Clinical trial NCT04102007
Conditions: Plaque Psoriasis
Keywords: Plaque Psoriasis Risankizumab Secukinumab Ixekizumab Psoriasis Biologic
Sponsor: AbbVie
Start date: 2019-11-12; Completion date: 2022-11-07
Enrollment: 244 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study will evaluate whether adult participants with moderate to severe plaque psoriasis who have been treated with secukinumab or ixekizumab for at least 6 months and are experiencing a suboptimal response may benefit from switching to risankizumab with regard to skin symptoms, quality of life symptoms and psoriasis symptoms.

Study duration will last for up to 64 weeks with risankizumab given by subcutaneous injection at Week 0, Week 4, and then every 12 weeks for 52 Weeks (With the last dose being administered at Week 40). An additional visit will occur at Week 8 for a physical exam and questionnaire collection. A final follow-up phone call will occur at Week 60.

Detailed description:

Arms: arm 1: Participants receive Risankizumab following suboptimal response to secukinumab or ixekizumab
Interventions: intervention 1: Risankizumab
Intervention descriptions: intervention 1: Risankizumab is administered as a subcutaneous (SC) injection in pre-filled syringe (PFS).

Protocol documents:
SAP_002.pdf: 
 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
1  
 
 
St ati sti c al A n al y si s Pl a n f or St u d y M 1 9 -1 6 4  
 
A P h a s e 3 b, M ulti c e nt er, I nt er v e nti o n al, Op e n -L a b el 
S t u d y of A d ult S u bj e ct s  wit h M o d er at e t o S e v er e 
P l a q u e P s ori a si s W h o  H a v e a S u b o pti m al R e s p o n s e 
t o S e c u ki n u m a b  or I x e ki z u m a b  a n d A r e S wit c h e d t o 
R i s a n ki z u m a b 
 
D at e:  3 1  J ul y  2 0 2 3  
 
V er si o n 4 . 0 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
2  
T a bl e of C o nt e nt s  
1. 0  
I ntr o d ucti o n ............................................................................. 5  
2. 0  
St u d y Desi g n a n d O bjecti ves  .................................................. 5  
2. 1  
O bjecti ves, H y p ot heses a n d Esti ma n ds  ..................................................... 5  
2. 2  
St u d y Desi g n O ver vie w  ............................................................................. 6  
2. 3  
Treat me nt Assi g n me nt a n d Bli n di n g  ......................................................... 7  
2. 4  
Sa m ple Size Deter mi nati o n  ........................................................................ 7  
3. 0  
E n d p oi nts  .................................................................................. 8  
3. 1  
Pri mar y E n d p oi nt  ....................................................................................... 8  
3. 2  
Sec o n dar y E n d p oi nts  ................................................................................. 9  
3. 3  
Ot her Effi cac y E n d p oi nts  ........................................................................... 9  
3. 4  
Safet y E n d p oi nts  ...................................................................................... 1 0  
3. 5  
A d diti o nal E n d p oi nts  ............................................................................... 1 0  
4. 0  
A n al ysis P o p ul ati o ns  ............................................................. 1 0  
5. 0  
S u bject Dis p ositi o n  ................................................................ 1 1  
6. 0  
St u d y Dr u g D ur ati o n a n d C o m pli a nce  ................................ 1 1  
7. 0  
De m o gr a p hics, B aseli ne C h ar acteristics, Me dic al 
Hist or y, a n d Pri or/ C o nc o mit a nt Me dic ati o ns  .................... 1 2  
7. 1  
De m o gra p hics a n d Baseli ne C haract eristics  ............................................ 1 2  
7. 2  
Me dical Hist or y  ....................................................................................... 1 3  
7. 3  
Pri or a n d C o nc o mita nt Me dicati o ns  ........................................................ 1 4  
8. 0  
H a n dli n g of P ote nti al I nterc urre nt E ve nts f or t he 
Pri m ar y a n d Ke y Sec o n d ar y E n d p oi nts  .............................. 1 4  
9. 0  
Effic ac y A n al yses  ................................................................... 1 6  
9. 1  
Ge ner al C o nsi derati o ns  ............................................................................ 1 6  
9. 2  
Ha n dli n g of Missi n g Data  ........................................................................ 1 7  
9. 3  
Pri mar y Efficac y E n d p oi nt a n d A nal yses  ................................................ 1 8  
9. 3. 1  
Pri mar y Efficac y E n d p oi nt  ...................................................................... 1 8  
9. 3. 2  
Mai n A nal ysis of Pri mar y Efficac y E n d p oi nt  .......................................... 1 8  
9. 3. 3  
Se nsiti vit y a n d S u p ple me ntar y A nal yses of t h e Pri mar y Efficac y 
E n d p oi nt  ................................................................................................... 1 9  
9. 4  
Sec o n dar y Efficac y E n d p oi nts a n d A nal yses  .......................................... 1 9  


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
3  
9. 4. 1  
Sec o n dar y Efficac y E n d p oi nts  ................................................................. 1 9  
9. 4. 2  
Mai n A nal yses of Sec o n dar y Effi cac y E n d p oi nts .................................... 1 9  
9. 4. 3  
Se nsiti vit y a n d S u p ple me ntar y A nal yse s f or Sec o n dar y Effi cac y 
E n d p oi nts  ................................................................................................. 2 2  
9. 5  
A d diti o nal Efficac y A nal yses  .................................................................. 2 3  
9. 6  
Efficac y S u b gr o u p A nal yses  .................................................................... 2 3  
1 0. 0  
S afet y A n al yses  ...................................................................... 2 4  
1 0. 1  
Ge ner al C o nsi derati o ns  ............................................................................ 2 4  
1 0. 2  
A d verse E v e nts  ........................................................................................ 2 4  
1 0. 2. 1  
Treat me nt -E mer ge nt A d verse E ve nts  ...................................................... 2 4  
1 0. 2. 2  
A d verse E v e nt O ver vi e w  ......................................................................... 2 5  
1 0. 2. 3  
Treat me nt -E mer ge nt A d verse E ve nts b y S O C a n d/ or P T  ....................... 2 5  
1 0. 2. 4  
Treat me nt -E mer ge nt A d verse E ve nts p er Patie nt -Years of 
E x p os ure  .................................................................................................. 2 6  
1 0. 2. 5  
S A Es (I n cl u di n g Deat hs) a n d A d vers e E ve nts Lea di n g t o St u d y 
Dr u g Disc o nti n uati o n  ............................................................................... 2 6  
1 0. 2. 6  
Area of Safet y I nt erest  ............................................................................. 2 7  
1 0. 3  
A nal ysis of La b or at or y Data  .................................................................... 2 7  
1 0. 4  
A nal ysis of Vital Si g ns  ............................................................................ 2 8  
1 0. 5  
Safet y S u b gr o u p A nal yses  ....................................................................... 2 9  
1 0. 6  
Ot her Safet y A n al yses  .............................................................................. 2 9  
1 1. 0  
Ot her A n al yses  ....................................................................... 2 9  
1 2. 0  
I nteri m A n al yses .................................................................... 2 9  
1 2. 1  
Data M o nit ori n g C o m mittee  .................................................................... 3 0  
1 3. 0  
O ver all T y pe -I Err or C o ntr ol .............................................. 3 0  
1 4. 0  
Versi o n Hist or y  ...................................................................... 3 1  
1 5. 0  
Refere nces  ............................................................................... 3 2  
 
Li st of T a bl e s  
Ta ble  1.  
S u m mar y of t he Esti ma n d Attri b utes of t he Pri mar y Efficac y 
E n d p oi nt  ................................................................................................... 1 9  
Ta ble  2.  
S u m mar y of t he Esti ma n d Attri b utes of t he Sec o n dar y Effi cac y 
E n d p oi nts  ................................................................................................. 2 0  


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
4  
Ta ble  3.  
S A P Ve rsi o n Hist or y S u m mar y ............................................................... 3 1  
 
Li st of Fi g ur e s  
Fi g ure  1.  
St u d y Sc he matic  ......................................................................................... 7  
Fi g ure  2.  
Statistical Precisi o n as Meas ure d b y Half -Wi dt h of 9 5 % 
C o nfi de nce I nter val vers us Var yi n g Sa m ple Size  ..................................... 8  
 
Li st of A p p e n di c e s  
A p pe n di x  A.  
Pr ot oc ol De viati o ns  .................................................................................. 3 3  
A p pe n di x  B.  
Defi niti o n of Area of Safet y I nt erest ........................................................ 3 4  
A p pe n di x  C.  
P ote ntiall y Cli nicall y I m p orta nt Criteria f or Safet y E n d p oi nts  ............... 3 6  
 
 
 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
5  
1. 0  
I ntr o d u cti o n 
T his Statistical A nal ysis Pla n ( S A P) descri bes t he statistical a nal yses f or ris a n kiz u ma b 
St u d y M 1 9 -1 6 4.  
St u d y M 1 9 -1 6 4 e xa mi nes t he efficac y a n d s afet y of risa n kiz u ma b i n a d ult s u bjects wit h 
m o derate t o se v ere pla q u e ps oriasis w h o  ha ve a s u b o pti mal res p o nse  t o sec u ki n u ma b or 
i xe kiz u ma b a n d are s witc he d t o risa n kiz u ma b . 
T he S A P will n ot be u p date d i n case of a d mi nistrati ve c ha n ges or a me n d me nts t o t he 
pr ot oc ol u nless t he c ha n g es i m pact t he a nal ysis.  
U nless n ote d ot her wise, all a nal yses will be perf or me d usi n g S A S Versi o n 9. 4 ( S A S 
I nstit ute I nc., C ar y, N C  2 7 5 1 3) or later u n d er t he U NI X o perati n g s yste m. 
T his S A P i ncl u des c ha n ges t o a nal yses des cri be d i n t he pr ot oc ol.  Details are o utli ne d i n 
Secti o n  1 4. 0 . 
2. 0  
St u d y D e si g n a n d O bj e cti v e s  
2. 1  
O bj e cti v e s, H y p ot h e s e s a n d E sti m a n d s  
T he o bjecti ve of t his st u d y is t o e val uate t he efficac y a n d safet y of s witc hi n g t o 
risa n kiz u ma b i n s u bjects wit h m o derate t o severe pla q ue ps oriasis, w h o ha ve bee n treate d 
wit h la bele d d ose of sec u ki n u ma b or i xe kiz u ma b f or at least 6 m o nt hs a n d are 
e x perie n ci n g a s u b o pti mal res p o nse.  S u b o pti mal res p o nse is defi n e d as a  static 
P h ysicia n's Gl o bal Assess me nt  (s P G A) 2 or 3, a n d a B o d y S urface Area ( B S A) 3 % - 
<  1 0 % aft er at least 6 m o nt hs treat me nt wit h sec u ki n u ma b or i xe kiz u ma b.  
T he st u d y assesses w h et her Risa n kiz u ma b i m pr o v e s s ki n s y m pt o ms a n d q ualit y of life i n 
s u bjects wit h m o derate -t o-se ver e pla q ue ps oriasis w h o ha d a s u b o pti mal res p o nse t o 
sec u ki n u ma b or i xe kiz u ma b . 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
6  
T he esti ma n d f or t he pri mar y e n d p oi nt is ac hie v e me nt of s P G A 0/ 1 at Wee k 1 6.  T he 
esti ma n ds f or t he sec o n d ar y e n d p oi nts are ac hi e ve me nt of s P G A 0 at Wee k 1 6, 
ac hie ve m e nt of Der mat ol o g y Life Q ualit y I n de x ( D L QI) 0/ 1 at Wee k 1 6, ac hie ve me nt of 
Ps oriasis S y m pt o ms Scale ( P S S) 0 at Wee k 1 6, ac hie ve me nt of s P G A 0/ 1 at Wee k 5 2, 
ac hie ve m e nt of s P G A 0 at Wee k 5 2, ac hie ve me nt of D L QI 0/ 1 at Wee k 5 2, ac hie ve m e nt 
of P S S 0 at Wee k 5 2, ti me t o ac hie v e s P G A 0/ 1 a n d ti me t o ac hie ve s P G A 0.  Please refer 
t o Secti o n 9. 3. 2  a n d Secti o n  9. 4. 2  f or t he detaile d descri pti o n of esti ma n ds. 
2. 2  
St u d y D e si g n O v er vi e w  
T his is a P hase 3 b, gl o bal, i nter ve nti o nal, m ultice nter, o pe n -la b el, si n gle-ar m st u d y 
e xa mi ni n g t he eff ect of risa n kiz u ma b 1 5 0 m g a d mi nistere d at Wee k 0, Wee k 4, a n d t he n 
e ver y 1 2 w ee ks ( q 1 2 w) t hereafter f or 5 2 we e ks i n a d ult s u bjects wit h m o derate t o se vere 
pla q ue ps oriasis w h o ha v e bee n tr eate d wit h la b ele d d ose of sec u ki n u ma b or i xe kiz u ma b 
f or at least 6 m o nt hs a n d are e x p erie n ci n g a s u b o pti mal res p o nse.  T he pati e nt p o p ulati o n 
m ust be o n t he la bele d sec u ki n u ma b  or i xe kiz u ma b f or at least 6 m o nt hs a n d are s witc h e d 
t o risa n kiz u ma b at Baseli ne ( Wee k 0)  ( wit hi n ± 1 wee k of n e xt sc he d ule d d ose f or 
sec u ki n u ma b or i xe kiz u ma b).  S u b o pti mal res p o nse is defi ne d as a n  s P G A 2 or 3 a n d a 
B S A 3 % - <  1 0 % . 
T he st u d y is desi g ne d t o e nr oll 2 5 0 s u bjects.  
Eli gi ble s u bjects will recei ve 2 i njecti o ns of acti ve risa n kiz u ma b 7 5 m g ( 1 5 0 m g t otal 
d osa ge) s u bc ut a ne o usl y ( S C) at Wee ks 0 a n d 4, a n d t he n e ver y 1 2 wee ks ( q 1 2 w) u ntil t he 
last d ose at Wee k 4 0.  
T he st u d y d urati o n will be u p t o 6 4 wee ks.  T h e st u d y c o m prises a 3 0 -d a y Scree ni n g 
Peri o d, a 5 2 -wee k o pe n -la bel st u d y peri o d, a n d a 2 0-wee k f oll o w -u p peri o d after t he l ast 
d ose at Wee k 4 0.  T he 5 2 -wee k o p e n la bel peri o d c o nsists of a n i nitial p hase ( Wee ks 0 -
1 6) a n d a mai nte n a nce p ha se ( Wee ks 1 6-5 2).  T h e f oll o w -u p peri o d c o nsists of a f oll o w -
u p p h o ne call 2 0 wee ks after t he last i njecti o n of st u d y dr u g (at Wee k 4 0).  


 Risa n kiz u ma b  
M 1 9 -1 6 4 – Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
7 
T he sc he matic of t he st u d y is s h o w n i n Fi g ure 1 .  F urt her d etails re g ar di n g st u d y 
pr oce d ur es ar e i n t he O p erati o ns Ma n ual.  
Fi g ure  1. 
St u d y Sc he m atic  
 
 
2. 3  
Tr e at m e nt A s si g n m e nt a n d Bli n di n g  
N o ra n d o mizati o n.  All s u bjects will recei v e o pe n -la bel risa n kiz u ma b. 
2. 4  
S a m pl e Si z e D et er mi n ati o n  
T here is n o p u blis he d literat ure or cli nical trial dat a t o acc uratel y esti mate t he pri mar y 
e n d p oi nt s P G A 0/ 1 res p o nse rate at Wee k 1 6 f or t his st u d y p o p ulati o n – s u b o pti mal 
res p o nse of s u bjects treat e d wit h sec u ki n u ma b or i xe kiz u ma b.  T he ass u m pti o n f or 
risa n kiz u ma b s P G A 0/ 1 r es p o nse rate is e x pect e d t o be bet wee n  
 base d o n t he 
s u bjects w h o self-r ep orte d pri or I L- 1 7 fail ure fr o m P hase 3 trials U L TI M M A 1 & 2 a n d 
I M M h a nce. 
T he statistical precisi o n meas ure d b y h alf - wi dt h of 9 5 % c o nfi d e nce i nter v al ( CI) is t he 
mai n criteria f or sa m ple size deter mi nati o n.  B y e x a mi ni n g it o ver var yi n g sa m ple size, a 
c h oice of 2 5 0 s u bjects is ass ociate d wit h a h alf - wi dt h of n o m ore t ha n  
 w hic h 


 Risa n kiz u ma b  
M 1 9 -1 6 4 – Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
8 
c orres p o n ds t o a res p o ns e rate of 5 0 % w he n variati o n is t he greatest acr oss all p ossi ble 
res p o nse r ates (Fi g ure 2 ). 
 
 
Fr o m hist orical data of e nr oll me nt of t he ps oriasis st u dies c o n d ucte d b y A b b Vie, t he 
pr ojecte d scree n fail ure ( S F) rate is  
.  T h us,  
s u bjects will be nee de d t o be 
scree n e d t o e nr oll 2 5 0 s u bjects. 
3. 0  
E n d p oi nt s  
3. 1  
Pri m ar y E n d p oi nt  
T he pri mar y e n d p oi nt is t he pr o p orti o n of s u bjects ac hie vi n g s P G A 0/ 1 at W ee k 1 6. 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
9  
3. 2  
S e c o n d ar y E n d p oi nt s  
T he or der of t he sec o n dar y e n d p oi nts d oes n ot refl ect a ra n ki n g.  
T he f oll o wi n g sec o n dar y e n d p oi nts will be e val uate d:  
● T he pr o p orti o n of s u bjects ac hie vi n g a n  s P G A cl ear res p o nse (s P G A 0) at 
Wee k 1 6;  
● T he pr o p orti o n of s u bjects ac hie vi n g a D er mat ol o g y Life Q ualit y I n de x ( D L QI) 
0 or 1 at Wee k 1 6;  
● T he pr o p orti o n of s u bjects ac hie vi n g a Ps oriasis S y m pt o ms Scale ( P S S) 0 at 
Wee k 1 6;  
● T he pr o p orti o n of s u bjects ac hie vi n g a n  s P G A 0/ 1 at Wee k 5 2; 
● T he pr o p orti o n of s u bjects ac hie vi n g a n  s P G A 0 at Wee k 5 2; 
● T he pr o p ort i o n of s u bjects ac hie vi n g a D L QI 0/ 1 at Wee k 5 2;   
● T he pr o p orti o n of s u bjects ac hie vi n g a P S S 0 at Wee k 5 2;   
● Ti me t o ac hie ve s P G A 0/ 1;   
● Ti me t o ac hie ve s P G A 0 .  
 
3. 3  
Ot h er Effi c a c y E n d p oi nt s  
T he e x pl orat or y effi cac y e n d p oi nts are:  
● T he c ha n g e fr o m bas eli ne i n D L QI b y visit;  
● Treat me nt satisfacti o n as meas ure d b y t he Treat me nt Satisfacti o n Q uesti o n naire 
f or Me dicati o n V ersi o n 9  ( T S Q M-9 ) at Baseli ne ( Wee k 0) a n d at eac h visit;  
● T he pr o p orti o n of s u bjects ac hie vi n g abs ol ute Ps oriasis Area Se v erit y I n de x 
( P A SI) at t hres h ol ds (e. g., P A SI ≤1, ≤3)  b y visit;  
● T he c ha n g e fr o m bas eli ne i n P A SI b y visit; 
● T he pr o p orti o n of s u bjects ac hie vi n g B S A ≤1 %, ≤3 %, b y visit;  
● T he c ha n g e  fr o m bas eli ne i n B S A b y visit; 
● T he c ha n g e  fr o m bas eli ne i n B S A x s P G A b y visit; 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
1 0  
● T he p r o p orti o n of s u bjects ac hie vi n g s P G A 0/ 1 at Wee k 1 6 a n d mai ntai ne d 
s P G A 0/ 1 res p o nse at Wee k 5 2. 
 
3. 4  
S af et y E n d p oi nt s  
T he f oll o wi n g e n d p oi nts will be i ncl u de d i n t he safet y a nal yses:  
● Treat me nt e mer ge nt a d v erse e ve nts ( T E A Es);  
● Seri o us a d verse e ve nts ( S A Es);  
● Ar eas of saf et y i nterest ( A SI);  
● A d verse e ve nts ( A Es) lea di n g t o disc o nti n uati o n;  
● Vital si g n s a n d la b orat or y tests 
 
3. 5  
A d diti o n al E n d p oi nt s  
N ot a p plica ble.  
4. 0  
A n al y si s P o p ul ati o n s  
Si g nifica nt n o n -c o m plia nce was i de ntifi e d at a site. As a res ult of t his fi n di n g, s u b jects 
e nr olle d i n t his site will n ot be i ncl u de d i n a n y a n al ysis p o p ulati o n a n d data c ollecte d fr o m 
t his site will n ot be i ncl u de d i n a n y a nal ysis.  
T he f oll o wi n g p o p ulati o n sets will be use d f or t he a nal yses.  
T he i nte nt -t o-Treat (I T T) P o p ulati o n, w hic h is defi ne d as all s u bjects w h o ha ve at least 
o ne d ose of st u d y dr u g i n St u d y M 1 9 -1 6 4, will be use d f or t he efficac y a n al yses.  
T he Safet y A n al ysis set , w hic h is defi ne d as all s u bjects w h o recei ve d at least o ne dose of 
st u d y dr u g i n St u d y M 1 9-1 6 4, will be use d f or all safet y a n al yses.  I n t his st u d y, t he safet y 
A nal ysis Set  is t he sa me as t he I T T p o p ulati o n. 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
1 1  
5. 0  
S u bj e ct Di s p o siti o n  
T he t otal n u m ber of s u bj ects w h o were scree n e d, e nr olle d, treate d, c o m plet e d a n d 
disc o n ti n ue d will be s u m marize d.   
A s u m mar y of s u bject acc o u nta bilit y will be pr o vi de d w here t he n u m ber of s u bjects i n 
eac h of t h e f oll o wi n g cat e g ories will be s u m marize d:  
● S u bjects e nr olle d i n t he st u d y;  
● S u bjects w h o t o o k at least o ne d ose of st u d y dr u g;  
● S u bjec ts w h o c o m plete d pr ot oc ol-s pecifi e d treat m e nt; 
● S u bjects w h o pre mat urel y disc o nti n ue d st u d y dr u g (all reas o ns a n d pri mar y 
reas o n). 
 
F or e n d of st u d y partici p ati o n, t he n u m ber a n d perce nta g e of s u bjects w h o c o m plete d t he 
pr ot oc ol defi ne d f oll o w -u p peri o d ( or  di d n ot wit h ass ociate d reas o ns) will be 
s u m marize d. 
6. 0  
St u d y Dr u g D ur ati o n a n d C o m pli a n c e  
D urati o n of treat me nt is defi ne d f or eac h s u bject as last d ose date mi n us first d ose date + 
8 4 da ys.   D urati o n of tr eat me nt will be s u m marize d usi n g t he n u m ber of s u bj ects treate d, 
mea n, sta n dar d d e viati o n, me dia n, mi ni m u m a n d ma xi m u m.   
Treat me nt c o m plia nce will be s u m marize d f or t h e I T T p o p ul ati o n f or t he e ntire treat me nt 
peri o d.  Treat me nt c o m plia nce is defi n e d as t he n u m ber of i njecti o ns act u all y ta ke n 
di vi de d b y t h e n u m ber of i njecti o ns t hat s h o ul d ha ve bee n ta k e n.  Perce nt c o m plia nce will 
be s u m marize d.  
T here will be a s u m mar y of t he n u m ber of s u bjects recei vi n g st u d y dr u g a n d d ose at eac h 
st u d y dr u g a d mi nistrati o n visit.  T his will be re peate d o n t he c u m ulati ve n um ber of d oses.  


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
1 2  
W he n c o m p uti n g c o m plia nce at eac h st u d y dr u g a d mi nistrati o n visit, t he de n o mi nat or will 
i ncl u de all s u bjects i n eac h a nal ysis p o p ulati o n w h o ha ve n ot pre mat urel y disc o nti n ue d 
t he st u d y dr u g pri or t o t he sc he d ule d st u d y dr u g i njecti o n. 
7. 0  
D e m o gr a p hi c s, B a s eli n e C h ar a ct eri sti c s, M e di c al 
Hi st or y, a n d Pri or /C o n c o mit a nt M e di c ati o n s  
De m o gra p hics, b aseli ne or disease c h aracteristics, me dical hist or y, a n d pri or a n d 
c o nc o mita nt me dicati o ns will be s u m marize d f or t he I T T P o p ulati o n .  Cate g orical 
varia bles  will be s u m marize d wit h t he n u m ber a n d perce nt a ge of s u bjects ; perce nt a ges 
will be calc ulate d b ase d o n t he n u m ber of n o n -missi n g o bser vati o ns.   C o nti n u o us 
varia bles will be s u m marize d wit h descri pti ve statistics ( n u m ber of n o n -missi n g 
o bser vati o ns, mea n a n d sta n dar d de viati o n, me dia n, mi ni m u m a n d ma xi m u m).  
7. 1  
D e m o gr a p hi c s a n d B a s eli n e C h ar a ct eri sti c s  
C o nti n u o us de m o gra p hic varia bles i ncl u de : 
● A ge  ( years), d efi ne d as t he n u m ber of y ears fr o m date of birt h t o date of first 
dr u g  
● W ei g ht ( k g) 
● H ei g ht (c m) 
● B o d y mass i n de x ( B MI , k g/ m2). 
 
Cate g orical de m o gr a p hic varia bles i ncl u de : 
● S e x ( Male, Fe male) 
● E t h nicit y ( His pa nic or Lati n o, N ot His pa nic or Lati n o) 
● R ace ( W hite, Blac k or Africa n A m erica n, Asia n, A merica n I n dia n or Alas ka 
Nati ve, Nati ve H a waiia n or Ot her Pacifi c Isla n der, M ulti Race)  
● A ge cat e g ories ( < 4 0, 4 0 –  6 5, ≥ 6 5  years)  
● Wei g ht cate g ories ( ≤ 1 0 0 or > 1 0 0 k g)  
● B MI cate g ories ( < 2 5, ≥ 2 5 - < 3 0, ≥ 3 0 k g/ m 2) 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
1 3  
● Re gi o n ( U ni te d States, Ger ma n y, Ital y, S pai n, U nite d Ki n g d o m, Israel, 
A ustralia, a n d Tai w a n)  
● T o bacc o us er ( C urre nt, F or mer, N e v er, U n k n o w n)  
● A lc o h ol user (C urr e nt, F or mer, N e v er, U n k n o w n).  
 
