Clinical trial NCT05470985
Conditions: Crohn Disease
Sponsor: Bristol-Myers Squibb
Start date: 2023-08-22; Completion date: 2024-09-13
Enrollment: 5 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the efficacy, safety, drug levels, and drug effects of ozanimod in pediatric participants with moderately to severely active Crohn's Disease.

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Ozanimod
Intervention descriptions: intervention 1: Specific dose on specific days

Protocol documents:
Prot_SAP_000.pdf: 
Offi ci al Titl e of St u d y:  
A P h a s e 2/ 3, M ulti c e nt er, R a n d o mi z e d, D o u bl e -bli n d St u d y t o E v al u at e t h e Effi c a c y, S af et y,  
P h ar m a c o ki n eti c s a n d P h ar m a c o d y n a mi c s of Or al O z a ni m o d ( R P C 1 0 6 3) i n P e di atri c  
P arti ci p a nt s wit h M o d er at el y t o S e v er el y A cti v e Cr o h n’ s Di s e a s e wit h a n I n a d e q u at e R e s p o n s e  
t o C o n v e nti o n al T h er a p y 
 
N C T N u m b er:  N C T 0 5 4 7 0 9 8 5  
D o c u m e nt D at e ( D at e i n w hi c h d o c u m e nt w a s l a st r e vi s e d): 1 4  A u g 2 0 2 3 
 
 
 


Pa ge:
1
Pr ot oc ol  N u m ber:
I M 0 4 7 0 2 3
Date :
2 5- Fe b- 2 0 2 2
Re vise d Date :
1 4-A u g - 2 0 2 3
C LI NI C A L P R O T O C O L I M 0 4 7 0 2 3
A P hase 2/ 3, M ult ice nter, Ra n d o mize d, D o u ble-bli n d St u d y  t o E valuate t he Efficac y, Safet y,  
P har mac o ki net ics a n d P har mac o d y na mics of Oral Oza ni m o d ( R P C 1 0 6 3) i n Pe diatric 
P arti cipa nt s wi t h M o deratel y t o Se verel y Acti ve Cr o h n’s Disease wit h a n I na de q uate Res p o nse 
t o C o n ve nti onal T hera p y
Brief Title:
Efficac y, S af et y,  Ph ar m ac o ki net ics, a n d P h ar mac o d y na mics of  Oral Oza ni m o d i n Pe diatri c 
P arti cipa nts wi t h M o deratel y t o Se verel y Acti ve Cr o h n’s Di sease wit h a n I na de q uate Res p o nse t o 
C o n ve nti o nal T hera p y
Pr ot oc ol A me n d me nt 0 2
Cli nical De vel o p me nt Lea d
Bri st ol-M yers S q ui b b C o m pa n y
8 6 M orris A ve n ue
S u m mit , NJ 0 7 9 0 1
e mail: 
Cli nical Scie nt ist
Bri st ol-M yers S q ui b b C o m pa n y
3 0 3 3 Scie nce Par k R oa d, S uite 3 0 0
Sa n Die g o, C A 9 2 1 2 1
e mail: 
2 4- hr E mer ge nc y Tele p h o ne N u m ber
U S A: 
I nter nati o nal: 
Cel ge ne I nter n ati o n al II S àrl
R o ute de Perre u x 1
2 0 1 7 B o u dr y , S wi t z erla n d
Tel: 
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4 -A u g -2 0 2 3
2
R E G U L A T O R Y A G E N C Y I D E N TI FI E R N U M B E R( S)
I N D: 1 2 6 7 4 0
E u dra C T: 2 0 2 1 - 0 0 5 0 1 9- 3 0
T his d oc u me nt is t he c o nfi de nti al a n d pr o priet ar y i nf or m ati o n of Brist ol -M yers 
S q ui b b 
C o m p a n y a n d its gl o b al affili ates ( B M S). B y re vie wi n g t his d oc u me nt, y o u a gree t o kee p it 
c o nfi de nti al a n d t o use a n d discl ose it s olel y f or t he p ur p ose of assessi n g w het her y o ur 
or g a niz ati o n will p artici p ate i n a n d/ or t he perf or m a nce of t he pr o p ose d B M S s p o ns ore d 
st u d y. A n y per mitte d disc l os ures will be m a de o nl y o n a c o nfi de nti al " nee d t o k n o w " b asis 
wit hi n y o ur or g a niz ati o n or t o y o ur i n de pe n de nt et hics c o m mittee(s). A n y ot her use, c o p yi n g, 
discl os ure or disse mi n ati o n of t his i nf or m ati o n is strictl y pr o hi bite d u nless e x pressl y 
a ut h orize d i n writi n g b y B M S. A n y s u p ple me nt al i nf or m ati o n (e g, a me n d me nts) t h at m a y 
be a d de d t o t his d oc u me nt is als o c o nfi de nti al a n d pr o priet ar y t o B M S a n d m ust be ke pt i n 
c o nfi de nce i n t he s a me m a n ner as t he c o nte nts of t his d oc u me nt. A n y pers o n w h o recei ves 
t his d oc u me nt wit h o ut d ue a ut h oriz ati o n fr o m B M S is re q ueste d t o ret ur n it t o B M S or 
pr o m ptl y destr o y it. Refere nces t o B M S i n t his pr ot oc ol m a y a p pl y t o p art ners t o w hic h B M S 
h as tr a nsferre d o bli g ati o ns (e g, a C o ntr act Rese arc h Or g a niz ati o n [C R O ]).
© 2 0 2 3 Brist ol -M yers S q ui b b C o m p a n y
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g -2 0 2 3
3
D O C U M E N T HI S T O R Y
D oc u me nt
D ate of Iss ue
S u m m ar y of C h a n ge s
Pr ot oc ol A me n d me nt 
0 2
1 4 -A u g -2 0 2 3
T he mai n p ur p ose of t his a me n d me nt is t o u p date t he
partici pa nt assess me nt sc he d ule , w hic h i ncl u des re m o val of 
re q uire me nts at 
all sites, re visi n g pr o hi bite d me dicati o ns, a n d clarif yi n g
rescree ni n g la n g ua ge, f or ali g n me nt wit h ot her pr ot oc ols 
wit hi n t he I nfla m mat o r y B o wel Disease pr o gra m s.
Pr ot oc ol A me n d me nt 
0 1
2 2- Dec - 2 0 2 2
T he mai n p ur p ose of t his a me n d me nt is t o u p date t he 
i ncl usi o n criteria t o (a) all o w f or p ositi ve varicella z oster 
vir us a nti b o d y titers t o hel p f ulfill t he vacci nati o n 
re q uire me nt a n d ( b) u p date t he dr u g cleara nce peri o d f or 
pri or bi ol o gics fr o m 8 wee ks t o 4 wee ks.
Ori gi nal Pr ot oc ol
2 5 -Fe b - 2 0 2 2
N ot a p plica ble
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
O V E R A L L R A TI O N A L E F O R P R O T O C O L A M E N D M E N T 0 2:
T he ma i n p ur p ose of  this a me n d me nt is t o u p date t he partici pa nt assess me nt sc he d ule, w hic h 
i ncl u des re m o val of  
 re q uire me nts at all sites, re visi n g pr o hi bite d me dicati ons, a n d clarif yi n g 
rescree ni n g la n g ua ge, f or ali g n me nt wit h ot her pr ot oc ols withi n t he I nfla m mat or y B o wel  Disease
pr o gra m s.
S U M M A R Y O F C H A N G E S F O R P R O T O C O L A M E N D M E N T 0 2
Secti o n N u m ber 
& Title
Descri pti o n of C h a n ge
Brief R ati o n ale
Title Pa ge

U p date d Cli nical Scie ntist a n d Cli nical Trial 
P h y sicia n c o ntact i nf or mati o n.

A d mi nistrati ve c ha n ge.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
4
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
S U M M A R Y O F C H A N G E S F O R P R O T O C O L A M E N D M E N T 0 2
Secti o n N u m ber 
& Title
Descri pti o n of C h a n ge
Brief R ati o n ale
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
5
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
S U M M A R Y O F C H A N G E S F O R P R O T O C O L A M E N D M E N T 0 2
Secti o n N u m ber 
& Title
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n 3. 1. 2 :
S u m mar y of 
Cli nical St u dies

U p date d s u m mar y of cli nical st u d y data.

U p date d base d o n t he latest 
versi o n ( v 1 6 ) of t he 
I n vesti gat or’s Br oc h ure.
Secti o n 5. 1 :
O verall Desi g n
 
 
 

U p date d f or c o nsist e nc y wit h t he 
rest of t he pr ot oc ol.
Secti o n 6. 1 :
I ncl usi o n Criteria

I ncl usi o n Criteri o n # 2)e)iii): C orrecte d 
ti mefra me fr o m “...starti n g 3 wee ks pri or t o 
Scree ni n g...” t o “...starti n g 2 wee ks pri or t o 
Scree ni n g...”

M o dificati o n
of sta ble d osi n g t o 
ali g n wit h oza ni m o d I B D 
pr o gra ms .

I ncl usi o n Criteri o n # 4: Re vise d “ F O C B P m ust 
ha ve a ne gati ve hi g hl y se nsiti ve ser u m pre g na nc y 
test (...) wit hi n 2 4 h o urs pri or t o t he start of st u d y 
i nter ve nti on ” t o “ F O C B P m ust ha ve a ne gati ve 
hi g hl y  se nsiti ve ser u m pre g na nc y test (...) pri or 
t o ra n d o mizati o n.”

U p date d, as testi n g is perf or me d 
o nce d uri n g t he scree ni n g 
wi n d o w o nl y .
Secti o n 6. 2 :
E xcl usi o n 
Criteria
Secti o n 7. 7. 2 :
Pr o hi bite d a n d/ or 
Restricte d 
Treat me nts

A d de d C Y P 2 C 8 i n d ucers (e g, rifa m pici n).

Re m o ve d breast ca ncer resista nce pr otei n 
i n hi bit ors (e g, c ycl os p ori ne, eltr o m b o pa g).

M o difie d t o ali g n wit h oza ni m o d 
c ore c o m pa n y data s heet.
Secti o n 6. 4 :
Scree n Fail ures

A d de d t he f oll o wi n g re gar di n g rescree ni n g of 
scree n fail ures: “Partici pa nts w h o fail t o meet t he 
i ncl usi o n/e xcl usi o n criteria ca n be rescree ne d 

A me n de d t o e ns ure t he pr ocess 
f or rescree ni n g a n d o btai ni n g 
a p pr o val is well -defi ne d.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
6
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
S U M M A R Y O F C H A N G E S F O R P R O T O C O L A M E N D M E N T 0 2
Secti o n N u m ber 
& Title
Descri pti o n of C h a n ge
Brief R ati o n ale
o nce per I n vesti gat or discreti o n. A d diti o nal 
scree ni n g atte m pts be y o n d t he first rescree n m ust 
be a p pr o ve d b y t he Cli nical Trial P h ysicia n or 
desi g nee pri or t o rescree ni n g .”
Secti o n 6. 4. 1 :
Retesti n g D uri n g 
Scree ni n g

Re m o ve d t he f oll o wi n g : “Partici pa nt 
Re -e nr oll me nt: T his st u d y per mits t he 
r e-e nr oll me nt of a partici pa nt w h o has 
disc o nti n ue d t he st u d y as a pretreat me nt fail ure 
(ie, partici pa nt has n ot bee n ra n d o mize d/ has n ot 
bee n treate d). If re -e nr olle d, t he partici pa nt m ust 
be re -c o nse nte d/re-asse nte d.”

T his la n g ua ge pertai ns t o 
partici pa nt ree nr oll me nt a n d n ot 
partici pa nt retesti n g; as s uc h, t he 
para gra p h is n ot rele va nt t o t he
secti o n.
Secti o n 7. 7. 1 :
Ster oi d Ta per

Clarifie d t hat ster oi d ta peri n g s h o ul d be 
c o m plete d wit hi n 6 m o nt hs after Wee k 1 2.

A d de d rec o m me n dati o n t o e ns ure 
ta peri n g is c o m plete d wit hi n 6 
m o nt hs a n d a v oi d l o n g -ter m 
c ortic oster oi d use i n pe diatric 
partici pa nts .

M o difie d t a peri n g sc he d ule f or b u des o ni de fr o m 
“...ta per t heir d ose of 9 m g/ da y t o 9 m g e ver y 
ot her da y f or 2 wee ks...” t o “ta per t heir d ose at a 
rate of 3 m g e ver y 3 wee ks...”

A me n de d t o ali g n wit h treat me nt 
i n cli nical practice.
Secti o n 7. 6 :
Treat me nt 
C o m plia nce

Clarifie d t hat partici pa nts will be as ke d t o ret ur n 
a n y re mai ni n g u n use d I P at t he e n d of t he st u d y, 
as well as at all visits d uri n g w hic h I P is 
dis pe nse d.

T o e ns ure dr u g c o m plia nce is 
pr o perl y m o nit ore d.
Secti o n 9 :
St u d y 
Assess me nts a n d 
Pr oce d ures

Re m o ve d t he f oll o wi n g:
o
“A scree n fail ure is defi ne d as a partici pa nt 
w h o has gi ve n c o nse nt/asse nt a n d w h ose 
L A R has gi ve n i nf or me d c o nse nt a n d faile d 
t o meet t he i ncl usi o n a n d/ or e xcl usi o n 
criteria. Partici pa nts w h o fail t o meet t he 
i ncl usi on/e xcl usi o n criteria ca n be 
rescree ne d per i n vesti gat or discreti o n. 
A d diti o nal scree ni n g atte m pts be y o n d t he 
first s h o ul d be a p pr o ve d b y t he Cli nical Trial 
P h y sicia n or desi g nee pri or t o rescree ni n g. 
Eac h partici pa nt m ust be re -c o nse nte d/re-
asse nte d, a n d the partici pa nt’s L A R m ust be 
r e-c o nse nte d pri or t o eac h scree ni n g 
atte m pt. ”
o
“ Eac h partici pa nt m ust be 
r e-c o nse nte d/re-asse nte d pri or t o eac h 
scree ni n g atte m pt.”

T o a v oi d re d u n da nc y wit hi n t he 
pr ot oc ol si nce alrea d y i ncl u de d i n 
Secti o n 6. 4 .
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
7
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
S U M M A R Y O F C H A N G E S F O R P R O T O C O L A M E N D M E N T 0 2
Secti o n N u m ber 
& Title
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n 9. 2. 5 :
Pre g na nc y

Re m o ve d t he f oll o wi n g: “I n or der f or t he 
S p o ns or or desi g nee t o c ollect a n y pre g na nc y 
s ur veilla nce i nf or mati o n fr o m t he fe male part ner, 
t he fe male part ner m ust si g n a n i nf or me d c o nse nt 
f or m (I C F) f or discl os ure of t his i nf or mati o n. 
I nf or mati o n o n t his pre g na nc y will be c ollecte d 
o n t he Pre g na nc y S ur veilla nce F or m.”

U p date d t o xic ol o gical fi n di n gs 
ha ve de m o nstrate d t here are n o 
si g nifica nt e x p os ure le vels 
e x pecte d i n male partici pa nts t hat 
c o ul d p ote ntiall y affect fe male 
part ners i n t he e ve nt of 
pr e g na nc y.
Secti o n 9. 4. 1 1 :
Vis ual Ac uit y 
Testi n g

A d de d ne w secti o n.

Defi ne d Vis ual Ac uit y testi n g 
ass ociate d wit h t he Sc he d ule of 
E ve nts.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
8
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
S U M M A R Y O F C H A N G E S F O R P R O T O C O L A M E N D M E N T 0 2
Secti o n N u m ber 
& Title
Descri pti o n of C h a n ge
Brief R ati o n ale
T hr o u g h o ut 
pr ot oc ol

Re place d “le gall y acce pta ble re prese ntati ve 
( L A R)” wit h “ pare nt(s) or g uar dia n(s).”

F or c o nsiste nc y wit h ot her B M S 
pr ot oc ols.

A d de d heart rate a n d bl o o d press ure i n t he 
sta n di n g p ositi o n.

F or assess me nt of ort h ostatic 
h y p ote nsi o n.

Mi n or e dit orial a n d f or matti n g c ha n ges, as well 
as clarificati o ns, t hat d o n ot affect c o nte nt.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
9
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


T A B L E O F C O N T E N T S  
 
 
TI T L E P A G E  ................................................................................................................ 
 
D O C U M E N T HI S T O R Y  .............................................................................................. 
 
O V E R A L L R A TI O N A L E F O R P R O T O C O L A M E N D M E N T  0 2:  ............................ 
 
S U M M A R Y O F C H A N G E S F O R P R O T O C O L A M E N D M E N T 0 2  ......................... 
 
T A B L E O F C O N T E N T S  .............................................................................................. 
 
1 P R O T O C O L S U M M A R Y  ......................................................................................... 
 
2 S C H E D U L E O F E V E N T S  ........................................................................................ 
 
3 I N T R O D U C TI O N  ..................................................................................................... 
 
3. 1 St u d y Rati o nale  ................................................................................................. 
 
3. 1. 1 S u m m ary of N o ncli nic al St u dies  .............................................................. 
 
3. 1. 2 S u m m ary of Cli nic al St u dies  .................................................................... 
 
3. 2 Bac k gr o u n d  ....................................................................................................... 
 
3. 3 Be nefit/ Ris k Assess me nt  .................................................................................. 
 
3. 3. 1 Risk Assess me nt  ....................................................................................... 
 
3. 3. 2 Be nefit Assess me nt  ................................................................................... 
 
3. 3. 3 Over all Be nefit/ Risk C o ncl usi o n  .............................................................. 
 
4 O BJ E C TI V E S A N D E N D P OI N T S  ........................................................................... 
 
5 S T U D Y D E SI G N ....................................................................................................... 
 
5. 1 O verall Desi g n  .................................................................................................. 
 
5. 1. 1 D at a M o nit ori n g C o m mittee a n d Ot her C o m mittees  ............................... 
 
5. 2 N u m ber of Partici pa nts  ..................................................................................... 
 
5. 3 E n d of St u d y Defi niti o n  .................................................................................... 
 
 
 
 
 
6 S T U D Y P O P U L A TI O N  ............................................................................................ 
 
6. 1 I ncl usi o n Criteria  .............................................................................................. 
 
6. 2 E xcl usi o n Criteria  ............................................................................................. 
 
6. 3 Lifest yle Restricti o ns  ........................................................................................ 
 
6. 4 Scree n Fail ures  .................................................................................................. 
 
6. 4. 1 Retesti n g D uri n g Scree ni n g  ..................................................................... 
 
7 S T U D Y I N T E R V E N TI O N ( S) A N D C O N C O MI T A N T T H E R A P Y  ....................... 
 
7. 1 St u d y I nter ve nti o ns A d mi nistere d  .................................................................... 
 
7. 2 Met h o d of St u d y I nter ve nti o n Assi g n me nt  ....................................................... 
 
7. 3 Bli n d i n g............................................................................................................. 
 
7. 4 D osa ge M o dificati o n  ......................................................................................... 
 
7. 5 Pre parati o n/ Ha n dli n g/ St ora ge/ Acc o u nta bilit y  .................................................. 
 
7. 6 Treat me nt C o m plia nce  ...................................................................................... 
 
7. 7 C o nc o mita nt T hera p y ........................................................................................ 
 
7. 7. 1 Ster oi d T a per  ........................................................................................... 
 
7. 7 . 2 Pr o hi bite d a n d/ or Restricte d Tre at me nts................................................. 
 
7. 7. 2. 1 I m a gi n g Restricti o n a n d Prec a uti o ns  ............................................. 
 
7. 8 C o nti n ue d Access t o St u d y I nter ve nti o n After t he E n d of t he St u d y  ............... 
 
8 DI S C O N TI N U A TI O N C R I T E RI A ........................................................................... 
 
8. 1 Disc o nti n uati o n Fr o m St u d y I nter ve nti o n  ........................................................ 
 
1
3
4
4
1 0
1 3
1 9
3 1
3 1
3 2
3 2
3 6
3 8
3 8
4 0
4 1
4 2
4 6
4 6
5 2
5 2
5 2
5 3
5 4
5 5
5 6
5 8
6 2
6 2
6 2
6 3
6 3
6 5
6 6
6 7
6 7
6 8
6 8
6 9
7 0
7 1
7 1
7 2
7 2
Cli nical Pr ot oc ol
B M S- 9 8 6 3 7 4
I M 0 4 7 0 2 3
Oza ni m o d
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 0
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


8. 1. 1 P ost -st u dy I nterve nti o n St u dy F oll o w-u p  ................................................ 
 
8. 2 Disc o nti n uati o n Fr o m t he St u d y  ....................................................................... 
 
8. 2. 1 I n divi d u al Disc o nti n u ati o n Criteri a  ........................................................ 
 
8. 3 L ost t o F oll o w -u p  .............................................................................................. 
 
9 S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  ..................................................... 
 
9. 1 Efficac y Assess me nts  ........................................................................................ 
 
9. 1. 1 Pe di atric Cr o h n’s Dise ase Activity I n dex  ................................................ 
 
9. 1. 2 Si m ple E n d osc o pic Sc ore f or Cr o h n's Dise ase  ........................................ 
 
9. 1. 3 Cr o h n’s Dise ase Activity I n dex  ................................................................ 
 
9. 1. 4 A b d o mi n al P ai n a n d St o ol Fre q ue ncy  ..................................................... 
 
9. 1. 5 E n d osc o pies a n d E n d osc o pic Bi o psies  .................................................... 
 
9. 1. 6 Eryt hr ocyte Se di me nt ati o n R ate  .............................................................. 
 
 
 
 
 
9. 1. 9 P artici p a nt Di aries  .................................................................................. 
 
9. 2 A d verse E ve nts  ................................................................................................. 
 
9. 2. 1 Ti me Peri o d a n d Fre q ue ncy f or C ollecti n g A E a n d S A E I nf or m ati o n  .... 
 
9. 2. 2 Met h o d of Detecti n g A Es a n d S A Es  ......................................................... 
 
9. 2. 3 F oll o w -u p of A Es a n d S A Es  ..................................................................... 
 
9. 2. 4 Re g ul at ory Re p orti n g Re q uire me nts f or S A Es  ......................................... 
 
9. 2. 5 Pre g n a ncy  ................................................................................................ 
 
9. 2. 6 L a b or at ory Test Res ult A b n or m alities  ..................................................... 
 
9. 2. 7 P ote nti al Dr u g -i n d uce d Liver I nj ury ....................................................... 
 
9. 2. 8 Ot her S afety C o nsi der ati o ns  .................................................................... 
 
9. 2. 9 A dverse Eve nts of S peci al I nterest  ........................................................... 
 
9. 3 O ver d ose  ........................................................................................................... 
 
9. 4 Safet y  ................................................................................................................ 
 
9. 4. 1 P hysic al Ex a mi n ati o ns  ............................................................................. 
 
9. 4. 2 Vit al Si g ns  ................................................................................................ 
 
9. 4. 3 Electr oc ar di o gr a ms  ................................................................................. 
 
9. 4. 4 Hei g ht a n d Wei g ht  ................................................................................... 
 
 
 
 
 
 
 
 
 
 
 
9. 4. 9 P ul m o n ary F u ncti o n Ev al u ati o ns  ............................................................ 
 
9. 4. 1 0 O p ht h al m ol o gic al Ev al u ati o ns  .............................................................. 
 
9. 4. 1 1 Vis u al Ac uity T esti n g ............................................................................. 
 
9. 4. 1 2 Cli nic al S afety L a b or at ory Assess me nts  ................................................ 
 
9. 4. 1 2. 1 He m at ol o gy  ................................................................................... 
 
9. 4. 1 2. 2 C he mistry  ...................................................................................... 
 
9. 4. 1 2. 3 Ser ol o gy  ........................................................................................ 
 
9. 5 P har mac o ki netics  .............................................................................................. 
 
 
 
 
 
7 5
7 5
7 5
7 6
7 6
8 0
8 0
8 0
8 1
8 2
8 3
8 3
8 3
8 4
8 4
8 4
8 4
8 6
8 6
8 6
8 6
8 7
8 7
8 7
8 7
9 0
9 1
9 1
9 1
9 1
9 1
9 1
9 2
9 2
9 2
9 3
9 5
9 6
9 6
9 6
9 7
9 9
9 9
1 0 0
1 0 2
1 0 2
Cli nical Pr ot oc ol
B M S- 9 8 6 3 7 4
I M 0 4 7 0 2 3
Oza ni m o d
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 1
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


9. 8 A d diti o nal Researc h  .......................................................................................... 
 
9. 9 Healt h Ec o n o mics O R Me dical Res o urce Utilizati o n a n d Healt h Ec o n o mics  . 
 
1 0 S T A TI S TI C A L C O N SI D E R A TI O N S  .................................................................... 
 
1 0. 1 Statistical H y p ot heses  ..................................................................................... 
 
1 0. 2 Sa m ple Size Deter mi nati o n  ............................................................................. 
 
1 0. 3 A nal ysis Sets  ................................................................................................... 
 
1 0. 4 Statistical A nal yses  ......................................................................................... 
 
1 0. 4. 1 Ge ner al C o nsi der ati o ns  ......................................................................... 
 
1 0. 4. 2 Pri m ary E n d p oi nt(s)  .............................................................................. 
 
1 0. 4. 3 Sec o n d a ry E n d p oi nt(s) ........................................................................... 
 
 
 
1 0. 4. 5 Ot her S afety A n alyses  ............................................................................ 
 
1 0. 4. 6 Ot her A n alyses  ....................................................................................... 
 
 
 
1 0. 4. 6. 2 Sc ori n g Al g orit h ms  ....................................................................... 
 
1 0. 4. 6. 3 Esti m a n d Fr a me w ork  .................................................................... 
 
 
 
1 1 R E F E R E N C E S  ........................................................................................................ 
 
1 2 A P P E N DI C E S  ......................................................................................................... 
 
A P P E N DI X 1 A B B R E VI A T I O N S A N D T R A D E M A R K S ........................................ 
 
A P P E N DI X 2 S T U D Y G O V E R N A N C E C O N SI D E R A TI O N S  ................................. 
 
A P P E N DI X 3 A D V E R S E E V E N T S A N D S E RI O U S A D V E R S E E V E N T S: 
D E FI NI TI O N S A N D P R O C E D U R E S F O R R E C O R DI N G , E V A L U A TI N G, 
F O L L O W -U P, A N D R E P O R TI N G  ....................................................................... 
 
A P P E N DI X 4 W O M E N O F C HI L D B E A RI N G P O T E N TI A L D E FI NI TI O N S A N D 
M E T H O D S O F C O N T R A C E P TI O N  ..................................................................... 
 
A P P E N DI X 5 C RI T E RI A T O D E FI N E I N A D E Q U A T E  R E S P O N S E ( P RI M A R Y),  
L O S S O F R E S P O N S E ( S E C O N D A R Y), A N D I N T O L E R A N C E T O P R E VI O U S 
S T A N D A R D O F C A R E M E D I C A TI O N( S) .......................................................... 
 
A P P E N DI X 6 P E DI A T RI C  C R O H N’ S DI S E A S E A C T I VI T Y I N D E X ( P CD AI)  ..... 
 
 
 
 
 
 
A P P E N DI X 9 P R O T O C O L A M E N D M E N T S U M M A R Y O F  C H A N G E HI S T O R Y
................................................................................................................................. 
 
 
1 0 3
1 0 4
1 0 4
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1 0 6
1 0 7
1 0 7
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1 0 8
1 0 8
1 0 8
1 0 9
1 0 9
1 0 9
1 0 9
1 1 2
1 1 3
1 1 7
1 1 8
1 2 2
1 3 3
1 3 7
1 4 1
1 4 3
1 4 4
1 4 5
1 4 6
Cli nical Pr ot oc ol
B M S- 9 8 6 3 7 4
I M 0 4 7 0 2 3
Oza ni m o d
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 2
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
1
P R O T O C O L S U M M A R Y
Pr ot oc ol Title:
A P h ase 2/ 3, M ul tice nter, Ra n d o mize d, D o u ble- b li n d St u d y  to E val uate t he Efficac y, Safet y,  
P har mac o ki net ics a n d P har mac o d y na mics of Oral Oza ni m o d ( R P C 1 0 6 3) i n Pe diatric Parti ci pa nts
wi t h 
Mo deratel y t o Se verel y Act i ve Cr o h n’s 
Di sease wi t h an I na de q uate Res p o nse 
t o 
C o n ve nti o nal T hera p y
Brief Title: Effi c a c y, Safet y , P har mac o ki net ics, a n d P har m ac o d y na mics of  Or al Oza ni mo d i n 
P e di atric P arti ci pa nts wi t h Mo deratel y t o Se verel y Act i ve Cr o h n’s Disease wi t h an I na de q uate 
Res p o nse t o C o n ve nt i onal T hera p y
R ati o n ale:
Des pite rece nt pr o gress i n Cr o h n’s disease ( C D) treat me nt, t here re mai ns a n u n met nee d f or oral 
a ge nts t hat are safe a n d c o n ve nie nt a n d t hat ca n pr o vi de effecti ve i n d ucti o n a n d l on g -t er m
mai nte na nce of  cli nical re missi on. Oza ni m o d is a s mall m o lec ule c o mp o u n d w hic h selecti vel y 
bi n ds wi t h hi gh affi nit y t o s p hi n g osi ne 1- p h os p hate ( S 1 P) rece pt ors 1 a n d 5. Ma n y cell ty pes 
e x press S 1 P 1, i ncl u di n g vasc ular e n d ot helial cells, brai n cells, a n d l y m p h oc ytes. Sti m ulat i on 
(a g o nis m) of  this rece pt or res ults i n bi o l ogical acti vities t hat i ncl u des l y m p h oc yt e rete ntio n i n 
p eri p heral  ly m p h o i d or ga ns (e g, l y m p h n o des a n d gastr oi ntesti nal Pe yer’s patc hes), res ulti n g i n 
re versi ble s yste mic re d uctio n i n circ ulati n g l y m p h oc ytes. Gi ve n 
t he i m m u ne-me d iate d 
i nfla m mati on i n C D, pre ve nt i on of  circ ulati on of  disease-e xacer bati n g, self-reacti ve l y m p h oc yt es 
t o t he g ut is li kel y t o ha ve sal utar y im m u n o m o d ulat or y  effects wi t h a co nse q ue nt da m pe ni n g of 
di sease pr ocesses.
T he be nefit /ris k pr ofile f or oza ni m o d has bee n e val uate d f or t he i n dicati o n of  CD i n a d ult 
parti ci pa nt s. I n a n o pe n -label P hase 2 st u d y i n a d ult partici pa nt s wit h m o deratel y t o se verel y act i ve 
C D
( R P C 0 1-2 2 0 1), oza ni m o d res ulte d i n e n d osc o pic, cli nical, a n d hist ol o gic i m pr o ve me nt at  
 as me as ure d b y ce ntrall y rea d Si m ple E n d osc o pic Sc ore f or Cr o h n’s D isease
(S E S -C D ) sc ores a n d hist o pat h ol o g y , Cr o h n’s D isease A ct i vity In de x ( C D AI) a n d 2- c o mp o ne nt 
pati e nt -re p orte d o utc o me (a b d o mi nal pai n a n d st o ol fre q ue nc y). 
 
 
Oza ni m o d is als o c urre ntl y bei n g st u die d i n P hase 3 st u dies i n a d ult parti ci pa nt s wi t h mo derate t o 
se vere C D as part of  a co m pre he nsi ve i nfla m mat or y bo w el  disease pr o gra m .
 
 
 
 
I n a d ditio n, oza ni m o d has bee n st u die d i n a c o mplete d P hase 2 ra n d omize d 
d o u ble -bli n d 
c o ntr olle d trial i n a d ults wi t h ulcerati ve c olit is ( U C; R P C 0 1 -2 0 2) a n d a c o m p lete d P hase 3 
ra n d omize d d o u ble -bli n d c o ntr olle d trial in a d ults wit h U C ( R P C 0 1-3 1 0 1). T hese st u dies ha ve
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 3
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
s h o w n hi g h parti ci pa nt rete ntio n, c o nsiste nt efficac y, a n d n o ne w safety si g nals e mer gi n g i n t his 
p o p ul at i on.
Gi ve n t he mec ha nis m of  act i on of  oza ni m o d, t he p osi tive res ults fr o m t he P h ase 2 C D st u d y 
( R P C 0 1- 2 20 1) a n d P hase 2 a n d 3 U C st u dies (R P C 0 1 -2 0 2 a n d R P C 0 1 - 3 1 0 1, res pecti vel y), as well 
as a n acce pta ble safet y pr ofile o bser ve d acr oss i n dicat i ons, oza ni m o d has t he p ote ntial t o a d dress 
a n u n met nee d i n t he pe diatri c C D p o p ul at i on. T his st u d y is bei n g c o n d ucte d t o c haracterize t h e 
p har mac o ki net ics ( P K) a n d p har mac o d y na mics ( P D) of  oza ni mo d o n ce dail y  a nd t o e val uate t he 
efficac y a n d safety o f oza ni m o d i n pe diatric part ici pa nts at d oses e q ui vale nt t o 0. 4 6 or 0. 9 2 m g/ da y
i n a d ults.
T a ble 1 :
O bjecti ves a n d E n d p oi nts
O bjecti ve
E n d p oi nt
Pri m ary – Effic acy

T o e val uate t he efficac y of oza ni m o d o nce dail y 
i n pe diatric partici pa nts wit h 
m o deratel y 
t o 
se verel y acti ve C D: cli nical re missi on b y P C D AI 
at Wee k 6 4

Pr o p orti o n o f partici pa nts w h o ac hie ve P C D AI < 1 0 
at Wee k 6 4

T o e val uate e n d osc o pic re missi o n at Wee k 6 4 b y 
S E S -C D

Pr o p orti o n of partici pa nts ac hie vi n g S E S -C D ≤ 2 or 
S E S -C D ≤ 4 p oi nts wit h n o S E S -C D s u bsc ore 
> 1 p oi nt at Wee k 6 4
Sec o n d ary – Effic acy ( Key)

T o e val uate t he efficac y of oza ni m o d o nce dail y 
i n pe diatric partici pa nts wit h 
m o deratel y 
t o 
se verel y acti ve C D: cli nical re missi on b y P C D AI 
at Wee k 1 2

Pr o p orti o n o f partici pa nts w h o ac hie ve P C D AI < 1 0 
at Wee k 1 2
Sec o n d ary – Effic acy ( Ot her)

T o e val uate e n d osc o pic res p o nse b y S E S -C D

Pr o p orti o n of partici pa nts w h o ac hie ve S E S -C D 
decrease fr o m Baseli ne of ≥5 0 % ( E R- 5 0) at Wee k 6 4; 
Wee k 1 2

T o e val uate cli nical res p o nse b y P C D AI

Pr o p orti o n of partici pa nts w h o ac hie ve re d ucti o n i n 
P C D AI sc ore ≥1 2. 5 a n d a t otal P C D AI sc ore of 
< 3 0 p oi nts at Wee k 6 4 ; Wee k 1 2

T o e val uate s y m pt o matic re missi o n (a d olesce nts 
o nl y )

Pr o p orti o n of a d olesce nt s w h o ac hie ve a n a vera ge 
dail y  ab d o mi nal pai n sc ore ≤1 p oi nt a n d a n a vera ge 
dail y  st o ol fre q ue nc y ≤3 p oi nts wit h a b d o mi nal pai n 
a n d st o ol fre q ue nc y n o w orse 
t ha n Baseli ne at 
Wee k
6 4 ; Wee k 1 2

T o e val uate c ha n ge i n C D s y m pt o ms o ver ti me

C ha n ge fr o m Baseli ne i n st o ol fre q ue nc y sc ore o ver 
ti m e

C ha n ge f r om Baseli ne i n a b d o mi nal pai n o ver ti me

T o 
e val uate 
cli nical 
r emissi o n 
b y 
C D AI 
(a d olesce nts o nl y)

Pr o p orti o n 
of 
a d olesce nt s wh o 
ac hie ve C D AI 
sc ore < 1 5 0 at Wee k 6 4 ; Wee k 1 2
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 4
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
T a ble 1 :
O bjecti ves a n d E n d p oi nts
O bjecti ve
E n d p oi nt

T o 
e val uate 
cli nical 
res p o nse 
b y 
C D AI 
(a d olesce nts o nl y)

Pr o p orti o n 
of 
a d olesce nt s wh o 
ac hie ve C D AI 
re d ucti on fr o m Baseli ne of ≥1 0 0 p oi nts or  CD AI 
sc ore < 1 5 0 at Wee k 6 4 ; Wee k 1 2

T o e val uate c ortic oster oi d -free re missi o n 

Pr o p orti o n of partici pa nts w h o ac hie ve a P C D AI 
sc ore < 1 0 at Wee k 6 4 w hile re mai ni n g c ortic oster oi d 
free i n t he pri or 1 2 wee ks

Pr o p orti o n of partici pa nts w h o ac hie ve a C D AI sc ore 
< 1 5 0 at Wee k 6 4 w hile re mai ni n g c ortic oster oi d free 
i n t he pri or 1 2 wee ks (a d olesce nts o nl y)

T o e val uate e n d osc o pic re missi o n at Wee k 1 2

Pr o p orti o n of partici pa nts ac hie vi n g S E S -C D ≤ 2 or 
S E S -C D ≤ 4 p oi nts wit h n o S E S -C D s u bsc ore 
> 1 p oi nt at Wee k 1 2
Sec o n d ary – P h ar m ac oki netics

T o c haracterize t he P K
of 2 d oses of or al 
oza ni m o d a n d its maj or 
acti ve meta b olites 
i n 
pe diatric partici pa nts wit h m o deratel y t o se verel y 
acti ve C D 

Stea d y state s yste mic e x p os ures of oza ni m o d a n d 
C C 1 1 2 2 7 3 at Wee k 2 0 a n d t hr o u g h o ut t he st u d y
Sec o n d ary – P h ar m ac o dy n a mics

T o e val uate t he P D of 2 d ose le vels of oza ni m o d 
(e g, effects o n A L C) i n pe diatric partici pa nts wit h 
m o deratel y t o se verel y acti ve C D

A bs ol ute a n d perce nt c h a n ge fr o m Baseli ne i n A L C 
at Wee k 6 4, Wee k
1 2 , a n d t hr o u g h o ut t he st u d y
Sec o n d ar y – S afety a n d T oler a bility

T o e val uate t he safet y a n d t olera bilit y of 2 d ose 
le vels of or al oza ni m o d o nce dail y  in pe diatric 
partici pa nts wit h m o deratel y  to se verel y acti ve 
C D

N u m ber a n d pr o p orti o n of partici pa nts e x perie nci n g 
A Es, S A Es, A Es lea di n g t o disc o nti n uati o n fr o m 
treat me nt, a n d A E SIs t hr o u g h o ut t he st u d y
A b bre viati o ns: A E, a d verse e ve nt; A E SI, a d verse e ve nt of s pecial i nterest; A L C, a bs ol ute l ym p h oc y te c o u nt ; C D, 
Cr o h n’s disease; C D AI, Cr o h n’s disease acti vit y in de x; S A E, seri o us a d verse e ve n t; S E S -C D, si m ple e n d osc o pic 
sc ore f or 
Cr oh n’s disease;
P C D AI , pe diatric Cr o h n’s disese acti vit y in de x ; P D, p har mac o d y na mics; P K, 
p har mac o ki netics .
O ver all St u d y Desi g n :
T his is a P hase 2/ 3, ra n d o mize d, d o u ble -bli n d st u d y t o e val uate t he efficac y, safety, a n d t olera bilit y
of  oral oza ni m o d o nce dail y i n pe diatric partici p a nts a ge d 2 t o 1 7 years , i ncl usi ve, wit h m o deratel y 
t o se verel y acti ve C D ( defi ne d as a Pe diatric Cr o h n’s Disease Acti vit y I nde x [ PC D AI ] sc ore of 
≥3 0 a n d a n S E S -C D sc ore of  ≥ 6 [or S E S -C D ≥4 i n parti ci pa nts wit h is olate d ileal disease]) wit h 
a n i na de q uate res p o nse, i ntolera nce, or l oss of  res p o nse t o pri or t hera p y f or C D. T he st u d y will 
als o e val uate t he P K a n d P D of  oral oza ni m o d a d mi nistere d o nce dail y  at 2 d ose levels ( 0. 4 6 or 
0. 9 2 m g/ d a y ad ul t e q ui vale nt d oses) i n pe di atric partici pa nt s d uri n g a 6 4 -wee k I n d ucti o n a n d 
Mai nte na nce treat me nt peri o d.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 5
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
 
. 
P arti cip a nts will be ra n d omize d i n a 1: 1 rati o t o recei ve eit her 0. 4 6 m g or 0. 9 2 m g / da y a d ult 
e q ui vale nt d oses of  oza ni mo d.
T he st u d y is c o mp ose d of  a 64- wee k d o u bl e-bli n d treat me nt p eri o d f oll owe d b y a n o pti o nal 
L o n g- t er m Ext e nsi o n ( L T E) P eri o d of  up t o a p pr o xi matel y 4. 5 ye ars. Parti ci pa nt s w h o meet t he 
earl y disc o nti n uati on crit eria aft er at least 7 wee ks of  treat me nt i n t he I n d ucti o n P eri o d, ha ve 
c o nfir me d disease w orse ni n g d uri n g t he M ai nt e na nce P eri o d , c o m p lete Wee k 
1 2 a n d are 
n o n -res p o n ders, or c o m pl ete Wee k 6 4 will ha ve t he o pti o n t o e nter t he L T E Peri o d.
N u m ber of P artici p a nts:
T he st u d y is t o e nr oll a p pr o xi matel y  
 pe diatric parti ci pa nt s. 
St u d y P o p ul ati o n:
A p pr o xi matel y  
pe diatri c parti ci pa nt s a ge d 2 t o 1 7 years, i ncl usi ve , wi t h m oderatel y t o se verel y 
acti ve C D ( defi ne d as a P C D AI ≥ 3 0 a n d a n S E S -C D sc o r e of ≥ 6 [or S E S -C D ≥ 4 i n part ici pa nts
wi t h is olate d ileal disease]) wi t h a n i na de q uate res p o nse, i ntol er a n c e, or loss of  res p o nse t o pri or 
t hera p y f or CD will be e nr o lle d i n t his st u d y.
I nter ve nti o n Gr o u ps a n d D ur ati o n:
P arti cipa nt s will be ra n d omize d i n a 1: 1 rati o t o recei ve eit her 0. 4 6 or 0. 9 2 m g/ da y a d ult e q ui vale nt 
d oses of  oza ni m o d. Wit hi n t he 
of  parti ci pa nt s a ged
, parti ci pa nt s will be 
 0. 4 6 a n d 0. 9 2 m g/ da y a d ult e q ui vale nt d oses 
.
P arti cipa nt s ma y s pe n d u p t o 8 1 wee ks i n t his st u d y, e xcl u di n g t he o pti o nal L T E Peri o d , i ncl u di n g 
u p t o 5 wee ks i n t he Scree ni n g P eri o d, 1 2 wee ks i n t he I n d ucti on P eri o d, 5 2 wee ks i n t he 
Mai nte na nce Peri o d, a n d u p t o  
 i n t he Safet y Fol l ow- U p Peri o d. Parti ci pa nt s t hat pr ocee d 
t o t he o pti o nal  LT E Peri o d will e nter t he Safet y F oll o w -U p P erio d at  the c o mpleti o n of  their 
parti ci pat i on i n t he L T E Peri o d.
T he o pti o nal  LT E Peri o d will all o w eli gi ble partici pa nt s t o c o nti n ue recei vi n g oza ni m o d f or u p t o 
a p pr o xi matel y 4.5 y ears or as per natio nal  or lo c al  r e q uire me nts.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 6
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
St u d y i nter ve nti o n :
All p a rtici pa nt s 
 

0. 4 6 m g/ da y d ose:
, t he n 0. 4 6 m g/ da y 
 a n d 
c o nti n ui n g 0. 4 6 m g/ da y 

0. 9 2 m g/ da y d ose:
 t he n 0. 4 6 m g/ da y 
, t he n 
0. 9 2 m g/ da y fr o m 
St atistic al Met h o ds
Efficac y will be e val uate d base d o n t he t otalit y o f t he data a n d a c o m pre he nsi ve a nal ysis base d o n 
descri pt i ve statistics. H y p ot hesis testi n g will n ot be perf or me d.
T he pri mar y  a nal yses of  t he 2 c o -pri mar y e n d p o i nts, pe diatric cli nical a n d e n d osc o pic re missi on 
at W ee k 6 4, will be base d o n t he i nte nt -t o-treat p o p ulat i on i n w hic h 
 
will be p o ol e d. T he esti mate d pr o p orti o ns alo n g wi t h their ass ociate d 2- side d 9 5 % Wal d 
c o nfi de nce i nter vals ( CI) usi n g a n or m al a p pr o xi mat i on f or a si n gle sa m ple pr o p orti o n will b e 
c o nstr ucte d. 
T he a nalyses of  t he k e y  sec o n dar y e nd p oi nt (e g, pe diatric cli nical re missio n  at Wee k 1 2) will be 
c o n d ucte d i n a si milar ma n ner as t he c o -pri mar y e n d p o i nt. 
D at a M o nit ori n g C o m mittee : Yes
A Data M o nit ori n g C o m mittee will be use d i n t he st u d y.
Ot her C o m mittee: Yes
T he 
S p o ns or will 
select a n 
 
 
 
 
Access t o treat me nt assi g n me nts will be strict l y li mite d t o gr o u ps direc tl y in v o l ve d wi t h dr u g 
di stri b uti on, pre parati o n of  u n bli n de d o ut p ut f or 
 a n d pers o n nel  in v o l ve d i n t he c o n d uct 
of  P D assa ys.
T o ass ure t hat all pers o n nel i n v ol ve d i n t he c o n d uct of t he st u d y re mai n bli n de d t o t h e res ults of 
i nteri m re vie ws, a bli ndi n g pl a n will  be s pecifie d i n t he D M C C harter.
Brief S u m m ar y:
T he p ur p ose of  this st u d y is to e val uate t he efficac y a n d safety of  oza ni m o d i n pe diatri c parti ci pa nts 
wi t h m o deratel y t o se verel y act i ve C D . T his will be e val uate d b y t he pr o p orti o n of  partici pa nts 
w h o ac hie ve P C D AI < 1 0 at Wee k 6 4 a n d t he pr o p ortio n of  p artici pa nts i n e n d osc o pic re missio n 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 7
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
(S E S -C D ≤2 or S E S -C D ≤ 4 p o i nts with n o  S E S-C D s u bsc ore > 1 p oi nt ) at Wee k 6 4 . St u d y  details 
i ncl u de t he f oll owi n g :

St u d y  durati o n: 8 1 wee ks (e xcl u di n g L T E peri o d)

St u d y  int er ve nt i on d urati o n: 6 4 wee ks

St u d y  visit fre q ue nc y: U p t o 3 ti mes d uri n g t he first 8 da ys o f the I n d uct i on Peri o d, t he n e ver y 
4 wee ks u nt il Wee k 1 2, t he n e ver y  8 wee ks starti n g at Wee k 2 0 i n t he Mai nte na nce Peri o d.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 8
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
2
S C H E D U L E O F E V E N T S
T a ble 2- 1:
Sc he d ule of E ve nts f or I n d ucti o n, M ai nte n a nce, a n d S afet y F oll o w -u p Peri o ds
Visit N u m ber
Wee k
St u d y E ntr y
I nf or me d 
c o nse nt/asse ntaa
I nclusi o n/e xcl usi o n 
criteria assess me nt
De m o gra p hics
Vira l ser ol o g y testi n ge
St o ol c ult ure f
T u b erc ul osis testi n g g
T D M
h
S af et y Assess me nts
Me dical hist or y i
Pri o r/c o nc o mita nt 
me d icati o ns
Pri o r/c o nc o mita nt 
pr oc e d ures
Pre g na nc y test a n d 
c o ntrace pti o n e d ucati o n
A Es
Vita l si g ns
Hei g ht
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 9
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
T a ble 2 - 1:
Sc he d ule of E ve nts f or I n d ucti o n, M ai nte n a nce, a n d S afet y F oll o w -u p Peri o ds
Visit N u m ber
Wee k
Wei g ht
 c ollecti o n
C o m plete p h ysical 
e xa mi nati o n m
I nteri m p h ysical 
e xa mi nati o n n
1 2- lea d E C G
Vis ual Ac uit y testz
O p ht hal m ol o gical
e val uati o n
P ul m o nar y f u ncti o n 
e val uati o n
He mat ol o g y
Bl o o d c he mistr y
Uri nal ysis
Effic ac y Assess me nts
Partici pa nt diar y f or C D 
acti vit y r
Brist ol St o ol Scale
(a d olesce nts 
)
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
2 0
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
T a ble 2 - 1:
Sc he d ule of E ve nts f or I n d ucti o n, M ai nte n a nce, a n d S afet y F oll o w -u p Peri o ds
Visit N u m ber
Wee k
C D AI (a d olesce nts 
C ol o n osc o p y/ S E S -C D/
c ol o nic bi o ps y s
P C D AI
E S R f or P C D AI
P K/ P D Assess me nts
Bl o o d sa m ple f or P K t,
Bl o o d sa m ple f or P D 
Ser u m sa m ple f or P D t,
St o ol sa m ple f or 
 
 bl o o d 
sa m plet,
I P
Dis pe nse I Px
A d mi nister I P i n cli nic
Re vie w dr u g c o m plia nce
A b bre viati o ns: A E , a d verse e ve nt; A V, atri o ve ntric ular ; B P, bl o o d press ure; C D , Cr o h n’s disease ; C D AI , Cr o h n’s Disease Acti vit y  In de x; d , da y s; 
 
 D N A , de o x yri b o n ucleic aci d, E C G , electr ocar di o gra m, E S R , er yt hr oc yte se di me ntati o n rate;
 
F/ U , f oll o w- u p;
H R, heart rate; I g G, im m u n o gl o b uli n G ; I g M, im m u n o gl o b uli n M ; I G R A, i nterfer o n 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
2 1
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
ga m ma release assa y ; I P, i n vesti gati o nal pr o d uct;
 P D , p har mac o d y na mic ; P K , p har mac o ki netic ; P C D AI , Pe diatric Cr o h n’s 
Disease Acti vit y  I n d e x;
S E S -C D , Si m ple E n d osc o pic Sc ore f or Cr o h n’s Disease ; S F U = Safet y 
F oll o w -u p Visit; T B , t u berc ul osis; T D M, thera pe utic dr u g m o nit ori n g ; V Z V, varicella z oster vir us.
 
 
 
 
 
 
 
 
f
At Scree ni n g, t he st o ol sa m ple s ho ul d be use d t o r ule o ut seri o us i nfecti o n a n d s h o ul d i ncl u de e val uati o n f or Cl ostri di oi de s difficile t o xi n as well as o va a n d
parasitic e xa mi nati o n.
g
Acti ve T B  m ust be r ule d o ut acc or di n g t o l ocal me dical practices. Late nt T B m ust be assesse d wit h a T B s ki n test, Q ua nti F E R O N G ol d test, or ot her I G R A (e g,
T- S P O T). A n y re peat testi n g f or late nt T B s h o ul d be a p pr o ve d b y t he Cli nical Trial P h ysicia n or desi g nee. Partici pa nts wit h lat e n t T B m ust ha ve d oc u me ntati o n
of pr o p h y lactic treat me nt b y l ocal sta n dar d of care. Par tici pa nts wit h late nt T B w h o ha ve i nitiate d pr o p h ylactic treat me nt b y l ocal sta n dar d of care, partici pa nts
wit h a n i ndeter mi nate test res ult, or  partici pa nts dia g n ose d wit h I G R A tests ot her t ha n Q ua nti F E R O N G ol d or  T-S P O T m ust be disc usse d f or eli gi bilit y o n a
case- b y-case basis b y t he S p o ns or, Cli nical Trial P h ysicia n , or  desi g nee.
h
O pti o nal t est f or partici pa nt s w h o are c urre ntl y bei n g treate d wit h bi ol o gical a ge nts t o be perf or me d via l ocal la b or at ories. T he re q uire d dr u g cleara nce peri o d
will be wa i ved f or partici pa nt s w h o ha ve u n detecta ble dr u g le vels o n T D M testi n g at S cree ni n g or pri or t o S cree ni n g ( Secti o n 9 ).
i
Me dical h ist or y will i ncl u de s m o ki n g hist o r y a n d detaile d C D me dical hist or y . T he Da y  
me dical his t or y ca n be a b bre viate d, n oti n g e ve nts t hat occ urre d
bet wee n S cree ni n g a n d Visit .
 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
2 2
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
 
 
 
 
 
m
T he c o m plete p h ysical e xa mi nati o n will i ncl u de a f ull e xa mi nati o n of t he s ki n f or lesi o ns, a c hec k f or vis ual s y m pt o ms (ie, b l urre d visi on or decrease d vi si o n), 
a n d hei g ht a n d wei g ht. A c hec k f or vis ual s y m pt o ms a n d a f ull e xa mi nati o n of t he s ki n s h o ul d be re peate d e ver y 6 m o nt hs.
n
T he i nteri m p h ysical e xa mi nati o n will i ncl u de wei g ht, a c h ec k f or vis ual s y m pt o ms, an d a n e val uati o n of b o d y s yste ms wit h pr e vi o usl y note d a b n or malities 
a n d/ or t h ose b o d y s yste ms ass ociate d wit h a n y ne w c o m plai nts fr o m t he partici pa nt (see Secti o n 9. 4. 1 ).
 
