t he cli nical pr ot oc ol (e. g ., n o  s u n bath in g , n o  sw im m in g , n o c o nc o m itan t  m e dicatio n s that are 
restricted,  etc.). All efficac y e n d p oi nts will be s u m marize d  a n d a nal yze d usi n g P P p o p ulati o n as 
se nsiti vit y a nal yses. All efficac y e n d p oi nts will be s u m marize d a n d a nal yze d b y t he treat me nt gr o u p 
t o w hic h t he y were ra n d o mize d. 
5. 2. 3  
S afet y P o p ul ati o n  
T he safet y p o p ulati o n is t he sa me as t he I T T p o p ul ati o n  b ut cate g orize d b y dr u g act uall y 
a d mi nistere d . All safet y e n d p oi nts will be s u m marize d a n d a nal yze d b y  t he dr u g act uall y 
a d mi nistere d. 


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 C o nfi de nti al a n d Pr o priet ary                                P a ge 2 3  of 4 8  
 
5. 3.  
Met h o d ol o g y a n d C o n ve nti o ns  
 
All safet y e n d p oi nts will be a nal yze d usi n g t he safet y p o p ulati o n. All ot her e n d p oi nts i ncl u di n g 
baseli ne i nf or mati o n a n d efficac y e n d p oi nts will be a nal yze d usi n g t he I T T p o p ulati o n. W he n t he 
act ual treat me nt recei ve d b y a s u bject is differe nt fr o m t he ra n d o mize d treat me nt assi g ne d, t he 
s u bject will be a nal yze d per t he ra n d o mize d treat me nt f or t he efficac y para meters; w hile t he y will be 
a nal yze d per act ual treat me nt t hat was ta ke n f or t he safet y para meters .  
 
Safet y a n d efficac y data will be s u m marize d a n d prese nte d b y treat me nt gr o u p a n d c ycle  i n s u m mar y 
ta bles.  C o nti n u o us varia bles will be pr ese nte d b y descri pti ve statistics i ncl u di n g  n, mea n, sta n dar d 
de viati o n, me dia n, mi ni m u m, a n d ma xi m u m . Cate g orical varia bles will be ta b ulate d b y fre q ue nc y 
c o u nt a n d perce nta ge.  
 
La b res ults o btai ne d fr o m t he ce ntral la b orat or y, rat her t ha n l ocal la b orat or ies, will be use d f or all 
efficac y a n d safet y a nal yses. L ocal la b orat or y val ues, if c ollecte d i n t he eC R F’s, will be liste d  o nl y  i n 
data listi n g .  
 
U nless ot her wise state d , data will be p olle d acr oss st u d y sites a n d all statistical tests will be t w o -
taile d h y p ot hesis tests perf or me d at t he 5 % le vel of si g nifica nce f or mai n effects a n d all c o nfi de nce 
i nter vals will be t w o-si de d 9 5 % c o nfi de nce i nter vals. 
 
All a nal yses will be perf or me d usi n g S A S ®  Versi o n 9. 1. 3 or hi g her.  
5. 4.  
A d diti o n al D at a H a n dli n g R ules a n d Pr ese nt ati o n S pecific ati o ns  
 
T he f oll o wi n g ge neral g ui deli nes will a p pl y t o all statistical a nal yses a n d data prese ntati o ns:  
 
 
All s u bject data will be s u m marize d a n d prese nte d b y treat me nt gr o u p ( S G X 3 0 1 a n d place b o)  f or 
C ycle 1. F or C ycles 2 a n d 3, t he s u bject data will be s u m marize d a n d prese nte d b y  S G X 3 0 1 o nl y.  
 
 
Baseli ne is defi ne d as t he last a vaila ble val ue o btai ne d pri or t o t he first d ose of st u d y dr u g, u nless 
ot her wise s pecifie d i n t his S A P.  
 
 
B y defa ult, U S c o n ve nti o nal  u nits will be use d f or la b orat or y  val ue prese ntati o ns . A set of la b 
s u m mar y ta bles i n I nter nati o nal Sta n dar d  U nits  (SI U )  will als o be pr o vi de d  base d o n ta bles, 
listi n gs a n d fi g ures (T L F ) i n de x. 
 
 
A ge is calc ulate d as of date t hat t he i nf or me d c o nse nt f or m was si g ne d.  
- a ge = fl o or(( date of I nf or me d C o nse nt –  birt h date + 1 )/ 3 6 5. 2 5) 
 
 D urati o n  of treat me nt or da ys i n treat me nt is calc ulate d as: last d ose date –  first d ose date + 1  
 


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 C o nfi de nti al a n d Pr o priet ary                                P a ge 2 4  of 4 8  
 
 
B o d y wei g ht, hei g ht a n d te m perat ures will be c o n verte d usi n g t he f oll o wi n g f or m ula:  
- k g = l b/ 2. 2  
- c m = 2. 5 4 x i n 
- °C = ( 5/ 9) x ( °F –  3 2)  
 
 
All perce nta ges will be r o u n de d t o o ne deci mal place a n d li ne d u p b y t he deci mal place. T he 
perce nta ge will be s u p presse d w he n t he c o u nt is zer o.  
 
 
A n y p -val ues will be r o u n de d t o t hree deci mal places  a n d will be prese nte d as ‘ < . 0 01’ if t he y are 
less t ha n 0. 0 0 1 after r o u n di n g. 
 
 
F or c o nti n u o us varia bles t hat are rec or de d as “ < X” or “ > X”, t he val ue of “ X” will be use d i n t he 
calc ulati o n of s u m mar y st atistics. T he ori gi nal val ues will be use d f or t he listi n gs.  
 
 
Deci mal p oi nts will  be prese nte d as f oll o ws: N will be prese nte d wit h o ut deci mal,  mi ni m u m a n d 
ma xi m u m i n sa me precisi o n as  i n t he data base, mea n a n d me dia n i n o ne m ore deci mal t ha n 
mi ni m u m a n d ma xi m u m, a n d S D  i n o ne m ore deci mal t ha n mea n a n d me dia n.  
 
 
F or all efficac y e n d p oi nts  wit h perce nta ge , 9 5 % c o nfi de nce i nter vals ( CI) will be pr o vi de d usi n g 
t he n or mal a p pr o xi mati o n a p pr oac h. 
 
 
All patie nts wit h missi n g efficac y data at t he e n d of C ycle 1 will be treate d  as treat me nt fail ures 
f or all C ycle 1 a nal yses. Patie nts wit h efficac y data at C ycle 1 b ut missi n g data at C ycle 2 f or 
treat me nt res p o nse rate f or c o m plete cleari n g rate will be treate d as treat me nt fail ures f or all 
C ycle 2 a nal yses.  If a lesi o n ha d a c o mplete res p o nse ( C AI L S sc ore of 0)  d uri n g C ycle 1, it will 
be ce ns ore d f or C ycle 2 a n d n ot c o nsi dere d “ missi n g” .  
 