 
Disease  c h aracteristics i n cl u de : 
● Ge ner al baseli ne c har act eristics: P A SI ( Ps or iasis Area Se v erit y I n de x), B S A 
( B o d y S urface Area), s P G A (static P h ysicia n's Gl o bal Assess me nt) cate g ories, 
D L QI ( D er mat ol o g y Life Q ualit y I n d e x), P S S ( Ps oriasis S y m pt o ms Scale), 
treat me nt satisfacti o n as meas ure d b y T S Q M-9 ( Treat me nt Satisfacti o n 
Q uesti o n naire f or Me dicati o n Versi o n 9)  
● D urati o n of pla q ue ps oriasis (i n years)  
● Car di o vasc ular diseases ( m y ocar dial i nfarcti o n, a n gi na pect oris, tra nsie nt 
isc he mic attac k, str o k e) 
● Car di o vasc ular ris k fact ors ( h y perte nsi o n, h y p erli pi de mia, dia betes mellit us, 
o besi t y, fa mil y hist or y of C V disease) 
● I m me diat e pri or tr eat me nt (sec u ki n u ma b or i xe kiz u ma b). 
 
7. 2  
M e di c al Hi st or y  
Me dical hist or y data will be c o de d usi n g t he Me di cal Dicti o nar y f or Re g ulat or y Acti vities 
( Me d D R A).  T h e act u al versi o n of t he Me d D R A c o di n g dicti o nar y will be n ote d i n t he 
statistical ta bles a n d cli nical st u d y re p ort.  T h e n u m ber a n d perce nt a ge of s u bjects i n eac h 
me dical hist or y cate g or y ( b y Me d D R A s yste m or g a n class a n d preferre d ter m) will be 
s u m marize d o ver all.  T he s yste m or ga n class ( S O C) will be  prese nte d i n al p ha betical 
or der, a n d t h e preferre d t er ms will be prese nt e d i n al p ha betical or d er wit hi n eac h S O C.  
S u bjects re p orti n g m ore t ha n o ne  c o n diti o n/ dia g n osis will be c o u nte d o nl y o nce i n eac h 
r o w ( S O C or preferre d ter m). 
Me dical hist or y will be s u m marize d a m o n g t he I T T P o p ulati o n.  


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
1 4  
7. 3  
Pri or a n d C o n c o mit a nt M e di c ati o n s  
Pri or a n d c o nc o mita nt m e dicati o ns will be s u m marize d b y ge n eric n a me.  A 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 date of t he first d ose of st u d y 
dr u g.  A c o nc o mita nt me dicati o n is defi ne d as a n y me dicati o n t hat starte d pri or t o t he date 
of t he first d ose of st u d y dr u g a n d c o nti n ue d t o be ta ke n o n or after t he first d ose of st u d y 
dr u g or a n y me dicati o n t hat starte d o n or after t he date of t he first d ose of  st u d y dr u g, b ut 
n ot after t he d ate of t he l ast d ose of st u d y dr u g pl us 1 4 0 da ys.  T he n u m ber a n d perce nta g e 
of s u bjects ta ki n g me dicati o ns will be s u m marize d b y ge neric dr u g na me b ase d o n t he 
W orl d Healt h Or ga nizati o n ( W H O) Dr u g Dicti o n ar y f or b ot h pri or a n d c o nc o mita nt 
me dicati o ns.  
I n a d diti o n, s u bjects' pri or bi ol o gic t hera p y f or ps oriasis will als o be s u m marize d b y t he 
reas o n f or disc o nti n uati o n. 
Pri or a n d c o nc o mita nt m e dicati o ns will be s u m marize d a m o n g t he I T T P o p ulati o n.  
8. 0  
H a n dli n g of P ot e nti al I nt er c u rr e nt E v e nt s f or t h e 
Pri m ar y a n d K e y S e c o n d ar y E n d p oi nt s  
T he pri mar y efficac y e n d p oi nt, pr o p orti o n of s u bjects ac hie vi n g s P G A 0/ 1 at Wee k 1 6 
( defi ne d i n Secti o n 3. 1 ) will be a nal yze d b ase d o n t he I T T p o p ulati o n a n d t he f oll o wi n g 
met h o ds will be use d t o a d dress p ote ntial i nterc urre nt e ve nts:  
● S u bjects w h o pre mat urel y disc o nti n ue d st u d y dr u g bef ore Wee k 1 6 d ue t o lac k 
of efficac y a n d/ or treat me nt -e mer g e nt a d verse e v e nts wil l be c o nsi dere d n ot 
ac hie vi n g t he pri mar y e n d p oi nt.  
● S u bjects w h o die bef or e assess me nt of t he pri mar y e n d p oi nt will c o u nt as 
fail ures t o ac hi e ve t he pri mar y e n d p oi nt. 
 
T he sec o n d ar y efficac y e n d p oi nts, pr o p orti o n of s u bjects ac hie vi n g s P G A 0 at Wee k 1 6, 
pr o p orti o n of s u bjects ac hie vi n g D L QI 0/ 1 at Wee k 1 6, a n d pr o p orti o n of s u bjects 
ac hie vi n g P S S 0 at Wee k 1 6 ( defi ne d i n Secti o n  3. 2 ) will be a nal yze d base d o n t he I T T 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
1 5  
p o p ulati o n a n d t he f oll o wi n g met h o ds will be use d t o a d dress t he p ote ntial i nterc urre nt 
e ve nts:  
● S u bjects w h o pre mat urel y disc o nti n ue d st u d y dr u g bef ore Wee k 1 6 d ue t o lac k 
of efficac y a n d/ or treat me nt -e mer g e nt a d verse e v e nts will be c o nsi dere d n ot 
ac hie vi n g t he a b o v e sec o n dar y e n d p oi nts. 
● S u bjects w h o die bef or e assess me nt of t he a b o v e sec o n dar y e n d p oi nts will 
c o u nt as fail ures t o ac hie ve t he a b o ve s ec o n dar y e n d p oi nts.  
 
T he sec o n d ar y efficac y e n d p oi nts, pr o p orti o n of s u bjects ac hie vi n g s P G A 0/ 1 at Wee k 5 2, 
pr o p orti o n of s u bjects ac hie vi n g s P G A 0 at Wee k 5 2, pr o p orti o n of s u bjects ac hie vi n g 
D L QI 0/ 1 at Wee k 5 2, a n d pr o p orti o n of s u bjects ac hie vi n g P S S 0 at Wee k 5 2 ( defi ne d i n 
Secti o n  3. 2 ) will be a nal yze d base d o n t he I T T p o p ulati o n a n d t he f oll o wi n g met h o ds will 
be use d t o a d dr ess t he p ote ntial i nterc urre nt e ve nts:  
● S u bjects w h o pre mat urel y disc o nti n ue d st u d y dr u g bef ore Wee k 5 2 d ue t o lac k 
of efficac y a n d/ or treat me nt -e mer g e nt a d verse e v e nts will be c o nsi dere d n ot 
ac hie vi n g t he a b o v e sec o n dar y e n d p oi nts.  
● S u bjects w h o die bef or e assess me nt of t he a b o v e sec o n dar y e n d p oi nts will 
c o u nt as fail ures t o ac hie ve t he a b o ve s ec o n dar y e n d p oi nts.  
 
T he sec o n d ar y efficac y e n d p oi nts o n ti me t o ac hie ve s P G A 0/ 1 a n d ti me t o ac hie ve s P G A 
0 ( defi ne d i n Secti o n  3. 2 ) will be a nal yze d b ase d o n t he I T T p o p ulati o n a n d t he f oll o wi n g 
met h o ds will be use d t o a d dress t he p ote ntial i nterc urre nt e ve nts:  
● S u bjects w h o pre mat urel y disc o nti n ue d st u d y dr u g or earl y wit h dre w fr o m t he 
st u d y d ue t o lac k of efficac y a n d/ or treat me nt-e mer ge nt a d verse e v e nts a n d 
ne ver attai n e d e n d p oi nts b y t he ti me of t he last visit w here s P G A was m eas ure d 
pri or t o disc o nti n uati o n will ha ve all data f or t he a b o ve sec o n d ar y e n d p oi nts be 
c o nsi dere d as ce ns ore d at t he ti me of disc o nti n uati o n of st u d y dr u g or st u d y d ue 
t o lac k of efficac y a n d/ or treat me nt-e mer ge nt a d v erse e ve nts, w hi c he ver occ urs 
first. 
 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
1 6  
9. 0  
Effi c a c y A n al y s e s  
9. 1  
G e n er al C o n si d er ati o n s  
All  efficac y a n al ys es will be c o n d ucte d i n t he I T T P o p ulati o n.    
T he pri mar y a n al ysis f or all efficac y e n d p oi nts pertai ni n g t o t he i nitial p hase ( Wee ks 0 -
1 6) will be perf or me d aft er t he last s u bject has c o m plete d t he Wee k 1 6 visit or has 
disc o nti n ue d fr o m t he st u d y partici pati o n, a n d t he data u p t o Wee k 1 6 ha ve bee n cle a ne d 
a n d w he n a d ata bas e l oc k will occ ur t o e na ble t h e a nal ysis.  T his will be t he o nl y a n d fi nal 
efficac y a n al ysis f or t he i nitial p hase.  
C ate g orical e n d p oi nts will be s u m marize d b y fre q ue ncies, perce nt a ges, a n d ass ociate d 
9 5 % c o nfi de n ce i nter v als ( CIs).   C o nti n u o us e n d p oi nts will be s u m marize d b y mea ns, 
sta n dar d de viati o ns as w ell as m o del base d least s q uare mea n s, sta n dar d err ors, a n d t he 
9 5 % CIs after acc o u nti n g f or rele v a nt baseli ne c haracteristics.   Ti me t o e ve nt e n d p oi nts 
will be a nal yze d usi n g K a pl a n-Meier esti mates a n d C o x re gressi o n m o dels wit h baseli ne 
s P G A a n d B S A meas ure me nts as c o variat es a n d h azar d rati o bet w ee n bas eli ne s P G A 2 
a n d baseli ne s P G A 3 a n d its 9 5 % c o nfi de nce i nter val will be re p orte d.  Ti m e t o e ve nt 
e n d p oi nts will be calc ulate d as : 
● Ti me t o first ac hie ve me nt ( wit h o bser ve d e v e nt) = [ date of first ac hie v e me nt] –  
[ date of first d ose] + 1 
● S u bjects wit h o ut s P G A meas ure me nts will n ot be i ncl u de d i n t he a n al ysis.  
● If a s u bject n e ver attai ns t he e n d p oi nt b y t he e n d of  t he e val uati o n peri o d, t hat 
s u bject's ti me t o first ac hie ve me nt will be ce ns ore d at t he last visit bef ore t h e 
e n d of t he e v al uati o n peri o d w here s P G A was meas ure d e xce pt t he sce n ari o 
descri be d i n S ecti o n 8. 0 . 
 
" Baseli ne" refers t o t he last n o n-missi n g o bser vati o n o n or bef ore t he first  a d mi nistrati o n 
of st u d y dr u g.   F or v aria bles w here assess me nt ti me is c ollecte d, t he b aseli ne 
meas ure me nt m ust be pri or t o t he ti me of t he first a d mi nistrati o n of st u d y dr u g.  


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
1 7  
9. 2  
H a n dli n g of Mi s si n g D at a  
Missi n g data c o ul d occ ur d ue t o vari o us reas o ns, i ncl u di n g missi n g visits/assess me nts, 
earl y wit h dra wal fr o m t h e st u d y, or missi n g d ue t o C O VI D -1 9 i nfecti o n or l o gistic 
restricti o n. 
T he C O VI D -1 9 p a n de mi c is i nterf eri n g wit h t he c o n d uct of ma n y o n g oi n g trials, wit h 
p ote ntial i m pacts o n treat me nt d urati o n a n d t he c ollecti o n, a nal ysis a n d t he i nter pretati o n 
of cli nical trial data.  S o me pr ot oc ol -s pecifie d visits i n t he cli nical trials ma y be i m pacte d 
d ue t o C O VI D -1 9 i nf ecti o n or l o gistical restricti o ns d uri n g t he pa n de mic.  F or e x a m ple, 
s o me sc he d ule d visits ma y be misse d d ue t o self-q uara nti ne or l o cal g o ver n me nt 
restricti o ns o n tra vel; s o me visits ma y als o be dela ye d or ca ncele d d ue t o h ealt hcare 
res o urce c o nstrai nts d uri n g t he pa n de mic.  I m pact e d visits d ue t o C O VI D -1 9 will be 
rec or d e d i n t he data b ase.  T he pr o ba bilit y of ha vi n g misse d visits a n d missi n g data d ue t o 
C O VI D -1 9 i nfecti o n or l o gistical restricti o ns relat e d t o t he C O VI D -1 9 p a n de mic ca n b e 
reas o na bl y ass u me d t o be u nrelate d t o t he u n o bs er ve d val ues.  T h eref ore, f or t he p ur p ose 
of statistical a nal ysis, it is reas o na ble t o ass u me t hat t hese missi n g data are missi n g at 
ra n d o m ( M A R) a n d t h e statistical m o dels t hat re q uire M A R ass u m pti o n are a p pr o pri ate.   
Ha n dl i n g of missi n g data f or t he efficac y a n al yses is descri be d bel o w. 
● N o n -Res p o n der I m p ut ati o n i nc or p orati n g m ulti ple i m p utati o n t o ha n dle 
missi n g data d ue t o C O VI D -1 9 ( N RI -C):  t he N RI -C a nal ysis will cate g orize 
a n y s u bject w h o d oes n ot ha ve e v al uati o n d uri n g  a s pecific visit wi n d o w as a 
n o n -res p o n der f or t hat visit.  T he e xce pti o ns are:  ( 1) if t he s u bject is a 
res p o n der b ot h b ef or e a n d after a s pecifi c visit wi n d o w i n t he partic ular p eri o d, 
t he n t he s u bject will be cate g orize d as a res p o n der f or t he visit; (2) missi n g data 
d ue t o a C O VI D -1 9 i nfecti o n or l o gistical restricti o ns relate d t o t he C O VI D -1 9 
pa n de mic will be ha n dle d t hr o u g h M ulti ple I m p utati o n ( MI).  T he N RI -C will 
be t he pri mar y missi n g data i m p utati o n a p pr oac h i n t he a nal yses of cate g orical 
varia bl es.  
● As -o bser ve d:  T h e as -o bs er ve d a n al ysis will i ncl u de all a vaila ble assess me nts 
o n a sc he d ule d visit.  N o missi n g assess me nts will be i m p ute d.  A n d t here will 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
1 8  
be n o o ver writi n g f or visits after s u bjects disc o nti n ue st u d y dr u g d ue t o lac k of 
efficac y a n d/ or treat me nt e mer ge nt a d v erse e ve nts.  T he as -o bser ve d a nal ysis 
will be t he se nsiti vit y a p pr oac h t o ha n dle missi n g data i n t he a nal ysis of t h e 
pri mar y a n d sec o n dar y cate g orical efficac y e n d p oi nts s pecifie d i n Secti o n  3. 1  
a n d Secti o n  3. 2 . 
● Mi xe d -Effect M o del Re p eat Meas ure me nt ( M M R M):  T he re p eate d meas ures 
a nal ysis will be c o n d ucte d usi n g a mi xe d m o del i ncl u di n g baseli ne val ue a n d 
o bser ve d meas ure me nts at all p ost -baseli ne visits.  T he mi xe d m o del i ncl u des 
t he cate g ori cal fi xe d eff ects of visits a n d t he fi xe d c o variates of baseli ne 
meas ure me nts.  A n u nstr uct ure d varia nce c o var ia nce matri x will be use d.  
Para meter esti mati o n is base d o n t he ass u m pti o n of data bei n g missi n g at 
ra n d o m a n d usi n g t he met h o d of restricti ve ma xi m u m li keli h o o d ( R E M L).  
M M R M will be t he pri mar y a p pr o ac h i n t he a nal ysis of c o nti n u o us varia bles.  
 
9. 3  
Pri m ar y Effi c a c y E n d p oi nt a n d A n al y s e s  
9. 3. 1  
Pri m ar y Effi c a c y E n d p oi nt  
T he pri mar y e n d p oi nt is t he pr o p orti o n of s u bjects ac hie vi n g s P G A 0/ 1 at Wee k 1 6.  
9. 3. 2  
M ai n A n al y si s of Pri m ar y Effi c a c y E n d p oi nt  
T he cate g orical varia bles will be s u m marize d b y fre q ue nci es, perce nta g es, a n d ass ociate d 
9 5 % c o nfi de n ce i nter v als ( CIs).  Missi n g data will be ha n dle d usi n g t he N RI -C met h o d.  
T he attri b utes of t he esti ma n d c orr es p o n di n g t o t he pri mar y efficac y e n d p oi nt is 
s u m marize d i n Ta ble  1 . 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
1 9  
T a ble  1 . 
S u m m ar y of t he Esti m a n d Attri b utes of t he Pri m ar y Effic ac y 
E n d p oi nt  
Esti m a n d  
L a bel  
Attri b utes of t he Esti m a n d  
Tre at m e nt  
E n d p oi nt  
P o p ul ati o n  
H a n dli n g of 
I nterc urre nt E ve nts 
St atistic al 
S u m m ar y  
Pri mar y 
efficac y 
e n d p oi nt of 
s P G A 0/ 1 
at Wee k 1 6 
Risa n kiz u ma b 
1 5 0  m g  
Ac hie ve me nt 
of s P G A 0/ 1 at 
Wee k 1 6  
S u bjects wit h 
m o derate t o 
se vere pla q ue 
ps oriasis, 
w h o ha ve 
bee n treate d 
wit h la bele d 
d ose of 
sec u ki n u ma b 
or 
i xe kiz u ma b 
f or at least 6 
m o nt hs a n d 
are 
e x perie nci n g 
a s u b o pti mal 
res p o nse 
S u bjects w h o 
pre mat urel y 
disc o nti n ue d st u d y 
dr u g bef ore Wee k 1 6 
d ue t o lac k of efficac y 
a n d/ or treat me nt -
e mer ge nt a d verse 
e ve nts will be 
c o nsi dere d n ot 
ac hie vi n g t he pri mar y 
e n d p oi nt; S u bjects 
w h o die bef ore 
assess me nt of t he 
pri mar y e n d p oi nt will 
c o u nt as fail ures t o 
ac hie ve t he pri mar y 
e n d p oi nt.  
Fre q ue ncies, 
perce nta ges, 
an d 
ass ociate d 
9 5 % 
c o nfi de nce 
i nter vals  
 
9. 3. 3  
S e n siti vit y a n d S u p pl e m e nt ar y A n al y s e s of t h e Pri m ar y 
Effi c a c y E n d p oi nt  
As -o bser ve d a nal ysis will als o be perf or me d t o ha n dle missi n g data as se nsiti vit y a nal ysis.  
9. 4  
S e c o n d ar y Effi c a c y E n d p oi nt s a n d A n al y s e s  
9. 4. 1  
S e c o n d ar y Effi c a c y E n d p oi nt s  
T he sec o n d ar y e n d p oi nts are as d efi ne d i n Secti o n 3. 2 . 
9. 4. 2  
M ai n A n al y s e s of S e c o n d ar y Effi c a c y E n d p oi nt s  
Cate g orical e n d p oi nts will be s u m mariz e d b y fre q ue ncies, perce nt a ges, a n d ass ociate d 
9 5 % c o nfi de n ce i nter v als ( CIs).  Missi n g data will be ha n dle d usi n g t he N RI -C met h o d.  


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
2 0  
Ti me t o e ve nt e n d p oi nts will be a nal yze d usi n g K a pla n -Meier esti mates a n d C o x 
re gressi o n m o dels wit h b aseli ne s P G A a n d B S A meas ure me nts as c o vari ates a n d hazar d 
rati o bet wee n b aseli ne s P G A 2 a n d bas eli ne s P G A 3 a n d its 9 5 % c o nfi de nce i nter val will 
be re p ort e d.  
T a ble  2 . 
S u m m ar y of t he Esti m a n d Attri b utes of t he Sec o n d ar y Effic ac y 
E n d p oi nt s 
Esti m a n d  
L a bel  
Attri b utes of t he Esti m a n d  
Tre at m e nt  
E n d p oi nt  
P o p ul ati o n  
H a n dli n g of 
I nterc urre nt E ve nts 
St atistic al 
S u m m ar y  
Sec o n dar y 
efficac y 
e n d p oi nt of 
s P G A 0 at 
Wee k 1 6  
Risa n kiz u ma b 
1 5 0  m g  
Ac hie ve me nt 
of s P G A 0 at 
Wee k 1 6  
S u bjects wit h 
m o derate t o 
se vere pla q ue 
ps oriasis, w h o 
ha ve bee n 
treate d wit h 
la bele d d ose of 
sec u ki n u ma b 
or i xe kiz u ma b 
f or at least 6 
m o nt hs a n d are 
e x perie nci n g a 
s u b o pti mal 
res p o nse 
S u bjects w h o 
pre mat urel y 
disc o nti n ue d st u d y 
dr u g bef ore Wee k 1 6 
d ue t o lac k of 
efficac y a n d/ or 
treat me nt-e mer ge nt 
a d verse e ve nts will 
be c o nsi dere d n ot 
ac hie vi n g t he 
e n d p oi nts; S u bjects 
w h o die bef ore 
assess me nt of t he 
e n d p oi nt will c o u nt 
as fail ures t o ac hie ve 
t he e n d p oi nts. 
Fre q ue ncies, 
perce nta ges, 
a n d 
ass ociate d 
9 5 % 
c o nfide nce 
i nter vals  
Sec o n dar y 
efficac y 
e n d p oi nt of 
D L QI 0/ 1 
at Wee k 1 6 
Ac hie ve me nt 
of D L QI 0/ 1 
at Wee k 1 6 
Sec o n dar y 
efficac y 
e n d p oi nt of 
P S S 0 at 
Wee k 1 6  
Ac hie ve me nt 
of P S S 0 at 
Wee k 1 6  
 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
2 1  
T a ble  2 . 
S u m m ar y of t he Esti m a n d Attri b utes of t he Sec o n d ar y Effic ac y 
E n d p oi nts ( C o nti n ue d)  
Esti m a n d  
L a bel  
Attri b utes of t he Esti m a n d  
Tre at m e nt  
E n d p oi nt  
P o p ul ati o n  
H a n dli n g of 
I nterc urre nt 
E ve nts  
St atistic al 
S u m m ar y  
Sec o n dar y 
efficac y 
e n d p oi nt of 
s P G A 0/ 1 at 
Wee k 5 2  
Risa n kiz u ma b 
1 5 0  m g  
Ac hie ve me nt 
of s P G A 0/ 1 
at Wee k 5 2 
S u bjects wit h 
m o derate t o 
se vere pla q ue 
ps oriasis, w h o 
ha ve bee n 
treate d wit h 
la bele d d ose of 
sec u ki n u ma b or 
i xe kiz u ma b f or 
at least 6 
m o nt hs a n d are 
e x perie nci n g a 
s u b o pti mal 
res p o nse 
S u bjects w h o 
pre mat urel y 
disc o nti n ue d st u d y 
dr u g bef ore Wee k 
5 2 d ue t o lac k of 
efficac y a n d/ or 
treat me nt-e mer ge nt 
a d verse e ve nts will 
be c o nsi dere d n ot 
ac hie vi n g t he 
e n d p oi nts; S u bjects 
w h o die bef ore 
assess me nt of t he 
e n d p oi nt will c o u nt 
as fail ures t o 
ac hie ve t he 
e n d p oi nts. 
Fre q ue ncies, 
perce nta ges, 
a n d 
ass ociate d 
9 5 % 
c o nfide nce 
i nter vals  
Sec o n dar y 
efficac y 
e n d p oi nt of 
s P G A 0 at 
Wee k 5 2  
Ac hie ve me nt 
of s P G A 0 at 
Wee k 5 2  
Sec o n dar y 
efficac y 
e n d p oi nt of 
D L QI 0/ 1 at 
Wee k 5 2  
Ac hie ve me nt 
of D L QI 0/ 1 
at Wee k 5 2 
Sec o n dar y 
efficac y 
e n d p oi nt of 
P S S 0 at 
Wee k 5 2  
Ac hie ve me nt 
of P S S 0 at 
Wee k 5 2  
 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
2 2  
T a ble  2 . 
S u m m ar y of t he Esti m a n d Attri b utes of t he Sec o n d ar y Effic ac y 
E n d p oi nts ( C o nti n ue d)  
Esti m a n d  
L a bel  
Attri b utes of t he Esti m a n d  
Tre at m e nt  
E n d p oi nt  
P o p ul ati o n  
H a n dli n g of 
I nterc urre nt E ve nts 
St atistic al 
S u m m ar y  
Sec o n dar y 
efficac y 
e n d p oi nt 
of ti me t o 
ac hie ve 
s P G A 0/ 1 
Risa n kiz u ma b 
1 5 0  m g  
Ti me t o 
ac hie ve 
s P G A 0/ 1 
S u bjects wit h 
m o derate t o 
se vere pla q ue 
ps oriasis, w h o 
ha ve bee n 
treate d wit h 
la bele d d ose of 
sec u ki n u ma b 
or i xe kiz u ma b 
f or at least 6 
m o nt hs a n d are 
e x perie nci n g a 
s u b o pti mal 
res p o nse 
S u bjects w h o 
pre mat urel y 
disc o nti n ue d  st u d y 
dr u g or earl y 
wit h dr ew fr o m  t he 
st u d y d ue t o lac k of 
efficac y a n d/ or 
treat me nt-e mer ge nt 
a d verse e ve nts a n d 
ne ver attai n e d  
e n d p oi nts b y t he ti me 
of last visit w here 
s P G A was meas ure d 
pri or t o 
disc o nti n uati o n will 
ha ve all data f or t he 
e n d p oi nts be 
c o nsi dere d as 
ce ns ore d at t he ti me 
o f disc o nti n uati o n of 
st u d y dr u g or st u d y 
d ue t o lac k of efficac y 
or treat me nt -e mer ge nt 
a d verse e ve nts , 
w hic he ver occ urs 
first. 
Ka pla n -Meier 
esti mates a n d 
C o x 
re gressi o n 
m o dels wit h 
baseli ne 
s P G A a n d 
B S A 
meas ure me nts 
as c o variates; 
hazar d rati o 
bet wee n 
base li ne 
s P G A 2 a n d 
baseli ne 
s P G A 3 a n d 
its 9 5 % 
c o nfi de nce 
i nter val will 
be re p orte d . 
Sec o n dar y 
efficac y 
e n d p oi nt 
of ti me t o 
ac hie ve 
s P G A 0 
Ti me t o 
ac hie ve 
s P G A 0 
 
9. 4. 3  
S e n siti vit y a n d S u p pl e m e nt ar y A n al y s e s f or S e c o n d ar y 
Effi c a c y E n d p oi nt s  
As -o bser ve d a nal ysis will als o be perf or me d t o ha n dle missi n g data f or cat e g orical 
e n d p oi nts as se nsiti vit y a nal ysis.  