 
 
 
 
 
 
 
 
 
 
 
 
 
r
At Scree ni n g, partici pa nts
will be iss ue d a partici pa nt diar y f or C D s y m pt o ms a n d will be trai ne d i n t he use of t he diar y. Partici pa nt c o m plia nce 
wit h t he c o m pleti o n of t he diar y data s h o ul d be assesse d at eac h st u d y visit.
s
C ol o n osc o p y s h o ul d be perf or me d u p o n c o nfir mati o n of eli gi bilit y base d o n P C D AI a n d ot her e ntr y criteria, if p ossi ble. A partici pa nt’s pre vi o us c ol o n osc o py 
m a y  be use d if wit hi n 3 5 da ys of ra n d o mizati o n ( Da y ). 
 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
2 3
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
t
B l o o d sa m ple c ollecti o n f or 
 P K, a n d 
 will be c o n d ucte d base d o n partici pa nt wei g ht a n d bl o o d c ollecti o n g ui deli nes (see 
Secti o n 9. 4. 1 2 . F or s pecific details o n la bor at or y dra ws b y  wei g ht, please refer t o t he La b Fl o w ch art .
 
 
 
 
 
 
 
x
C urre nt I P will be re dis pe nse d f or partici pa nts w h o are n ot e nteri n g t he L T E P er i o d o n t he sa me da y. C urre nt I P will n ot be re dis pe nse d f or partici pa nts w h o are 
enteri n g t he L T E P eri o d o n t he sa me da y; L T E I P will be dis pe nse d i nstea d.
z
Vis ual ac uit y test res ults will be rec or de d ba se d o n t he a ge-a p pr o priate tests perf or me d i n all partici pa nts b y a n i n di vi d ual wit h a p pr o priate trai ni n g .
aa O nce a partici pa nt t ur ns 1 8 years of a ge ( or l ocal a ge of maj orit y), he/s he ma y nee d t o si g n a c o nse nt f or m, i n acc or da nce wi t h re gi o nal or l ocal re g ulati o ns.
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
2 4
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
T a ble 2 - 2:
Sc he d ule of E ve nts f or L o n g -ter m E xte nsi o n a n d S afet y F oll o w-u p Peri o ds
V isit N u m ber
Wee k
S afet y Assess me nts
P ri or/c o nc o mita nt 
m e dicati o ns
P ri or/c o nc o mita nt 
p r oce d ures
P re g na nc y test a n d 
co ntrace pti o n e d ucati o n
A d verse e ve nts
V ital si g ns
H ei g ht
W ei g ht
 c ollecti o n
C o m plete p h ysical 
exa mi nati o n g
Interi m p h ysical 
exa mi nati o n h
1 2- lea d E C Gi
V is ual Ac uit y Testt
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
2 5
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
T a ble 2 - 2:
Sc he d ule of E ve nts f or L o n g -ter m E xte nsi o n a n d S afet y F oll o w-u p Peri o ds
Visit N u m ber
Wee k
O p ht hal m ol o g i c
e val uati o n
P ul m o nar y f u ncti o n 
e val uati o n
He mat ol o g y
Bl o o d c he mistr y
Uri nal ysis
Effic ac y Assess me nts
Partici pa nt diar y f or C D 
acti vit ym
Brist ol St o ol Scale
(a d olesce nts 
)
C D AI (a d olesce nts 
)
Re mi n der p h o ne call f or 
partici pa nt diar y e ntr y
C ol o n osc o p y/ S E S -
C D/c ol o nic bi o ps y n
P C D AI
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
2 6
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
T a ble 2 - 2:
Sc he d ule of E ve nts f or L o n g -ter m E xte nsi o n a n d S afet y F oll o w-u p Peri o ds
Visit N u m ber
Wee k
E S R f or P C D AI
P K/ P D Assess me nts
Bl o o d sa m ple f or P K o ,p
Bl o o d sa m ple f or P D 
p
Ser u m sa m ple f or P D p
St o ol sa m ple f or 
 
 bl o o d 
sa m plesq
I P
Dis pe nse I P
A d mi nister I P i n cli nic
Re vie w dr u g c o m plia nce
A b bre viati o ns: C D , Cr o h n’s disease ; C D AI , Cr o h n’s Disease Acti vit y I n de x; d, da y s;
E C G , electr ocar di o gra m; E S R ,
er yt hr oc yte se di me ntati o n rate;
I P, i n vesti gati o nal pr o d uct; L T E, 
l o n g-ter m e xte nsi o n; N A, n ot a p plica ble; 
P D , p har mac o d y na mic ; P K , p har mac o ki netic ; P C D AI , Pe diatric Cr o h n’s Disease 
Acti vit y  I n de x;
S E S -C D , Si m ple E n d osc o pic Sc ore f or Cr o h n’s Disease.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
2 7
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
 
 
 
 
 
 
 
g
F or all partici pa nts, a c o m plete p h ysical e xa mi nati o n ( w hic h i ncl u des hei g ht a n d wei g ht) will be perf or me d at 
 T he c o m plete 
p h y sical e xa mi nati o n c o nsists of a f ull e xa mi nati o n of t he s ki n f or lesi o ns as well as a c h ec k f or vis ual s y m pt o ms (ie, bl urre d visi o n or  decrease d visi o n ). A 
chec k f or vis ual s y m pt o ms a n d a f ull e xa mi nati o n of t he s ki n s h o ul d be re peate d e ver y 6 m o nt hs. 
h
At all ot her visits, ot her 
, a n i nteri m p h ysical ma y be perf or me d. T he i nteri m p h ysical e xa mi nati o n will i ncl u de b o d y  s yste ms wit h 
p re vi o usl y n ote d a b n or malities a n d/ or t h ose b o d y s yste ms ass ociate d wit h a n y ne w c o m plai nts fr o m t he partici pa nt.
i
If a partici pa nt e nters t he L T E peri o d earl y pri or t o c o m pleti n g t he I n d ucti o n Peri o d a nd di d n ot recei ve a  
 E C G i n t he I n d ucti o n Peri o d, a 1 2 -lea d E C G 
sh o ul d be c o n d ucte d at t he st u d y visit t hat c oi nci des cl osest wit h c o m pleti o n of 
 of treat me nt.
 
 
 
 
 
 
 
 
 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
2 8
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
 
 
 
m
Partici pa nts 
 w h o partici pate i n t he L T E Peri o d wil l c o m plete diaries f or at least 1 4 da y s pri or t o eac h sc he d ule d visit, 
 Safety 
F oll o w -u p Visit. Site staff will call partici pa n ts at least 1 4 da ys pri or t o eac h st u d y visit t o re mi n d t he m t o c o m plete t heir diaries.
n
C ol o n o sc o p y is n ot re q uire d at a n y s pecific ti me p oi nt i n t he L T E Peri o d; h o we ver, if perf or me d, res ults of c ol o n osc o p y e val uati o n s h o ul d be d oc u me nte d.
o
A bl o o d sa m ple f or P K s h o ul d be c ollecte d a p pr o xi matel y e ver y 4 8 wee ks d uri n g treat me nt wit h oza ni m o d, o n th e  sa me da y as a pla n ne d he mat ol o g y c ollecti o n. 
O ne sa m ple s h o ul d be c ollecte d at a n y ti me p ost -d ose.
p
Bl o o d sa m ple c ollecti o n f or 
 P K, a n d 
 will be c o n d ucte d base d o n partici pa nt wei g ht a n d bl o o d c ollecti o n g ui deli nes (see 
Secti o n 9. 4. 1 2 ). F or s pecific details o n la bor at or y dra ws b y  wei g ht, please refer t o t he La b Fl o w ch art .
 
t
Vis ual ac uit y test res ults will be rec or de d base d o n t he a ge-a p pr o priate tests perf or me d i n all partici pa nts b y a n i n di vi d ual wit h a p pr o priate trai ni n g .
 
N ote: O nce a partici pa nt t ur ns 1 8 years of a ge ( or l ocal a ge of maj orit y), he/s he ma y nee d t o si g n a c o nse nt f or m, i n acc or da nce wi t h re gi onal or l ocal re g ulati o ns .
It is rec o m me n de d t hat st u d y visits are sc he d ule d i n t he mor ni n g (e xce pt f or 
 at w hic h partici pa nts are t o a d mi nist er I P at h o me 
at least 
 pri or t o arri vi n g f or t his visit ). O n st u d y visit da ys w he n pre -d ose (tr o u g h) P K sa m ples are t o be dra w n, parti ci pa nt s 
s h o uld be i nstr ucte d t o wi t hh o l d t he d ose u ntil t he st u d y visit, a n d t he d ose will be a d mi nistere d d uri n g t he visit.
W he ne ver p ossi ble, t he se q ue nce of  assess me nts s h o uld r e mai n c o nsta nt a n d at a p pr o xi matel y t he sa me ti me of  da y thr o u g h o ut t he 
st u d y. It is rec om me n de d t hat pr oce d ures are perf or me d i n t he f o ll o wi n g or der ( n ote t hat n ot all pr oce d ures are perf or me d at e ver y visit):

S p o nta ne o us or s olicite d A E re p orti n g

E C G

V ital si g ns

C li nical la b orat or y tests, incl u di n g pre -d ose P K sa m pli n g
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
2 9
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d

P h ysical e xa mi nat i on

E fficac y assess me nts

I P a d mi nistrati o n ( o n visits w he n pre -d ose P K bl o o d dra ws are c ollecte d ; see Sectio n 9. 5 )
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
3 0
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
3 
I N T R O D U C TI O N
Oza ni m o d h y dr oc hl ori de ( R P C 1 0 6 3; hereafter referre d t o as oza ni m o d) is a s mall mol ec ule 
c o mp o u n d w hic h 
selecti vel y bi n ds wi t h hi g h affi nit y t o s p hi n g osi ne 1- p h os p hate ( S 1 P) 
rece pt ors 1 a n d 5. I n vit r o, oza ni m o d has little acti vit y on t he ot her S 1 P rece pt ors, s h o wi n g half 
ma xi mal effect i ve c o nce ntratio n greater t ha n 1 0, 0 0 0 n M f or S 1 P 2, > 5 0 0 0 n M f or S 1 P 3, a n d 
> 2 0 0 0 n M f or S 1 P 4.
Ma n y  c ell t ypes e x press S 1 P 1, i ncl u di n g vasc ular e n d ot helial cells, brai n cells, a n d l y m p h oc yt es. 
Sti m ulat i on (a g o nis m) of  this rece pt or res ults i n bi o l ogical  act i vities t hat i ncl u de l y m p h oc yt e 
rete ntio n i n peri p heral  ly m p h o i d or ga ns (e g, l y m p h n o des a n d gastr oi ntesti nal [ GI] Pe yer’s 
patc hes), res ulti n g i n re versi ble s yste mic re d uctio n i n circ ulati n g l y m p h oc ytes. Gi ve n t he 
i m m u ne-me diate d 
i nfla m mati on i n C D, pre ve nti o n of  circ ulat i on of  disease-e xacer bat i n g, 
self-reacti ve l y m p h oc ytes t o t he g ut is li kel y t o ha ve sal utar y im m u n o m o d ulat or y  effects wit h a 
c o nse q ue nt da m pe ni n g of disease pr ocesses.
Oza ni m o d is e xte nsi vel y meta b o lize d i n h u ma ns t o f or m se veral circ ulati n g acti ve met a b o lites, 
i ncl u di n g 2 maj or acti ve meta b o lite s ( C C 1 1 2 2 7 3 [als o referre d t o as R P 1 1 2 2 7 3]) a n d C C 1 0 8 4 0 3 7 
[ als o referre d t o as R P 1 0 0 7 9 8]). Oza ni m o d a n d its acti ve met a b o lites ha ve si milar c he mical 
str uct ures, activit y, a n d selecti vity f or S 1 P 1 a n d S 1 P 5 rece pt ors. F o ll owi n g m ult i ple d ose 
a d mi nistrati o n o f oza ni m o d i n healt h y a d ult parti ci pa nt s, a p pr o xi matel y 9 4 % of  circ ulat i n g t otal 
acti ve dr u g e x p os ure is re prese nte d b y oza ni m o d ( 6 %), C C 1 1 2 2 7 3 ( 7 3 %), a n d C C 1 0 8 4 0 3 7 ( 1 5 %). 
Oza ni m o d has n o u ni q ue h u ma n meta b o lites, wit h all n ota ble h u ma n meta b olites prese nt i n o ne or 
m o re a ni mal s pecies use d f or safety testi n g.
Des pite rece nt pr o gress i n C D treat me nt, t here re mai ns a n u n met nee d f or oral a ge nts t hat are safe,
c o n ve nie nt , a n d a ble t o pr o vi de effect i ve i n d uctio n a n d l on g -t er m mai nte na nce of cli nical 
re missi o n.
T he pri mar y  mo de of  act i on f or oza ni m o d is t ho u g ht t o be via t he S 1 P 1 -me d iate d i n hi biti on of 
l y m p h oc yt e traffic ki n g.
M ore 
s pecificall y, 
S 1 P 1 
a g o nis m 
ca uses 
i nter nalizat i on 
of 
t he S 1 P 1 rece pt ors o n l y m p h oc ytes, res ulti n g i n t heir rete nti o n i n l y m p h oi d tiss ues s uc h as l y m p h 
n o des, a n d t hus decrease d le vels of  l y m p h oc ytes prese nt i n the c irc ulati o n. T his ma y res ult i n fe wer 
i m m u ne cells traffic ki n g t o i nfla m mat or y sit es s uc h as t he g ut a n d, s u bse q ue ntl y, less 
i nfla m mati on.
3. 1
St u d y R ati o n al e
Oza ni m o d is bei n g st u die d i n a c o m pre he nsi ve i nfla m mat or y b owel  disease (I B D) pr o gra m , w hic h 
i ncl u des parti ci pa nts wi t h CD as well  as partici p a nts wi t h ulcerati ve c o litis ( U C). T he a d ult C D 
pr o gra m c o nsists of  a co m plete d, o pe n -label P hase 2 stu d y d e m o n strati n g i m pr o ve me nts i n 
e n d osc o pic a n d cli nical o ut c o m es, an d a n o n g oi n g P hase 3 pi v otal pr o gra m . Res ults fr o m a 
 
treate d wit h oza ni m o d 0. 4 6 a n d 0. 9 2 m g dail y  su g geste d efficac y f or i n d ucti on a n d mai nte na nce 
of  cli nical re missio n  an d a d ose res p o nse relatio ns hi p. Res ul ts fr om a P hase 3 st u d y co nfi r me d 
0. 9 2 m g/ da y f or i n d ucti on a n d mai nte n a nce of  cli nical re missio n  for m o derate t o se vere U C.
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
3 1
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
 
 
 
I n a d diti on, oza ni m o d has bee n st u die d f or t he treat me nt of patie nts wit h m ult i ple scler osis ( M S). 
I n M S P h ase 3 pi v ot al  trials, tr e at me nt wit h oza ni m o d 0. 9 2 m g a n d 0. 4 6 m g/ da y d e m o n strate d 
statisticall y si g nifica nt, cli nicall y mea ni n gf ul 
re d uctio ns i n a n nualize d r ela pse rate (A R R )
c o mpare d wi t h int erfer o n beta -1a (I F N β -1a) at 1 2 m o nt hs a n d 2 4 m o nt hs , wit h a d ose-de pe n de nt 
effect fa v ori n g t he oza ni m o d 0. 9 2 m g/ da y d ose.
T his st u d y is bei n g c o n d ucte d t o e val uate t he efficac y an d safet y o f oza ni m o d i n C D i n t he pe diatric 
p o p ul at i on.
3. 1. 1
S u m m ar y of N o n cli ni c al St u di e s
T he n o ncli nical safety assess me nt f or oza ni m o d i ncl u de d re peate d d ose t o xicit y (r o de nt a n d
n o n- r o de nt), 
ge n ot o xicit y, 
carci n o ge nicit y, 
re pr o d ucti ve 
a n d 
de vel o p m e nt al  
to xi cit y,
p h ot ot o xi cit y, a n d i m m un ot o xi c o l og y  st u dies.
T he maj o rit y of t he fi n di n gs i n t he c hr o nic t o xic o l og y , carci n o ge nicit y, a n d re pr o d uctiv e 
t o xic o l og y  st u dies are c o nsi dere d tar get-me d iate d effects of  S1 P 1 a n d S 1 P 5 a g o nists. 
 
 
 
 
 
 
 
 
 
 
 
 
 
3. 1. 2
S u m m ar y of Cli ni c al St u di e s
M ulti ple Scler osis
T he M S de vel o p me nt pr o gra m c o mprises t he f oll owi n g st u dies: 1 P hase 2 st u d y (R P C 0 1 -2 0 1 A), 
2 P hase 3 st u dies ( R P C 0 1 -2 0 1 B a n d R P C 0 1 -3 0 1), a n d 1 P hase 3 o pe n -la bel e xte nsi on ( O L E) st u d y 
( R P C 0 1-3 0 0 1). I n t he P hase 2 st u d y R P C 0 1-2 0 1 A, n u merical re d uct i ons i n A R R of a p pr o xi matel y 
5 3 % a n d 3 1 % r elat i ve t o place b o were o bser ve d f or oza ni m o d 0. 9 2 m g / da y a n d oza ni m o d 
0. 4 6 m g/ da y, res pecti vel y. I n P hase 3 St u di es R P C 0 1 -2 0 1 B a n d R P C 0 1 -3 0 1, treat me nt wi t h 
oza ni m o d 0. 9 2 m g / da y a n d 0. 4 6 mg/ da y  r es ulte d i n statisticall y si gnifica nt, cli nicall y  mea ni n gf ul 
re d uctio ns i n A R R c o m pare d wit h I F N β -1a at 1 2 m o n t hs a n d 2 4 m o n t hs. A d ose-de pe n de nt effect 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
3 2
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
was o bser ve d fa v ori n g t he oza ni m o d 0. 9 2 m g/ da y d ose o ver t he 0. 4 6 m g/ da y d ose i n t he p o ol e d 
a nal ysis a n d b ot h P hase 3 st u dies. As o f t he last data c ut -off date f or t he O L E st u d y R P C 0 1-3 0 0 1 
( 01 -Fe b - 2 02 2 ), partici pa nt s w h o ha d recei ve d I F N β- 1a or oza ni m o d i n t he pare nt st u dies ha d 
si milar c u m ulati ve parti ci pa nt -years of  ex p os ure t o o pe n -lab el  oza ni m o d, a n d t he maj o rit y of 
parti ci pa nt s ha d recei ve d oza ni m o d 0. 9 2 m g/ da y i n t he O L E f or a mi ni m u m of  36 m o nt hs. A n 
o verall u na dj uste d A R R of  0. 1 3 2 was o bser ve d i n t he O L E st u d y with little varia bilit y acr oss 
pare nt treat me nt gr o u ps.
Acr oss t he M S st u di es, t h e most f re q ue ntl y re p orte d treat me nt -e mer ge nt a d verse e ve nts ( T E A Es)
occ urri n g i n ≥ 5 % parti ci pa nt s i n a n y treat me nt gr o u p i ncl u de d nas o p har y n git is, hea dac he, a n d 
u p per res pirat or y tract i nfecti on. I n t he act i ve-c o ntr olle d P hase 3 st u dies, t he i nci de nce of  
nas o p har y n git is was sli g htl y hi g her i n t he oza ni m o d treat me nt gr o u ps t ha n i n t he I F N β- 1a 
treat me nt gr o u p, b ut n o d ose effect was o bser ve d. T he i nci de nces of  hea dac he a n d u p per 
res pir at or y tract i nfecti on were si milar acr oss t he 3 treat me nt gr o u ps. I n t he c o m bi ne d safet y p o ol 
of  all M S st u dies, t he i nci de nce of  all T E A Es was sli g htl y hi g her i n t he oza ni m o d 0. 9 2 m g/ da y 
treat me nt gr o u p t ha n i n t he oza ni m o d 0. 4 6 m g/ d a y  treat me nt gr o u p. A greater pr o p orti o n of 
parti ci pa nt s i n t he oza ni m o d 0. 9 2 m g/ da y 
treat me nt gr o u p re p orte d i ncrease d ala ni ne 
a min otra nsferase ( A L T) as c o m pare d t o t he oza ni m o d 0. 4 6 m g/ da y (all rela psi n g M S
st u dies) a n d 
I F N β- 1a treat m e nt gr o u ps ( P hase 3 stu dies). I nfecti o ns m o re fre q ue ntl y re p orte d wit h oza ni m o d 
pri maril y i n v ol ve d t he u p per res pirat or y tract or uri nar y tr a ct. I mp or ta ntl y, r e d u ctio ns i n a bs ol ute 
l y m p h oc yt e c o u nt di d n ot a p pear t o be ass ociate d wit h a n i ncrease d i nci de nce of i nfect i ons.
Ulcer ati ve C olitis
T he de vel o p me nt pr o gra m  in a d ul ts wit h mo deratel y t o se verel y acti ve U C i ncl u des a c o mplete d 
P hase 2 ra n d o mize d d o u bl e- bli n d c o ntr olle d trial in a d ults ( R P C 0 1-2 0 2) a n d a c o m p lete d 
P hase 3 ra n d o mize d d o u ble-bli n d c o ntr olle d tri al in a d ults ( R P C 0 1-3 1 0 1). Partici pa nt s fr o m b ot h 
trials were offere d t he o p p ort u ni t y t o r oll o ver i nt o a n a d dit i onal o n g oi n g O L E trial ( R P C 0 1-3 1 0 2). 
T he ke y efficac y e n d p o i nts i n b ot h c o mplete d st u dies were t he pr o p orti o n of  p arti ci pa nt s i n cli nical 
re missi o n at t he e n d of t he i n d ucti o n a n d mai nte na nce p hases.
T he P hase 2 U C tri al (R P C 0 1 -2 0 2) de m o nstrate d t hat, at t he c o nclusi o n  of t he 9 -wee k in d uct i on 
p hase, t he pr o p orti o n of  part ici pa nts ac hie vi n g cli nical re missi on ( 4-c o mp o ne nt Ma y o sc ore 
≤2 p oi nts wi t h no i n di vi d ual s u bsc ore > 1 p oi nt ) wit h oza ni m o d 0. 9 2 m g/ da y was greater t ha n 
pl ace b o , a n d t he differe nce was b ot h cli nicall y mea ni n gf ul a n d st atisticall y si g nifica nt. I n a d diti on,  
all sec o n dar y en d p o i nts at t he c o nclusi o n  of t he i n d ucti on p hase, i ncl u di n g cli nical res p o nse 
( a re d ucti o n of  4-c o mp o ne nt Ma y o sc ore of  ≥ 3 p oi nts a n d at least 3 0 % wit h a re d uctio n fr om 
B aseli ne i n t he Rectal  Blee di ng s u bsc ore of  ≥ 1 p oi nt), c ha n ge i n t he Ma y o sc ore, a n d m uc osa l 
i m pr o ve me nt o n e n d osc o p y, were 
p osi tive a n d n o mi nall y 
si g nifica nt f or t he oza ni m o d 
0. 9 2 m g/ da y d ose c o mpare d t o place b o. 2 Tre n ds were als o o bser ve d wi t h the 0. 4 6 m g/ da y d ose, 
c o nsiste nt wit h a d ose -res p o nse relati ons hi p.
At  t he c o ncl usi on of t he 3 2 -wee k mai nte na nce p hase, t he pr o p orti o n of U C partici pa nt s ac hie vi n g 
cli nical re missi o n wit h eit her oza ni m o d 0. 4 6 m g / da y or 0. 9 2 m g/ da y was greater t ha n place b o a n d 
t he differe nce was b ot h cli nicall y mea ni n gf ul a n d statisticall y sig nifica nt. M uc osal i m pr o ve me nt 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
3 3
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
o n e n d osc o p y was p osi tive a n d statisticall y si g nifica nt f or b ot h d oses as well. T he sec o n dary 
e n d p o i nts of  cli nical res p o nse a n d c ha n ge i n M a y o sc ore were als o p osi tive a n d st atisticall y 
sig nifi ca nt f or t he oza ni m o d 0. 9 2 m g/ da y d ose. Tre n ds f or t h ose e n d p oi nts were o bser ve d wit h t he 
0. 4 6 m g/ da y d ose b ut statistical si g nifica nce was n ot ac hie ve d, a gai n c o nsiste nt wi t h a dose 
res p o nse.
T he o verall a d verse e ve nt ( A E) pr ofile i n t he I n d ucti on a n d M ai nt e na nce P erio ds a p peare d 
c o mpara ble bet wee n t he oza ni m o d d ose gr o u ps a n d place b o. W o rse ni n g of  UC was t he m o st 
c o m m o n serio us A E ( S A E), e x p erie nce d b y 3 place b o parti ci pa nt s a n d 2 oza ni m o d 0. 9 2 m g/ da y 
parti ci pa nt s. All S A Es were assesse d as u nrelate d or u nli kel y relate d t o st u d y treat me nt a n d all 
were res ol ve d. T he m o st fre q ue ntl y re p orte d T E A Es lea di n g t o treat me nt disc o nt i n uati on were 
Cr o h n’s disease ( C D; 5 oza ni m o d parti ci pa nt s) a n d a b d omi nal a bscess ( 2 oza ni m o d parti c i pa nts). 
All ot h er T E A Es lea di n g t o tr e at me nt disc o nti n uati o n occ urre d i n 1 partici pa nt eac h. All T E A Es 
lea di n g t o treat me nt disc o nti n uati on als o le d t o st u d y  wit hdra wal.
A d verse e ve nts of  special i nterest (A E SIs ) bei n g m o nit ore d i ncl u de d
 
ma c ular e de ma, ma li g na nc y, 
serio us or o p p ort u ni stic i nfecti on, p ul m o nar y  effects, a n d he pat ic effects. T here were n o si gnifica nt 
car diac A Es, car diac A Es re p orte d as A E SI s, fi ndi n gs o n electr ocar di o gra m ( E C G) , or fi n di n gs o n 
2 4- h o ur H o lter m o nit ori n g i n oza ni m o d -treate d partici pa nt s, w hic h i n dicates a fav ora ble o verall 
car diac safety pr ofile a n d s u g gests a p ote ntial be nefit of  dose escalat i on d uri n g i nitiati o n of  
oza ni m o d t hera p y.  Data fr o m t he O L E
p orti o n of  RP C 0 1 - 2 0 2 ( > 3 years) has s h o w n hi g h 
parti ci pa nt rete nti o n, c o nsiste nt efficac y, a n d n o ne w safet y si g nals e mer gi n g i n t his p o p ulat i on.
R P C 0 1 -3 1 0 1, a P hase 3 st u d y  in a d ult parti ci pa nt s wit h mo derate t o se vere U C, met b ot h p ri mary 
e n d p o i nts, de mo nstrati n g hi g hl y stati sticall y si g nifica nt res ults f or i n d ucti on of cli nical re missi o n 
at Wee k
1 0 a n d i n mai nte na nce at Wee k
5 2. T he st u d y als o met ke y sec o n dar y e n d p o i nts of  cli nical 
res p o nse a n d e n d osc o pic i m pr o ve me nt c o m pare d t o pl ace b o i n i n d ucti on at Wee k
1 0 a n d i n 
mai nte na nce at Wee k 5 2. 3
 
 
 Oza ni m o d was ge nerall y w ell t olerate d, wit h 
a l ow rate of  disc o nti n uati on a n d l ow i nci de nce of S A Es. T he m o st fre q ue ntl y re p orte d T E A Es 
wi t h lo n g- t er m use of  oza ni m o d 1 m g (≥ 5 % of  parti ci pa nt s) w hic h occ urre d at a ≥ 1 % hi g her 
i nci de nce c o mp ar e d wi t h place b o were c o nsiste nt wit h t he k n o w n safet y pr ofile of oza ni m o d a n d 
i ncl u de d l y m p h o pe nia, nas o p har y n git is, a ne mia, i ncrease d A L T, decrease d l y m p h oc yte c o u nt, 
hea dac he, art hralgia, a n d u p per res pir at or y tract i nfecti on. 
 
 
 
N o partici pa nt s e x perie nce d a serio us i nfecti on or o p p ort u ni stic i nfecti on c o nc urre nt wi t h an 
 O verall, t here is 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
3 4
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Cr o h n’s Dise ase
T he de vel o p me nt pr o gra m  in a d ul ts wit h m o deratel y t o se verel y acti ve C D i ncl u des a c o mplete d 
P hase 2 o pe n -label trial in a d ults ( R P C 0 1-2 2 0 1), o n g oi n g d o u bl e- bli n d, place b o -c o ntr olle d
P hase 3 i n d uct i on a n d mai nte na nce trials i n a d ults ( R P C 0 1-3 2 0 1, R P C 0 1 -3 2 0 2, R P C 0 1 -3 2 0 3) , a n d 
a n O L E trial ( R P C 01- 3 2 0 4).
R P C 0 1 -2 2 0 1, a P hase 2 st u d y, was c o n d ucte d i n C D t o e xa mi ne e n d osc o pic a n d cli nical o utc o mes 
f oll owi n g treat m e nt wit h oza ni mo d 0. 9 2 m g dail y f or 1 2 wee ks i n t he I n d uctio n P eri o d a n d u p t o 
1 4 8 wee ks i n t he E xte n de d P eri o d. Si m ple E n d osc o pi c Sc ore for Cr o h n’s Disease ( S E S-C D) 
re d uctio ns of  ≥5 0 % fr o m B aseli ne were see n i n 2 8. 6 % of  partici pa nt s ( o bser ve d cases), wit h 
greater e n d osc o pic res p o nse i n parti ci pa nt s wit h B aseli ne S E S -C D sc ore ≤1 2 a n d a s h orter disease 
d urati o n. At  W ee k 5 2, t he pr o p orti o n o f parti ci pa nt s ac hie vi n g re d uctio ns of  ≥ 5 0 % was mai ntai ne d 
at 2 6. 7 %. Cli nical res p o nse was see n i n 6 8. 5 % a n d 9 3. 8 % of  parti ci pa nt s ( o bser ve d cases) at 
Wee k
1 2 a n d Wee k 
5 2, res pecti vel y. Cli nical re missio n  was see n i n 4 6. 3 % a n d 6 5. 6 % of 
parti ci pa nt s ( o bser ve d cases) at Wee k 1 2 a n d Wee k 5 2, res pecti vel y. 
 
 
T he safet y a n d t olera bilit y res ults fr o m t he 1 2 -we e k I n d ucti o n Peri o d of R P C 0 1 -2 2 0 1 s u g gest t hat 
oza ni m o d 0. 9 2 m g dail y  is well t olerate d a n d has a n acce pta ble safet y pr ofile i n parti ci pa nt s wit h 
m o deratel y  to se verel y acti ve C D. I n t he o pe n -lab el  perio d ( O L P), oza ni m o d 0. 9 2 m g was well 
t olerate d a n d t her e were n o ne w safety c o ncer ns. T he A Es re p orte d i n t he st u d y were ge nerall y 
c o nsiste nt wit h t hose see n i n part ici pa nts wit h mo deratel y  t o se verel y acti ve U C. N o e ve nts were 
desi g nate d b y t he in vest i gat ors as A E SI s f or t he cate g ories of p ul mo n ar y, o p ht hal mic, or c ar diac 
d uri n g t he first 1 2 wee ks of  the st u d y, a n d t here were n o  cli nicall y si g nifica nt e pis o des of 
bra d ycar dia or car diac c o n d uct i on a b n or malit ies. A E SI s f or t he cate g or y of i nfecti on were re p orte d 
i n 1 5. 9 % of partici pa nts i n R P C 0 1-2 2 0 1, wi t h a b d o mi nal a bscess a n d her pes z oster eac h re p orte d 
i n 2. 9 % of partici pa nts.
T he P hase 3 a d ult CD pr o gra m ( R P C 0 1-3 2 0 1, 3 2 0 2, 3 2 0 3, 3 2 0 4) is bei n g c o n d ucte d t o e xa mi ne 
i n d ucti on a n d mai nte na nce of  cli nical re missi on a n d e n d osc o pic i m pr o ve me nt o ver 1 2 -wee k 
In d uct i on a n d 5 2- wee k 
M ai nte na nce P erio d s i n part ici pa nts a d mi nistere d or al  oza ni m o d 
at 0. 9 2 m g/ da y. 
 
 
 
S u m m ar y
Gi ve n t he mec ha nis m o f act i on of oza ni m o d, data fr o m t he precli nical a ni mal m o del, t he p osi ti ve 
res ults fr o m t he P hase 2 C D st u d y ( R P C 0 1-2 2 0 1) a n d P hase 2 a n d 3 U C st u dies ( R P C 0 1 -2 0 2 a n d 
R P C 0 1 -3 1 0 1, res pecti vel y), a n d a n acce pta ble safety pr ofile o bser ve d acr oss i n dicati o ns, 
oza ni m o d has t he p ote ntial t o a d dress a n u n met nee d i n t he pe diatr ic C D p o p ulati on. T his st u d y  is 
bei n g c o n d ucte d t o c haracterize t he p har mac o ki net ics ( P K) a n d p har mac o d y na mics ( P D) of 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
3 5
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
oza ni m o d o nce dail y  an d t o e val uate t he efficac y a n d safety of  oza ni m o d d oses i n pe diatri c 
parti ci pa nt e q ui vale nt t o 0. 4 6 or 0. 9 2 m g/ da y i n a d ults.
3. 2
B a c k gr o u n d
C D is a n i m m u ne -me diate d i nfla m mat or y disease of t he GI tract. A n n ual i nci de nce i n a d ults varies 
ge o gra p hi call y, wi t h esti mates ra n gi n g fr om 3. 1 t o 1 4. 6 per 1 0 0, 0 0 0 pe o ple i n t he U nite d States 
a n d fr o m 0. 1 t o 1 6 per 1 0 0, 0 0 0 w orl d wi de. 4 A d ult a n d pe diatric parti ci pa nt s wit h C D s uffer fr o m 
di arr hea, rectal blee di n g, wei g ht l oss, a b d omi nal pai n, a n d fe ver.
C D is c haracterize d b y a lifel on g c hr o nic c o urse of re missi o n s a n d e xacer batio ns. T he pat h ol o g y 
of  this disease is c haracterize d b y tra ns m ural infiltrat i on of  ly m p h oc ytes a n d macr o p ha ges, 
gra n ul o mas, fiss uri n g ulcerat i on, a n d s u b mu c os al  fi br osis. T he tra ns m ur al infla m mat or y  pr ocess 
of  CD pre dis p oses partici pa nt s t o t he f or mat i on of  fist ulas a n d it has bee n est i mate d t hat 
a p pr o xi matel y 35 % of  partici pa nt s will ha ve at least 1 fist ula d uri n g t he c o urse of  t heir disease. 5
Acc or di n g t o a rece nt st u d y, 5 0 % of a d ul ts wit h C D ha d u n der g o ne b o wel s ur ger y withi n 1 0 years 
of  dia g n osis. 6
T he c urre nt sta n dar d of  me dical care f or partici pa nt s wi t h mo deratel y t o se verel y act i ve C D 
c o nsists 
of  
ant i-i nfla m mat or y 
ap pr oac hes, 
s uc h 
as 
c ortic oster oids, 
azat hi o pri ne 
( A Z A)/6 merca p t o p uri ne ( 6-M P), m et h otre xate ( M T X), a n d bi o l ogics s uc h as a nt i-t u mor necr osi s 
fact or ( T N F) α, a nti-i nterle u ki n (I L) -1 2/I L -2 3, or a nt i-i nte gri ns.
I mm u n o m o d ul at ors ai d i n c ortic oster oid wi t hdra wal  an d i n pre ve nt i n g r ela pse b ut are als o
ass ociat e d wit h c o nsid era ble si de effects. I nfli xi ma b, a n a nt i-T N F α t hera p y , ca n re d uce si g ns a n d 
s y m pt o ms a n d i n d uce a n d mai ntai n re missi on i n m o st partici pa nt s f or w hic h it is i n dicate d. 
H o we ver, i n a lar ge P hase 3 ma i nte na nce trial of infli xi ma b f or C D i n a d ults ( A C C E N T I), o nl y 
4 5 % of  partici pa nt s were c o nsi dere d i n re missi on at Wee k 3 0 i n t he hi g hest d ose gr o u p ( w here 
re missi o n was defi ne d as t he a bilit y t o ac hie ve a Cr o h n’s Disease Act i vity I nde x [ C D AI] 
of < 1 5 0 p oi nts). 7 Si milarl y, t he pri mar y res p o nse rates i n a d ult tria ls of  adali m u ma b 8 a n d 
cert oliz u ma b 9 were a p pr o xi matel y 4 7 % a n d 3 7 %, res pecti vel y. T h us, a siza ble pr o p orti o n of  t he 
patie nt p o p ulat i on is u nres p o nsi ve t o b ot h c o n ve nt i onal t hera p y an d T N F 
a nta g o nists. 
Ve d oliz u ma b, a g ut -s pecific a nti-i nte gri n t hera p y, is a ls o i n dicate d f or ac hie vi n g cli nical res p o nse 
a n d cli nical re missi on i n t his p o p ul at i on. H o we ver, i n a lar ge cli nical trial of ve d o liz u ma b, o nl y 
3 1 % of  parti ci pa nt s ha d a cli nical res p o nse at Wee k 6, a n d o nl y  39 % of  partici pa nts recei vi n g 
ve d o liz u ma b e ver y 8 wee ks t hat were i n d ucti on res p o n ders were i n re missi on at Wee k 
5 2. 1 0
Uste ki n u ma b, a m o n o cl o n al a nti b o d y  t o t h e p 4 0 s u b u nit of I L-1 2 a n d I L-2 3, was stu die d i n a d ult 
C D 
pati e nts w h o 
faile d, ha d l oss of  res p o nse, or were 
i ntol era nt t o treat me nt wi t h 
i m m u n om o d ulat ors, c o rtic oster oids, or 1 or m o re T N F a nta g o nists. H o we ver, i n t he i n d ucti on 
trials of  uste ki n u ma b, o nl y 3 2 % of  p arti ci pa nt s were res p o n ders at Wee k 6, 1 1 a n d 5 3 % of  i n d ucti on 
res p o n ders were i n re missi o n a t Wee k 5 2 of t he mai nte na nce trial.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
3 6
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Cr o h n’s Dise ase i n t he Pe di atric P o p ul ati o n
A p pr o xi matel y  20 % t o 3 0 % of  all cases of  IB D are di a g n ose d i n c hil dre n a n d a d o lesce nts,
wi t h 8 0 % of  t hese p arti ci pa nt s bet wee n t he a ges of 1 0 a n d 1 8. 1 2 Si milar t o a d ul ts, prese nt atio n of  
C D i n t his patie nt p o p ul at i on de pe n ds o n t he di sease l ocat i on a n d t he e xte nt of  infla m mat i on.  
I n v ol ve me nt of b ot h s mall bo w el  an d c olo n are see n i n o ver half of  t he p o p ul at i on a n d t he m o st 
c o m m o nl y  e nc o u ntere d GI s y m pt o ms are a b d o mi nal pai n, diar r hea, a n d wei g ht l oss.1 3
A 
lar ge pr o p orti o n of  chil dre n a n d a d o lesce nts prese nt wit h 
c o m p licati ons s uc h as 
strict uri n g/ pe netrati n g p he n ot y pe a n d e xte nsi ve s mall b o wel  disease i n v ol ve me nt. T hese ris k 
fact ors prese nt as or pr o gress t o d e v elo pi n g i ntest i nal c o m p licati ons i ncl u di n g fist ulae, l ocalize d 
p eri t o nitis, a b d omi nal a bscesses a n d s mall b o wel o bstr ucti o n. 1 4 ,1 5 ,1 6
Gi ve n t hat prese ntati o n i n t he pr e-p u bertal or peri -p u bertal  p erio d i s c o m mo n , p u bertal d ela y a nd 
gr o wt h restricti on are als o of  si gnifica nt c o ncer n. A p pr o xi matel y 1 0 % t o 3 0 % of  chil dre n a n d 
a d olesce nts prese nt wit h gr o wt h fail ure me d iate d b y se veral fact ors i ncl u di n g i nfla m mati on,  
mal n utrit i on, a n d gl uc oc ortic o i d t hera p y.1 7
Treat me nt 
m o dalit ies 
i ncl u de 
c ortic oster oi ds, 
e xcl usi ve 
e nteral 
nutri tio n 
( E E N), 
i m m u n om o d ulat ors , a n d bi o l ogics. C orti c oster oi ds are effect i ve f or t he i n d ucti on of  cli nical 
re missi o n i n C D; h o we ver , a p pr o xi matel y half of t he parti ci pa nt s bec o me de pe n de nt o n l o n g -ter m 
c ortic oster oids or re q uire s ur ger y. Less t ha n o ne-t hir d of  par tici pa nt s wi t h C D i n cli nical re missi on 
wi t h c ortic ost er oid treat me nt ac hie ve m uc osal heali n g. Treat me nt wit h E E N ca n i n d uce re missi o n 
b ut is less effect i ve t ha n c ortic oster oids. E E N is als o use d less fre q ue ntl y d ue t o c o ncer ns wi t h 
i n vasi ve ness a n d p o or co m plia nce. 1 8
A p pr o xi matel y 7 0 % t o 8 0 % of  pe diatric part ici pa nts treate d wit h i m m u n os u p pressa nts s uc h as 
A Z A, 6 -M P, a n d M T X,
or bi o l ogi cs s uc h as i nfli xi ma b a n d a dali m u ma b, d o n ot e x perie nce 
pr ol o n ge d cli nical re missio n . Ma n y  re q uire d ose i nte nsificat i on t o ma i ntai n re missio n , a n d a s u bset 
of  these part ici pa nts e x perie nce l oss of  res p o nse des pite d ose i nte nsificati o n d ue t o t he 
de vel o p me nt of a nt i-dr u g a nt i b o dies. O ne-t hir d of parti ci pa nt s di sc o nti n ue i nfli xi ma b wit hi n 2 t o 
3 years, eit her beca use of  primar y  n o nres p o nse, l oss of  res p o nse, or A E s.1 9 Ma n y  ex peri e nce 
t o xicities s uc h as m yel os u p pressi o n a n d seri o us i nfecti o ns. W hile re missi o n rates f or a dali m u ma b 
are si milar t o i nfli xi ma b f or i nfli xi ma b -naï ve parti ci pa nt s, t h ose w h o ha ve bee n pre vi o usl y treate d 
wi th infli xi ma b ha ve s h o w n si g nifica nt l y l ower re missi o n  rates (a p pr o xi matel y 2 0 %).
I n c o nclusi o n , alt ho u g h c hil dre n d e m o nstrate res p o nse t o treat me nt wit h 
c ortic oster oids, 
i m m u n om o d ulat ors, a n d bi o l ogi c t hera pies, barriers or rel ucta nce t o use t hese t hera pie s i n c hil dre n 
i ncl u de fe wer a vaila ble a p pr o ve d t hera pies, m o re i m pactf ul l on g -t er m effects w he n a d mi nistere d 
earlier i n life, a n d i nterfere nce wi t h chil dre n’s q uali t y of life i ncl u di n g ps yc h os ocial nee ds. 2 0
T heref ore, t here is a n u n met nee d f or a C D treat ment  that is safe, effect i ve, a n d c o n ve nie nt t o 
a d mi nister i n t he pe diatric p o p ulat i on.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
3 7
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
3. 3
B e n efit/ Ri s k A s s e s s m e nt
Des pite rece nt pr o gress i n C D treat me nt, t here re mai ns a n u n met nee d f or oral a ge nts t hat are safe, 
c o n ve nie nt , a n d ca n pr o vi de effect i ve i n d ucti on a n d l on g -t er m mai nte na nce of  cli nical re missi on 
i n pe diatric parti ci pa nt s. T he be nefit/ris k pr ofile f or oza ni m o d has bee n e val uate d i n patie nts wit h
C D. Res ults fr o m st u dies i n a d ult parti ci pa nt s wi t h mo derate t o se vere di sease w h o faile d pri or 
t hera p y a n d were treate d wit h oza ni m o d 0. 9 2 m g dail y f or at least 1 2 wee ks s u g geste d cli nical a n d 
e n d osc o pic be nefit ( R P C 0 1-2 2 0 1). I n a d dit i on, safety res ults s u g gest t hat oza ni m o d is well 
t olerate d i n pat ient s wi t h CD a n d are c o nsiste nt wit h t hose o bser ve d i n ot h er patie nt p o p ulati o ns 
treate d wit h oza ni m o d ( U C a n d M S). 
O verall, t he c urre nt data s u g gest t hat oza ni m o d has 
a p ote nti all y fa v ora ble be nefit /ris k pr ofile f or pe diatri c parti ci pa nt s wi t h mo derate t o se vere C D
w h o ha ve i na d e q uate res p o nse, i nt olera nce, or l oss of res p o nse t o t hese t hera pies f or t he pe diatric 
p o p ul at i on: c orti c oster oids, i m m u n o m o d ul at ors, or bi o l ogi cs.
3. 3. 1
Ri s k A s s e s s m e nt
As of  t he I B data c ut -off date ( 1 9-Ma y -2 0 2 2 ), 
partici pa nt s o verall ha ve bee n e x p ose d t o at 
least 1 d ose of i n vesti gati onal pr o d uct (I P) acr oss 3 1 c o mpa n y -s p o ns ore d st u dies i n v o l vi n g health y 
parti ci pa nt s or partici pa nt s wi t h MS, U C, or C D. T his i ncl u des 
partici pa nt s e x p ose d t o at 
least 1 d ose of  oza ni m o d. I mp orta nt p ote ntial ris ks base d o n e x perie nce wi t h no n -selecti ve 
S 1 P a g o nists i ncl u de s y m pt o matic bra d ycar dia, atrio v e ntric ular c o n d uctio n dis or der, li ver i nj ur y, 
mac ular e de ma, p osteri or re versi ble e nce p halo pat h y  sy n dr o me ( P R E S), a n d e m br yof et al t o xicit y
i n e x p ose d pre g na nt fe males, mali g na ncies, i nfect i o ns, a n d p ul m onar y  effects. 
T a ble 3. 3. 1 - 1:
Ris k Assess me nt
P ote nti al Ris k of Cli nic al 
Si g nific a nce
S u m m ar y of D at a/ R ati o n ale f or 
Ris k
Miti g ati o n Str ate g y
St u d y I nter ve nti o n(s)
S y m pt o matic b r a d ycar dia
I n c o ntr olle d U C st u dies, bra d ycar dia 
was re p orte d i n 2 partici pa nts d uri n g 
t he i n d ucti o n peri o d ( 1 o n Da y 1) a n d 
n o partici pa nts d uri n g t he M ai nte na nce 
P eri o d o n oza ni m o d a n d n o ne o n 
place b o. T he e ve nts were n ot
s ym pt o matic a n d di d n ot re q uire 
c ha n ges i n d osi n g.
E xcl u de hi g h -ris k partici pa nts; 
re q uire first-d ose o bser vati o n i n all 
partici pa nts .
Se vere li ver i nj ur y
I n c o ntr olle d U C st u dies, ele vati o ns of 
A L T t o 5 -f ol d t he U L N or greater 
occ urre d i n 0. 9 % of partic i pa nts 
treate d wit h 0. 9 2 m g d uri n g i n d ucti o n 
a n d 0. 9 % d uri n g mai nte na nce. 
Ele vati o ns of A L T t o 3 -f ol d t he U L N 
or  greater occ urre d i n 2. 6 % of 
partici pa nts d uri n g i n d ucti o n a n d 2. 3 % 
d uri n g mai nte na nce. I n U C st u dies, t he 
maj orit y ( 9 6 %) of partici pa nts wit h 
A L T greater t ha n 3 -f ol d t he U L N 
c o nti n ue d treat me nt wit h val ues 
M o nit or L F T s. Per ma ne nt 
disc o nti n uati o n f or c o nfir me d 
se vere ele vati o ns.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
3 8
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
T a ble 3. 3. 1 - 1:
Ris k Assess me nt
P ote nti al Ris k of Cli nic al 
Si g nific a nce
S u m m ar y of D at a/ R ati o n ale f or 
Ris k
Miti g ati o n Str ate g y
ret ur ni n g t o less t ha n 3-f ol d t he U L N 
wit hi n a p pr o xi matel y 2 t o 4 wee ks. 
T he disc o nti n uati o n rate d ue t o 
ele vati o ns i n he patic e nz y mes was 
0. 4 %. N o cases of se vere dr u g -i n d uce d 
li ver i nj ur y were re p orte d.
Seri o us o p p ort u nistic i nfecti o ns ,
i ncl u di n g P M L
I n oza ni m o d st u dies, t he rate of seri o us 
i nfecti o ns was l o w a n d si milar 
bet wee n oza ni m o d a n d c o ntr ol ar ms. 
O ne seri o us o p p ort u nistic i nfecti o n of 
P M L was re p orte d i n a n M S O L E
st u d y.
M o nit or W B C, m o nit or f or P M L 
s ym pt o ms, d ose i nterr u pti o n f or 
s us pecte d cases of P M L, a n d 
per ma ne nt disc o nti n uati o n u p o n 
c o nfir mati on of P M L .
Mac ular e de ma
I n acti ve-c o ntr olle d M S cli nical trials 
wit h oza ni m o d, mac ular e de ma was 
o bser ve d i n 1 ( 0. 1 %) p artici pa nt wit h 
oza ni m o d 0. 9 2 m g a n d 3 ( 0. 3 %) 
partici pa nt s wit h oza ni m o d 0. 4 6 m g, 
all of w h o m ha d pre-e xisti n g ris k 
fact ors. I n t he U C st u dies, mac ular 
e de ma was re p orte d i n u p t o 0. 4 % of 
partici pa nt s, us uall y wit h ris k fact ors, 
s uc h as dia betes, pri or oc ular s ur ger y, 
a n d h ist or y of u veitis.
M o nit or vis ual s y m pt o ms (e g,
bl urre d visi o n, decrease d vis ual 
ac uit y).
Mali g na nc y
Mali g na ncies ha ve bee n re p orte d wit h 
oza ni m o d. T he rate of mali g na ncies, 
i ncl u di n g n o n-mela n o ma s ki n ca ncers, 
was c o m par a ble t o t hat re p orte d i n real 
w orl d data a n d f o u n d t o be si milar.
Cl ose m o nit ori n g f or mali g na ncies, 
i ncl u di n g c o m plete der mat ol o gic 
e xa m.
P osteri or re versi ble 
e nce p hal o pat h y s y n dr o me
O ne case re p orte d i n a patie nt wit h M S 
a n d a ut o n o mic i nsta bilit y.
M o nit or s y m pt o ms , dose 
i nterr u pti o n f or s us pecte d cases, 
a n d per ma ne nt disc o nti n uati o n 
u p o n c o nfir mati o n .
E m br y ofetal t o xicit y i n e x p ose d 
pre g na nt fe males
N o n -cli nical data wit h terat o ge nicit y. 
Cli nical data wit h o ut s u g gesti o n of 
terat o ge nicit y as of 3 0- Se p - 2 0 2 0.
Hi g hl y  effecti ve c o ntrace pti o n a n d 
re g ular pre g na nc y testi n g i n 
F O C B P. A v oi d use d uri n g 
lactati on .
St u d y Pr oce d ures
C ol o n osc o p y
P ote ntial perf orati o n or blee di n g .
Sta n dar d me dical care .
A b bre viati o ns: A L T, ala ni ne a mi n otra nsferase; F O C B P, fe males of c hil d beari n g p ote ntial; L F T, li ver f u ncti o n tests; 
M S, m ulti ple scler osis; O L E, o pe n -la bel e xte nsi o n; P M L, pr o gressi ve m ultif ocal le u k oe nce p hal o pat h y; U C, ulcerati ve 
c olitis; U L N, u p per li mit of n or mal; W B C , w h ite bl o o d cells.
 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
3 9
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3. 3. 2
B e n efit A s s e s s m e nt
Oza ni m o d has s h o w n efficac y a n d t olera bilit y acr oss t he 3 i n dicati ons t hat ha ve bee n st u die d i n 
t he cli nical setti n g. I n P hase 3 M S 
St u dies R P C 0 1 -2 0 1 B a n d R P C 0 1 -3 0 1, treat me nt wit h 
oza ni m o d 0. 9 2 m g / da y a n d 0. 4 6 mg/ da y  r es ulte d i n st atisticall y si g nifica nt, cli nicall y mea ni n gf u l 
re d uctio ns i n A R R c o m pare d wi t h IF N β -1a at 1 2 m o nt hs a n d 2 4 m o nt hs. S af et y res ults s h o we d 
t hat oza ni m o d was ge nerall y well t olerate d (see Secti o n 3. 1. 2 f or A E s u m mar y). 
T he P hase 2 U C tri al (R P C 0 1 -2 0 2) de m o nstrate d t hat, at t he c o nclusi o n  of t he 9- wee k i n d ucti on 
p hase a n d 3 2 -wee k mai nte na nce p hase, t he pr o p orti o n of part ici pa nts ac hie vi n g cli nical re missi on 
wi t h oza ni m o d 0. 9 2 m g/ da y was greater t ha n place b o a n d t he differe nce was b ot h cli nicall y 
mea ni n gf ul a n d statisticall y si gnifica nt. I n a d diti o n, sec o n dar y en d p o i nts i ncl u di n g cli nical 
res p o nse, c ha n ge i n t he M a yo sc ore, a n d m uc osal  im pr o ve me nt o n e n d osc o p y , w er e p ositive a n d 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
4 0
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
n o mi nall y si g nifica nt f or t he oza ni m o d 0. 9 2 m g/ d a y  dose c o m pare d t o place b o. 2 R P C 0 1 -3 1 0 1, 
a P hase 3 st u d y in a d ult partici pa nt s wi t h mo derate t o se vere U C, met  bot h pri mar y e n d p o i nts, 
d e m o nstrati n g hi g hl y  statisticall y si g nifica nt res ults f or i n d ucti on of  cli nical re missi on at 
Wee k
1 0 a n d i n mai nte na nce at Wee k 5 2. 3 T he st u d y als o met ke y sec o n dar y e n d p o i nts of cli nical 
res p o nse a n d e n d osc o pic i m pr o ve me nt c o m pare d t o place b o i n i n d ucti on at Wee k
1 0 a n d i n 
mai nte na nce at Wee k 5 2.
T he P hase 2 C D trial ( R P C 0 1 -2 2 0 1) de m o nstrate d re d uctio ns o f ≥5 0 % fr o m B aseli ne i n S E S-C D
f or 2 8. 6 % of partici pa nt s ( o bser ve d cases), wit h greater e n d osc o pic res p o nse i n parti ci pa nt s wit h 
B aseli ne S E S -C D sc ore ≤1 2 a n d a s h orter disease d ur ati o n. T he safet y an d t olera bilit y r es ults fr om 
t he 1 2- wee k I n d ucti on P eri o d of  RP C 0 1 -2 2 0 1 s u g gest t hat oza ni m o d 0. 9 2 m g dail y is w ell 
t olerate d a n d has a n acce pta ble safety pr ofile i n p arti ci pa nt s wi t h mo deratel y t o se verel y act i ve 
C D. I n t he O L P, oza ni m o d 0. 9 2 m g was w ell t olerate d a n d t here were n o ne w safet y c o ncer ns.
 