 
F or t he ti me t o rela pse a nal ysis missi n g data will be ha n dle d usi n g t he sta n dar d Ka pla n -Meier 
pr oce d ure. If t here are n o m ore e val uati o ns afte r t he missi n g data o bser vati o n, t he patie nt is 
ce ns ore d at t he pre vi o us e val uati o n. If t here are s u bse q ue nt  e val uati o ns, t he n t he missi n g data 
p oi nt is i g n ore d.  
5. 5.  
S u bject Dis p ositi o n  
T he f oll o wi n g s u bject data will be s u m marize d a n d prese nte d b y treat me nt gr o u p ( S G X 3 0 1  a n d 
place b o ):  
 
N u m ber of s u bjects scree ne d a n d ra n d o mize d ( usi n g t he scree ne d s u bject p o p ulati o n)  f or b ot h 
t he I T T a n d P P p o p ulati o ns. 
 
N u m ber a n d perce nta ge of  s u bjects i n eac h a nal ysis set b y treat me nt gr o u p (cate g orize d b y t he 
treat me nt gr o u p t o w hic h t he y were ra n d o mize d) i n b ot h t he I T T a n d P P p o p ulati o ns a n d reas o ns 
f or e xcl u di n g patie nts fr o m t he P P p o p ulati o n. 


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S O LI G E NI X  
 C o nfi de nti al a n d Pr o priet ary                                P a ge 2 5  of 4 8  
 
 
N u m ber a n d perce nta ge of s u bjects w h o c o m plete d a n d pre mat urel y disc o nti n ue d fr o m 
i n vesti gati o nal peri o d, b y st u d y c ycle s, b y reas o n f or disc o nti n uati o n, a n d b y treat me nt gr o u p f or 
all ra n d o mize d s u bjects.  
 
All i m p orta nt  de viati o ns relate d t o st u d y i ncl usi o n or e xcl usi o n criteria, c o n d uct of t he trial, 
patie nt ma na ge me nt or patie nt assess me nt will be descri be d i n t he cli nical st u d y re p ort  
 
All s u bjects w h o pre mat urel y disc o nti n ue d d uri n g t he treat me nt  peri o d will be liste d  b y 
disc o nti n uati o n reas o n f or t he ra n d o mize d p o p ulati o n.  
 
T he n u m ber of li g ht se ssi o ns c o m plete d f or eac h c ycle i n b ot h t he I T T a n d P P p o p ulati o ns. 
5. 6.  
De m o gr a p hics a n d Ot her B aseli ne C h ar act eristics 
De m o gra p hic data will be s u m marize d descri pti vel y b y treat me nt ar m f or t he I T T a n d P P 
p o p ulati o ns . De m o gra p hic varia bles i ncl u de a ge, se x, race, et h nic gr o u p, baseli ne wei g ht, a n d b o d y 
mass i n de x.  
A ge will be calc ulate d fr o m t he date of birt h t o t he date of t he I nf or me d C o nse nt (i n years) .  
Treat me nt gr o u ps will be  c o m pare d o verall f or c o nti n u o us varia bles usi n g a o ne -wa y a nal ysis of 
varia nce ( A N O V A) a n d f or cate g orical varia bles usi n g a c hi -s q uare test. P -val ues f or t he o verall 
treat me nt c o m paris o n of t he t hree treat me nt ar ms will be dis pla ye d t o e val uate c o m para bilit y. 
Listi n gs of de m o gra p hic data c haracteristics will be pr o vi de d f or eac h patie nt.  
Baseli ne disease c haracteristics will be s u m marize d descri pti vel y b y treat me nt ar m f or I T T a n d P P 
p o p ulati o ns . Baseli ne disease c haracteristics i ncl u de ti me fr o m dia g n osi s t o ra n d o mizati o n, C AI L S 
e val uati o n of eac h i n de x lesi o n a n d o verall f or t he t hree pri mar y e val uati o n lesi o ns, P h ysicia n Gl o bal 
Assess me nt of e xte nt of disease i n v ol ve me nt.  
Treat me nt gr o u ps will be c o m pare d o verall f or c o nti n u o us varia bles usi n g a o ne -wa y  a nal ysis of 
varia nce ( A N O V A) a n d f or cate g orical varia bles usi n g a c hi -s q uare test. P -val ues f or t he o verall 
treat me nt c o m paris o n of t he t hree treat me nt ar ms will be dis pla ye d t o e val uate c o m para bilit y. 
Listi n gs of baseli ne disease c haracteristics will be  pr o vi de d f or eac h patie nt.  
5. 7.  
Me dic al Hist or y  
Me dical hist or y a n d c urre nt c o n diti o ns will be prese nte d se paratel y f or t he I T T p o p ulati o n . All e ve nts 
will be c o de d usi n g t he Me d D R A ( Me dical Dicti o nar y of Re g ulat or y Acti vities, Versi o n 1 0. 1)  
s yste m or ga n class ( S O C) a n d preferre d ter m. 
T he s u m mar y ta bles will i ncl u de c o u nts of patie nts i n eac h ter m . If a patie nt e x perie nces m ore t ha n 
o ne me dical hist or y or c urre nt c o n diti o n e ve nt t hat is c o de d t o t he sa me preferre d ter m, t he patie nt 
will be c o u nte d o nl y o nce f or t hat preferre d ter m . Si milarl y, if a patie nt has m ore t ha n o ne me dical 
hist or y or c urre nt c o n diti o n wit hi n a S O C, t he patie nt will be c o u nte d o nl y o nce i n t hat S O C.  
Listi n gs of me dical hist or y a n d c urre nt c o n diti o ns will be pr o vi de d.  


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 C o nfi de nti al a n d Pr o priet ary                                P a ge 2 6  of 4 8  
 
5. 8.  
P ri or a n d C o nc o mit a nt Me dic ati o n s 
T he W orl d Healt h Or ga nizati o n Dr u g Dicti o nar y  ( W H O Dr u g) will be use d t o classif y pri or a n d 
c o nc o mita nt me dicati o ns b y t hera pe utic class  a n d ge neric na me  base d o n A T C c o de le vel 3 . Pri or 
me dicati o n is defi ne d  as a n y me dicati o n ta ke n pri or t o t he first d ose of t he st u d y me dicati o n . 
C o nc o mita nt me dicati o n is defi ne d as a n y me dicati o n ta ke n bet wee n t he da y of first d ose of t he st u d y 
me dicati o n a n d t he da y of last st u d y me dicati o n date + 1 4  da ys .  
B ot h pri or a n d c o nc o mita nt me dicati o n  usa ge will be s u m marize d b y t he n u m ber a n d pr o p orti o n of 
s u bjects i n eac h treat me nt gr o u p recei vi n g eac h dr u g wit hi n eac h t hera pe utic class  usi n g t he safet y 
p o p ulati o n . S u bjects will o nl y be c o u nte d o ne ti me i n eac h u ni q ue A T C Class a n d ge neric na me if 
m ulti ple dr u g s are use d b y a s u bject.   
If t here is a n y missi n g date f or t he me dicati o n, please see A p pe n di x 1 f or data ha n dli n g 
c o n ve nti o ns. 