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
2 3  
9. 5  
A d diti o n al Effi c a c y A n al y s e s  
Cate g orical e x pl or at or y efficac y e n d p oi nts will be s u m marize d b y fre q ue n cies, 
perce nt a ges, a n d ass ociat e d 9 5 %  c o nfi d e nce i nter vals ( CIs).  Missi n g data will be ha n dle d 
usi n g t he N RI -C met h o d.  
C o nti n u o us e x pl orat or y efficac y e n d p oi nts will be s u m marize d b y mea ns, st a n dar d 
de viati o ns as well m o del base d least s q uare mea n s, sta n dar d err ors, a n d t h e 9 5 % CIs after 
acc o u nti n g f or rele v a nt baseli ne c haracteristics.   Missi n g data will be ha n dle d usi n g t he 
M M R M met h o d.  
9. 6  
Effi c a c y S u b gr o u p A n al y s e s  
T o e val uate t he c o nsiste n c y of t he efficac y o ver de m o gra p hic a n d ot her bas eli ne 
c haracteristics, s u m maries a n d a nal yses will be perf or me d f or selecte d s u b gr o u ps f or t he 
pri mar y efficac y e n d p oi nt if data all o ws.  
● A ge gr o u p ( < 4 0 years, ≥ 4 0 –  < 6 5 years, ≥ 6 5 years)  
● Se x ( male, fe m ale)  
● S m o ki n g (c urre nt, e x , ne ver)  
● B MI ( n or mal: < 2 5, o ver wei g ht: ≥ 2 5 –  < 3 0, o bes e: ≥ 3 0)  
● Baseli ne Wei g ht ( ≤ 1 0 0 k g, > 1 0 0 k g)  
● Baseli ne Wei g ht ( b y q uartiles)  
● Baseli ne P A SI ( b y m e dia n)  
● Baseli ne B S A ( b y me dia n)  
● Baseli ne s P G A ( 2 , 3 ) 
● I m me diat e pri or tr eat me nt (sec u ki n u ma b or i xe kiz u ma b) 
 
I n a d diti o n, f or t he sec o n dar y efficac y e n d p oi nts ti me t o ac hie ve s P G A 0/ 1 a n d ti me t o 
ac hie ve s P G A 0, Ka pla n -Meier esti mates will be p erf or me d f or t he f oll o wi n g s u b gr o u p s:  
● Baseli ne s P G A ( 2 , 3 ) 
 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
2 4  
1 0. 0  
S af et y A n al y s e s  
1 0. 1  
G e n er al C o n si d er ati o n s  
Safet y data will be s u m m arize d f or t he Safet y A nal ysis Set .  Safet y a nal yses will i ncl u de 
a d verse e ve nts, la b or at or y, a n d vital si g n meas ure me nts . 
Missi n g safet y data will n ot be i m p ute d.  
1 0. 2  
A d v er s e E v e nt s  
A d verse e ve nts ( A Es) will be s u m marize d a n d prese nte d usi n g pri mar y Me d D R A S yste m 
Or ga n Classes ( S O Cs) a n d preferre d t er ms ( P Ts) acc or d i n g t o t he versi o n of t he Me d D R A 
c o di n g dicti o nar y use d f or t he st u d y at t he ti me of data base l oc k.   T he act ual versi o n of 
t he Me d D R A c o di n g dicti o nar y use d will be n ote d i n t he A E ta bles a n d i n t he cli nical 
st u d y re p ort.  S pecific a d verse e v e nts will be c o u nte d o nce f or eac h s u bject f or cal c ulati n g 
perce nt a ges, u nless state d ot her wise.   I n a d diti o n, if t he sa me a d v erse e ve nt occ urs 
m ulti ple ti mes wit hi n a s u bject, t he hi g hest se verit y a n d le vel of relati o ns hi p t o 
i n vesti gati o nal pr o d uct will be re p orte d. 
1 0. 2. 1  
T r e at m e nt-E m er g e nt A d v er s e E v e nt s  
Treat me nt -e mer ge nt A Es are defi ne d as a n y A E wit h t he o nset t hat is after t he first  d ose 
of st u d y dr u g a n d wit hi n 2 0 wee ks ( 1 4 0 d a ys) after t he last d ose of st u d y dr u g.  E ve nts 
w here t he o ns et date is t h e sa me as t he st u d y dr u g start date are ass u me d t o be treat me nt 
e mer ge nt.  All treat me nt -e mer ge nt A Es will be s u m marize d o verall, as well as b y pri mar y 
Me d D R A S O C a n d Preferre d Ter m.  T he S O Cs will be prese nte d i n al p h a betical or der, 
a n d t he P Ts will be prese nte d i n al p ha beti cal or d er wit hi n eac h S O C.  
T he n u m ber a n d p erce nta ge of s u bjects e x p erie n ci n g treat me nt -e mer ge nt A Es will be 
s u m marize d. 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
2 5  
1 0. 2. 2  
A d v er s e E v e nt O v er vi e w  
A n o ver vie w of T E A Es will be prese nte d c o nsisti n g of t he n u m ber a n d p erce nta ge of 
s u bjects e x perie n ci n g at l east o ne e v e nt f or eac h of t he f oll o wi n g A E cat e g ories:  
● A n y treat me nt -e mer ge nt A E  
● A n y treat me nt -e mer ge nt A E relate d t o st u d y dr u g acc or di n g t o t he i n vesti g at or  
● A n y se ver e treat me nt -e m er ge nt A E  
● A n y seri o us treat me nt -e mer ge nt A E  
● A n y treat me nt -e mer ge nt A E lea di n g t o disc o nti n uati o n of st u d y dr u g  
● A n y treat me nt -e mer ge nt A E lea di n g t o deat h  
● A n y a dj u dicate d M A C E  
● A n y seri o us i nfecti o n  
● A n y t u berc ul osis  
● A n y mali g na nt t u m or  
● A n y mali g na nt t u m or e xcl u di n g N M S C  
● A n y seri o us h y pers e nsiti vit y  
 
All deat hs will als o be s u m marize d:  
● Deat hs occ urri n g ≤ 1 4 0 d a ys after l ast d ose of st u d y dr u g  
● Deat hs occ urri n g > 1 4 0 d a ys after l ast d ose of st u d y dr u g.  
 
1 0. 2. 3  
Tr e at m e nt -E m er g e nt A d v er s e E v e nt s  b y S O C a n d/ or P T  
Treat me nt -e mer ge nt ad v erse e v e nts will be s u m marize d b y S O C a n d P T; b y ma xi m u m 
relati o ns hi p t o st u d y dr u g as assesse d b y t he i n v esti gat or (e. g., reas o na ble p ossi bilit y or n o 
reas o na bl e p ossi bilit y) a n d b y S O C a n d P T; b y ma xi m u m se verit y a n d b y S O C a n d P T; 
a n d b y S O C a n d P T li sti n g ass ociate d s u bject n u m ber.  W he n s u m mari zi n g t he n u m ber 
a n d perce nta ges of s u bjects, s u bjects wit h m ulti ple occ urre n ces of t he s a me a d vers e e v e nt 
will be c o u nte d o nce, a n d o nl y t he ma xi m u m se verit y le vel will be pres e nte d i n t he 


 Risa n kiz u ma b  
M 1 9 -1 6 4 – Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
2 6  
se verit y s u m maries, an d t he w orst/ hi g hest relati o ns hi p le vel i n t he relati o ns hi p 
s u m maries. 
I n a d diti o n, treat me nt-e m er ge nt a d v erse e ve nts will be s u m marize d b y P T a n d s orte d b y 
decreasi n g fr e q ue nc y. 
1 0. 2. 4  
Tr e at m e nt - Em er g e nt A d v er s e E v e nt s  p er P ati e nt -Y e ar s of 
E x p o s ur e  
E x p os ure- a dj uste d A Es p er 1 0 0 patie nt- y ears will be pr o vi de d, w h ere A Es per 1 0 0 
patie nt - years of e x p os ur e are defi ne d as t he n u m b er of A Es di vi de d b y t he t otal e x p os ure 
i n 1 0 0 patie nt-years.  
N ote t hat o ne e v e nt per preferre d t er m per d a y per s u bject will be c o u nte d i n t he 
calc ulati o n of t he n u m ber of A Es (i.e., a preferre d ter m will n ot be c o u nte d t wice o n t he 
sa me da y f or t h e sa me s u bject).  See t he calc ulati o n met h o d bel o w. 
, 
 
w here t otal patie nt y ears is defi ne d as t he s u m of t he st u d y dr u g e x p os ure ( defi ne d as d ate 
of last d ose – date of first d ose + 1 4 0 da ys ( 5 h alf-li ves)) of all s u bjects n or malize d b y 
3 6 5. 2 5, a n d r o u n de d t o o ne deci mal place. 
1 0. 2. 5  
S A E s (I n cl u di n g D e at h s) a n d A d v er s e E v e nt s L e a di n g t o 
St u d y Dr u g Di s c o nti n u ati o n  
Treat me nt - e mer ge nt S A Es (i ncl u di n g deat hs) a n d A Es lea di n g t o st u d y dr u g 
disc o nti n uati o n will be s u m marize d b y S O C a n d P T a n d i n listi n g f or mat. 
A listi n g of pre-treat me nt S A Es wit h o nset dates pri or t o t he first d ose of st u d y dr u g will 
be pr o vi de d. 
 
Years
Pati e nt 
 
T ot al
T E A Es
 
of
N u m b er 
1 0 0 ×


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
2 7  
1 0. 2. 6  
Ar e a o f S af et y I nt er e st 
Detaile d i nf or mati o n a b o ut t he searc h criteria f or areas of safet y i nterest ( A SIs) are 
pr o vi de d i n A p pe n di x  B . 
T he fi nal list will be  base d o n t he m ost u p date d fi nal versi o n of risa n kiz u m a b Pr o d uct 
Safet y Statistical A nal ysis Pla n, w hic h is c o nsiste nt t o t he m ost u p date d risa n kiz u ma b 
Ris k Ma na ge me nt Pla n.  
Ta b ular listi n gs of select e d area of safet y i nterest will be pr o vi de d.  
1 0. 3  
A n al y si s of  L a b or at or y D at a  
Data c ollecte d fr o m ce ntr al a n d l ocal la b orat ories, i ncl u di n g a d diti o nal la b orat or y  testi n g 
d ue t o a n S A E, will be use d i n all a nal yses , e x ce pt f or Baseli ne w h ere S A E-relate d 
la b orat or y ass ess me nts o n or bef or e t he first d ose of st u d y dr u g will be e xcl u de d .  T he 
cli nical la b orat or y tests d efi ne d i n t he pr ot oc ol o p erati o ns ma n ual (e. g., he mat ol o g y a n d 
cli nical c he mistr y) will b e s u m marize d.  
Eac h la b or at or y varia ble will be s u m marize d f or all a p plica ble ti me p oi nts (starti n g wit h 
Baseli ne ) wit h t he n u m ber of n o n-missi n g o bser v ati o ns, mea n a n d sta n dar d de viati o n, 
me dia n, mi ni m u m a n d ma xi m u m.  Mea n c ha n g e fr o m baseli ne t o eac h a p plica ble p ost -
baseli ne visit will be s u m marize d f or selecte d la b orat or y vari a bles, wit h t he n u m ber of 
o bser vati o ns , baseli ne m ea n, a n d visit mea n.  T h e c ha n ge fr o m baseli ne m ea n, sta n dar d 
err or, a n d 9 5 % c o nfi de nce i nter val will be prese nt e d f or t he mea n c h a n ge fr o m baseli ne . 
C ha n ges i n la b orat or y p ara meters will be ta b ul ate d usi n g s hift ta bles base d o n t he t o xicit y 
gr a des acc or di n g t o N CI C T C A E Versi o n 4. 0 3 1 of t he la b orat or y use d f or eac h sa m ple.  A 
s hift ta ble fr o m baseli ne t o mi ni m u m a n d ma xi m u m val ue ( base d o n to xicit y gra des ), will 
be create d.  A si milar s hift ta ble will be pr o vi de d t o s u m marize s hifts fr o m baseli ne t o t he 
fi nal p ost-baseli ne val u e.  
La b orat or y a b n or malities  meeti n g C T C  criteria gra de 3 a n d 4 will be s u m marize d.  


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
2 8  
La b orat or y a b n or malities will be e val uate d b ase d o n P ote ntiall y C li nicall y Im p ort a nt 
( P CI) criteria (A p pe n di x  C ).  F or eac h la b orat or y P CI criteri o n, t he n u m ber a n d 
perce nt a ge of s u bjec ts w h o ha ve a la b orat or y v al ue meeti n g t he criteria will be 
s u m marize d.  Listi n gs will be pr o vi de d t o s u m marize s u bject -le v el la b orat or y data f or 
s u bjects meeti n g P CI criteria. 
I n a d diti o n, A L T/ S G P T, A S T/ S G O T, al kali ne p h os p hatase, a n d t otal bilir u bi n will be 
cate g orize d as f oll o ws:  
● < 1. 5 × U L N  
● ≥ 1. 5 × U L N –  < 3. 0 × U L N  
● ≥ 3. 0 × U L N –  < 5. 0 × U L N  
● ≥ 5. 0 × U L N –  < 1 0. 0 × U L N  
● ≥ 1 0. 0 × U L N –  < 2 0. 0 × U L N  
● ≥ 2 0. 0 × U L N  
 
A listi n g of p ote ntiall y cli nicall y i m p orta nt li ver f u ncti o n la b orat or y val u es will i ncl u de 
all s u bjects w h o met a n y of t he f oll o wi n g f o ur criteria: 
● A L T ≥ 3 × U L N, or  
● A S T ≥ 3 × U L N, or  
● Al kali ne P h os p hatase ≥ 1. 5 × U L N, or  
● T otal bilir u bi n ≥ 2 × U L N.  
 
A listi n g of p ossi ble H y's La w cas es, defi n e d as t h ose w h o meet all of t he f oll o wi n g 
c o n diti o ns, will be pr o vi de d:  A L T > 3 × U L N or A S T > 3 × U L N a n d bilir u bi n ≥ 2 × 
U L N.  
1 0. 4  
A n al y si s of Vit al Si g n s  
Vital si g n meas ure me nts of s yst olic a n d diast olic bl o o d pres s ure will be s u m marize d.  


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
2 9  
Eac h vital si g n varia ble will be s u m marize d f or all ti me p oi nts (starti n g wit h Baseli ne) 
wit h t he n u m ber of n o n -missi n g o bser vati o ns, mea n a n d sta n dar d de viati o n, me dia n, 
mi ni m u m a n d ma xi m u m.  Mea n c ha n g e fr o m b aseli ne t o eac h a p pl ica ble p ost-baseli ne 
visit will be s u m marize d f or eac h vital si g n varia bl e, wit h t he n u m ber of o bs er vati o ns, 
baseli ne mea n, a n d visit mea n.  T he c h a n ge fr o m baseli ne mea n, sta n d ar d err or, a n d 9 5 % 
c o nfi de nce i nter val will be prese nt e d f or t he m ea n c ha n ge fr o m baseli ne.  
Vital si g n varia bles will be e val uat e d base d o n p ote ntiall y cli nicall y i m p orta nt ( P CI) 
criteria (A p pe n di x  C ).  F or eac h vital si g n P CI crit eri o n, t he n u m ber a n d p erce nt a ge of 
s u bjects w h o ha ve a vital si g n val ue meeti n g t he criteria will be s u m marize d.  Listi n gs 
will be pr o vi de d t o s u m marize s u bject -le vel vital si g n data f or s u bjects meeti n g P CI 
criteria.  
1 0. 5  
S af et y S u b gr o u p A n al y s e s  
N o s u b gr o u p f or safet y a nal yses. 
1 0. 6  
Ot h er S af et y A n al y s e s  
N o ot her saf et y a nal yses.  
1 1. 0  
Ot h er A n al y s e s  
N o ot her  a nal ys es. 
1 2. 0  
I nt eri m A n al y s es  
A n  i nteri m a nal ysis f or efficac y a n d safet y data of t he i nitial p hase (Wee k 0 – 1 6 ) will be 
c o n d ucte d after 5 0 % of all c o nti n ui n g s u bject s c o m plete Wee k 1 6 a n d w he n a n i nteri m 
data b ase l oc k will occ ur t o e na ble t he a nal ysis.   T hat is, t he i nteri m a nal ysis will be 
c o n d ucte d 1 6 w ee ks after 1 2 5 s u bjects c o m plete st u d y e nr oll me nt.  
T he pri mar y a n al ysis f or t he i nitial p hase ( Wee k 0-1 6) will be perf or me d after t he last 
s u bject has c o m plete d t h e Wee k 1 6 visit or has disc o nti n ue d fr om t he st u d y partici pati o n, 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
3 0  
a n d t he data u p t o Wee k 1 6 ha ve bee n clea ne d a n d w he n a dat a base l oc k will occ ur t o 
e na ble t he a nal ysis.  
1 2. 1  
D at a M o nit ori n g C o m mitt e e    
N ot a p plica ble.  
1 3. 0  
O v er all T y p e -I Err or C o ntr ol 
N ot a p plica ble.  


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
3 1  
1 4. 0  
V er si o n Hi st or y  
T a ble  3 . 
S A P Versi o n Hist or y S u m m ar y  
Versi o n  
D ate  
S u m m ar y  
1. 0  
0 5 Dece m ber 2 0 1 9  
Ori gi nal versi o n  
2. 0  
0 2  Fe br uar y  2 0 2 1  
Clarifie d wei g ht a n d B MI cate g ories i n de m o gra p hics.  
Re m o ve d Fra nce fr o m t he cate g ories f or Re gi o n i n de m o gra p hics.  
Clarifie d ite ms t o be s u m marize d f or dis p ositi o n t o ali g n wit h t he ne w 
sta n dar d ta ble.  
U p date d t he defi niti o n of c o nc o mita nt me dicati o n t o ali g n wit h t he 
m ost u p date d risa n kiz u ma b P S S A P.  
Clari fie d P CI f or safet y a nal ysis t o ali g n wit h t he m ost u p date d 
risa n kiz u ma b P S S A P. 
U p date d  t he defi niti o n of H y's La w t o ali g n wit h t he m ost u p date d 
risa n kiz u ma b P S S A P. 
A d de d details a b o ut h o w t o ha n dle missi n g data d ue t o C O VI D -1 9.  
A d de d as -o bser ve d a nal ysis  t o ha n dle missi n g data f or t he pri mar y a n d 
sec o n dar y efficac y e n d p oi nts as se nsiti vit y a nal ysis. 
A d de d pri mar y e n d p oi nt s u b gr o u p a nal ysis f or baseli ne wei g ht b y 
q uartiles.  
A d de d s u b gr o u p a nal ysis f or t he sec o n dar y efficac y e n d p oi nts ti me t o 
ac hie ve s P G A 0 / 1 a n d ti me t o ac hie ve s P G A 0. 
Clarifie d statistical a nal ysis t o be perf or me d f or sec o n dar y efficac y 
e n d p oi nts ti me t o ac hie ve s P G A 0/ 1 a n d ti me t o ac hie ve s P G A 0.  
U p date d S A P acc or di n g t o t he m ost u p date d S A P te m plate; a d de d 
esti ma n ds a n d t heir attri b utes  f or t he pri mar y a n d sec o n dar y e n d p oi nts 
i n Secti o n 2. 1 , Secti o n 8. 0 , Secti o n 9. 3 , a n d Secti o n 9. 4 . 
3. 0  
1 3  Ma y 2 0 2 1  
A d de d m ore details f or t he a nal ysis of ti me t o e ve nt e n d p oi nts i n 
Secti o n 8. 0 , Secti o n 9. 1 , a n d Secti o n 9. 4. 2 . 
Clarifie d t hat t here will be n o o ver writi n g d ue t o i nterc urre nt e ve nts f or 
as-o bser ve d a nal ysis.  
U p date d t he s u b gr o u p a nal ysis of s m o ki n g.  
U p date d t hat c ha n ges i n la b orat or y para meters will be ta b ulate d usi n g 
s hift ta bles base d o n t o xicit y gra des i nstea d of n or mal ra n ges. 
4. 0  
3 1  J ul y 2 0 2 3 
Secti o n  4. 0 : A d ded state me nt a b o ut e xcl u di n g a site fr o m all a nal yses 
d ue t o  n o n -c o m plia nce. 
 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
3 2  
1 5. 0  
R ef er e n c e s  
1.  
C o m m o n Ter mi n ol o g y Criteria f or A d vers e E ve nts ( C T C A E) v 4. 0 3.  A vail a ble 
fr o m:  htt ps://e vs. nci. ni h. g o v/ft p 1/ C T C A E/ C T C A E _ 4. 0 3/ C T C A E _ 4. 0 3 _ 2 0 1 0 -0 6 -
1 4 _ Q uic k Refere nce _ 5 x 7. p df . 2 0 1 0.  
 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
3 3  
A p pe n di x  A.  
Pr ot oc ol D e vi ati o ns  
T he n u m ber a n d p erce nta ge of s u bjects w h o re p ort e d at least o ne of t he f oll o wi n g 
pr ot oc ol de viati o n cate g ories will be pr o vi de d.  
● S u bject e ntere d i nt o t he st u d y e ve n t h o u g h s/ he di d n ot satisf y e ntr y criteri a . 
● S u bject de vel o pe d wit h dra wal criteria d uri n g t he st u d y a n d was n ot wit h dra w n . 
● S u bject recei v e d wr o n g treat me nt or i nc orrect d ose of st u d y . 
● S u bject t o o k pr o hi bite d c o nc o mita nt m e dicati o n. 
 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
3 4  
A p pe n di x  B.  
Defi niti o n of Are a of S afet y I nterest  
A rea of saf et y i nterest ( A SI) will be i de ntifie d usi n g t he f oll o wi n g searc h criteria:  
Are a of S afet y 
I nterest 
Se arc h Criteri a  
I ncl u de i n A E O ver vie w 
( Y/ N) 
M A C E  
A dj u dicate d ter ms will be i de ntifie d as descri be d 
i n P S S A P Ta ble  3  usi n g C E C A T a n d C E T E R M 
fr o m t he C E S D T M dataset. 
Y  
E xte n de d M A C E  
A dj u dicate d ter ms will be i de ntifie d as descri be d 
i n P S S A P Ta ble  3  (f or M A C E +) usi n g C E C A T 
a n d C E T E R M fr o m t he C E S D T M dataset.  
N  
Seri o us I nfecti o ns  
Seri o us A Es i n t he I nfecti o ns a n d I nfestati o ns 
S O C  
Y  
T u berc ul osis  
Acti ve T u berc ul osis C M Q (c o de  8 0 0 0 0 1 8 8 ) 
Y  
O p p ort u nistic 
I nfecti o ns 
O p p ort u nistic i nfecti o n e xcl u di n g t u berc ul osis 
a n d her pes z oster  C M Q (c o de 8 0 0 0 0 1 8 9 ) 
N  
F u n gal I nfecti o ns  
F u n gal i nfecti o ns C M Q (c o de 8 0 0 0 0 0 6 3)  
N  
Mali g na nt T u m o urs  
Narr o w  
Mali g na nt t u m o urs ( S M Q 2 0 0 0 0 1 9 4)  
Y  
N o n -mela n o ma S ki n 
Ca ncer ( N M S C)  
Br oa d  
S ki n mali g na nt t u m o urs ( S M Q 
2 0 0 0 0 2 0 4) e xcl u di n g ter ms i de ntifie d 
b y t he Mela n o ma C M Q (c o de 
8 0 0 0 0 1 1 9)  
N  
Mali g na nt T u m o urs 
e xcl u di n g N M S C  
' Mali g na nt T u m o urs e xcl u di n g N M S C' is 
i de ntifie d b y t he ' Mali g na nt T u m o urs' searc h 
e xcl u di n g ter ms i de ntifie d b y t he ' N o n -mela n o ma 
s ki n ca ncer ( N M SC)' searc h.  
Y  
H y perse nsiti vit y  
Narr o w  
H y perse nsiti vit y ( S M Q 2 0 0 0 0 2 1 4)  
Y –  seri o us e ve nts o nl y 
A dj u dicate d 
A na p h ylactic 
Reacti o n *  
A dj u dicate d ter ms will be i de ntifie d usi n g S D T M 
data (e. g., C E a n d P R d o mai ns).  
N  


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
3 5  
Are a of S afet y 
I nterest 
Se arc h Criteri a  
I ncl u de i n A E O ver vie w 
( Y/ N) 
He patic E ve nts  
Br oa d  
He patic fail ure, fi br osis a n d cirr h osis 
a n d ot her li ver da ma ge -relate d 
c o n diti o ns ( S M Q 2 0 0 0 0 0 1 3)  
N  
Br oa d  
He patitis, n o n -i nfecti o us ( S M Q 
2 0 0 0 0 0 1 0)  
N  
Br oa d  
C h olestasis a n d ja u n dice of he patic 
ori gi n ( S M Q 2 0 0 0 0 0 0 9)  
N  
Br oa d  
Li ver relate d i n vesti gati o ns, si g ns a n d 
s y m pt o ms ( S M Q 2 0 0 0 0 0 0 8)  
N  
Narr o w  
Li ver -relate d c oa g ulati o n a n d 
blee di n g dist ur ba nces 
( S M Q 2 0 0 0 0 0 1 5)  
N  
*  
E ve nts will b e i d e ntifie d f or a dj u dicati o n b y A n a p h ylactic Reacti o n S M Q Br o a d searc h as s p ecifie d i n t h e RI S A 
A A C C h arter.   
 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
3 6  
A p pe n di x  C.  
P ote nti all y Cli nic all y I m p ort a nt Criteri a f o r S afet y E n d p oi nts  
T he criteri a f or P ote ntiall y Cli nicall y I m p orta nt ( P CI) la b orat or y fi n di n gs are descri be d i n 
Ta ble C -1 a n d T a ble C -2, a n d t he P CI criteria f or vital si g n fi n di n gs are descri be d i n 
Ta ble C -3.  
T a ble C -1.  
Criteri a f or P ot e nti all y Cli nic all y I m p ort a nt He m at ol o g y V al ues  
He m at ol o g y V ari a bles  
U nits  
Defi niti o n of P ote nti all y Cli nic all y I m p ort a nt N CI 
C T C A E ( Versi o n 4) Gr a de 3 or Gre ater  
Ver y L o w  
He m o gl o bi n  
g/ d L  
< 8. 0  
Platelets c o u nt  
1 0 9/ L 
< 5 0. 0  
W B C c o u nt  
1 0 9/ L 
< 2. 0  
Ne utr o p hils  
1 0 9/ L 
< 1. 0  
L y m p h oc ytes  
1 0 9/ L 
< 0. 5  
N ote:  
A p ost -b aseli n e gra d e m ust b e m ore e xtre me t h a n t h e b aseli n e gra de t o b e c o nsi d ere d a p ote ntiall y cli nicall y 
i m p orta nt fi n di n g. 
 