 
 
 
Pl ease re fer t o t he I B f or detaile d i nf or mati o n c o ncer ni n g t he a vaila ble p har mac ol og y , t o xic o l og y , 
dr u g m eta b o lis m, cli nical st u dies, a n d A E pr ofile of t he I P.
3. 3. 3
O v er all B e n efit /Ri s k C o n cl u si o n
I M 0 4 7- 0 2 3 has bee n desi g ne d t o cl o sel y m onit or st u d y part ici pa nts’ safety t hr o u g h o ut t he d urati o n 
of  t he st u d y. A c o m pre he nsi ve safety m o nit ori n g pla n utilizes fre q ue nt assess me nts t o m o nit or f or 
di sease rela pse w hic h allo ws t he p arti ci pa nt s t o pr ocee d t o o pe n-label treat m e nt. A d ditio nall y, at 
t he i n vesti gat or’s di screti on, resc ue t hera p y ca n be i nitiate d or d osi n g of st u d y me dicatio n c a n b e 
di sc o nti n ue d at a n y t i me d uri n g the st u d y. A c o m pre he nsi ve m o nit ori n g of  safet y will  be c on d ucte d
b y t he i n vesti gat ors, Cli nical Trial P h ysicia n s, a n d a n i n de pe n de nt D M C. 
Gi ve n t he mec ha nis m o f act i on of oza ni m o d, data fr o m t he precli nical a ni mal m o del, t he p ositi ve 
res ults fr o m t he P hase 2 ( R P C 0 1-2 0 2) a n d P hase 3 ( R P C 0 1-3 1 0 1) U C stu dies, t he P hase 2 C D 
st u d y ( R P C 0 1-2 2 0 1), a n d a n acce pta ble safet y  pr ofile o bser ve d acr oss i ndicat i ons, oza ni m o d h as 
t he p ote ntial t o a d dress a n u n met nee d i n t he pe diatric C D p o p ulat i on. I M 0 4 7 -0 2 3 has a p ote ntial 
fa v ora ble be nefit/ris k pr ofile f or pe di atric pati e nts wi t h mo derate t o se vere C D
w h o ha ve 
i na de q uate res p o nse or i nt olera nce t o c ortic oster oi ds, i m m u n om o d ul at ors, or biol o gi c t hera p y.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
4 1
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
4
O B J E C TI V E S A N D E N D P O I N T S
T a ble 4 - 1:
O bjecti ves a n d E n d p oi nts
O bjecti ve
E n d p oi nt
Pri m ary – Effic acy

T o e val uate t he efficac y of oza ni m o d o nce dail y 
i n pe diatric partici pa nt s wit h 
m o deratel y 
t o 
se verel y acti ve C D: cli nical re missi on b y P C D AI 
at Wee k 6 4

Pr o p orti o n o f partici pa nt s w h o ac hie ve P C D AI < 1 0
at Wee k 6 4

T o e val uate e n d osc o pic re missi o n at Wee k 6 4 b y 
S E S -C D

Pr o p orti o n of partici pa nts ac hie vi n g S E S -C D ≤ 2 or 
S E S -C D ≤ 4 p oi nts wit h n o S E S -C D s u bsc ore 
> 1 p oi nt at Wee k 6 4
Sec o n d ary – Effic acy ( Key)

T o e val uate t he efficac y of oza ni m o d o nce dail y 
i n pe diatric partici pa nts wit h 
m o deratel y 
t o 
se verel y acti ve C D: cli nical re missi on b y P C D AI 
at Wee k 1 2

Pr o p orti o n o f partici pa nts w h o ac hie ve P C D AI < 1 0 
at Wee k 1 2
Sec o n d ary – Effic acy ( Ot her)

T o e val uate e n d osc o pic res p o nse b y S E S -C D

Pr o p orti o n of partici pa nts w h o ac hie ve S E S -C D 
decrease fr o m Baseli ne 
of ≥
5 0 % ( E R - 5 0) at 
Wee k
6 4; Wee k 1 2

T o e val uate cli nical res p o nse b y P C D AI

Pr o p orti o n of partici pa nts w h o ac hie ve re d ucti o n i n 
P C D AI sc ore ≥1 2. 5 a n d a t otal P C D AI sc ore of 
< 3 0 p oi nts at Wee k 6 4 ; Wee k 1 2

T o e val uate s y m pt o matic re missi o n (a d olesce nts 
o nl y )

Pr o p orti o n of a d olesce nt s w h o ac hie ve a n a vera ge 
dail y  ab d o mi nal pai n sc ore ≤1 p oi nt a n d a n a vera ge 
dail y  st o ol fre q ue nc y ≤3 p oi nts wit h a b d o mi nal pai n 
a n d st o ol fre q ue nc y n o w orse 
t ha n B aseli ne at 
Wee k 6 4 ; Wee k 1 2

T o e val uate c ha n ge i n C D s y m pt o ms o ver ti me

C ha n ge fr o m B aseli ne i n st o ol fre q ue nc y sc ore o ver 
ti m e

C ha n ge f r om B aseli ne i n a b d o mi nal pai n o ver ti me

T o 
e val uate 
cli nical 
r emissi o n 
b y 
C D AI 
(a d olesce nts o nl y)

Pr o p orti o n 
of 
a d olesce nt s wh o 
ac hie ve C D AI 
sc ore < 1 5 0 at Wee k 6 4 ; Wee k 1 2

T o 
e val uate 
cli nical 
res p o nse 
b y 
C D AI 
(a d olesce nts o nl y)

Pr o p orti o n 
of 
a d olesce nt s wh o 
ac hie ve C D AI 
re d ucti on fr o m B aseli ne of ≥1 0 0 p oi nts or  CD AI 
sc ore < 1 5 0 at Wee k 6 4 ; Wee k 1 2

T o e val uate c ortic oster oi d -free re missi o n 

Pr o p orti o n of partici pa nts w h o ac hie ve a P C D AI 
sc ore < 1 0 at Wee k 6 4 w hile re mai ni n g c ortic oster oi d
free i n t he pri or 1 2 wee ks

Pr o p orti o n of partici pa nts w h o ac hie ve a C D AI sc ore 
< 1 5 0 at Wee k 6 4 w hile re mai ni n g c ortic oster oi d free 
i n t he pri or 1 2 wee ks (a d olesce nts o nl y)
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
4 2
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
T a ble 4 - 1:
O bjecti ves a n d E n d p oi nts
O bjecti ve
E n d p oi nt

T o e val uate e n d osc o pic re missi o n at Wee k 1 2

Pr o p orti o n of partici pa nts ac hie vi n g S E S -C D ≤ 2 or 
S E S -C D ≤
4 p oi nts wit h n o S E S -C D s u bsc ore 
> 1 p oi nt at Wee k 1 2
Sec o n d ary – P h ar m ac oki netics

T o c haracterize t he P K
of 2 d oses of or al 
oza ni m o d a n d its maj or 
acti ve meta b olites 
i n 
pe diatric partici pa nts wit h m o deratel y t o se verel y 
acti ve C D 

Stea d y state s yste mic e x p os ures of oza ni m o d a n d 
C C 1 1 2 2 7 3 at Wee k 2 0 a n d t hr o u g h o ut t he st u d y
Sec o n d ary – P h ar m ac o dy n a mics

T o e val uate t he P D effects of 2 d ose le vels of 
oza ni m o d (e g,
effects o n A L C) 
i n pe diatric 
partici pa nts wit h m o deratel y  to se verel y acti ve 
C D

A bs ol ute a n d perce nt c h a n ge fr o m B aseli ne i n A L C 
at Wee k 6 4 , Wee k
1 2, a n d t hr o u g h o ut t he st u d y
Sec o n d ary – S afety a n d T oler a bility

T o e val uate t he safet y a n d t olera bilit y of 2 d ose 
le vels of or al oza ni m o d o nce dail y  in pe diatric 
partici pa nts wit h m o deratel y  to se verel y acti ve 
C D

N u m ber a n d pr o p orti o n of partici pa nts e x perie nci n g 
A Es, S A Es, A Es lea di n g t o disc o nti n uati o n fr o m 
treat me nt, a n d A E SIs t hr o u g h o ut t he st u d y
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
4 3
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
T a ble 4 - 1:
O bjecti ves a n d E n d p oi nts
O bjecti ve
E n d p oi nt
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
4 4
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
E n d p oi nt Defi niti o ns
Ke y st u d y  defi nitio n s are pr o vi de d belo w ( see Ta ble 4- 2 ).
T a ble 4- 2:
Selecte d E n d p oi nt Defi niti o ns
E n d p oi nt
Defi niti o n
Cli nical re missi o n
C D AI < 1 5 0
P C D AI < 1 0 p oi nts
Cli nical res p o nse
C D AI re d ucti o n fr o m B aseli ne of ≥1 0 0 p oi nts or C D AI sc ore < 1 5 0
P C D AI re d ucti o n fr o m B aseli ne of ≥ 1 2. 5 a n d a t otal P C D AI sc ore of 
< 3 0 p oi nts
E n d osc o pic re missi o n
S E S -C D ≤ 2 or S E S -C D ≤4 p oi nts a n d wit h n o S E S -C D s u bsc ore > 
1 p oi nt 
E n d osc o pic res p o nse
≥ 5 0 % i m pr o ve me nt fr o m B aseli ne i n t he S E S -C D
C ortic oster oi d -free re missi o n
P C D AI sc ore < 1 0 at Wee k 6 4 w hile re mai ni n g c ortic oster oi d free i n 
t he pri or 1 2 wee ks
C D AI < 1 5 0 at Wee k 6 4 a n d recei vi n g n o c ortic oster oi ds f or C D i n t he 
pri or 1 2 wee ks
Hist ol o gic re missi o n
 
 
L oss of res p o nse
 
 
S y m pt o matic re missi o n (a d olesce nts 
o nl y )
A vera ge dail y a b d o mi nal pai n sc ore ≤ 1 p oi nt a n d a vera ge dail y st o ol 
fre q ue nc y ≤ 3 p oi nts wit h a b d o mi nal pai n a n d st o ol fre q ue nc y n o 
w orse t ha n B aselin e
A b bre viati o ns: C D AI , Cr o h n’s Disease Acti vit y I n de x;
P C D AI , Pe diatric 
Cr o h n’s Disease Acti vit y I n de x ;
 S E S -C D , Si m ple E n d osc o pic Sc ore f or Cr o h n’s 
Disease .
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
4 5
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
5
S T U D Y D E SI G N
5. 1
O v er all D e si g n
T his is a P hase 2/ 3, ra n d o mize d, d o u ble- bli n d st u d y desi g ne d t o e val uate t he efficac y , safet y, a n d 
t olera bilit y o f oral oza ni m o d o nce dail y i n pe diatric parti ci pa nt s a ge d 2 t o 1 7 years i ncl usi ve, wit h 
m o deratel y  t o se verel y acti ve C D ( defi ne d as a Pe diatri c Cr o h n’s Disease Act i vity I n de x [ P C D AI ]
sc ore of  ≥ 3 0 a n d a n S E S -C D sc ore of  ≥ 6 [ or S E S -C D ≥ 4 i n parti ci pa nts wi t h is olate d ileal 
di sease] wi t h an i na de q uate res p o nse, i ntol era nce , or l oss of  res p o nse t o pri or t hera p y f or C D. 
T he st u d y will als o e val uate t he P K a n d P D of  oral oza ni m o d a d mi nistere d o nce dail y  at 2 d ose 
le vels ( 0. 4 6 or 0. 9 2 m g/ da y a d ult e q ui vale nt d oses) i n pe diatri c part ici pa nts d uri n g a 6 4 -wee k 
I n d ucti on a n d Mai nte na nce treat me nt peri o d.
T he c o -pri mar y e n d p o i nts of  the st u d y are t he pr o p orti o n of  part ici pa nts i n cli nical re missio n 
( PC D AI < 1 0) at  
Wee k 6 4
a n d t he pr o p orti o n of  partici pa nts i n e n d osc o pic re missi on
(S E S -C D ≤2 or S E S -C D ≤ 4 p oi nts wit h n o S E S -C D s u bsc ore > 1 p oi nt ) at Wee k 
6 4 . 
Ke y sec o n dar y e n d p oi nts are pr o vide d i n  Sect i on 4 .
T he st u d y  desi g n sc he matic is prese nte d i n
T he st u d y  is t o e nr oll a p pr o xi matel y 
 pe diatric parti ci pa nt s se q ue ntiall y acr oss 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
4 6
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
 
 
 
 
 
 
 
 
 
 
 
 
 
T he mi ni m u m wei g ht re q uir e me nt 
 
h o we ver, f or parti ci pa nt s bel o w t he 5t h perce nt ile i n wei g ht f or a ge ( per Ce nters f or Disease 
C o ntr ol  [C D C ] gr o wt h c harts 2 1 ), t he i n vesti gat or s h oul d c o ntact t he Cli nical Tri al P h ysicia n or 
desi g nee pri or t o e nr oll me nt.
 a nal yses 
will deter mi ne t he 0. 4 6 a n d 0. 9 2 m g/ da y a d ult
e q ui vale nt d oses 
.
 partici pa nt s (a ge d 1 2 t o 1 7 years, i ncl usi ve) will be ra n d o mize d i n a 1: 1 ratio t o recei ve 
eit her 0. 4 6 or 0. 9 2 m g/ da y of  oza ni m o d. 
 
 
 
 
 
 
 
All partici pa nt s will u n der g o 
 will i nitiate 
treat me nt 
 as it has 
s uccessf ull y atte n uate d t he ne gati ve car diac effects of S 1 P m o d ulati on i n a d ults 

0. 4 6 m g d os e: 
, t he n 0. 4 6 m g/ da y 
, a n d c o nti n ui n g 
0. 4 6 m g/ da y 

0. 9 2 m g/ da y d ose :
, t he n 0. 4 6 m g/ da y 
, t he n 
0. 9 2 m g/ da y 
 
a n d 
stea d y state P K data will be e val uate d t o a dj ust t he escalati o n re gi me n as re q uire d.
T he treat me nt t hat eac h parti cipa nt will recei ve will n ot be discl ose d t o t he i n vesti gat or, site staff, 
parti ci pa nt , S p o ns or, or t he cli nical staff at t he c o ntract researc h or ga nizat i on ( C R O) i n v ol ve d wit h 
st u d y c o n d uct or data c ollecti on/a nal ysis. Access t o treat me nt assi g n me nts will be strictl y li mite d 
t o gr o u ps direct l y i n v ol ve d wi t h dr ug distri b ut i on, pre parati o n of  un bli n de d o ut p ut f or t he 
, 
Cli nical Scie nce, safety pers o n nel u n bli n de d t o treat me nt f or S A E cases, a n d pers o n nel i n v ol ve d 
i n t he c o n d uct of P K assa ys.
T he bli n d s h o uld be mai ntai ne d f or pers o ns res p o nsi ble f or t he o n g oi n g c o n d uct of  the st u d y 
t hr o u g h t he c o m p leti o n of  t he L o n g- t er m E xt e nsio n  (L T E ) Peri o d. Bli n de d pers o ns ma y i ncl u de 
b ut are n ot li mite d t o t he Cli nical Tri al  P h ysicia n, Cli nical  Scie nt ist, Cli nical Trial Ma na ger, St u d y 
Stati sticia n, Data Ma na ger, Pr o gra m mers a n d Cli nical Researc h Ass ociates.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
4 7
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S -9 8 6 3 7 4
Oza ni m o d
T he st u d y will be c o n d ucte d i n c o m plia nce wit h t he I nter nati o nal C o u ncil o n Har m o nisat i on (I C H) 
of  Tec h nical Re q uire me nts f or Re gistrati o n of  Phar mace ut icals f or H u m a n Use/ G o o d Cli nica l 
Practi ce ( G C P) a n d a p plica ble re g ulat or y re q uire me nts.
 
 will i nitiate with ra n d o mizat i on ( 1: 1) t o eit her a 0. 4 6 m g/ da y 
or 0. 9 2 m g/ da y d ose of oral oza ni m o d. 
 
 
 
 
 
(ie, 0. 4 6 a n d 0. 9 2 m g/ da y) 
 
 
 
 
 
 
 
.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
4 8
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
 
 Partici pa nt s will be ra n d o mize d 1: 1 t o oral 
oza ni m o d 
at 
t he 
d oses 
t hat 
pr o vi de 
c o m p ara ble 
e x p os ures 
as 
a d ults a d mi nistere d 
eit her 0. 4 6 or 0. 9 2 m g/ da y oza ni m o d. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
E arl y Disc o nti n u ati o n
After at least 7 wee ks of treat me nt ( 5 wee ks o n st u d y a n d a c o nfir mati on visit at least 2 wee ks later 
as descri be d b el o w ), partici pa nt s will ha ve t he o pti o n t o e nter t he L T E Peri o d 
 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
4 9
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
 
 
 
P arti cipa nt s wit h c o nc omit a nt c ortic oster oi d use fr o m B aseli ne w h o ha ve i nit iate d a c ortic oster oi d 
ta per are per mitte d t o i ncrease t heir d ose of  corti c oster oids bac k t o B aseli ne d ose level (see 
Secti o n 7. 7 ). Parti ci pa nt s w h o i nitiate t hera p y with c ortic oster oi ds or i ncrease a b o ve Baseli ne d ose 
le vel d uri n g t he d o u bl e- bli n d p eri o d are c o nsi dere d a treat me nt fail ure a n d m u st be disc o nt i n ue d 
fr om the c urre nt peri o d b ut are eli gi ble t o pr ocee d t o t he L T E Peri o d .
At  an y time, t he deci sio n  to disc o nt i n ue part ici pati on i n t he st u d y is left t o t he discret i on of  the 
parti ci pa nt , t he partici pa nt’s pare nt or le gal g uar dia n, or in vest i gat or.
L o n g -ter m E xte nsi o n ( L T E) Peri o d
P arti cipa nt s will be e nteri n g t he L T E Peri o d fr o m t he I n d ucti on or Mai nte na nce P erio d of  this 
st u d y. P arti ci pa nt s eli gi ble f or t he L T E Peri o d will ha ve eit her met  earl y disc o nti n uati on crit eria 
(see Secti o n 8), c o mplete d Wee k 1 2 a n d are n o n -res p o n ders, or ha ve c om p lete d Wee k 6 4.
T he d ose at w hic h a parti ci pa nt e nters t he L T E will be deter mi ne d b y t heir cli n ical res p o nse at t he 
ti me of  e ntr y int o t h e L T E Peri o d. Parti ci pa nt s w h o ha ve c o m p lete d Wee k 6 4 a n d are i n cli nical 
re missi o n w he n e nteri n g t he L T E will recei ve oza ni m o d at t h e sa me d ose as a d mi nistere d i n t he 
I n d ucti on a n d Mai nte na nce
P erio d s. Parti ci pa nt s w h o are n ot i n cli nical re missio n at t he ti me of  
e nteri n g t he L T E will recei ve oza ni m o d at t h e of  0. 9 2 m g/ da y a d ult e q ui vale nt d ose. I n ge neral, 
t he last visit of t he I n d uctio n/ Mai nte na nce P erio d or t he earl y ter mi nati on (E T ) visit will ser ve as 
t he first visit of t his L T E Perio d.
 
 
P arti cipa nt s w h o were n ot i n cli nical re missi on w he n e nteri n g t he L T E Peri o d a n d w h o meet L T E 
di sc o nti n uati on cr iteria descri be d a b o ve aft er at least 7 wee ks of treat me nt ( 5 wee ks i n L T E Peri o d 
a n d a c o nfir mat i on visit at least 2 wee ks later) i n t he L T E Peri o d will be disc o nt i n ue d fr om t he 
st u d y.
P arti cipa nt s w h o c o mplete d Wee k 6 4 a n d were i n cli nical re missi on w he n e nteri n g t he L T E Peri o d, 
a n d w h o meet disc o nt i n uati on crit erio n descri be d a b o ve aft er 5 wee ks of  treat me nt i n t he L T E 
P eri o d (wit h c o nfir mat i on at least 2 wee ks later), will recei ve oza ni m o d at t h e 0. 9 2 m g/ da y a d ult  
e q ui vale nt d ose a p pr o priat e for t hei r a g e for a n a d di tio nal  5 w e e ks. If t he partici pa nt c o nt i n ues t o 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
5 0
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
m e et t h e di sc o nti n uatio n cri t erio n  aft er t h e 5 a d ditio n al w e e ks of tr e at me nt (wi t h c o nfir matio n at 
least 2 wee ks later [mi ni m u m of  14 wee ks i n L T E Peri o d] ), t he parti ci pa nt will be disc o nt i n ue d 
fr om t he st u d y.
P arti cipa nt s ca n i nitiate or i ncrease t he d ose of c o nc o mit a nt me d icati ons f or t h e tr e at me nt of CD 
d uri n g t he L T E Peri o d a n d c o nc o mit a nt me d icatio ns are n ot s u bject t o d ose sta bilizati on 
re q uire me nts. T he f oll owi n g me dicati o ns are all o we d at a t hera pe utic d ose f or C D ( d osa ge regi me n 
ca n be a dj uste d t o acc o mm o d at e m g/ k g/ da y d osi n g as a p pr o priate) : or al  5-a mi n o salic ylic aci d 
( 5-A S A s) a n d c ortic oster oids ( pre d nis one 1. 0 m g/ k g/ da y  f or weig hts ≤ 4 0 k g, ≤4 0 m g/ da y f or 
w ei g hts > 4 0 k g or e q ui vale nt, oral b u des o ni de ≤9 m g per d a y , oral becl o met has o ne ≤ 5 m g per 
d a y ). 
P arti cipa nts w h o re q uire i nitiati o n of  a n i m m u n o m o d ulat or y a ge nt , i ncl u di n g, b ut n ot li mite d t o,
6- M P, A Z A, or bi o l ogi c t hera p y; or w h o re q uire > 3 da ys of  treat me nt wit h hi g her d oses of 
s yste mic c ortic oster oi ds (e. g. pre d nis o ne > 1. 0 m g/ k g/ da y f or wei g hts ≤ 4 0 k g or > 4 0 m g/ da y f or 
w ei g hts > 4 0 k g or e q ui vale nt ) will be disc o nti n ue d fr om t he st u d y.
St u d y D ur ati o n f or P artici p a nt s
P arti cipa nt s ma y s pe n d u p t o 6 9 wee ks i n t his st u d y  (e xcl u di n g t he 
 i n t he S afet y F ol l ow-
u p Peri o d) pri or t o e nteri n g t he L T E Peri o d. T his i ncl u des u p t o 5 wee ks i n t he Scree ni n g 
P eri o d , 1 2 wee ks i n t he I n d ucti on P eri o d, a n d 5 2 wee ks i n t he Mai nte na nce 
P eri o d . F or 
parti ci pa nt s n ot e nteri n g L T E, a 
 Safety F o ll o w- up Peri o d will be c o m p lete d f or u p t o a t otal 
of  8 1 wee ks i n t he st u d y. 
P arti cipa nt s w h o meet earl y disc o nti n uati on crit eria ( aft er at  least 7 wee ks of  treat me nt) as 
descri be d i n Secti o n 8 , partici pa nt s w h o are n o n- res p o n ders at Wee k 1 2, a n d partici pa nt s w h o 
c o mplete t he Wee k 6 4 visit, will be eli gi ble t o e nt er t he o pti o nal L T E Peri o d (see Secti o n 8 ). 
P arti cipa nt s e nteri n g t he L T E Peri o d w h o c o ntin ue t o de m o nstrate cli nical be nefit will recei ve oral 
oza ni m o d dail y f or u p t o a p pr o xi matel y 4. 5 y ears fr o m t heir first d ose (Da y 1 ), or u p o n oza ni m o d 
a p pr o val for pe di atric C D parti ci pa nt s i n t heir c o u ntr y, or as per l ocal or re gi o nal re q uire me nts. 
F or p artici pa nts w h o e nter t he o pti o nal  LT E Peri o d, a 
 Safet y F o ll ow- u p P eri o d will b e 
c o mplete d a n d t he e ntire partici pati o n peri o d of  t he st u d y ma y be u p t o a p pr o xi matel y 6 years fr o m 
t he partici pa nt ’s first d ose ( Da y 1).
P artici p a nt I n p ut i n St u d y Desi g n
Pare nts of , a n d c hil dre n li vi n g wi t h Cr o h n’s Di sease are u ni q uel y p osi tio ne d t o hel p i n t he dr u g 
de vel o p me nt pr ocess, a n d t heir v o ices ha ve bee n i nc or p orate d i nt o t his pr ot oc ol.
Pare nts/ g uar dia ns/ pa rtici pa nts belie ve cli nical trials are val ua ble a n d a d va nce t he scie nce a n d 
ma na ge me nt of C D. T he y tr ust t heir healt hcare pr o vi ders t o disc uss a n d rec o m me n d cli nical trials 
a vaila ble wit hi n t h e I B D c o m m u nit y.
 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
5 1
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
 
 
 
5. 1. 1
D at a M o nit ori n g C o m mitt e e a n d Ot h er C o m mitt e e s
 
 
A n e xter nal, i n de pe n de nt D M C will be c har ge d wit h m o nit ori n g acc u m ulat i n g data fr o m t he st u d y, 
as well as ge neral as pects of st u d y c o n d uct.
T he c o m mittee will meet peri o di call y d uri n g t he st u d y t o r e vie w a g gre gate a nal yses b y tr e at me nt 
gr o u p c o ncer ni n g e nr oll me nt, treat me nt c o m plia nce, a d here nce t o foll o w -u p sc he d ule, a n d safety 
a n d efficac y data fr o m t he st u d y. T he D M C will ma ke d ose select i on a n d d ose a dj ust me nt 
decisi o ns base d o n t he  
 rec o m me n dat i ons. T he D M C ma y rec om me n d m o dif yi n g t he st u d y 
or st o p pi n g t he st u d y  earl y d ue t o safety c o ncer ns base d o n data re vie ws. 
T o ass ure t hat all pers o n nel i n v ol ve d i n t he c o n d uct of t he stu d y re mai n bli n de d t o t h e res ults of 
i nteri m re vie ws, a bli n di n g pla n will  be s pecifie d i n t he D M C C harter.
A D M C c harter will descri be t he pr oce d ures relate d t o t he c o m mittee o perati o ns i n greater detail.
5. 2
N u m b er of P arti ci p a nt s
A p pr o xi matel y  
 pe diatri c parti ci pa nt s a ge d 2 t o 1 7 years, i ncl usi ve, wi t h m oderatel y t o se verel y 
acti ve C D wi t h a n i na de q uate res p o nse, i ntol era nce, or l oss of  res p o nse t o pri or t h era p y for C D 
will 
be 
e nr o lle d i n t his st u d y. 
 
 
5. 3
E n d of St u d y D efi niti o n
T he start of t he trial is defi ne d as t he first partici pa nt first visit.
E n d of  trial is defi ne d as t he last parti ci pa nt last visit or t he date of  recei pt of  t he last data p oi nt 
fr om t he last partici pa nt t hat is re q uire d f or pri mar y , sec o n dar y, a n d/ or e x pl orat or y a nal ysis, as 
pre -s pecifie d i n t he pr ot ocol , w hic he ver is t he later date. 
St u d y  co m plet i on is defi ne d as t he fi nal date o n w hic h data f or t he pri mar y e n d p oi nt were or are
e x pecte d t o be c ollecte d, if t his is n ot t he sa me.
P arti cipa nt s w h o 
c o nti n ue t o de m o nstrate cli nical be nefit will 
be eli gi ble
t o recei ve 
S p o ns or -s u p plie d st u d y treat me nt f or a ma xi m u m tr e at me nt d urati o n as s pecifie d per l ocal or 
r e gio nal re q uire me nts (see Secti o n 7 ).
T he S p o ns or reser ves t he rig ht t o t er mi nate access t o S p o ns or -s u p plie d st u d y tr e at me nt if a n y of 
t he f oll owi n g occ ur: a) t he st u d y is ter mi nate d d ue t o safety c o ncer ns; b) t he de vel o p me nt of 
oza ni m o d is ter mi nate d f or a n y reas o n, i ncl u di n g b ut n ot li mite d t o, lac k of  efficac y an d/ or n ot 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
5 2
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
meet i n g st u d y o bjecti ves; c) t he parti ci pa nt ca n o btai n oza ni m o d fr o m a g o ver n me nt -s p o ns ore d or 
pri vate healt h pr o gra m. I n all cases , t he S p o ns or will f o ll o w lo c al  re q uire me nts.
A parti ci pa nt is c o nsi dere d t o ha ve c o m p lete d t he st u d y if he/s he has c o m p lete d t he last visit or 
t he last pr oce d ure s h o w n i n  Secti o n 2 .
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
5 3
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
5 4
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
6
S T U D Y P O P U L A TI O N
Pr os pecti ve a p pr o val of pr ot oc ol de viat i ons t o recr uit me nt a n d e nr oll me nt crit eria, als o k n o w n as 
pr ot oc ol  wai vers or e xe m pti ons, i s n ot per mitte d.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
5 5
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
6. 1
I n cl u si o n Crit eri a
P arti cipa nts are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if all o f t he fol l owi n g criteria a p pl y:
1)
Si g ne d Writte n I nf or me d C o nse nt
P arti cip a nts a n d t heir pare nt or g uar dia n m ust ha ve sig ne d a n d date d a n I nstituti o nal  Re vie w 
B oar d (I R B)/I n de pe n de nt Et hi cs C o m mittee (I E C)-a p pr o ve d wri tte n i nf or me d c o nse nt f or m 
(I C F) a n d asse nt i n acc or da nce wi t h re g ulat or y, l ocal, a n d i nstituti o nal  gui deli nes. T his m u st 
be o btai ne d bef ore t he perf or m a nce of  an y pr ot oc ol -relate d pr oce d ures t hat are n ot part of  
n or m al patient  care.
2)
T y pe of P artici p a nt a n d T ar get Dise ase C h ar acteristics
a)
P arti cipa nt is willi n g a n d a ble t o a d here t o t he st u d y visit sc he d ule a n d ot her pr ot oc ol 
re q uire me nts i ncl u di n g is willi n g a n d a ble t o s wall ow a  
 u nt il a 
 
of  oza ni m o d is a vaila ble.
b)
P arti cipa nt has bee n dia g n ose d wi t h CD ≥ 3 m o nt hs pri or t o t he Scree ni n g Vi sit. T he 
di a g n osis s h o uld be c o nfir me d b y cli nical a n d e n d osc o pic e vi de nce a n d c orr o b orate d b y  a 
hist o pat h ol o g y  re p ort ( Note: L ocal hist o pat h ol o g y sa m ple c olle ctio n a n d a nal ysis ma y als o  
be perf or m e d d uri n g e n d osc o p y at Scree ni n g if n o pri o r re p ort is rea dil y a vaila ble).
c)
P arti cipa nt has met  eac h of t he f oll owi n g 2 cri t eria:
i)
A P C D AI sc ore ≥ 3 0.
ii) P arti cipa nt has a S E S -C D sc ore ≥ 6 ( or S E S -C D ≥ 4 i n parti ci pa nt s wit h is olate d ileal 
di sease).
d)
P arti cipa nt has a n i na de q uate res p o nse, i nt olera nce, or l oss of  res p o nse t o at le ast 1 of t he 
f oll owi n g treat m e nts f or C D (see A p pe n di x 5 ).
i)
c ortic oster oids (e g, oral pre d nis o ne, or al  b u des o ni de M M X, i ntra ve n o us [I V]
c ortic oster oids) .
ii) i m m u n om o d ulat ors (e g, A Z A , 6-M P , c yclos p ori ne, M T X).
iii) bi o l ogic t hera p y (e g, uste ki n u ma b, a batace pt, i nfli xi ma b, eta nerce pt, a dali m u ma b, 
a na ki nra, rit u xi ma b, ve d o liz u ma b).
i v) ot her s y ste mic i m m u n om o d ul at or y t hera pies for C D .
e)
If t he part ici pa nt is ta ki n g t he f oll owi n g bac k gr o u n d t hera pies f or C D, a sta ble d ose m ust 
be ma i ntai ne d as i n dicate d bel o w ( dosa ge re gi me n ca n be a djuste d t o acc o m m o date 
m g/ k g/ da y  d osi n g as a p pr o priate) :
i)
Or al  a mi n osalic ylates (e g, mesala mi ne, s ulfasalazi ne, olsalazi ne, balsalazi de), t he d ose 
m ust ha ve bee n sta ble starti n g 3 wee ks pri or t o Scree ni n g e n d osc o p y .
ii) Pre d nis o ne ( ≤ 0. 5 m g/ k g/ da y u p t o 2 0 m g /da y), t he d ose m ust ha ve bee n sta ble starti n g 
2 wee ks pri or t o S cree ni n g e n d osc o p y a n d m ust re mai n sta ble t hr o u g h t he first 5 wee ks 
of  treat me nt.
iii) Or al  bu des o ni de t hera p y ( d oses ≤ 9 m g per da y) or or al  becl o m et has o ne ( d oses ≤ 5 m g 
per da y), t he d ose m ust ha ve bee n sta ble starti n g 2 wee ks pri or t o Scree ni n g e n d osc o p y 
a n d m ust re mai n sta ble t hr o u g h t he first 5 wee ks of treat me nt.
a)
P arti cipa nt m ust ha ve d oc u me ntati o n of vacci nati o ns per sta n dar d i m m u nizati o n sc he d ule
i ncl u di n g c o m plete varicella vacci nati o n at least 3 0 da ys pri or t o ra n d o mizat i on ( Da y
or 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
5 6
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
d oc u m e nt atio n o f p ositi ve varicella z oster vir us ( V Z V) i m m u n o gl o b uli n G (I g G) a nt i b o d y 
pri or t o ra n d o mizat i on ( Da y  
.2 8
3)
A ge of P artici p a nt
a)
P arti cipa nt m ust be a ge 2 t o 1 7 years , i ncl usi ve
 at t he ti me of 
i nf or me d c o nse nt/asse nt.
N ote: Parti ci pa nt s wit h a wei g ht bel o w t he 5t h perce nt ile f or a ge ( per C D C gr o wt h c harts) 2 1
s h o uld be disc usse d wit h t he Cli nical Trial P h ysicia n or desi g nee pri or t o e nr oll me nt.
4)
Re pr o d ucti ve St at us
F or t he p ur p oses of  this st u d y, fe male of c hil d beari n g p ote ntial ( F O C B P) is defi ne d as a fe male 
parti ci pa nt ≥ 1 2 years of  age or has reac he d me narc he, a n d 1) has n ot u n der g o ne a 
h ysterect o m y (t he s ur gical re mo v al of t he ut er us) or bilateral o o p h orect o m y  (t he s ur gical 
r e mo val  of b ot h ovaries) or 2) has n ot bee n p ost me n o pa usal f or at least 2 4 c o nsec uti ve m o nt hs 
(t hat is, has ha d me nses at a n y time d uri n g t he prece di n g 2 4 c o nsec ut i ve m o nt hs).
I n vesti gat ors s hall c o u nsel F O C B P part ici pa nts o n t he i m p orta nce of  pre g na nc y pre ve nt i on 
a n d t he i m plicat i ons o f a n u ne x pecte d pre g na nc y.

T he in vest i gat or s hall e val uate t he effecti ve ness of t he c o ntrace pti ve met h o d i n relati o ns hi p t o 
t he first d ose of st u d y int er ve nt i on.

L ocal  la ws a n d re g ulat i ons ma y re q ui r e t h e us e of alter nati ve a n d/ or a d ditio n al  co ntrace pti o n 
met h o ds.
a)
Fe m ale P artici p a nts :
i)
Fe males w h o are n ot of  chil d beari n g p ote nti al are e xe mpt fr o m c o ntrace pti ve 
re q uire me nts.
( 1) If at a n y ti me d uri n g t he st u d y t he a bility t o bec o me pre g na nt c ha n ges , t he y will n o 
l on ger be e xe m pt fr o m c o ntrace pti ve re q uire me nts. T he in vest i gat or will e d ucate
t he parti cip a n t re gar di n g a bst i ne nce or c o ntrace pti o n o pti o ns a n d t he c orrect a n d 
c o nsiste nt use of  effecti ve c o ntrace pti ve met h o ds i n or der t o s uccessf ull y pre ve nt 
pre g na nc y.
ii) F O C B P
m u st ha ve a ne gat i ve hi g hl y se nsiti ve ser u m p re g na nc y t est ( mi ni m um 
se nsitivi t y 25 I U/ L or e q ui vale nt u nits of  h u ma n c h orio nic g o na d otr o pi n ) pri or t o 
ra n d omizat i on .

A d dit i onal re q ui re me nts f or pre g na nc y testi n g d uri n g a n d after st u d y int er ve ntio n are l ocate d 
i n Secti o n 2 .

T he in vest i gat or is res p o nsi ble f or re vie w of  me dical hist or y , me nstr ual  hist or y, a n d rece nt 
se x ual act i vity t o decrease t he ris k f or i ncl usi on of  a wo m a n wi t h an earl y un detecte d 
pre g na nc y . At  eac h visit, t he i n vesti gat or will as k t he partici pa nt if me narc he has occ urre d
si nce t he last visit a n d t his i nf or mati on will be rec or de d i n t he electr o nic case re p ort f or m 
(e C R F).
iii) F O C B P m ust a gree t o f oll ow i nstr uctio ns f or me t ho d(s) of  co ntrace pti o n defi ne d i n 
A p pe n di x 4 a n d as descri be d bel o w a n d i ncl u de d i n t he I C F.
i v) F O C B P
are per mitte d t o use h or m o nal c o ntrace ptio n met h o ds 
(as descri be d i n 
A p pe n di x 4) .
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
5 7
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
v)
A female partici pa nt is eli gi ble t o partici pate if s he is n ot pre g na nt or breastfee di n g, 
a n d at least 1 of  t he f oll owi n g c o n di tio ns a p pl ies:
( 1) Is n ot a F O C B P
O R
( 2) Is a F O C B P a n d usi n g a c o ntrace pti ve met h o d t hat is hi g hl y effect i ve ( wit h a fail ure 
rate of  
< 1 % 
per 
year), 
wit h 
l ow 
user 
de pe n de nc y , as descri be d 
i n 
A p pe n di x 4 d uri n g t he i nter ve nti o n peri o d a n d f or at least 9 0 da ys aft er a n d a grees 
n ot t o d o nate e g gs ( o va, o oc ytes) f or t he p ur p ose of re pr o d ucti o n f or t he sa me ti me 
p eri o d
6. 2
E x cl u si o n Crit eri a
P arti c i pa nts are e xcl u de d fr o m t he st u d y if a n y of t he f o ll owi n g cri t eria a p pl y:
1)
Me dic al C o n diti o ns
a)
P arti cipa nt
has cli nicall y rele va nt car di o vasc ular, he pat ic, ne ur ol o gical, p ul m o nar y , 
o p ht hal m o l ogical , e n d ocri ne, ps yc hiatric, 
or ot her 
maj o r s yste mic disease
ma ki n g 
i m ple me ntati o n of  the pr ot oc ol or i nter pretatio n of t he st u d y diffic ult or t hat w o ul d p ut t he 
parti ci pa nt at  ris k b y partici pati n g i n t he st u d y.
i)
Cli nicall y rele va nt p ul m o nar y c o n ditio n s i ncl u de, b ut are n ot li mite d t o, hist or y  of 
se vere or c hr o nic l un g di sease, br o nc h o p ul m onar y d ys plasia, c ystic fi br osis, or se vere 
ast h ma (ie, t hat i nterferes wit h n or mal act i vities of dail y  li vi n g).
b)
P arti cipa nt is li kel y t o re q uire, i n t he p h ysic ia n’s j u d g me nt, b o wel resectio n wi t hi n 
1 2 wee ks of e ntr y  int o t he st u d y .
c)
P arti cipa nt has a dia g n osis of  U C , i n deter mi nate c olit is, ra diatio n c o litis, or isc he mic 
c olit is, or has strict ures wi t h preste n otic dilatati o n, re q uiri n g pr oce d ural  int er ve nti o n, or 
wi t h o bstr ucti ve s y m pt o ms. I n a d diti on, parti ci pa nt s wit h c ol o nic or ileal strict ures t hat are 
n ot passa ble wi t h an a ge-a p pr o priate c o l on osc o pe t hat t he e n d osc o pist n or m all y uses i n 
cli nical pract ice, or strict ures i n t he ile u m or ile ocecal val ve t hat are fi br otic i n nat ure, will 
be e xcl u de d.
d)
P arti cipa nt has c urre nt st o ma, il eal-a nal p o uc h a nast o m osis, fist ula t hat is li kel y t o re q uire, 
i n t he p h ysicia n’s j u d g me nt, s ur gical or me dical i nter ve nt i on wit hi n 1 2 wee ks of e ntr y i nt o 
t he st u d y or nee d f or ile ost o m y or c olost o m y.
e)
P arti cipa nt has e xte nsi ve s mall bo w el  resect i on ( > 1 0 0 c m) or k n o w n di a g n osis of  sh ort 
b o wel  s y n dr o me or partici pa nt re q uires t otal pare nteral n utriti on.
f)
P arti cipa nt has s us pecte d or dia g n ose d i ntra-a b d o mi nal or peria nal a bscess t hat has n ot 
bee n a p pr o priatel y treate d.
g)
P arti cipa nt
has d o c u m e nt atio n of  posi tive test f or t o xige n ic Cl ostri di oi des difficile
(f or merl y Cl ostri di u m difficile [C difficile ]) b y p ol y merase c hai n reacti on e xa mi nat i on of 
t he st o ol duri n g S cree ni n g. If p osi tive, partici p a nt s ma y be rescree ne d aft er a p pr o priate 
treat me nt a n d ne gat i ve retest n o earlier t ha n 7 da ys after c o m pleti o n o f treat me nt.
h)
P arti cipa nt has d oc u me ntati o n of  posi tive e xa mi natio n f or pat h o ge ns ( o va, parasites, a n d 
bacteri a). If p ositive, parti ci pa nt s ma y be treate d a n d rescree ne d.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
5 8
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
i)
P arti cipa nt re q uires or is e x pecte d t o u n der go a p heresis (e g, A dac o l um n a p heresis) wit hi n 
2 wee ks of ra n d o mizat i on ( D a y ).
j)
P arti cipa nt
is pre g na nt, lactati n g, has a p osi ti ve ser u m β-s u b u nit h u ma n c h orio ni c 
g o na d otr o pi n ( β-h C G) meas ure d d uri n g Scree ni n g or a p osi ti ve uri ne pre g na nc y t est o n 
D a y  .
k)
P arti cipa nt has a hist or y  or prese nce of  the f oll owi n g cli nicall y rele va nt car di o vasc ular 
c o n ditio ns:
i)
Str uct ural car diac di sease (e g, h y pertr o p hic o bstr ucti ve car dio m y o pat h y, u nre paire d 
c o n ge nital heart defects). Parti cipa nt s wit h re paire d c o n ge nital heart defects s h o uld be 
di sc usse d wit h t he Cli nical Trial P h ysicia n or desi g nee pri or t o e nr oll me nt.
ii) Car di ac e ve nts (e g, m y o car dial infarcti o n) or diseases t hat pre dis p ose t o car diac 
c o mplicat i ons.
iii) Hi st or y of str o ke, heart fail ure, or s y m pt o matic bra d ycar dia defi ne d as < 5t h perce nt ile
of  n or mal si n us r h yt hm H R f or a ge.2 9
i v) Sec o n d de gree ( M o bitz t y pe II) A V bl oc k or hi g her, sic k si n us s y n dr o me, or si n o -atrial 
bl oc k.
v)
 
 
 
vi) D uri n g eit her Scree ni n g or Da y 
 
 
 
vii) Se vere u ntreate d slee p a p nea .
l)
P arti cipa nt has a hist or y  of dia betes mellit us ( D M) t ype 1, or u nc o ntr olle d D M t ype 2 
(he m o gl o bi n A 1c [H b A 1c ] > 9 %) or is a dia bet ic parti cipa nt wit h si g nifica nt c o m o r bi d 
c o n ditio ns s uc h as reti n o pat h y  or ne p hr o pat h y.
m)
P arti cipa nt has a hist or y  of u vei tis wi t hi n t he last year pri or t o Scree ni n g, or hist or y  or 
e vi de nce of reti nal disease (e g, mac ular e de ma).
n)
P arti cipa nt has a n y k n o w n acti ve bacterial, viral, f u n gal (e xcl u di n g f u n gal i nfecti o n of nail 
be ds, mi n or u p per res pirat or y tract i nfecti ons, a n d mi n or s ki n i nfecti o ns), m yc o bacterial 
i nfecti on (incl u di n g t u berc ulosis [ T B] or at y p ical m yc o bacterial disease), or a n y ot h er 
i nfecti on t hat re q uire d h os pi talizati on or treat me nt wit h I V a nti bi ot ics wi t hi n 3 0 da ys of 
Scree ni n g or oral a nt i bi otics wit hi n 1 4 da ys of Scree ni n g.
N ote: I n t he case of  prior S A R S -C o V - 2 i nfecti o n, s y m pt o ms m ust ha ve c o m p letel y 
res ol ve d a n d base d o n i n vest i gat or assess me nt i n c o ns ultat i on wi t h the Cli nical Tri al 
P h ysicia n or desi g nee , t here are n o se q uelae t hat w o ul d pl ace t he partici pa nt at a hi g her 
ris k w he n recei vi n g I P. S A R S -C o V 2 t estin g ma y be c o n d ucte d pri or t o ra n d o mizati on 
( D a y ) if re q uire d b y a n d i n acc or da nce wit h nati o nal, l ocal, or i nstit uti o nal g ui deli nes.
o)
P arti cipa nt has a rec urre nt or c hr o nic i nfect i on (e g, he patit is A vir us, he pat itis B vir us, 
he pat itis C vir us, h u ma n i m m u n o deficie nc y vir us [ HI V]); rec urre nt uri nar y tract i nfecti o ns 
are all o we d.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
5 9
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
p)
P arti cipa nt
has a n y hist or y  of ca ncer, i ncl u di n g s oli d t u mors a n d he mat ol o gical 
mali g na ncies (e xce pt b asal cell a n d i n sit u s q ua m o us cell carci n omas of t he s ki n or cer vica l 
d y s plasia/ca ncer t hat ha ve bee n e xcise d a n d res ol ve d) or c o l onic d y s plasia t hat has n ot 
bee n c o m p letel y r e mo v e d. P arti ci pa nts at hi g h ris k (ie, famil y h ist or y, C D d urati o n ) f or 
c olo nic mali g na nc y
has d oc u me nte d e vi de nce of  ha vi n g ha d a s ur veilla nce c o l on os oc p y 
wi t hi n t he last 2 year s or acc or di n g t o l ocal a n d nati o nal me dical g ui deli n e s t o e val uate f or 
p ol y ps, d ys plasia , or m ali g na nc y (t his ca n be d o ne as part of  t he c olo n osc o p y  p erf or m e d 
d uri n g scree ni n g as nee de d).
q)
P arti cipa nt has a hist or y o f or c urre ntl y acti ve pri mar y or sec o n dar y i m m u n o deficie nc y, or 
parti ci pa nt s wit h k n o w n ge netic dis or ders as a ca use f or c olitis.
2)
Re pr o d ucti ve St at us
a)
Fe males w h o are breastfee di n g .
3)
Pri or/ C o nc o mit a nt T her a p y
a)
P arti cipa nt has h y perse nsit i vity t o acti ve i n gre die nts or e xci pie nts of oza ni m o d.
b)
P arti cipa nt has pri or partici pat i on i n a n oza ni m o d cli nical trial.
c)
P arti cipa nt has bee n treate d wi t h a biol o gic a ge nt wi t hi n 4 wee ks pri or t o t he first d ose of 
I P. U n detecta ble dr u g le vels o n t hera pe ut ic dr u g m o nit ori n g ( T D M) assa ys ma y be utilize d 
(see Secti o n 6. 1 ).
d)
P arti cipa nt has bee n treate d wit h a n i n vesti gati onal a ge nt, i ncl u di n g f or S A R S -C o V -2 
i nfecti on , wit hi n 5 eli mi nati on half -li ves of t hat a ge nt pri or t o t he first d ose of I P. 
e)
P arti cipa nt has recei ve d a li ve or l i ve atte n uate d vacci ne wi t hi n 4 wee ks pri or t o t h e first 
d ose of I P.
N ote: N o n -li ve vacci nati ons ca n be a d mi nistere d d uri n g t he st u d y .
f)
P arti cipa nt has recei ve d a n y pre vi o us treat me nt wi t h ly m p h oc y t e-de pl et i n g t hera pies 
(e g, Ca m pat h ®, 
a nt i-C D 4, 
cla dri bi ne, rit u xi ma b, ocreliz u ma b, 
c yclo p h os p ha mi de, 
mit o xa ntr o ne, t otal b o d y  irra diati on, b o ne marr o w tra ns pla ntati o n, ale mt uz u ma b, or 
dacliz u ma b).
g ) P arti cipa nt has recei ve d treat me nt wit h D- pe nicilla mi ne, lefl u n omi d e, or t hali d o mi de 
wi t hi n 8 wee ks of first d ose of I P.
h)
P arti cipa nt
has recei ve d pre vi o us treat me nt wit h nat aliz u ma b, fi n g oli m o d, or ot her 
S 1 P rece pt or m o d ulat ors.
i)
P arti cipa nt has a hist or y  of tr e at me nt wit h I V i m m u ne glo b uli n (I VI g), or pl as ma p heresis 
wi t hi n 3 mo n t hs prior t o fi rst d ose of I P.
j)
P arti cipa nt has recei ve d pre vi o us treat me nt wit h or al  c yclos p o ri ne, tacr oli m us, sir oli m us, 
or m yc o p he n o late mof et il withi n 1 6 wee ks of i nit iatio n of  Scree ni n g.
k ) P arti cipa nt s ha vi n g dela ye d gr o wt h or dela ye d p u bertal  de velo p me nt a n d u na ble t o 
mai ntai n a sta ble d ose of c ortic oster oi ds t hr o u g h  
.
l)
P arti cipa nt h as a hist or y o f treat me nt wit h t o pical rectal t hera p y ( 5-A S A o r c ortic oster oi ds) 
wi t hi n 2 wee ks of  Scree ni n g e n d osc o p y or has pla n ne d c o nc urre nt use of  an y per rect u m 
t hera p y.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
6 0
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
m)
P arti cipa nt pla ns c o nc urre nt treat m e nt wit h im m u n o m o d ul at or y age nts (e g, A Z A, 6 -M P, 
c yclos p ori ne, or M T X) aft er ra n d o mizati on ( Da y ). Partici pa nt s recei vi n g A Z A, 6 -M P, 
or M T X at  Scree ni n g m ust di sc o nti n ue tr e at me nt wit h t hese a ge nts pri or t o fi rst dose of 
I P.
n)
P arti cipa nt
has 
c hr o nic 
n o nster oi d al  
ant i-i nfla m mat or y 
dr u g 
( N S AI D) 
u se 
(N ot e : O ccasi o nal use of  NS A I Ds a n d aceta mi n o p he n [e g, f or treat me nt of  hea dac he, 
art hritis, m yal gias, or me nstr ual cra m ps] a n d as piri n u p t o 3 2 5 m g/ da y is per mitt e d).
o)
P arti cipa nt s recei vi n g treat me nt wit h Class Ia or Cl ass III a nti-arr h yt hmic dr u gs or wit h 
2 or m ore a ge nts i n c o m bi nati o n k n o w n t o pr ol o n g P R i nter val.
p)
E xcl usi o n cri t erio n n o l o n ger a p plica ble , per Pr ot oc ol A me n d me nt 0 2.
q)
P arti cipa nt s ha ve recei ve d c h o lestyr a mi ne or ot her dr u gs i nterferi n g wi t h ent er o he patic 
circ ulati on wi t hi n 3 wee ks of Scree ni n g.
r)
P arti cipa nt s recei vi n g treat me nt wit h a n y of the f oll o wi n g dr u gs or i nter ve nt i ons wi t hi n 
t he c orres p o n di n g ti mefra me:
i)
T w o wee ks pri or t o ra n d o mizati o n ( Da y )
( 1) M o n oa mi ne o xi dase i n hi bit ors (e g, sele gili ne, p he nelzi ne)
ii) At  ra n d o mizati on ( D a y 
( 1) C Y P 2 C 8 i n d ucers (e g, rifa m pici n)
4)
P h ysic al a n d L a b or at or y Test Fi n di n gs
a)
E C G s h o wi n g a n y  cli nicall y si g nifica nt a b n or mality.
b)
P arti cipa nt ’s ser u m creat i ni ne is > 1. 4 m g/ d L f or fe males or > 1. 6 m g/ d L f or males.
c)
P arti cipa nt has li ver f uncti o n i m pair me nt or persist i n g ele v atio ns of  AL T or as partate 
a mi n otra nsferase ( A S T) > 2 × u p per li mit of n or mal ( U L N); or direct bilir u bi n > 1. 5 × U L N.
N ote: U L N ma y differ bet wee n 
 a n d s h o uld be deter mi ne d b y la b orat or y 
sta n dar ds.
d)
P arti cipa nt ’s pl at elet c o u nt is < 1 0 0, 0 0 0/ μ L.
e)
P arti cipa nt ’s he m o gl obi n is < 8. 0 g/ d L.
N ote: He m o gl o bi n at t he ti me of eac h st u d y  visit blo o d dra w s h o ul d be > 7. 0 g/ d L.
f)
P arti cipa nt ’s ne utr o p hil c o u nt is < 1 5 0 0/ μ L.
g)
P arti cipa nt ’s a bs ol ute w hite bl o o d c o u nt < 3 5 0 0 / μ L.
h)
P arti cipa nt ’s A L C is < 8 0 0/ μ L.
i)
P arti cipa nt ’s st o ol is p ositive f or pat h o ge ns.
 
