A Phase 2/3, Multicenter, Randomized, Double-blind Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Oral Ozanimod (RPC1063) in Pediatric Participants With Moderately to Severely Active Crohn's Disease With an Inadequate Response to Conventional Therapy
Phase: PHASE2
Conditions: Crohn Disease
Sponsor: Bristol-Myers Squibb

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
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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
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1 0 0
1 0 2
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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
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9 3 0 1 8 1 7 8 7
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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
................................................................................................................................. 
 
 
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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
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v
A p p r o v e d
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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