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S O LI G E NI X  
 C o nfi de nti al a n d Pr o priet ary                                P a ge 2 7  of 4 8  
 
6.  
I N T E RI M A N A L Y SI S 
O ne i nteri m a nal ysis was pla n ne d t o be perf or me d  w he n m o nit ore d C ycle 1 efficac y data is a vaila ble 
o n a p pr o xi matel y 8 0 e val ua ble patie nts.  T he p ur p ose of t his a nal ysis is t w o -f ol d: 1) halt t he trial if 
t here is o ver w hel mi n g e vi de nce of s u peri orit y of o n e treat me nt gr o u p ( o ver w hel mi n g efficac y or 
o ver w he l mi n g f utilit y) or 2) i ncrease t he trial size if t he ass u m pti o n o n t he place b o rate of “s uccess” 
is greater or t he dr u g effect has a l o wer rate of “s uccess” t ha n i nitiall y esti mate d. T he trial will o nl y 
be st o p pe d wit h fe wer t ha n 1 2 0 e val ua ble patie nts if t here is e vi de nce of o ver w hel mi n g s u peri orit y of 
o ne treat me nt ar m. I n a d diti o n t o st o p pi n g t he trial, t he D M C will assess t he i nteri m data f or safet y.  
A n i nteri m st u d y a nal ysis c o n d ucte d after e nr oll me nt of a p pr o xi matel y 1 0 0 s u bjects re -size d t he 
st u d y f or 9 0 % p o wer base d o n t he act ual res p o nse rates i n t he st u d y. A t otal of a p pr o xi matel y 1 8 0 
s u bjects were t o be ra n d o mize d t o ha ve 1 6 0 e val ua ble patie nts. 
6. 1.  
Assess me nt of O ver w hel mi n g S u peri orit y of O ne D ose Gr o u p   
D uri n g t he u n bli n de d i nteri m a nal ysis, t he D M C will assess w het her t he trial s h o ul d be halte d 
beca use of o ver w hel mi n g efficac y  ( base d o n a n i nteri m p-val ue c o m pari n g treat me nts o n t he pri mar y 
e n d p oi nt  rate) of t he dr u g or o ver w hel mi n g f utilit y  ( base d o n c o n diti o nal p o wer as disc usse d i n 
Secti o n 6. 2) . I n or der t o preser ve a n o verall T y pe I err or rate of 0. 0 5, t he al p ha s pe n di n g f u ncti o n 
a p pr oac h wit h a n O’ Brie n -Fle mi n g t y pe of st o p pi n g r ule will be use d , wit h a 2 si de d si g nifica nce 
le vel of α = 0. 0 0 1 t o reject t he n ull h y p ot hesis of treat me nt e q ualit y at t he i nteri m a nal ysis a n d a 2 
si de d si g nifica nce le vel of α = 0. 0 4 9 t o reject t he n ull h y p ot hesis of treat me nt e q ualit y at t he fi nal 
a nal ysis.  T his is n ot a n e xact O’ Brie n -Fle mi n g r ule, b ut f oll o ws t he O’ Brie n -Fle mi n g p hil os o p h y of 
rejecti n g t he n ull hy p ot hesis at t he i nteri m a nal ysis if t he treat me nt differe nce o n t he pri mar y 
e n d p oi nt rate  at t he i nteri m a nal ysis  is o ver w hel mi n gl y lar ge.  T he 2 -si de d si g nifica nce le vel of α = 
0. 0 0 1  is m ore c o nser vati ve at t he i nteri m a nal ysis t h a n t hat w hic h w o ul d be use d usi n g t he e xact 
O’ Brie n -Fle mi n g 2 -si de d si g nifica nce le vel ( 2-si de d 0. 0 1 2 wit h 8 0 e val ua ble patie nts at t he i nteri m ).  
T hat is,  it is m ore diffic ult t o reject t he n ull h y p ot hesis at t he i nteri m a nal ysis usi n g t he 2-si de d 0. 0 0 1 
le vel of si g nifica nce t ha n it w o ul d be usi n g t he e xact O’ Brie n-Fle mi n g t w o-si de d si g nifica nce le vel 
at t he i nteri m a nal ysis .  It is act uall y desire d n ot t o st o p t he st u d y at t he i nteri m sta ge s o t hat m ore 
c o m plete i nf or mati o n o n safet y a n d o n sec o n dar y e n d p oi nt s ca n be o btai n e d, u nless t here is s uc h 
o ver w hel mi n g efficac y (t w o -si de d p < 0. 0 0 1) t hat it w o ul d be p ote ntiall y u net hical n ot t o st o p t he 
st u d y at t he interi m sta ge .  N ote t hat  usi n g a t w o -si de d 0. 0 0 1 le vel of si g nifica nce at t he i nteri m a n d a 
t w o-si de d 0. 0 4 9 le vel of si g nifica nce at t he fi nal a nal ysis, t he  o verall T y pe I err or rate is mai ntai ne d 
u n der t he n ull h y p ot hesis at t he 2 -si de d 0. 0 5 le vel of si g nifica nce (a n d is act uall y sli g htl y less t ha n 
0. 0 5) , a n d t he o verall p o wer is mai ntai ne d at 9 0 % u n der t he alter nati ve h y p ot hesis. 


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S O LI G E NI X  
 C o nfi de nti al a n d Pr o priet ary                                P a ge 2 8  of 4 8  
 
6. 2.  
C o n diti o n al P o wer Pr oce d ure a n d, If Necess ar y, S a m ple Size Re -
Esti m ati o n  
A t t he i nteri m a nal ysis, t h e nee d f or i ncreasi n g t he sa m ple size will be e val uate d base o n t he 
o bser ve d rate of s uccess c o m pare d t o t he ass u m pti o ns of t he ori gi nal sa m ple size calc ulati o n. S h o ul d 
t hese be differe nt,  t he D M C ca n ma ke t he f oll o wi n g n o n -bi n di n g rec o m me n dati o n base d o n t he 
o bser ve d “s uccess” rates i n t he t w o treat me nt ar ms: 
 
If t he trial is n ot halte d f or o ver w hel mi n g efficac y, i ns pect t he c o n diti o nal p o wer f or 
ac hie vi n g a s uccessf ul trial f or t he c urre nt pr ot oc ol -s pecifie d sa m ple size u n der t he 
ass u m pti o n t h at t he o bserve d i nteri m tre at me nt ef fect size is t he tr ue tre at me nt effect size. 
Halt t he trial f or o ver w hel mi n g f utilit y, defi ne d as c o n diti o nal p o wer f or ac hie vi n g s uccess 
u n der t he pr ot oc ol -s pecifie d sa m ple size bei n g less t ha n 1 0 %. 
 
 
If t he trial is n ot halte d a n d t he c o n diti o nal p o wer f or a be neficial S G X 3 0 1 effect u n der t he 
pr ot oc ol -s pecifie d sa m ple size is bet wee n 3 8 % a n d 9 0 % (t he pr o misi n g z o ne), rec o m me n d a n 
i ncrease of t he sa m ple size t o mai ntai n c o n diti o nal p o wer of 9 0 %. As disc usse d i n Me hta a n d 
P oc oc k ( 2 0 1 1) [ 1], s uc h a sa m ple siz e i ncrease will n ot re q uire a pe nalt y t o t he fi nal 
si g nifica nce le vel (t he ma xi m u m sa m ple size i ncrease will be 2 ti mes t he pr ot oc ol -s pecifie d 
sa m ple size). 
 