N ote: U p t o 2 re peat tests ma y be p erf or m e d f or sig nifica nt variat i ons d uri n g Scree ni n g P eri o d. 
A p pr o val fr o m t he Cli nical Trial P h ysicia n or desi g nee m ust be o btai ne d f or a d dit i onal retesti n g.
5)
Ot her E xcl usi o n Criteri a
a)
Pris o ners or partici pa nt s w h o are i n v olu ntaril y  incarcerate d. ( N ote: U n der certai n s pecific 
circ u msta nces a n d o nl y i n c o u ntries w here l ocal re g ulat i ons per mit, a pers o n w h o has bee n 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
6 1
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
i m pris o ne d ma y be i ncl u de d or per mitte d t o c o nti n ue as a partici pa nt . Strict c o n ditio ns 
a p pl y, a n d B M S a p pr o val is re q uire d.)
Eli gi bilit y crit eria f or t his st u d y ha ve bee n caref ull y c o nsi dere d t o e ns ure t he safet y of t he st u d y 
parti ci pa nt s a n d t hat t he res ults of  the st u d y ca n be use d. It is i m perati ve t hat partici pa nt s f ull y 
meet all eli gi bilit y criteria.
6. 3
Lif e st yl e R e stri cti o n s
N ot a p plica ble. N o restrict i ons are re q uire d .
6. 4
S cr e e n F ail ur e s
Scree n fail ures are defi ne d as partici pa nts w h o c o nse nt t o partici pate i n t he cli nical st u d y b ut w h o 
are n ot s u bse q ue nt l y ra n d o mize d i n the st u d y/i ncl u de d i n t he a na l ysis p o p ulati o n. Parti ci pa nts w h o 
fail t o meet
t he i ncl usio n /e xcl usio n crit eria ca n be rescree ne d o nce per I n vesti gat or discreti o n. 
A d dit i onal scree ni n g atte mpts be y o n d t he first rescree n m ust be a p pr o ve d b y t he Cli nical Trial 
P h ysic ia n or d esi g nee pri or t o rescree ni n g.
A mi ni mal s et of  scree n fail ure i nf or mati on is re q uire d t o e ns ure tra ns pare nt re p orti n g of  scree n 
fail ure partici pa nts, t o meet 
t he C o ns oli date d Sta n dar ds of  Re p orti n g Tri als ( C O N S O R T) 
p u blis hi n g re q uire me nts, as a p plica ble, a n d t o res p o n d t o q ueries fr om re g ulat or y aut h ori ties. 
Mi ni mal 
i nf or mati on i ncl u des date of  co nse nt, d e m o gra p h y , scree n fail ure details, eli gi bilit y 
criteria, a n d a n y S A Es.
6. 4. 1
R et e sti n g D uri n g S cr e e ni n g
Retesti n g of  la b orat or y para meters a n d/ or ot her assess me nts at scree ni n g will  be per mitte d (i n 
a d ditio n t o a n y para meters t hat re q uire a c o nfir mat or y val ue).
A 
parti ci pa nt’s pre vi o us 
c olo n os c o p y  may be use d if p erf or m e d wi t hi n 3 5 da ys of ra n d o mizat i on ( Da y ) a n d is n ot re q uire d 
t o be re peate d. T he per mitte d fre q ue nc y of  re- t esti n g f or e xclusi o n  crit eria is pre -s pecifie d i n 
Secti o n 6. 2 .
T he m o st c urre nt res ult pri or t o a d mi nistrati o n of  st u d y int er ve nt i on is t he val ue b y w hic h st u d y 
i ncl usi on will  be assesse d, beca use it re prese nts t he partici pa nt ’s m o st c urre nt cli nical stat e.
La b orat or y  para meters a n d/ or assess me nts t hat are i ncl u de d i n 
ma y be re peate d i n a n 
eff ort t o fi n d all p ossi ble well-q ualifie d parti ci pa nt s. C o ns ultati o n with t he Cli nical Trial P h ysicia n
or desi g nee ma y be nee de d t o i de ntif y w het her re peat t estin g of  an y parti c ular para m eter is 
cli nicall y rele va nt.
U p t o 2 retests per pr oce d ure ma y be p erf or m e d (
 c o l on osc o p y , or a n y 
pr oce d ures f or e val uat i on of  late nt T B) f or sig nifica nt variat i ons i n pr ot oc ol -re q uire d tests at  t he 
di scretio n of  the in vest i gat or or at t he re q uest of  the S p o ns or. Retests m ust be c o m m u nicate d t o 
t he Cli nical Tri al Ph ysicia n or desi g nee. A p pr o val fr o m t he Cli nical Tri al Ph ysicia n or desi g nee
m ust be o btai ne d if a test is re q uire d t o be re peate d > 2 ti mes a n d t he per mitte d fre q ue nc y is o utsi d e 
t he li mits pre -s pecifie d i n t he pr ot oc ol. 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
6 2
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
S A R S -C o V - 2-rel ate d Retesti n g
Testi n g f or as y m pt o mat ic S A R S -C o V - 2 i nfecti on is n ot re q uire d b ut ma y be perf or me d acc or di n g 
t o nati o nal or i nstituti o nal  gui deli nes . H o we ver, s o me parti ci pa nts ma y d e v el o p s us pecte d or 
c o nfir me d s y m pt o mat ic S A R S -C o V - 2 i nfecti on or be f ou n d t o ha ve as y m pt o m at ic S A R S -C o V - 2
i nfecti on d uri n g t he S cree ni n g P erio d. I n s uc h cases, partici pa nt s ma y be c o nsi dere d eli gi ble f or 
t he st u d y after meet i n g all i ncl usi o n/e xcl usi on cr iteria relate d t o acti ve i nfect i on, a n d after meeti n g 
t he f o ll owi n g cri t eria:

At  least 1 0 da ys ( 2 0 da ys f or se vere/critical ill ness) ha ve passe d si nce s y m pt o ms first a p peare d 
or p osit i ve test res ult, a n d

At  least 2 4 h o urs ha ve passe d si nce last fever wi t h o ut t he use of  fe ver -re d uci n g me dicat i ons,  
a n d

S y m pt o m s (e g, c o u g h, s h ort ness of breat h) ha ve res ol ve d, a n d

I n t he o pi ni o n of  the in vesti g at or, t here are n o S A R S -C o V - 2 se q uelae t hat ma y place t h e 
parti ci pa nt at a hi g her ris k of recei vi n g i n vest i gati onal treat me nt

A n e gat i ve f oll o w-u p m o lec ular test f or S A R S -C o V - 2 ma y a ls o be perf or me d if rec om me n de d 
base d o n i ns tit utio nal , lo c al , or r e gi o nal  g ui deli nes
7
S T U D Y I N T E R V E N TI O N( S) A N D C O N C O MI T A N T T H E R A P Y 
St u d y  i nter ve nti o n is defi ne d as a n y i n vesti gati o nal i nter ve nt i on (s), mar kete d pr o d uct(s), place b o ,
pr oce d ure(s), or me dical de vice i nte n de d t o be a d mi nistere d t o a s t u d y partici pa nt acc or di n g t o t he 
st u d y pr ot oc ol .
St u d y  int er ve nt i on i ncl u des b ot h I n vesti gati onal [ Me dici nal] Pr o d uct (I P/I M P); see Secti o n 7. 1 )
a n d 
N o n 
i n vesti gati o nal/ A u xiliar y [ Me dici nal] 
Pr o d uct 
( N o n-I P/ N o n-I M P/ A x M P; s e e 
Secti o n 7. 7 ).
A n I P, als o k n o w n as I M P i n s ome r e gio ns, is defi ne d a s a p har mace ut ical f or m of a n act i ve 
s u bsta nce or place b o bei n g teste d or use d as a refere nce i n a cli nical st u d y, i ncl u di n g pr o d ucts 
alrea d y wit h a mar keti n g a ut h orizati on b ut use d or asse m ble d ( f or mulate d or pac ka ge d) differe nt l y 
fr om t he a ut h orize d f or m, or use d f or a n u na ut h orize d i n dicati on, or w he n use d t o gai n f urt her 
i nf or mat i on a b o ut t he a ut h orize d f or m.
Ot her me d icatio ns use d as s u p p ort or esca pe me d icatio n f or pre ve ntati ve, dia g n osti c, o r t hera pe utic 
reas o ns, as c o mp o ne nts of  the sta n dar d of  care f or a gi ve n di a g n osis, ma y be c o nsi dere d as 
I Ps/ A x M Ps.
7. 1
St u d y I nt er v e nti o n s A d mi ni st er e d
Oza ni m o d 
 
, 0. 4 6, a n d 0. 9 2 m g, de vel o pe d f or a d ults will be a d mi nistere d i n 
parti ci pa nt s 
. T he a d ult  
 
f or mulat i ons , wi t h a sma ll 
 size 
 a n d 
 
all o w f or ease of  swall o wi n g. 
 e xci pie nts i ncl u de 
 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
6 3
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
 
 
 
 
Oza ni m o d 
 will be pac ka ge d i n 
 
 f or treat me nt me d icati on 
 i n t he d ose escalat i on ki ts), 
close d wi t h a 
 T he ca p o n t he treat me nt 
 will be 
, a n d t he 
 T he labeli n g will be 
i n acc or da nce wit h G C P a n d a n y ot her l ocal re g ulat or y  re q uire me nts.
 
T he la bel(s) f or I P will i ncl u de S p o ns or na me, a d dress a n d t ele p h o ne n u m ber, t he pr ot oc ol  n um ber, 
I P na me, d osa ge f or m an d stre n gt h ( w here a p plica ble), a mo u nt of  IP per c o nt ai ner, l ot n u m ber, 
e x pir y date ( w here a pplica ble), m e dicatio n i de ntificati o n/ kit n u m ber, d osi n g i nstr uctio ns, st ora ge 
c o n ditio ns, a n d re q uire d ca ut i on state me nts a n d/ or re g ulat or y state me nts as a p plica ble or as 
di ctate d b y t he site’s Sta n dar d O perati n g Pr oce d ure. A d dit i onal i nf or mat i on ma y be i nclu de d o n 
t he la bel as a p plica ble per l ocal re g ulat i ons.
 
 
 
 
 
P arti cipa nt s s h o ul d be i nstr ucte d t o ta ke t he oza ni m o d or al  d ose wi t h or wit h o ut f o o d . I nstr ucti o ns 
f or a d mi nistratio n of  t he pe diatric d osa ge f or m (c urre ntl y i n de vel o p me nt) will be pr o vi de d i n t he 
I nstr uctio ns f or Use o nce a vaila ble. 
 partici pa nt s will c o nt i n ue t o recei ve t he 
bli n de d 0. 4 6 or 0. 9 2 m g/ da y a d ult e q ui vale nt d ose 
 
 
 
 
 
 0. 4 6 or 0. 9 2 m g/ da y 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
6 4
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
 
 
 
 0. 9 2 m g/ da y a d ult e q ui vale nt d ose 
 
P arti cipa nt s s h o ul d be i nstr ucte d t hat if t he y for g et t o ta ke a d ose, t he y ca n ta ke t he d ose wit hi n 
4 h o urs of t he n or m al d osi n g ti m e. If t he parti c i pa nt v o mit s t he d ose , he/s he s h o uld be i nstr ucte d 
n ot t o ta ke a n ot her d ose o n t he sa me d a y , b ut t o ta ke t he ne xt d ose at t he re g ular ti me o n t he 
f oll owi n g da y.
If a si n gle d ose is misse d d uri n g t he first 2 wee ks of treat me nt, or f or m ore t ha n 7 c o nsec ut i ve da ys 
d uri n g Da ys 1 5 t o 2 8, treat me nt m ust be rei nitiat ed usi n g t he 7 -da y d ose escalat i on re gi me n 
 oza ni m o d 0. 4 6 m g dail y f or t he 
0. 9 2 m g d ose . If a parti ci pa nt misses a d ose d uri n g d ose escalat i on, t he Cli nical Tri al P h ysicia n
or desi g nee s h o uld be c o ntacte d t o disc uss c o mpleti n g t he d ose escalat i on sc he d ule. T he misse d 
d ose a n d e xte n de d da ys f or escalat i on nee d t o be d oc u me nte d as a p pr o priate i n t he eC R F.
If a part ici pa nt misses m ore t ha n 1 4 c o nsec ut i ve d oses f or a n y reas o n, t he Cli nical Trial P h ysicia n
or desi g nee m ust be c o ntacte d t o disc uss pr oce d ures f or res u mi n g t hera p y, w hic h ma y i ncl u de 
car diac m o nit ori n g a n d d ose escalat i on pr oce d ures o n t he first da y t hat t he partici pa nt res u mes 
d osi n g.
descri bes car diac m o nit ori n g pr oce d ures t o be f oll o we d as i n dicate d d uri n g 
d ose escalat i on.
7. 2
M et h o d of St u d y I nt er v e nti o n A s si g n m e nt
P arti cipa nt s m ust 
pr o vi de pr o per i nf or me d c o nse nt/asse nt bef ore a n y trial pr oce d ures are 
perf or m e d. 
 
 I n a d dit i on, a pare nt or 
g uar di a n of  all partici pa nt s
 ( or l ocal age of  majori t y) m u st sig n a n I C F. O nce a parti ci pa nt
t ur ns 1 8 years of  age ( or l ocal age of  majori t y), he/s he ma y nee d t o sig n a c o nse nt f or m, i n 
acc or da nce wi t h re gio nal or l ocal re g ulat i ons. C o nse nte d/asse nte d parti ci pa nt s me eti n g all 
eli gi bilit y crit eria will be assi g ne d t o treat me nt/ra n d o mize d usi n g I R T. F urt her i nstr ucti o ns o n t he 
use of t he s yste m wi ll be pr o vi de d i n a se parate I R T ma n ual.
 
 
 partici pa nt s will be ra n d omize d i n a d o u bl e- bli n d ma n ner t o 
or al  o z a ni mo d i n a 1: 1 rati o. 
 
 

Oza ni m o d 0. 9 2 m g/ da y 
 orall y starti n g 
 
 0. 4 6 m g/ da y 
,  
 0. 9 2 m g/ da y 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
6 5
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d

Oza ni m o d 0. 4 6 m g/ da y 
 orall y 
 
 0. 4 6 m g/ da y 
 0. 4 6 m g/ da y 
 
, 
parti ci pa nt s will be ra n d omize d 1: 1 t o or al  oza ni m o d 0. 4 6 m g/ da y or 0. 9 2 m g/ da y a d ult e q ui vale nt 
d oses 
 
7. 3
Bli n di n g
T his i s a d o u ble- bli n d st u d y . Access t o treat me nt c o des will be restricte d fr o m all partici pa nts a n d 
sit e a n d S p o ns or pers o n nel pri or t o fi nal data base l oc k.
Bli n di n g of  st u d y tr e at me nt assi g n me nt is critical t o t he i nte grit y of t his cli nical st u d y. H o we ver, 
i n t he e ve nt of a me dical e mer ge nc y or pre g na nc y i n a n i n di vi d ual p arti ci pa nt i n w hic h k n o wle d ge 
of  t he I P is critical t o t he parti ci pa nt 's ma na ge me nt, t he bli n d for t h at partici pa nt ma y be br o ke n 
b y t he in vest i gat or. T he parti ci pa nt ’s safety ta kes pri ori t y over a n y ot h er c o nsi derati o ns i n 
deter mi ni n g if a treat me nt assi g n me nt s h o ul d be u n bli n de d.
Bef ore brea ki n g t he bli n d of  an i n di vi d ual p arti ci pa nt ’s treat me nt, the in vest i gat or s h o ul d 
deter mi ne t hat t he u n bli n de d i nf or mati on is necessar y (ie, t hat it will alt er t he partici pa nt ’s 
i m me diate ma na ge me nt). I n ma n y cases, partic ularl y w he n t he e mer ge nc y is clearl y n ot relate d t o 
t he I P, t he pr o ble m ma y be pr o perl y ma na g e d b y ass u mi n g t hat t he parti ci pa nt is recei vi n g t he
hi g hest d ose of t he I P. It is hi g hl y  desira ble t hat t he deci sio n  to u n bli n d treat me nt assi g n me nt be 
di sc usse d wi t h the Cli nical Tri al P h ysicia n or desi g nee , b ut t he in vest i gat or al wa ys has ul timate 
a ut h orit y for t he deci sio n  to u n bli n d. T he act ual tas k of  un bli n di n g ca n be dele gate d b y t he 
in vesti gat or t o a desi g nee assi g ne d t he tas k o n t he Del e gat i on of  Aut h ori t y. T he in vest i gat or or 
a p p oi nte d desi g nee s h o uld o nl y cal l i n f or e mer ge nc y u n bli n di n g aft er t he decisi o n t o u n bli n d t he 
parti ci pa nt has bee n d oc u me nte d .
F or t his st u d y, t he met h o d of  un bli n di n g f or e mer ge nc y p ur p oses is t hr o u g h t he I R T b y usi n g a n 
e mer ge nc y un bli n di n g pers o nal i de ntificat i on n u m ber, a n d t he i n vest i gat or s h o ul d call I R T f or 
u n bli n de d d ose i nf or mat i on.
I n cases of acci de ntal u n bli n di n g, c o ntact t he Cli nical Trial P h ysicia n or desi g nee a n d e ns ure e ver y 
atte mpt is m a de t o mi ni mize a d dit i onal discl os ure a n d t he i m pact of u n bli n di n g.
A n y re q uest t o u n bli n d a parti ci pa nt f or n o ne mer ge nc y p ur p oses s h o uld be disc usse d wi t h the 
Cli nical Trial P h ysicia n or desi g nee .
A n y res ults s hare d b y t he N o n c li nical Dis p ositi on a n d Bi oa nal ysis gr o u p wit h t he S p o ns or’s st u d y 
tea m will be bli n de d t o e ns ure i nte grit y of  t he st u d y.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
6 6
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Bli n d b re a k (IR T )
T he I R T will be pr o gra m me d wit h bli n d -br ea ki n g i nstr ucti o ns. I n case of a n 
e mer ge nc y, t he in vesti gat o r has t he s ole res p o nsi bilit y f or deter mi ni n g if u n bli n di n g of 
a partici pa nt ’s i nter ve nti o n assi g n me nt is warra nte d. Partici pa nt safet y m ust al wa ys be 
t he first c o nsi derati o n i n ma ki n g s uc h a deter mi nati o n. If t he in vesti gat or deci des t hat 
u n bli n di n g is warra nte d, t he in vesti gat or s ho ul d ma ke e ver y eff ort t o c o ntact t he 
S p o ns or pri or t o u n bli n di n g a partici pa nt’s i nter ve nti o n assi g n me nt u nless t his c o ul d 
dela y  e mer ge nc y treat me nt of t he partici pa nt. If a partici pa nt’s i nter ve nti o n assi g n me nt 
is u n bli n de d, t he S p o ns or m ust be n otifie d wit hi n 2 4 h o urs after br ea ki n g t he bli n d. 
T he date a n d reas o n that t he bli n d was br o ke n m ust be rec or de d i n t he s o urce 
d oc u me ntati o n a n d eC R F , as a p plica ble.
7. 4
D o s a g e M o difi c ati o n
 T here ma y 
be a m o dificat i on t o t his sc he d ule if t here is misse d d osi n g as refere nce d i n Sect i on 7. 1 . 
 oza ni m o d 
0. 4 6 or 0. 9 2 m g/ da y a d ult e q ui vale nt d ose le vels . If t his is t he case, it will be c om m u nicate d t o t he 
in vesti g at or .
a n d 
t he d ose s h o ul d n ot be ot her wise m o difie d o utsi de t he para meters pr o vi de d i n t he pr ot oc ol.
7. 5
Pr e p ar ati o n/ H a n dli n g/ St or a g e/ A c c o u nt a bilit y
T he I P m ust be st ore d i n a sec ure area acc or di n g t o l ocal re g ulati o ns. It is t he res p o nsi bilit y of  t he 
in vesti g at or , or desig nee w here per mitte d, t o e ns ure t hat I P is o nl y dis pe nse d t o st u d y p artici pa nts. 
T he I P m ust be dis pe nse d o nl y fr o m o fficial st u d y sites b y a ut h orize d pers o n nel acc or di n g t o l ocal 
re g ulat i ons.
T he pr o d uct st ora ge ma na ger s h o ul d e ns ure t hat t he st u d y i nter ve nt i on is store d i n acc or da nce wit h 
t he e n vir o n me ntal c o n ditio n s (t e mperat ure, li ght , a n d h u mi dit y)  as deter mi ne d b y B M S. If 
c o ncer ns re gar di n g t he q ualit y o r a p peara nce of t he stu d y i nter ve nt i on arise, t he stu d y i nter ve nt i on
s h o uld n ot be di s pe nse d, a n d B M S s h o uld be c o ntacte d i m me diatel y.
St u d y  int er ve nt i on n ot s u p plie d b y  B M S will be st ore d i n acc or da nce with t he pac ka ge i nsert.
I P d oc u me ntati o n ( w het her s u p plie d b y B M S or n ot) m u st be mai ntai ne d t hat i ncl u des all pr ocesses 
re q uire d t o e ns ure t he d r u g is acc uratel y a d mi nistere d. T his i ncl u des d oc u m e ntatio n of  dr u g 
st ora ge, a d mi nistrati o n a n d, as a p plica ble, st ora ge t e mperat ures, rec o nstit uti o n, a n d use of  re q uire d 
pr ocesses ( e g, re q uire d dil ue nts, a d mi nistrati o n sets).

T he in vest i gat or or desi g nee m ust c o nfir m a p pr o priate t e mperat ure c o n diti o ns ha ve bee n 
mai ntai ne d d uri n g tra nsit f or all st u d y i nter ve nt i on recei ve d a n d a n y discre pa ncies are re p orte d 
a n d res o l ve d bef ore use of t he st u d y  int er ve nt i on.

T he in vest i gat or, i nstituti o n, or t he hea d of  the m e dical inst itut i on ( w here a p plica ble) is 
res p o nsi ble f or stu d y i nter ve nt i on acc o u nta bilit y, rec o nciliati on, a n d rec or d ma i nte na nce 
(ie, receipt, rec o nciliat i on, a n d fi nal dis p osit i on rec or ds).
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
6 7
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
7. 6
Tr e at m e nt C o m pli a n c e
It is t he in vest i gat or’s res p o nsi bility t o e ns ure t hat partici pa nt s are c orrectl y i nstr ucte d o n h o w 
t o ta ke t heir I P a n d t hat eac h parti ci pa nt is f ull y co m plia nt wit h t heir assi g ne d d osa ge re gi me n. 
Rec or ds of I P use d a n d i nter vals bet wee n visits will be ke pt d uri n g t he st u d y. Dr u g acc o u nta bilit y 
will be n ote d b y  t he mo ni t or d uri n g site visits a n d at t he c o mpleti o n of  t he st u d y. Parti ci pa nt s will 
be as ke d t o r et ur n a n y re mai ni n g u n use d I P at  all visit s d uri n g w hic h I P is di s pe nse d (e xce pt f or 
D a y
) a n d at t he e n d of t he st u d y. T he I P s h o ul d be dis pe nse d b y t he in vesti gat or, or b y a q ualifie d 
i n di vi d ual u n der t he in vesti gat or’s s u per visi on. A n u p- t o-date treat me nt i n ve nt or y/ dis pe nsi n g 
rec or d must be mai ntai ne d as d escri be d bel o w.
P arti cipa nt s w h o ta ke less t ha n 8 0 % or m o re t ha n 1 2 0 % of  I P d uri n g t he e nt ire tr e at me nt peri o d 
are c o nsi dere d n o n-c o mplia nt.
At  eac h visit, pre vi o usl y dis pe nse d I P will be c o llecte d b y t he in vest i gat or a n d c o m plia nce will be 
assesse d o n a p artici pa nt dis pe nsi n g l og. Partici pa nt s e x hi bit i n g p o or c o m p lia nce as assesse d b y 
I P c o u nts ( 2 or m o re misse d I P da ys i n 1 wee k) s h oul d be c o u nsele d o n t he i m p orta nce of  go o d 
c o mplia nce t o t he st u d y dosi n g re gi me n. Parti cipa nt s w h o are persi ste ntl y n o n -c o mplia nt  
( < 8 0 % or > 1 2 0 %) s h o ul d be disc usse d wit h t he Cli nical Trial P h ysicia n or desi g nee t o deter mi ne 
w het her t he y s h o uld be wi t hdra w n fr o m  t he st u d y.
7. 7
C o n c o mit a nt T h er a p y
All treat me nts ot her t ha n oza ni m o d bei n g ta ke n b y t he partici pa nt s o n e ntr y t o t he st u d y or at a n y 
ti me d uri n g t he st u d y, i ncl u di n g t hr o u g h t he 
S af et y F oll o w - u p Visi t, are re gar de d as 
c o nc o mita nt me d icati ons a n d m ust be d o c u m e nte d o n t he a p pr o priate secti o n of  the e C R F. 
C o m plete hist or y  of pre vio us tr e at m e nts f or C D m ust be d oc u me nt e d. 
N O T E: Pri or t o r a n d o mi z ati o n ( D a y ), all pri or me dicat i ons f or t he ma na ge me nt of  CD s h o uld 
be rec or de d o n t he pri or C D me d icati ons e C R F. After ra n d o mizat i on ( Da y 
, me dicati ons f or t he 
ma na ge me nt of  CD s h o uld be rec or de d o n t he c o nc o mit a nt me d icatio ns e C R F (t his e C R F als o 
ca pt ures o n g oi n g 
C D 
me dicat i ons).
All 
pri or 
me d icati ons 
(incl u di n g 
o ver -t he- c o u nter 
me dicat i ons) a d mi nistere d 3 0 d a y s pri or t o t he date of  inf or me d c o nse nt/asse nt a n d a n y 
c o nc o mita nt t hera p y ad mi nistere d t o t he partici pa nt d uri n g t he c o urse of  the st u d y unt il 
 
aft er t he fi nal d ose of  IP will be rec or de d. A d diti o nall y, all dia g n osti c, t hera pe utic, or s ur gical 
pr oce d ures relati n g t o C D s h o ul d be rec or de d.  An y me dicat i on t hat is c o nsi dere d necessar y  for 
t he parti cip a nt’ s heal t h (incl u di n g e nteral nutri tio n) a n d t hat is n ot e x pecte d t o i nterfere wi t h t he 
e val uat i on of or i nteract wit h I P ma y  c o nti n ue d uri n g t he st u d y.
P arti cipa nt s w h o are recei vi n g oral c ortic oster oi ds at Scree ni n g m ust kee p t heir prescri be d d osa ge 
stea d y at least t hr o u g h 
 aft er w hic h t he d ose s h o uld be ta pere d as descri be d i n 
Secti o n 7. 7. 1 . Oral 5-A S A or oral c ortic oster oi ds s h o ul d n ot be starte d i n partici pa nt s w h o are n ot 
recei vi n g t he m. P arti ci pa nts recei vi n g 5 -A S A m ust kee p t heir prescri be d d osa ge stea d y at least 
t hr o u g h  
 a n d s h o uld m ai ntai n a sta ble d ose t hr o u g h Wee k 6 4.
It is als o a d vise d, if p ossi ble, t o kee p t he prescri be d d ose of  pre- a n d/ or pr o bi otic s u p ple me nts 
stea d y a n d t o a v oi d i nitiati n g treat me nt wit h pre- a n d/ or pr o bi otic s u p ple me nts t hr o u g h Wee k 6 4.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
6 8
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
C o nc o mita nt treat me nt wit h me dicat i ons liste d i n Secti o n 7. 7. 2 is n ot all o we d d uri n g t he st u d y .
T he decisi o n t o te m p oraril y i nterr u pt d osi n g f or treat me nt of a n i nterc urre nt me dical c o n dit i on, or 
f or maj o r s ur ger y t hat c o uld prese nt a n u nreas o na ble ris k t o t he parti ci pa nt, re mai ns t he 
res p o nsi bility o f the treati n g p h ysicia n, w hic h will n ot be dela ye d or ref use d b y t he S p o ns or. Pri or 
t o i nterr u pti o n of  dosi n g, t he i n vesti gat or ma y c o ntact t he Me di cal M o ni t or a n d f or war d 
a p pr o priate s u p p orti n g d oc u m e nts f or re vie w a n d disc ussi o n. T h e i n vesti gat or will re p ort t he 
actio n ta ke n wi t h IP. T he Me dical M o ni t or s h o uld b e c o ntacte d t o disc uss tr e at me nt rei nitiati on.  
See Secti o n 8 f or per ma ne nt disc o nti n uati on of I P.
A d mi nistrati o n of  co nc o mit a nt me d icati ons m ust be re p orte d i n t he a p pr o priate secti o n of  the 
e C R F alo n g wi t h dosa ge i nf or mati o n, dates of  ad mi nistrati o n, a n d reas o ns f or use. F or me dicat i ons 
wi t h a si n gle acti ve i n gre die nt, ge neric na mes f or c o nc o mita nt me d icati on s h o uld be use d, if 
p ossi ble. F or c o m bi nat i on pr o d ucts, bra n d na mes s h o uld be use d. T he t ot al dail y d ose s h o uld be 
fille d i n w he ne ver p ossi ble.
I n a d ditio n, S A R S -C o V -2 vacci nes a d mi nistere d a n y time pri or t o or d uri n g t he st u d y must be 
d oc u m e nte d, i ncl u di n g ma n ufact urer details a n d dates f or eac h d ose. Hist ori es of  all ot h er pri or 
me dicat i ons ta ke n d uri n g t he 3 0 da ys pri or t o t he date of  inf or me d c o nse nt/asse nt m ust als o b e 
d oc u m e nte d. 
If vacci nat i on f or S A R S - Co V -2 is p urs ue d, i deall y ra n d o mizati on ( Da y ) s h o uld occ ur aft er t he 
f ull d osi n g sc he d ule has bee n a d mi nistere d a n d aft er res ol uti on o f an y ac ute reacti o ns (e g, reacti o ns 
occ urri n g wit hi n 2 4 h o urs of vacci ne a d mi nistrati o n). If a partici pa nt has recei ve d a S A R S -C o V -2 
vacci nati o n, vacci ne details (e g, ma n ufact urer a n d d ose n u m ber) s h o uld be rec or de d o n t he 
c o nc o mita nt me dicat i on pa ge, if gi ve n d uri n g t he st u d y , or t he past hist or y pa ge, if gi ve n prior t o 
e nr o ll me nt.
7. 7. 1
St er oi d T a p er 
Ster oi d ta peri n g ca n start as earl y as  
, a n d t he I n vest i gat or m ust atte m pt t o i nitiate ta peri n g 
after Wee k 1 2 a n d ha ve it c o mplete d wi t hi n 6 m o nt hs after Wee k 12. C o nsi derat i ons t o ta per at a n 
earlier ti me p o i nt for a d verse e ve nts or safet y c o ncer ns s h o ul d first be disc usse d wi t h t he Cli nical 
Tri al Ph ysicia n or desi g nee . Bel o w is t he rec o m me n de d ta peri n g sc he d ule. M o difica tio n ca n b e 
ma de base d o n b o d y  w eig ht f ol l owi n g disc ussi o n wi t h t he Cli nical Trial P h ysicia n or desi g nee.
P arti cipa nt s recei vi n g pre d nis o ne at a d ose of  > 10 m g/ da y ( or e q ui vale nt) are rec o m me n de d t o 
ha ve t heir d ose re d uce d at  a rat e of  5 m g ( or e q ui vale nt) per wee k u ntil a ≤1 0 m g/ da y d ose ( or 
e q ui vale nt) is ac hie ve d. Parti ci pa nt s recei vi n g pre d nis o ne at d oses of 1 0 m g/ da y ( or e q ui vale nt) or 
ha ve ac hie ve d a 1 0 m g/ da y d ose ( or e q ui vale nt) b y ta peri n g are rec o m me n de d t o ha ve t heir d os e 
re d uce d at a rate of  2. 5 m g/ wee k u nt il t he ster oi d is disc o nt i n ue d. Parti ci pa nt s recei vi n g oral 
b u des o ni de are rec o m me n de d t o ta per t heir d ose at a rate of  3 mg e ver y 3 wee ks a n d t he n 
di sc o nti n ue treat me nt. Parti ci pa nt s recei vi n g or al becl o m et has o ne are rec o m me n de d t o ta per t heir 
d ose o ver a peri o d of u p t o 6 wee ks.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
6 9
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
F or partici pa nt s w h o ca n n ot t olerate t he c ortic oster oid ta per wit h o ut rec urre nce of  cli nical 
s y m pt o ms of eit her C D or ster oi d wit h dra wal, t he c ortic oster oi d d ose ma y be i ncrease d ( u p t o t he 
d ose at st u d y  e ntr y if re q uire d), b ut ta peri n g s h o ul d be atte m pte d a gai n wit hi n 2 wee ks.
7. 7. 2
Pr o hi bit e d a n d/ or R e stri ct e d Tr e at m e nt s
T he f oll owi n g me dicat i ons ca n n ot be use d d uri n g t he st u d y t hr o u g h t he 
S af et y F o ll ow- u p 
Vi sit, u nless ot her wise n ote d t o be pr o hi bite d t hr o u g h e n d of treat me nt o nl y:

Treat me nt wit h Class I a or Cl ass III a nti-arr h yt hmic dr u gs (e xa m ples of  Class Ia or Cl ass III 
ant i-arr h yt hmic dr u gs a n d a d di tio nal pr o hi bi te d s yste mic car diac me dicat i ons are pr o vi de d i n 
Ta ble 7. 7. 2 -1 ) or treat me nt wit h 2 or m ore a ge nts i n c o m bi nat i on k n o w n t o pr ol o n g P R i nter va l 
(e g, c o m bi nat i on of  a beta bl oc ker a n d a n o n- di h y dr o p y ridi ne calci u m-c ha n nel bl oc ker) are 
pr o hi bite d d uri n g t he st u d y  u nless a p pr o ve d b y t he S p o ns or’s re prese ntati ve

B i ol ogi c t hera pies i ncl u di n g b ut n ot li mite d t o a batace pt, i nfli xi ma b, eta nerce pt, a dali m u ma b, 
a na ki nra, rit u xi ma b, ve d o liz u ma b, uste ki n u ma b, a n d g oli m u ma b 

S y ste mic im m u n o m o d ul at or y a ge nts (e g, A Z A, 6- M P, c yclos p ori ne, M T X , m yc o p he n o late 
m o fetil, tacr oli m us, or sir oli m us; s mall m olec ules [e g, u pa daciti ni b]) 

P os t-baseli ne i nitati on, or i ncrease a b o ve baseli ne d ose , of s yste mic c ortic oster oids d uri n g 
I n d ucti on or Mai nte na nce . I ncrease i n s yste mic c ortic oster oi ds, s uc h as or al  pre d nis one 
> 1. 0 m g/ k g/ d a y f or w eig hts ≤ 4 0 k g, > 4 0 m g /d a y f or weig hts > 4 0 k g, or e q ui vale nt d uri n g 
L T E .

A n y per -rect u m thera p y i ncl u di n g e ne mas (e g, 5 -A S A, c ortic oster oi d), ot her t ha n t hat re q uir e d 
f or e n d osc o p y pre paratio n ( pr o hi bite d t hr o u g h e n d of treat me nt o nl y)

A n y i n vest i gati onal dr u g ot her t ha n t he I P s pecifie d i n t his stu d y

C hr o nic N S AI D use (pr o hi bite d t hr o u g h e n d of treat me nt o nl y . N ote: occasi o nal use of  
N S AI Ds a n d aceta mi n o p he n [e g, hea dac he, art hritis, m yal gias, or me nstr ual  cr a mps] a n d 
as pirin as nee de d or u p t o 3 2 5 m g/ da y if o n a sta ble d ose at ra n d o mizati on [Da y  ] is 
per mitte d .)

Li ve vacci nes or li ve atte n uate d vacci nes are n ot all o we d wi t hi n 4 wee ks 
pri or t o 
ra n d omizat i on ( D a y )

I VI g or plas ma p heresis is n ot all o we d withi n 3 m o nt hs pri or t o ra n d o mizat i on ( Da y )

Treat me nt wit h D -pe nicilla mi ne, lefl u n o mi d e, or thali d o mi de 

Treat me nt wit h nataliz u ma b, fi n g o li m o d, etrasi m od, or ot her S 1 P m o d ulat ors

I mm u n os u p pressi ve a ge nts t hat de plete l y m p h oc y t es 

A nt i-ne o pl ast ic me dicat i ons

M o n oa mi ne o xi dase i n hi bit ors (e g, sele gili ne, p he nelzi ne)

C Y P 2 C 8 i n d ucers (e. g. rifa m pici n)
F or a n y s yste mic t hera pies f o r C D n ot me nt i one d a b o ve, please c o ntact t he Cli nical Tri al P h ysicia n 
or desi g nee .
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
7 0
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
T a ble 7. 7. 2 - 1:
E x a m ples of Pr o hi bite d C ar di ac Me dic ati o ns ( S yste mic Use)
P h ar m ace utic al Cl ass
E x a m ple Me dic ati o ns
A nti- arr h yt h mic dr u gs
a mi o dar o ne, be pri dil h y dr oc hl ori de, dis o p yra mi de, d ofetili de, dr o ne dar o ne, 
flecai ni de, i b utili de, s otal ol, li d ocai ne, pr ocai na mi de, pr o pafe n o ne, q ui ni di ne, 
t ocai ni de
T he f o ll owi n g me dicat i ons s h o ul d n ot be use d bet wee n t he 
 Safety F oll o w - u p Visit a n d t he 
 S afet y F o ll ow- u p Visi t:

Treat me nt wit h Class I a or Cl ass III a nti-arr h yt hmic dr u gs (e xa m ples of  Class Ia or Cl ass III 
a nt i-arr h yt hmic dr u gs a n d a d di tio nal pr o hi bi te d s yste mic car diac me dicat io ns ar e pr o vi de d i n 
Ta ble 7. 7. 2 -1 ) or treat me nt wit h 2 or m ore a ge nts i n c o m bi nat i on k n o w n t o pr ol o n g P R i nter va l 
(e g, c o m bi nat i on of  a beta bl oc ker a n d a calci u m-c ha n nel bl oc ker) are pr o hi bite d d uri n g t he 
st u d y u nless a p pr o ve d b y t he S p o ns or’s re prese ntati ve

Treat me nt wit h nataliz u ma b, fi n g oli m o d, etrasi m o d , or ot her S 1 P m o d ulat ors

I mm u n os u p pressi ve a ge nts t hat de plete l y m p h oc y t es

M o n oa mi ne o xi dase i n hi bit ors (e g, sele gili ne, p he nelzi ne)

Li ve vacci nes or li ve atte n uate d vacci nes
7. 7. 2. 1
I m a gi n g R e stri cti o n a n d Pr e c a uti o n s
It is t he l ocal i ma gi n g facilit y’s res p o nsi bility t o deter mi ne, base d o n partici p a nt attri b utes 
(e g, aller g y hist or y , dia betic hist or y , a n d re nal st at us), t he a p pr o priate i ma gi n g m o dalit y a n d 
c o ntrast re gi me n per i ma gi n g st u d y. I ma gi n g c o ntrai n dicat i ons a n d c o ntrast ris ks are t o be 
c o nsi dere d i n t his assess me nt. Partici pa nts wit h re nal i ns ufficie nc y are t o be assesse d as t o w het her 
or n ot t he y  s h o uld recei ve c o ntrast a n d if s o, w hi c h c o ntrast a ge nt a n d d ose is a p pr o priate. Pl ease 
see Secti o n 9. 1. 2 f or details o n i ma gi n g assess me nts f or t his st u d y.
7. 8
C o nti n u e d A c c e s s t o St u d y I nt er v e nti o n A ft er t h e E n d of t h e St u d y
At  t he c o nclusi o n  of t he st u d y, if t he st u d y int er ve nt i on is n ot a vai la ble as a n a p pr o ve d treat me nt 
i n t he l ocal co u ntr y , parti ci pa nt s w h o c o nt i n ue t o d e m o nstrate cli nical be nefit will be eli gi ble t o 
recei ve B M S-s u p plie d st u d y i nter ve nti on per l ocal or re gi o nal re q uire me nts . If t he st u d y treat me nt 
is n ot a vaila ble as a n a p pr o ve d a n d a vaila ble treat me nt , st u d y int er ve nt i on will be pr o vi de d via a n 
e xte nsi o n o f the st u d y, a r oll o ver st u d y re q uiri n g a p pr o val b y t he res p o nsi ble H e alt h Aut h ori t y an d 
et hics c o m mitt e e, or t hr o u g h a n ot he r mec ha nis m at t he discret i on of B M S.
B M S reser ves t he rig ht t o ter mi nate access t o B M S -s u p plie d st u d y int er ve nt i on if a n y of t he 
f oll owi n g occ ur: a) t he st u d y is ter mi nate d d ue t o safety c o ncer ns; b) t he de vel o p me nt of  oza ni m o d
is ter mi nate d f or ot her reas o ns, i ncl u di n g, b ut n ot li mi te d t o, lac k of  efficac y a n d/ or n ot meeti n g 
t he st u d y object i ves; c) t he parti ci pa nt ca n o btai n me d icati on fr om a g o ver n me nt -s p o ns ore d or 
ot her healt h pr o gra m . I n all cases, B M S will f o ll ow l o c al  re g ulati ons .
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
7 1
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
8
DI S C O N TI N U A TI O N C R I TE RI A
8. 1
Di s c o nti n u ati o n F r o m St u d y Int er v e nti o n
P arti cipa nt s M U S T disc o nti n ue I P f or a n y of t he f ollo wi n g reas o ns:

P arti cipa nt ’s re q uest t o st o p st u d y i nter ve nt i on. Parti ci pa nts w h o re q uest t o di sc o nti n ue st u d y 
i nter ve nt i on will re mai n i n t h e st u d y a nd m ust c o nti n ue t o be f oll o w e d f or pr ot oc ol-s pecifie d 
f oll ow- u p pr oce d ures. T he o nl y  e xc e ptio n t o t his is w he n a partici pa nt s pecificall y with dra ws 
c o nse nt f or a n y f urt her c o ntact wit h hi m/ her or pers o ns pre vi o usl y a ut h orize d b y t he partici pa nt 
t o pr o vide t his i nf or mati o n .

If a parti ci pa nt w h o d oes n ot meet e nr oll me nt criteria is i na d verte ntl y e nr olle d, t he Cli nica l 
Tri al P h ysicia n or desi g nee m ust be c o ntacte d, a n d t hat partici pa nt will be wit h dra w n fr o m t he 
st u d y if c o nti n uati on is deter mi ne d t o be a safety ris k.

A n y cli nical A E, lab orat or y  ab n or malit y, or i nterc urre nt ill ness w hic h, i n t he o pi ni o n of  the 
in vesti gat or, i n dicates t hat c o nti n ue d partici pat i on i n t he st u d y is n ot i n t he best i nterest of t he 
parti ci pa nt .

Ter mi nat i on of  t he st u d y b y B M S .

L oss of  abilit y t o freel y pr o vi de c o nse nt t hr o u g h i m pris o n me nt or i n v ol unt aril y i ncarcerati o n 
f or treat me nt of  either a ps yc hiatric or p h ysical (e g, i nfecti ous di sease) ill ness. ( N ote: U n der 
s pecific circ u msta nces a n d o nl y i n c o u ntries w here l ocal re g ulat i ons per mit , a partici pa nt w h o 
has bee n i m pris o ne d ma y be per mitte d t o c o nt i n ue as a partici pa nt. Stri ct c o n dit i ons a p pl y , a n d 
B M S a p pr o val is re q uire d.)

P arti cipa nt meets li ver -relat e d la b orat or y a b n or malities (see Secti on 9. 2. 9 ).

U n bli n di n g 
of  a partici pa nt ’s treat me nt assi g n me nt f or a n y reas o n ( e mer ge nc y or 
n o ne mer ge nc y) .

I na bility or fail ure t o c o m pl y wit h pr ot oc ol  re q uire me nts.

Pre g na nc y, p osi tive pre g na nc y test, or partici pa nt n o l on ger wis hes t o c o m p l y with st u d y
re q uire me nts relat i n g t o pre ve nti on of pre g na nc y  (see Secti o n 9. 2. 5 ).

P arti cipa nts w h o re q uire i nitiati o n of  an i m m u n o m o d ulat or y a ge nt i ncl u di n g, b ut n ot li mite d 
t o 6-M P, A Z A, or bi o l ogic t hera p y; or w h o re q uire > 3 da ys of treat me nt wit h hi g her d oses of 
s yste mic c ortic oster oi ds (e. g. pre d nis o ne > 1. 0 m g/ k g/ da y  for wei g hts ≤ 4 0 k g or > 4 0 m g/ da y 
f or w eig hts > 4 0 k g or e q ui vale nt) will be disc o nt i n ue d fr om t he st u d y.
Reas o ns f or disc o nt i n uati on i ncl u de, b ut are n ot li mite d t o, t he f oll owi n g:

P h ysicia n decisi o n: T he in vesti gat or m u st disc o nti n ue I P if it is deter mi ne d t hat it is n ot safe 
or i n t he partici pa nt ’s best i nterest t o recei ve f urt her treat me nt. I n partici pa nt s w h o o btai n a 
p ul m o n o l og y  or o p ht hal m o l og y c o ns ultat i on as o utli ne d i n Sect i on 9. 4. 9 a n d Secti o n 9. 4. 1 0 , 
di sc o nti n uati on ma y 
be rec o m me n de d b y t he c o ns ult i n g p h ys icia n. T he Cli nical Tri al 
P h ysicia n or d esi g nee s h o uld be pr o m pt l y n otifie d of t he decisi o n.

N o nc o m plia nce wi t h IP: After c o ns ultat i on bet wee n t he in vest i gat or, t he Cli nical Tri al 
P h ysicia n or desi g nee , a n d t he S p o ns or w he n a p pr o priate, a partici pa nt ma y b e di sc o nti n ue d 
fr om t he st u d y for f ail ure t o c o m pl y wit h d osi n g re gi me n as s pecifie d b y  t he pr ot oc ol.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
7 2
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d

N o nc o m plia nce wi t h pr ot oc ol/ pr ot oc ol de viati on: After c o ns ultati o n bet wee n t he in vest i gat or, 
t he Cli nical Trial P h ysicia n or d esi g nee , a n d t he S p o ns or w he n a p pr o priate, a partici pa nt ma y 
be disc o nt i n ue d fr o m t he st u d y for fail ure t o f oll o w pr ot oc ol pr oce d ures, or ot her e ve nt or 
decisi o n t hat sta n ds i n c o ntrast t o t he g ui deli nes set i n t he pr ot oc ol.

A d verse e ve nt: A parti ci pa nt m u st be disc o nt i n ue d fr o m I P if, i n t he j u d g me nt of  the 
in vesti g at or or if s pecifie d i n t he pr ot oc ol , t he partici pa nt de vel o ps a n A E s uc h as a n 
i nterc urre nt ill ness or c o m plicat i on t hat j ust ifies disc o nti n uati o n of I P.

P arti c ularl y, if a part ici pa nt has d e velo pe d a n y  of the f o ll owi n g A E SIs (see Sect i on 9. 2. 9 ):
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
7 3
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
 
 
 
 
 
 

Lac k of efficac y: Decisi o n b y t he partici pa nt a n d/ or t he in vest i gat or t o disc ont i n ue I P d ue t o a 
lac k of  ex pecte d or desire d effect relate d t o t hera p y or if earl y disc o nti n uati on criteria were 
met (see Secti o n 5. 1 ).

Wit h dra wal b y part ici pa nt ( or partici pa nt ’s pare nt or g uar dia n ): T he partici pa nt
( or 
parti ci pa nt ’s pare nt or g uar di a n) ma y c h o os e t o disc o nti n ue I P at a n y time. T he parti ci pa nt is 
e x pecte d t o c o nti n ue i n t he st u d y a n d e ver y  effort s h o ul d be m a de wit hi n t he b o u n ds of safety 
a n d t he parti ci pa nt a n d t heir pare nt or g uar di a n’sc h o ice t o ha ve eac h parti ci pa nt c o mplete t he 
E T Visit a n d S af et y F o ll ow- u p Vi sits. If a partici pa nt or partici pa nt ’s pare nt or g uar dia n
wi t hdra ws c o nse nt/asse nt, t he o nl y  ad di tio n al i n vesti gati onal data t o be c ollecte d will be t he 
f oll ow- u p of  S A Es as ma n date d b y t he pr ot oc ol.

Pre g na nc y: If a fe male parti ci pa nt
bec o me s pre g na nt, I P m ust 
be disc o nt i n ue d (see 
Secti o n 9. 2. 5 ).