 Risa n kiz u ma b  
M 1 9 -1 6 4 –  Statistical A nal ysis Pla n  
Versi o n 4 . 0 –  3 1  J ul y 2 0 2 3  
 
 
3 7  
T a ble C -2.  
Criteri a f or P ot e nti all y Cli nic all y I m p ort a nt C he mistr y V al ues  
C he mistr y V ari a bles  
U nits  
Defi niti o n of P ote nti all y Cli nic all y I m p ort a nt N CI 
C T C A E ( Versi o n 4) Gr a de 3 or Gre ater  
Ver y L o w  
Ver y Hi g h  
T B L  
mc m ol/ L  
 
> 3. 0 × U L N  
A L P  
U/ L  
 
> 5. 0 × U L N  
S G O T/ A S T  
U/ L  
 
> 5. 0 × U L N  
S G P T/ A L T  
U/ L  
 
> 5. 0 × U L N  
Al b u mi n  
g/ L  
< 2 0  
 
Gl uc ose  
m m ol/ L  
< 2. 2  
> 1 3. 9  
Tri gl yceri des  
m m ol/ L  
 
> 5. 7  
Creati ni ne  
mc m ol/ L  
 
> 3. 0 × U L N or > 3. 0 × baseli ne  
S o di u m  
m m ol/ L  
< 1 3 0  
> 1 5 5  
P otassi u m  
m m ol/ L  
< 3. 0  
> 6. 0  
Calci u m  
m m ol/ L  
< 1. 7 5  
> 3. 1  
C P K  
U/ L  
 
> 5. 0 × U L N  
T otal C h olester ol  
m m ol/ L  
 
> 1 0. 3 4  
G G T  
 
 
> 5. 0 × U L N  
N ote:  
A p ost -b aseli n e gra d e m ust b e m ore e xtre me t h a n t h e b aseli n e gra de t o b e c o nsi d ere d a p ote ntiall y cli nicall y 
i m p orta nt fi n di n g. 
 
T a ble C -3.  
Criteri a f or P ot e nti all y Cli nic all y I m p ort a nt Vit al Si g n V al ues  
Vit al Si g ns V ari a bles  
Criteri o n  
Defi niti o n of P ote nti all y Cli nic all y I m p ort a nt 
S yst olic Bl o o d Press ure 
( m m H g) 
L o w  
Val ue ≤ 9 0 m m H g a n d decrease ≥ 2 0 m m H g fr o m Baseli ne  
Hi g h  
Val ue ≥ 1 6 0 m m H g a n d i ncrease ≥ 2 0 m m H g fr o m Baseli ne  
Diast olic Bl o o d 
Press ure ( m m H g)  
L o w  
V al ue ≤ 5 0 m m H g a n d decrease ≥ 1 0  m m H g fr o m Baseli ne  
Hi g h  
Val ue ≥ 1 0 0 m m H g a n d i ncrease ≥ 1 0 m m H g fr o m Baseli ne  
 

Prot_000.pdf: 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
TABLE OF CONTENTS
1
SYNOPSIS
5
2
INTRODUCTION
8
2.1
BACKGROUND AND RATIONALE
8
2.2
BENEFITS AND RISKS TO SUBJECTS
9
3
STUDY OBJECTIVES AND ENDPOINTS
11
3.1
OBJECTIVES
11
3.2
PRIMARY ENDPOINT
11
3.3
SECONDARY ENDPOINTS
11
3.4
EXPLORATORY ENDPOINTS
12
3.5
SAFETY PARAMETERS
12
3.6
BIOMARKER RESEARCH
12
4
INVESTIGATIONAL PLAN
13
4.1
OVERALL STUDY DESIGN AND PLAN
13
4.2
DISCUSSION OF STUDY DESIGN
14
5
STUDY ACTIVITIES
15
5.1
ELIGIBILITY CRITERIA
15
5.2
CONTRACEPTION RECOMMENDATIONS
18
5.3
PROHIBITED MEDICATIONS AND THERAPY
19
5.4
PRIOR AND CONCOMITANT THERAPY
20
5.5
WITHDRAWAL OF SUBJECTS AND DISCONTINUATION OF STUDY
21
5.6
FOLLOW-UP FOR SUBJECT WITHDRAWAL FROM STUDY
22
5.7
STUDY DRUG
22
5.8
RANDOMIZATION/DRUG ASSIGNMENT
23
5.9
PROTOCOL DEVIATIONS
24
6
SAFETY CONSIDERATIONS
24
6.1
COMPLAINTS AND ADVERSE EVENTS
24
6.2
CARDIOVASCULAR ADJUDICATION COMMITTEE (CAC)
28
6.3
ANAPHYLAXIS ADJUDICATION COMMITTEE
28
Page 2 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
7
STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
29
7.1
STATISTICAL AND ANALYTICAL PLANS
29
7.2
DEFINITION FOR ANALYSIS POPULATION
29
7.3
STATISTICAL ANALYSES FOR EFFICACY
29
7.4
STATISTICAL ANALYSES FOR SAFETY
31
7.5
INTERIM ANALYSIS
31
8
ETHICS
31
8.1
INDEPENDENT ETHICS COMMITTEE/INSTITUTIONAL REVIEW BOARD (IEC/IRB)
31
8.2
ETHICAL CONDUCT OF THE STUDY
32
8.3
SUBJECT CONFIDENTIALITY
32
9
SOURCE DOCUMENTS AND CASE REPORT FORM COMPLETION
32
10
DATA QUALITY ASSURANCE
32
11
COMPLETION OF THE STUDY
33
12
REFERENCES
33
LIST OF TABLES
TABLE 1.
IDENTITY OF INVESTIGATIONAL PRODUCT
23
TABLE 2.
AREAS OF SAFETY INTEREST
27
LIST OF FIGURES
FIGURE 1.
STUDY SCHEMA
14
FIGURE 2.
STATISTICAL PRECISION AS MEASURED BY HALF-WIDTH OF 95% CONFIDENCE INTERVAL VERSUS 
VARYING SAMPLE SIZE
30
LIST OF APPENDICES
APPENDIX A.
STUDY SPECIFIC ABBREVIATIONS AND TERMS
36
APPENDIX B.
RESPONSIBILITIES OF THE INVESTIGATOR
39
Page 3 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX C.
LIST OF PROTOCOL SIGNATORIES
40
APPENDIX D.
ACTIVITY SCHEDULE
41
APPENDIX E.
OPTIONAL BIOMARKER RESEARCH SAMPLE ACTIVITY TABLE
45
APPENDIX F.
PROTOCOL SUMMARY OF CHANGES
46
APPENDIX G.
OPERATIONS MANUAL
48
Page 4 of 89
 








STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
2 INTRODUCTION
2.1 Background and Rationale
Why Is This Study Being Conducted?
Psoriasis is a chronic debilitating immune-mediated disease characterized by marked inflammation of 
the skin that results in thick, erythematous, scaly plaques involving the skin.  In most developed 
countries, prevalence is between 1.5 and 5%.1  Twenty-five percent of patients have moderate to severe 
disease with a considerable negative impact on psychosocial and economic status.2  It is increasingly 
recognized that psoriasis is more than a superficial disease, with up to 30% of patients having joint 
involvement and a high correlation between psoriasis and obesity, diabetes, depression, metabolic 
syndrome, and cardiovascular disease.3  While the majority of mild psoriasis patients are managed with 
topical therapies, those with moderate or severe and/or refractory disease usually require phototherapy 
and/or systemic therapy.
Oral systemic agents provide modest efficacy; therefore, patients are increasingly being treated with 
biologic agents, such as Tumor Necrosis Factor (TNF)-alpha inhibitors (etanercept or adalimumab), the 
interleukin (IL)-12/23 inhibitor (ustekinumab),4 and IL-17A inhibitors (secukinumab and ixekizumab).  
Ustekinumab, a monoclonal antibody (mAb) targeting the common p40 subunit of IL-12 and IL-23, was 
approved for the treatment of psoriasis and psoriatic arthritis (PsA) in 2009, and for Crohn's disease in 
2016.
Secukinumab and ixekizumab are anti-IL-17A antibodies and have been approved by the United States 
(US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment 
of psoriasis in 2015 and 2016, respectively.  In addition, other recently approved systemic agents for the 
treatment of psoriasis include an IL-17RA inhibitor (brodalumab), IL-23p19 inhibitors, guselkumab and 
tildrakizumab.  Mirikizumab, another IL-23 inhibitor, is still under investigation.
While the clinical efficacy of ustekinumab indicates a role for both IL-12 and IL-23 in the pathogenesis of 
psoriasis,5 more recent data suggest that IL-23 is disproportionately involved in the maintenance of 
chronic psoriasis.6  IL-23 is thought to be involved in the pathophysiology of psoriasis via induction and 
maintenance of Th17 type cells, and other IL-23 responsive cells.  This is supported by recent clinical 
data indicating that monoclonal antibodies that block IL-17A (the cytokine produced by Th17 cells), IL-
17RA, and direct blockade of IL-23 with IL-23p19 inhibitors, have high efficacy in psoriasis.5,7-9
There is still clinical need for increased efficacy as the most effective anti-TNF and anti-IL-12/23 agents 
provide approximately 75% improvement in psoriasis in about 50 to 80% of patients and these 
responses can be lost over time.  While the anti-IL-17A, -IL-17RA, and -IL-23p19 agents 
(i.e., secukinumab, ixekizumab, brodalumab and guselkumab) may provide better efficacy than anti-TNF 
therapies and ustekinumab, they require monthly or every other month injections.5,7-9
Risankizumab is approved for use in moderate to severe chronic plaque psoriasis in the United States 
(US), the European Union (EU), Japan, Canada, Brazil, and Switzerland, with additional global reviews of 
marketing applications ongoing.  Clinical studies are ongoing evaluating risankizumab for use in the 
treatment of Crohn's disease, ulcerative colitis, PsA, hidradenitis suppurativa, and atopic dermatitis.
Page 8 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Risankizumab is a humanized mAb of the immunoglobin (Ig) G1 subclass directed towards IL-23p19.  The 
antibody (Ab) has been engineered to reduce Fcγ receptor and complement binding and potential 
charge heterogeneity.  Risankizumab binds with high affinity to human IL-23.
Today there are multiple treatments with different modes of action available to treat plaque psoriasis 
efficiently.  The risankizumab clinical program assessed the efficacy versus placebo and other commonly 
used biological therapies such as adalimumab and ustekinumab up to 1 year.  Risankizumab showed 
high levels of sustained clearance in these clinical trials.  A head-to head randomized controlled trial 
(RCT) is ongoing to compare risankizumab versus secukinumab up to 1 year.  Ixekizumab is another 
approved IL-17A inhibitor.  No head-to-head data are currently available.
Important evidence is lacking on the efficacy and safety of patients with suboptimal response on 
secukinumab or ixekizumab switching to risankizumab and the impact this switch has on patient's 
quality of life and treatment satisfaction.
This study aims to evaluate whether those suboptimal responders on secukinumab or ixekizumab 
benefit significantly from a switch to risankizumab with regards to skin symptoms, as well as quality of 
life and psoriasis symptoms.
Clinical Hypothesis
Risankizumab will significantly improve skin symptoms and quality of life in subjects with moderate-to-
severe plaque psoriasis who had a suboptimal response to secukinumab or ixekizumab.
2.2 Benefits and Risks to Subjects
Risankizumab is a monoclonal antibody antagonist specific for IL-23, which has been implicated in the 
pathophysiology of immune-mediated inflammatory diseases.  Non-clinical studies have shown that 
risankizumab has no inhibitory effects on IL-12, the inhibition of which has been associated with 
increased risk of serious infections.10,11  Selective IL-23 inhibition may not increase risk of serious 
infection, including mycobacterial infections.12  Despite the availability of various psoriasis therapies, 
many subjects still do not respond adequately to these treatments, or gradually lose response over time.  
In Phase 1 and Phase 2 studies of risankizumab in subjects with psoriasis, the majority of subjects 
receiving risankizumab achieved 90% improvement of their disease and risankizumab was well 
tolerated.  Recently, positive top-line results were observed from 3 pivotal Phase 3 clinical trials 
evaluating risankizumab compared to ustekinumab, placebo, or adalimumab, for the treatment of 
subjects with moderate to severe plaque psoriasis.13-15  After 16 weeks of treatment, all 3 studies met 
their co-primary endpoints of at least a 90% improvement in the Psoriasis Area Severity Index (PASI 90) 
and a static physician global assessment (sPGA) score of clear or almost clear (sPGA 0 or 1) for 
risankizumab (150 mg) treatment versus ustekinumab, placebo and adalimumab.13-15  The safety profile 
was consistent with that observed in Phase 2 clinical trials, with no important identified risks for 
risankizumab.  As with many immune modulating agents, risankizumab may impair immune function 
resulting in a risk of infection.  This will be monitored by collection of all adverse events (AEs) during the 
treatment and observation periods.  In addition, subjects with clinically important active infection will 
not be included in the study.
Page 9 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
In the Phase 3 clinical trial program for risankizumab, up to 57% of subjects had prior exposure to 
biologics including IL-17 inhibitors.  Consistent PASI 90 responses were observed regardless of prior 
psoriasis treatment, including those who were bio-naïve or who reported prior biologic exposure to 
IL-17 inhibitors at Week 16 (74 - 77%) and Week 52 (78 - 81%).16  Even in subjects who reported failing 
prior biologics (including those with primary or secondary non-response), risankizumab treatment 
resulted in high levels of PASI 90 response.  In terms of safety, the Phase 3 clinical trials ranged from 
30% prior biologic exposure in UltIMMa –1 and –2 to 57% in IMMhance and there were no differences 
observed in the safety profile across the trials.  Furthermore, no additional safety concerns were 
identified in the 270 subjects who switched from adalimumab to risankizumab without a washout 
period in the IMMvent study.
This study is required to learn more about the potential treatment effect of risankizumab in adult 
subjects with moderate to severe plaque psoriasis who have been treated with labeled dose of 
secukinumab or ixekizumab for at least 6 months and are experiencing a sub-optimal response.
As with many immune modulating agents, risankizumab may impair immune function, resulting in a risk 
of infection.  This will be monitored by collection of all AEs during the treatment and observation 
periods.  In addition, subjects with active infection will not be included in the study.
Subjects with a positive QuantiFERON®-TB (or interferon gamma release assay [IGRA] equivalent)/TB
skin test result for TB must fulfill entry criteria as specified in Section 5.1 of this protocol.  IL-23 inhibition 
is not known to increase the risk of TB infection or impair the response to TB infection in animal 
models.17,18  Thus, subjects with positive QuantiFERON®-TB Gold testing (or IGRA equivalent)/TB skin 
test who have latent TB (defined by local guidelines) are not required to be treated (unless 
recommended by local guidelines or by investigator judgement) with anti-TB therapy prior to receiving 
risankizumab but should be carefully monitored for any sign of TB reactivation.
Published literature indicates that inhibition of IL-23 is unlikely to increase the risk for cancer.  
Expression of IL-23 is increased in human tumors.19-21  Moreover, preclinical data have demonstrated a 
beneficial effect of IL-23 p19 inhibition in animal models, both for pre-existing and tumor-induction 
models.22  While there is not enough clinical information at this time to rule out a risk of cancer with 
risankizumab, this risk is considered small.
Although rare, a potential for hepatic AEs is under constant surveillance by sponsors and regulators.  
Therefore, this study requires timely detection, evaluation, and follow-up of laboratory alterations in 
selected liver laboratory parameters to ensure subjects' safety.
Increases in major adverse cardiovascular (MACE) events, including myocardial infarction, 
cerebrovascular accident, and cardiovascular death, were initially reported with anti-IL-12/23 agents, 
such as ustekinumab, have not been observed in longer term studies.  While the likelihood of increased 
MACE is small, all suspected cardiovascular or cerebrovascular events (serious or non-serious) observed 
in this study will be adjudicated by an independent Cardiovascular Adjudication Committee (CAC).  The 
committee will remain blinded to treatment allocation (Section 6.2).
Local reactions to subcutaneously (SC) administered biologic therapies are usually limited to redness, 
swelling, or induration at the injection site.  Manifestations of systemic hypersensitivity reactions 
include anaphylaxis, pruritus, hypotension, and respiratory distress.  Both local and systemic 
hypersensitivity reactions are readily detectable, transient in nature, and manageable with standard 
Page 10 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
medical treatment.  Subjects will be closely monitored during study drug administration.  An 
independent Anaphylaxis Adjudication Committee (AAC) will adjudicate observed systemic 
hypersensitivity and anaphylactic events.  The AAC will remain blinded to treatment allocation 
(Section 6.3).
There are no important identified risks for risankizumab.23
In conclusion, the benefit-risk profile of risankizumab is considered appropriate for this stage of clinical 
development.15  Based on data from the integrated safety analyses, risankizumab is safe and well-
tolerated and demonstrates a favorable benefit-risk profile.
For further details, please see findings from completed studies, including safety data in the risankizumab 
Investigator Brochure.23
Given that eligible subjects for inclusion are those who have been on either secukinumab or ixekizumab 
treatment for at least 6 months and are experiencing a sub-optimal response, physicians in routine 
practice would switch those patients to another biologic to improve skin symptoms and patient's quality 
of life.  Current international guidelines for the treatment of moderate to severe psoriasis adopted "skin 
clearance" as a new treatment goal, as newer biologic treatments are able to provide this clearance to a 
majority of patients, which directly links to the improvement of patient's quality of life and 
workability.24-26
In view of the Coronavirus Disease – 2019 (COVID-19) pandemic, the benefit-risk profile of various 
immunomodulatory therapies on COVID-19 is being evaluated based on real world and clinical trial data.  
At this time, the effects of risankizumab on the course of COVID-19 are not well defined.
3 STUDY OBJECTIVES AND ENDPOINTS
3.1 Objectives
The objective of this study is to evaluate the efficacy and safety of switching to risankizumab in subjects 
with moderate to severe plaque psoriasis, who have been treated with labeled dose of secukinumab or 
ixekizumab for at least 6 months and are experiencing a sub-optimal response.  Suboptimal response is 
defined as a sPGA 2 or 3, and a Body Surface Area (BSA) 3% - < 10% after at least 6 months treatment 
with secukinumab or ixekizumab.
3.2 Primary Endpoint
The primary endpoint is the proportion of subjects achieving sPGA 0/1 at Week 16.
3.3 Secondary Endpoints
The secondary endpoints are:

The proportion of subjects achieving a sPGA clear response (sPGA 0) at Week 16;

The proportion of subjects achieving a Dermatology Life Quality Index (DLQI) 0 or 1 at Week 16;
Page 11 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

The proportion of subjects achieving a Psoriasis Symptoms Scale (PSS) 0 at Week 16; 

The proportion of subjects achieving a sPGA 0/1 at Week 52;

The proportion of subjects achieving a sPGA 0 at Week 52;

The proportion of subjects achieving a DLQI 0/1 at Week 52;

The proportion of subjects achieving a PSS 0 at Week 52;

Time to achieve sPGA 0/1;

Time to achieve sPGA 0; 
3.4 Exploratory Endpoints

The change from baseline in DLQI by visit; 

Treatment satisfaction as measured by the Treatment Satisfaction Questionnaire for Medication 
Version 9 (TSQM-9) at Baseline (Week 0) and at each visit;

The proportion of subjects achieving absolute Psoriasis Area Severity Index (PASI) by visit 
(e.g., PASI ≤ 1, ≤ 3);

The change from baseline in PASI by visit;

The proportion of subjects achieving BSA ≤ 1%, ≤ 3%, by visit;

The change from baseline in BSA by visit;

The change from baseline in BSA (%) × sPGA by visit;

The proportion of subjects achieving sPGA 0/1 at Week 16 and maintained sPGA 0/1 response at 
Week 52; 
3.5 Safety Parameters
Safety evaluations include AE monitoring, physical examinations, vital sign measurements, 
electrocardiograms (ECG), and clinical laboratory testing (hematology, chemistry and urinalysis) as a 
measure of safety and tolerability for the entire study duration.
3.6 Biomarker Research
For subjects who consent, optional samples (whole blood, serum, plasma and tissue) will be collected at 
specific visits as listed in the Optional Biomarker Research Sample Activity Schedule (Appendix E) to 
evaluate known and or novel disease related or drug related biomarkers.  Types of biomarkers may 
include nucleic acids, proteins, lipids, and/or metabolites.  The objective of research is to analyze 
samples for biomarkers that will help to understand psoriasis, related conditions, response to treatment 
with risankizumab or similar compounds.  Research on samples collected in Germany will be limited to 
psoriasis and risankizumab.  Research may also include changes in epigenetics, gene expression, and 
Page 12 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
proteomics that may associate with psoriasis, related conditions, or the subject's response to treatment.  
This research is exploratory in nature and the results may not be included with the clinical study report.
Blood Samples
Blood samples will be collected for genetic, transcriptomic and proteomic testing as per the Optional 
Biomarker Research Sample Activity Table (Appendix E) and as described in the laboratory manual.
Skin Biopsy and Skin Tapes
Lesional skin punch biopsies and tape strip samples should be collected at the Baseline (Week 0) and 
Week 16 visits.
Skin punch biopsy and tape strip samples will be obtained for investigations including, but not limited to 
epigenetics, transcriptomics, proteomics, immunohistochemistry (IHC), and targeted investigations.
4 INVESTIGATIONAL PLAN
4.1 Overall Study Design and Plan
This is a Phase 3b, global, interventional, multicenter, open-label, single-arm study examining the effect 
of risankizumab 150 mg administered at Week 0, Week 4, and then every 12 weeks (q12w) thereafter 
for 52 weeks in adult subjects with moderate to severe plaque psoriasis who have been treated with 
labeled dose of secukinumab or ixekizumab for at least 6 months and are experiencing a sub-optimal 
response.  The subject population must be on the labeled secukinumab or ixekizumab for at least 6 
months and are switched to risankizumab at Baseline (Week 0) (within ± 1 week of next scheduled dose 
for secukinumab or ixekizumab).  Suboptimal response is defined as a sPGA 2 or 3 and a BSA 3% - < 10%.
The study is designed to enroll 250 subjects.
Eligible subjects will receive 2 injections of active risankizumab 75 mg (150 mg total dosage) SC at Weeks 
0 and 4, and then q12w until the last dose at Week 40.
The study duration will be up to 64 weeks.  The study comprises a 30-day Screening Period, a 52-week 
open-label study period, and a 20-week follow-up period (after Week 40).  The 52-week open label 
period consists of an initial phase (Weeks 0 – 16) and a maintenance phase (Weeks 16 – 52).  The follow-
up period consists of a follow-up phone call 20 weeks after the last injection of study drug (at Week 40).
The study schematic is shown in Figure 1.  Further details regarding study procedures are in the 
Operations Manual (Appendix G).
Page 13 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Figure 1.
Study Schema
BSA = body surface area; sPGA = Static Physician Global Assessment
4.2 Discussion of Study Design
Choice of Control Group
There is no control group for this open-label study.  The study design is consistent with current 
standards investigating the efficacy and safety of a new treatment in psoriasis.  As subjects have 
experienced a suboptimal psoriasis response for 6 months or longer, the single-arm design was chosen 
in order to prevent subjects from remaining on sub-optimal treatment by switching to risankizumab, 
which provides an opportunity to benefit subject's skin symptoms and quality of life outcomes.  This 
reflects routine clinical practice, where patients are switched to another biologic without any wash-out 
period.
Appropriateness of Measurements
Standard statistical, clinical, and laboratory procedures will be utilized in this study.  All efficacy 
measurements in this study are standard for assessing disease activity in subjects with moderate to 
severe plaque psoriasis.  All clinical and laboratory procedures in this study are standard and generally 
accepted.  All patient-reported outcomes (PRO) measures in this study were adequately developed and 
validated to measure specific concepts of interest relevant to this study.
Suitability of Subject Population
Subjects must have a previous diagnosis of moderate to severe plaque psoriasis and have to be eligible 
for biologic therapy prior to receiving secukinumab.  To qualify for this study, subjects have been treated 
with a labeled dose of secukinumab or ixekizumab for at least 6 months and are experiencing a sub-
optimal response at time of Screening and Baseline visits, defined by a sPGA of 2 or 3 and a BSA of 3% -
< 10% at Baseline visit.
Selection of Doses in the Study
The risankizumab dose of 150 mg SC selected for this study is the same as the approved labeled dose in 
the treatment of moderate to severe plaque psoriasis tested in global Phase 3 studies in subjects with 
Page 14 of 89
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
moderate to severe plaque psoriasis.  The risankizumab 150 mg SC dose has been shown to be 
efficacious with an acceptable safety profile and considered appropriate for the treatment of subjects 
with plaque psoriasis.
5 STUDY ACTIVITIES
5.1 Eligibility Criteria
Subjects must meet all of the following criteria in order to be included in the study.
1. Subjects or their legally authorized representative must voluntarily sign and date an informed 
consent, approved by an independent ethics committee (IEC)/institutional review board (IRB), 
prior to the initiation of any screening or study-specific procedures.
2. Employees of the sponsor and/or study sites and their family members may not be enrolled in 
this study.
Demographic and Laboratory Assessments
3. Adult male or female, at least 18 years old (subjects must also meet the legal age of majority 
per local law).
4. Laboratory values meeting the following criteria within the screening period prior to the 
first dose of study drug:

Serum aspartate transaminase (AST) < 2 × upper limit of normal (ULN);

Serum alanine transaminase (ALT) < 2 × ULN;

Serum total bilirubin ≤ 2.0 mg/dL; except for subjects with isolated elevation of indirect 
bilirubin relating to Gilbert syndrome;

Total white blood cell (WBC) count > 3,000/µL;

Absolute neutrophil count (ANC) > 1,500/µL;

Platelet count > 100,000/µL;

Hemoglobin > 10.0 g/dL (100 g/L).
Subject History
5. Subject is judged to be in good general health, as determined by the investigator based upon 
the results of a medical history, physical examination, laboratory profile, and a 12-lead 
electrocardiogram (ECG) performed during the Screening period;
6. Subject must not have a history of erythrodermic psoriasis, generalized or localized pustular 
psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate 
psoriasis;
Page 15 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
7. Subject must not have a history of active skin disease other than plaque psoriasis that could 
interfere with the assessment of plaque psoriasis;
8. Subject must not have a history of clinically significant (per investigator's judgment) drug or 
alcohol abuse within the last 6 months;
9. Subject must not have a history of an allergic reaction or significant sensitivity to constituents 
of the study drug (and its excipients) and/or other products in the same class;
10. Subject must not have had major surgery performed within 12 weeks prior to randomization 
or planned during the conduct of the study (e.g., hip replacement, aneurysm removal, stomach 
ligation);
11. No known active SARS-CoV-2 infection.  If a subject has signs/symptoms suggestive of 
SARS-CoV-2 infection, they should undergo molecular (e.g., polymerase chain reaction [PCR]) 
testing to rule out SARS-CoV-2 infection.  In addition, if based on the answers to the SARS-CoV-2 
Infection Risk Assessment Tool the site considers the subject currently at risk for developing 
SARS-CoV-2 infection, then the subject should either be tested or advised to come back for 
study screening after 14 days.  Subjects who do not meet SARS-CoV-2 infection eligibility criteria 
must be screen failed and may only rescreen after they meet the following SARS-CoV-2 infection 
viral clearance criteria:

At least 14 days since first PCR test result have passed in asymptomatic patients or 14 days 
since recovery, defined as resolution of fever without use of antipyretics and improvement 
in symptoms.
12. Subject must not have evidence of:

Hepatitis B (HBV) or hepatitis C (HCV) infection, defined as:

HBV:  Hepatitis B surface antigen (HBs Ag) positive (+) test or detected sensitivity on the 
HBV deoxyribonucleic acid (DNA) PCR qualitative test for subjects who are hepatitis B 
core antibody (HBc Ab) positive (+) (and for hepatitis B surface antibody [HBs Ab] 
positive [+] subjects where mandated by local requirements);

HCV:  HCV ribonucleic acid (RNA) detectable in any subject with anti-HCV antibody 
(HCV Ab);

Human immunodeficiency virus (HIV), defined as confirmed positive anti-HIV antibody 
(HIV Ab) test.  Note:  In case a screened subject has a confirmed positive HIV Ab test, 
eligibility criterion 5 should be selected in electronic case report form (eCRF) for 
documentation of screening failure;

Active TB.  For subjects with latent TB, please see Section 3.12 of the Operations Manual.

Active systemic infection/Clinically important infection during the last 2 weeks prior to 
Baseline (Week 0) Visit as assessed by the investigator.
13. Subject must not have any of the following medical diseases or disorders:

Recent (within past 6 months) cerebrovascular accident or myocardial infarction; 

History of an organ transplant which requires continued immunosuppression; 
Page 16 of 89
 
  
 
 
 
 
 
 
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Active or suspected malignancy or history of any malignancy within the last 5 years except 
for successfully treated non-melanoma skin cancer (NMSC) or localized carcinoma in situ of 
the cervix.
14. Subject must not have a concurrent clinically significant medical condition other than the 
indication being studied or any other reason that the investigator determines would interfere 
with the subject's participation in this study, would make the subject an unsuitable candidate 
to receive study drug, or would put the subject at risk by participating in the study.
Disease Activity
15. Subject must have been previously diagnosed moderate to severe chronic plaque psoriasis 
prior to initiation of secukinumab or ixekizumab treatment;
16. Subject must have been on labeled secukinumab or ixekizumab treatment for at least 
6 months and are experiencing a sub-optimal response at time of Screening and Baseline 
(Week 0) visits; treated with 300 mg secukinumab by SC injection at Weeks 0, 1, 2, 3, and 4 
followed by 300 mg every 4 weeks for at least 6 months total treatment or treated with 160 mg 
ixekizumab at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then maintenance 
dosing of 80 mg every 4 weeks; 
17. Subject must have 3% - < 10% BSA psoriasis involvement, sPGA score of 2 or 3 at Screening 
and Baseline (Week 0) Visits;
18. Subject must be eligible for continued biologic therapy as assessed by the investigator.
Contraception
19. For all females of child-bearing potential; a negative serum pregnancy test at the Screening 
Visit and a negative urine pregnancy test at Baseline (Week 0) prior to the first dose of study 
drug is required;
20. Female subjects of childbearing potential must practice at least 1 protocol-specified method 
of birth control, that is effective from Study Day 0 through at least 140 days (20 weeks or as 
guided by the local risankizumab label [if approved], whichever is longer) after the last dose of 
study drug (local practices may require 2 methods of birth control).  Female subjects of non-
childbearing potential do not need to use birth control;
21. Female subjects may not be pregnant, breastfeeding, or considering becoming pregnant
during the study or for approximately 140 days (20 weeks or as guided by the local risankizumab 
label [if approved], whichever is longer) after the last dose of study drug.
Concomitant Medications (Prior Medication Restrictions)
22. Subject must not have prior exposure to risankizumab or any IL-23 inhibitors (guselkumab, 
tildrakizumab, mirikizumab);
23. Subject must not be currently using any approved psoriasis therapy other than secukinumab 
or ixekizumab for at least 6 months;
Page 17 of 89
 
  
 
 
 
 
 
 
 
 
 
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
24. Subject must not be using topical psoriasis treatments, including but not limited to 
corticosteroids, anthralin, calcipotriene, topical vitamin D derivatives, retinoids, urea, alpha- or 
beta-hydroxyl acids, and medicated shampoos (for example those that contain > 3% salicylic 
acid, corticosteroids, coal tar or vitamin D3 analogues) for at least 2 weeks prior to baseline;
25. Subject must not have received any live viral or bacterial vaccine within 6 weeks prior to the 
first dose of study drug or expect the need for live vaccine administration during study 
participation including at least 140 days (20 weeks or as guided by the local risankizumab label 
[if approved], whichever is longer) after the last dose of study drug;
26. Subject must not have been treated with any investigational drug within 30 days or 
5 half-lives of the drug (whichever is longer) prior to the first dose of study drug or be currently 
enrolled in another interventional clinical study.
5.2 Contraception Recommendations
Contraception@Abbvie.com
Contraception Requirements for Females
Subjects must follow the following contraceptive guidelines as specified:

Females, Non-Childbearing Potential
Females do not need to use birth control during or following study drug treatment if considered 
of non-childbearing potential due to meeting any of the following criteria:

Postmenopausal, age > 55 years with no menses for 12 or more months without an 
alternative medical cause.

Postmenopausal, age ≤ 55 years with no menses for 12 or more months without an 
alternative medical cause AND a follicle-stimulating hormone (FSH) level > 40 IU/L.

Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy, or 
hysterectomy).

Females, of Childbearing Potential

Females of childbearing potential must avoid pregnancy while taking study drug(s) and for 
at least 140 days (20 weeks or as guided by the local risankizumab label [if approved], 
whichever is longer) after the last dose of study drug.  Females must commit to one of the 
following methods of birth control:

Combined (estrogen and progestogen containing) hormonal birth control (oral, 
intravaginal, transdermal, injectable) associated with inhibition of ovulation initiated at 
least 30 days prior to study Baseline (Week 0).

Progestogen-only hormonal birth control (oral, injectable, implantable) associated with 
inhibition of ovulation initiated at least 30 days prior to study Baseline (Week 0).

Bilateral tubal occlusion/ligation (can be via hysteroscopy, provided a 
hysterosalpingogram confirms success of the procedure).
Page 18 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Intrauterine device (IUD).

Intrauterine hormone-releasing system (IUS).

Vasectomized partner (provided the partner has received medical confirmation of the 
surgical success of the vasectomy and is the sole sexual partner of the trial subject).

Practice true abstinence, defined as:  Refraining from heterosexual intercourse when 
this is in line with the preferred and usual lifestyle of the subject (periodic abstinence 
[e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are 
not acceptable).
Contraception recommendations related to use of concomitant therapies prescribed should be based on 
the local label.
5.3 Prohibited Medications and Therapy
During the study, no other biologic treatment other than risankizumab is allowed.
Therapies including but not limited to the following biologic therapies are prohibited medications during 
the study:  
1.
Any other approved biologic therapy to treat moderate to severe plaque psoriasis, other than 
risankizumab:

Adalimumab, infliximab, certolizumab pegol and biosimilar versions;

Etanercept and biosimilar versions;

Secukinumab, ixekizumab, brodalumab, and other IL-17 inhibitors;

Ustekinumab, efalizumab, guselkumab, tildrakizumab, mirikizumab, and other IL-23 
inhibitors.
2.
Systemic (including oral) non-biologic therapy to treat psoriasis or possibly benefit psoriasis, 
including but not limited to cyclosporine, corticosteroids, methotrexate, oral retinoids, 
apremilast, and fumaric acid derivatives.
3.
Phototherapy treatment, laser therapy, tanning booth, or extended sun exposure that could 
affect disease severity or interfere with disease assessments.
4.
Topical psoriasis treatments, including but not limited to corticosteroids, anthralin, 
calcipotriene, topical vitamin D derivatives, retinoids, urea, alpha- or beta-hydroxyl acids, and 
medicated shampoos (for example those that contain > 3% salicylic acid, corticosteroids, coal tar 
or vitamin D3 analogues).
5.
Treatment with an experimental biologic or non-biologic drug for psoriasis.
6.
Live attenuated vaccines are not permitted during study participation and including up to 
140 days (20 weeks or as guided by the local risankizumab label [if approved], whichever is 
longer) after the last dose of study drug.  Examples of live attenuated vaccines include, but are 
not limited to, the following:
Page 19 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Bacille Calmette-Guérin (BCG)

Zoster vaccine live (Zostavax)

Measles-mumps-rubella or measles mumps rubella varicella

Monovalent live attenuated influenza A (intranasal)

Oral polio vaccine

Rotavirus

Seasonal trivalent live attenuated influenza (intranasal)

Smallpox

Oral typhoid vaccine

Varicella (chicken pox)

Yellow fever
Treatment with any investigational drug within the past 30 days or 5 half-lives of the drug (whichever is 
longer) prior to the first dose of study drug or is currently enrolled in another clinical study.
Washout Period of Biologic Therapies
Subjects must have discontinued biologic therapies prior to the first dose of study drug as specified in 
the washout procedures (Protocol Section 5.1 Concomitant Medications [Prior Medication Restrictions]).  
At a minimum of 6 months prior to screening, no other biologics other than secukinumab or ixekizumab 
are allowed.  For all other biologic therapies, the required washout period is at least five times the mean 
terminal elimination half-life of the medication prior to the first dose of study drug.   
5.4 Prior and Concomitant Therapy
Stable doses of other concomitant therapies for chronic conditions, for which neither the condition nor 
the treatment are judged to exclude the subject from participation, are permissible.  All concomitant 
medications should be carefully evaluated by the investigator.
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, and/or 
herbal supplements) that the subject has received from 4 weeks prior to screening or receives during 
the study must be recorded along with the reason for use; date(s) of administration, including start and 
end dates; and dosage information including dose, route, and frequency on the appropriate electronic 
case report form (eCRF).
A detailed history of all prior biologic use will be obtained in the electronic data capture (EDC) system.
Any questions regarding concomitant or prior therapy should be raised to the AbbVie emergency 
contact.  Information regarding potential drug interactions with risankizumab can be located in the 
risankizumab Investigator's Brochure.23
Page 20 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Subjects must be able to safely discontinue any prohibited medications 5 half-lives or 4 weeks prior to 
initial study drug administration.  Subjects must be consented for the study prior to discontinuing any 
prohibited medications for the purpose of meeting study eligibility.
5.5 Withdrawal of Subjects and Discontinuation of Study
AbbVie may terminate this study prematurely, either in its entirety or at any site.  The investigator may 
also stop the study at his/her site if he/she has safety concerns.  If AbbVie terminates the study for 
safety reasons, AbbVie will promptly notify the investigator.
A subject may voluntarily withdraw or be withdrawn from the study drug and/or study at any time for 
reasons including, but not limited to, the following:

The subject requests withdrawal from the study.

The investigator believes it is in the best interest of the subject.

Clinically significant abnormal laboratory results or AEs, which rule out continuation of the study 
drug, as determined by the investigator or the AbbVie TA MD.

Subject is non-compliant with TB prophylaxis (if applicable) or develops active TB at any time 
during the study.

Malignancy, except for localized NMSC or carcinoma in-situ of the cervix, where discontinuation 
is at the discretion of the Investigator.

The subject becomes pregnant while on study drug.

Eligibility criteria violation was noted after the subject started study drug and continuation of 
the study drug would place the subject at risk.

Introduction of prohibited medications or dosages when continuation of the study drug would 
place the subject at risk.

Subject is significantly noncompliant with study procedures, which would put the subject at risk 
for continued participation in the trial.

Post-Baseline occurrence of one or more of the following hepatic test abnormalities (confirmed 
on a second separate sample):

ALT or AST > 8 × ULN;

ALT or AST > 5 × ULN for more than 2 weeks;

ALT or AST > 3 × ULN and Total Bilirubin > 2 × ULN or international normalized ratio [INR] 
> 1.5;

ALT or AST > 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant 
pain or tenderness, fever, rash, and/or eosinophilia (> 5%).
Page 21 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
COVID-19 Pandemic-Related Acceptable Protocol Modification
During the COVID-19 pandemic, it has been necessary to employ mitigation strategies to enable the 
investigator to ensure subject safety and continuity of care.  Acceptable mitigation strategies are 
identified and included in the Operations Manual in Appendix G.
The investigator should contact the sponsor medical contact before discontinuing a subject from the 
study for a reason other than "planned per protocol," to ensure all acceptable mitigation steps have 
been explored.
Refer to the Operations Manual in Appendix G for details on how to handle study activities/procedures.
5.6 Follow-Up for Subject Withdrawal from Study
Discontinuation of Study Drug and Continuation of Study Participation
To minimize missing data for efficacy and safety assessments, subjects who prematurely discontinue 
study drug treatment should continue to be followed for all regularly scheduled visits, unless subjects 
have decided to discontinue the study participation entirely (withdrawal of informed consent).  Subjects 
should be advised on the continued scientific importance of their data even if they discontinue 
treatment with study drug early.
Premature Discontinuation of Study (Withdrawal of Informed Consent)
If a subject prematurely discontinues study participation (withdrawal of informed consent), the 
procedures outlined for the Premature Discontinuation visit (PD visit) should be completed as soon as 
possible, preferably within 2 weeks.  In addition, if subject is willing, a follow-up phone call 140 days 
after the last dose of study drug may be completed to ensure all treatment-emergent adverse events 
(TEAEs)/serious adverse events (SAEs) have been resolved.
For subjects to be considered lost to follow-up, reasonable attempts must be made to obtain 
information on the subject's final status.  At a minimum, 2 telephone calls must be made, and 1 certified 
letter must be sent and documented in the subject's source documentation.
In the event a subject withdraws consent from the clinical study, biomarker research will continue 
unless the subject explicitly requests analysis to be stopped.  When AbbVie is informed that samples are 
withdrawn from research, samples will not be analyzed, no new biomarker analysis data will be 
collected, and the samples will be destroyed.  A subject may withdraw consent for optional biomarker 
research at any time and remain in the clinical study.  Data generated from biomarker research, before 
subject withdrawal of consent, will remain part of the study results.
5.7 Study Drug
Study site staff will administer risankizumab 150 mg SC [2 × 75 mg pre-filled syringe] (Table 1).
AbbVie will not supply drug other than risankizumab.
Page 22 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Risankizumab will be packaged in quantities sufficient to accommodate study design.  Risankizumab will 
be provided as two prefilled syringes per carton to accommodate the study design.  Each kit will be 
labeled per local requirements and this label must remain affixed to the kit.  Upon receipt, study drug 
should be stored as specified on the label in their original packaging and kept in a secure location. A 
temperature log must be maintained for documentation.  Each kit will contain a unique kit number.  This 
kit number is assigned to a subject via interactive response technology (IRT) and encodes the 
appropriate study drug to be dispensed at the subject's corresponding study visit.  All blank spaces on 
the label will be completed by the site staff prior to administering to subjects.  Study drug will only be 
used for the conduct of this study.  Instructions for drug administration will be provided by AbbVie.
Table 1.
Identity of Investigational Product
Study Drug 
Dosage Form
Strength
Route of 
Administration
Manufacturer
Risankizumab 
(ABBV-066)
Pre-filled syringe
75 mg per syringe
SC
Boehringer-
Ingelheim Pharma 
GmbH & Co. KG
SC = subcutaneously
Interruption/Discontinuation of Study Drug Due to COVID-19
Delays in study drug dosing due to a subject with COVID-19 must be discussed with the AbbVie medical 
contact, along with the possibility of premature discontinuation from the study drug dosing period.  
Follow protocol Section 5.6 for subjects who discontinued study drug.
5.8 Randomization/Drug Assignment
There is no randomization in this open-label study.  All subjects will be administered risankizumab 
150 mg.
All subjects will be assigned a unique identification number by the IRT at the screening visit.  For 
subjects who do not meet the study eligibility criteria, the site personnel must register the subject as a 
screen failure in both IRT and electronic Case Report Form (eCRF) systems.
Rescreening

Subjects that initially screen fail for the study may be permitted to re-screen once/one time 
following re-consent; the screening number assigned by the IRT at the initial screening visit 
should be used.

There is no minimum period of time a subject must wait to re-screen for the study.

A repeat of all screening procedures is needed with the possible exceptions noted below:

If the subject had a complete initial Screening visit including the assessment of a PPD test (or 
equivalent), or QuantiFERON-TB Gold test, and ECG, these tests will not be required to be 
repeated for the rescreening visit, provided the conditions noted in Section 5.1 are met and 
no more than 90 days have passed since the original screening visit.
Page 23 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

If there is an exclusionary laboratory result during screening, a re-test of that particular value is 
allowed without repeating all other lab tests provided no more than 30 days have passed since 
the original screening visit.

The subject must meet all inclusion and none of the exclusion criteria at the time of re-screening 
to qualify for the study.

As appropriate, sites are encouraged to contact the AbbVie TA MD to confirm if subjects should 
or should not be re-screened.
5.9 Protocol Deviations
AbbVie does not allow intentional/prospective deviations from the protocol except when necessary to 
eliminate an immediate hazard to study subjects.  The investigator is responsible for complying with all 
protocol requirements, written instructions, and applicable laws regarding protocol deviations.  If a 
protocol deviation occurs (or is identified, including those that may be due to the COVID-19 pandemic), 
the investigator is responsible for notifying independent ethics committee (IEC)/independent review 
board (IRB), regulatory authorities (as applicable), and AbbVie.
6 SAFETY CONSIDERATIONS
6.1 Complaints and Adverse Events
Complaints
A complaint is any written, electronic, or oral communication that alleges deficiencies related to the 
physical characteristics, identity, quality, purity, potency, durability, reliability, safety, effectiveness, or 
performance of a product/device.  Complaints associated with any component of this investigational 
product must be reported to AbbVie.
Product Complaint
A product complaint is any complaint related to the biologic or drug component of the product or to the 
medical device component(s).
For a product this may include, but is not limited to, damaged/broken product or packaging, product 
appearance whose color/markings do not match the labeling, labeling discrepancies/inadequacies in the 
labeling/instructions (e.g., printing illegible), missing components/product, device not working properly, 
or packaging issues.
Product complaints concerning the investigational product and/or device must be reported to AbbVie 
within 1 business day of the study site's knowledge of the event.  Product complaints occurring during 
the study will be followed up to a satisfactory conclusion.
Medical Complaints/Adverse Events and Serious Adverse Events
An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a causal relationship with 
Page 24 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
this treatment.  An AE can, therefore, be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not the event is considered causally related to the use of the 
product.
The investigators will monitor each subject for clinical and laboratory evidence of AEs on a routine basis 
throughout the study.  All AEs will be followed to a satisfactory conclusion.
An elective surgery/procedure scheduled to occur during the study will not be considered an AE if the 
surgery/procedure is being performed for a pre-existing condition and/or the surgery/procedure has 
been pre-planned prior to study entry.  However, if the pre-existing condition deteriorates unexpectedly 
during the study (e.g., surgery performed earlier than planned), then the deterioration of the condition 
for which the elective surgery/procedure is being done will be considered an AE.
If an AE, whether associated with study drug or not, meets any of the following criteria, it is to be 
reported to AbbVie clinical pharmacovigilance or contract research organization (CRO) (as appropriate) 
as an SAE within 24 hours of the site being made aware of the SAE (refer to Section 4.3 of the 
Operations Manual [Appendix G] for reporting details and contact information).
Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the investigator, would have resulted in 
immediate fatality if medical intervention had not been taken.  This does 
not include an event that would have been fatal if it had occurred in a 
more severe form.
Hospitalization or 
Prolongation of 
Hospitalization
An event that results in an admission to the hospital for any length of 
time or prolongs the subject's hospital stay.  This does not include an 
emergency room visit or admission to an outpatient facility.
Congenital Anomaly
An anomaly detected at or after birth, or any anomaly that results in 
fetal loss.
Persistent or Significant
Disability/Incapacity
An event that results in a condition that substantially interferes with the 
activities of daily living of a study subject.  Disability is not intended to 
include experiences of relatively minor medical significance such as 
headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle).
Page 25 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Important Medical Event 
Requiring Medical or 
Surgical Intervention to 
Prevent Serious Outcome
An important medical event that may not be immediately life-
threatening or result in death or hospitalization, but based on medical 
judgment may jeopardize the subject and may require medical or 
surgical intervention to prevent any of the outcomes listed above 
(i.e., death of subject, life threatening, hospitalization, prolongation of 
hospitalization, congenital anomaly, or persistent or significant 
disability/incapacity).  Additionally, any elective or spontaneous abortion 
or stillbirth is considered an important medical event.  Examples of such 
events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not 
result in inpatient hospitalization, or the development of drug 
dependency or drug abuse.
All adverse events reported from the time of study drug administration until 140 days (20 weeks) after 
discontinuation of study drug administration will be collected, whether solicited or spontaneously 
reported by the subject.  In addition, SAEs and protocol-related nonserious AEs will be collected from 
the time the subject signs the study-specific informed consent.
AbbVie will be responsible for Suspected Unexpected Serious Adverse Reactions (SUSAR) reporting for 
the Investigational Medicinal Product (IMP) in accordance with global and local requirements.
Adverse events will be monitored throughout the study to identify any of special interest that may 
indicate a trend or risk to subjects.
Areas of Safety Interest
Infections, especially opportunistic infections, are a theoretical risk with immunomodulators.  Subjects 
will be screened and monitored throughout the study for Areas of Safety Interest (ASI).  Screening 
procedures are outlined in the Activity Schedule (Appendix D).
In consideration of the ASI, the following supplemental report form(s) must be completed if AEs in any 
of the following areas are reported during the study (Table 2).
Page 26 of 89
 




STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
The investigator will use the following definitions to assess the relationship of the AE to the use of study 
drug:
Reasonable 
Possibility
After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is 
sufficient evidence (information) to suggest a causal relationship.
No Reasonable 
Possibility
After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is 
insufficient evidence (information) to suggest a causal relationship.
Pregnancy
While not an AE, pregnancy in a study subject must be reported to AbbVie within 1 working day after 
the site becomes aware of the pregnancy.  Subjects who become pregnant during the study must be 
discontinued (Section 5.5).  If a pregnancy occurs in a study subject, information regarding the 
pregnancy and the outcome will be collected.
The pregnancy outcome of an elective or spontaneous abortion, stillbirth or congenital anomaly is 
considered a SAE and must be reported to AbbVie within 24 hours after the site becomes aware of the 
event.
6.2 Cardiovascular Adjudication Committee (CAC)
An independent adjudication committee will adjudicate all observed cardio- and cerebro-vascular events 
and will remain blinded to treatment allocation.  The events that are adjudicated and the adjudication 
process will be detailed in the Cardiovascular Adjudication Committee (CAC) Charter.  Dedicated eCRFs 
will be used as outlined in Table 2.
In addition, the site may be contacted for additional source documentation for relevant events.
6.3 Anaphylaxis Adjudication Committee
While no concerns with anaphylaxis/systemic hypersensitivity have been identified with the use of 
risankizumab, the sponsor has established an independent, blinded, expert committee to adjudicate 
events of anaphylaxis based on pre-specified definitions.  This independent external Anaphylaxis 
Adjudication Committee (AAC) will adjudicate suspected anaphylactic reactions and will remain blinded 
to treatment allocation. The event terms to be adjudicated and the adjudication process are detailed in 
the AAC Charter.  A supplemental Hypersensitivity Reactions Signs and Symptoms eCRF will be used to 
collect information pertinent to the events.  In addition, the site may be contacted for additional source 
documentation.
If a suspected systemic hypersensitivity reaction occurs at the investigative site, subjects should be 
tested for tryptase and histamine levels.  If a systemic hypersensitivity reaction such as anaphylaxis is 
observed or reported while the subject is not at the investigative site, every effort should be made to 
obtain tryptase and histamine levels from the treating facility to help better characterize the diagnosis.
Page 28 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
7 STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
7.1 Statistical and Analytical Plans
The objectives of the statistical analyses are to evaluate the efficacy and safety of subjects with 
moderate to severe plaque psoriasis, who have been treated with labeled doses of secukinumab or 
ixekizumab for at least 6 months and are experiencing a sub-optimal response at time of Screening and 
Baseline visits and are switched to risankizumab at Baseline (Week 0).
For ease of description, Period A refers to Weeks 0 - 16 and Period B refers to the rest of the study.
The Primary Analysis for all efficacy endpoints pertaining to Period A will be conducted after all 
continuing subjects completed Week 16 and all data pertaining to Period A are cleaned and when a 
database lock will occur to enable the analysis.  This is the one and final efficacy analysis for Period A.  
The results will be included in an interim clinical study report to support the efficacy and safety 
evaluation of the initial 16 weeks of treatment.
The Primary Analysis for all efficacy endpoints in Period B will be conducted at the study completion.
The statistical analyses will be described and fully documented in the Statistical Analysis Plan (SAP).  The 
SAP will be finalized prior to the database lock for the Primary Analysis for Period A.  The statistical 
analyses will be performed using SAS (SAS Institute Inc., Cary, North Carolina, USA).
7.2 Definition for Analysis Population
The Intent-to-Treat (ITT) Population, which is defined as all subjects who have at least 1 dose of study 
drug in Study M19-164, will be used for the efficacy analyses.  The Safety Analysis Set consists of all 
subjects who received at least 1 dose of study drug in Study M19-164 and will be used for all safety 
analyses.  In this study, the Safety Analysis Set is the same as the ITT Population.
7.3 Statistical Analyses for Efficacy
Primary Analysis
For all efficacy endpoints, the analysis will be conducted in the ITT Population.  No statistical tests will be 
performed considering single-arm design.
The last non-missing observation collected on or before the date of the first dose of study drug injection 
will be used as Baseline for safety and efficacy analyses.  Descriptive statistics will be reported at 
baseline, primary time point of Week 16 and at study end of Week 52 in overall population and clinically 
important subgroups.  Categorical endpoints will be summarized by frequencies, percentages, and 
associated 95% confidence intervals (CIs).  Continuous endpoints will be summarized by means, 
standard deviations as well model based least square means, standard errors, and the 95% CIs after 
accounting for relevant baseline characteristics.  Stratified analysis by prior use of secukinumab or 
ixekizumab will be considered.
Page 29 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Missing data will be handled by non-responder imputation incorporating multiple imputation for missing 
data due to COVID-19 (NRI-C) for categorical endpoints and mixed effect model repeat measurements 
(MMRM) for continuous endpoints.  As-observed analysis will also be performed to handle missing data 
as sensitivity analysis for the primary and secondary endpoints.
Non-Responder Imputation incorporating multiple imputation to handle missing data due to COVID-19 
(NRI-C):  Missing data due to a COVID-19 infection or logistical restrictions related to the COVID-19 
pandemic will be handled through multiple imputation (MI).  Missing data at a scheduled assessment 
visit due to reasons other than the COVID-19 pandemic will be handled by NRI for that visit.
Details on the efficacy analyses are provided in the SAP.
Sample Size Estimation
There is no published literature or clinical trial data to accurately estimate the primary endpoint of sPGA 
0/1 response rate at Week 16 for this study population – suboptimal response of subjects treated with 
secukinumab or ixekizumab.  The assumption for risankizumab sPGA 0/1 response rate at Week 16 is 
expected to be between 
 based on the subjects who self-reported as prior IL-17 failure in 
Phase 3 trials ULTIMMA 1 & 2 and IMMhance.
The statistical precision measured by half-width of 95% confidence interval (CI) is the main criteria for 
sample size determination.  By examining it over varying sample size, a choice of 250 subjects is 
associated with a half-width of no more than 
 across all possible response rates (Figure 2).
Page 30 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
A total of 250 subjects will be enrolled in this study.  From historical data of enrollment of the psoriasis 
studies conducted by AbbVie, the projected screen failure (SF) rate is 
.  Thus, 
 subjects will be 
needed to be screened to enroll 250 subjects.
7.4 Statistical Analyses for Safety
The safety analyses will be carried out using the Safety Analysis Set.  Safety will be assessed by AEs, 
physical examination, laboratory assessments, and vital signs.  Analysis details will be specified in the 
SAP.
Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA).  Treatment-
emergent AEs are defined as those that began or worsened in severity after the first dose of study drug 
and within 140 days (20 weeks) after the last dose of study drug.  The number and percentage of 
subjects experiencing TEAEs will be tabulated using the MedDRA system organ class (SOC) and preferred 
term (PT), by severity, and by relationship to the study drug as assessed by the investigator.  Summaries 
(including percentages and events per 100 patient-years) of SAEs, deaths, AEs leading to discontinuation 
and Area of Safety Interest (ASI) will be provided as well.  Pre-treatment AEs will be summarized 
separately.
For selected laboratory and vital signs, mean change from baseline and percentage of subjects with 
evaluations meeting criteria for pre-defined Potentially Clinically Significant (PCS) values will be 
summarized.
7.5 Interim Analysis
The interim analysis for all efficacy and safety data of Period A (Week 0 – 16) will be conducted after 
50% of all continuing subjects completed Week 16 visit and when an interim database lock will occur to 
enable the analysis.  The goal is to preliminarily assess response rates and potentially enable a potential 
earlier scientific communication.
8 ETHICS
8.1 Independent Ethics Committee/Institutional Review Board 
(IEC/IRB)
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the IEC/IRB for review and approval.  Approval of both the protocol and the informed 
consent form(s) must be obtained before any subject is enrolled.  Any amendment to the protocol will 
require review and approval by the IEC/IRB before the changes are implemented to the study.  In 
addition, all changes to the consent form(s) will be IEC/IRB approved.
Page 31 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
8.2 Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, Operations Manual, International Council 
for Harmonisation (ICH) guidelines, applicable regulations, and guidelines governing clinical study 
conduct and the ethical principles that have their origin in the Declaration of Helsinki.  Responsibilities of 
the investigator are specified in Appendix B.
In the event of a state of emergency due to the COVID-19 pandemic leading to difficulties in performing 
protocol-specified procedures, AbbVie will engage with study site personnel in efforts to ensure the 
safety of subjects, maintain protocol compliance, and minimize risks to the integrity of the study while 
trying to best manage subject continuity of care.  This may include alternative methods of assessments 
(e.g., phone contacts or virtual site visits), alternative locations for data collection (e.g., use of a local 
laboratory instead of a central laboratory), and study visit schedule modification.  Refer to the 
Operations Manual in Appendix G for additional details.  In all cases, these alternative measures must be 
allowed by local regulations and permitted by IRB/IEC.  Investigators should notify AbbVie if any urgent 
safety measures are taken to protect the subjects against any immediate hazard.
8.3 Subject Confidentiality
To protect subjects' confidentiality, all subjects and their associated samples will be assigned numerical 
study identifiers or "codes."  No identifiable information will be provided to AbbVie.
9 SOURCE DOCUMENTS AND CASE REPORT FORM 
COMPLETION
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the 
data reported.  All source documents should be attributable, legible, contemporaneous, original, 
accurate, and complete to ensure accurate interpretation of data.  Clinical site monitoring is conducted 
to ensure that the rights and well-being of human subjects are protected, that the reported trial data 
are accurate, complete, and verifiable, and that the conduct of the trial is in compliance with the 
currently approved protocol, ICH Good Clinical Practice (GCP), and applicable local regulatory 
requirement(s).
During the COVID-19 pandemic, remote monitoring of data may be employed if allowed by the local 
regulatory authority, IRB/IEC, and the study site.
10
DATA QUALITY ASSURANCE
AbbVie will ensure that the clinical trial is conducted with a quality management system that will define 
quality tolerance limits in order to ensure human subject protection and reliability of study results.  Data 
will be generated, documented, and reported in compliance with the protocol, ICH GCP, and applicable 
regulatory requirements.
Page 32 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
11
COMPLETION OF THE STUDY
The investigator will conduct the study in compliance with the protocol and complete the study within 
the timeframe specified in the contract between the investigator and AbbVie.  Continuation of this study 
beyond this date must be mutually agreed upon in writing by both the investigator and AbbVie.  The 
investigator will provide a final report to the IEC/IRB following conclusion of the study and will forward a 
copy of this report to AbbVie or their representative.
The investigator must submit, maintain, and archive any records related to the study according to ICH 
GCP and all other applicable regulatory requirements.  If the investigator is not able to retain the 
records, he/she must notify AbbVie to arrange alternative archiving options.
AbbVie will select the signatory investigator from the investigators who participate in the study.  
Selection criteria for this investigator will include level of participation as well as significant knowledge 
of the clinical research, investigational drug, and study protocol.  The signatory investigator for the study 
will review and sign the final study report in accordance with the European Agency for the Evaluation of 
Medicinal Products (EMEA) Guidance on Investigator's Signature for Study Reports.
The end-of-study is defined as the date of the last subject's last contact, which will be a follow-up phone 
call 20 weeks after the last dose.
12
REFERENCES
1.
World Health Organization. Global report on psoriasis. 2016. Available from: 
http://apps.who.int/iris/handle/10665/204417. Accessed on: 30 October 2017.
2.
Menter A, Griffiths CE. Current and future management of psoriasis. Lancet. 2007;370(9583):272-84.
3.
Pathirana D, Ormerod AD, Saiag P, et al. European S3-guidelines on the systematic treatment of 
psoriasis vulgaris. J Eur Acad Dermatol Venereol. 2009;23(Suppl 2):1-70.
4.
Davidovici BB, Sattar N, Prinz J, et al. Psoriasis and systemic inflammatory diseases: potential 
mechanistic links between skin disease and co-morbid conditions. J Invest Dermatol. 
2010;130(7):1785-96.
5.
Lebwohl M, Strober B, Menter A, et al. Phase 3 Studies Comparing Brodalumab with Ustekinumab in 
Psoriasis. N Engl J Med. 2015;373(14):1318-28.
6.
Reich K, Puig L, Paul C, et al. One-year safety and efficacy of ustekinumab and results of dose 
adjustment after switching from inadequate methotrexate treatment: the TRANSIT randomized trial 
in moderate-to-severe plaque psoriasis. Br J Dermatol. 2014;170(2):435-44.
7.
Smith RL, Warren RB, Eyre S, et al. Polymorphisms in the IL-12beta and IL-23R genes are associated 
with psoriasis of early onset in a UK cohort. J Invest Dermatol. 2008;128(5):1325-7.
8.
Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque 
Psoriasis. N Engl J Med. 2016;375(4):345-56.
Page 33 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
9.
Reich K, Armstrong AW, Foley P, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 
monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to 
severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-
blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. 
2017;76(3):418-31.
10. Meeran SM, Mantena SK, Meleth S, et al. Interleukin-12-deficient mice are at greater risk of UV 
radiation-induced skin tumors and malignant transformation of papillomas to carcinomas. Mol 
Cancer Ther. 2006;5(4):825-32.
11. Filipe-Santos O, Bustamante J, Chapgier A, et al. Inborn errors of IL-12/23- and IFN-gamma-mediated 
immunity: molecular, cellular, and clinical features. Semin Immunol. 2006;18(6):347-61.
12. Chackerian AA, Chen SJ, Brodie SJ, et al. Neutralization or absence of the interleukin-23 pathway 
does not compromise immunity to mycobacterial infection. Infect Immun. 2006;74(11):6092-9.
13. AbbVie. Data on File, RRT165191.
14. AbbVie. Data on File, RRT165192.
15. AbbVie. Data on File, RRT165055.
16. Gordon KB, Strober B, Lebwohl M, et al. Efficacy and safety of risankizumab in moderate-to-severe 
plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-
controlled and ustekinumab-controlled phase 3 trials. Lancet. 2018;392(10148):650-61.
17. Khader SA, Pearl JE, Sakamoto K, et al. IL-23 compensates for the absence of IL-12p70 and is 
essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-
specific IFN-gamma responses if IL-12p70 is available. J Immunol. 2005;175(2):788-95.
18. O'Garra A, Redford PS, McNab FW, et al. The immune response in tuberculosis. Annu Rev Immunol. 
2013;31:475-527.
19. Qian X, Gu L, Ning H, et al. Increased Th17 cells in the tumor microenvironment is mediated by IL-23 
via tumor-secreted prostaglandin E2. J Immunol. 2013;190(11):5894-902.
20. Baird AM, Leonard J, Naicker KM, et al. IL-23 is pro-proliferative, epigenetically regulated and 
modulated by chemotherapy in non-small cell lung cancer. Lung Cancer. 2013;79(1):83-90.
21. Hu WH, Chen HH, Yen SL, et al. Increased expression of interleukin-23 associated with progression of 
colorectal cancer. J Surg Oncol. 2017;115(2):208-12.
22. Langowski JL, Zhang X, Wu L, et al. IL-23 promotes tumour incidence and growth. Nature. 
2006;442(7101):461-5.
23. AbbVie. Risankizumab Investigator's Brochure Edition 5. 13 May 2019.
Page 34 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
24. Smith CH, Jabbar-Lopez ZK, Yiu ZZ, et al. British Association of Dermatologists guidelines for biologic 
therapy for psoriasis 2017. Br J Dermatol. 2017;177(3):628-36.
25. Canadian Psoriasis Guidelines Addendum Committee. 2016 addendum to the Canadian guidelines 
for the management of plaque psoriasis 2009. J Cutan Med Surg. 2016;20(5):375-431.
26. Armstrong AW, Siegel MP, Bagel J, et al. From the Medical Board of the National Psoriasis 
Foundation: treatment targets for plaque psoriasis. J Am Acad Dermatol. 2017;76(2):290-8.
27. US Department of Health and Human Services. Common Terminology Criteria for Adverse Events 
(CTCAE) Version 5.0 27 November 2017 [Available from: 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Refer
ence_8.5x11.pdf.
Page 35 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX A. STUDY SPECIFIC ABBREVIATIONS AND TERMS
Abbreviation
Definition
AAC
Anaphylaxis Adjudication Committee
Ab
Antibody
AE
Adverse event
Ag
Antigen
ALT
Alanine aminotransferase
ANC
Absolute neutrophil count
ASI
Areas of special interest
AST
Aspartate aminotransferase
ATEMS
AbbVie Temperature Excursion Management System
BCG
Bacille Calmette-Guérin
BSA
Body surface area
BUN
Blood urea nitrogen
CAC
Cardiovascular Adjudication Committee
CI
Confidence interval
CK
Creatine kinase
COVID-19
Coronavirus Disease - 2019
CRO
Contract research organization
CTCAE
Common Terminology Criteria for Adverse Events
DLQI
Dermatology Life Quality Index
DNA
Deoxyribonucleic acid
ECG
Electrocardiogram
eCRF
Electronic case report form
EDC
Electronic data capture
EMA
European medicines agency
EMEA
Evaluation of Medicinal Products
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FSH
Follicle-stimulating hormone
GCP
Good clinical practice
GGT
Gamma-glutamyl transferase
Page 36 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
HB
Hepatitis B
HBc Ab
Hepatitis B core antibody
HBs Ab
Hepatitis B surface antibody
HBs Ag
Hepatitis B surface antigen
HBV
Hepatitis B virus
HBV Ab
Hepatitis B virus antibody
HCV
Hepatitis C virus
HCV Ab
Hepatitis C virus antibody
HDL-C
High density lipoprotein cholesterol
HIV
Human immunodeficiency virus
HIV Ab
Human immunodeficiency virus antibody
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
IEC/IRB
Independent Ethics Committee/Institutional Review Board
Ig
Immunoglobulin
IGRA
Interferon gamma release assay
IHC
Immunohistochemistry
IL
Interleukin
IMP
Investigational medicinal product
INR
International normalized ratio
IRB
Institutional review board
IRT
Interactive response technology
ITT
Intent-to-treat
IU
International unit
IUD
Intrauterine device
IUS
Intrauterine hormone-releasing system
LDL-C
Low density lipoprotein cholesterol
mAb
Monoclonal antibody
MACE
Major adverse cardiac event
MCV
Mean corpuscular volume
MedDRA
Medical Dictionary for Regulatory Activities
MI
Multiple imputation
MMRM
Mixed effect model repeat measurements
NCI
National cancer institute
Page 37 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
NMSC
Non-melanoma skin cancer
NRI
Non-responder imputation
NRI-C
Non-responder imputation incorporating multiple imputation for missing data due 
to COVID-19
PASI
Psoriasis Area Severity Index
PCR
Polymerase chain reaction
PCS
Potentially clinically significant
PD
Premature discontinuation
PD visit
Premature Discontinuation visit
PPD
Purified protein derivative (tuberculin)
PRO
Patient-reported outcome
PsA
Psoriatic arthritis
PSS
Psoriasis Symptoms Scale
PT
Preferred term
q12w
Every 12 weeks
RBC
Red blood cell
RCT
Randomized controlled trial
RNA
Ribonucleic acid
RSI
Reference Safety Information
SAE
Serious adverse event
SAP
Statistical analysis plan
SC
Subcutaneously
SOC
System organ class
sPGA
Static Physician Global Assessment
SUSAR
Suspected unexpected serious adverse reactions
TB
Tuberculosis
TEAE
Treatment-emergent adverse event
TNF
Tumor necrosis factor
TSQM-9
Treatment Satisfaction Questionnaire for Medication Version 9
ULN
Upper limit of normal
UACR
Urine albumin-to-creatinine ratio
US
United States
WBC
White blood cell
Page 38 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX B. RESPONSIBILITIES OF THE INVESTIGATOR
Protocol M19-164:  A Phase 3b, multicenter, interventional, open-label study of adult subjects with 
moderate to severe plaque psoriasis who have a suboptimal response to secukinumab or ixekizumab 
and are switched to risankizumab
Protocol Date:  27 January 2021
Clinical research studies sponsored by AbbVie are subject to the International Council for Harmonisation 
(ICH) Good Clinical Practices (GCP) and local regulations and guidelines governing the study at the site 
location.  In signing the Investigator Agreement, the investigator is agreeing to the following:
1.
Conducting the study in accordance with ICH GCP, the applicable regulatory requirements, 
current protocol and operations manual, and making changes to a protocol only after notifying 
AbbVie and the appropriate Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC), except when necessary to protect the subject from immediate harm.
2.
Personally conducting or supervising the described investigation(s).
3.
Informing all subjects, or persons used as controls, that the drugs are being used for 
investigational purposes and complying with the requirements relating to informed consent and 
ethics committees (e.g., IEC or IRB) review and approval of the protocol and its amendments.
4.
Reporting complaints that occur in the course of the investigation(s) to AbbVie.
5.
Reading the information in the Investigator's Brochure/safety material provided, including the 
instructions for use and the potential risks and side effects of the investigational product(s).
6.
Informing all associates, colleagues, and employees assisting in the conduct of the study about 
their obligations in meeting the above commitments.
7.
Maintaining adequate and accurate records of the conduct of the study, making those records 
available for inspection by representatives of AbbVie and/or the appropriate regulatory agency, 
and retaining all study-related documents until notification from AbbVie.
8.
Maintaining records demonstrating that an ethics committee reviewed and approved the initial 
clinical protocol and all of its amendments.
9.
Reporting promptly, all changes in the research activity and all unanticipated problems involving 
risks to human subjects or others, to the appropriate individuals (e.g., coordinating investigator, 
institution director) and/or directly to the ethics committees and AbbVie.
10. Providing direct access to source data documents for study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s).
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)
Page 39 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX C. LIST OF PROTOCOL SIGNATORIES
Name
Title
Functional Area
Therapeutic Area Lead
Global Medical Affairs
Scientific Director
Global Medical Affairs
Program Lead
Clinical Program Development
Director
Data and Statistical Sciences Biometrics
Senior Medical Writer
Medical Writing
Page 40 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX D. ACTIVITY SCHEDULE
The following table shows the required activities across the Screening and subsequent study visits.  The 
individual activities and allowed modifications due to COVID 19 are described in detail in the Operations 
Manual (Appendix G).
Page 41 of 89
 






STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
h.
A complete (full) physical exam is required at the visits indicated.  A symptom-directed (targeted) physical exam may be performed when necessary (e.g., to evaluate a reported 
adverse event).
i.
The ECG should be performed prior to blood collection.  For subjects with a normal ECG taken within 90 days of Screening, a repeat ECG at Screening will not be required; 
provided all protocol-required documentation is available, and nothing has changed in the subject's health status since the time of the test that warrants a repeat test.
j.
At Screening visit until prior to the first dose of study drug, serious AEs and protocol-related non-serious AEs that occur after a subject signs the informed consent have to be 
collected.  From the time of first study drug administration until 140 days (20 weeks) following discontinuation of study treatment has elapsed, all AEs and SAEs will be 
collected, whether solicited or spontaneously reported by the subject.  If appropriate, a targeted physical exam should be performed.  If an anaphylactic reaction is suspected, a 
serum tryptase and a plasma histamine sample will be drawn.
k.
For all female subjects of childbearing potential, collect urine for pregnancy test at Baseline and all subsequent visits when the female subjects will receive study drug.  More 
frequent pregnancy tests will be performed throughout the study if required per local/country requirements.  If urine pregnancy test (which is performed at the site) is 
negative, begin or continue dosing.  If urine pregnancy test is positive, withhold study drug dosing and perform a serum pregnancy test.  Pregnant subjects must discontinue 
from study drug treatment.  Refer to Section 6.1 Complaints and Adverse Events for additional details.
l.
A urine dipstick macroscopic urinalysis will be completed by the central laboratory.  A microscopic analysis will be performed in the event the dipstick results show leukocytes, 
nitrite, protein, ketones, or blood greater than negative or glucose greater than normal.
m.
HIV testing will be performed at Screening Visit.  The Investigator must discuss any local reporting requirements to local health agencies with the subject.  The site will report 
confirmed positive results to their health agency per local regulations, if necessary.  If a subject has a confirmed positive result, the Investigator must discuss with the subject 
the potential implications to the subject's health and subject should receive or be referred for clinical care promptly.  A subject will not be eligible for study participation if test 
results indicate a positive HIV infection.  AbbVie will not receive results from the testing and will not be made aware of any positive result.
n.
FSH should be tested at Screening if the female subject is < 55 years of age AND has had no menses for ≥ 12 months AND has no history of permanent surgical sterilization.
o.
For all women of childbearing potential, collect serum for pregnancy test at Screening.  If the serum pregnancy test is positive the subject is considered a screen failure.  If the 
serum pregnancy test comes back borderline, a repeat test is necessary (pregnancy is an exclusion criterion).  If still borderline ≥ 3 days later, this will be considered 
documentation of continued lack of a positive result and the subject can be enrolled into the study.
p.
TB testing will be performed at Screening Visit.  Refer to Tuberculosis Testing section of the Operations Manual for further information.
q.
Lipid testing required at Baseline (Week 0), Week 16, and Week 52.  A minimum 8-hour fast is requested.  If a subject is not able to fast when necessary, due to unforeseen 
circumstances, the non-fasting status will be recorded in study source documentation and lab requisition.
r.
Study drug will be administered at the study site by authorized site personnel (e.g., study nurse) after all study procedures have been completed.
Note:
Visit window is ± 3 days for the visits Week 4 up to Week 16, and ± 7 days thereafter.  Any of the procedures may be performed at an unscheduled visit at the discretion of 
the Investigator.
Page 44 of 89
 




STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX F. PROTOCOL SUMMARY OF CHANGES
Previous Protocol Versions
Protocol
Date
Version 1.0
07 August 2019
Administrative Change 1
21 August 2020
The purpose of this version is to update the Sponsor emergency medical contact information based on 
Administrative Change 1, incorporate necessary protocol modifications due to the COVID-19 pandemic, 
and to modify the eligibility criteria as follows:

Title page – changed number of sites from 50 to 70.
Rationale:  Mitigation to enrollment issues.

Section 2.2 – included information on the re-evaluation of the benefit and risk to subjects 
participating in the study.  There is no anticipated additional risk to subjects.
Rationale:  To account for the emerging COVID-19 pandemic.

Section 2.2 – removed language that no active TB cases have been observed.
Rationale:  To reflect current safety database.

Section 5.1 – removed psoriatic arthritis exclusion criterion.
Rationale:  Given the additional approval of secukinumab and ixekizumab for PsA and the 
significant PsA and PsO patient overlap, the removal of PsA as an exclusion criterion will result in 
a more practical and relevant translation of the study outcomes into real life clinical settings.

Section 5.1 – added criterion to exclude active SARS-CoV-2 infection.
Rationale:  To account for the emerging COVID-19 pandemic.

Section 5.3 – revised item #2 to clarify systemic (including oral) non-biologic therapy to treat 
psoriasis or possibly benefit psoriasis in prohibited medications and therapy.
Rationale:  For clarification.

Section 5.5 – added instructions to refer to Operations Manual for necessary changes to 
activities or procedures.
Rationale:  To account for the emerging COVID-19 pandemic and ensure consistency between 
the study protocol and Operations Manual.

Section 5.7 – provided instructions in the event of temporary study drug interruption/halt due 
to COVID-19.
Rationale:  To account for the emerging COVID-19 pandemic.

Section 5.9 – clarified that protocol deviations may include modifications due to COVID-19.
Rationale:  To account for the emerging COVID-19 pandemic.
Page 46 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Section 7.3 – added NRI-C to incorporate handling of missing data due to COVID-19.
Rationale:  To account for the emerging COVID-19 pandemic.

Section 7.3 – added as-observed analysis to incorporate handling of missing data as sensitivity 
analysis for the primary and secondary endpoints.
Rationale:  To assess robustness of findings and potential impact of missing data handling.