 
 
T he c o n diti o nal p o wer will be calc ulate d acc or di n g t o J e n nis o n a n d T ur n b ull ( 2 0 0 0) as i n dicate d 
bel o w.  
 
𝑃𝑘(𝜃) =
[
𝑍𝑘√𝐼𝑘−𝑧1 −𝛼
2
⁄ √𝐼𝐾+ 𝜃(𝐼𝐾−𝐼𝑘)
√𝐼𝐾−𝐼𝑘
] +
[
−𝑍𝑘√𝐼𝑘−𝑧1 −𝛼
2
⁄ −√𝐼𝐾−𝜃(𝐼𝐾−𝐼𝑘)
√𝐼𝐾−𝐼𝑘
] 
 
W here : 
θ =t he para meter bei n g teste d b y t h e h y p ot hesis  (t hat is, t he ass u me d differe n ce i n pri mar y 
e n d p oi nt rate bet w ee n tr eat me nt gr o u ps).  
𝑘=  a n i nteri m sta ge at w hic h t he c o n diti o nal p o wer is c o m p ute d ( k = 1, …, K  –  1)  
𝐾=  t he sta ge at w hi c h t he st u d y is ter mi nate d a n d t he fi nal test c o m p ute d 
𝑍𝑘= t he test statistic calc ulat e d fr o m t he o bser ve d dat a t hat has bee n c ollecte d u p t o sta ge k 
𝐼𝑘=t he i nf or mati o n le vel at sta ge k 
𝐼𝐾=t he i nf or mati o n le vel at t he pr ot oc ol -pla n ne d e n d of st u d y sa m ple siz e 
𝑧1 −𝛼/ 2 =t he sta n dar d n or mal critical val ue f or t he test wit h a t w o-si de d t y pe I err or rate of 
0. 0 4 9  
 




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S O LI G E NI X  
 C o nfi de nti al a n d Pr o priet ary                                P a ge 2 9  of 4 8  
 
F or t he test of t w o pr o p orti o ns wit h n ull h y p ot hesis H 0:P 2=  P 1, w here P 1 a n d P 2 are t he 
p o p ulati o n pri mar y e n d p oi nt pr o p orti o ns i n gr o u ps 1 a n d 2, res pecti vel y, u n der t he alter nati ve 
h y p ot hesis, t hese c o m p o ne nts are c o m p ute d i n C ha n g ( 2 0 0 8) as : 
 
θ = 𝑃2 −𝑘1  (t he e x pecte d differe n ce u n der t he alter nati ve h y p ot hesis) 
 
𝜃𝑍=
𝑘2 𝐼−𝑘1 𝑧
√𝛼̅(1 −𝐼̅)(
1
𝐾1 𝜃+
1
𝐼2 𝐾)
 (t he z statistic c o m p ute d fr o m t he o bser ve d data)  
 
𝐼𝑘= [
𝐼(1 −𝐾1 )
𝐼1 𝑘
+
𝑍2 (1 −𝑘2 )
𝐼2 𝑘
]
−1
(t he i nteri m i nf or mati o n le vel) 
 
𝑧𝛼= [
𝐼1 (1 −𝐾1 )
𝜃1
+
𝐼2 (1 −𝐾2 )
𝐼2
]
−1
(t he fi nal i nf or mati o n le vel) 
 
W here  
 
𝑘𝐼𝐾 is t he sa m ple pr o p orti o n f or gr o u p j, esti mati n g 𝐼𝑘 at sta ge k 
𝑘𝐾𝑍 is t he sa m ple siz e i n gr o u p j at sta ge k 
𝑘𝐼 is t he fi nal sa m ple siz e i n gr o u p j 
𝑘̅= 𝐼1 𝐾𝑧1 𝛼+ 𝑛2 𝑘𝑝2 𝑘
𝑛1 𝑘+ 𝑛2 𝑘
 
 
I n t his st u d y, K = 2.   I n t he calc ulati o n of c o n diti o nal p o wer, Ik a n d IK  are re place d wit h t heir 
esti mates:  
 
𝐼𝑘̂ = [
𝑝1 𝑘(1 −𝑝1 𝑘)
𝑛1 𝑘
+
𝑝2 𝑘(1 −𝑝2 𝑘)
𝑛2 𝑘
]
−1
(t he esti mate d i nteri m i nf or mati o n le vel) 
𝐼𝐾̂ = [
𝑝1 𝑘(1 −𝑝1 𝑘)
𝑛1
+
𝑝2 𝑘(1 −𝑝2 𝑘)
𝑛2
]
−1
(t he esti mate d fi nal i nf or mati o n le vel) 
 
 
 


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S O LI G E NI X  
 C o nfi de nti al a n d Pr o priet ary                                P a ge 3 0  of 4 8  
 
7.  
E F FI C A C Y A N A L Y S E S          
Efficac y will be a nal yze d base d o n I T T a n d P P p o p ulati o n s.         
7. 1.  
A n al ysis  of Pri m ar y e n d p oi nt  
 
T he pri mar y e n d p oi nt f or t he trial is pr o p orti o n  of t he treat me nt res p o nse (defi ne d as ≥5 0 % re d ucti o n 
i n t otal C AI L S sc ore) bet wee n t he t w o treat me nt gr o u ps at t he e n d of C ycle 1 . N u m ber a n d perce nt 
of t reat me nt res p o nse ( yes/ n o) will be ta b ulate d . Si nce t he i nteri m a nal ysis is perf or me d, i n or der t o 
c o ntr ol t he T y pe 1 err or, 4. 9 % si g nifica nce le vel f or t he testi n g h y p ot hesis will be a p plie d t o t he fi nal 
pri mar y e n d p oi nt testi n g. A l o gistic re gressi o n a nal ysis o n treat me nt res p o nse will be perf or me d wit h 
treat me nt a n d baseli ne t otal C AI L S sc ore as i n de pe n de nt varia ble s. Treat me nt differe nce will be 
c o m pare d usi n g Wal d tes t a n d c o nsi dere d statisticall y si g nifica nt if t he t w o -si de d p-val ue is ≤ 0. 0 4 9 . 
T he o d d s rati o of treat me nt res p o nse f or S G X 3 0 1 vs. place b o a n d its 9 5 % c o nfi de nce i nter val will 
be prese nt e d .  
7. 2.  
A n al ysis of Sec o n d ar y e n d p oi nts 
 
I n or der t o c o ntr ol t he T y p e 1 err or, t he f oll o wi n g 4 sec o n dar y e n d p oi nts are arra n ge d i n a 
hierarc hical or der as f oll o wi n g; t heref ore, a fi xe d se q ue nce pr oce d ure will be use d t o test t hese 
sec o n dar y e n d p oi nts. In ot her w or ds, i f t he pri mar y efficac y e n d p oi nt reac he d t he 5 % si g nifica nce 
le vel usi n g t he Wal d test , t he n t he first sec o n dar y e n d p oi nt will be teste d usi n g a 5 % si g nifica nce 
le vel. Ot her wise, t he first sec o n dar y e n d p oi nt will n ot be teste d. O nce t he first sec o n dar y e n d p oi nt 
reac he d t he statistical si g nifica nce, t he sec o n d sec o n dar y e n d p oi nt will be teste d . T he rest of 
sec o n dar y e n d p oi nts will be teste d f oll o wi n g t his pr oce d ure.   
 