St u d y ter mi nati on b y S p o ns or

L ost t o f oll o w - u p

Ot her

F or partici pa nt s w h ose A L C le vel is c o nfir me d < 2 0 0 cells/ μ L a n d p er m a ne ntl y disc o nti n ue 
I P, a n E T Visit s h o uld be c o m p lete d. Ce ntral  la b orat or y testi n g will be c o n d ucte d e ver y 
1 4 d a y s ( ± 3 da ys) after t he E T Visit u ntil it is a b o ve t he l o wer li mit of n or mal or u ntil t he A L C 
is c o nsi dere d t o ha ve sta bilize d a n d/ or reac he d a le vel t hat is n ot cli nically si g nifica nt (see 
Secti o n 9. 4. 1 2 ).
Wit h t he e xce pt i on of  partici pa nt s w h o wit h dra w c o nse nt /asse nt or are l ost t o f oll ow- u p, 
parti ci pa nt s w h o disc o nt i n ue t he st u d y sh o ul d c o mplete t he 
 
 Safet y F oll o w-u p Visit after t he last d ose f or t he c ollect i on of safet y data a n d t o assess 
t heir disease stat us. Alter nati ve treat me nt f or C D ca n be starte d, if nee de d, after t he E T Visit (see 
Secti o n 7. 7. 2 f or pr o hi bite d c o nc o mita nt me dicati ons wit hi n t he 
-d a y S afet y Fol l ow - u p Perio d) .
P arti cipa nt s w h o wit h dra w fr om t he st u d y will n ot be re place d.
Refer t o Secti o n 2 f or data t o be c ollecte d at t he ti me of treat me nt disc o nti n uatio n a n d f oll ow- u p 
a n d f or a n y furt her e val uat i ons t hat ca n be c o m p lete d.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
7 4
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
All parti ci pa nt s w h o di sc o nti n ue st u dy i nter ve nt i on s h o uld c o m p l y with pr ot oc ol -s pecifie d 
f oll ow- u p pr oce d ures as o utli ne d i n Secti o n 2 . T h e o nl y e xce ptio n t o t his re q uire me nt is w he n a 
parti ci pa nt wit h dra ws c o nse nt f or all st u d y  pr oce d ures, i ncl u di n g p ost-treat me nt st u d y fol l ow- u p ,
or l oses t he a bilit y t o c o nse nt freel y (e g, is i m pris o ne d or i n v ol unt aril y incarcerate d f or t he 
treat me nt of eit her a ps yc hi atric or p h ysical ill ness).
If st ud y  int er ve ntio n is disc o nti n ue d pri or t o t he parti ci pa nt ’s c o m p leti o n of t he st u d y, t he reas o n 
f or t he disc o nt i n uati o n m ust be d oc u m e nte d i n t he parti ci pa nt ’s me d ical rec or ds per l ocal 
re g ulat or y r e q uire me nts i n eac h re gi o n/c o u ntr y a n d e ntere d o n t he a p pr o pri ate eC R F pa ge.
8. 1. 1
P o st - st u d y Int er v e nti o n St u d y F oll o w -u p
I n t his st u d y, t he p r o p ortio n of  parti ci pa nt s w h o ac hie ve P C D AI < 1 0 at  
Wee k 6 4 a n d t he 
pr o p orti o n of  participa nts w h o ac hie ve a n S E S -C D decrease fr o m B aseli ne of  ≥5 0 % ( E R-5 0) at  
Wee k 6 4 are ke y e n d p o i nts. P ost -st u d y fol l ow- u p is of  critical i m p orta nce a n d is esse nt ial t o 
preser vi n g parti ci pa nt safety a n d t he i nte grit y of t he st u d y. Parti ci pa nts w h o disc o nt i n ue st u d y 
i nter ve nt i on m u st c o nt i n ue t o be f oll owe d
(in t his st u d y or a r oll over st u d y) f or c ollect i on of 
o utc o m es a n d/ or s ur vi val f oll o w- u p data as re q uire d a n d i n li ne wi t h S ectio n 5 u nt il deat h or t h e 
c o nclusi o n  of t he st u d y.
8. 2
Di s c o nti n u ati o n F r o m t h e St u d y
P arti cipa nt s w h o re q uest t o disc o nt i n ue st u d y i nter ve nt i on will re mai n i n t he st u d y an d m ust  
c o nti n ue t o be f o ll owe d f or pr ot oc ol -s pecifie d f oll o w-u p pr oce d ures. T he o nl y e xce pt i on t o t his is 
w he n a partici p a nt s pecific all y wit hdra ws c o nse nt f or a n y f urt her c o ntact wit h hi m/ her or pers o ns 
pre vi o usl y a ut h orize d b y t he parti ci pa nt t o pr o vide t his i nf or mat i on.

P arti cipa nts s h o uld n otif y  the in vesti g at or of  the decisi o n t o wit h dra w c o nse nt fr o m f ut ure 
f oll ow- u p.

T he wi t hdra w al  of c o nse nt s h o ul d be e x plai ne d i n detail i n t he me d ical rec or ds b y t he 
in vesti gat or, as t o w het her t he wit h dra wal is fr o m f urt her treat me nt wit h st u d y i nter ve nt i on
o nl y  or als o fr o m st u d y pr oce d ures a n d/ or p ost-treat me nt st u d y fol l ow- u p, a n d e ntere d o n t he 
a p pr o priate eC R F pa ge.

I n t he e ve nt t hat vit al stat us ( w het her t he partici pa nt is ali ve or dea d) is bei n g meas ure d, 
p u blicl y  availa ble i nf or mati on s h o uld be use d t o deter mi ne vit al stat us o nl y as a p pr o priatel y 
di recte d i n acc or da nce wit h l ocal la w.

If t he part ici pa nt wi t hdra ws c o nse nt /asse nt f or discl os ure of  fut ure i nf or mati on, t he S p o ns or 
ma y retai n a n d c o nt i n ue t o use a n y data c ollecte d bef ore s uc h a wit h dra wal o f c o nse nt.
8. 2. 1
I ndi vi d u al Di s c o nti n u ati o n Crit eri a

A part ici pa nt ma y wit hdra w c o m p letel y fr om t he st u d y at a n y ti me at his/ her o w n re q uest, or 
ma y be wi t hdra w n at a n y ti me at t he discret i on of  the in vest i gat or f or safety,  be ha vior al , 
c o mplia nce, or a d mi nistrati ve reas o ns. T his is e x pecte d t o be u nc o m m o n. St o p pi n g st u d y 
i nter ve nt i on is n ot c o ns i dere d wit h dra wal fr om t he st u d y.

At  t he ti me of disc o nti n ui n g fr o m t he st u d y, e ver y eff ort s h o ul d be ma de wit hi n t he b o u n ds of 
safety a n d part ici pa nt a n d parti ci pa nt’s pare nt or g uar dia n c h oice t o ha ve eac h parti ci pa nt  
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
7 5
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
c o mplete a n E T visit, if p ossi ble, as s h o w n i n Secti o n 2 . See t he Secti o n 2 f or data t o be 
c ollecte d at t he ti me of  st u d y disc o nti n uati on a n d f oll ow- u p a n d f or a n y f urt her e val uat i ons 
t hat nee d t o be c o m plete d.

If t he partici p a nt wit h dra ws c o nse nt f or discl os ure of  fu t ure i nf or mati on, t he S p o ns or ma y 
retai n a n d c o nti n ue t o use a n y data c ollecte d bef ore s uc h a wit h dra wal of c o nse nt /asse nt.
8. 3
L o st t o F oll o w - u p
T he f o ll owi n g acti o ns m ust be ta ke n if a partici pa nt fails t o ret ur n t o t he cli nic f or a re q uire d st u d y 
visit:

All reas o na ble efforts m u st be ma de t o l ocate partici pa nt s t o deter mi ne a n d re p ort t heir o n g oi n g 
stat us. T his i ncl u des f oll ow- u p wi t h pers o ns a ut h orize d b y t he partici pa nt .

L ost t o f oll ow- u p is defi ne d b y t he i na bility t o reac h t he partici pa nt aft er a mi ni m u m of  
t hree ( 3) d oc u me nte d p h o ne calls, fa xes, or e mails , as well as lac k of  res p o nse b y p arti ci pa nt
t o o ne ( 1) re gistere d mail letter. All at t e mpts s h o uld be d oc u me nte d i n the partici pa nt’s me d ical 
rec or ds.

If it is deter mi ne d t hat t h e partici pa nt has di e d, t he sit e will use per missi ble l ocal met h o ds t o 
o btai n date a n d ca use of deat h.

If t he in vesti gat or’s use of  thir d -part y  re prese ntati ve t o assist i n t he f oll ow- u p p orti o n of  the 
st u d y has bee n i ncl u de d i n t he parti ci pa nt’s i nf or me d c o nse nt, t he n t he i n vestig at or m a y use a 
S p o ns or -retai ne d t hir d-part y  re prese ntative t o assist site staff wi t h o btai ni n g t he parti ci pa nt’s 
c o ntact i nf or mati o n or ot her p u blic vit al stat us data necessar y t o c o m p lete t he f oll ow- u p 
p orti o n of  t he st u d y. 

T he si t e st aff a nd re prese ntati ve will c o ns ult p u blicl y a vaila ble s o urces, s uc h as p u blic healt h 
r e gistries a n d data bases, i n or der t o o bta i n u p date d c o ntact i nf or mati o n.

If, aft er all att e mpts, t he parti ci pa nt re mai ns l ost t o foll o w -u p, t he n t he last k n o w n ali ve date 
as det er mi ne d b y t he in vesti gat or s h o ul d be re p orte d a n d d oc u m e nte d i n t he parti ci pa nt’s 
me dical rec or ds.
9
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S
St u d y  pr oce d ures a n d ti mi n g are s u m marize d i n Secti o n 2 . Wai vers or e xe m pti ons fr o m  pr ot oc ol-
re q uire d e val uati ons are n ot all o we d. 
All i m me diate safety c o ncer ns m u st be di sc usse d wi t h the S p o ns or’s Cli nical Tri al Ph ys icia n or 
desi g nee i m me diatel y u p o n occ urre nce or a ware ness t o deter mi ne w het her a partici pa nt s h o uld 
c o nti n ue or disc o nt i n ue treat me nt.
A d here nce t o t he st u d y desi g n re q uire me nts, i ncl u di n g t hose s pecifie d i n Sect i on 2 , is esse nt ial 
a n d re q uire d f or st u d y c o n d uct.
All S cree ni n g e val uati o ns m ust be c o mplete d a n d re vie we d t o c o nfir m t hat p ote ntial part ici pa nts 
meet all eli gi bilit y criteria bef ore ra n d o mizati on ( Da y ).
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
7 6
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
I M P O R T A N T N O T E: It is rec o m me n de d t hat t he st u d y visits are sc he d ule d i n t he mor ni n g. O n 
da ys of  st u d y visits w he n tr o u g h ( pre-d ose) P K sa m ples are t o be dra w n, parti ci pa nt s s h o uld b e 
i nstr ucte d t o wit h h old t he d ose u ntil t he st u d y visit, a n d t he d ose will be a d mi nistere d d uri n g t he 
visit.
At  
, P K e valu ati o ns will be 
 T heref ore, partici pa nt s 
s h o uld be i nstr ucte d t o ta ke I P at h o me a n d n ote t he ti me ta ke n, all o wi n g f or at least  
 pri or 
t o arri vi n g f or t his visit.
W he ne ver p os si ble, t he se q ue nce of assess me nts s h o ul d re mai n c o nsta nt a n d at a p pr o xi matel y t he 
sa me ti me of da y t hr o u g h o ut t he st u d y.
It is rec o m me n de d t hat pr oce d ures are perf or me d i n t he f oll owi n g or der ( n ote t hat n ot all 
pr oce d ures are perf or me d at e ver y  visit):

S p o nta ne o us or s olicite d A E re p orti n g

E C G

Vi t al si g ns

Cli nical la b orat or y  tests, incl u di n g pre -d ose P K sa m pli n g w he n a p plica ble

P h ysical e xa mi nat i on

Efficac y assess me nts

I P a d mi nistrati o n ( o n visits w he n tr o u g h P K bl o o d dra ws are c ollecte d)
Wr itt e n, sig ne d, a n d date d i nf or me d c o nse nt/asse nt fr o m t he parti ci pa nt or partici pa nt ’s pare nt or 
g uar di a n m ust be o btai ne d b y t he in vest i gat or or desi g nee prior t o t h e p erf or ma nce o f a n y st u d y-
r elate d pr oce d ures. Asse nt will be o btai ne d fr o m partici pa nt s i n a n a ge-a p pr o priate ma n ner i n 
c o nju nct i on wi t h ap plica ble l ocal re g ulat i ons. A c o p y of t he sig ne d I C F/asse nt m ust be gi ve n t o 
t he partici pa nt’s pare nt or g uar dia n f or his/ her rec or ds.
Scree ni n g Peri o d
Scree ni n g pr oce d ures m ust be c o m p lete d wit hi n 3 5 da ys pri or t o receivi n g t he first d ose of I P. All 
Scree ni n g assess me nts a n d pr oce d ures as per Secti o n 9 are t o be perf or me d b y t he in vest i gat or or 
a q ualifie d desi g nee.
Act i ve T B m ust be r ule d o ut acc or di n g t o l ocal me dical practices. Late nt T B m ust be assesse d f or 
wi t h a T B s ki n test, Q ua nti F E R O N G ol d test, or ot her i nterfer o n ga m ma release assa y (I G R A; e g, 
T- S P O T). A n y re peat testi n g f or late nt T B s h o uld be a p pr o ve d b y t he Cli nical Tri al P h ysicia n or 
desi g nee. Parti ci pa nt s wit h late nt T B m ust ha ve d oc u me ntati o n of pr o p h ylact ic treat me nt b y l ocal 
sta n dar d of  care. Participa nt s wit h late nt T B w h o ha ve i nitiate d pr o p h ylact ic treat me nt b y l oc al 
sta n dar d of  care, parti ci pa nt s wi t h an i n deter mi nate t est res ult, or partici pa nt s di a g n ose d wi t h 
I G R A tests ot her t ha n Q ua nt i F E R O N G o l d or T- S P O T, m ust be disc usse d f or eli gi bilit y o n a 
case- b y-case basis b y t he S p o ns or Cli nical Trial P h ysicia n or desi g nee.
T D M assa ys t hat meas ure dr u g levels of bi o l ogic a ge nts ca n be use d as a n o pti o nal test d uri n g t he 
S cree ni n g P erio d. T D M will be perf or me d l ocall y. T he bi o l ogic was h o ut peri o d ma y be wai ve d i n 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
7 7
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
parti ci pa nt s w h o ha ve a n u n detecta bl e dr u g level o n a T D M assa y, perf or m e d eit her d uri n g a 
ro uti ne cli nic visit pri or t o S cree ni n g or d uri n g t he S cree ni n g P erio d. If a T D M assa y is use d as a n 
alter nati ve t o t he was h o ut peri o d f or a n y of  the bi o l ogics, t he res ult of  the T D M assa y m ust be 
a vaila ble i n s o urce d oc u me nts, a n d t he partici pa nt m ust n ot recei ve a n ot her d ose of t hat bi o l ogic 
a ge nt pri or t o ra n d o mizat i on ( D a y ).
D uri n g Scree ni n g , t he parti ci pa nt ’s pri or use of me d icati ons t o treat C D a n d w het her t he y 
res p o n de d t o a de q uate treat me nt wit h eac h me dicati o n will be assesse d a n d d o c u m e nte d (see 
A p pe n di x 5 ).
Pr o hi bite d treat me nts are liste d i n  Secti o n 7. 7. 2 .
D ose sta bilizati o n r ules are o utli ne d i n Secti o n 7. 7 . Briefl y, 5-A S As a n d oral c ortic oster oi ds ( s uc h 
as pre d nis o ne ≤ 0. 5 m g/ k g/ da y f or w ei g hts ≤ 4 0 k g, ≤ 2 0 m g / d a y f or weig hts > 4 0 k g, or e q ui vale nt ;
b u des o ni de ≤ 9 m g / da y; or becl o met has o n e ≤5 m g / da y) are all o we d a n d are s u bject t o d ose 
sta bilizati o n r ules.
Scree ni n g P erio d sc he d ule a n d pr oce d ures are pr o vi de d i n Sect i on 2 . A partici pa n t’s c ol o n osc o p y 
fr om a pre vio us S cree ni n g i n t his st u d y ma y be use d if wi t hi n 3 5 da ys of  ra n d o mizatio n ( Da y 
 
T o a v oi d parti ci pa nt ’s recei vi n g u n necessar y e n d osc o p y, t his pr oce d ure s h o ul d be perf or me d o nl y 
after t he partici pa nt meets all ot her necessar y i ncl usi o n/e xcl usi o n cri t eria.
I n d ucti o n a n d M ai nte n a nce Peri o d
At  t he Da y  st u d y visit, partici pa nt s w h o ha ve c o m plete d t he Scree ni n g pr oce d ures a n d meet t he 
eli gi bilit y cr iteria will be ra n d o mize d i n a 1: 1 rati o t o recei ve eit her 0. 4 6 or 0. 9 2 m g/ da y e q ui vale nt 
d oses f or t he 1 2 -wee k i n d ucti on p hase. T he ra n d o mizati on pr ocess is o utli ne d i n Sect i on 7. 2 . 
P arti cipa nt s will f oll o w t he 
-a p pr o priate d ose escalati o n ( mi ni m u m of 7 da ys) u nt il t he f ull 
dail y d ose is attai ne d (see Sect i on 7. 1 ), w hic h t he y will c o nti n ue t o ta ke t hro u g h o ut t he I n d uct i on 
a n d Mai nte na nce treat me nt peri o ds.
Vi sits, assess me nts, a n d pr oce d ures will be p erf or m e d as s pecifie d i n Sect i on 2 . Pri or t o each 
sc he d ule d visit, t he partici pa nt di ar y s h o uld be re vie we d t o e ns ure st o ol fre q ue nc y a n d a b d o mi nal 
pai n data are e ntere d dail y. A d o lesce nt partici pa nt s s h o ul d be e d ucate d o n t he i m p orta nce of diar y 
c o mplet i on ar o u n d t he visit at w hic h C D AI sc ores are t o be c alc ulate d. If t he parti ci pa nt re mai ns 
n o n- c o m p lia nt o n diar y  ent ries, t he part ici pa nt s h o uld be c o u nselle d a b o ut pr o per stu d y 
pr oce d ures.
T he vi de o rec or di n g of  eac h pr oce d ure will be re vie we d b y a ce ntral rea der, or rea ders, t o 
deter mi ne t he S E S -C D. F or f urt her details re gar di n g e n d osc o p y an d e n d osc o pic bi o psies, see 
Secti o n 9. 1. 5 .
Di sc o nti n uatio n crit eria are detaile d i n Sect i on 8 . Parti ci pa nt s w h o di sc o nti n ue st u d y treat me nt 
s h o uld c o m p lete a n E T visit a n d Safet y F o ll ow- u p V isits as s pecifie d i n Sect i on 2 . F or partici pa nt s 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
7 8
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
w h o di sc o nti n ue st u d y treat me nt, e n d osc o p y is e nc o ura ge d b ut n ot re q uire d at t he E T visit. A n 
e n d osc o p y is n ot re q uire d d uri n g t he L T E Peri o d or at t he E T Visit f or partici pa nt s w h o disc o nti n ue 
t he st u d y duri n g t he L T E P eri o d. If p erf or m e d ( e g, f or disc o nt i n uati on or cli nical e val uat i on), 
res ults of e n d osc o pic e val uat i on s h o ul d be d oc u m e nte d.
All p artici pa nt s w h o ta ke at least 1 d ose of st u d y treat me nt will be f o ll owe d f or pr ot oc ol -s pecifie d 
p ost -treat me nt fol l ow -u p pr oce d ures. T he o nl y e xce pti o n t o t his is w he n a partici pa nt s pecificall y 
wi t hdra ws c o nse nt/asse nt f or a n y f urt her c o ntact wit h hi m/ her or wit h pers o ns pre vi o usl y 
a ut h orize d b y t he parti ci pa nt t o pr o vid e t h is i nf or mati o n.
P arti cipa nt s w h o are li kel y t o deri ve a cli nical be nefit fr o m o n g oi n g parti ci pat i on i n t he st u d y 
f oll owi n g Wee k 6 4, as j u d ge d b y t he in vest i gat or, are eli gi ble t o e nter t he L T E Peri o d. Partici pa nt s 
w h o meet t he earl y disc o nt i n uati on crit eria aft er at least 7 wee ks of  treat me nt i n t he I n d ucti on 
P erio d , ha ve c o nfir me d disease w orse ni n g d ur in g t he Mai nte na nce Peri o d , c o m p lete Wee k 1 2 a n d 
are n o n-res p o n ders, or c o mplete Wee k 6 4 will , ha ve t he o pti o n t o e nter t he L T E Peri o d.
E arl y Ter mi n ati o n
E val uat i ons will be perf or me d as s pecifie d i n Sect i o n 2 .
L T E Peri o d
E val uat i ons will be perf or me d as s pecifie d i n Secti o n 2 .
T he st u d y will be c o n d ucte d i n c o mplia nce wit h t he I C H of  Tec h nical Re q uire me nts f or 
Re gistrati o n o f P har mace ut icals f or H u ma n Use/ G C P a n d a p plica ble re g ulat or y re q uire me nts.
S afe t y F oll o w-u p Peri o d
F or partici pa nt s w h o disc o nti n ue t he st u d y f or a n y reas o n, e ver y atte m pt s h o ul d be ma de t o ret ur n 
t o t he st u d y site t o c o m plete t he assess me nts detaile d i n t he 
 Safet y F oll ow -u p Visit s 
i n Secti on 2 . 
 
 
 
 
 
 
 
 
 I n a d diti on, a d dit i onal safety assess me nts ma y be re q uire d 
f or parti ci pa nt s w h o ha ve a n o n g oi n g A E or s af et y iss ue at t he 
 S af et y Fol l ow -u p Visi t, at 
t he in vesti gat or’s di scretio n. P arti ci pa nt s ma y be f oll owe d as necessar y f or a n a d ditio n al  perio d 
aft er t he 
 S af et y F o ll ow -u p Vi sit t o re vie w t he res ults of  an y assess me nts w hic h were 
c o n d ucte d at t he 
 Safety F o ll ow- u p Visi t.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
7 9
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
9. 1
Effi c a c y A s s e s s m e nt s
9. 1. 1
P e di atri c Cr o h n’ s Di s e a s e A cti vit y I n d e x
T he P C D AI is a n i nstr u me nt t hat was de vel o pe d a n d vali date d f or n u merical assess me nt of  disease 
acti vit y i n c hil dre n a n d a d olesce nts wit h C D.3 0 T he P C D AI has a sc ori n g ra n ge of 0 t o 1 0 0. Mil d 
di sease c orres p o n ds t o sc ores of 1 1 t o 3 0; mo derate t o se vere disease c orres p o n ds t o sc ores > 3 0. 
Re missi o n (ie, n o disease acti vit y) is defi ne d as a P C D AI sc ore < 1 0. T he P C D AI i ncl u des 
parti ci pa nt hist orical i nf or mat i on, p h ysical e xa mi nati o n fi n di n gs, o bject i ve la b orat or y para meters, 
data o n w ei g ht gai n/l oss, a n d hei g ht vel ocit y.  The cate g or y o f se verity f or eac h i n de x ite m is 
assi g ne d a sc ore: 0 = n or mal; 5 = mil d a b n or malit y; 1 0 = se vere a b n or malit y. T he P C D AI als o 
i ncl u des 3 la b orat or y para meters (ie, he mat ocrit, er ythr oc y te se di me ntati o n rate ( S R), a n d al b u mi n 
le vel) w hic h are part of t he calc ulati on. F or he mat ocrit a n d er y t hr o c yt e S R , t he ma xi m u m sc ore = 
5. F o r al b u mi n le vel, t he ma xi m u m sc ore = 1 0 (see A p pe n di x 6 ). Cli nical p ar a m et ers nee de d f or 
calc ulat i on of  the P C D AI will be c ollecte d fr o m t he parti ci pa nt at t he sc he d ule d visit (see
Secti o n 2 ). T he P C D AI c o nsists of t he f oll owi n g 1 1 varia bles:
1.
A b d o mi nal pai n ( 1 wee k)
2.
St o ol s per da y ( 1 wee k)
3.
P ati e nt fu nct i oni n g/ g e neral well bei n g ( 1 wee k)
4.
Wei g ht
5.
H ei g ht vel ocit y (c urre nt visit hei g ht c o mpare d wit h hei g ht me as ure d 6 t o 1 2 m o nt hs earlier 
e x presse d as a sta n dar d de viat i on sc ore)
6.
A b d o mi nal te n der ness, mass, g uar di n g
7.
P eri -rectal disease
8.
E xtra -i ntesti nal ma nifestati o ns 
(fe ver, art hritis, u vei tis, er yt he ma n o d os u m, p y o d er m a 
ga n gre n os u m)
9.
H e m at o crit ( %) for ma les/fe males
1 0. Er y t hr o c yte se di me ntatio n rate ( E S R; m m/ h o ur)
1 1. Al b u mi n ( g/ d L)
T he a b d o mi nal pai n, st o ol fre q ue nc y, a n d ge neral well b ei n g sc ores fr o m t he wee k pri or t o eac h 
st u d y visit will be us e d t o calc ulate t he P C D AI. If t he partici pa nt is u n der g o i n g a pla n ne d 
c olo n os c o p y , t he da y(s) of b o wel pre paratio n s h o ul d be e xcl u de d fr o m c o nsi derat i on.
9. 1. 2
Si m pl e E n d o s c o pi c S c or e f or Cr o h n' s Di s e a s e
T he S E S -C D assesses t he de gree of  infla m mati o n. 3 1 T he S E S - CD assesses t he f oll owi n g 
4 c o mp o ne nts: size o f ulcers, ulcerate d s urface, affecte d s urface, a n d prese nce of narr o wi n g. Eac h 
of  t hese c o mp o ne nts are sc ore d o n a scale of 0 t o 3 as o utli ne d i n Ta ble 9. 1. 2 - 1.
I n t he S E S-C D, eac h of t hese 4 c o m p o ne nts are assesse d i n t he 5 se g me nts of t he ile u m a n d c ol o n: 
ile u m, ri g ht, tra ns verse, left ( desce n di n g a n d si g m oi d), a n d rect u m. T he S E S-C D is t he s u m of t he 
i n di vi d ual sc ores of eac h of t he c o mp o ne nts acr oss t he 5 se g me nts.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
8 0
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
E n d osc o pic res p o nse is defi ne d i n t his st u d y as 5 0 % or greater decrease i n S E S -C D fr o m B aseli ne. 
E n d osc o pic re missi o n is n o t yet vali date d a n d ma y be defi ne d as S E S-C D ≤ 4 p o i nts a n d a S E S -C D 
decrease fr o m B aseli ne ≥ 2 p oi nts, a n a bse nce of lar ge ulcers, a bse nce o f ulcers, or S E S -C D is ≤2 
p oi nts. F or t he p ur p oses of  this st u d y, e n d osc o pic re missi on is defi ne d as t he pr o p orti o n of 
parti ci pa nt s ac hie vi n g S E S-C D ≤ 2 or S E S -C D ≤ 4 p oi nt s wit h no S E S -C D s u bsc ore > 1 p oi nt at 
Wee k s 1 2 a n d 6 4 .
T o e ns ure q ualit y data a n d sta n dar dizati on, t he sa me e n d osc o pist a n d t he sa me di a meter 
c olo n osc o pe as use d i n S cree ni n g s h o uld be use d t hr o u g h o ut t he st u d y where ver p ossi ble. 
C ol o n os c o pi es will be rea d at a ce ntralize d rea di n g facilit y i n a pr ocess o utli ne d i n t he E n d osc o p y 
I ma ge C harter. Ce ntralize d rea di n g will be t he pri mar y  assess me nt f or e n d osc o p y; l ocal e n d osc o p y 
sc ores will als o be c ollecte d.
T a ble 9. 1. 2 - 1:
Defi niti o ns of Si m ple E n d osc o pic Sc ore f or Cr o h n's Dise ase ( S E S -
C D)
S E S -C D V al ues
V ari a ble
0
1
2
3
Size of ulcers
N o ne
A p ht h o us ulcers 
( 0. 1 t o 0. 5 c m)
L ar ge ulcers 
( 0. 5 t o 2 c m)
Ver y  lar ge ulcers 
( > 2 c m)
Ulcerate d s urface
N o ne
< 1 0 %
1 0 %- 3 0 %
> 3 0 %
Affecte d s urface
U n affecte d se g me nt
< 5 0 %
5 0 %- 7 5 %
> 7 5 %
Prese nce of 
narr o wi n gs
N o ne
Si n gle, ca n be 
passe d
M ulti ple, ca n be 
passe d
Ca n n ot be passe d
A da pte d
fro m: Da per n o
M,
D’ Hae ns
G,
Va n
Assc he
G,
et al. De vel o p me nt
a n d vali dati o n of a ne w, si m plifie d 
e n d o sc o pic acti vit y sc ore f or Cr o h n’s disease: t he S E S -C D. Gastr oi ntest E n d osc 2 0 0 4; 6 0( 4): 5 0 5 -1 2.
9. 1. 3
Cr o h n’ s Di s e a s e A cti vit y I n d e x
T he C D AI is a c o mp osi t e s c or e t h at is us e d t o meas ure t he cli nical acti vit y of C D. C D AI will be 
c ollecte d f or a d olesce nt partici pa nt s (see Secti o n 5 ). T he C D AI uses a q uest i on naire wi t h 
res p o nses sc ore d n u mericall y a n d wei g hte d. Sc ores ra n ge fr om 0 t o a p pr o xi matel y 6 0 0, w ith 
hi g her sc ores i n dicati n g greater disease acti vit y.  The 8 c o mp o ne nts use d t o assess t he C D AI a n d 
t heir wei g hti n g fact ors are n ote d i n Ta ble 9. 1. 3 - 1. T he defi nit i ons of  mil d, m o derate, a n d se vere 
C D are pr o vi de d i n Ta ble 9. 1. 3 - 2.
Cli nical re missi o n base d o n C D AI sc ore is defi ne d as a C D AI sc ore of < 1 5 0. Cli nical res p o nse is 
defi ne d as C D AI re d ucti o n fr om B aseli ne of ≥ 1 0 0 p oi nts or C D AI sc ore of < 1 5 0. S y m pt o m atic 
re missi o n base d o n a b d o mi nal pai n a n d st o ol fre q ue nc y is defi ne d as a n a vera ge dail y  st o ol 
fre q ue nc y sc ore ≤ 3 p oi nts a n d a n a vera ge a b d o mi nal pai n sc ore ≤ 1 p oi nt wit h a st o ol fre q ue nc y 
n o w orse t ha n B aseli ne.
P arti cipa nt -re p orte d c o m p o ne nts of t he C D AI (st o ol fre q ue nc y, a b d o mi nal p ai n c o m p o ne nts , a n d 
ge neral well bei n g) will be c o llecte d i n a n electr o nic di ar y. Parti ci pa nts will c o m p lete t heir 
ele ctr o nic diar y starti n g at t he first Scree ni n g visit a n d will c o nti n ue t hr o u g h o ut t he st u d y.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
8 1
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
P arti cipa nts will be i nstr ucte d o n t he use a n d c o m plet i on of q uest i ons o n t he electr o n ic diar y.
T he parti ci pa nt’s electr o nic diar y e ntries will be re vie we d b y site pers o n nel d uri n g Scree ni n g a n d 
t hr o u g h o ut t he st u d y.
T a ble 9. 1. 3 - 1:
Cr o h n’s Dise ase Acti vit y I n de x Assess me nt
Cli nic al or L a b or at or y V ari a ble
Wei g hti n g F act or, ×
N u m ber of li q ui d or s oft st o ols eac h da y f or 7 da ys a
2
A b d o mi nal pai n ( gra de d fr o m 0 -3 o n se verit y) eac h 
da y  f or 7 da ys
5
Ge neral well bei n g, assesse d fr o m 0 ( well) t o 4 
(terri ble) dail y f or 7 da ys
7
Prese nce of c o m plica ti o nsb
2 0
Ta ki n g di p he n o x ylate/atr o pi ne, l o pera mi de, or o piates 
f or diarr hea
3 0
Prese nce of a n a b d o mi nal mass ( 0 as n o ne, 2 as 
q uesti o na ble, 5 as defi nite)
1 0
He mat ocrit 4 7 -H C T i n males a n d 4 2-H C T i n fe males
6
Perce nta ge de viati o n fr o m sta n dar d wei g ht
1
T ot al Sc ore
A b bre viati o n: H C T = he mat ocrit.
a
Li q ui d o r s oft st o ols are c haracterize d b y Brist ol St o ol Scale T y pes 6 a n d 7. 
b
O ne p oi nt eac h is a d de d f or eac h set of c o m plicati o ns: art hritis or  art hral gia; iritis or u veitis; er yt he ma n o d os u m, 
p y o der ma ga n gre n os u m, a p ht h o us st o matitis; a nal fiss ure, fist ula or perirectal a bscess; ot her b o wel -relate d fist ula; 
fe brile (fe ver) e pis o de o ver 1 0 0 de grees d uri n g t he past wee k.
T a ble 9. 1. 3 - 2:  
Cr o h n's Dise ase Se verit y Defi niti o ns
Se verit y
C D AI Sc ore
Mil d
1 5 0- 2 1 9
M o derate
2 2 0- 4 5 0
Se ver e
> 4 5 0
A b bre viati o n: C D AI = Cr o h n’s Disease Acti vit y I n de x.
9. 1. 4
A b d o mi n al P ai n a n d St o ol Fr e q u e n c y
T he a b d o mi nal pai n a n d st o ol fre q ue nc y sc ores are base d o n 2 c o mp o ne nts of  the P C D AI a n d 
C D AI. 3 0 , 3 2 See Se ct i on s 9. 1. 1 a n d 9. 1. 3 f or more details.
St o ol  fre q ue nc y a n d a b d omi nal pai n will be o btai ne d a n d calc ulate d wit h o ut a wei g hti n g fact or f or 
use as p art of  t he i ncl usi on criteria. T hese u n wei g hte d partici pa nt -re p orte d assess me nts will als o 
be use d as efficac y e n d p oi nts (see Secti o n 4 ).
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
8 2
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
T he Brist ol  St o ol Scale 3 3 is a n a d ditio nal t o ol for t he vis ual e val uat i on of  diarr hea, a n d will  be 
pr o vi de d t o hel p wit h t he dail y d oc u me ntati o n of t he n u m ber of ver y s o ft (l oose) or li q ui d ( water y) 
st o ols ( Brist ol St o ol Scale T ypes 6 or 7) rec or de d i n t he parti ci pa nt ’s electr o nic diar y .
9. 1. 5
E n d o s c o pi e s a n d E n d o s c o pi c Bi o p si e s
E n d osc o pies a n d e n d osc o pic bi o psies will be s u b mitte d t o a n i ma gi n g c ore la b.
E n d osc o p y : C o l on osc o p y  will be p erf or m e d as i n dicate d i n Secti o n 2 . A n e n d osc o p y is n ot 
re q uire d d uri n g t he L T E Peri o d or at t he E T Visit f or partici pa nt s w h o disc o nti n ue t he st u d y d uri n g 
t he L T E P erio d. H o we ver, if perf or m e d ( e g, for disc o nti n uati o n or cli nical  e v al u atio n), res ul ts of 
e n d osc o pic e val uat i on s h o ul d be d oc u me nte d.
T o e ns ure q ualit y data a n d sta n dar dizati on, t he sa me e n d osc o pist s h o ul d be use d t hr o u g h o ut t he 
st u d y where ver p ossi ble. E n d osc o p y  vi de os will be o btai ne d d uri n g eac h e n d osc o p y an d will be 
se nt f or ce ntral rea di n g a n d deter mi nati on of t he S E S -C D. A detaile d I ma ge Re vie w C harter fr o m 
t he ce ntral rea di n g la b orat or y will descri be t he a p pr oac h f or utilizati on of vi de o ca pt ure t o ols a n d 
pr ocesses f or t he ca pt ure, tra ns missi on, a n d assess me nt of e n d osc o p y vi de o re c or di n gs e n d osc o pic 
pr oce d ures. T he e n d osc o pic rec or di n gs will be rea d ce ntrall y i n a bli n de d ma n ner f or m u c osal 
lesio ns a n d e n d osc o pic se verity b y a q ualifie d gastr oe nter ol o gist acc or di n g t o t h e I ma ge Re vie w 
C harter.
 
 
 
 
 
 
 
 
 
9. 1. 6
Er yt hr o c yt e S e di m e nt ati o n R at e
T he E S R will be assesse d at visit s w he n t he P C D AI is p erf or me d at t he fre q ue nc y s pecifie d i n 
Secti o n 2 . T he E S R res ult is ge nerate d at t he site fr o m a s u p pl y ki t pr o vi de d b y t he ce ntral 
la b orat or y, a n d t h e sit e will r e c or d t h e E S R res ult i nt o t he a p pr o priat e electr o nic e ntr y scree n f or 
calc ulatin g t he P C D AI.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
8 3
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
9. 1. 9
P arti ci p a nt Di ari e s
P arti cipa nt ( or pare nt/ g uar dia n )-re p orte d c o m p o ne nts of  the C D AI (e g, st o ol fre q ue nc y, a b d o mi na l 
pai n c o m p o ne nts , a n d ge neral  well bei n g) will be c ollecte d i n a n electr o nic diar y . A d o lesce nt 
p artici pa nt s will e nter t heir si g ns a n d s y m pt o ms as pr om pt e d b y t he electr o nic diar y fr o m t he first 
Scree ni n g visit u ntil t he Wee k 6 4 vi sit or E T visit (see Sectio n 2 ). Parti ci pa nt s w h o partici pate i n 
t he L T E Peri o d will c o m p lete diaries prior t o eac h sc he d ule d visit or E T visit.
P arti cipa nt s ( or pare nt/ g uar dia n ) will be i nstr ucte d o n t he use a n d c o mpleti o n of  q u estio ns o n t he 
ele ctr o nic diar y.
T he di ar y ent ries will be re vie we d b y sit e pers o n nel d uri n g Scree ni n g ( prior t o d osi n g, if 
a p plica ble) a n d d uri n g all st u d y visits, e xce pt f or t he Safet y Fol l ow- u p Vi sits.
T he st o ol fre q ue nc y a n d a b d o mi nal pai n diar y e ntries will be use d t o calc ulate t he C D AI. Beca use 
c olo n os c o p y  pre paratio ns ca n i nterfere wi t h the assess me nt of  ot her cli nical para meters, diar y 
e ntr ies o n t he da y s of t h ose assess me nts ca n n ot be use d t o calc ulate C D AI sc ores.
F or a d di tio nal  d et ail, please refer t o Sectio n s 2 a n d 9. 1. 3 .
9. 2
A d v er s e E v e nt s
T he defi nit i ons of a n A E or S A E ca n be f o u n d i n A p pe n di x 3 .
A Es will be re p orte d b y t he parti ci pa nt ( or, w he n a p pr o priate, b y a care gi ver, a s urr o gate, or t h e 
parti ci pa nt’s pare nt or g uar dia n ).
T he in vest i gat or a n d a n y q ualifie d desi g nees are res p o nsi ble f or detecti n g, d oc u m e nt i n g, a n d 
re p orti n g e ve nts t hat meet t he defi niti on of a n A E or S A E a n d re mai n res p o nsi ble f or f oll o wi n g u p
o n A Es t hat are seri o us, c o nsi dere d relate d t o t he st u d y i nter ve nt i on or t he st u d y, or t hat ca use d 
t he partici pa nt t o disc o nt i n ue bef ore c o m pleti n g t he st u d y. 
Refer t o A p pe n di x 3 f or S A E re p orti ng.
9. 2. 1
Ti m e P eri o d a n d Fr e q u e n c y f or C oll e cti n g A E a n d S A E I nf or m ati o n
All S A Es m u st be c ollecte d fr o m t he time of  si g ni n g t he c o nse nt, i ncl u di n g t hose t ho u g ht t o be 
ass ociate d wi t h pr ot oc ol-s pecifie d pr oce d ures , a n d wit hi n 
f oll owi n g disc o nt i n uati on of
d osi n g.
T he in vesti gat or m u st re p ort a n y S A E t h at o c c urs after t hese ti me p eri o ds a n d t hat is belie ve d t o 
be relate d t o stu d y i nter ve nt i on or pr ot oc ol -s pecifie d pr oce d ure (e g, a f oll o w-u p s ki n bi o ps y).

Me dical occ urre nces t hat be gi n b ef or e t he start of  st u d y i nter ve ntio n b ut aft er o btai ni n g 
i nf or me d c o nse nt will be rec or de d o n t he a p pr o priate secti o n o f t he eC R F m o d ule .
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
8 4
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d

All S A Es will be rec or de d a n d re p orte d t o S p o ns or or desi g nee wi t hi n 2 4 h o urs , as in d icate d 
i n A p pe n di x 3 .

T he in vesti gat or will s u b mit a n y u p date d S A E data t o t he S p o ns or or desi g nee wi t hi n 2 4 h o urs
of u p date d i nf or mat i on bei n g a vaila ble.
I n vesti gat ors are n ot o bli gate d t o acti vel y see k A Es or S A Es i n f or mer st u d y partici pa nts. 
H o we ver, if t he in vest i gat or learns of  a n y S AE, i ncl u di n g a deat h, at a n y time aft er a partici pa nt 
has bee n disc har ge d fr o m t he st u d y, a n d he/s he c o nsi ders t he e ve nt reas o na bl y relate d t o t he st u d y 
i nter ve nt i on or st u d y  p artici pat i on, t he in vest i gat or m ust pr o m ptl y n otif y t he S p o ns or.
T he met h o d of  eval uati n g a n d assessi n g ca usalit y of  AEs a n d S A Es a n d t he pr oce d ures f or 
c o mplet i n g a n d re p orti n g/tra ns mittin g S A E re p or ts are pr o vide d i n A p pe n di x 3 .
All partici pa nt s will be m o nit ore d f or A Es d uri n g t he st u d y. Assess me nts ma y i ncl u de m o nit ori n g 
of  an y or all of  t he f oll owi n g para m eters: t he partici pa nt ’s cli nical s y m pt o ms; la b orat or y, 
pat h ol o gi cal, r a diol o gi cal, or s ur gical fi n di n gs; p h ysical  exa mi nat i on fi n di n gs; or fi n di n gs fr om 
ot her tests a n d/ or pr oce d ures.
All A E s ( S A Es a n d n o nseri o us A Es), i ncl u di n g S A R S -C o V - 2 i nfecti on, m u st be c ollecte d fr om 
t he ti me t he partici pa nt si gns i nf or me d c o nse nt u ntil 9 0 d a y s aft er t he last d ose of  IP, as well as 
t hose S A Es ma de k n o w n t o t he i n vesti gat or at a n y ti me t hereafter t hat are s us pecte d of  bei n g 
r elate d t o I P.
All A Es (serio us/ n o n -serio us) m u st be rec or de d o n t he e C R F a n d i n t he parti ci pa nt’s s o urce 
d oc u m e nts. All S A Es m ust ha ve d ata tra ns mitte d electr o nicall y t o S p o ns or Dr u g Safet y ( or 
desi g nee) wi t hi n 2 4 h o urs of  the i n vesti gat or’s k n o wle d ge of  the e ve nt. I n t he e ve nt electr o nic 
tra ns missi on is n ot a vaila ble, a pa per S A E Re p ort F or m will be c o m plete d a n d se nt directl y t o t he 
S p o n s or’s Dr u g Safet y ( or desig nee), e ns uri n g t he e ve nt is rec or de d o n t he e C R F as well.
A b use, wit h dra wal, se nsiti vity,  or t o xicit y to a n I P s h o ul d be re p orte d as a n A E. O ver d ose, 
accid e nt al  or i nte nt i onal, if it is ass ociate d wit h a n A E, s h o uld be re p orte d o n t he St u d y  Dr u g 
E x p os ure e C R F. A n y se q uelae of  an acci de ntal or int e nt i onal o ver d ose of  an I P w hic h meets t he 
defi nit i on o f a n A E s h o ul d be re p orte d as a n A E o n t he e C R F. If t he se q uela of a n o ver d ose meets 
serio us cri t eria, t he n it must be mar ke d as seri o us o n t he e C R F. T he o ver d ose i tself s h o uld n ot be 
re p orte d as a n A E.
P articipa nt s will be i nstr ucte d t o c o nt act t he in vest i gat or at a n y ti me if the y de vel o p a n i nterc urre nt 
ill ness or si g ns or s y m pt o ms a n d/ or a dia g n osis of S A R S -C o V -2 i nfect i on w hic h will e na ble cl ose 
m o nit ori n g a n d a d dit i onal scree ni n g f or t he i nfect i o n bet wee n st u d y visits.
I n parti ci pa nt s w h o are e x hi biti n g s y m pt o ms c o nsiste nt wit h S A R S -C o V -2 i nfecti o n , t he S p o ns or 
a d vises t he in vest i gat or t o c o nsi der h o l di n g d osi n g of I P a n d c o ns ult t he Cli nical Tri al P h ysicia n
or desi g nee . If a parti cipa nt has a p osi ti ve test f or S A R S -C o V - 2, or if no t es ti n g is a vaila ble, t he 
S p o ns or a d vises t he in vesti gat or t o c o nsi der h ol di n g parti ci pa nt d osi n g u nt il s uc h ti me as 
s y m pt o ms res ol ve. If a p osi ti ve S A S -C o V - 2 test res ult is re p orte d, please c o ns ult wit h t he Cli nica l 
Tri al P h ysicia n or desi g nee o n w het her res ol uti on of s y m pt o ms al o ne is s uffic ie nt t o res u me d osi n g 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
8 5
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
of  the I P (Secti o n 3. 3. 1 ). U p o n a p osi tive t est res ult f or S A R S -C o V - 2 i nfecti o n, t he i nfecti on 
s h o uld be re p orte d t o t he S p o ns or wit hi n 2 4 h o urs.
S A R S -C o V - 2-relate d A Es/ S A Es will be ca pt ure d i n s pecific cli nical safety pr o gra m e C R F pa ges.
9. 2. 2
M et h o d of D et e cti n g A E s a n d S A E s
A Es ca n be s p o nta ne o usl y re p orte d or elicite d d uri n g o pe n -e n de d q uest i oni n g, e xa mi nat i on, or 
e val uat i on o f a parti ci pa nt . Care s h o ul d be ta ke n n ot t o i ntr o d uce bias w he n c ollecti n g A E s a n d/ or 
S A Es. I n q ui r y a bo ut s p e cific A Es s h o uld b e g ui d e d b y  cli nical j u d g me nt i n t he c o nt e xt of k n o w n 
A E s, w he n a p pr o priate f or t he pr o gra m or pr ot oc ol.
9. 2. 3
F oll o w -u p of A E s a n d S A E s

N o nseri o us A Es s h o ul d be f oll owe d t o res ol ut i on or s ta bilizati on, or re p orte d as S A Es if t he y 
bec o me seri o us (see A p pe n di x 3 ).

F o ll ow - u p is als o re q uire d f or n o nseri o us A Es t h at ca use i nterr u pti o n or disc o nt i n uati o n of  
st u d y i nter ve ntio n a n d f or t h ose pre se nt at t he e n d of st u d y i nter ve nt i on as a p pr o priate.

All i de ntifie d n o nseri o us A Es m u st be rec or de d a n d descri be d o n t he n o nseri o us A E pa ge of 
t he eC R F ( pa per or electr o nic). C o m plet i on of s u p ple me ntal eC R Fs ma y  be re q ueste d f or A Es 
a n d/ or la b orat or y a b n or malities t hat are re p orte d/i de nt ifie d d uri n g t he c o urse of t he st u d y.
After t he i nit ial A E/ S A E re p ort, t he i n vest i gat or is re q uire d t o pr oacti vel y f oll ow eac h parti ci pa nt 
at s u bse q ue nt visit s/c o ntacts. All S A Es, a n d n o nseri o us A E SI s (as defi ne d i n S e cti o n 9. 2. 9 ) will 
be f oll owe d u nt il r es olut i on, u nt il t he c o n ditio n sta bilizes, u ntil t he e ve nt is ot h er wise e x plai ne d, 
or u ntil t he partici pa nt is l ost t o f o ll ow- u p (as defi ne d i n Secti o n 8. 3 ).
F urt her i nf or mat i on o n f o ll ow- u p pr oce d ures i s gi ve n i n A p pe n di x 3 .
9. 2. 4
R e g ul at or y R e p orti n g R e q uir e m e nt s f or S A E s

Pr o m pt n otificat i on b y t he in vest i gat or t o t he S p o ns or of  SA Es is esse nt ial s o t hat le gal 
o bli gat i ons a n d et hical res p o nsi bilities t o war d t he safety of  part ici pa nts a n d t he safety of  a 
pr o d uct u n der cli nical i n vesti gati o n are met.

A n in vest i gat or w h o recei ves a n in vest igat or safet y re p ort descri bi n g S A Es or ot h er s pecific 
safety i nf or mati o n (e g, s u m m ar y or listi n g of  SA Es) fr om t he S p o ns or will file it alo n g wi t h 
t he I B a n d will n otif y t he I R B/I E C, if a p pr o priate acc or di n g t o l ocal re q uire me nts.
T he S p o ns or or desi g nee m ust
re p ort A E s t o re g ulat or y aut h ori ties a n d et hics c o m mittees 
acc or di n g t o l ocal ap plica ble la ws a n d re g ulat i ons . A s us pecte d, u ne x pecte d serio us a d verse 
reactio n ( S U S A R ) is a s u bset of  SA Es a n d m u st be re p orte d t o t he a p pr o priate re g ulat or y 
a ut h orities a n d in vest i gat ors f oll owi n g l o c al  a n d gl o bal g uideli nes a n d re q ui re me nts.
9. 2. 5
Pr e g n a n c y
If, f oll owi n g i ni tiat i on of t he st u d y  i nter ve nt i on , it is s u bse q ue ntl y disc o vere d t hat a partici pa nt is 
pre g na nt or ma y ha ve bee n pre g na nt at t he ti me of st u d y ex p os ure, i ncl u di n g d uri n g at least 
aft er st u d y pr o d uct a d mi nist r atio n , t he in vest i gat or m u st i m me diatel y n otif y 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
8 6
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
t he B M S Cli nical Trial P h ysicia n or desi g nee o f this e ve nt a n d c o m plete a n d f or war d a Pre g na nc y 
S ur veilla nce F or m  to t he B M S d esig nee wi t hi n 2 4 h o urs of  aware ness of  the e ve nt a n d i n 
acc or da nce wit h S A E re p o rti n g pr oce d ures descri be d i n A p pe n di x 3 .
F o ll ow- u p i nf or mati on re gar di n g t he c o urse of  the pre g na nc y, i ncl u di n g peri natal  an d ne o natal 
o utc o m e a n d, w here a p plica ble, offs pri n g i nf or mati on, m u st be re p orte d o n t he Pre g na nc y 
S ur veilla nce F or m. Pr ot oc ol -re q uire d pr oce d ures f or st u d y disc o nti n uati on a n d f o ll ow- u p m ust be 
perf or m e d o n t he partici pa nt.
9. 2. 6
L a b or at or y T e st R e s ult A b n or m aliti e s
T he f o ll owi n g la b orat or y  test res ult a b n or malities s h o ul d be ca pt ure d o n t he n o nseri o us A E eC R F 
pa ge or S A E e C RF, as a p pr o priate. Pa per f or ms are o nl y i nte n de d as a bac k - u p o pti o n w he n t he 
ele ctr o nic s yste m is n ot f u ncti oni n g.