Section 8.2 – noted that AbbVie will modify the study protocol as necessary due to the 
pandemic, referring to the Operations Manual in Appendix G for additional details.  Investigators 
must also notify AbbVie if any urgent safety measures are taken.
Rationale:  To account for the emerging COVID-19 pandemic and ensure consistency between 
the study protocol and Operations Manual.

Section 9 – noted that remote monitoring may be employed as needed.
Rationale:  To account for the emerging COVID-19 pandemic.

Appendix D – added reference to Operations Manual for allowed modification.
Rationale:  To account for the emerging COVID-19 pandemic and ensure consistency between 
the study protocol and Operations Manual.

Appendix G – Operations Manual updated to include details on how to perform specific 
activities/procedures that may be impacted by changes in global/local regulations due to the 
pandemic.
Rationale:  To account for the emerging COVID-19 pandemic and ensure consistency between 
the study protocol and Operations Manual.
Page 47 of 89
 


STUDY M19-164  |  Version 2.0  |  EudraCT 2019-000904-14
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX G. OPERATIONS MANUAL
Page 48 of 89
 




p. 2 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1 CONTACTS
Sponsor/
Non-
Emergency 
Contact
 PhD
Scientific Director Dermatology
Global Medical Affairs
AbbVie
Mainzer Strasse 81
65189 Wiesbaden, Germany
Cell:
EMAIL:
Sponsor/
Emergency 
Medical 
Contact
 MD
Global TA Lead, Global Medical Affairs 
(GMA)
GMA Biotherapeutics
Immunology 
AbbVie
Montehiedra Office Center
9615 Los Romeros Avenue, Suite 600
San Juan, Puerto Rico 00926-7038
EMERGENCY 24-hour Number:  
+1 (973) 784-6402
Mobile:
Email:
Safety 
Concerns
Immunology Safety Team
Dept. R48S, Bldg. AP51-3
1 North Waukegan Road 
North Chicago, IL 60064, USA
CTPS Safety Line:
(833) 942-2226 (Toll free)
Email:
GPRD_SafetyManagement_Immunology@abbvie.com
Serious 
Adverse 
Event 
Reporting 
outside of 
RAVE
Email:
PPDINDPharmacovigilance@abbvie.com
Fax: +1 (847) 938-0660
Protocol 
Deviations
Study Project Manager I
1 North Waukegan Road
North Chicago, IL 60064
Office:
Email:
Certified 
Clinical Lab
Covance Central Laboratory Services SA
8211 Scicor Drive
Indianapolis, IN 46214, USA
Phone:
+1 (866) 762-6209 (Toll free)
+1 (317) 271-1200 (Local calls)
Fax:
+1 (317) 616-2362
For country specific toll-free numbers, please refer to 
Covance Lab Manual.
Page 50 of 89
 


p. 3 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
TABLE OF CONTENTS
1
CONTACTS
2
2
PROTOCOL ACTIVITIES BY VISIT
5
2.1
INDIVIDUAL TREATMENT PERIOD VISIT ACTIVITIES
5
2.2
INDIVIDUAL POST-TREATMENT PERIOD VISIT ACTIVITIES
9
3
STUDY PROCEDURES
9
3.1
SUBJECT INFORMATION AND INFORMED CONSENT
9
3.2
MEDICAL HISTORY
10
3.3
ADVERSE EVENT ASSESSMENT
10
3.4
SUBJECT QUESTIONNAIRES
10
3.5
EFFICACY ASSESSMENTS
11
3.6
BIOMARKER RESEARCH SAMPLING
12
3.7
12-LEAD ELECTROCARDIOGRAM
13
3.8
HEIGHT, WEIGHT, AND BODY CIRCUMFERENCE
14
3.9
VITAL SIGNS
14
3.10
PHYSICAL EXAMINATION
14
3.11
STUDY DRUG ADMINISTRATION
14
3.12
CLINICAL LABORATORY TESTS
15
3.13
SUBJECT WITHDRAWAL FROM STUDY
22
3.14
OUT OF WINDOW VISITS DUE TO COVID-19 PANDEMIC
23
4
SAFETY MANUAL
23
4.1
METHODS AND TIMING OF SAFETY ASSESSMENT
23
4.2
RECORDING DATA AND ANALYSES OF SAFETY FINDINGS
23
4.3
REPORTING ADVERSE EVENTS AND INTERCURRENT ILLNESSES
24
4.4
REPORTING PRODUCT COMPLAINTS
26
5
COUNTRY-SPECIFIC REQUIREMENTS
26
5.1
SUSAR REPORTING
26
6
STUDY DRUG
26
6.1
TREATMENTS ADMINISTERED
26
Page 51 of 89
 


p. 4 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
6.2
PACKAGING AND LABELING
27
6.3
METHOD OF ASSIGNING SUBJECTS TO TREATMENT GROUPS
27
6.4
SELECTION AND TIMING OF DOSE FOR EACH SUBJECT
27
7
REFERENCES
28
8
APPENDICES
29
8.1
DERMATOLOGY LIFE QUALITY INDEX (DLQI)
29
8.2
PSORIASIS SYMPTOM SCALE (PSS)
30
8.3
TREATMENT SATISFACTION QUESTIONNAIRE FOR MEDICATION VERSION 9 (TSQM-9)
31
8.4
PSORIASIS AREA AND SEVERITY INDEX (PASI)
34
8.5
STATIC PHYSICIAN GLOBAL ASSESSMENT
36
8.6
BODY SURFACE AREA (BSA)
38
8.7
CLINICAL CRITERIA FOR DIAGNOSING ANAPHYLAXIS
39
LIST OF TABLES
TABLE 1.
CLINICAL LABORATORY TESTS
17
LIST OF FIGURES
FIGURE 1.
INTERPRETATION AND MANAGEMENT OF HBV SEROLOGIC TEST RESULTS
20
FIGURE 2.
SAFETY ASSESSMENT
23
Page 52 of 89
 












p. 10 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
the informed consent statement will be reviewed, signed, and dated by the subject or their legally 
authorized representative, the person who administered the informed consent, and any other 
signatories according to local requirements.  A copy of the signed informed consent will be given to the 
subject and the original will be placed in the subject's medical record.  An entry must also be made in 
the subject's dated source documents to confirm that informed consent was obtained prior to any 
study-related procedures and that the subject received a signed copy.
Information regarding benefits for subjects and information regarding provisions for treating and/or 
compensating subjects who are harmed as a consequence of participation in the study can be found in 
the informed consent form.
Optional biomarker research samples will only be collected if the subject has voluntarily signed and 
dated a written consent form describing the research.  The written consent may be part of the main 
consent form.  If the subject does not consent to providing optional samples, the subject will still be 
allowed to participate in the study.
Due to the COVID-19 pandemic, it is possible that additional protocol modifications not outlined in this 
protocol may become necessary.  If this situation arises, in addition to the study informed consent, 
additional verbal consent may be obtained prior to these adaptations or substantial changes in study 
conduct in accordance with local regulations.
3.2 Medical History
A complete medical and surgical history including history of hepatitis B vaccination, tuberculosis (TB) 
screening, tobacco, alcohol, and drug use will be taken at screening.  The subject's medical and surgical 
history will be updated at the Study Baseline (Week 0) visit.  This updated medical history will serve as 
the baseline for clinical Drug and Alcohol Screen.
Subjects should have no history of clinically significant (per investigator's judgment) drug or alcohol 
abuse within the last 6 months.
3.3 Adverse Event Assessment
Please refer to Section 4.2.
3.4 Subject Questionnaires
Subjects will complete the self-administered patient-reported outcome (PRO) instrument (when allowed 
per local regulatory guidelines).  Subjects should be instructed to follow the instructions provided with 
the instrument and to provide the best possible response to each item.  Site personnel shall not provide 
interpretation or assistance to subjects other than encouragement to complete the tasks.  Subjects who 
are functionally unable to read any of the instruments may have site personnel read the questionnaire 
to them.  Site personnel will encourage completion of the instrument at all specified visits.
The subject should complete the questionnaires before site personnel perform any clinical assessments 
and before any interaction with site personnel has occurred to avoid biasing the subject's response.
Page 58 of 89
 


p. 11 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
PROs will be completed prior to any clinical assessments and treatment administration following the 
schedule of activities outlined in the protocol.
Dermatology Life Quality Index (DLQI)
The DLQI is a self-administered, 10-question questionnaire covering 6 domains (symptoms and feelings, 
daily activities, leisure, work and school, personal relationships, and bother with psoriasis treatment) 
(Appendix 8.1).  The response options range from 0, not affected at all, to 3, very much affected.  This 
gives an overall range of 0 to 30 where lower scores mean better quality of life.
Psoriasis Symptoms Scale (PSS)
The PSS is a 4-item patient-reported outcome (PRO) instrument that assesses the severity of psoriasis 
symptoms in patients with moderate to severe psoriasis (Appendix 8.2).  The symptoms included are:  
pain, redness, itching and burning from psoriasis.  Current symptom severity is assessed as a daily diary, 
using a 5-point Likert-type scale ranging from 0 (none) to 4 (very severe). The PSS was developed based 
on published evidence supporting the development of two similar, proprietary PRO instruments:  the 
Psoriasis Symptom Inventory and the Psoriasis Symptom Diary.
Treatment Satisfaction Questionnaire for Medication Version 9 (TSQM-9)
The abbreviated 9-item TSQM (TSQM-9) assesses patient's satisfaction with medication through 9 items 
representing 3 domains:  Effectiveness (3 items), Convenience (3 items), and Global Satisfaction scale 
(3 items), scored by dimension ranging from 0 to 100, with higher scores indicating higher satisfaction 
(Appendix 8.3).
The TSQM-9 is a validated 9-item questionnaire designed as a general measure of treatment satisfaction 
with medication.  The recall period is the last 2 to 3 weeks, or since the last medication use.
A score can be obtained for each domain by summing of the corresponding items transformed on a 0 –
100 scale (0 = complete dissatisfaction, 100 = maximum satisfaction).  Higher values indicate higher 
satisfaction, better perceived effectiveness, lower burden associated to side-effects, and better 
convenience.
3.5 Efficacy Assessments
Efficacy assessments will be recorded on paper worksheets and entered into the electronic case report 
form (eCRF) and conducted at the study visits specified in the protocol.  To minimize variability, the 
same assessor should evaluate the subject at each visit for the duration of the trial.  A back-up assessor 
should be identified.  The assessor must be a qualified medical professional (e.g., nurse, physician's 
assistant, or physician).  Any assessor must have completed training for skin assessments (PASI, BSA, and 
sPGA) as detailed by sponsor, and be competent in performing such assessments.  It is the responsibility 
of the site investigator to ensure that all assessors are qualified and trained to perform assessments and 
that all training is documented.  If the assessor is not available, the pre-identified back-up assessor 
should perform such assessments.
Page 59 of 89
 


p. 12 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Psoriasis Assessments
Psoriasis Area Severity Index (PASI)
The PASI is a measure of psoriasis severity.  Four anatomic sites – head, upper extremities, trunk, and 
lower extremities – are assessed for erythema, induration and desquamation using a 5-point scale 
(Appendix 8.4).  Based on the extent of lesions in a given anatomic site, the area affected is assigned a 
numerical value.  Since the head, upper extremities, trunk and lower extremities correspond to 
approximately 10, 20, 30 and 40% of body surface area, respectively; the PASI score is calculated using 
the formula:
PASI = 0.1(Eh + Ih + Dh)Ah + 0.2(Eu + Iu + Du)Au + 0.3(Et + It + Dt)At + 0.4(El + Il + Dl)Al
Where E, I, D, and A denote erythema, induration, desquamation, and area, respectively, and h, u, t, and 
l denote head, upper extremities, trunk, and lower extremities, respectively.  PASI scores range from 
0.0 to 72.0 with the highest score representing complete erythroderma of the severest possible degree.
Typically scores of 3 or less represent mild disease, scores over 3 and up and including 15 represent 
moderate disease and scores over 15 are considered to be associated with severe disease.
Static Physician Global Assessment (sPGA)
This sPGA is a 5-point score ranging from 0 to 4, based on the physician's assessment of the average 
thickness, erythema, and scaling of all psoriatic lesions (Appendix 8.5).
The assessment is considered "static" which refers to the patient's disease state at the time of the 
assessments, without comparison to any of the patient's previous disease states, whether at Baseline or 
at a previous visit.
Body Surface Area (BSA) – Psoriasis
The subject's right or left hand should be selected as the measuring device.  For purposes of clinical 
estimation, the total surface of the palm plus five digits will be assumed to be approximately equivalent 
to 1%.  Measurement of the total area of involvement by the physician is aided by imagining if scattered 
plaques were moved so that they were next to each other and then estimating the total area involved 
(Appendix 8.6).
3.6 Biomarker Research Sampling
For subjects who consent, optional samples (whole blood, serum, plasma, and tissue) will be collected 
for biomarker research.  Please refer to Section 2.1 for the schedule of biomarker research sample 
collections.  All biomarker samples should be labeled and shipped as outlined in the study-specific 
laboratory manual.  AbbVie (or people or companies working with AbbVie) will store the samples and 
data in a secure storage space with adequate measures to protect confidentiality.  The samples may be 
retained while research on risankizumab (or drugs of this class) or psoriasis and related conditions 
continues, but for no longer than 20 years after study completion, or per local requirement.
Page 60 of 89
 


p. 13 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Whole Blood
The whole blood sample will be collected for genetic, transcriptomic and proteomic analysis.  Baseline 
(Week 0) samples will be collected at pre-dose.  Week 4, Week 16, and Week 52/Premature 
Discontinuation samples will be collected at any time during the visit.
Skin Punch Biopsy Samples
Skin biopsies should be between 4.5 and 5 millimeters.  Suitable sites for skin biopsy will include any 
cutaneous surface except the head and neck, genitals, hands, feet, elbows, lower leg or knees.  Skin 
biopsies should be 5 millimeters (not less than 4.5 mm).  Skin punch biopsy samples will be taken from 
lesional skin.  As described in the laboratory manual, a baseline 5 mm lesional biopsy should be taken 
from the most involved, chronic active erythematous, scaly lesion.  The subsequent biopsy samples 
should be obtained from the same area and location as the baseline lesional sample (> 5 mm but not 
further than 1 cm from the baseline biopsy site).
If the lesion has cleared, collect the sample close to the previous biopsies scar (> 5 mm but not further 
than 1 cm from the biopsy scar).  Do not biopsy the previous biopsy scar.  Baseline (Week 0) samples will 
be collected at pre-dose.  Week 16 samples will be collected at any time during the visit.
Skin Tape Biopsy Samples
Skin tape strip samples will be taken from adjacent sites used for skin punch biopsies.  Patches will be 
applied to the skin briefly and then removed.  Each sample will consist of 4 patches applied to the same 
exact area in succession.  Skin tape strip samples should be taken from the same lesional area for each 
visit.  Skin tape strip samples should be taken prior to skin punch biopsies.  Baseline (Week 0) samples 
will be collected at pre-dose.  Week 16 samples will be collected at any time during the visit.
3.7 12-Lead Electrocardiogram
A 12-lead ECG will be performed at the designated study visits, as specified in Section 2.1.
For subjects with a normal ECG taken within 90 days of Screening, a repeat ECG at Screening will not be 
required, provided all protocol-required documentation is available and nothing has changed in the 
subject's health status since the time of the test that warrants a repeat test.  The ECG should be 
performed prior to blood collection.
The ECGs will be evaluated by an appropriately trained physician at the site ("local reader").  The local 
reader from the site will sign and date all ECG tracings and will provide his/her global interpretation as a 
written comment on the tracing using the following categories:

Normal ECG

Abnormal ECG – not clinically significant

Abnormal ECG – clinically significant
Clinically significant ECG findings noted at screening will be captured in Medical History.
Page 61 of 89
 


p. 14 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Only the local reader's evaluation of the ECG will be collected and documented in the subject's source 
folder.  The automatic machine reading (i.e., machine-generated measurements and interpretation that 
are automatically printed on the ECG tracing) will not be collected but will be retained in subject's 
source records.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
In the event this may not be performed due to study modifications related to the COVID-19 pandemic, 
perform the 12-lead ECG at the next earliest feasible visit or arrange to have an alternative acceptable 
local facility perform the ECG for the subject.
3.8 Height, Weight, and Body Circumference
Height will be measured at screening only, without shoes.  Body weight and waist circumference should 
be measured at scheduled visits as specified in Section 2.1.  The subject will wear lightweight clothing 
and no shoes during weighing.  If the screening weight is missed, it should be done at the Baseline 
(Week 0) visit prior to the first dose.  Waist circumference should also be measured at Screening; 
however, if missed, it can be recorded at the Baseline (Week 0) visit.
3.9 Vital Signs
Vital sign determinations of systolic and diastolic blood pressure, pulse rate, and body temperature will 
be obtained at visits as specified in Section 2.1.  Blood pressure and pulse rate should be measured after 
the subject has been sitting for at least 3 minutes.  Clinically significant abnormalities in vital signs will 
also be reported as an AE or SAE.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
Due to the COVID-19 pandemic, subject visits may be conducted via phone or video conference.  In 
these situations, vital signs may be obtained by the subject or caregiver as needed.
3.10 Physical Examination
A complete physical examination will be performed at the designated study visits as specified in 
Section 2.1.  The physical examination performed on Baseline (Week 0) will serve as the baseline 
physical examination for the entire study.  Any significant physical examination findings after the 
first dose will be recorded as adverse events.  All findings, whether related to an AE or part of each 
subject's medical history, will be captured on the appropriate eCRF page.
At any time, a symptom-directed physical examination can be performed as deemed necessary by the 
investigator.
3.11 Study Drug Administration
Study drug will be administered to subjects beginning at Baseline (Week 0) and as specified in 
Section 2.1.  All subcutaneous (SC) doses of risankizumab will be administered by designated or qualified 
Page 62 of 89
 


p. 15 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
study site personnel under the direction of the investigator.  Date and exact time (to the nearest 
minute) of study drug administration will be recorded on eCRFs.  The first dose of study drug will be 
administered after all other Baseline (Week 0) procedures are completed.  Injection site locations 
include lower abdomen, thigh, or outer upper arm.  Study drug administration instruction for 
risankizumab pre-filled syringes (PFS) will be provided to the site. 
Monitoring for Hypersensitivity Reactions
Therapeutic protein products, such as biologics, may elicit a range of acute effects, from symptomatic 
discomfort to sudden, fatal reactions and may encompass a wide range of clinical events, including 
anaphylaxis and other events that may not be directly related to antibody (Ab) responses, such as 
cytokine release syndrome.
Subjects should be closely monitored at the site for signs and symptoms of hypersensitivity reactions, 
including allergic reactions and anaphylaxis, for approximately 1 hour after all PFS dosing of study drug 
have been administered at each dosing visit.  A medical person qualified in the treatment of acute 
hypersensitivity reactions must be present during the injections.
All appropriate medical support measures (e.g., diphenhydramine, steroids, epinephrine, oxygen) for the 
treatment of suspected hypersensitivity reactions should be available for immediate use in the event 
that a suspected hypersensitivity reaction occurs.  Subjects who manifest any new signs or symptoms 
during the injection should be monitored for appropriate resolution prior to leaving the site.  Subjects 
are encouraged to report any symptoms related to a possible injection-related reactions or local 
injection site reaction or late phase reactions to the site any time during the study.  A patient 
information card listing the symptoms of these reactions will be provided to the participants.
Subjects will be monitored throughout the study for signs and symptoms suggestive of hypersensitivity 
reactions, including allergic reactions and anaphylaxis.  In the event of a suspected 
anaphylactic/systemic hypersensitivity reaction, in addition to the standard AE eCRF, the supplemental 
Hypersensitivity Reaction Signs and Symptoms eCRF should also be completed by the site.  The clinical 
criterion for diagnosing anaphylaxis is provided in Appendix 8.7 for reference; symptoms of anaphylactic 
reaction usually occur within 24 hours after exposure to an allergen.  These are guidelines that are used 
to help diagnose anaphylaxis.  The investigator is encouraged to report any suspected reactions.
In the event of a suspected anaphylactic reaction, blood and serum samples should also be collected as 
described in Section 3.12.
3.12 Clinical Laboratory Tests
A certified laboratory will be utilized to process and provide results for the clinical laboratory tests 
(Table 1).  Laboratory reference ranges will be obtained prior to the initiation of the study.  Instructions 
regarding the collection, processing, and shipping of these samples will be provided by the central 
laboratory.
The blood samples for serum chemistry tests will be collected following a minimum 8-hour fast for 
Baseline (Week 0), Week 16, and Week 52 visits.  If a subject is not able to fast at those visits, due to 
unforeseen circumstances, the non-fasting status will be recorded in study source documentation and 
lab requisition.  Blood samples at other visits can be drawn without prior fast.  The Baseline laboratory 
Page 63 of 89
 


p. 16 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
test results for clinical assessment for a particular test will be defined as the last measurement prior to 
the initial dose of study drug.
Blood draws should be performed after all questionnaires, clinical assessments, and vital sign 
determinations are obtained.  Unscheduled clinical labs may be obtained at any time during the study if 
deemed appropriate per investigator's discretion.
For any laboratory test value outside the reference range that the investigator considers to be clinically 
significant, the investigator should apply the standard of care for medical evaluation and treatment per 
local guidelines:

The investigator will repeat the test to verify the out-of-range value.

The investigator will follow the out-of-range value to a satisfactory clinical resolution.
A laboratory test value that requires a subject to be discontinued from study drug or requires a subject 
to receive treatment will be recorded as an AE.
Instructions regarding the collection, processing, and shipping of these samples will be provided by the 
central laboratory and sent to the following certified laboratory addresses:
Covance Central Laboratory Services SA
8211 Scicor Drive
Indianapolis, IN 46214
Page 64 of 89
 


p. 17 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Table 1.
Clinical Laboratory Tests
Clinical Laboratory Tests
HEMATOLOGY
CLINICAL CHEMISTRY
URINALYSIS
Hematocrit
Hemoglobin
Mean corpuscular volume (MCV)
Red blood cell (RBC) count/
Erythrocytes
White blood cell (WBC) count/
Leukocytes
Platelet count/Thrombocytes
Diff. Automatic (absolute count):
Neutrophils
Eosinophils
Basophils
Monocytes
Lymphocytes
Manual Differential (ONLY IF 
Automated Differential is 
abnormal):
Neutrophils, bands (Stabs)
Neutrophils, polymorphonuclear
Eosinophils
Basophils
Monocytes
Lymphocytes
Coagulation:
International normalized ratio 
(INR)a
Enzymes
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Alkaline phosphatase (AP)
Gamma-glutamyl transferase
(GGT/γ-GT)
Creatine kinase (CK)
Only if CK is elevated:
Troponin (point-of-care) OR
Troponin (central lab)
Electrolytes
Sodium
Potassium
Chloride
Bicarbonate
Calcium
Phosphorus
Substrates
Glucoseb
Blood urea nitrogen (BUN)
Creatinine
Bilirubin total
Bilirubin direct (if total is elevated)
Bilirubin indirect (if total is elevated)
Albumin
hsCRP
Cholesterol, totalb
LDL-Cb
HDL-Cb
Triglyceridesb
FSHc
Dipstick Urinalysis
Urine nitrite
Urine protein
Urine glucose
Urine ketone
Urobilinogen
Urine bilirubin
Urine RBC/erythrocytes
Urine WBC/leukocytes
Urine pH
Urine creatinine
Urine Sediment (microscopic
examination, ONLY IF 
urine analysis is abnormal):
Urine
Urine albumin-to-creatinine 
ratio (UACR)
Page 65 of 89
 


p. 18 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Clinical Laboratory Tests
ADDITIONAL TESTING
INFECTION SCREENING
PREGNANCY TESTINGe
N/A
Hepatitis B surface antigen (HBs Ag)
(qualitative)d
Hepatitis B surface antibody (HBs Ab)
(qualitative)d
Anti-Hepatitis B core (HBc) total
(qualitative)d
HBV DNA (quantitative)d
Anti-HCV (qualitative)d
HCV RNA (quantitative)d
HIV-1 and HIV-2 Ab (qualitative)d
QuantiFERON®-TB (or Interferon
gamma release assay [IGRA]
equivalent) and/or purified
protein derivative (PPD)
Urine pregnancy test (local)f
Serum pregnancy testg
ANAPHYLAXIS TESTINGh
Tryptase
Histamine
Ab = antibody; ALT = alanine aminotransferase; AP = alkaline phosphatase; AST = aspartate aminotransferase; BUN = blood urea 
nitrogen; CK = creatine kinase; DNA = deoxyribonucleic acid; FSH = follicle-stimulating hormone; GGT/ γ-GT = gamma-glutamyl 
transferase; HBc = hepatitis B core; HBs Ab = hepatitis B surface antibody; HBs Ag = hepatitis B surface antigen; HBV = hepatitis 
B virus; HCV = hepatitis C virus; HDL-C = high density lipoprotein cholesterol; HIV = human immunodeficiency virus; 
hsCRP = high-sensitivity c-reactive protein; IGRA = interferon gamma release assay; INR = international normalized ratio; 
LDL-C = low density lipoprotein cholesterol; MCV = mean corpuscular volume; PCR = polymerase chain reaction; PPD = purified 
protein derivative; RBC = red blood cell; RNA = ribonucleic acid; TB = tuberculosis; UACR = urine albumin-to-creatinine ratio; 
ULN = upper limit of normal; WBC = white blood cell
a.
INR test only performed if ALT or AST > 3 × ULN (upper limit of normal).
b.
Performed at Baseline (Week 0), Week 16, and Week 52 visits (following a minimum 8-hour fast).
c.
FSH testing is to be done at Screening in all women aged ≤ 55 years with no menses for 12 or more months without an 
alternative medical cause.
d.
Performed only at Screening.  Per regional requirements:  for subjects with HBs Ab (+) and/or HBc Ab (+) at Screening, the 
HBV-DNA PCR test should be performed again as noted in the Operations Manual, Section 2.1.  Retesting is not necessary 
for subjects that have a history of HBV vaccine and are HBs Ab (+).
e.
Pregnancy testing is not required for female subjects of non-childbearing potential (defined in Protocol Section 5.2).
f.
Urine pregnancy test will be performed at every visit from Baseline (Week 0) through Week 52/Premature Discontinuation 
Visit and must be conducted prior to study drug dosing.  Negative urine pregnancy test results must be confirmed prior to 
study drug dosing.
g.
Serum pregnancy test is conducted at Screening and at other visits only if urine pregnancy test is positive.  Negative serum 
pregnancy test results must be confirmed prior to study drug dosing.
h.
Only performed in case of a suspected anaphylactic reaction.  Refer to anaphylaxis testing Section 3.12 below.
Urinalysis
Dipstick urinalysis will be completed by the central laboratory at the Screening visit.  Specified abnormal 
macroscopic urinalyses defined as leukocytes, nitrite, protein, ketones, or blood greater than negative, 
or glucose greater than normal will be followed up with a microscopic analysis at the central laboratory.
Page 66 of 89
 


p. 19 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Pregnancy Tests (Serum and Urine)
Pregnancy testing should not be performed for postmenopausal women.  Determination of 
postmenopausal status will be made during the Screening period based on the subject's history and 
confirmed by FSH, if appropriate.
A pregnant or breastfeeding female will not be eligible for participation or continuation in this study.
Pregnant subjects must discontinue from study drug treatment.  Refer to Section 6.1 of the protocol for 
additional details.
Serum Pregnancy Test
A serum pregnancy test will be performed for all female subjects of childbearing potential (defined in 
the protocol) at Screening.  The serum pregnancy test will be sent to and performed by the central 
laboratory.  If the serum pregnancy test is positive, the subject is considered a screen failure.  If the 
serum pregnancy test is borderline, it should be repeated to determine eligibility.
If the repeat serum pregnancy test is:

Positive, the subject is considered a screen failure;

Negative, the subject can be enrolled into the trial;

Still borderline ≥ 3 days later:  If no clinical suspicion of pregnancy and there are other 
pathological causes of borderline results, the borderline results will be considered 
documentation of continued lack of a positive result and the subject can be enrolled into the 
study.
Urine Pregnancy Test
A urine pregnancy test will be performed for all females of childbearing potential at the Baseline Visit 
prior to the first dose of study drug.  Additional urine pregnancy tests for female subjects of childbearing 
potential will be performed at visits indicated in Section 2.  More frequent pregnancy tests will be 
performed throughout the study if required per local/country requirements.
If the urine pregnancy test (which is performed at the site) is negative, dosing may begin or continue.  If 
the urine pregnancy test is positive, dosing should be withheld and a serum pregnancy test performed.  
Pregnant subjects must discontinue from the study.
Follicle-Stimulating Hormone
Follicle-stimulating hormone (FSH) should be tested at Screening if the female subject is ≤ 55 years of 
age AND has had no menses for ≥ 12 months AND has no history of permanent surgical sterilization.
Hepatitis B and C Testing
All subjects will be tested for the presence of the hepatitis B virus (HBV) and hepatitis C virus (HCV) at 
Screening (Figure 1).  Subjects with hepatitis B (hepatitis B surface antigen [HBs Ag] positive [+] or 
detected sensitivity on the HBV DNA polymerase chain reaction [PCR] qualitative test) or hepatitis C 
(HCV RNA detectable in any subject with anti-HCV antibodies) will be excluded.  Subjects who have been 
Page 67 of 89
 


p. 20 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
vaccinated against hepatitis B and are HBs Ab positive may be enrolled.  If HBs Ag is negative but 
Hepatitis B core antibodies (HBc Ab) total is positive, HBV DNA will be quantified.  If HBV DNA level is 
undetectable at Screening, the subject can participate in this trial.  
Where mandated by local requirements, subjects with HBs Ab+ and/or HBc Ab+ and negative HBV DNA 
at screening should have HBV DNA PCR testing performed every 12 weeks (q12w).  HBV DNA PCR testing 
q12w is not necessary when the subject has a history of HBV vaccine and is HBs Ab+ and HBc Ab–.
Per regional requirements:  for subjects with HBs Ab (+) and/or HBc Ab (+) at Screening, the HBV DNA 
PCR test should be performed as outlined in the Operation Manual Section 2.1.  In cases where the 
recurrence of HBV-DNA is observed, the subject should be discontinued from the study drug.  Retesting 
is not necessary for subjects that have a history of HBV vaccine and are HBs Ab (+).
If HCV antibodies are positive, HCV RNA will be quantified.  If HCV RNA level is undetectable at 
Screening, the subject can participate in this trial.
Figure 1.
Interpretation and Management of HBV Serologic Test Results
DNA = deoxyribonucleic acid; HBc Ab = hepatitis B core antibody; HBs Ab = hepatitis B surface antibody; HBs Ag = hepatitis B 
surface antigen; HBV = hepatitis B virus; PCR = polymerase chain reaction
*
A positive test result for HBs Ab is expected for subjects who have had a HBV vaccination.  For subjects without a history of
HBV vaccination (and where mandated by local requirements), a positive result for HBs Ab requires HBV DNA PCR testing.
Human Immunodeficiency Virus (HIV) Testing
Human immunodeficiency virus testing will be performed at Screening.  The Investigator must discuss 
any local reporting requirements to local health agencies with the subject.  The site will report 
confirmed positive results to their health agency per local regulations, if necessary.  If a subject has a 
confirmed positive result, the Investigator must discuss with the subject the potential implications to the 
subject's health and subject should receive or be referred for clinical care promptly.  A subject will not 
be eligible for study participation if test results indicate a positive HIV infection.  AbbVie will not receive 
results from the testing and will not be made aware of any positive result.  In case a screened subject 
Page 68 of 89
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 


p. 21 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
has a confirmed positive HIV Ab test, eligibility criterion 5 should be selected in eCRF for documentation 
of screening failure.
Tuberculosis Testing
All subjects will be tested for TB by either the QuantiFERON-TB Gold Test (or IGRA equivalent) or a TB 
Skin Test (PPD) at the Screening visit, as specified in the study activity table.
At Screening, all subjects will be assessed for evidence of TB and TB risk factors.  Subjects who have had 
a TB test performed within 90 days of the Screening Visit will not need to have the test repeated, 
provided all of the protocol required documentation is available at the site, and no new TB risk factors 
have been identified.
The QuantiFERON®-TB Gold assay test will be supplied and analyzed by the central laboratory.  
(QuantiFERON-TB test is preferred over TB Skin Test.)  Details on the collection, shipment of samples 
and reporting of results by the central laboratory are provided to investigators in the laboratory manual.

If the QuantiFERON-TB Gold Test (or IGRA equivalent) is NOT possible or if both the 
QuantiFERON-TB Gold Test [or IGRA equivalent] and the PPD Skin Test are required per local 
guidelines, the PPD Skin Test will be performed according to standard clinical practice.

The PPD Skin Test should be read by a licensed healthcare professional between 48 and 
72 hours after administration.  A subject who does not return within 72 hours will need to 
be rescheduled for another skin test.

The reaction will be measured in millimeters (mm) of induration and induration ≥ 5 mm is 
considered a positive reaction.  The absence of induration will be recorded as "0 mm," not 
"negative."

If subject had a positive QuantiFERON-TB Gold (or IGRA equivalent) or PPD test at Screening, the 
test should not be repeated.  Subjects who have had an ulcerating reaction to the TB Skin Test in 
the past should not be re-exposed and should not be tested by a PPD skin test.

If the TB screening test (either PPD or the QuantiFERON-TB Gold test [or IGRA equivalent]) is 
positive, or if there is a repeat indeterminate QuantiFERON-TB Gold test (or IGRA equivalent) 
upon retesting, subjects may participate in the study if further work-up (according to local
practice/guidelines) establishes conclusively that the patient has no evidence of active TB.  If the 
presence of latent TB is established, subjects are not required to be treated with prophylactic 
anti-TB therapy prior to or during the study, if the subject is considered low risk (i.e., no risk 
factors identified using the TB risk assessment questionnaire or defined by local guidelines or 
investigator judgment) for reactivation.

If the subject is diagnosed with active TB, the subject should not be randomized in the study and 
should not receive study drug.  Subject will be considered as a screening failure.

If the subject is diagnosed with active TB after being randomized, the subject should not receive 
any further study drug and follow the Premature Discontinuation Visit procedure.
If TB (latent or active) is diagnosed during the study, it is also necessary to report it as an AE in the 
source documents and eCRFs.  In the case of a TB-related AE, a TB supplemental form that provides 
additional information will be completed by the investigator or designee.
Page 69 of 89
 


p. 22 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Suspected Anaphylactic/Systemic Hypersensitivity Reaction Testing
Clinical criteria for diagnosing anaphylaxis are provided in Appendix 8.7.  Blood tests to be conducted in 
the event of a suspected anaphylactic reaction are:

Serum tryptase:  15 minutes to 3 hours of symptom onset, and no later than 6 hours (as tryptase
may remain elevated for 6 or more hours after the onset and therefore may still be informative 
if obtained after 3 hours); 

a follow-up tryptase level should be collected a minimum of 2 weeks after the recorded 
event or at the next study visit.

Plasma histamine:  5 to 15 minutes of symptom onset, and no later than 1 hour.
Subjects will be closely monitored on site during study drug administration at Baseline (Week 0), 
Week 4, Week 16, Week 28, and Week 40.  A medical person qualified in the treatment of acute 
hypersensitivity reactions must be present during the injections.  The duration of the post-dose safety 
surveillance is for 1 hour post-dose at all visits.
In the event that a suspected anaphylactic reaction occurs while the subject is not on site at the study 
clinic, please advise the treating facility to perform serum tryptase and histamine to help better 
understand and characterize the diagnosis.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
If logistical restrictions or other changes in local regulations in light of the COVID-19 pandemic prevent 
the subject from having blood drawn for laboratory testing at the study site, if possible, arrange for 
subjects to have laboratory work done at a local lab, hospital, or other facility.  Local lab results should 
be obtained along with reference ranges and kept with the subjects' source documentation.  Local lab 
results should be reviewed by the investigator as soon as possible.
If laboratory samples cannot be obtained, study drug administration may be continued provided the 
investigator has reviewed all prior laboratory results and confirms and discusses with the subject that 
there is no safety concern for the subject to continue use of the study drug in the absence of current 
labs.  The subject should be scheduled for laboratory draws as soon as feasible.
3.13 Subject Withdrawal from Study
All attempts must be made to determine the date of the last study drug dose and the primary reason for 
discontinuation of study drug or study participation.  The information will be recorded on the 
appropriate eCRF page.  However, these procedures should not interfere with the initiation of any new 
treatments or therapeutic modalities that the investigator feels are necessary to treat the subject's 
condition.  Following discontinuation of study drug, the subject will be treated in accordance with the 
investigator's best clinical judgment, irrespective of whether or not the subject decides to continue 
participation in the study.
Page 70 of 89
 


p. 23 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
3.14 Out of Window Visits Due to COVID-19 Pandemic
If a visit can be performed onsite out of window (OOW), consult with the sponsor to determine if the 
OOW visit is permitted.
Regardless of whether an onsite OOW visit can occur, a phone call from the site to the enrolled subject 
should be conducted as close to the date of the study visit as possible to query for any AEs and to review 
concomitant medications.
4 SAFETY MANUAL
4.1 Methods and Timing of Safety Assessment
All serious adverse events (SAEs) as well as protocol-related non-serious AEs (e.g., bruising related to 
blood draw) will be collected from the time the subject signed the study-specific informed consent until 
study drug administration.  From the time of study drug administration until 20 weeks (140 days) after 
discontinuation of study treatment, all AEs and SAEs will be collected, whether solicited or 
spontaneously reported by the subject.
Figure 2.
Safety Assessment
AEs = adverse events; SAEs = serious adverse events
4.2 Recording Data and Analyses of Safety Findings
An AE can result from use of the drug as stipulated in the protocol, as well as from accidental or 
intentional overdose, drug abuse, or drug withdrawal.  Any worsening of a pre-existing condition or 
illness is considered an AE.  Worsening in severity of a reported AE should be reported as a new AE.  
Laboratory abnormalities and changes in vital signs are considered to be AEs only if they result in 
discontinuation from the study, necessitate therapeutic medical intervention, meet criteria as specified 
Page 71 of 89
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 






p. 26 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
4.4 Reporting Product Complaints
Product Complaints concerning the investigational product and/or device must be reported to the 
sponsor within 24 hours of the study site's knowledge of the event via the Product Complaint form.  
Product Complaints occurring during the study will be followed-up to a satisfactory conclusion.  All 
follow-up information is to be reported to the sponsor (or an authorized representative) and 
documented in source as required by the sponsor.  Product Complaints associated with adverse events 
will be reported in the study summary.  All other complaints will be monitored on an ongoing basis.
Product Complaints may require return of the product with the alleged complaint condition.  In 
instances where a return is requested, every effort should be made by the investigator to return the 
product within 30 days.  If returns cannot be accommodated within 30 days, the site will need to 
provide justification and an estimated date of return.
5 COUNTRY-SPECIFIC REQUIREMENTS
5.1 SUSAR Reporting
AbbVie will be responsible for Suspected Unexpected Serious Adverse Reactions (SUSAR) reporting for 
the Investigational Medicinal Product (IMP) in accordance with global and local guidelines and 
Appendix A of the Investigator Brochure will serve as the Reference Safety Information (RSI).  The RSI in 
effect at the start of a DSUR reporting period serves as the RSI during the reporting period. For 
follow-up reports, the RSI in place at the time of occurrence of the 'suspected' Serious Adverse Reaction 
will be used to assess expectedness.
6 STUDY DRUG
6.1 Treatments Administered
The study drug (risankizumab) will be administered by a healthcare professional in the form of a SC 
injection at the visits listed in Section 2.1.
Risankizumab will be provided by AbbVie as solution for injection in pre-filled syringe.
Study site staff will administer 2 injections of risankizumab 75 mg (150 mg total dosage) SC at Weeks 0 
and 4, and then every 12 weeks (q12w) until the last dose at Week 40.
Study drug must not be dispensed without contacting the interactive response technology (IRT) system.  
Study drug may only be dispensed to subjects enrolled in the study through the IRT system.  At the end 
of the Treatment Period or at the Early Termination Visit, the site will contact the IRT system to provide 
visit date information and study drug return information for each kit.
Page 74 of 89
 


p. 27 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
6.2 Packaging and Labeling
Study drug packaged in pre-filled syringe will be provided in an open-label fashion and administered at 
each dosing visit.
Each kit will be labeled as required per local requirements.  Each kit label will contain a unique kit 
number.  This kit number is assigned to a subject via the IRT and encodes the appropriate study drug to 
be administered at the subjects corresponding study visit.
All labels must remain affixed to the study drug at all times and should never be removed for any 
reason.  All blank spaces should be completed by site staff prior to dispensing to subject.
Storage and Disposition of Study Drug
Risankizumab kits will be kept protected from light in their original packaging, in a refrigerator between 
2°C to 8°C (36°F to 46°F), and within a secure limited access storage area, and in accordance with the 
recommended storage conditions on the label.  Risankizumab must not be frozen at any time.
The refrigerator temperature must be recorded each business day.  Malfunctions or any temperature 
excursion must be reported to the sponsor immediately upon notice.  Study drug should be quarantined 
and not dispensed until AbbVie or AbbVie Temperature Excursion Management System (ATEMS) deems 
the drug as acceptable.
All clinical supplies must be stored and locked in a secure place until they are dispensed for subject use, 
are destroyed at the site or are returned to AbbVie or a local destruction depot.  Investigational 
products are for investigational use only and are to be used only within the context of this study.
6.3 Method of Assigning Subjects to Treatment Groups
This is a non-randomized, open-label, single arm study.  All eligible subjects will receive risankizumab 
150 mg total dosage through last dose at Week 40.
At the screening visit, all subjects will be assigned a unique subject number through the use of the IRT.  
For subjects who do not meet the study selection criteria, the site personnel must contact the IRT 
system and identify the subject as a screen failure.
Subjects who are enrolled will retain their subject number assigned at the screening visit throughout the 
study.  Upon receipt of study drug, the site will acknowledge receipt in the IRT system.
Contact information and user guidelines for IRT use will be provided to each site.
6.4 Selection and Timing of Dose for Each Subject
Subjects will receive 2 injections of active risankizumab (150 mg total dosage) SC at Weeks 0, 4 and 
every 12 weeks (q12w) thereafter until the last dose at Week 40.
Page 75 of 89
 


p. 28 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
7 References
1.
Robinson A, Kardos M, Kimball AB. Physician Global Assessment (PGA) and Psoriasis Area and 
Severity Index (PASI): why do both? A systematic analysis of randomized controlled trials of biologic 
agents for moderate to severe plaque psoriasis. J Am Acad Dermatol. 2012;66(3):369-75.
2.
Fredriksson T, Pettersson U. Severe psoriasis--oral therapy with a new retinoid. Dermatologica. 
1978;157(4):238-44.
3.
Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and 
management of anaphylaxis: summary report - Second National Institute of Allergy and Infectious 
Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 
2006;117(2):391-7.
Page 76 of 89
 


p. 29 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
8 Appendices
8.1 DERMATOLOGY LIFE QUALITY INDEX (DLQI)
Page 77 of 89
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


p. 30 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
8.2 PSORIASIS SYMPTOM SCALE (PSS)
Listed below are a set of problems that people with psoriasis have said are important.  For each 
question, click on the circle that best describes the severity of your symptoms during the past 24 hours.
Please answer every question.
1.
How severe was your pain from your psoriasis during the past 24 hours?

None

Mild

Moderate

Severe

Very severe
1.
How severe was the redness from your psoriasis during the past 24 hours?

None

Mild

Moderate

Severe

Very severe
2.
How severe was your itching from your psoriasis during the past 24 hours?

None

Mild

Moderate

Severe

Very severe
3.
How severe was your burning from your psoriasis during the past 24 hours?

None

Mild

Moderate

Severe

Very severe
Page 78 of 89
 


p. 31 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
8.3 TREATMENT SATISFACTION QUESTIONNAIRE FOR MEDICATION 
VERSION 9 (TSQM-9)
Page 79 of 89
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


p. 32 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Page 80 of 89
 
 
 
 
 
    
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


p. 33 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Page 81 of 89
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


p. 34 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
8.4 PSORIASIS AREA AND SEVERITY INDEX (PASI)
The PASI is an established measure of clinical efficacy for psoriasis medications.1
The PASI is a tool that provides a numeric scoring for subjects overall psoriasis disease state, ranging 
from 0 to 72.  It is a linear combination of percent of surface area of skin that is affected and the severity 
of erythema, induration, and desquamation over four body regions.
The endpoints used are based on the percent reduction from baseline, generally summarized as a 
dichotomous outcome based on achieving over an X% reduction (or PASI X), where X is 50, 75, 90 and 
100.
To calculate the PASI, the four main body areas are assessed:  head (h), trunk (t), upper extremities (u) 
and lower extremities (l).  These correspond to 10, 30, 20 and 40% of the total body area respectively.
The area affected by psoriasis within these four areas site is estimated as a percentage of the total area 
of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement as 
follows:

0 = no involvement

1 = < 10%

2 = 10% to < 30%

3 = 30% to < 50%

4 = 50% to < 70%

5 = 70% to < 90%

6 = 90% to 100%
The signs of severity, erythema (E), induration (I) and desquamation (D) of lesions are assessed using a 
numeric scale 0 – 4 where 0 is a complete lack of cutaneous involvement and 4 is the severest possible 
involvement; scores are made independently for each of the areas, h, t, u and l and represents a 
composite score for each area.  The signs of severity, erythema (E), induration (I) and desquamation (D)
of lesions are assessed using a numeric scale 0 to 4:

0 = No symptoms

1 = Slight

2 = Moderate

3 = Marked

4 = Very marked
Page 82 of 89
 


p. 35 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Assignments for the following body regions are as follows:

Neck:  include with the head

Buttocks:  include with the lower extremities

Axillae:  include with the trunk

Genitals:  include with the trunk

The inguinal canal separates the trunk and legs anteriorly
The PASI for each body region is obtained by multiplying the sum of the severity scores by the area 
score, then multiplying the result by the constant weighted value assigned to that body region.  Since 
the head, upper extremities, trunk, and lower extremities correspond to approximately 10%, 20%, 30%, 
and 40% of BSA, respectively, the PASI is calculated according to the following formula:
PASI = 0.1(Eh + Ih + Dh)Ah + 0.3(Et + It + Dt)At + 0.2(Eu + Iu + Du)Au + 0.4(El + Il + Dl)Al
where E, I, D, and A denote erythema, induration, desquamation, and area, respectively, and h, u, t, and 
l denote head, upper extremities, trunk, and lower extremities, respectively.  PASI ranges from 0.0 to 
72.0 with the highest score representing complete erythroderma of the severest degree.
Typically scores of 3 or less represent mild disease, scores over 3 and up and including 15 represent 
moderate disease and scores over 15 are considered to be associated with severe disease.
Note:
Fredriksson 1978.2
Erythemaa
Desquamation
Induration
0 = none
No redness
No scaling
No elevation over normal 
skin
1 = slight
Faint redness
Fine scale partially covering 
lesions
2 = moderate
Red coloration
Fine to coarse scale covering 
most of all of the lesions
Slight but definite 
elevation, typically edges 
indistinct or sloped
Moderate elevation with 
rough or sloped edges
3 = marked
Very or bright red 
coloration
4 = very marked
Extreme red 
coloration; dusky to 
deep red coloration
Coarse, non-tenacious scale 
predominates covering most 
or all of the lesions
Coarse, thick, tenacious scale 
over most or all lesions; 
rough surface
Marked elevation typically 
with hard or sharp edges
Very marked elevation 
typically with hard sharp 
edges
a.
Do not include residual hyperpigmentation or hypopigmentation as erythema.
Page 83 of 89
 


p. 36 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
8.5 STATIC PHYSICIAN GLOBAL ASSESSMENT
This Static Physician Global Assessment (sPGA) is a 5-point score ranging from 0 to 4, based on the 
physician's assessment of the average thickness, erythema, and scaling of all psoriatic lesions.
The assessment is considered "static" which refers to the patient's disease state at the time of the 
assessments, without comparison to any of the patient's previous disease states, whether at Baseline or 
at a previous visit.
A lower score indicates less body coverage, with 0 being clear and 1 being almost clear.  The efficacy 
assessor scores the erythema, induration and scaling of all psoriatic lesions from 0 – 4 based on the 
following descriptors:
Erythema
0    Normal (post-inflammatory hyper/hypopigmentation may be present)
1    Faint, diffuse pink or slight red coloration
2    Mild (light red coloration)
3    Definite red coloration (Dull to bright red)
4    Bright to Deep red coloration of lesions
Induration (Plaque Elevation)
0    None
1    Just detectable (possible slight elevation above normal skin)
2    Mild thickening (slight but definite elevation, typically edges are indistinct or sloped)
3    Clearly distinguishable to moderate thickening (marked definite elevation with rough or sloped 
edges)
4    Severe thickening with hard edges (marked elevation typically with hard or sharp edges)
Scaling
0    No scaling
1    Minimal focal scaling (surface dryness with some desquamation)
2    Predominately fine scaling (fine scale partially or mostly covering lesions)
3    Moderate scaling (coarser scale covering most or all of the lesions)
4    Severe/coarse scaling covering almost all or all lesions (coarse, nontenacious scale 
predominates)
Page 84 of 89
 


p. 37 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Scoring
A composite score is generated from the above data and the final sPGA is determined from this 
composite score as follows:
Clear                      0 = 0 for all three
Almost clear         1 = mean > 0, < 1.5
Mild                       2 = mean ≥ 1.5, < 2.5
Moderate             3 = mean ≥ 2.5, < 3.5
Severe                   4 = mean ≥ 3.5
Page 85 of 89
 


p. 38 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
8.6 BODY SURFACE AREA (BSA)
The subject's right or left hand should be selected as the measuring device.  For purposes of clinical 
estimation, the total surface of the palm plus five digits will be assumed to be approximately equivalent 
to 1%.  Measurement of the total area of involvement by the physician is aided by imagining if scattered 
plaques were moved so that they were next to each other and then estimating the total area involved.
Page 86 of 89
 


p. 39 of 39
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M19-164 Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
8.7 CLINICAL CRITERIA FOR DIAGNOSING ANAPHYLAXIS
Anaphylaxis3 is highly likely when any one of the following 3 criteria is fulfilled:
1.
Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, 
or both (e.g., generalized hives, pruritus or flushing, swollen lips-tongue-uvula)
AND AT LEAST ONE OF THE FOLLOWING
a.
Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia)
b.
Reduced blood pressure (BP) or associated symptoms of end-organ dysfunction 
(e.g., hypotonia [collapse], syncope, incontinence)
2.
Two or more of the following that occur rapidly after exposure to a likely allergen for that 
patient (minutes to several hours):
a.
Involvement of the skin-mucosal tissue (e.g., generalized hives, itch-flush, swollen lips-
tongue-uvula)
b.
Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia)
c.
Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, incontinence)
d.
Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting)
3.
Reduced BP after exposure to known allergen for that patient (minutes to several hours):
a.
Infants and children:  low systolic BP (age specific) or greater than 30% decrease in systolic 
BP*
b.
Adults:  systolic BP of less than 90 mm Hg or greater than 30% decrease from that person's 
baseline.
PEF = peak expiratory flow; BP = blood pressure
*
Low systolic BP for children is defined as less than 70 mm Hg from 1 month to 1 year, less than (70 mm Hg + [2 × age]) 
from 1 to 10 years, and less than 90 mg Hg from 11 to 17 years.
Serious Systemic Hypersensitivity Reaction:  A hypersensitivity reaction is a clinical sign or symptom, or 
constellation of signs or symptoms, caused by an inappropriate and excessive immunologic reaction to
study drug administration.  A systemic hypersensitivity reaction is a hypersensitivity reaction that does 
not occur at the local site of study drug administration (e.g., not an injection site reaction).  A serious 
systemic hypersensitivity reaction is a systemic hypersensitivity reaction that fulfills criteria for a serious 
adverse event.
In the event of an anaphylactic reaction, blood samples will be drawn per Section 3.12 after the onset of 
the reaction.  This will include:  histamine and tryptase.  Separate instructions for the collection, 
handling, storage and shipping of these labs will be provided outside of the study protocol.
Page 87 of 89