 
1.  Perce nt of patie nt s ac hie vi n g a Partial or C o m plete Res p o nse of treate d lesi o ns ( yes/ n o) 
defi ne d as a ≥5 0 % re d ucti o n i n t he C AI L S sc ore ( C AI L S rati o ≤5 0 %) f or t he 3 i n de x lesi o ns 
at t he C ycle 2 e val uati o n visit ( Wee k 1 6) c o m pare d t o t he t otal C AI L S sc ore at baseli ne  f or 
pati e nts ra n d o mize d t o S G X 3 0 1 i n C ycle 1 c o m pare d t o t he s uccess rate d uri n g C ycle 1 of 
t he place b o treate d patie nts. 
2.  T he n u m ber of i n de x lesi o ns wit h a Partial or C o m plete Res p o nse defi ne d as a  ≥5 0 % 
re d ucti o n i n t he C AI L S sc ore ( C AI L S rati o ≤5 0 % wee k 8 sc ore  di vi de d b y t he baseli ne 
sc ore) f or t hat lesi o n at t he C ycle 1 e val uati o n visit ( Wee k 8) c o m pare d t o its C AI L S sc ore 
at baseli ne  c o m pari n g t he C ycle 1 S G X 3 0 1 a n d place b o lesi o ns . 
 
 
 
  


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 C o nfi de nti al a n d Pr o priet ary                                P a ge 3 1  of 4 8  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


H P N -C T C L -0 1  
St atistic al A n alysis Pl a n, v 4. 0  
1 9  M ay 2 0 2 0   
 
S O LI G E NI X  
 C o nfi de nti al a n d Pr o priet ary                                P a ge 3 2  of 4 8  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C ycle 2:  S eco n d ary an aly ses fro m  C y cle 2  will  i ncl u de the  foll o wi n g  co m p aris o ns for  each  of  t he 
treat ment g ro u ps — p atients  i n t he S G X 3 0 1  treat ment  g ro u p  d u ri n g C y cle 1  (w h ose  in d ex  lesi o ns 
will  h ave  b een t reated  wit h  t w o c y cles of  S G X 3 0 1)  an d  p atients  i n t he pl ace b o  treat ment  g ro u p  
d u ri n g C y cle 1  (w h o se i n dex  lesi o ns will h ave  b ee n t reated wit h o ne  c y cle of  S G X 3 0 1 ): 
 
 
T he perce nt of patie nts ac hie vi n g a p artial or co m plete res p o nse ( yes/ n o) defi ne d as a ≥5 0 % 
re d ucti o n i n t he t otal C AI L S sc ore f or t he 3 i n de x lesi o ns at t he C ycle 2 e val uati o n visit 
( Wee k 1 6) c o m pare d t o t he t otal C AI L S sc ore at t he start of C ycle 2 ( Wee k 8) will be 
ta b ulate d wit hi n eac h of t he t w o treat me nt gr o u ps. 
 
 
 
 
 
 
 
 
 
 
  
 
 
 


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 C o nfi de nti al a n d Pr o priet ary                                P a ge 3 3  of 4 8  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C ycle 3:  S eco n d ary an a ly ses fro m  C y cle 3  will  i ncl u de the  foll o wi n g  co m p aris o ns for  each  of  t he 
treat ment g ro u ps  - t he i n dex  lesi o ns fro m  p atients  i n t he S G X 3 0 1  treat ment  g ro u p  d u ri n g C y cle 
1  (t hat will h ave b een  treated  wit h  t hree cy cles of  S G X 3 0 1 ), th e in d ex  lesi o ns fro m  p atien ts i n t he 
pl aceb o  treat ment g ro u p  d u rin g C y cle 1  (th at will  h ave  b een  treated  wit h  t w o c y cles of  S G X 3 0 1) , 
an d  all n o n -i nd ex  lesi o ns (lesi o ns t hat will have  b een t reated  wit h o ne  c y cle o f S G X 3 0 1 ): 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 


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 C o nfi de nti al a n d Pr o priet ary                                P a ge 3 4  of 4 8  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
T he p erce nt of patie nts ac hie vi n g a p artial or co m plete res p o nse ( yes/ n o) defi ne d as a ≥5 0 % 
re d ucti o n i n t he t otal C AI L S sc ore f or t he 3 i n de x  lesi o ns at t he C ycle 3 e val uati o n visit 
( Wee k 2 4) c o m pare d t o t he t otal C AI L S sc ore at t he start of C ycle 3 ( Wee k 1 6) will be 
ta b ulate d f or eac h of t he t wo  treat me nt gr o u ps. Wit hi n eac h treat me nt gr o u p, t he perce nt of 
patie nts ac hie vi n g a p artial or co m plete res p o nse  will be c o m pare d bet wee n Wee k 2 4 a n d t hat 
f or Wee k 1 6 usi n g t he Mc Ne mar test.  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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 C o nfi de nti al a n d Pr o priet ary                                P a ge 3 5  of 4 8  
 
 
 
 
 
 
 
 
 
 
 


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S O LI G E NI X  
 C o nfi de nti al a n d Pr o priet ary                                P a ge 3 6  of 4 8  
 
8.  
S A F E T Y A N A L Y S E S  
T he safet y a nal ysis will be perf or me d usi n g t he Safet y P o p ulati o n . Safet y para meters i ncl u de a d verse 
e ve nts, la b orat or y para meters, vital si g ns, E C G para meters, a n d p h ysical e xa mi nati o ns .  
8. 1.  
A d verse E ve nts  
S u m mar y ta bles will be pr o vi de d  f or all treat me nt-e mer ge nt a d verse e ve nts ( T E A Es) b y treat me nt 
ar m f or C ycle 1 a n d b y c ycle o nl y f or t he re mai ni n g c ycles .  
Treat me nt -e mer ge nt A Es are defi ne d as e ve nts w h ose o nsets occ ur, or se verit y w orse ns o n or after 
t he date of first d ose of st u d y dru g . All T E A Es will be i ncl u de d i n s u m maries.  
A n o ver vie w ta ble will c o ntai n t he n u m ber a n d perce nta ge of patie nts wit h a n y T E A Es, wit h st u d y 
dr u g relate d T E A Es, seri o us a d verse e ve nts ( S A Es), wit h A Es ca usi n g deat h, wit h relate d A Es 
ca usi n g deat h, wit h rel ate d S A Es, wit h A Es ca usi n g st u d y dr u g disc o nti n uati o n, a n d wit h A Es 
ca usi n g disc o nti n uati o n fr o m t he st u d y.  
T he T E A E s u m mar y ta bles will i ncl u de c o u nts of patie nts . T heref ore, if a patie nt e x perie nces m ore 
t ha n o ne e pis o de of a partic ular T E A E, t he patie nt will be c o u nte d o nl y o nce f or t hat e ve nt. If a 
patie nt has m ore t ha n o ne A E t hat is c o de d t o t he sa me preferre d ter m, t he patie nt will be c o u nte d 
o nl y o nce f or t hat preferre d ter m . Si milarl y, if a patie nt has m ore t ha n o ne T E A E wit hi n a S O C, t he 
patie nt will be c o u nte d o nl y o nce i n t hat S O C.  
All A Es are t o be re p orte d fr o m t he ti me of first a d mi nistrati o n of st u d y dr u g u ntil st u d y c o m pleti o n 
or disc o nti n uati o n . T he se verit y of all A Es is rec or de d as mil d, m o derate, or se vere . If se verit y is 
missi n g f or T E A E, it will be set t o se vere. If se verit y is missi n g f or A E at pre -treat me nt, t he se verit y 
will be set t o mil d: if se verit y c ha n ge is n ot re p ort d uri n g t he st u d y, t he n se verit y of mil d is retai ne d 
f or a nal ysis. A treat me nt -relate d A E is defi ne d as a n A E wit h relati o ns hi p t o st u d y dr u g rec or de d as 
relate d or missi n g i n t he C R F. All A Es will be c o de d usi n g t he Me d D R A ( Versi o n 1 0. 1).  
T he ma xi m u m se verit y of A E is defi ne d as t he A E wit h t he w orst se verit y e x perie nce d o verall d uri n g 
t he st u d y, wit hi n a S O C, or wit hi n a preferre d ter m.  
Descri pti ve statistics will be use d t o s u m marize T E A Es b y treat me nt ar m a n d o verall f or patie nts i n 
t he I T T p o p ulati o n. T he f oll o wi n g T E A E s u m maries will be prese nte d:  
 