A n y la b orat or y  test res ult t hat is cli nicall y si g nifica nt or meets t he defi niti on of a n S A E 

A n y la b orat or y t est r es ult a b n or malit y t hat r e quire d t he parti ci pa nt t o ha ve st u d y i nter ve nt i on
di sc o nti n ue d or i nterr u pte d

A n y la b orat or y test res ult a b n or malit y t hat re q uire d t he parti ci pa nt t o recei ve s pecific 
c orrecti ve t hera p y
It is ex pecte d t hat , w here ver p ossi ble, t he cli nical rat her t ha n la b or at or y ter m w o ul d be use d b y t he 
re p orti n g in vest i gat or (e g, a ne mia vs l o w he m o gl o bi n val ue).
9. 2. 7
P ot e nti al Dr u g -in d u c e d Li v er I nj ur y
S pecific criteria f or i de nt if yi n g a pote nti al dr u g -i n d uce d li ver i nj ur y (DI LI ) are o utli ne d i n Secti o n 
9. 2. 9 alo n g wi t h instr ucti o ns o n re p orti n g a n d f oll o w- u p of t hese cases.
9. 2. 8
Ot h er S af et y C o n si d er ati o n s
A n y si g nifica nt w orse ni n g of  co n di tio n s n ote d d uri n g i nteri m or fi nal p h ysical e xa mi nat i ons, E C G , 
or a n y ot h er p ote ntial safety assess me nt re q uire d or n ot re q uire d b y t he pr ot oc ol  sh o ul d als o b e 
rec or de d as a n o nseri o us A E or S A E, as a p pr o priate, a n d re p orte d acc or di n gl y.
T he in vest i gat or will re p ort t he o ut c o m e of t he e ve nt f or eac h A E.
All S A Es t hat ha ve n ot res ol ve d u p o n disc o nti n uati o n of t he partici pa nt ’s partici pati o n i n t he st u dy 
m ust be f o ll o we d u ntil rec o vere d (ret ur ne d t o B aseli ne), rec o vere d wit h se q uelae, or deat h ( d ue t o 
t he S A E).
9. 2. 9
A d v er s e E v e n t s of S p e ci al I nt er e st
All A Es a n d S A Es t hat arise i n t h e st u d y will be re p orte d a n d i n vesti gate d. H o we ver, beca use of 
t he c haracteristics of  the d isease u n der st u d y an d o za ni m o d, i n part ic ular, s ome A Es are c o nsi dere d 
A E S Is. A E S Is ma y be serio us or n o nseri o us. S uc h e ve nts ma y re q uire f urt her i n vesti gati on t o 
better c haracterize a n d u n dersta n d t he m. I n t he oza ni m o d cli nical de vel o p me nt pr o gra m, p ote ntial
A E S Is t hat ma y be a c o nse q ue nce of S 1 P1 m o d ul atio n  will be cl osel y m onit ore d d uri n g t he st u d y. 
T he se A E S Is i ncl u de 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
8 7
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
 
 
A n i n de pe n de nt D M C 
f or t he st u d y will perf or m re g ular safet y re vie ws starti n g after t he first partici pa nt is d ose d.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
8 8
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
8 9
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9. 3
O v er d o s e
F or t his st u d y, a n y d ose of  oza ni m o d greater t ha n t he d ose descri be d i n t he pr ot oc ol will be 
c o nsi dere d a n o ver d ose. O ver d oses t hat meet t he re g ulat or y  defi nitio n  of S A E will be re p orte d as 
a n S A E (see A p pe n di x 3 ).
A n y o ver d ose, wit h or wit h o ut ass ociate d A Es, m ust be pr o m pt l y re p orte d t o t he Cli nical Trial 
P h ysicia n or ot h er d esi g nate d Dr u g Safet y  Ce nter. T he o ver d ose s h o uld be rec or de d i n t he S t u d y 
Dr u g E x p os ure e C R F. A Es ass o ciate d wi t h an o ver d ose s h o ul d be re p orte d o n rele va nt A E/ S A E 
secti ons i n t he e C R F.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
9 0
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
I n t he e ve nt of  over d ose, t he partici pa nt s h o ul d be m o nit ore d as a p pr o priate a n d s h o uld recei ve 
s u p p orti ve meas ures as necessar y. T h ere is n o k n o w n s pecific a ntid ot e f or oza ni m o d o ver d ose. 
Act ual  treat me nt s h o uld de pe n d o n t he se verity of  the cli nical sit u atio n a n d t he j u d g me nt a n d 
e x perie nce o f t he treati n g p h ysicia n.
9. 4
S af et y
Pl a n ne d ti me p o i nts f or all safety assess me nts are liste d i n Secti o n 2 .
9. 4. 1
P h y si c al E x a mi n ati o n s
C o m plete a n d i nteri m p h ysical e xa mi nat i ons will be perf or me d as i n dicate d i n Sect i on 2 .
C o m plete p h ysical e xa mi nat i ons will i ncl u de e val uati o n of hear t, lu n gs, hea d a n d nec k, a b d o me n,  
s ki n, a n d e xtre mities, as well as a c hec k f or vis ual or ne ur ol o gic s y m pt o ms. All si g nifica nt fi n di n gs 
t hat are prese nt at Scree ni n g m u st be re p orte d o n t he r ele va nt me d ical hist or y/c urre nt me d ical 
c o n ditio ns e C R F. A f ull e xa mi nat i on of  the s ki n a n d a c hec k f or vis ual s y m pt o ms s h o uld be 
re peate d e ver y 6 m o nt hs. D er m at olo gical  eval uati o ns s h o uld be p erf or m e d b y t he treati n g 
in vesti gat or or desi g nee as part of  p h ysical e xa mi nati o ns. Parti ci pa nt s with a n y s us pici o us fi n di n gs 
n o te d d uri n g t he e xa mi nat i on will be r eferre d t o a n a p pr o priatel y q ualifie d d er m at olo gist f or 
e val uat i on a n d treat me nt, if warra nte d.
At  all ot h er visit s f oll owi n g S cree ni n g (e xce pt Wee k 
1 2, Wee k 
6 4/ E T) , a n i nteri m p h ysical 
e xa mi nat i on will be perf or me d. T he i nteri m p h ysical e xa mi nat i on will i ncl u de wei g ht, a c hec k f or 
vis ual s y m pt o ms, a n d a n e val uat i on of  bo d y  s yste ms wi t h pre vi o usl y n ote d a b n or malit ies a n d/ or 
t hose b o d y  s yste ms ass ociate d wit h a n y ne w c o mplai nts fr o m t he parti ci pa nt .
Si g nifica nt fi n di n gs ma d e af t er r a n d o mizatio n ( Da y
t hat meet t he defi nitio n  of a n AE m ust be 
rec or de d o n t he A E e C R F.
9. 4. 2
Vit al S i g n s
S y st olic a n d diast olic B P a n d H R will be assesse d i n a seate d a n d sta n di n g p osi tio n at e v er y  visit 
as i n dicate d i n Secti o n 2 . A n a ut o mate d vali date d de vice ma y be use d, if a vaila ble. I n case t he c uff 
sizes a vaila ble are n ot lar ge/s mall e n o u g h f or t he partici pa nt ’s ar m circ u mfere nce, 
a 
s p h y g m oma n o met er wi t h a n ap pr o pri atel y size d c uff ma y be use d. 
 
 
9. 4. 3
El e ctr o c ar di o gr a m s
Refer t o Sc he d ule of E ve nts (see Secti o n 2 ).
9. 4. 4
H ei g ht a n d W ei g ht
Refer t o Sc he d ule of E ve nts (see Secti o n 2 ). 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
9 1
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
9 2
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
9 3
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
9 4
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
9. 4. 9
P ul m o n ar y F u n cti o n E v al u ati o n s
At  Scree ni n g, part ici pa nts wi t h an u n derl yi n g hist or y  of se vere or c hr o nic l u n g disease, 
br o nc h o p ul m o nar y  dys plasia, c ystic fi br osis, se vere ast h ma (ie, t hat i nterferes wi t h nor m al 
acti vit ies of dail y li vi n g) , or ot her cli nicall y rele va nt p ul m o nar y  c o n ditio ns m ust be e xcl u d e d.
D uri n g t he st u d y , c o nsi deri n g t he e x pecte d varia bilit y of res ults a n d t he nee d f or a g e-a p pr o priate 
pr oce d ures f or yo u n ger parti ci pa nts, p ul m o nar y  e v aluat i ons s h o uld be perf or m e d as f o ll ows:
 
 
 
 
 
 
 
As part of  the c o ns ultat i ons d uri n g t he treat me nt peri o d, rele va nt me d ical hist or y  incl u di n g 
i nfecti on, res pir at or y sy m pt o m s, e x p os ure t o as best os, a n d cigarette s m oki n g m ust be c o llecte d 
a n d d oc u me nte d.
 
 
 
 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
9 5
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
P arti cipa nt s w h o e x perie nce A E s or s y m pt o ms s u g gesti ve of  decli ne i n p ul m o n ar y fu nct i on ma y 
o btai n a d ditio n al p ul m o n ar y  ev al u ati o ns at t he di scretio n of  the in vest i gat or or at  t he re q uest of 
t he S p o ns or.
9. 4. 1 0
O p ht h al m ol o gi c al E v al u ati o n s
A t Scree ni n g, parti cip a nts wi t h un derl yi n g hist or y or e vi de nce of  reti nal dis or ders (e g, m ac ular 
ed e m a) or ot her cli nicall y rele va nt o p ht hal mol o gi c al  c o n ditio ns m ust be e xcl u de d.
D uri n g t he st u d y , c o nsi deri n g t he e x pecte d varia bilit y of  r es ults a n d t he nee d f or a ge-a p pr o priate
assess me nts, o p ht hal m o l ogic e val uat i ons s h o uld be perf or m e d as f o ll ows:
 
 
 
 are c o nsi dere d s o urce 
d oc u m e nts t hat s h o uld b e m a de a vaila ble t o t he S p o ns or u p o n re q uest.
As part of t he o p ht hal m o l ogical  e va l uati ons d uri n g t he treat m e nt perio d, rel e v a nt me dical hist or y 
a n d vis ual ac uit y (see Sect i on 9. 4. 1 1 ) m ust be c ollecte d a n d d o c u m e nte d. Parti ci pa nts w h o 
e x perie nce s y m pt o ms (e g, bl urre d visi o n, dist orte d visi o n, decrease d visi o n, di m mi n g) at a n y p oi nt 
d uri n g t he st u d y ma y rece iv e a d di tio n al o c ular e val uatio ns at t h e di screti on of  t he in vest i gat or or 
at t he re q uest of t he S p o ns or. F or f o ll ow -u p e xa mi nat io ns f or s us pecte d a n d/ or c o nfir me d mac ular 
e de ma, a pe diatric reti nal s pecialist is preferre d w here ver p ossi ble.
9. 4. 1 1
Vi s u al A c uit y T e sti n g
Vi s u al Ac uit y testi n g is a meas ure of t he a bilit y of t he e y e t o disti n g uis h s ha pes a n d t he details of 
o bj ects at a gi ve n dista nce . Vis ual ac uit y test res ults will be rec or de d base d o n a ge-a p pr o priat e 
tests perf or me d i n all part ici pa nts b y a n i n di vi d ual wi t h ap pr o pri ate trai ni n g at t he ti me p oi nts 
i n dicate d i n 
9. 4. 1 2
Cli ni c al S af et y L a b or at or y A s s e s s m e nt s
In vest i gat ors m ust d oc u me nt t heir re vie w of eac h la b orat or y safety r e p ort. A n a b n or mal la b orat or y 
val ue is c o nsi dere d a n A E if t he a b n or malit y:

R es ults i n disc o nti n uatio n f r o m t he st u d y

Re q ui res treat me nt, m o dificat i on/ i nterr u pti o n of  IP d ose, or a n y o t her t hera pe utic i nter ve nt i on ,
or

Is j u d ge d t o be of  sig nifica n t cli nical i m p orta nce b y t he in vest i gat or (e g, o ne t hat i n dicates a 
ne w disease pr ocess a n d/ or or ga n t o xicity or is a n e xacer bat i on or w o rse ni n g of  an e xist i n g 
c o n ditio n )
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
9 6
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Re gar dless o f se verity gra de, o nl y la b orat or y a b n or malities t hat f ulfill a seri o us ne ss criteri o n nee d 
t o be d oc u me nte d as an S A E .
If a la b orat or y a b n or malit y is o ne c o mp o ne nt of a di a g n osis or s y n dr o me, t he n o nl y t he dia g n osis 
or s y n dr o me s h o uld be rec or de d as t he A E . If t he a b n or malit y was n ot a part of  a dia gn osis or 
s y n dr ome, t he n t he lab orat or y  ab n or m alit y sh o ul d be rec or de d as t he A E. If p ossi ble, t he lab orat or y 
a b n or malit y s h o uld be rec or de d as a me dical ter m a n d n ot si m pl y as a n a b n or mal la b orat or y res ult  
( eg , rec or d t hr o m b oc yt o pe nia rat her t ha n decrease d platelets).
T he ce ntral la bor at or y  will a nal yze r o uti ne sa m ples, u nless ot her wise s pecifie d i n t he pr ot oc ol . 
L ocal  la b orat ories ma y als o be use d t o c o n d uct safety tests t hat re q uire q uic k res ults ( w he n t he 
ce ntral la b orat or y is u na ble t o pr o vi de) o nl y if d u plicate test sa m ples are collecte d at t he sa me ti me 
a n d se nt t o b ot h t he ce ntral la b orat or y a n d t he l ocal la b orat or y. Pri or t o utilizi n g a l ocal la b orat or y, 
t he I n vesti gat or m u st c o nt act t he Cli nical Tri al  P h ysicia n or d esi g nee f or disc ussi o n. Li mitat i ons 
of  bl oo d v ol u me c ollect i on s h o uld be c o nsi dere d caref ull y. T he i n vesti gat or m ust e ns ure t hat t he 
l ocal la b orat or y certificates a n d refere nce ra n ges are pr o vi de d t o t he S p o ns or.
Details re gar di n g c ollect i on of  sa mples, s hip m e nt of  sa mples, re p orti n g of  res ults, lab orat or y 
refere nce ra n ges, a n d alert i n g a b n or mal val ues will be s u p plie d t o t he sit e b efor e si te i nitiat i on i n 
a st u d y L a b Fl o w chart . T he res ults of t he a nal ysis will be ma de a vaila ble t o eac h site b y t he ce ntral 
la b orat or y.
I n vesti gat ors will be as ke d t o c o m me nt o n t h ose a b n or malit ies o n t he res pecti ve lab orat or y  r es ult 
pa ge, i ncl u di n g a n otati o n of t he cli nical si g nifica nce of eac h a b n or mal fi n di n g i n t he parti ci pa nt’s 
s o urce d oc u me nts. T he la b orat or y s heets will be file d wit h t he partici pa nt ’s s o urce d oc u me nts.
T he decisi o n t o t e mp oraril y  int err u pt d osi n g beca use of  a la b orat or y ab n or m alit y ot her t ha n 
A L C < 2 0 0 cells/ μ L re mai ns t he res p o nsi bilit y o f the t reati n g p h ysicia n, w hic h will n ot be dela ye d 
or ref use d b y t he S p o ns or. H o we ver, pri or t o i nterr u ptio n, t he in vest i gat or ma y c o ntact t he Cli nica l 
Tri al Ph ysicia n or desi g nee a n d f or war d a p pr o priate s u p p orti n g d oc u m e nts f or re vie w a n d 
di sc ussi on. T he in vest i gat or will re p ort t he actio n ta ke n wi t h IP. See Secti o n 8. 1 f or per ma ne nt 
di sc o nti n uati on of I P.
T he a mo u nt of  blo o d ta ke n fr o m partici pa nt s at eac h visit a n d c u m ulati vel y o ver t he c o urse of t he 
e nt ire st u d y is wi t hi n t he safety li mits ( 1 % t o 3 % of  total  bl oo d v ol u me, [T B V ]) as descri be d i n 
t he Re g ul at i on ( Eur o pea n U ni o n ) g ui da nce N o 5 3 6/ 2 0 1 4
a n d W o rld Heal t h Or ga niz atio n 
g ui da nce. 4 0 ,4 1 T he v ol u me of  bl oo d dra w n d uri n g t he st u d y will n ot e xcee d 1 % of  T B V o ver 
2 4 h o urs or 3 % of  TB V o ver 4 wee ks f or a n y partici pa nt s at a n y visit s. Pl ease r efere nce t he L a b 
Fl o w c hart f or st u d y visit blo o d v ol u mes .
9. 4. 1 2. 1
H e m at ol o g y
Re d bl o o d cell c o u nt, t otal a n d differe ntial w hi te bl o o d cell (W B C ) c o u nt ( bas o p hils, e osi n o p hils, 
l y m p h oc ytes, m o n oc y t es, a n d ne utr o p hils), pl at elet c o u nt, he m o gl o bi n, he mat ocri t, mea n 
c or p usc ular v ol u me, mea n 
c or p usc ular he m o gl o bi n
a n d me a n c or p usc ular he m o gl o bi n 
c o nce ntrati o n, a n d E S R will be c o llecte d (see Secti o n 2 ). D uri n g t he treat me nt peri o d, partici pa n ts 
s h o uld mai ntai n a he m o gl o bi n le vel > 7. 0 g/ d L. F or partici pa n ts wi t h a he mo gl o bi n le vel
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
9 7
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
≤7. 0 g/ d L, t he I n vesti gat or s h o ul d c o ntact t he Cli nical Tri al Ph ysic ia n or desi g nee f or f urt her 
di sc ussi on. T ot al  WB C c o u nt a n d all  differe ntial W B C c o u nts will be bli n de d i nf or mati o n f or t he 
treati n g in vest i gat or aft er i nitiati on of  IP. Of  note, W B C, 
bas o p hil, e osi n o p hil, l y m p h oc yt e, 
m o n oc y te, a n d ne utr o p hil c o u nts will not be di s clos e d t o preser ve t he bli n d.
 
 
 
 
T he test res ults will n ot be discl ose d t o t he S p o ns or n or site pers o n nel d uri n g t he bli n de d p orti o ns 
of  the st u d y a n d t hr o u g h Wee k 1 2 of  the L T E Peri o d . Alerts f or o ut- of -ra n ge val ues will be fla g ge d 
f or t he site w hile kee pi n g t he n u merical res ults bli n de d.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
9 8
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
9. 4. 1 2. 2
C h e mi str y

F ull c he mistr y pa nel at Scree ni n g: S o di u m , p otassi u m , c hlori d e, calci u m, ma g nesi u m, 
p h os p hate, bl o o d urea nit r o ge n, gl u c ose, H b A 1c, al b u mi n, al kali ne p h os p hatase, creati ni ne, 
A L T, A S T, ga m ma gl uta m yl tra nsferase ( G G T), t otal bilir u bi n, di rect bilir u bi n, t otal 
c h o lester ol, trigl yceri des, hi g h -de nsit y li p o pr otei n, l o w-de nsit y li p o pr otei n, a n d 

All ot h er visits: S o di u m , p o tassiu m , c hlori de, calci u m, ma g nesi u m, p h os p hate, bl o o d urea 
nit r o ge n, al b u mi n, al kali ne p h os p hatase, creati ni ne, A L T, A S T, G G T, t otal bilir u bi n, di rect 
bilir u bi n, a n d 
. T ot al c h olest er ol, trigl yceri des, hi g h -de nsit y li p o pr otei n, a n d l ow- de nsit y 
li p o pr otei n will be i ncl u de d at t he  
 E T visit.
 
 
 

T he in vesti gat or s h o ul d esta blis h ca usalit y. A d di tio nal  testi n g ma y 
be nee de d, i n 
c o ns ultati o n wit h t he Cli nical Trial P h ysicia n or desi g nee , w hic h ma y incl u de c oa g ul at i on 
pa nel, viral he pat itis ser olo g y , a nti n uclear a n d a nti-s mo ot h m uscle a nt i b o dies, I g G le vels, 
a n d a n a b d o mi nal ultras o u n d.

Uri nal ysis: Le u k oc y tes, s pecific gra vit y,  bilir u bi n, bl o o d, gl uc ose, ket o nes, p H, pr otei n, a n d 
ur o bili n o ge n 
9. 4. 1 2. 3
S er ol o g y
Testi n g will be p erf or m e d at Scree ni n g t o deter mi ne t he parti ci pa nt ’s i m m u ne stat us wit h res pect 
t o t he f oll o wi n g viral i nfecti ons:

V Z V

A V Z V tit er ma y be per f or me d t o deter mi ne w het her t he parti ci pa nt has i m m u nit y ( p osi tive
res ult f or V Z V I g G a nt i b o d y). If VZ V a nt i b o d y titer is ne gati ve, t he partici pa nt ma y c h o ose 
t o recei ve V Z V vacci nat i on i n or der t o q ualif y f or t he st u d y. If t he part ici pa nt recei ves a 
V Z V vacci nati o n, ra n d omizat i on ( Da y ) ca n occ ur at  a mi ni m u m of  30 da ys aft er 
vacci na tio n has bee n a d mi nister e d.

HI V

A HI V a nti b o d y t est will be p erf or me d. Parti ci pa nt s testi n g p osi tive f or HI V ( E LI S A test 
res ult, c o nfir me d b y Wester n blot) will be e xcl u de d fr o m t he trial. 

H A V

A n a nti-he pat itis A vir us ( H A V) a nt i b o d y (a nti-H A V I g M) test w ill be p erf or m e d. 
P arti cipa nt s testi n g p osi tive will  be e xcl u de d fr o m t he trial, u nless t he y are i n dicati ve of 
pri or h e patitis A, t hat is c o nsi dere d c ure d a n d acc o m pa nie d b y n or m al li ver tra nsa mi nase 
val ues.

He pati tis B Vir us (H B V )

H e patitis B s urface ( H Bs) a nt i ge n a n d he pat itis B cor e ( H Bc) a nti b o d y test will b e 
perf or m e d.

P arti cipa nt s w h o test p osit i ve f or H Bs a nti ge n will be e xcl u de d fr om t he trial.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
9 9
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d

F or partici pa nt s w h o 
t est p osit i ve o nl y  for a nt i b o d y to H Bc 
a nti ge n, a n H B V 
de o x y rib o n ucleic aci d ( D N A ) t est m ust be perf or me d.

If t he H B V D N A test is ne gati ve ( wit h o ut a nti-viral t hera p y) a n d t he L F Ts are n or mal, t he 
parti ci pa nt will be eli gi ble f or t his trial. T hese parti ci pa nt s will u n der g o p eri o dic 
m o nit ori n g f or H B V D N A d uri n g t he trial.

He pati tis C Vir us (H C V )

A H C V a nt i b o d y (a nti-H C V I g G or I g M) test will be perf or m e d.

P arti cipa nt s testi n g p osi tive f or H C V a nti b o d y an d a p osi tive c o nfir mat or y test will b e 
e xcl u de d fr o m t he trial.
9. 5
P h ar m a c o ki n eti c s
Bl o o d sa m ples will be c ollecte d i n v ol u mes a p pr o priate f or c hil dre n acc or di n g t o t he f oll o wi n g 
sc he d ule 
A d dit i onal sa m ples are t o be c ollecte d at E T a n d t he 
 S afet y F ol l ow- u p visi ts.
Pl ease refere nce t he La b Fl o w c hart f or st u d y visit bl o o d sa mple v o l umes.
I n t he L T E Perio d, bl o o d sa m ple s f or P K s h o uld be c oll e ct e d after e ver y a p pr o xi matel y 1 year of 
treat me nt wit h oza ni m o d, o n t he sa me d a y  as a pla n ne d he mat ol o g y  an d st o ol col lecti on. 
O ne sa m ple s h o uld be c oll ecte d at a n y ti me p ost-d ose.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 0 0
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Pl as ma c o nce ntrati o ns o f oza ni m o d, C C 1 1 2 2 7 3 , a n d C C 1 0 8 4 0 3 7 will be deter mi ne d i n t he bl o o d 
usi n g a vali date d bi oa nal yt ical met h o d. T he c o nce ntratio n -ti me data of oza ni m o d a n d C C 1 1 2 2 7 3 
will be e val uate d usi n g t he 
Treat me nt assi g n me nts will  be release d t o t he bi oa nal yt ical la b orat or y in or der t o mi ni mize 
u n necessar y  a nal ysis a n d/ or rea nal ysis of P K sa m ples.
C o nce ntrati o n a nal yses f or oza ni m o d will  be perf or me d b y vali date d bi oa nal ytical met h o d(s).
Bi oa nal y tic al sa m ples desi g nate d f or assess me nts 
 fr o m 
t he sa me c ollecti o n ti me p oi nt ma y be use d i nterc ha n gea bl y f or a nal yses, if re q uir e d 
 
 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 0 1
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 0 2
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
9. 8
A d diti o n al R e s e ar c h
T his pr ot oc ol will i ncl u de
 f or a d ditio nal  researc h.
F or All S ites:
A d dit i onal researc h is re q uire d f or all st u d y p artici pa nts, e xce pt w here pr o hi bit ed b y I R Bs/et hics 
c o m mittees, pr o hi bite d b y l ocal la ws or re g ulat i ons, or aca de mic/i nst ituti o nal re q ui re me nts.

If t he I R B/et hics c o m mittees a n d sit e a gree t o t he ma n dat or y  ad di tio nal  researc h rete ntio n 
a n d/ or c o llecti on, t he n t he st u d y partici pa nt m ust a gree t o t he ma n dat or y  ad di tio nal  researc h 
as a re q uir e me nt for i ncl usi o n  in t he st u d y .

If o pti o nal parti ci pat i on is p er m itte d a n d a p pr o ve d, t he n t he st u d y p artici pa nts ma y o pt o ut of 
t he a d ditio n al  researc h rete nti on a n d/ or c ollect i on.
A d dit i onal
researc h is i nte n de d t o e x pa n d t he researc h a n d de vel o p me nt
ca pa bilit y at  
Bri st ol-M yers S q ui b b a n d will s u p p ort as yet u n defi ne d researc h ai ms t hat will a d va nce o ur 
u n dersta n di n g of  disease a n d o pti o ns f or treat me nt. T his ma y als o i ncl u de ge netic/ ge n o mic 
e x pl orat i on ai me d at e x pl ori n g disease pat h wa ys, pr o gressi o n a n d res p o nse t o treat me nt , et c.
S a m ple C ollecti o n a n d St or a ge
 
S a m ples ke pt f or f ut ure researc h will  be st ore d at t he B M S Bior e p osi t or y in 
 or 
a n i n de pe n de nt, B M S-a p pr o ve d st ora ge ve n d or.
T he ma n a g er of  t hese sa m ples will e ns ur e t h e y are pr o perl y use d t hr o u g h o ut t heir usa ble life a n d 
will destr o y  the sa m ples at t he e n d of  the sc he d ule d st ora ge peri o d, n o l on ger t ha n fiftee n ( 1 5) year s 
after t he e n d of t he st u d y or t he ma xi m u m all o wed b y  a p plica ble la w.
Tra nsfers of sa m ples b y S p o ns or t o t hir d parties will be parti ci pa nt t o t he reci pie nt’s a gree me nt t o 
esta blis h si milar st ora ge pr oce d ures.
S a m ples will be st ore d i n a c o de d fas hi o n, a n d n o researc her will ha ve access t o t he ke y . T he ke y 
is sec urel y hel d b y t he i n vestigat or at t he cli nical  site, s o t here is n o direct a bilit y for a researc her 
t o c o n nect a sa m ple t o a s pecific i n di vi d ual.
F urt her details of  sa m ple c ollecti o n a n d pr ocessi n g will be pr o vi de d t o t he sit e i n t he pr oce d ure 
ma n u al .
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 0 3
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
9. 9
H e alt h E c o n o mi c s O R M e di c al R e s o ur c e Utili z ati o n a n d H e alt h 
E c o n o mi c s
Heal t h ec o n o mics/ m e dical res o urce u tilizati on a n d h e alt h ec o n o mics
para meters will n ot be 
e val uate d i n t his st u d y.
1 0
S T A TI S TI C A L C O N SI D E R A T I O N S
1 0. 1
St ati sti c al H y p ot h e s e s
N o pr os pecti ve h y p ot heses are bei n g f or mall y e val uate d.
1 0. 2
S a m pl e Si z e D et er mi n ati o n 
T he P C D AI sc ore is hi g hl y  corr el ate d wit h C D AI sc ore4 2 , t heref ore gi ve n t he lac k of  data o n 
P C D AI cli nical re missi o n, C D AI cli nical re missi o n is use d t o deter mi ne sa m ple size of t he c urre nt 
pe di atric st u d y. Cli nical re missi o n rates refere nce d bel o w are base d o n C D AI. 
Ass u mi n g t he tr u e pr o p orti o n of  cli nical re missi on rate is 2 1. 7 % at Wee k 6 4 f or all t he pe di atric 
parti ci pa nt s (a ges 2 t o 1 7 years) recei vi n g eit her oza ni m o d 0. 4 6 m g or 0. 9 2 m g/ da y, 1 0 0 e val ua ble 
parti ci pa nt s will pr o vi de 9 0 % pr o ba bilit y t o clai m t he est i mate d l ower 9 5 % CI b o u n d of  cli nical 
re missi o n rate is grea t er t ha n 9. 4 %. T he ass u m pt i on of  21. 7 % cli nical re missi on rate at Wee k 6 4 
is base d o n t he est i mate d cli nical re missi on rate at Wee k 5 2 fr om a n o pe n -la bel P hase 2 cli nical 
trial (R P C 0 1 -2 2 0 1). T he esti mate d r at e of 9. 4 % cli nical re missi on f or place b o is base d u p o n t he 
u p per b o u n d of 9 5 % Wal d CI of t he cli nical
re missi on rate fr o m a pri or trial usi n g a si milar st u d y 
desi g n a n d i ncl usi o n cri t eria i n a d ult parti ci pa nt s with acti ve C D .4 3
I n a d ditio n, acce pta bl e c o n versio n  fact ors ha ve bee n use d t o c o n vert t he C D AI cli nical re missi o n 
( C D AI < 1 5 0) rate t o P C D AI cli nical re missi on ( P C D AI < 1 0) rate.4 4 Ba se d o n a c o n versi on fact or 
of  1. 3 8, a sa m ple size of  1 0 0 partici pa nts will pr o vi de a pr o ba bilit y of  7 3 % t o clai m t he esti mate d 
l ower 9 5 % CI b o u n d of  o za ni mo d pe diatri c cli nical re missio n rate ( 1 5. 8 % as c o n verte d fr o m 
2 1. 7 % C D AI cli nical re missio n  rate) is greater t ha n t he pl ace b o pe di atric cli nical re missio n  rate 
( 6. 8 % as c o n verte d fr o m 9. 4 % C D AI cli nical re missi on rate ). 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 0 4
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
T o acc o u nt f or partici pa nt dr o p -o ut d uri n g t he st u d y, t he stu d y pla ns t o e nr oll a p pr o xi matel y 
partici pa nt s.
Half wi dt h ( precisio n ) a n d t he e x pecte d l ower a n d u p per b o u n d of  the 9 5 % Wal d 
CI of  the 
esti mate d cli nical re missi o n rate f or o verall a n d 
 are pr o vi de d i n Ta ble 1 0. 2 - 1.
T a ble 1 0. 2 -1 :
S a m ple Sizes t o E v al u ate Wee k 6 4 Cli nic al Re missi o n ( C D AI < 1 5 0) 
R ates
S a m ple S ize
Precisi o n ( H alf -
wi dt h of
9 5 % CI a)
E x pecte d L o wer 
B o u n d of 9 5 % CI a
of O z a ni m od
E x pecte d U p per 
B o u n d of 9 5 % CI a
of O z a ni m o d
O verall
1 0 0
8. 1 %
1 3. 7 %
2 9. 8 %
A b bre viati o ns: C D AI, Cr o h n’s Disease Acti vit y I n de x; CI, c o nfi de nce i nter val.
a
CI o btai ne d ass u mi n g a n esti mate d oza ni m o d Wee k 6 4 cli nical re missi o n ( C D AI < 1 5 0) rate of 2 1. 7 %. T he n or mal 
a p pr o xi mati o n f or c o nstr ucti n g t he 9 5 % CIs m a y  pr o d uce a n u n us uall y c o nser vati ve l o wer b o u n d f or sa m ple sizes 
u n der 1 0 0.
F or t he c o -pri mar y e n d p o i nt of en d osc o pi c remissi o n at Wee k 6 4, Ta ble 1 0. 2 - 2 pr o vi des half wi dt h 
( precisio n ) a n d t he e x pecte d l o wer a n d u p per b o u n d of 9 5 % Wal d CI of t he esti mate d e n d osc o pic 
r emissi o n
rate f or o verall partici pa nts a n d 
 T he 
calc ulati o n assu mes
a 5. 8 % e n d osc o pic re missi o n rate f or t he oza ni m o d ar ms ( eit her d ose gr o u p), w hic h is t he 
esti mate d oza ni m o d e n d osc o pic re missi o n rate i n st u d y R P C 0 1- 2 2 0 1.
T a ble 1 0. 2 - 2: 
S a m ple Sizes t o E v al u ate Wee k 6 4 E n d osco pic Re missi o n R ates
S a m ple S ize
Precisi o n 
( H alf-wi dt h of
9 5 % CI) a
E x pecte d 
L o wer
B o u n d of 9 5 % 
CI a
of O z a ni m o d
E x pecte d 
U p per
B o u n d of 9 5 % 
CI a
of O z a ni m o d
O verall
1 0 0
4. 6 %
1. 2 2 %
1 0. 4 %
A b bre viati o ns: CI, c o nfi de nce i nter val.
a
CI o btai ne d ass u mi n g a n esti mate d oza ni m o d Wee k 
6 4 e n d osc o pic r emissi o n
rate of 5. 8 %.
T he n or mal 
a p pr o xi mati o n f or c o nstr ucti n g t he 9 5 % CI s ma y pr o d uce a n u n us uall y c o nser vati ve l o wer b o u n d f or sa m ple sizes 
u n der 1 0 0.
F or t he e n d p o i nt of  pr o p ortio n of  parti ci pa nts ac hie vi n g cli nical re missio n  (C D AI
< 1 5 0) at  
Wee k
1 2, Ta ble 1 0. 2 - 3 pr o vi des hal f wi dt h ( precisi o n) a n d t he e x pecte d l o wer a n d u p per b o u n d of 
9 5 % Wal d CI of  the est i mate d cli nical re missi on rate f or o verall parti ci pa nt s a n d
 
T he calc ulat i on ass u mes a 3 3. 3 % cli nical re missi on rate f or t he oza ni m o d ar ms ( eit her d ose gr o u p) , 
w hic h is t he est i mate d oza ni m o d cli nical re missi on rate i n st u d y  R P C 0 1- 2 2 0 1.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 0 5
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
T a ble 1 0. 2 - 3:
S a m ple Sizes t o E v al u ate Wee k 1 2 Cli nic al Re missi o n ( C D AI < 1 5 0) 
R ates
S a m ple S ize
Precisi o n ( H alf -
wi dt h of
9 5 % CI a )
E x pecte d L o wer
B o u n d of 9 5 % 
CI a
of O z a ni m o d
E x pecte d U p per
B o u n d of 9 5 % CI a
of O z a ni m o d
O verall
1 0 0
9. 2 %
2 4. 1 %
4 2. 6 %
A b bre viati o ns: C D AI, Cr o h n’s Disease Acti vit y I n de x; CI, c o nfi de nce i nter val.
a
CI o btai ne d ass u mi n g a n esti mate d oza ni m o d Wee k 1 2 cli nical re missi o n ( C D AI < 1 5 0) rate of 3 3. 3 %. T he n or mal 
a p pr o xi mati o n f or c o nstr ucti n g t he 9 5 % CI s ma y pr o d uce a n u n us uall y c o nser vati ve l o wer b o u n d f or sa m ple sizes 
u n der 1 0 0.
T he a nal yses of  t he k e y  sec o n dar y e nd p oi nt (e g, pe diatric cli nical re missio n  at W ee k 1 2) will be 
c o n d ucte d i n t he si milar ma n ner as t he c o -pri mar y e n d p o i nt (e g, pe diatric cli nical re missi on at 
Wee k 6 4). Details will be
descri be d i n t he S t atistical Anal ysis P la n (S A P ).
 
 
 
 
 T he met h o d of 
sa m ple size deter mi nat i on f or P K e val uat i on i n t his st u d y is base d o n pre vi o usl y p u blis he d 
met h o ds .4 5
1 0. 3
A n al y si s S et s
F or t he p ur p oses of  a nal ysis, the f oll owi n g p o p ul atio n s are defi ne d:
T a ble 1 0. 3 - 1:
P o p ul ati o ns f or A n al ysis
P o p ul ati o n
Descri pti o n
I nte nt-t o-Treat
T he I T T a nal ysis p o p ulati o n will c o nsist of all ra n d o mize d partici pa nt s fro m t he 
scree ne d a nal ysis p o p ulati o n t hat recei ve at least 1 d ose of I P. Par tici pa nts i n 
t he I T T a nal ysis p o p ulati o n will be a nal yze d acc or di n g t o t he ra n d o mize d 
treat me nt, re gar dless of t he treat me nt recei ve d.
Safet y
T he safet y a nal ysis p o p ulati o n is defi ne d as all partici pa nt s w ho ar e ra n d o mize d 
a n d recei ve at least 1 d ose of I P, a nal yze d b y act ual treat me nt recei ve d.
P K
T he P K p o p ulati o n will c o nsist of I T T partici pa nt s w h o ha ve at least 1 p ost -
Scree ni n g P K assess me nt.
Ra n d o mize d
All partici pa nts w h o were ra n d o mize d usi n g I R T .
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 0 6
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
T a ble 1 0. 3 - 1:
P o p ul ati o ns f or A n al ysis
P o p ul ati o n
Descri pti o n
Per -pr ot oc ol
T he P P p o p ulati o n will c o nsist of all partici pa nt s i n t he I T T p o p ulati on. T h ose 
partici pa nt s w h o ha ve s pecific reas o ns f or warra nti n g e xcl usi o n fr o m t his 
p o p ulati o n w ill be d oc u me nte d pri or t o data base l oc k a n d ma y i ncl u de b ut are 
n ot li mite d t o pr ot oc ol d e viati o ns t hat s u bsta ntiall y affect t he ke y  efficac y 
e n d p oi nt.
A b br e viati o ns: I P, i n vesti gati o nal pr o d uct; I R T, i nte grate d res p o nse tec h n ol o g y; I T T, i nte nt-t o-treat; P K, 
p har mac o ki netic; P P, per -pr ot oc ol.
T he pri mar y a nal ysis p o p ulat i on f o r all efficac y e n d p oi nts will be t he i nte nt -t o-treat (I T T) a nal ysis 
p o p ul at i on. All safet y a nal yses will be carrie d o ut o n t he Safet y p o p ul atio n. T he P K a nal yses will 
be carrie d o ut o n t he P K p o p ul atio n. T he selecte d efficac y/safet y a nal ysis will be carrie d o ut o n 
t he P P p o p ulat i on as s pecifie d.
P arti cipa nt de m o gra p hics will  be s u m marize d f or t he I T T p o p ulat i on a n d will i ncl u de a ge, se x, 
race, et h nicity, hei g ht, wei g ht, a n d B MI .
Baseli ne c haracteristics will be s u m marize d f or t he I T T p o p ulat i on a n d will i ncl u de a ge at C D 
s y m pt o m o ns et, a ge at  CD dia g n osis, years si nce C D s y m pt o m o nset, ye ars si nce C D dia g n osi s, 
pri or a nti-T N F use, c o rtic oster oid use at Scree ni n g, c o nc o mita nt C D me d icati on use at Baseli ne, 
eac h c o mp o ne nt of  t he C D AI sc ore, a n d P C D AI. Parti cipa nt s s h o uld c o nti n ue t o be assesse d f or 
P C D AI t hr o u g h o ut t he trial, re gar dless of a ge c ha n ge.
C o m plia nce wi t h ra n d o mize d I P will be s u m marize d a n d will i ncl u de t he n u m ber of  partici pa nt s 
esti mate d t o be < 8 0 % c o mplia nt, 8 0 % t o 1 0 0 % c o mplia nt, > 1 0 0 % c o m p lia nt, a n d > 1 2 0 %
c o mplia nt.
1 0. 4
St ati sti c al A n al y s e s
1 0. 4. 1
G e n er al C o n si d er ati o n s
T his is a gl o b al, m ult ice nter, ra n d o mize d, d o u ble -bli n d P h ase 2/ 3 st u d y to e v al uate t he efficac y, 
safety, a n d t olera bilit y of  oza ni m o d i n pe diatri c parti ci pa nt s a ge d 2 t o 1 7 years i ncl usi ve wi t h 
m o deratel y  to se verel y act i ve C D, defi ne d as a P C D AI sc ore of  ≥ 3 0, S E S -C D sc ore 
of ≥6 ( or S E S -C D ≥ 4 i n parti cipa nts wit h is olate d ileal disease) , wit h a n i na de q uate res p o nse,
i ntol era nce, or l oss of  res p o nse t o c o n v e ntio nal  t h er a p y for C D. T h e st u d y will als o e val uate t he 
P K a n d P D a n d e val uate t he safet y of  oza ni mo d i n pe di atric parti ci pa nt s.
A nal ysis details n ot e x plai ne d i n t he statist ical sectio n  of t he pr ot oc ol will be pr o vi de d i n t he S A P 
a n d P K A nal ysis Pla n.
T he detaile d defi nit i ons of  all e fficac y e n d p o i nts are descri be d i n Sect i on 4 . Efficac y will  be 
e val uate d base d o n t he t otalit y of t he data a n d a c o mpre he nsi ve a nal ysis base d o n descri pt i ve 
statistics. H y p ot hesis testi n g will n ot be perf or me d.
T he n u m ber a n d perce nta ge of parti ci pa nts i n eac h p o p ul at i on will be s u m marize d. Patie nt  
d is p ositi on, i ncl u di n g t he n u m ber of  parti ci pa nt s scree ne d, ra n d omize d, d ose d, c o mplet i n g 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 0 7
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Wee k
6 4, a n d n ot c o m p leti n g Wee k 6 4 ( o verall a n d b y reas o n f or dr o p o ut) , will be s u m marize d 
f or t he I T T p o p ulatio n.
1 0. 4. 2
Pri m ar y E n d p oi nt( s)
T he pri mar y  a nal yses of  t he 2 c o- pri mar y e n d p o i nts, pe diatric cli nical a n d e n d osc o pic re missi on 
at W ee k 6 4, will be base d o n t he I T T p o p ulat i on i n w hic h all 
 will be 
p o ol e d. T he est i mate d pr o p orti o ns alo n g wi t h their ass ociate d 2- side d 9 5 % Wal d CI usi n g a n or mal 
a p pr o xi mat i on f or a si n gle sa m ple pr o p orti o n will be c o nstr ucte d. S u m mar y statistics o n t he 
n u m ber of e ve nts, sa m ple size, a n d pr o p orti o ns f or t he o verall gr o u p a n d b y 
 
will als o be pr o vi de d.
F or partici pa nts w h ose pe di atric cli nica l a n d e n d osc o pic re missi on at W ee k 6 4 ca n n ot be 
a de q uatel y deter mi ne d (incl u di n g missi n g data, disc o nti n uat i on, or l ost t o f oll ow- u p), t heir missi n g 
pe di atric cli nical a n d e n d osc o pic re missi o n will be i m p ute d usi n g a n o n-res p o n der i m p utati o n. 
I n a d ditio n t o t he pri mar y o verall  anal ysis, a s u b gr o u p a nal ysis will be c o n d ucte d f or eac h of  
 A s u m mar y will  be ta b ulate d a n d a f orest pl ot s h o wi n g t he pr o p orti o ns wi t h 
ass ociate d 9 5 % CIs will be pr o d uce d.
Details o n t he a nal yses a n d t he e val uat i ons f or t he c o-pri mar y e n d p o i nts will be pr o vi de d i n t he 
S A P, w hic h will i ncl u de c o mparis o ns wi t h the e xt er nal place b o c o ntr ols as well as data fr om 
o za ni m o d C D a d ult tr ials.
1 0. 4. 3
S e c o n d ar y E n d p oi nt( s)
T he a nal yses of  t he k e y  sec o n dar y e nd p oi nt (e g, pe diatric cli nical re missio n  at W ee k 1 2) will be 
c o n d ucte d i n a si milar ma n ner as t he c o-pri mar y e n d p o i nt. 
 
 
 
 
 
1 0. 4. 5
Ot h e r S af et y A n al y s e s
All parti ci pa nt s w h o ta ke at least 1 d ose of I P will be i ncl u de d i n t he safet y a nal yses. A Es will be 
s u m marize d b y w orst se verity gra de. A Es , wit h parti c ular f oc us o n T E A Es, will be s u m marize d 
usi n g t he Me dical Dict i onar y  for R e g ul at or y Acti vit ies s yste m or ga n class a n d preferre d ter m.
T he i nci de nce of  TE A Es, I P-relate d T E A Es, T E A Es lea di n g t o disc o nt i n uati on fr om treat me nt, 
e ve nts assesse d as C o m m o n Ter mi n o l og y  Criteria f or A d verse E ve nts ( C T C A E) Gra de 3 or 
Gra de 4 ( or m o derate/se vere if ot her rati n g scale is use d), S A E, a n d A E SIs (see Secti on 9. 2. 9 ) will 
be s u m marize d f or 
 T h e i nci de nce of  T E A Es b y se verit y an d b y 
r elat i ons hi p t o stu d y dr u g will als o be s u m marize d. S A E s will be prese nte d b y 
 
 a n d b y relati ons hi p t o st u d y dr u g. S u m mar y  ta bles will prese nt i nci de nce est i mates a n d 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 0 8
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
i n di vi d ual e ve nt rates b y s yst e m or ga n class as well as wi t hi n eac h s yste m or ga n class. 
P arti cip a nts e x perie nci n g a n e ve nt m ore t ha n o nce wit h var yi n g se verit y w ill be c o u nte d o nl y o nce 
wi t h the ma xi m u m se verity wi t hi n eac h s yste m or ga n class/ preferre d t er m. F or i nci de nce of 
r elat i ons hi p t o st u d y  dr u g, parti ci pa nt s will be c o u nte d o nl y o nce, i n t he cate g or y of t he str o n gest 
r elat i ons hi p t o stu d y dr u g wi t hi n eac h s yste m or ga n class/ preferre d t er m. B y -part ici pa nt listi n gs 
of  deat h a n d A E s lea di n g t o deat h will be pr o vi de d.
La b orat or y  values, vital si g ns, a n d E C G data will be prese nte d i n a p pr o priate s u m mar y  ta bles.
Cr oss ta b ulati o ns will be pr o vi de d t o s u m marize fre q ue ncies of a b n or malit ies.
Descri pt i ve statistics will be pr o vi de d f or vital si g n a n d b o d y wei g ht data.
B y -part ici pa nt listi ngs will be pr o vi de d f or all rele va nt safet y data.  Gra p hical dis pla ys a n d fi g ures 
will be pr o vi de d w here usef ul t o assist i n t he i nter pretati o n of res ults.
1 0. 4. 6
Ot h er A n al y s e s 
 
 
 
 
 
 
 
1 0. 4. 6. 2
S c ori n g Al g orit h m s
Detaile d al g orit h ms o n h o w t o c o m p ute t he C D AI sc ores a n d s u bsc ores are pr o vi de d i n t he S A P.
1 0. 4. 6. 3
E sti m a n d Fr a m e w or k
F or eac h ke y  efficac y e nd p oi nt (i e, pri mar y efficac y e nd p oi nt a n d sec o n dar y  efficac y e n d p o i nts), 
t he fol l owi n g pri mar y esti ma n d is s pecifie d f oll owi n g t he fi nal versi o n of  I C H E 9 ( R 1) g uida nce 
( A d o pte d in Ma y 2 0 2 1). Ot her details o n est i ma n d will be pr o vi de d i n t he S A P.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 0 9
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Tre at me nt C o n diti o n of I nterest
A d ult e q ui vale nt d oses of 0. 4 6 m g a n d 0. 9 2 m g of  oza ni m o d will be e val uate d 
 
 0. 4 6 m g a n d 0. 9 2 m g a d ult 
e q ui vale nt d oses will be deter mi ne d 
 
 
T he parti ci pa nt s are all o we d t o ta ke c o nc o mita nt me dicat i ons (see Sect i on 7. 7 ) b ut are pr o hi bite d 
fr om ta ki n g s o me me dicat i ons (see Secti o n 7. 7. 2 ).
P o p ul ati o n of P artici p a nts
P e di atric parti ci pa nt s a ge d 2 t o 1 7 years, i ncl usi ve, wit h m o deratel y t o se verel y act i ve C D with a n 
i na de q uate res p o nse, l oss of  res p o nse, or i nt olera nce t o pri or t h era p y f or C D are e nr olle d i n t his 
st u d y.
T a ble 1 0. 4. 6. 3 - 1:
V ari a bles t o be O bt ai ne d f or E ac h P artici p a nt
Me as ure
E n d p oi nt
Pri m ary – Effic acy
P C D AI re missi o n
Pr o p orti o n of partici pa nt s wh o ac hie ve P C D AI < 1 0 at Wee k 6 4
S E S -C D e n d osc o pic 
remissi o n
Pr o p orti o n of partici pa nts ac hie v i n g S E S -C D ≤ 2 or S E S -C D ≤ 4 p oi nts wit h n o 
S E S -C D s u bsc ore > 1 p oi nt at Wee k 6 4
Sec o n d ary – Effic acy ( Key)
P C D AI re missi o n
Pr o p orti o n of partici pa nt s wh o ac hie ve P C D AI < 1 0 at Wee k 1 2
Sec o n d ary – Effic acy ( Ot her)
S E S -C D e n d osc o pic 
res p o nse
Pr o p orti o n of partici pa nts w h o ac hie ve a S E S -C D decrease fr o m Baseli ne of ≥5 0 % 
( E R-5 0) at Wee k 6 4
Pr o p orti o n of partici pa nts w h o ac hie ve a S E S -C D decrease fr o m Baseli ne of ≥ 5 0 % 
( E R-5 0) at Wee k 1 2
P C D AI cli nic al res p o nse
Pr o p orti o n of partici pa nts w h o ac hie ve a decrease fr o m B aseli ne i n P C D AI 
sc ore ≥1 2. 5 a n d a t otal P C D AI sc ore of < 3 0 p oi nts at Wee k 6 4
Pr o p orti o n of partici pa nts w h o ac hie ve a decrease fr o m B aseli ne i n P C D AI 
sc ore ≥1 2. 5 a n d a t otal P C D AI sc ore of < 3 0 p oi nts at Wee k 1 2
Sy m pt o m atic re missi o n 
( a d olesce nts o nly)
Pr o p orti o n of partici pa nt s wh o ac hie ve a n a vera ge dail y a b d o mi nal pai n sc ore 
≤1 p oi nt a n d a vera ge dail y st o ol fre q ue nc y ≤3 p oi nts wit h a b d o mi nal pai n a n d st o ol 
fre q ue nc y n o w orse t ha n B aseli ne at Wee k 6 4
Pr o p orti o n of partici pa nts w h o ac hie ve a n a vera ge dail y a b d o mi nal pai n sc or e 
≤1 p oi nt a n d a vera ge dail y st o ol fre q ue nc y ≤3 p oi nts wit h a b d o mi nal pai n a n d st o ol 
fre q ue nc y n o w orse t ha n B aseli ne at Wee k 1 2
Sy m pt o ms over ti me
C ha n ge f r om B aseli ne i n st o ol fre q ue nc y sc ore o ver ti me
C ha n ge f r om B aseli ne i n a b d o mi nal pai n o ver ti me
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 1 0
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
T a ble 1 0. 4. 6. 3 - 1:
V ari a bles t o be O bt ai ne d f or E ac h P artici p a nt
Me as ure
E n d p oi nt
C D AI cli nic al re missi o n 
( a d olesce nts o nly)
Pr o p orti o n of partici pa nts w h o ac hie ve C D AI sc ore < 1 5 0 at Wee k 6 4
Pr o p orti o n of partici pa nts w h o ac hie ve C D AI sc ore < 1 5 0 at Wee k 1 2
C D AI cli nic al res p o nse 
( a d olesce nts o nly)
Pr o p orti o n of partici pa nts w h o ac hie ve C D AI re d ucti o n fr o m B aseli ne of ≥ 1 0 0 
p oi nts or C D AI sc ore < 1 5 0 at Wee k 6 4
Pr o p orti o n of partici pa nts w h o ac hie ve C D AI re d ucti o n fr o m B aseli ne of ≥1 0 0 
p oi nts or C D AI sc ore < 1 5 0 at Wee k 1 2
C ortic oster oi d -free 
re missi o n
Pr o p orti o n of partici pa nts w h o ac hie ve a P C D AI sc ore < 1 0 at Wee k 6 4 w hile 
re mai ni n g c ortic oster oi d free i n t he pri or 1 2 wee ks
Pr o p orti o n of partici pa nts w h o ac hie ve a C D AI sc ore < 1 5 0 at Wee k 6 4 w hile 
re mai ni n g c ortic oster oi d free i n t he pri or 1 2 wee ks (a d olesce nts o nl y)
E n d osc o pic re missi o n 
Pr o p orti o n of partici pa nts ac hie vi n g S E S -C D < 2 or S E S -C D ≤4 p oi nts wit h n o 
S E S -C D s u bsc ore > 1 p oi nt at Wee k 1 2
A b bre viati o ns: C D AI , Cr o h n’s Disease Acti vit y I n de x; E R -5 0, S E S -C D decrease fr o m Baseli ne of ≥ 5 0 % ; P C D AI ,
Pe diatric Cr o h n’s Disease Acti vit y I n de x; S E S -C D , Si m ple E n d osc o pic Sc ore f or Cr o h n’s Disease .
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 1 1
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
P o p ul ati o n -Le vel S u m m ar y
F or eac h of  t he pri mar y a n d sec o n dar y efficac y en d p oi nts, t he a nal ysis will  be base d o n t he I T T 
p o p ul at i on i n w hic h 
 will be p o ol e d. T he esti mate d pr o p orti o n 
alo n g wi t h its ass ociate d 2-side d 9 5 % Wal d CI usi n g a n or m al a p pr o xi mat i on f or a si n gle sa m ple 
pr o p orti o n will be c o nstr ucte d.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 1 2
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
1 1
R E F E R E N C E S
 
 
 
2
Sa n d b or n WJ, Fea ga n B G, W olf D, et al . Oza ni mo d i n d uct i on a n d ma i nte na nce treat me nt for 
ul cerat i ve c olitis. N E n gl J Me d 2 0 1 6; 3 7 4: 1 7 5 4-6 2.
3
Sa n d b or n W, D’ Hae ns G R, W o lf D C, et  al. Oza ni m o d as i n d ucti on t hera p y in m o de rate t o 
se vere ul cerati ve c o litis: res ults fr o m the P hase III, ra n d o mize d, d o u bl e- bli n d, pl ace b o -
c o ntr olle d tr ue n ort h st u d y. 2 0 2 0; 8( 1 0): 1 2 5 8-1 2 7 5.
4
La kat os P L. Rece nt tre n ds i n t he e pide mi ol o g y  of infla m mat or y  bo w el  diseases: u p or d o w n? 
W o rld J Gastr oe nter ol 2 0 0 6; 1 2: 6 1 0 2 -8.
5
Sc h wartz D A, L oft us E V Jr, Tre m ai ne W, et  al. The nat ural hist or y  of fist ulizi n g Cr o h n's 
di sease i n Ol mste d C o u nt y, Mi n nes ota. Gastr oe nter ol o g y 2 0 0 2; 1 2 2: 8 7 5-8 0.
6
P e y rin- Bi r o ulet L, L oft us E V Jr, C o l om bel J F, et al. T he nat ural  hist or y of a d ult Cr o h n's 
di sease i n p o p ulat i on- base d c o h orts. A m J Gastr oe nter ol 2 0 1 0; 1 0 5: 2 8 9 - 9 7.
7
Ha na uer S B, Fea ga n B G, Lic hte nstei n G R, et al. Mai nte na nce i nfli xi ma b f or Cr o h n's disease: 
t he A C C E N T I ra n d o mise d trial. La ncet 2 0 0 2; 3 5 9: 1 5 4 1- 9.
8
C ol o m bel J F, Sa n d b or n WJ, 
R ut geerts P, et al.  Adali m u ma b f or ma i nte na nce of  cli nical 
res p o nse a n d re missio n i n patient s wit h Cr o h n's disease: t he C H A R M tri al. Gastr oe nter olo g y 
2 0 0 7; 1 3 2: 5 2 - 6 5.
9
Sa n d b or n WJ, Fea ga n B G, St oi n o v S, et al. Cert oliz u ma b pe g o l f or t he treat me nt of  Cr o h n's 
di sease. N E n gl J Me d 2 0 0 7; 3 5 7: 2 2 8- 3 8.
1 0
Sa n d b or n WJ, Fea ga n B G, R ut geerts P, et  al. Ve d oliz u ma b as i n d ucti on a n d mai nte na nce 
t hera p y for Cr o h n's di sease. N E n gl J Me d 2 0 1 3; 3 6 9: 7 1 1- 2 1.
1 1
Fea ga n B G, Sa n d b or n WJ, Gasi n k C, et al. Uste ki n u ma b as i n d uct i on a n d mai nte na nce t hera p y 
f or Cr o h n's disease. N E n gl J Me d 2 0 1 6; 3 7 5: 1 9 4 6- 6 0.
1 2
R ose n M J, D ha wa n A, Saee d S A . I nfla m mat or y bo w el  disease i n c hil dre n a n d ad ol esce nts. 
J A M A Pe diatr 2 0 1 5;1 6 9: 1 0 5 3 – 6 0.
1 3
M üller K E, La kat os P L, Arat ó A, et  al. Inci de nce, Pari s classificat i on, a n d f oll ow- u p i n a 
nat i on wi de i nci de nt c o h ort of  pe diatric pati e nts wit h i nfla m mat or y b o wel  disease. J Pe di atr 
Gastr oe nter ol N utr 2 0 1 3; 5 7: 5 7 6 - 8 2.
1 4
G u pta N, B o str o m AG, Kir sc h ner B S, et  al. Inci de nce of  strict uri n g a n d pe netrati n g 
c o mplicat i ons of  Cr o h n's disease di a g n ose d i n pe di atric pat ient s. I nfla m m B o wel  Dis. 
2 0 1 0; 1 6: 6 3 8 - 4 4.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 1 3
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
1 5
D u bi ns k y M C, Li n Y C, D utri d ge D, et  al. Ser u m i m m u ne res p o nses pre di ct ra pi d disease 
pr o gressi o n a mo n g c hil dre n wi t h Cr o h n's di sease: i m m u ne res p o nses pre di ct disease 
pr o gressi o n. A m J Gastr oe nter ol 2 0 0 6; 1 0 1: 3 6 0 - 7.
1 6
Pfeffer k or n M D, 
Mars hallec k 
F E, Saee d S A, et al. N A S P G H A N cli nical re p ort o n t he 
e val uat i on a n d treat me nt of  pe diatric pat ient s wi t h int er nal pe netrati n g Cr o h n di sease: 
i ntraa b d omi nal a bscess wi t h an d wi t ho ut fist ula. J Pe di atr Gastr oe nter ol N utr 2 0 1 3; 5 7: 3 9 4 -
4 0 0.
1 7
Vasse ur F, G o wer -R o ussea u C, Ver nier -Mass o uille G, et  al. Nutri tio nal stat us a n d gr o wt h i n 
pe di atric Cr o h n's disease: a p o p ulat i on- base d st u d y. A m J Gastr oe nt er ol 2 0 1 0; 1 0 5: 1 8 9 3 1 9 0 0.
1 8
Nar ul a N, D hillo n  A, Z ha n g D, et al. E nt er al nutri tio n al t hera p y for i n d uct i on of  re missio n  in 
Cr o h n's disease. C oc hra ne Data base S y st Re v 2 0 1 8; 4: C D 0 0 0 5 4 2.
1 9
Ca mer o n F L, Wils o n M L, Bas heer N, et al. A nt i-T N F t hera p y f or pae dia tric I B D: t he Sc ottis h 
nat i onal e x perie nce. Arc h Dis C hil d 2 0 1 5; 1 0 0: 3 9 9 - 4 0 5.
2 0
Dr oz d o wi cz L B , B ost wic k J M. Ps yc hiatric a d verse effects of  pe diatric c ortic oster oid use. 
Ma y o Cli n Pr oc 2 0 1 4, 8 9: 8 1 7 - 3 4.
2 1
Ce nters f or Disease C o ntr ol. Cli nical g r o wt h charts [cite d 2 0 2 0 Ja n 1 7]. A vaila ble fr om U R L : 
ht t ps:// w w w.c dc. g o v/ gr o wt hc harts/cli nical _c harts. htm.
 