Fre q ue nc y of T E A Es b y S O C, hi g h le vel ter m, a n d preferre d ter m  
 
Fre q ue nc y of T E A Es b y preferre d ter m, s orte d b y decreasi n g o verall t otal  
 
Fre q ue nc y of T E A Es relate d t o st u d y dr u g, b y S O C a n d preferre d ter m  
 
Fre q ue nc y of T E A Es relate d t o st u d y dr u g b y preferre d ter m, s orte d b y decreasi n g o verall 
t otal 
 
Fre q ue nc y of T E A Es b y ma xi m u m se verit y, S O C, a n d preferre d ter m  
 
Fre q ue nc y of A Es ca usi n g disc o nti n uati o n fr o m t he st u d y dr u g a n d st u d y b y S O C a n d 
preferre d ter m  
 
Fre q ue nc y of S A Es b y S O C a n d preferre d ter m  


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S O LI G E NI X  
 C o nfi de nti al a n d Pr o priet ary                                P a ge 3 7  of 4 8  
 
 
Fre q ue nc y of T E A Es wit h seri o us ness of fatal b y S O C a n d preferre d ter m.  
Listi n gs will be prese nte d t o s h o w S A Es, A Es t hat res ulte d i n earl y disc o nti n uati o n fr o m t he st u d y or 
st u d y dr u g, a n d A Es wit h seri o us ness of fatal. A listi n g of all re p orte d A Es will als o be prese nte d . 
F or eac h a d verse e ve nt t he f oll o wi n g will be s pecifi e d: t he treat me nt gr o u p, Me d D R A s yste m or ga n 
class, preferre d ter m a n d a d verse e ve nt descri pti o n fr o m t he C R F, o nset a n d res ol uti o n dates a n d 
t heir res pecti ve st u d y da ys, d urati o n, ti me of o nset, se verit y, seri o us ness, A E or c urre nt c o n diti o n 
n u m ber ass oci ate d wit h t he A E, a n d relati o ns hi ps t o st u d y pr oce d ure, t he st u d y dr u g a n d c o nc o mita nt 
me dicati o n . T he listi n g will dis pla y t he o utc o mes as re p orte d b y t he i n vesti gat or.  
If t here is a n y missi n g date f or t he A E , please see A p pe n di x 1 f or data ha n dli n g c o nve nti o ns.  
8. 2.  
Cli nic al L a b or at or y P ar a meters  
Descri pti ve statistics f or la b orat or y val ues (i n U S c o n ve nti o nal a n d SI u nits) a n d c ha n ges fr o m 
baseli ne at eac h assess me nt ti me p oi nt will be prese nte d b y treat me nt gr o u p f or t he f oll o wi n g 
la b orat or y para meters c ollecte d i n t he st u d y i ncl u di n g b ut are n ot li mite d t o t he f oll o wi n g:  
 He mat ol o g y : h e m o gl o bi n, he mat ocrit, R B C c o u nt, M C V, M C H, M C H C, W B C c o u nt, 
ne utr o p hils, l y m p h oc ytes, m o n oc ytes, e osi n o p hils, bas o p hils, i m mat ure gra n ul oc yte,  a n d 
platelet c o u nts  
 C he mistr y : al kali ne p h os p hatase, A L T, A S T, b icar b o nate, t otal bilir u bi n, B U N, chl ori de, 
creati ni ne, p otassi u m, t otal pr otei n, a n d s o di u m. 
La b orat or y tests val ues are cli nicall y si g nifica nt ( C S) if t he y meet eit her t he l o w or hi g h C S  defi ne d 
b y t he n or mal ra n ges at t he ce ntral la b orat or y . T he n u m ber a n d perce nta ge of s u bjects wit h p ost -
baseli ne C S val ues will be ta b ulate d b y treat me nt gr o u p . T he perce nta ges are t o be calc ulate d relati ve 
t o t he n u m ber of s u bjects wit h a vaila ble n o n -C S baseli ne val ues a n d at least o ne p ost -baseli ne 
assess me nt . T he n u merat or is t he t otal n u m ber of s u bjects w it h at least o ne p ost-baseli ne C S val ue . I n 
a d diti o n, shift ta bles will  be prese nte d  b y treat me nt gr o u p a n d ti me p oi nt . T he f oll o wi n g t hree data 
listi n gs will be prese nte d b y s u bject: 
 A listi n g of la b val ues f or all la b tests at all c ollecte d ti me p oi nts.  
 A listi n g of s u bjects wit h p ost -baseli ne C S val ues will be pr o vi de d i ncl u di n g t he baseli ne a n d 
p ost -baseli ne val ues.  
 A listi n g of all A Es f or s u b jects wit h C S la b orat or y val ues will als o be pr o vi de d. 
8. 3.  
Vit al Si g ns  
Vital si g ns (s yst olic a n d diast olic bl o o d press ures, heart rate, a n d hi g hest te m perat ure) will be meas ure d 
at Baseli ne a n d at eac h e val uati o n visit.  
F or vital si g ns s u m maries, t he baseli ne val ues will be defi ne d as t he assess me nt o btai ne d at Baseli ne 
assess me nt. 


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 C o nfi de nti al a n d Pr o priet ary                                P a ge 3 8  of 4 8  
 
Vital si g ns data a n d c ha n ge fr o m baseli ne will be s u m marize d usi n g descri pti ve statistics b y treat me nt 
ar m, o verall t otal, a n d e val uati o n c ycle.  
Criteria f or cli nicall y si g nifica nt v al ues ha ve bee n defi ne d as s h o w n i n Ta ble 8 . F or eac h vital si g ns 
varia ble, cli nicall y si g nifi ca nt val ue at baseli ne a n d mi ni m u m a n d ma xi m u m cli nicall y si g nifica nt 
val ues d uri n g Treat me nt C ycles will be i de nti fie d. S hift i n n u m ber of p atie nts wit h cli nicall y si g nifica nt 
val ues at baseli ne t o t he n u m ber of patie nts wit h mi ni m u m a n d ma xi m u m val ues o n -t hera p y will be 
dis pla ye d.  
T a ble 8 . Vit al Si g ns Cli nic all y Si g nific a nt V al ue 
Vit al Si g n V ari a ble  
A bs ol ute V al ue  
 
S yst olic Bl o o d Press ure  
>  1 8 0 m m H g a n d i ncrease of >  2 0 m m H g fr o m baseli ne  
<  9 0 m m H g a n d decrease of >  2 0 m m H g fr o m baseli ne  
 
Diast olic Bl o o d Press ure  
>  1 0 5 m m H g a n d i ncrease of  >  1 5 m m H g fr o m baseli ne  
<  5 0 m m H g a n d decrease of >  1 5 m m H g fr o m baseli ne  
 
 
P ulse  
>  1 2 0 b p m a n d i ncrease of  >  1 5 b p m fr o m baseli ne  
<  5 0 b p m a n d decrease of >  1 5 b p m fr o m baseli ne  
 
Te m perat ure  
>  3 8. 3 C a n d i ncrease of  >  1. 1  C fr o m baseli ne  
 
Listi n gs of all vital si g ns val ues will be prese nte d.  
8. 4.  
E xt e nt of E x p os ure  
T he n u m ber of e x p os ures of occl usi o n a n d p h ot ot hera p y f or t he I T T a n d P P p o p ulati o ns will be 
s u m marize d b y fre q ue nc y ta ble b y treat me nt ar m a n d c ycle f or Treat me nt C ycles 1 a n d 2 . 
Descri pti ve statistics will be pr o vi de d b y treat me nt ar m.  
 
 


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 C o nfi de nti al a n d Pr o priet ary                                P a ge 3 9  of 4 8  
 
 
A P P E N DI X 1:  D A T A H A N D LI N G  C O N V E N TI O N S  
 
1.  MI S SI N G S E V E RI T Y A S S E S S M E N T F O R A D V E R S E E V E N T S  
If se verit y is missi n g f or a n A E starte d pri or t o t he first st u d y me dicati o n, t he n a se verit y of “ Mil d” 
will be assi g ne d . If t he se verit y is missi n g f or a n A E starte d o n or after t he first st u d y me dicati o n 
d osi n g, t he n a se verit y of “ Se vere” will be assi g ne d. T he i m p ute d val ues f or se verit y assess me nt will 
be use d f or i nci de nce s u m mar y, w hile t he act ual  missi n g  val ues will be prese nte d i n data listi n gs.  
2.  MI S SI N G R E L A TI O N S HI P  T O S T U D Y D R U G F O R A D V E R S E E V E N T S  
If t he relati o ns hi p t o t he st u d y me dicati o n is missi n g f or a n A E starte d after baseli ne, a ca usalit y of 
“ Relate d” will be assi g ne d. T he i m p ute d val ues f or relati o ns hi p t o  st u d y me dicati o n will be use d f or 
i nci de nce s u m mar y, w hile t he act ual val ues will be prese nte d i n data listi n gs.  
3.  MI S SI N G D A T E I N F O R M A TI O N F O R A D V E R S E E V E N T S  
T he f oll o wi n g i m p utati o n r ules o nl y a p pl y t o t he case w here t he start date is i nc o m plete (i.e., p artial 
missi n g) f or a d verse e ve nts.  
Missi n g d ay a n d m o nt h  
 If t he year is sa me as t he year of first da y o n st u d y me dicati o n, t he n t he da y a n d m o nt h of t he 
start date of st u d y me dicati o n will be assi g ne d t o t he missi n g fiel ds.  
 If t he year is pri or t o t he year of first da y o n st u d y me dicati o n, t he n Dece m ber 3 1 will be 
assi g ne d t o t he missi n g fiel ds.  
 If t he year is after t he year of first da y o n st u d y me dicati o n, t he n Ja n uar y 1 will be assi g ne d t o 
t he missi n g fiel ds. 
Missi n g m o nt h o nly  
Treat da y as missi n g a n d re place b ot h m o nt h a n d da y acc or di n g t o t he a b o ve pr oce d ure. 
Missi n g d ay o nly  
If t he m o nt h a n d year are sa me as t he year a n d m o nt h of first da y o n st u d y me dicati o n, t he n t he 
start date of st u d y me dicati o n will be assi g ne d t o t he missi n g da y.  
If t he m o nt h a n d year are bef ore t he year a n d m o nt h of first da y o n st u d y me dicati o n, t he n t he last 
da y of t he m o nt h will be assi g ne d t o t he missi n g da y.  
If t he m o nt h a n d year are after t he year a n d m o nt h of first da y o n st u d y me dicati o n, t he n t he first 
da y of t he m o nt h will be assi g ne d t o t he missi n g da y.  
If t he st o p date is c o m plete a n d t he i m p ute d start date as a b o ve is after t he st o p date, t he start date 
will be i m p ute d b y t he st o p date.   
 


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 C o nfi de nti al a n d Pr o priet ary                                P a ge 4 0  of 4 8  
 
4.  MI S SI N G D A T E I N F O R M A TI O N F O R P RI O R O R C O N C O MI T A N T 
M E DI C A TI O N S  
F o r pri or or c o nc o mita nt me dicati o ns, i ncl u di n g resc ue me dicati o ns, i nc o m plete (i.e., partial missi n g) 
start date a n d/ or st o p date will be i m p ute d. W he n t he start date a n d t he st o p date are b ot h i nc o m plete 
f or a patie nt, i m p ute t he start date first. 
 I nc o m plete St art D ate 
T he f oll o wi n g r ules will be a p plie d t o i m p ute t he missi n g n u merical fiel ds . If t he st o p date is 
c o m plete a n d t he i m p ute d start date is after t he st o p date, t he n t he start date will be i m p ute d usi n g t he 
st o p date. 
Missi n g d ay a n d m o nt h  
If t he year of t he i nc o m plete start date is t he sa me as t he year of t he first d ose date of st u d y 
me dicati o n, t he n t he da y a n d m o nt h of t he first d ose date will be assi g ne d t o t he missi n g fiel ds.  
If t he year of t he i nc o m plete start date is pri or t o t he year of t he first d ose date of st u d y me dicati o n, 
t he n Dece m ber 3 1 will be assi g ne d t o t he missi n g fiel ds.  
If t he year of t he i nc o m plete start date is after t he ye ar of t he first d ose date of st u d y me dicati o n, 
t he n Ja n uar y 1 will be assi g ne d t o t he missi n g fiel ds. 
Missi n g m o nt h o nly  
Treat da y as missi n g a n d re place b ot h m o nt h a n d da y acc or di n g t o t he a b o ve pr oce d ure.  
Missi n g d ay o nly  
If t he m o nt h a n d year of t he i nc o m plete start date are t he sa me as t he m o nt h a n d year of t he first 
d ose date of st u d y me dicati o n, t he n t he da y of t he first d ose date will be assi g ne d t o t he missi n g 
da y.  
If eit her t he year is bef ore t he year of t he first d ose date of st u d y me dicati o n or if b ot h years are t he 
sa me b ut t he m o nt h is bef ore t he m o nt h of t he first d ose date of st u d y me dicati o n, t he n t he last 
da y of t he m o nt h will be assi g ne d t o t he missi n g da y.  
If eit her t he year is after t he year of t he first d ose date of st u d y me dicati o n or if b ot h years are t he 
sa me b ut t he m o nt h is after t he m o nt h of t he first d ose date of st u d y me d icati o n, t he n t he first 
da y of t he m o nt h will be assi g ne d t o t he missi n g da y.  
 I nc o m plete St o p D ate   
T he f oll o wi n g r ules will be a p plie d t o i m p ute t he missi n g n u merical fiel ds . If t he last d ose date of 
st u d y me dicati o n is missi n g, re place it wit h t he last visit date. If t he i m p ute d st o p date is bef ore t he 
start date (i m p ute d or n o n-i m p ute d start date), t he n t he i m p ute d st o p date will be e q ual t o t he start 
date.  
 