 
 
 
2 5
E ur o pea n Me dici nes A ge nc y. G ui deli ne o n t he de vel o p me nt of ne w me dici nal pr o d ucts f or t he 
treat me nt of  Cr o h n’s d isease. 2 8 J u ne 2 0 1 8 C P M P/ E W P/ 2 2 8 4/ 9 9 Re v. 2, C o m mittee f or 
Me dici n al Pr o d ucts f or H u ma n Use ( C H M P).
 
 
 
2 8
Ce nters f or Disease C o ntr ol. Vacci nes a n d Pre ve nta ble Diseases F or Healt hcare Pr ofessi o nals. 
V ari cella. 
2 8 -A pr -2 0 2 1. 
A vaila ble 
fr o m 
U R L: 
ht t ps:// w w w.c dc. g o v/ vacci nes/ v p d/ varicella/ hc p/i n de x. ht ml
2 9
H u g hes H, Ka hl L. T he Harriet La ne ha n d b o o k: a ma n ual f or pe diatriac h o use officers. 2 1st 
e d. P hila del p hia ( P A): Else vier; 2 0 1 8.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 1 4
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
3 0
H y a ms J S, Ferr y  GD, Ma n del F S, et al. De vel o p me nt a n d vali dati o n of  a pe diatric Cr o h n’s 
di sease acti vity i n de x. J Pe diatr Gastr oe nter ol N utr 1 9 9 1; 1 2: 4 3 9- 4 7.
3 1
Da per n o M, D' Hae ns G, Va n Assc he G , et al. De vel o p me nt a n d vali dati on o f a ne w, si m plifie d
e n d osc o pic acti vit y sc ore f or Cr o h n’s disease: t he S E S-C D. Gastr oi ntest E n d osc 2 0 0 4; 6 0: 5 0 5 -
1 2.
3 2
K ha n na R, Z o u G, D' Hae ns G, et al. A retr os pecti ve a nal ysis: t he de vel o p me nt of  patie nt  
re p orte d o utco m e meas ures f or t he assess me nt of Cr o h n's disease act i vity.  Ali me nt P har mac ol 
T her 2 0 1 5; 4 1: 7 7 - 8 6.
3 3
Le wis SJ, Heat o n K W. St o ol f or m scale as a usef ul  gui de t o i ntesti nal tra nsit ti me. Sca n d J 
Gastr oe nter ol 1 9 9 7; 3 2: 9 2 0 - 4.
 
 
 
 
 
 
 
 
 
4 0
E ur o pea n C o m missi o n. Et hi cal co nsi derati o ns f or cli ncial trials o n me dici nal 
pr o d ucts 
c o n d ucte d 
wit h 
mi n ors. 
2 0 1 7. 
A vaila ble 
fr om 
U R L: 
ht t ps://ec.e ur o pa.e u/ health/sites/ defa ult/files/files/e u drale x/ v o l-
1 0/ 2 0 1 7 _ 0 9 _ 1 8 _et hi cal _c o nsi d _ct _ wit h_ mi n ors. p df
4 1
H o wi e S R C. Bl o o d sa m ple v o l umes i n c hil d healt h researc h: re vie w o f safe li mits. B ull W orl d 
Heal t h Or ga n 2 0 1 1; 8 9: 4 6- 5 3.
4 2
Otl e y A, L o o ne n H, Pare k h N, et al. Assessi n g acti vit y of  pe diatric Cr o h n’s disease: w hic h 
i n de x t o use? Gastr oe nter ol 1 9 9 9; 1 1 6: 5 2 7 - 3 1.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 1 5
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
4 3
Sa n ds B E, Fea ga n B G, Sa n d b or n WJ, et al. ( G E D- 0 3 0 1) f or acti ve Cr o h n’s disease: res ults of 
a P hase 3 st u d y . A m J Gastr oe nter ol 2 0 2 0; 1 1 5: 7 3 8- 4 5.
4 4
U. S. F o o d a n d Dr u g A d mi nistrati o n, Ce nter f or Dr u g E val uat i on a n d Researc h. H u mira 
(a dali m u ma b). B L A 
1 2 5 0 5 7/ 4 5 
a p pr o val 
pac ka ge. 
0 3 -Oct -2 0 0 5. 
A vaila ble 
fr om:  
ht t ps:// w w w.access data.f da. g o v/ dr u gsatf da _ d ocs/ bla/ 2 0 0 5/ 1 2 5 0 5 7 Ori g 1s 0 4 5. p df. 
Accesse d 
0 9 - Fe b- 2 0 2 2.
4 5
Wa n g Y, Ja d ha v P R, Lala M, et al. Cl arificat i on o n preci sio n  criteria t o deri ve sa m ple size 
w he n desi g ni n g pe diatric p har mac o ki net ic st u dies. J Cli n P har mac ol 2 0 1 2; 5 2: 1 6 0 1 - 6.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 1 6
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
1 2
A P P E N DI C E S
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 1 7
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
A P P E N DI X 1
A B B R E VI A TI O N S A N D T R A D E M A R K S
Ter m
Defi niti o n
5- A S A
5- a mi n osalic ylic aci d
β- h C G
β- s u b u nit h u ma n c h ori o nic g o na d otr o pi n
A E
a d verse e ve nt
A E SI
a d verse e ve nt of s pecial i nterest
A L C
a bs o l ute l y m p h oc yte c o u nt
A L T
ala ni ne a mi n otra nsferase
A R R
a n n ualize d rela pse rate
A S T
as partate a mi n otra nsferase
A U C
area u n der t he c o nce ntrati o n-ti me c ur ve
A V
atrio ve ntri c ular
A Z A
azat hi o pri ne
B C R P
breast ca ncer resista nce pr otei n
B MI
b o d y  mass i n de x
B P
bl o o d press ure
B P M
beats per mi n ute
B M S
Bri st ol- M yers S q ui b b
C difficile
Cl ostri di u m  difficile
C D
Cr o h n’s disease
C D AI
Cr o h n’s Disease Act i vity I nd e x
C D C
Ce nter f or Disease C o ntr ol
CI
c o nfi de nce i nter val
C O VI D - 1 9
c or o na vir us disease 2 0 1 9
C V
c oefficie nt of variat i on
DI LI
dr u g -i n d uce d li ver i nj ur y
D M
di a betes mellit us
D M C
Data M o nit ori n g C o m mittee
D N A
de o x y rib o n ucleic aci d
E C G
electr ocar dio gr a m
e C R F
ele ctr o nic Case Re p ort F or m
E E N
e xcl usi ve e nteral n utrit i on
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 1 8
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Ter m
Defi niti o n
E R - 5 0
decrease fr o m baseli ne of ≥ 5 0 % 
E S R
er yt hr o c yte se di me ntatio n rate
E T
earl y ter mi nati on
F O C B P
fe male of c hil d beari n g p ote ntial
G C P
G o o d Cli nical Pract ice
G G T
ga m ma -gl uta m yl  tra nsferase 
GI
gastr oi ntesti nal
H A V
he pat itis A vir us
H b A 1c
he m o gl o bi n A 1 c
H Bc
he pat itis B c ore
H Bs
he pat itis B s urface
H B V
he pat itis B vir us
H C V
he pat itis C vir us
HI P A A
Heal t h I ns ura nce P orta bility a n d Acc o u nta bilit y Act
HI V
h u ma n i m m u n o deficie nc y vir us
H R
heart rate
I B
I n vesti gat or’s Br oc h ure
I B D
i nfla m mat or y bo w el  disease
I C F
i nf or me d c o nse nt f or m
I C H
I nter nati o nal C o nfere nce o n Har m o nisati o n 
I E C
I n de pe n de nt Et hics C o m mittee
IF N β- 1a
i nterfer o n β- 1a
I g G
i m m u n o glo b uli n G
I g M
i m m u n o glo b uli n M
I L
i nterle u ki n
I N R
I nter nati o nal N or malize d Rati o
I P
I n vesti gati onal Pr o d uct
I R B
I nstituti o nal  Re vie w B oar d
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 1 9
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Ter m
Defi niti o n
I R T
I nteracti ve Res p o nse Tec h n ol og y
I T T
i nte nt -t o-treat
I V
i ntra ve n o us
I VI g
i ntra ve n o us i m m u ne gl o b uli n
J C V
J o h n C u n ni n g ha m vir us
L A R
le gall y acce pta ble re prese ntati ve
L F T
li ver f u ncti on test
L H
l utei nizi n g h or m o ne
L T E
l on g -t er m e xte nsi on
6- M P
6 merca pt o p uri ne
M RI
ma g net ic res o na nce i ma gi n g
M S
m ult i ple scler osis
M T X
met h otre xate
N
n u m ber of partici pa nts or o bser vati o ns
N S AI D
n o nster oi dal a nt i-i nfla m mat or y dr u g
O L E
o pe n -label e xte nsi o n
O L P
o pe n -label peri o d
P D
p har mac o d y na mic s
P C D AI
P e di atric Cr o h n’s Disease Act i vity I nd e x
P K
p har mac o ki net ics
P M L
pr o gressi ve m ult if oc al le u k oe nce p hal o pat h y
P R E S
p os t eri or re versi ble e nce p hal o pat h y  sy n dr o me
 
S 1 P
s p hi n g osi ne 1-p h os p hate
S A E
serio us a d verse e ve nt
S A P
Stati stical A nal ysis Pla n
 de viati on
S E
sta n dar d err or
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 2 0
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Ter m
Defi niti o n
S E S -C D
Si m ple E n d osc o pic Sc ore f or Cr o h n’s Disease
S F U
safety f oll ow- u p
T E A E
treat me nt - e mer ge nt a d verse e ve nt
T B
t u berc ulosis
T B V
t otal blo o d v ol u me
T D M
t hera pe utic dr u g mo ni t ori n g
T N F
t u mor necr osis fact or
U C
ul cerat i ve c olitis
U L N
u p per li mit of n or mal
V Z V
varicella z oster vir us
W B C
w hite bl o o d cell
Y O
years -ol d
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 2 1
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
A P P E N DI X 2
S T U D Y G O V E R N A N C E C O N SI D E R A TI O N S
T he t er ms “ participa nt ” a n d “su bject” refer t o a pers o n w h o has c o nse nte d t o partici pate in t he 
cli nical researc h st u d y. T y p icall y, the t er m “ partici pa nt” is use d i n t he pr ot oc ol a n d t he t er m
“su bject ” is use d i n t he C ase R e p ort F or m  (C R F ).
R E G U L A T O R Y A N D E T HI C A L C O N SI D E R A TI O N S
T his st u d y  will be c o n d ucte d i n acc or da nce with:

C o nse ns us et hic al princi ples deri ve d fr om i nter nati o nal g ui deli nes , i ncl u di n g t he Decl arat i on 
of  Helsi n ki a n d C o u ncil f or I nter nati onal Or ga nizat i ons of  
Me dical Scie nces ( CI O M S) 
I nter nati o nal Et hical G ui deli nes

A p plica ble I nter nati onal C o u ncil f or Har m o nisati o n (I C H) G o o d Cli nical Pract ice ( G C P)
G ui deli nes

A p plica ble la ws, r e g ulat i ons, a n d re q uire me nts
T he 
st u d y 
will be 
c o n d ucte d i n c o mplia nce 
wit h 
t he pr ot oc ol. 
T he 
pr ot oc ol ,
a n y 
re visi ons/ a me n d me nts,
a n d t he parti ci pa nt
i nf or me d c o nse nt f or m (I C F) will  recei ve 
a p pr o val/fa v ora ble 
o pi ni o n 
b y 
I nstitut i on al  
Re vie w 
B oar d/I n de pe n de nt 
Et hi cs 
C o m mittee (I R B/I E C), a n d re g ulat or y aut h ori ties acc or di n g t o a p plica ble re g ulatio ns pri or t o 
i nitiati on of t he st u d y .
All p ot e nti al serio us breac hes m ust be re p orte d t o t he S p o ns or or desi g nee i m me diatel y. A 
p ote nti al seri o us breac h is defi ne d as a Q ualit y I ss ue (e g, pr ot oc ol de viat i on) t hat is li kel y t o affect, 
t o a si gnifica nt de gree , o ne or m o re of  the f oll owi n g: ( 1) t he rig hts, p h ysical safety or me nt al 
i nte grit y of one or m ore partici pa nts; ( 2) t he scie nt ific val ue of t he cli nical trial (e g, relia bility a n d 
r o b ust ness of ge nerate d data). Ite ms ( 1) or ( 2) ca n be ass ociat e d wit h eit her G C P re g ulat i on(s) or 
trial pr ot o c ol(s).
Pers o n nel i n v ol ve d i n c o n d ucti n g t his st u d y will be q ualifie d b y e d ucat i on, trai ni n g, a n d 
e x perie nce t o perf or m t heir res pecti ve tas ks.
T his st u d y will n ot use t he ser vices of  stu d y  pers o n nel w here sa nctio ns ha ve bee n i n v o ke d or w here 
t here has bee n scie nt ific misc o n d uct or fra u d (e g, l oss of me dical lice ns ure, de bar me nt). 
I N S TI T U TI O N A L R E VI E W B O A R D/I N D E P E N D E N T E T HI C S C O M MI T T E E
Bef ore st u d y init iati on, t he in vest i gat or m u st ha ve wri tte n a n d date d a p pr o val/fa v ora ble o pi ni o n 
fr om t he I R B/I E C f or t he pr ot oc ol, I n vesti gat or’s Br oc h ure, pr o d uct labeli n g i nf or mati on, I C F, 
parti ci pa nt recr uit me nt materials (e g, a d vert ise me nts), a n d a n y ot her wri tte n i nf or mati on t o be 
pr o vi de d t o partici pa nts.
T he in vest i gat or, S p o ns or ,or desi g nee s h o uld pr o vi de t he I R B/I E C wit h r e p orts, u p dates , a n d ot her 
i nf or mat i on (e g, e x pe dite d safety re p orts, a me n d me nts, a d mi nistrati ve letters) a n n uall y, or m o re 
fre q ue ntl y, i n acc or da nce wit h re g ulat or y re q uire me nts or i nstit utio n pr oce d ures.
T he i n vesti gat or is res p o nsi ble f or pr o vi di n g o versi g ht of t he c o n d uct of t he stu d y at t h e site a n d 
a d here nce t o re q uire me nts of t he f o ll owi n g w here a p plica ble :
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 2 2
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d

I C H gui deli nes, 

U nite d States C o de of Fe deral Re g ulati o ns, Tit le 2 1, Part 5 0 ( 2 1 C F R 5 0)

E ur o pea n U ni o n Di recti ve 2 0 0 1/ 2 0/ E C; or

E ur o pea n R e g ulatio n 5 3 6/ 2 0 1 4 f or cli nical st u dies (if a p plica ble), 

E ur o pea n Me dical De vice Re g ulat i on 2 0 1 7/ 7 4 5 f or cli nical de vice r esearc h (if a p plica ble),

t he I R B/I E C

a n d all ot her a p plica ble l ocal re g ulat i ons .
C O M P LI A N C E WI T H T H E P R O T O C O L A N D P R O T O C O L R E VI SI O N S
T he in vest i gat or s h o ul d n ot i m ple me nt a n y de viati o n or c ha n ge t o t he pr ot oc ol  with o ut pri or 
re vie w a n d d o c u m e nte d a p pr o val/fa v ora ble o pi ni o n  of a n a me n d me nt fr o m t he I R B/I E C (a n d, if 
a p plica ble, als o b y t he l ocal Healt h Aut h ori t y), e xce pt w here necessar y t o elimi nate a n i m me diate 
hazar d(s) t o st u d y  p artici pa nts. 
If a de viati on or c ha n ge t o a pr ot oc ol is i m ple me nte d t o eli mi nate a n i m me diate hazar d(s) pri or t o 
o btai ni n g r ele v a nt a p pr o val/fa v ora ble o pi ni o n(s) , t he de viat i on o r c ha n ge will  be s u b mitte d as s o o n 
as p ossi ble t o:

I R B/I E C

Re g ulat or y  aut h ori t y(ies), if a p plica ble b y lo c al  r e g ulat i ons ( per nat i onal re q uire me nts)
D oc u m e nt atio n of  ap pr o val /fa v ora ble o pi ni o n si g ne d b y t he c hair pers o n or desi g nee of  the 
I R B(s)/I E C(s) a n d, if a p plica ble, als o b y t he l ocal Healt h Aut h ori t y, m ust be se nt t o Brist ol -M yers 
S q ui b b ( B M S ).
If a n a me n d me nt s u bsta ntiall y alters t he st u d y desi g n or i ncreases t he p ote ntial ris k t o t he 
parti ci pa nt: ( 1) t he I C F m u st be re vise d a n d s u b mitt e d t o t he I R B(s)/I E C(s) f or re vie w a n d 
a p pr o val/fav ora ble o pi ni o n; ( 2) t he re vise d f or m m ust be use d t o o btai n c o nse nt fr o m part ici pa nts 
c urre ntl y e nr olle d i n t he st u d y if t he y are affecte d b y t he a me n d me nt; a n d ( 3) t he ne w f or m must 
be use d t o o btai n c o nse nt fr o m ne w partici pa nts pri or t o e nr oll me nt.
FI N A N CI A L DI S C L O S U R E
I n vesti gat ors a n d s u b-in vest i gat ors will pr o vi de t he S p o ns or wit h s ufficie nt, acc urate fi na ncial 
i nf or mat i on, i n acc or da nce with re g ulati o ns , t o all o w t he S p o ns or t o s u b mit c om p lete a n d acc urate 
fi na ncial certificati on or discl os ure state me nt s t o t he a p pr o priate H ealt h A ut h ori ties. I n vest i gat ors 
are res p o nsi ble f or pr o vi di n g i nf or mat i on o n fi na ncial i nterests d uri n g t he c o urse of t he st u d y  a n d 
f or 1 year after c o mplet i on of t he st u d y .
I N F O R M E D C O N S E N T P R OC E S S
I n vesti gat ors m u st e ns ure t hat partici pa nts are clearl y a n d f ull y inf or me d a b o ut t he p ur p ose, 
p ote nti al ris ks, a n d ot h er crit ical iss ues re gar di n g cli nical st u dies i n w hic h t he y vol u nteer t o 
parti ci pate. 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 2 3
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
T he S p o ns or or desi g nee will pr o vi de t he i nvest i gat or wit h a n a p pr o priate sa mple I C F, w hic h will 
i ncl u de all ele me nts re q uire d b y t he I C H G C P , a n d a p plica ble re g ulat or y re q uire me nts. T he sa mpl e 
I C F will a d here t o t he et hical pri nci ples t hat ha ve t heir ori gi n i n t he Declarati o n of Helsi n ki.
T he i n vest i gat or or hi s/ her re prese ntati ve m u st:

O btai n I R B/I E C wri tte n a p pr o val/fa v ora ble o pi ni o n of  the wri tte n I C F a n d a n y ot h er 
i nf or mat i on t o be pr o vid e d t o t h e parti ci pa nt prior t o t he be gi n ni n g of t he st u d y  a nd af ter a n y 
re visi ons are c o m plete d f or ne w i nf or mat i on.

Pr o vi d e a c o p y of t he I C F a n d wri tte n i nf or mati on a b o ut t he st u d y in t he lan g ua ge i n w hic h 
t he partici pa nt is pr oficie nt pri or t o cli nical st u d y partici pat i on. T he lan g ua ge m ust be 
n o ntec h nical a n d easil y u n derst o o d. 

E x plai n t he nat ure of  the st u d y t o t he partici pa nt or his/ her le gall y acce pta ble re prese ntati vea n d 
a ns wer all q uest i ons re gar di n g t he st u d y .

I nf or m partici pa nt t hat his/ her
parti ci pat i on is v ol u ntar y . Parti ci pa nt or his/ her le gall y 
acce pta ble re prese ntative will be re q uire d t o sig n a state me nt of i nf or me d c o nse nt t hat meets 
t he re q uire me nts of 2 1 C F R 5 0, l ocal re g ulat i ons, I C H g ui deli nes, Healt h I ns ura nce P orta bilit y 
a n d Acc o u nta bilit y Act ( HI P A A) re q uire me nts, w here a p plica ble, a n d t he I R B/I E C or stu d y 
ce nter.

All o w ti me nece ssar y for partici pa nt or his/ her le gall y acce pta ble re prese ntati ve t o i n q uire 
a b o ut t he details o f t he st u d y.
O btai n 
a n I C F si g ne d a n d pers o nall y date d b y partici p a nt or his/ her le gall y acce pta ble 
re prese ntati vea n d b y t he pers o n w h o c o n d ucte d t he i nf or me d c o nse nt disc ussi o n. 

Incl u de a state me nt i n partici pa nt’s me d ical rec or d t hat writte n i nf or me d c o nse nt was o btai ne d 
bef ore partici pa nt was e nr olle d i n t he st u d y a n d t he date t he writte n c o nse nt was o btai ne d. T he 
a ut h orize d pers o n o btai ni n g t he i nf or me d c o nse nt m ust als o si g n t h e I C F.

Re- c o nse nt partici pa nt t o t he m ost c urre nt versi o n of t he I C F(s) d uri n g his/ her parti ci pat i on i n 
t he st u d y, as a p plica ble.
Re vise t he I C F w he ne ver i m p orta nt ne w i nf or mati o n bec o mes a vaila ble t hat is r ele va nt t o t he 
parti ci pa nt ’s c o nse nt. T he in vesti gat or, or a pers o n desi g nate d b y t he in vest i gat or, s h o ul d f ull y 
i nf or m the parti ci pa nt or his/ her le gall y acce pta ble re prese ntati ve of  all pert i ne nt as pects of  the 
st u d y an d of a n y ne w i nf or mat i on rele va nt t o t he partici pa nt ’s willi n g ness t o c o nti n ue partici patio n 
i n t he st u d y. T his c o m m u nicati on s h o ul d be d oc u me nte d. 
T he c o nfi de nt iality of  rec or ds t hat c o uld i de ntif y parti ci pa nts m u st be pr otecte d, res pecti n g t he 
pri vac y  an d c o nfi de nt iality r ules a p plica ble t o re g ulat or y re q uire me nts, t he partici pa nt ’s si g ne d 
I C F, a n d, i n t he U S, t he partici pa nt ’s si g ne d HI P A A A ut h orizati on.
T he I C F m ust als o i ncl u de a state me nt t hat B M S a n d l ocal a n d f orei g n re g ulat or y a ut h orities ha ve 
di rect access t o partici pa nt rec or ds. 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 2 4
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
I n sit u atio ns w here c o nse nt ca n n ot be gi ve n b y part ici pa nts, t heir le gall y acce pta ble re prese ntatives 
(as per c o u ntr y re g ulat i on) are clearl y a n d f ull y inf or m e d a b o ut t he p ur p ose, p ote ntial ris ks, a n d 
ot her cri tical iss ues re gar di n g cli nical st u dies i n w hic h t he partici pa nt v olu nteers t o parti ci pate. 
If i nf or me d c o nse nt is i nitiall y gi ve n b y a partici pa nt’s le gall y acce pta ble re prese ntati ve or l e g al 
g uar di a n a n d t h e p artici pa nt s u bse q ue nt l y bec o me s ca pa ble of ma ki n g a n d c o m m u nicati n g his or 
her i nf or me d c o nse nt d uri n g t he st u d y, c o nse nt m ust a d diti o nall y be o btai ne d fr o m t he partici pa nt.
F or mi n ors, acc or di n g t o l ocal le gislati on, o ne or b ot h pare nts or a le gall y acce pta ble re prese ntati ve 
m ust be i nf or me d of  t he st u d y pr oce d ures a n d m ust si gn t he I C F a p pr o ve d f or t he st u d y prior t o 
cli nical st u d y part ici pati on. T he e x plicit wis h of  a mi n or, w h o is ca pa ble of  for m i n g a n o pi ni o n 
a n d assessi n g t his i nf or mat i on t o ref use partici pati o n i n, or t o be wit h dra w n fr o m, t he cli nical st u dy 
at a n y ti me, s h o uld be c o nsi de r e d b y t he in vest i gat or. 
Mi n ors w h o are j u d ge d t o be of a n a ge of reas o n m ust als o gi ve t heir writte n c o nse nt . Mi n ors w h o 
reac h t he a ge of maj ority ( le gal a d ulth o o d) d uri n g t he cli nical trial m ust gi ve t heir writte n c o n se nt.
T h e ri g hts, s af et y,  a nd w ell - bei n g of t he st u d y partici pa nts are t he m o st i m p orta nt c o nsid er ati o ns 
a n d s h o ul d pre vail o ver i nterests of scie nce a n d s ociet y.
B M S C O M MI T M E N T T O DI V E R SI T Y I N C LI NI C A L T RI A L S
T he missi o n of  BM S is t o tr a nsfor m  patie nts’ li ves t hr o u g h scie nce b y disc o veri n g, de vel o pi n g, 
a n d deli veri n g i n n o vat i ve me d ici nes t hat hel p t he m pre vail o ver seri o us diseases.
B M S is c o m mitte d t o d oi n g its part t o e ns ure t hat patie nts ha ve a fair a n d j ust o p p ort u ni t y to 
ac hie ve o pti mal healt h o utc o mes.
B M S is w or ki n g t o i m pr o ve t he rec r uit me nt of a di verse particip a nt p o p ul at i on wi t h t he g o al t hat 
t he cli nical trial bec o mes m ore reflect i ve of t he real-w orl d p o p ul at i on a n d t he pe o ple i m pacte d b y 
t he diseases st u die d.
D A T A P R O T E C TI O N, D A T A P RI V A C Y, A N D D A T A S E C U RI T Y
B M S c ollects a n d pr oce sses pers o nal data of  st u d y part ici pa nts, patie nts, healt h care pr o vi ders, 
a n d researc hers f or bi o p har mace ut ical researc h a n d de vel o p me nt t o a d va nce i n n ovat i ve, 
hi g h -q ualit y me dici nes t hat a d dress t he me d ical nee ds of  patie nts. B M S e ns ures t he pri vac y, 
pr o tectio n, a n d c o nfi de nt iality of  suc h pers o nal  dat a t o co m pl y wi t h ap plica ble la ws. T o ac hie ve 
t hese g oals, B M S has i nter nal p o licies t hat i n dicate meas ures a n d c o ntr ols f or pr ocessi n g pers o nal 
data. B M S a d heres t o t hese sta n dar ds t o e ns ure t hat c ollect i on a n d pr ocessi n g of pers o nal data are 
li mite d a n d pr o p orti o nate t o t he p ur p ose f or w hic h B M S c ollects s uc h pers o nal data. T his p ur p ose 
is clearl y a n d u na m bi g u o usl y n otifie d t o t he i n di vi d ual at t he ti me of  collect i on of  pers o nal data. 
I n t he tr ue s pirit of scie nce, B M S is de di cate d t o s hari n g cli nical trial inf or mat i on a n d data wit h 
parti ci pa nts, me dical/researc h c o m m u nit ies, t he me dia, p olic y ma kers, a n d t he ge neral p u blic. T his 
is d o ne i n a ma n ner t hat safe g uar ds partici pa nt pri vac y a n d i nf or me d c o nse nt w hile res pecti n g t he 
i nte grit y of nat i onal re g ulat or y syste m s. Cli nical 
trial data, healt h -relate d researc h, a n d 
p har mac o vi gila nce act i vities o n ke y-c o de d healt h data tra nsferre d b y B M S acr oss nati onal b or ders 
is d o ne i n c o m plia nce wit h t he rele va nt data pr otecti o n la ws i n t he c o u ntr y a n d G C P re q uire me nts.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 2 5
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
B M S pr otects Pers o nal I nf or mati on wi t h ade q uate a n d a p pr o priate sec urity c o ntr ols as i n dicate d 
u n der t he data pr otecti o n la ws. T o ali g n wi t h the rec o m me n de d sec urity sta n dar ds, B M S has 
a d o pte d i nter nal sec urity sta n dar ds a n d p olicies t o pr otect pers o nal data at e ver y sta ge of  its 
pr ocessi n g.
T o s u p ple me nt t hese sta n dar ds, B M S e nters i nto Cli nical Tri al Agree me nts wi t h co nfi de nt iality 
o bli gat i ons t o e ns ure pr o per ha n dli n g a n d pr otecti o n of  pers o nal d at a b y t hir d parti es accessi n g 
a n d ha n dli n g pers o nal data.
B M S ta kes u na ut h orize d access a n d discl os ure of  Pers o nal I nf or mat i on v er y  serio usl y. B M S has 
a d o pte d t he sec urity sta n dar ds t hat i ncl u de Nati o nal I nstitute of  Sta n dar ds a n d Tec h n o l og y 
C y bersec urit y Fra me w or k f or st u dies i n t he U S. B M S ali g ns with t hese sta n dar ds t o c o nti n u o usl y 
assess a n d i m pr o ve its a bilit y t o pr otect, detect, a n d res p o n d t o c y ber attac ks a n d ot her 
u na ut h ori ze d atte mpts t o access pers o nal data. T hese sta n dar ds als o aid i n mit i gati n g p ossi ble
a d verse effects. F urt her m ore, B M S I nf or mat i on Tec h n o l og y  has defi ne d 6 pri nci ples t o pr otect o ur 
di gi t al res o urces a n d i nf or mat i on:
1) Res p o nsi bilit ies of I T Pers o n nel
2) Sec uri n g t he B M S Di gital I nfrastr uct ure
3) I de nti t y a n d Access Ma na ge me nt
4) E xter na l Part ner C o n necti o ns
5) C y ber T hreat Detecti o n a n d Res p o nse
6) I nter nal  C y ber I nci de nt I n vesti gati on
S O U R C E D O C U M E N T S
S o urce d oc u m e nts pr o vi de e vide nce f or t he e xiste nce of  the parti ci pa nt a n d s u bsta ntiate t he 
i nte grit y of t he data c ollecte d. S o urce d oc ume nt s are file d at t he in vest i gat or’s site.
Data re p orte d o n t he C R F or e ntere d i n t he e lectr o nic C R F (e C R F) t hat are tra nscri be d fr om s o urce 
d oc u m e nts must be c o nsiste nt wit h t he s o urce d oc u me nts or t he discre pa ncies m ust be e x plai ne d. 

T he in vest i gat or ma y nee d t o re q uest pre vi o us m e di cal rec or ds or tra nsfer rec or ds, de pe n di n g 
o n t he st u d y . Als o, c urre nt me dical rec or ds m ust be a vaila ble.

Defi nit i ons of w hat c o nst itut es s o urce data ca n be f o u n d
T he in vest i gat or is res p o nsi ble f or e ns uri n g t hat t he s o urce data are acc urate, le gi ble, 
c o nte m p ora ne o us, origi nal , a n d attri b uta ble, w het her t he data are ha n d writte n o n pa per or e ntere d 
ele ctr o nicall y. If s o urce data are create d (first e ntere d), m o difie d, mai ntai ne d, arc hi ve d, retrie ve d, 
or tra ns mitte d ele ctr o nicall y via c o m p uterize d s yste ms (a n d/ or a n y ot h er ki n d of  electr o nic 
de vices) as part of  re g ulate d cli nical trial act i vities, s uc h s yste ms m ust be c o mplia nt wit h all 
a p plica ble la ws a n d re g ulatio ns g o ver ni n g use of  electr o nic rec or ds a n d/ or electr o nic si g natures. 
S uc h s yste ms ma y i ncl u de, b ut are n ot li mite d t o, electr o nic me d ical rec or ds/electr o nic healt h 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 2 6
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
rec or ds, a d verse e ve nt ( A E) trac ki n g/re p orti n g, pr ot oc ol -re q uire d assess me nts, a n d/ or dr u g 
acc o u nta bilit y rec or ds.
W he n 
pa per rec or ds fr o m s uc h s yste ms are use d i n place of  a n electr o nic f or mat t o perf or m 
re g ulate d acti vit ies, s uc h pa per rec or ds s h o uld be certifie d c o pies. A certifie d c o p y co nsists of  a 
c o p y of origi nal i nf or mati on t hat has bee n verifie d, as i n dicate d b y a d at e d sig nat ure, as a n e xact 
c o p y ha vi n g all of t he sa me attri b utes a n d i nf or mati o n as t he ori gi nal. 
S T U D Y I N T E R V E N TI O N R E C O R D S
Rec or ds f or st u d y i nter ve nt i on ( w het her s u p plie d b y B M S, its ve n d ors, or t he sit e) m ust 
s u bsta ntiate st u d y i nter ve nti o n i nte grit y a n d tracea bility fr om receipt, p re parati o n, a d mi nistrati o n, 
a n d t hr o u g h destr ucti o n or ret ur n. Rec or ds m ust be ma de a vaila ble f or re vie w at t he re q uest of 
B M S/ desi g nee or a Healt h A ut h orit y.
If
T he n
S u p plie d b y B M S ( or its ve n d ors):
Rec or ds 
or l ogs m ust 
c o m p l y wi t h ap plica ble 
re g ulat i on s a n d g uideli nes a n d s h o ul d i ncl u de :

a mo u nt recei ve d a n d place d i n st ora ge area

a mo u nt c urre ntl y  in st ora ge area

la bel i de ntificati on n u m ber or batc h n u m ber

a mo u nt dis pe nse d t o a n d ret ur ne d b y  eac h 
parti ci pa nt , i ncl u di n g u ni q ue parti ci pa nt
i de ntifiers

a mo u nt tra nsferre d t o a n ot her area/site f or 
di s pe nsi n g or st ora ge

n o nst u d y  dis p ositio n (e g, l ost, waste d) 

a mo u nt destr o y e d at st u d y sit e, if a p plica ble

a mo u nt ret ur ne d t o B M S

retai n sa m ples f or 
bi oa vaila bilit y/ bi oe q ui vale nce / bio c o m para bili t y, 
if a p plica ble 

dates a n d i nit ials of pers o n res p o nsi ble f or 
In vest i gati onal P r o d uct 
di s pe nsi n g/acc o u nta bility,  as per t he Dele g atio n 
of  A ut h orit y F or m
S o urce d b y s ite a n d n ot s u p plie d b y B M S 
or its ve n d ors (e xa m ples i ncl u de I P 
s o urce d 
fr o m 
t he 
sites st oc k 
or 
c o m mercial 
su p pl y 
or 
a 
s pecialt y 
p har mac y)
T he in vest i gat or or desi g nee acce pts res p o nsi bility 
f or d oc u m e nt i n g tracea bility a n d st u d y treat me nt
i nte grit y i n acc or da nce with re q uire me nts a p plica ble 
u n der 
la w 
a n d 
t he 
sta n dar d 
o perati n g 
pr oce d ures /sta n dar ds of t he s ourci n g p har mac y
B M S or its desi g nee will pr o vi de f or ms t o facilitate i n ve nt or y c o ntr ol if t he i n vesti gati onal sit e 
d oes n ot ha ve a n esta blis he d s yste m t hat meets t hese re q uire me nts.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 2 7
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
C A S E R E P O R T F O R M S
A n in vesti g at or i s re q uire d t o pre pare a n d mai ntai n a de q uate a n d acc urate case hist ories desi g ne d 
t o rec or d all o bser vat i ons a n d ot h er data perti ne nt t o t h e i n vesti gati on o n eac h i n di vi d ual treate d 
or e ntere d as a c o ntr ol in t he i n vesti gati on. Data t hat are deri ve d fr om s o urce d oc u me nts a n d 
re p orte d o n t he C R F m u st be c o nsiste nt wit h t he s o urce d oc u me nts, or t h e di scre pa ncies m ust be 
e x plai ne d. A d dit i onal cli nical i nf or mati on ma y be c ollecte d a n d a nal yze d i n a n eff ort t o e n ha nce 
u n dersta n di n g o f pr o d uct safet y.  C R Fs ma y be re q ueste d f or A Es a n d/ or la b orat or y a b n or malities 
t hat are re p orte d or i de nt ifie d d uri n g t he c o urse of t he st u d y.
F or sites usi n g t he S p o ns or or desi g nee electr o nic data ca pt ure ( E D C) t o ol, e C R Fs will be pre pare d 
f or all data c o llecti on fiel ds e xce pt f or fiel ds s pecific t o S A Es a n d pre g na nc y,  whic h will be 
re p orte d o n t he ele ctr o nic S A E f or m an d Pre g na nc y S ur veilla nce F or m , res pecti vel y. If t he 
ele ctr o nic S A E f or m is n ot a vaila ble, a pa per S A E f or m ca n be use d. 
T he c o nfi de nt iality of  rec or ds t hat c o uld i de ntif y parti ci pa nts m u st be pr otecte d, res pecti n g t he 
pri vac y  a nd c o nfi de nt iality r ules i n acc or da nce wit h t he a p plica ble re g ulat or y re q uire me nt(s).
T he in vest i gat or will mai ntai n a si g nat ure s heet t o d oc u me nt si g nat ures a n d i nit ials of all pers o ns 
a ut h orize d t o ma ke e ntries a n d/ or correcti o ns o n C R Fs. 
T he c o m plete d C R F a n d S A E/ pre g na nc y C R Fs m ust be pr o m pt l y re vie we d, sig ne d, a n d date d b y 
t he in vest i gat or or q ualifie d p h ysicia n w h o is a s u b-in vest i gat or a n d w h o is dele gate d t his tas k o n 
t he D el e gat i on of  Aut h ori t y For m . S u b -in vest i gat ors in Ja pa n ma y n ot be dele gate d t he C R F 
a p pr o val t as k. T he in vest i gat or must retai n a c o p y of t he C R Fs, i ncl u di n g rec or ds of t he c ha n ges 
a n d c orrecti o ns.
Eac h 
i n di vi d ual electr o nicall y si gni n g e C R Fs m ust 
meet 
S p o ns or or desi g nee
trai ni n g 
re q uire me nts an d m ust o nl y  access t he B M S E D C t o ol usi n g t he u ni q ue user acc o u nt pr o vi de d b y 
t he S p o ns or or desi g nee. User acc o u nts are n ot t o be s hare d or reassi g ne d t o ot her i n di vi d uals .
M O NI T O RI N G
M o ni t ori n g details descri bi n g strate g y, i ncl u di n g defi nit i on of  st u d y critical data ite ms a n d 
pr ocesses (e g, ris k-base d i nitiati ves i n o perati o ns a n d q uali t y suc h as ris k ma na ge me nt a n d 
mit i gati on strate gies a n d a nal ytical ris k-base d m o nit ori n g), met h o ds, res p o nsi bilities, a n d 
re q uire me nts, i ncl u di n g ha n dli n g of  no nc o m p lia nce iss ues a n d m o nit ori n g tec h ni q ues (ce ntral, 
r e mot e , or o n-sit e mo ni t orin g) are pr o vi de d i n t he m o nit ori n g pla n .
Re prese ntati ves of B M S m ust be all o we d t o visit all st u d y  sit e lo c ati o ns peri o di call y t o assess t he 
data q ualit y a n d st u d y  i nte grity.  O n site, t he y will re vie w st u d y rec or ds a n d directl y c o m pare t he m 
wi t h s o urce d oc u me nts, disc uss t he c o n d uct of t he st u d y wit h t he in vest i gat or, a n d verif y t hat t he 
facilities re mai n acce pta ble.
Certai n C R F pa ges a n d/ or electr o nic files ma y ser ve as t he s o urce d oc u me nts .
I n a d ditio n, t he st u d y ma y be e val uate d b y t he S p o ns or or desi g nee i nter nal a u dit ors a n d 
g o ver n me nt i ns pect ors w h o m ust be all o we d access t o C R Fs, s o urce d oc u me nts, ot her st u d y files, 
a n d st u d y facilities. B M S a u dit re p orts will be ke pt c o nfi de ntial.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 2 8
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
T he in vesti gat or m ust n otif y B M S pr o m ptl y of a n y i ns pecti o ns sc he d ule d b y re g ulat or y a ut h orities 
a n d pr o m pt l y f or war d c o pies of ins pect i on re p orts t o t he S p o ns or or desi g nee.
R E C O R D S R E T E N TI O N
T he in vest i gat or ( or hea d of  the st u d y site i n Ja pa n) m u st retai n all st u d y rec or ds a n d s o urce 
d oc u m e nts f or t he ma xi m u m p eri o d re q uire d b y a p plica ble re g ulati ons a n d g ui deli nes, or 
i nstituti o n pr oce d ures, or f or t he peri o d s pecifie d b y B M S or its desi g nee, w hic he ver is l on ger. 
T he in vest i gat or ( or hea d of  the st u d y site i n Ja pa n) m u st c o ntact B M S pri or t o destr o yi n g a n y 
rec or ds ass ociat e d wit h t he st u d y.
B M S or its desi g nee will n otif y t he in vest i gat or ( or hea d of t he st u d y site i n Ja pa n) w he n t he st u d y 
rec or ds are n o l o n ger nee de d.
If t he in vesti g at or wit h dra ws fr om t he st u d y (e g, rel ocati o n, r etire me nt), t he rec or ds s hall b e 
tra nsferre d t o a mut uall y  a gree d-u p o n desi g nee ( e g, a n ot her in vest i gat or, st u d y site, I R B). N otic e 
of  s uc h tra nsfer will be gi ve n i n writi n g t o B M S or its desi g nee. 
R E T U R N O F S T U D Y T R E A T M E N T
F or t his st u d y, st u d y treat me nts (t h ose s u p plie d b y B M S
or a ve n d or or s ource d b y t he 
in vesti g at or) , s uc h as part iall y use d st u d y treat me nt c o ntai ners, vials , a n d s yri n ges, ma y b e 
destr o y e d o n sit e. 
If
T he n
St u d y  tr e at me nts s u p plie d b y B M S (incl u di n g 
its ve n d ors)
A n y u n use d st u d y i nter ve nt i ons s u p plie d b y 
B M S 
ca n o nl y be destr o y e d aft er bei n g 
i ns pecte d a n d rec o ncile d b y t he res p o nsi ble 
St u d y  
Mo ni t or,
u nless 
st u d y treat me nts 
c o ntai ners m ust be i m me diatel y destr o y e d as 
re q uire d f or safety,  or t o meet l ocal re g ulati o ns 
(e g, c yt ot o xics or biol o gi cs).
Parti all y use d 
st u d y int er ve nt i ons 
a n d/ or 
e mpt y c o ntai ners ma y 
be destr o y e d aft er 
pr o per rec o nciliati on a n d d oc u me ntati o n. B ut 
u n use d I M P m u st be rec o ncile d b y sit e 
m o nit or/ Cli nical Researc h Ass oci ate pri or t o 
destr ucti o n .
If st u d y tr e at me nts will be ret ur ne d, t he ret ur n 
will be ar ra n ge d b y t he res p o nsi ble St u d y 
M o ni t or.
St u d y  treat me nts s ource d b y sit e, n ot s u p plie d 
b y B M S ( or its ve n d ors ; e g, stu d y treat me nts 
It 
is 
t he 
in vesti gat or’s 
or 
desi g nee’s 
res p o nsi bility t o dis p ose of  all c o ntai ners 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 2 9
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
If
T he n
s o urce d fr o m t he sit e’s st oc k or c o m mercia l 
s u p pl y or a s pecialt y p har mac y)
acc or di n g t o t he i nstituti o nal  gui deli nes a n d 
pr oce d ures.
It is t he in vest i gat or’s or desi g nee’s res p o nsi bility t o arra n ge f or dis p osal of  st u d y i nter ve nt i ons , 
pr o vi de d t hat pr oce d ures f or pr o per dis p osal ha ve bee n esta blis he d acc or di n g t o a p plica ble fe deral, 
state, l ocal, a n d i nstitut i onal g ui deli nes a n d pr oce d ures, a n d pr o vi de d t hat a p pr o priate rec or ds of 
di s p osal are ke pt. T he f ollo wi n g mi ni mal  sta n dar ds must be m et:

O n -site dis p osal practices m ust n ot e x p ose h u ma ns t o ris ks fr o m t he dr u g.

O n -sit e dis p osal pract ices a n d pr oce d ures are i n a gree me nt wi t h ap plica ble la ws a n d 
re g ulat i ons, i ncl u di n g a n y s pecial re q uire me nts f or c o ntr olle d or hazar d o us s u bsta nces.

Wr itte n pr oce d ures f or o n -sit e di s p osal are a vaila ble a n d f oll owe d. T he pr oce d ures m u st be 
file d wit h t he site’s sta n dar d o perati n g pr oce d ures a n d a c o p y pr o vide d t o B M S u p o n re q uest.

Rec or ds are ma i ntai ne d t hat all o w f or tracea bility of  eac h c o ntai ner, i ncl u di n g t he date 
di s p ose d of , q u a ntit y dis p ose d, a n d i de ntificati o n of  t he pers o n dis p osi n g t he c o ntai ners. T he 
met h o d of  dis p osal (e g, i nci nerat or, lice nse d sa nit ar y la n dfill, or lice nse d waste -dis p osal 
ve n d or ) m ust be d oc u me nte d.