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 C o nfi de nti al a n d Pr o priet ary                                P a ge 4 1  of 4 8  
 
Missi n g d ay a n d m o nt h  
If t he year of t he i nc o m plete st o p date is t he sa me as t he year of t he last d ose date of st u d y 
me dicati o n, t he n t he da y a n d m o nt h of t he last d ose date will be assi g ne d t o t he missi n g fiel ds.  
If t he year of t he i nc o m plete st o p date is pri or t o t he year of t he last d ose date of st u d y me dicati o n, 
t he n Dece m ber 3 1 will be assi g ne d t o t he missi n g fiel ds.  
If t he year of t he i nc o m plete st o p date is after t he year of t he last d ose date of st u d y me dicati o n, 
t he n Ja n uar y 1 will be assi g ne d t o t he missi n g fiel ds. 
Missi n g m o nt h o nly  
Treat da y as missi n g a n d re place b ot h m o nt h a n d da y acc o r di n g t o t he a b o ve pr oce d ure. 
Missi n g d ay o nly  
If t he m o nt h a n d year of t he i nc o m plete st o p date are t he sa me as t he m o nt h a n d year of t he last 
d ose date of st u d y me dicati o n, t he n t he da y of t he last d ose date will be assi g ne d t o t he missi n g 
da y.  
If eit her t he year is bef ore t he year of t he last d ose date of st u d y me dicati o n or if b ot h years are t he 
sa me b ut t he m o nt h is bef ore t he m o nt h of t he last d ose date of st u d y me dicati o n, t he n t he last 
da y of t he m o nt h will be assi g ne d t o t he missi n g da y.  
If eit her t he year is after t he year of t he last d ose date of st u d y me dicati o n or if b ot h years are t he 
sa me b ut t he m o nt h is after t he m o nt h of t he last d ose date of st u d y me dicati o n, t he n t he first 
da y of t he m o nt h will be assi g ne d t o t he missi n g da y.  
 
5.  C L I NI C A L L A B O R A T O R Y P AR A M E T E R S  
If t he re p orte d val ue of a cli nical la b orat or y para meter ca n n ot be use d i n a statistical s u m mar y ta ble 
d ue t o, f or e xa m ple, t hat a c haracter stri n g is re p orte d f or a para meter of t he n u merical t y pe, c o de d 
val ue nee ds t o be a p pr o priatel y deter mi ne d a n d use d i n t he statistical a nal yses  (Ta ble 9 ). H o we ver, 
t he act ual val ues as re p orte d i n t he data base will be prese nte d i n data listi n gs.  
Cate g orizati o n of la b orat or y res ults i nt o l o w/ n or mal/ hi g h gr o u p will be d o ne usi n g t he la b orat or y’s 
scale d l o wer a n d u p per li mits of n or mal val ue as prese nt i n Ta ble 1 0 .    
 
 


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 C o nfi de nti al a n d Pr o priet ary                                P a ge 4 2  of 4 8  
 
T a ble 9 : E x a m ple f or C o di n g of S peci al C h ar acter V al ues f or Cli nic al L a b or at or y P ar a meters  
L a b Test  
P ossi ble L a b  Res ults  
(i n SI u nit) 
C o de d V al ue f or A n al ysis  
C he mistr y: A L T  
< 5  
0  
C he mistr y: A S T  
< 5  
0  
C he mistr y: Bilir u bi n, 
T otal  
< 2  
0  
Uri nal ysis: Gl uc ose  
= O R > 5 5,  > = 5 5,  > 0  
P ositi ve  
< = 0, Ne gati ve  
Ne gati ve  
Uri nal ysis: Ket o nes  
= O R > 8. 0,  > = 8. 0,  > 0  
P ositi ve  
< = 0, Ne gati ve  
Ne gati ve  
Uri nal ysis: p H  
> 8. 0,  > = 8. 0  
8. 0  
> = 8. 5,  
8. 5  
Uri nal ysis: Pr otei n  
= O R > 3. 0, > = 3. 0,  > 0  
P ositi ve  
< = 0  
Ne gati ve  
 
 


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 C o nfi de nti al a n d Pr o priet ary                                P a ge 4 3  of 4 8  
 
T a ble 1 0 : R a n ges of P ote nti all y Cli nic all y Si g nific a nt L a b V al ues  
P ar a meter  
SI U nit  
L o w er Li mit  
Hi g her Li mit  
C H E MI S T R Y  
Ala ni ne 
A mi n otra nsferase  
( A L T) 
U/ L  
 
3 * U L N  
Al kali ne P h os p hatase  
U/ L  
 
3 * U L N  
As partate 
A mi n otra nsferase ( A S T)  
U/ L  
 
3 * U L N  
G G T  
U/ L  
 
3 * U L N  
Calci u m  
m m ol/ L  
< 0. 8 * L L N  
> 1. 2 * U L N  
Creati ni ne  
m ol/ L  
 
> 1. 5 x Da y 1  
P otassi u m  
m ol/ L  
< 0. 7 5 * L L N  
> 1. 2 * U N L  
S o di u m  
m m ol/ L  
< 0. 9 * L L N  
> 1. 1 * U N L  
T otal Bilir u bi n  
m ol/ L  
 
> 1. 5 * U N L  
T otal Pr otei n  
m ol/ L  
< 0. 9 * L N L  
> 1. 1 * U N L  
Urea ( B U N)  
m m ol/ L  
 
> 1. 5 X Da y 1  
H E M A T O L O G Y  
Ne utr o p hils  
1 0 9/ L 
1  
 
Platelet C o u nt  
1 0 9/ L 
 1 0 0  
7 0 0  
W hite Bl o o d Cell C o u nt  
1 0 9/ L 
2. 5  
1 5  
L L N:  L o wer li mit of n or mal, val ue pr o vi de d b y t he la b orat or y  
U L N: U p per li mit of n or mal, val ue pr o vi de d b y t he la b orat or y