Acc o u nta bilit y a n d dis p osal  rec or ds are c o mpl ete, u p- t o-date, a n d a vaila ble f or t he St u d y 
M o ni t or t o re vie w t hr o u g h o ut t he cli nical trial peri o d.
It is t he in vest i gat or’s or desi g nee’s res p o nsi bility t o arra n ge f or dis p osal of all e m pty c o ntai ners.
If c o n diti ons f or destr ucti o n ca n n ot be met , t he res p o nsi ble St u d y M o nit or will make arra n ge me nts 
f or ret ur n of  st u d y treat me nts pr o vi de d b y B M S ( or its ve n d ors). Destr ucti o n of  no n -st u d y 
treat me nts s o urce d b y t he site, n ot s u p plie d b y B M S, is s olel y t he res p o nsi bilit y o f the in vest i gat or 
or desi g nee.
S T U D Y A N D SI T E S T A R T A N D C L O S U R E
T he S p o ns or /desi g nee reser ves t he ri g ht t o cl ose t he st u d y site or t o t er mi nate t he st u d y at a n y ti me 
f or a n y reas o n at t he s ole di screti on of  the S p o ns or. St u d y  sites will be close d u p o n stu d y 
c o mplet i on. A st u d y site is c o nsi dere d cl ose d w he n all re q uire d d oc u me nts a n d st u d y s u p plies ha ve 
bee n c o llecte d a n d a st u d y-sit e clos ure visit has bee n perf or me d.
T he in vest i gat or ma y i nitiate st u d y-site clos ure at a n y t i me, pr o vi de d t here is reas o na ble ca use a n d 
s ufficie nt n otice is gi ve n i n a d va nce o f t he i nte n de d ter mi nati on.
Reas o ns f or t he earl y clos ure of  a st u d y site b y t he S p o ns or or in vest i gat or ma y i ncl u de, b ut are 
n ot li mite d t o:

Fail ure of  the in vesti gat or t o c o m p l y wi t h the pr ot oc ol , t he re q uire me nts of  the I R B/I E C or 
l ocal H ealt h Aut h ori ties, t he S p o ns or ’s pr oce d ures, or G C P g ui deli nes

I na de q uate recr uitme nt  of p artici pa nts b y t he in vesti gat or
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 3 0
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d

Di sc o nti n uatio n of  furt her st u d y  int er ve nt i on de vel o p m e nt
If t he st u d y is pre mat urel y  ter mi nate d or s us pe n de d, t he S p o ns or s hall pr o m ptl y i nf or m the 
in vesti g at ors, t he I E Cs/I R Bs, t he re g ulat or y a ut h orities, a n d a n y c o ntract researc h or ga nizat i on(s) 
use d i n t he stu d y of  the reas o n f or ter mi nati on or s us pe nsi on, as s pecifie d b y t he a p plica ble 
re g ulat or y r e q uire me nts. T he in vest i gat or s hall pr o m ptl y i nf or m t he pa rtici pa nt a n d s h o ul d ass ure 
a p pr o priate partici pa nt t hera p y a n d/ or f ollo w - u p.
DI S S E MI N A TI O N O F C LI NI C A L S T U D Y D A T A
I n or der t o be nefit p ote ntial st u d y p artici pa nts, patie nts, healt hcare pr o vi ders a n d researc hers, a n d 
t o hel p B M S h o n or its c o m mit me nts t o stu d y p arti ci pa nts, B M S will ma ke i nf or mati on a b o ut 
cli nical researc h st u dies a n d a s u m mar y of  their res ults a vaila ble t o t he p u blic as per re g ulat or y 
a n d B M S re q uire me nts. B M S will p ost st u d y i nf or mati on o n l o c al , n atio nal  or r e gio nal  data bases 
i n c om p lia nce wit h nat i onal a n d i nter nat i onal sta n dar ds f or discl o s ure. B M S ma y als o v olu ntaril y 
di s close i nf or mat i on t o a p plica ble data bases.
C LI NI C A L S T U D Y R E P O R T
A Si g n at or y  I n vesti gat or m ust be selecte d t o si g n t he C li nical S t u d y Re p ort ( C S R). 
F or eac h C S R related t o t his pr ot oc ol , t he f oll owi n g crit eria will be use d t o select t he S i gnat or y 
In vest i gat or:
S CI E N TI FI C P U B LI C A TI O N S
T he data c o llecte d d uri n g t his st u d y are c o nfi de ntial a n d pr o pri etar y to t he S p o ns or or desi g nee. 
A n y p u blicati o ns or a bstracts ari si n g fr om t his st u d y must a d here t o t he p u blicati o n r e q ui re me nts 
set f ort h i n t he C li nical T rial A gree me nt ( C T A g) g o ver ni n g parti ci pat i on i n t he st u d y. T hese 
re q uire me nts i ncl u de, b ut are n ot li mite d t o, s u b mitti n g pr o p ose d p u blicat i ons t o t he S p o ns or or 
desi g nee at t he earliest practica ble ti me pri or t o s u b missi o n  or prese ntati o n a n d ot her wi se wi t hi n 
t he ti me peri o d set f ort h i n t he C T A g.
S ci e nt ific p u blicat i ons (s uc h as a bstracts, c o n gress p o di u m prese nt atio ns a n d p osters, a n d 
ma n uscri pts) of t he st u d y  r es ults will be a c olla b orati ve eff ort bet wee n t he st u d y S p o ns or a n d t he 
e xter nal a ut h ors. N o p u blic prese ntati o n or p u blicati o n of a n y i nteri m res ults ma y be ma de b y a n y 
P ri nci pal In vesti gat or, s u b-in ves tigat or , or a n y ot h er me m ber of  t he st u d y st aff wit ho ut t h e pri or 
wri tte n c o nse nt of t he S p o ns or.
A ut h ors hi p of  pu blicat i ons at B M S is ali g ne d wi t h t he criteria of  t he I nter nati o nal C o m mittee of 
Me dical J o ur nal E dit ors (I C MJ E, w w w.ic mje. or g). A ut h ors hi p se lecti on is base d u p o n si g nifica nt 
c o ntri b uti o ns t o t he st u d y (ie, I C MJ E criteri o n # 1). A ut h ors m ust me et all 4 I C MJ E crit eria f or 
a ut h ors hi p:
1)
S u bsta nt ial i ntellect ual c o ntri b uti on t o t he c o nce pti o n or desi g n of t he w or k; or t he ac q uisit i on 
of  d at a (ie, e va l ua ble part ici pa nts wi t h q u alit y data), a nal ysis, or i nter pretatio n of  d at a for t h e 
w or k (e g, pr o ble m s ol vi n g, a d vice, e val uati on, i nsi g hts a n d c o ncl usi o n) ; A N D
2)
Drafti n g t he w or k or re visi n g it crit icall y f or i m p orta nt i ntellect ual c o nte nt; A N D
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 3 1
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
3)
Fi nal a p pr o val of t he versi o n t o be p u blis he d; A N D
4)
A gree me nt t o be acc o u nta ble f or all as pects of  t he w or k i n e ns uri n g t hat q uesti o ns relate d t o 
t he acc urac y or i nte grit y of a n y p art of t he w or k are a p pr o priatel y i n vesti gate d a n d res ol ve d.
T h ose w h o ma ke t he m o st sig nifica nt c o ntri b ut i ons, as defi ne d a b o ve, will be c o nsi dere d b y B M S 
f or a ut h ors hi p of  t he pri mar y p u blicat i on. S u b -in vesti gat ors will ge nerall y  not be c o nsi dere d f or 
a ut h ors hi p i n t he pri mar y p u blicati on. Ge o gra p hic re prese ntati o n will als o be c o nsi dere d.
A ut h ors will be liste d b y  or d er of si g nifica nt c o ntri b uti ons ( hi g hest t o l o west), wi t h t he e xce pti on 
of  the last a ut h or. A ut h ors i n first a n d last p osi tio n ha ve pr o vi de d t he m o st sig nifica nt c o ntri b uti o ns 
t o t he w or k. 
F or sec o n dar y a nal yses a n d r elate d p u blicat i ons, a ut h or list a n d a ut h or or der ma y v ar y  fr o m 
pri mar y t o reflect a d di tio nal c o ntri b ut i ons.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 3 2
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
A P P E N DI X 3
A D V E R S E E V E N T S A N D S E RI O U S A D V E R S E E V E N T S: 
D E FI NI TI O N S A N D P R O C E D U R E S F O R R E C O R DI N G, 
E V A L U A TI N G, F O L L O W -U P , A N D R E P O R TI N G
A D V E R S E E V E N T S
A d verse E ve nt D efi niti o n:
A n ad verse e ve nt ( A E) is defi ne d as a n y ne w u nt o war d me d ical occ urre nce or w orse ni n g of  a 
pre -e xist i n g me d ical c o n ditio n i n a cli nical i n vesti gati o n parti ci pa nt a d mi nistere d st u d y 
treat me nt t hat d oes n ot necessaril y ha ve a ca usal relat i ons hi p wit h t hi s treat me nt. 
A n A E ca n t heref ore be a n y u nf a v ora ble a n d u ni nte n de d sig n (s uc h as a n a b n or mal la b orat or y 
fi n di n g), s y m pt o m, or disease te m p orall y ass ociate d wit h t he use of st u d y treat me nt, w het her or 
n ot c o nsi dere d rel ate d t o t he st u d y treat me nt.
E ve nts Meeti n g
t he A E Defi niti o n

A n y a b n or mal la b orat or y test res ults ( he mat olo g y , cli nical c he mistr y, or uri nal ysis) or 
res ults fr o m ot her safety a ssess me nts (e g, electr ocar di o gra ms, ra di ol ogi c al sca ns, vital si g ns 
meas ure me nts), i ncl u di n g t h ose t hat w orse n fr o m baseli ne, c o nsi dere d cli nicall y si g nifica nt 
i n t he me dical a n d scie ntific j u d g me nt of  the in vesti gat or. N ote t hat a b n or mal la b tests or 
ot her safety assess me nts s h o uld o nl y b e re p orte d as A Es if t he fi nal dia g n osis is n ot 
a vaila ble. O nce t he fi nal dia g n osis is k n o w n, t he re p orte d ter m  s ho ul d be u p date d t o be t he 
di a g n osis.

E xacer bat i on of a c hr o nic or i nter mitte nt pre -e xisti n g c o n dit i on, i ncl u di n g eit her a n i ncrease 
i n fre q ue nc y a n d/ or i nte nsit y of t he c o n dit i on.

Ne w c o n dit i ons detecte d or dia g n ose d aft er st u d y int er ve nt i on a d mi nistrati o n, e ve n t ho u g h 
it ma y ha ve bee n prese nt bef ore t he start of t he st u d y.

Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d dr u g -dr u g i nter actio n.

Si g ns, s y m pt o ms, or t he cli nical se q uelae of  a sus pecte d o ver d ose of  either st u d y i nter ve nt i on 
or a c o nc o mit a nt me dicat i on. O ver d ose, as a ver bati m ter m (as re p orte d b y t he in vest i gat or), 
s h o uld n ot be re p orte d as a n A E/ serio us a d verse e ve nt (S A E ) u nless it is a n i nte nt i onal 
o ver d ose ta ke n wi t h possi ble s uici dal/self-har mi n g i nte nt. S uc h o ver d oses s h o uld b e 
re p orte d re gar dless of  se q uelae a n d s h o uld s pecif y “i nte nt i onal o ver d ose ” as t he ver bat i m 
t er m.
E ve nts N O T Meeti n g t he A E Defi niti o n

Me dical o r s ur gical pr oce d ure (e g, e n d osc o p y, a p pe n dect o m y) ; t he c o n ditio n  that lea ds t o 
t he pr oce d ure is t he A E.

Si t u atio ns i n w hic h 
a n u nt o war d me d ical occ urre nce di d n ot occ ur (s ocial a n d/ or 
c o n ve nie nce a d missi o n t o a h os pital).
D E FI NI TI O N O F S A E
If a n e ve nt is n ot a n A E per defi nit i on a b o ve, t he n it ca n n ot be a n S A E , e ve n if seri o us c o n dit i ons 
are met.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 3 3
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
S E RI O U S A D V E R S E E V E N T S
A s eri o us a d verse eve nt ( S A E) is defi ne d as a n y u nt o w ar d me dic al occ urre nce t h at, at a n y 
d ose:
Res ults i n deat h .
Is life-t hreate ni n g ( defi ne d as a n e ve nt i n w hic h t he parti ci pa nt w as at ri s k of deat h at t he ti me 
of  the e ve nt; it d oes n ot refer t o a n e ve nt w hic h h y p ot heticall y mi g ht ha ve ca use d deat h if it were 
m o re se vere).
Re q ui res i n patient  h os pitalizati o n or ca uses pr olo n g ati o n of  e xisti n g h os pi talizati on (see N O T E 
bel o w) .
N O T E: 
T he f o ll owi n g h os pitalizat i ons are n ot c o nsi dere d S A Es i n Brist ol -M yers S q ui b b ( B M S ) cli nical 
st u dies: 

A visit t o t he e mer ge nc y r o o m or ot her h os pital de part m e nt < 2 4 h o urs t hat d oes n ot res ul t 
i n a d missi o n ( u nless c o nsi dere d a n i m p orta nt me dical or life -t hreate ni n g e ve nt).

E lecti ve s ur ger y, pla n ne d pri or t o si g ni n g c o nse nt.

A d missi o n s as per pr ot oc ol for a pla n ne d me dical/s ur gical pr oce d ure .

R o uti ne 
heal t h 
assess me nt re q uirin g 
a d missio n  for 
baseli ne/tre n di n g 
of  
healt h 
stat us ( e g, r o uti ne c ol o n osc o p y).

M e dical/s ur gical a d missi o n ot h er t ha n t o re me d y ill heal t h an d pla n ne d pri or t o e ntr y int o 
t he st u d y. A p pr o priate d oc u me nt atio n is re q ui re d i n t hese cases.

A d missi o n  e nc o u ntere d f or a n ot her life circ u msta nce t hat carries n o beari n g o n health stat us 
a n d re q uires n o me dical/s ur gical i nter ve ntio n (e g , lac k of  ho usi n g, ec o n o mic i na de q uac y, 
care gi ver res pite, fa mil y circ u msta nces, a d mi nistrati ve reas o n).

A d missi o n  for a d mi nistrati o n of  ant ica ncer t hera p y i n t he a bse nce of  an y ot h er 
S A Es (a p plies t o o nc ol o g y pr ot oc ols).
Res ults i n persiste nt or si g nifica nt disa bilit y/ i nca pacity.
Is a c o n ge nital a n oma l y/ birt h defect.
Is a n i m p orta nt me d ical e ve nt ( defi ne d as a me di cal e ve nt [s] t hat ma y n ot be i m me diatel y 
life-t hreate ni n g or res ult i n deat h or h os pitalizat i o n b ut, base d u p o n a p pr o priate me d ical an d 
scie ntific j u d g me nt, ma y je o par dize t he parti ci pa nt or ma y re q uire i nter ve nt i on [e g, me d ical, 
s ur gical] t o pre ve nt o ne of t he ot her serio us o utc o mes liste d i n t he defi nit i on a b o ve) . E xa m ples 
of  suc h e ve nts i ncl u de, b ut are n ot li mite d t o, i nte nsi ve tr e at me nt i n a n e mer ge nc y ro o m  or at 
h o me f or aller gic br o nc h os pas m a n d bl o o d d y s cr asias or c o n v ulsi o ns t hat d o n ot res ult i n 
h os pi talizatio n. P ote nti al dr u g -i n d uce d li ver i nj ur y (DI LI) is als o c o nsi dere d a n i m p orta nt 
me dical e ve nt. ( See  Secti o n 9. 2. 7 f or t he defi niti on of p ote nti al DI LI.) 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 3 4
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Pre g na nc y a n d DI LI m ust f ol l ow t he sa me tra ns missi o n ti mi n g a n d pr ocesses t o B M S as use d f or 
S A Es . ( See S ecti o n 9. 2. 5 f or re p orti n g pre g na ncies.)
E V A L U A TI N G A E S A N D S A E S
Assess me nt of C a us alit y

T he in vest i gat or is o bli gate d t o assess t he relat i ons hi p bet wee n st u d y  i nter ve nt i on a n d eac h 
occ urre nce of eac h A E/ S A E.

A “reas o na ble p ossi bilit y” of  a relat i ons hi p c o n ve ys t hat t here are facts, e vi de nce, a n d/ or 
ar g u me nts t o s u g gest a ca usal relati o ns hi p, rat her t ha n a relat i ons hi p ca n n ot be r ul e d o ut.

T he in vest i gat or will use cli nical j u d g me nt t o deter mi ne t he relati ons hi p.

Alt er nat i ve ca uses, s uc h as u n derl yi n g disease(s), c o nc o mita nt t hera p y, a n d ot her ris k 
fact ors, as well as t he te m p oral relati ons hi p o f the e ve nt t o stu d y i nter ve nt i on a d mi nistrati o n ,
will be c o nsi dere d a n d i n vest i gate d.

T he in vest i gat or will als o c o ns ult t he I n vesti gat or’s Br oc h ure a n d/ or p r o d uct inf or m at i on f or 
mar kete d pr o d ucts i n his/ her assess me nt.

F or eac h A E/ S A E, t he in vest i gat or m u st d oc u me nt i n t he me d ical n otes t hat he/s he has 
re vie we d t he A E/ S A E a n d has pr o vi de d a n assess me nt of ca usalit y.

T here ma y be sit u atio ns i n w hic h a n S A E has o c c urre d a n d t he in vest i gat or has mi ni ma l 
i nf or mat i on t o i ncl u de i n t he i nit ial re p ort t o t he S p o ns or. H o we ver, it is ver y i m p orta nt t hat 
t he in vest i gat or al wa ys ma ke
a n assess me nt of  ca usalit y f or e ver y e ve nt bef ore t he i nitial 
tra ns missi on of t he S A E data t o t he S p o ns or.

T he in vest i gat or ma y c ha n ge his/ her o pi ni o n of  ca usalit y i n li g ht of  fol l ow- u p i nf or mati on 
a n d se n d a n S A E f o ll ow- u p re p ort wi t h t he u p date d ca usalit y assess me nt.

T he ca usalit y assess me nt is o ne of  t he criteria use d w he n deter mi ni n g re g ulat or y re p orti n g 
re q uire me nts.

Assess me nt of I nte nsit y
T he in vest i gat or will ma ke a n assess me nt of i nte nsity f or eac h A E a n d S A E re p orte d d uri n g t he 
st u d y a n d assig n i t t o 1 of  t h e foll o wi n g cate g ories: 

Mil d: A n e ve nt t hat is easil y t olerate d b y t he partici pa nt, ca usi n g mi ni mal disc o mf o rt a n d 
n ot i nterferi n g wit h e ver y da y act i vities.

M o derate: A n e ve nt t hat ca uses s ufficie nt disc o mf ort a n d i nterferes wi t h nor mal  ever y da y 
acti vit ies.

Se vere: A n e ve nt t hat pre ve nts n or mal e ver y da y acti vit ies. A n A E t hat is assesse d as se vere 
s h o uld n ot be c o nf use d wit h a n S A E. Se vere is a cate g or y  utilize d f or rati n g t he i nte nsity of  
a n e ve nt , a n d b ot h A Es a n d S AEs ca n be assesse d as se vere.
A n e ve nt is defi ne d as “serio us ” w he n it meets at least 1 of  the pre defi ne d o utc o mes as descri be d 
i n t he defi niti on of a n S A E, N O T w he n it is rate d as se vere.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 3 5
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
F oll o w -u p of A Es a n d S A Es
If o nl y 
li mite d i nf or mati on 
is i nitiall y a vaila ble, 
f oll ow- u p 
re p orts are re q uire d. 
( N ote: F oll o w -u p S A E re p orts m ust i ncl u de t he sa me in vest i gat or ter m[s] i nitiall y re p orte d.) 
If a n o n g oi n g S A E c ha n ges i n its i nte nsit y or relati ons hi p t o st u d y treat me nt or if ne w 
i nf or mat i on bec o me s availa ble, t he S A E re p ort m ust be u p date d a n d s u b mitte d wit hi n 2 4 h o urs 
t o B M S ( or desi g nee) usi n g t he sa me pr oce d ure use d f or tra ns mitti n g t he i nitial S A E re p ort.
All S A Es m ust be f o ll owe d t o res ol ut i on or sta bilizati o n.
R E P O R TI N G O F S A E S T O S P O N S O R O R D E SI G N E E

S A Es, w he t her r elate d or n ot relate d t o st u d y tr e at m e nt, a n d pre g na ncies m ust be re p orte d 
t o B M S ( or desi g nee) i m me diatel y withi n 2 4 h o urs of a ware ness of t he e ve nt.

S A Es m ust be rec or de d o n t he S A E Re p ort F or m.

T he re q uire d met h o d f or S A E data rep orti n g is thr o u g h t he electr o nic case re p ort 
f or m (e C R F).

T he pa per S A E Re p ort F or m  is i nte n de d o nl y  as a bac k - u p o pti o n w he n t he electr o nic 
data ca pt ure s yste m is u na vaila ble/ n ot f u nct i oni n g f or tra ns missi o n of t he e C R F t o B M S 
( or desi g nee).

I n t his case, t he pa per f or m is tra ns mitte d via e mail or c o nfir me d facsi mile 
tra ns missi on.

W he n pa per f or ms are use d, t he ori gi nal pa per f or ms are t o re mai n o n site .

Pre g na ncies m u st be rec or de d o n pa per Pre g na nc y S ur veilla nce F or m s a n d tra ns mitte d via 
e mail or c o nfir me d facsi mile tra ns missi o n.
S A E E m ail A d dress:
S A E F acsi mile N u m ber: Will be pr ovi de d by l oc al site m o nit or.
S A E Tele p h o ne C o nt act (re q uire d f or S A E a n d pre g na nc y re p orti n g): Will be pr ovi de d by l oc al 
site m o nit or.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 3 6
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
A P P E N DI X 4
W O M E N O F C HI L D B E A RI N G P O T E N T I A L D E FI NI TI O N S A ND 
M E T H O D S O F C O N T R A C E P TI O N
A p pe n di x 4 pr o vi des ge neral  inf or m at i on a n d defi ni tio ns relate d t o W o ma n of  Chil d beari n g 
P ote nti al a nd m et h o ds of c o ntrace ptio n t hat ca n be a p plie d t o m ost cli nical trials. F or i nf or mat i on 
s pecific t o t his st u d y re gar di n g acce pta ble c o ntrace pti o n re q uire me nts f or female a n d ma le 
parti ci pa nts, refer t o t he Met h o ds of C o ntrace ptio n ta ble i n t his a p pe n di x. O nl y t he c o ntrace ptio n 
met h o ds t hat are hi g hl y effecti ve ( wit h a fail ure rate of < 1 % per year), wit h l o w user de pe n de nc y,
are acce pta ble f or t his st u d y.
D E FI NI TI O N S
W o m a n of C hil d be ari n g P ote nti al ( W O C B P)
A w o m a n is c o nsi dere d fertile f oll owi n g me narc he a n d u nt il bec o mi n g p ost m e n o pa usal unless 
p er m a ne nt l y sterile. 
P er m a ne nt 
sterilizati on 
met h o ds 
i ncl u de h ysterect o m y, 
bilateral 
sal pi n gect o m y, a n d bilateral o o p h orect o m y.
W o me n i n t he f oll o wi n g c ate g ories are n ot c o nsi dere d W O C B P :

Pr e m e narc hal

Pr e m e n o pa usal fe male wit h 1 of t h e fol l owi n g:

D oc u m e nte d h ysterect o m y

D oc u m e nte d bilateral sal pi n gect o m y

D oc u m e nte d bilateral o o p h orect o m y
N ote:
D o c u me ntati o n ca n c o me fr om t he sit e pers o n nel’s re vie w of  the parti ci pa nt’s me dica l 
rec or ds, me dical e xa mi nati on, or m e dical hist or y int er vie w.

P os t me n o pa usal fe male

A p ost m e n o pa usal st at e is defi ne d as 1 2 m o nt hs of  ame n orr hea i n a w o m a n o ver a ge 
4 5 years i n t he a bse nce of  ot her bi o l ogi cal or p h ysi ol o gi cal ca uses. I n a d ditio n, females 
u n der t he a ge of  55 years m ust ha ve a ser u m fol licle-sti m ulati n g h or m o ne ( F S H) le vel 
> 4 0 mI U/ m L t o c o nfir m me n o pa use.
N ote:
Fe males treate d wit h h or m o ne re place me nt t hera p y (H R T) are li kel y t o ha ve art ificiall y 
s u p presse d F S H le vels a n d ma y re q uire a was h o ut peri o d i n or der t o o btai n a p h ysi ol o gic F S H 
le vel. T he d urati o n of  the was h o ut peri o d is a f u ncti on of  the t ype of  HR T u se d. S u g geste d 
g ui deli nes f or t he d urati o n of  the was h o ut peri o d s f or H R T t ypes are prese nte d bel o w. In vest i gat ors 
s h o uld use t heir j u d ge me nt i n c hec ki n g ser u m F S H le vels. 

1 -wee k mi ni m u m f or va gi nal h or m o nal pr o d ucts (ri n gs, crea ms, gels)

4 -wee k mi ni m u m f or tra ns der m al pr o d ucts

8 -wee k mi ni m u m f or oral pr o d ucts
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 3 7
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Ot her pare nteral pr o d ucts ma y re q uire was h o ut peri o ds as l on g as 6 m o nt hs. If t he ser u m FS H 
le vel is > 4 0 mI U/ m L at a n y time d uri n g t he was h o ut peri o d, t he w o m a n ca n be c o nsid er e d 
p ost m e n o pa usal.
E n d of Rele v a nt S yste mic E x p os ure
E n d of  rele va nt s yste mic e x p os ure is t he ti me p oi nt w here t he In vest i gati onal M e dici nal P r o d uct 
(I M P) or a n y acti ve maj or met a b o lites ha ve decrease d t o a c o nce ntrati o n t hat is n o l on ger 
c o nsi dere d t o be r ele va nt f or h u ma n t erat o ge nicit y or fetot o xi cit y. T his s h o uld be e val uate d i n 
c o nte xt of  safety mar gi ns fr o m t he n o -o bser ve d -a d verse-effect le vel or t he ti me re q uire d f or 5 half-
li ves of t he I M P t o pass.
M E T H O D S O F C O N T R A C E P TI O N
L ocal  la ws a n d re g ulati ons ma y re q uire use of alter nati ve a n d/ or a d diti onal c o ntrace pti o n met h o ds.
Hi g hl y Effecti ve C o ntr ace pti ve Met h o ds T h at Are User De pe n de nt
F ail ure r ate of < 1 % per ye ar w he n use d c o nsiste ntly a n d c orrectly. a

C o m bi ne d (estr o ge n- a n d pr o gest o ge n -c o ntai ni n g) h or m o nal  c o ntrace ptio n ass ociate d wi t h 
i n hi biti on of o v ulat i on a n d/ or i m pla ntati o n . ( T his met h o d of c o ntrace pti o n ca n o nl y be use d 
b y W O C B P parti ci pa nts i n st u dies w here h or mo nal  c o ntrace ptio n is per mitte d b y  t he st u d y 
pr ot oc ol .)b

O r al ( birt h c o ntr ol pills)

Int ra vagi nal  (ri n gs)

T ra ns der mal

C o m bi ne d (estr o ge n-a n d pr o gest o ge n -c o ntai ni n g) h or m o nal  co ntrace pti o n m u st be gi n at 
least 3 0 da ys prior t o i ni tiatio n of  st u d y t hera p y.

Pr o gest o ge n -o nl y h or m o nal c o ntrace ptio n ass ociate d wit h i n hi biti on of  ov ulat i on. ( T h is
met h o d
of  co ntrace pti o n ca n o nl y be use d b y W O C B P parti ci pa nts i n st u dies w here 
h or m o nal  c o ntrace ptio n is per mitte d b y  t he st u d y pr ot oc ol.)b

O r al

Injecta ble

P r o gest o ge n-o nl y  hor m o nal c o ntrace ptio n m u st be gi n at least 3 0 d a y s pri or t o i ni tiat i on of 
st u d y t hera p y.
Hi g hl y Effecti ve Met h o ds T h at Are User I n de pe n de nt

I mpla nta ble pr o gest o ge n -o nl y  hor m o n al  co ntrace pti o n ass ociate d wit h 
i n hi biti on of 
o v ul at i on a n d/ or i m pla ntatio n . (T h is met h o d of  c o ntrace ptio n ca n o nl y be use d b y  W O C B P 
parti ci pa nts i n st u dies w here h or m o nal c o ntrace pti o n is per mitte d b y  t he st u d y pr ot oc ol.)b

I ntra uteri ne de vice.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 3 8
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d

I ntra uteri ne h or m o ne- releasi n g s yste m (I U S). (T h is met h o d
of  co ntrace pti o n ca n o nl y be 
use d b y W O C B P parti ci pa nts i n st u dies w here h or m o n al c o ntrace ptio n is per mitte d b y t h e 
st u d y pr ot o c ol.)b , c

Bilateral t u bal occl usi o n.

Vasect o mize d part ner 
Ha vi n g a vasect o mize d part ner is a hi g hl y effecti ve c o ntrace ptio n met h o d
pr o vi de d t hat t he 
part ner is t he s ole male se x ual part ner of  the W O C B P 
a n d t he a bse nce of  sp er m  has bee n 
c o nfir me d. If n ot, a n a d dit i onal hi g hl y  effecti ve met h o d of c o ntrace pti o n s h o ul d be use d.

Se x ual a bst i ne nce.
Sex u al a bsti ne nce is c o nsi dere d a hi g hly effective met h o d
o nly if defi ne d as refr ai ni n g fr o m 
heter osex u al i nterc o urse d uri n g t he e ntire peri o d of risk ass oci ate d wi t h t he st u dy tre at me nt. 
T he reli a bility of sex u al a bsti ne nce nee ds t o be ev al u ate d i n rel ati o n t o t he d ur ati o n of t he st u dy 
a n d t he preferre d a n d us u al lifestyle of t he p artici p a nt.

C o nti n u o us a bsti ne nce m ust be gi n at least 3 0 da ys pri or t o i nit iati on of st u d y  t hera p y.

It is n ot necessar y t o use a n y ot her met h o d of  co ntrace pti o n w he n c o m p lete a bsti ne nce is 
electe d.

W O C B P parti ci pa nts w h o c h o ose c o m p lete a bsti ne nce m u st c o nti n ue t o ha ve pre g na nc y 
tests, as s pecifie d i n Secti o n 2.

Acce pta ble alter nate met h o ds of  hi ghl y  effecti ve c o nt race pti o n m u st be disc usse d i n t he 
e ve nt t hat t he W O C B P partici pa nt
c h o oses t o f ore g o c o m plete a bst i ne nce.

P erio dic a bst i ne nce (incl u di n g , b ut n ot li mite d t o, cale n dar, s y m pt ot her mal, p ost o v ulat i on 
met h o ds), wit h dra wal ( c oit us i nterr u pt us), s per mici des o nl y, a n d lactatio nal a me n orr hea 
met h o d ( L A M) are n ot acce pta ble met h o ds of c o ntrace pti o n f or t his st u d y .
N O T E S: 
a
T y pical use fail ure rates ma y differ fr o m fail ure rates w h e n c o ntrace pti ve met h o ds are use d c o nsiste ntl y a n d 
c orrectl y. Use s h o ul d be c o nsiste nt wit h l ocal re g ulati o ns re gar di n g t he use of c o ntrace pti ve met h o ds f or 
partici pa nts i n cli nical st u dies. 
b
H or m o nal c o ntrace pti o n m a y  be s usce pti ble t o i nteracti o n wit h t he st u d y treat me nt, w hic h m a y  re d uce t he 
efficac y of t he c o ntrace pti ve met h o d. H or m o nal c o ntrace pti o n is per missi ble o nl y  wh e n t here is s ufficie nt 
e vi de nce t hat t he I M P a n d ot her st u d y me dicati o ns will n ot alter h o r m o nal e x p os ures s uc h t hat c o ntrace pti o n 
w o ul d be i neffecti ve or res ult i n i ncrease d e x p os ures t hat c o ul d be p ote ntiall y hazar d o us. I n t his case, alter nati ve 
met h o ds of c o ntrace pti on s h o ul d be utilize d. F or i nf or mati o n s pecific t o t his st u d y re gar di n g per missi bilit y of 
h or m o nal c o ntrace pti o n, refer t o .Secti o ns 6. 1  I N C L U SI O N C RI T E RI A a n d 7. 7. 1 P R O HI BI T E D A N D/ O R 
R E S T RI C T E D T R E A T M E N T S of t he pr ot oc ol.
c
I U Ss are acce pta ble met h o ds of c o ntrace pti o n i n t he a bse nce of defi niti ve dr u g i nteracti o n st u dies w he n h or m o ne 
e x p os ures fr o m i ntra uteri ne de vices d o n ot alter c o ntrace pti o n effecti ve ness. F or i nf or mati o n s pecific t o t his 
st u d y re gar di n g per missi bilit y of h or m o nal c o ntrace pti o n, r efer t o . Secti o ns 6. 1 I N C L U SI O N C RI T E RI A a n d 
7. 7. 1 P R O HI BI T E D A N D / O R R E S T RI C T E D T R E A T M E N T S of t he pr ot oc ol.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 3 9
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Less T h a n Hi g hl y Effecti ve C o ntr ace pti ve Met h o ds T h at Are User De pe n de nt 
F ail ure r ate of > 1 % per ye ar w he n use d c o nsiste ntly a n d c orrectly.

Male or female c o n d o m wi t h or wit h o ut s per mici de. Mal e a n d female c o n d o ms ca n n ot be 
use d si m ulta ne o usl y .

Di a p hra g m wit h s per mici de.

Cer vical ca p wit h s per mici de .

Va gi nal sp o n ge wi t h s per mici de.

Pr o gest o ge n -o nl y  or al hor m o n al  co ntrace pti o n, w here i n hi biti on of  ov ulati o n is n ot t he 
pri mar y  mec ha nis m of  actio n . ( T his met h o d
of  co ntrace pti o n ca n n ot be use d b y W O C B P 
parti ci pa nts i n st u dies w here h or m o nal c o ntrace pti o n is pr o hi bite d .)
U n acce pt a ble Met h o ds of C o ntr ace pti o n

P eri o dic a bst i ne nce (cale n dar, s y m pt other mal, p ost o v ulat i on met h o ds) .

Wit h dra wal ( c oit us i nterr u pt us).

S per mici de o nl y .

L A M .
C O L L E C TI O N O F P R E G N A N C Y I N F O R M A TI O N
G ui da nce f or c o llecti o n of  pre g na nc y inf or m atio n a n d o ut c o m e of  pre g na nc y o n t he Pre g na nc y 
S ur veilla nce F or m is pr o vi de d i n Sect i on 9. 2. 5 a n d A p pe n di x 3 .
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 4 0
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
A P P E N DI X 5
C RI T E RI A T O D E FI N E I N A D E Q U A T E R E S P O N S E ( P RI M A R Y), 
L O S S O F R E S P O N S E ( S E C O N D A R Y), A N D I N T O L E R A N C E T O 
P R E VI O U S S T A N D A R D O F C A R E M E DI C A TI O N( S)
F or a n y me dicat i on or tr e at m e nt re gi me n t hat satisfies t he i ncl usi on crit eria a n d is n ot descri be d 
here, pl ease c o ntact t he Cli nical Trial P h ysicia n or desi g n ee.
It will be d o c u m e nte d w he n t he s u bject has ha d i na de q uate res p o nse, l oss of  res p o nse, or bee n 
i ntol era nt t o (e g, u na ble t o ac hie ve d oses, d ose levels, or treat me nt d urati o ns eit her beca use of 
treat me nt -relate d si de effects a n d/ or la b orat or y a b n or malit ies) prior t hera p y .
Me dic ati o n Cl ass
Q u alif yi n g Criteri a 
Oral 5 -A S As
A n y  O N E ( or m ore) of t he f oll o wi n g:
Si g ns a n d s y m pt o ms of persiste ntl y acti ve disease des pite a hist or y of at least o ne 
4 -wee k re gi me n at hi g hest d ose or  per i nstit uti o nal practice
D oc u me nte d hist or y of i nt olera nce t o oral 5 -A S As w here s u bject de vel o pe d a d verse 
reacti o ns i ncl u di n g, b ut n ot li mite d t o, hea dac hes, na usea/ v o miti n g, a n ore xia, 
a b d o mi nal pai n, diarr hea, pericar ditis, or pa ncreatitis 
C ortic oster oi ds (e g, oral 
pre d nis o ne, b u des o ni de 
M M X, i ntra ve n o us 
c ortic oster oi ds)
A n y  O N E ( or m ore) of t he f oll o wi n g:
Si g ns a n d s y m pt o ms of persiste ntl y acti ve disease des pite a hist or y of at least o ne
i n d ucti on re gi me n of a c ortic oster oi d f or t he treat me nt of C D f or at least 2 wee ks or  
per i nstit uti o nal practice
I na bilit y t o st o p ster oi ds wit hi n 3 m o nt hs wit h o ut rec urre nt acti ve disease
E x perie nce d a rela pse re q uiri n g ster oi ds wit hi n 3 m o nt hs of st o p pi n g ster oi ds 
At least 2 faile d atte m pts t o ta per c ortic oster oi ds bel o w a d ose t hat is e q ui vale nt t o 
or al pre d nis o ne 1 0 m g/ da y ( or e q ui vale nt) or b u des o ni de 3 m g/ da y ( or e q ui vale nt) o n 
2 se parate occasi o ns ( dosa ge re gi me n ca n be a dj uste d t o acc o m m o date m g/ k g/ da y 
d osi n g as a p pr o priate)
D oc u me nte d hist or y of i nt olera nce t o c or tic oster oi ds w here s u bject de vel o pe d 
a d verse reacti o ns i ncl u di n g, b ut n ot li mite d t o, C us hi n g's s y n dr o me, 
oste o pe nia/ oste o p or osis, h y per gl yce mia, i ns o m nia, cataracts, refract or y ster oi d ac ne, 
or  i nfecti o n
I m m u n o m o d ulat ors (e g, 
azat hi o pri ne, 6-
merca pt o p uri ne, 
c ycl os p ori ne, 
met h otre xate)
A n y  O N E ( or m ore) of t he f oll o wi n g:
Si g ns a n d s y m pt o ms of persiste ntl y acti ve disease des pite a hist or y of at least o ne 8 -
1 2 wee k re gi me n of i m m u n o m o d ulat or gi ve n at a sta n dar d mai nte na nce d ose or per 
i nstit uti o nal practice
Hist or y of i nt olera nce t o at least 1 i m m u n o m o d ulat or w here s u bject de vel o pe d 
a d verse reacti o ns i ncl u di n g, b ut n ot li mite d t o, na usea/ v o miti n g, a b d o mi nal pai n, 
pa ncreatitis, li ver f u ncti o n test a b n or malities, l y m p h o pe nia, m yel os u p pressi o n, or 
pa ncreatitis
Bi ol o gic t hera p y (e g, 
uste ki n u ma b, a batace pt, 
i nfli xi ma b, eta nerce pt, 
a dali m u ma b, a na ki nra, 
rit u xi ma b, a n d 
ve d oliz u ma b )
A n y  O N E ( or m ore) of t he f oll o wi n g:
Si g ns a n d s y m pt o ms of persiste ntl y acti ve disease des pite a n a de q uate st u d y of 
i n d ucti on treat me nt p er c o u ntr y’s a p pr o ve d la bel (if a p plica ble) or per i nstit uti o nal 
practice
Rec urre nce of s y m pt o ms d uri n g mai nte na nce d osi n g f oll o wi n g pri or cli nical be nefit
Hist or y of i nt olera nce t o at least 1 bi ol o gic t hera p y w here s u bject de vel o pe d a d verse 
reacti o ns i ncl u di n g, b ut n ot li mite d t o, i nf usi o n-relate d reacti o n, de m yeli nati o n, 
c o n gesti ve heart fail ure, de vel o p me nt of a nti -dr u g a nti b o dies, i nfecti o n, art hral gia, o r 
li ver test a bn or malities
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 4 1
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Me dic ati o n Cl ass
Q u alif yi n g Criteri a 
Ot her s yste mic 
i m m u n o m o d ulat or y 
treat me nts f or C D 
A n y  O N E ( or m ore) of t he f oll o wi n g:
Si g ns a n d s y m pt o ms of persiste ntl y acti ve disease des pite a n a de q uate st u d y of 
i n d ucti on treat me nt per c o u ntr y’s a p pr o ve d la bel (if a p plica bl e) or per i nstit uti o nal 
practice
Rec urre nce of s y m pt o ms d uri n g mai nte na nce d osi n g f oll o wi n g pri or cli nical be nefit
Hist or y of i nt olera nce w here partici pa nt de vel o pe d a d verse reacti o n(s)
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 4 2
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S -9 8 6 3 7 4
Oza ni m o d
A P P E N DI X 6
P E DI A T RI C C R O H N’ S DI S E A S E A C T I VI T Y I N D E X ( P CD AI)
S o urce: H ya ms J S, Ferr y G D, Ma n del F S, et al. De vel o p me nt a n d vali dati o n of a pe diatric Cr o h n’s disease acti vit y i n de x. J Pe diatr Gas tr oe nter ol N utr 1 9 9 1; 1 2: 4 3 9 -
4 7. 
N ote: T he a b d o mi nal pai n, st o ol fre q ue nc y a n d ge neral  well bei n g sc ores fr o m t he wee k pri or t o eac h st u d y visit will be use d t o calc ulate 
t he P CD AI. If t he s u bject is u n der g oi n g a pla n ne d c ol o n osc o p y, the da y (s) of  b o wel pre parati o n s h o ul d be e xcl u de d fr o m c o nsi derat i on.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 4 3
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 4 4
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 4 5
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
A P P E N DI X 9
P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E HI S T O R Y
O ver all R ati o n ale f or Pr ot oc ol A me n d me nt 0 1, 2 2 -Dec - 2 0 2 2
T he mai n rati onale f or t his a me n d me nt is t o u p date t he i ncl usi on crit eria t o ( a) allo w f or p ositive 
varicella z oster vir us ( V Z V) a nt i b o d y titers t o hel p f ulfill t he vacci nat i on re q uire me nt a n d 
( b) u p date t he dr u g cleara nce peri o d f or pri or bi o l ogi cs fr o m 8 wee ks t o 4 wee ks. T he ta ble bel o w 
hi g hli g hts t he ke y c ha n ges ma de t o t he pr ot oc ol. A d dit i onal re visi o ns as o utli ne d bel o w, i ncl u di n g 
t o secti o ns of t he Pr ot oc ol S u m mar y, ha ve bee n ma de t o e ns ure ali g n me nt t hr o u g h o ut t he pr ot oc ol.
S U M M A R Y O F C H A N G E S F O R P R O T O C O L A M E N D M E N T 0 1
Secti o n N u m ber 
& Title
Descri pti o n of C h a n ge
Brief R ati o n ale
Title Pa ge

A d de d Cel ge ne I nter nati o nal II Sàrl 
tele p h o ne n u m ber

U p date d Cli nical Trial P h ysicia n c o ntact 
details

A d mi nistrati ve c ha n ges
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 4 6
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
S U M M A R Y O F C H A N G E S F O R P R O T O C O L A M E N D M E N T 0 1
Secti o n N u m ber 
& Title
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n 3. 1. 1:
S u m mar y of 
N o ncli nical St u dies

Re vise d te xt re gar di n g j u ve nile t o xicit y 
st u dies

U p date d base d o n a d diti o nal data a vaila ble a n d 
t o ali g n wit h t he I n vesti gat or’s Br oc h ure
Secti o n 3. 3. 1:
Ris k Assess me nt 
 
 
 
 
 
 
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 4 7
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
S U M M A R Y O F C H A N G E S F O R P R O T O C O L A M E N D M E N T 0 1
Secti o n N u m ber 
& Title
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n 5. 1:
O verall Desi g n

Re m o ve d t he f oll o wi n g state me nt: “ T he 
fi nal decisi o n t o disc o nti n ue t he participa nt 
earl y f or e ntr y i nt o t he L T E Peri o d will be 
left t o t he discreti o n of t he i n vesti gat or.” 

Treat me nt disc o nti n uati o n para meters m ust be 
f oll o we d per t he S p o ns or g ui da nce i n t he best 
i nterest of t he partici pa nt

M o ve d st u d y disc o nti n uati o n la n g ua ge t o t he 
st u d y disc o nti n uati o n secti o n

State me nt m o ve d t o a p pr o priate secti o n wit hi n 
t he pr ot oc ol f or clarit y
Secti o n 6. 1:
I ncl usi o n Criteria

I ncl usi o n criteri o n (I C) # 2 b: M o difie d te xt 
re gar di n g l ocal hist o pat h ol o g y sa m ple 
c ollecti o n

T o all o w f or t he c ollecti o n of l ocal hist ol o g y 
sa m ples f or disease c o nfir mati o n

I C # 2f: A d de d d oc u me ntati o n of p ositi ve 
V Z V I g G a nti b o d y

I n a d diti o n t o d oc u me ntati o n of varicella 
vacci nati o n, p ositi ve V Z V a nti b o d y titers are 
als o c o nsi dere d a n acce pta ble f or m of 
i m m u nit y a n d ca n be use d t o hel p f ulfill t he 
vacci nati o n re q uire me nt f or eli gi bilit y

I C # 4: Re m o ve d te xt re gar di n g c o u nseli n g of 
male partici pa nts t hat are se x uall y acti ve 
wit h fe males of c hil d beari n g p ote ntial

C o u nseli n g is u n necessar y, as t here are n o 
safet y c o ncer ns re gar di n g re pr o d ucti ve stat us 
of male partici pa nts f oll o wi n g st u dies o n male 
re pr o d ucti ve effects
Secti o n 6. 2:
E xcl usi o n Criteria

E xcl usi o n criteri o n ( E C) # 1j: A d de d a 
p ositi ve uri ne pre g na nc y testi n g o n Da y 1

Clarifie d t hat partici pa nts are n ot eli gi ble f or 
partici pati o n if pre g na nt o n Da y 1

E C # 1 p: A d de d d oc u me nte d e vi de nce of 
s ur veilla nce f or p ol y ps, d ys plasia, or 
mali g na nc y i n t he last 2 years or per l ocal 
a n d nati o nal me dical g ui deli nes

Clarifie d ca ncer s ur veilla nce g ui deli nes, gi ve n 
t he ris k of c olorectal ca ncer i n t his p o p ulati o n

E C # 3c: S h orte ne d t he ti me re q uire d 
bet wee n treat me nt wit h a bi ol o gic a ge nt a n d 
t he first d ose of st u d y treat me nt

Gi ve n t he ris ks ass ociate d wit h i m m u ne 
s u p pressi o n a n d treat me nt para meters use d i n 
cli nical practice, t he pr o p ose d ti mefra me 
o pti mizes t he treat me nt -free peri o d bet wee n t he 
pre vi o us li ne of t hera p y a n d t he c urre nt st u d y
Secti o n 6. 4. 1

A d de d la n g ua ge t o all o w f or use of pri or 
c ol o n osc o pies

T o ali g n wit h i ncl usi o n criteria
Secti o n 7. 2:
Met h o d of St u d y 
I nter ve nti o n 
Assi g n me nt

A d de d t he o pti o n f or a n a ge ra n ge f or 
c o nse nt/asse nt, per l ocal or c o u ntr y 
g ui deli nes

A ge ra n ges f or i nf or me d c o nse nt f or m a n d 
asse nt si g nat ures ma y be g o ver ne d b y l ocal or 
c o u ntr y re g ulati o ns
Secti o n 7. 3:
Bli n di n g

Re m o ve d te xt re g ar di n g s hi p pi n g of 
ra n d o mizati o n sc he d ules t o, bli n di n g, a n d 
i n v ol ve me nt i n st u d y c o n d uct of p har macist 
or ot her i n di vi d ual res p o nsi ble f or t he 
dis pe nsi n g of bli n de d st u d y treat me nt

Sites are n ot re q uire d t o ha ve a n y u n bli n de d 
site staff
Secti o n 7. 7. 1:
Ster oi d Ta per

Re vise d i nstr ucti o ns f or ster oi d ta peri n g

Ster oi d ta per ca n be i nitiate d pri or t o t he e n d of 
i n d ucti o n gi ve n t he p ote ntial safet y iss ues wit h 
ster oi d use i n c hil dre n
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 4 8
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
S U M M A R Y O F C H A N G E S F O R P R O T O C O L A M E N D M E N T 0 1
Secti o n N u m ber 
& Title
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n 7. 7. 2:
Pr o hi bite d a n d/ or 
Restricte d 
Treat me nts

A d de d p ost -baseli ne i nitiati o n or i ncrease i n 
s yste mic c ortic oster oi ds d uri n g I n d ucti o n or 
Mai nte na nce Peri o ds, a n d i ncrease i n 
s yste mic c ortic oster oi ds > 4 0 m g/ da y 
pre d nis o ne or e q ui vale nt d uri n g L T E

F or c o nsiste nc y t hr o u g h o ut pr ot oc ol

Clarifie d t hat s yste mic i m m u n o m o d ulat or y 
a ge nts are pr o hi bite d a n d/ or restricte d d uri n g 
t he st u d y

T o clarif y t hat t o pical use is all o we d d uri n g t he 
st u d y

A d de d s yste mic c ortic oster oi d d oses f or 
s pecific wei g ht gr o u ps

Clarificati o n
Secti o n 8. 1:
Disc o nti n uati o n 
Fr o m St u d y 
I nter ve nti o n 

Re m o ve d re q uire me nt f or treat me nt 
disc o nti n uati o n f or partici pa nts meeti n g a n y 
of t he criteria f or treat me nt fail ure d uri n g t he 
I n d ucti o n Peri o d

Partici pa nts w h o meet treat me nt fail ure criteria 
m a y  c o nti n ue i n t he Ope n -la bel E xte nsi o n 
( O L E) Peri o d of t he st u d y

Re m o ve d t he f oll o wi n g se nte nce: 
“ Partici pa nts recei vi n g a n y me dical or 
s ur gical i nter ve nti o n f or t he treat me nt of 
Cr o h n’s Disease t hat meet t he criteria f or 
treat me nt fail ure 
 d uri n g 
t he I n d ucti o n peri o d will be disc o nti n ue d 
fr o m t he st u d y a n d will n ot be eli gi ble f or 
t he L T E Peri o d.”

Partici pa nts w h o meet treat me nt fail ure criteria 
m a y  c o nti n ue i n t he O L E Peri o d of t he st u d y

A d de d s yste mic c ortic oster oi d d oses f or 
s pecific wei g ht gr o u ps

Clarificati o n
Secti o n 9:
St u d y  Assess me nts 
a n d Pr oce d ures

Clarifie d t hat t hera pe utic dr u g m o nit ori n g 
( T D M) will be perf or me d l ocall y

T D M ca n be use d t o c o nfir m dr u g le vels (f or 
pri or bi ol o gic use) a n d will be perf or me d 
l ocall y b y t he site

M o difie d t o le n gt he n t he wi n d o w f or 
e n d osc o p y f or t he assess me nt of efficac y at 

T o all o w f or fle xi bilit y i n sc he d uli n g

Clarifie d t hat f oll o w -u p is re q uire d f or all 
partici pa nts w h o recei ve d ≥ 1 d ose of st u d y 
treat me nt

Clarificati o n of partici pa nts w h o re q uire 
f oll o w-u p visits

 
 
 
 
 
 
 

Clarificati o n of t he criteria b y w hic h 
partici pa nts ma y e nter t he L T E Peri o d

A d de d s yste mic c ortic oster oi d d oses f or 
s pecific wei g ht gr o u ps

Clarificati o n
Secti o n 9. 2. 5

Re m o ve d re q uire me nt trac ki n g pre g na ncies 
i n fe male part ners of male partici pa nts

Esti mati o n of se me n le vels a n d va gi nal 
a bs or pti o n were perf or me d, a n d cli nicall y 
mea ni n gf ul e x p os ures were n ot ac hie ve d. I n 
a d diti o n, t he S p o ns or has n ot o bser ve d a n y 
i ncrease d ris k i n t he pre g na nc y o utc o mes f or 
fe male part ners of male s u bjects.
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 4 9
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
S U M M A R Y O F C H A N G E S F O R P R O T O C O L A M E N D M E N T 0 1
Secti o n N u m ber 
& Title
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n 9. 4. 1 1:
Cli nical Safet y 
La b orat or y 
Assess me nts 

Re vise d t he r oles of ce ntral a n d l ocal 
la b orat ories a n d relate d re q uire me nts

Data fr o m t he ce ntral la b orat or y will be use d 
f or a nal ysis, b ut l ocal la b orat ories ma y be use d, 
if nee de d, u n der s pecific circ u msta nces
Secti o n 9. 4. 1 1. 1:
He mat ol o g y

A d de d t hat alerts f or o ut -of -ra n ge val ues will 
be fla g ge d f or t he sit e w hile kee pi n g t he 
n u merical res ults bli n de d

Alt h o u g h w hite bl o o d cell c o u nts a n d 
differe ntials are bli n de d gi ve n t he 
p har mac o d y na mic effect of oza ni m o d o n 
a bs ol ute l y m p h oc yte c o u nts, sites will be 
alerte d t o f oll o w-u p o n o ut -of -ra n ge val ues

A d de d i nstr ucti o n t o c o ntact t he Cli nical 
Trial P h ysicia n/ Me dical M o nit or if t he 
partici pa nt’s he m o gl o bi n le vel is ≤ 7. 0 g/ d L 
d uri n g t he st u d y

T he sti p ulati o n f or he m o gl o bi n le vel t o be 
mai ntai ne d a b o ve 7. 0 d/ d L has bee n pre vi o usl y 
n ote d i n t he eli gi bilit y crite ria. T he i nstr ucti o n 
t o c o ntact t he Cli nical Trial P h ysicia n/ Me dical 
M o nit or f or disc ussi o n has bee n a d de d t o t his 
secti o n t o rei nf orce t he nee d t o m o nit or 
partici pa nts t hr o u g h o ut t he st u d y f or safet y 
reas o ns.
Secti o n 9. 4. 1 1. 3:
Ser ol o g y 

A d de d testi n g f or V Z V a nti b o d y titer

Titers ca n be teste d t o f ulfill t he vacci nati o n 
re q uire me nt f or eli gi bilit y
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 5 0
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v


Cli nical Pr ot oc ol
I M 0 4 7 0 2 3
B M S - 9 8 6 3 7 4
Oza ni m o d
S U M M A R Y O F C H A N G E S F O R P R O T O C O L A M E N D M E N T 0 1
Secti o n N u m ber 
& Title
Descri pti o n of C h a n ge
Brief R ati o n ale
A p pe n di x 2:
St u d y  G o ver na nce 
C o nsi derati o ns 

A d de d 2 ne w secti o ns: “ B M S C o m mit me nt 
t o Di versit y i n Cli nical Trials” a n d “ Data 
Pr otecti o n, Data Pri vac y, a n d Data Sec urit y”

T o ali g n t he pr ot oc ol wit h B M S’ c o m mit me nt 
t o di versit y a n d t he E ur o pea n U ni o n Cli nical 
Trials Re gister
T hr o u g h o ut t he 
pr ot oc ol 

Clarifie d t hat ra n d o mizati o n a n d Da y 
are 
t he sa me

C ha n ge d t he ter m “s u bject” t o “ partici pa nt”

A d de d “ oral” t o b u des o ni de a n d 
becl o met has o ne refere nces f or clarit y

Mi n or e dit orial a n d f or matti n g c ha n ges t hat 
d o n ot affect c o nte nt

Clarificati o ns
Pr ot oc ol A me n d me nt N o.: 0 2
Date: 1 4- A u g- 2 0 2 3
1 5 1
3 . 0
A p p r o v e d
9 3 0 1 8 1 7 8 7
3 . 0
v
A p p r o v e d
1 . 0
v