A Prospective, Open-label, Single Center Abatacept in IgG4-Related Disease 10-patient Proof-of-concept Study
Phase: PHASE2
Conditions: IgG4-related Disease
Sponsor: Massachusetts General Hospital

Brist ol  M yers  S q uib b  
Pr ot oc ol  S yno psis:  A batace pt in  I g G 4 -R D  
Clinica l  St ud y  S yno psis 
C O N FI D E N TI A L  
Pa ge 1  of 6 6  
V 3. 1: O ct 2 8, 2 0 1 8  
 
 
1  
TI T L E  P A G E  
C LI NI C A L  S T U D Y  P R O T O C O L  
A pros pe cti ve, o pe n -l a bel,  si ngle ce nte r a bat ace pt i n  I g G 4-R el ate d Dis e as e 1 0 -patie nt pro of - 
of- c o nce pt  s t u dy  
 
 
B M S Pr ot oc ol   N o.: 
I M 1 0 1- 7 4 4 
Trial  Re gistrat io n  N u mber/ E U D R A C T   N o.:  
N C T 0 3 6 6 9 8 6 1 
Test  Pr o d uct: 
A batace pt  
I ndicatio n: 
I g G 4-Relate d  Disease  
S p o ns or: 
Massac husetts  Ge neral   H os pital 
De velo p me nt  P hase:  
P hase  2 
Principa l  I nvestiga t or : 
J o hn  H.  St o ne, M D,  M P H  
J H St o ne @ mgh. har var d.e d u 
 
Date of  t he  Pr ot oc ol: 
O ct o ber 2 8, 2 0 1 8 
 
Versio n  of  t he Pr ot oc ol: 
 3. 1

Brist ol  M yers  S q uib b  
Pr ot oc ol  S yno psis:  A batace pt in  I g G 4 -R D  
Clinica l  St ud y  S yno psis 
C O N FI D E N TI A L  
Pa ge 2  of 6 6  
V 3. 1: O ct 2 8, 2 0 1 8  
 
 
 
P R O T O C O L  S Y N O P SI S  
 
Prot oc ol  Title:  
A pr os pective,  o pe n -la bel,  single  ce nter  a batace pt  in  I g G 4-Relate d  Disease 
1 0 -patie nt  pr o of-of-c o nce pt  st ud y 
Prot oc ol  S hort 
 
A batace pt  in  I g G 4 -Relate d  Dise ase:  A 1 0 -patie nt  pr o of-of-c o nce pt  st ud y 
St u dy  N u m be r:  
B M S Pr ot oc ol  N o.: I M 1 0 1 -7 4 4  
I nvesti g ati o nal 
 
A batace pt  
D e vel o p me nt 
 
P hase 2  
I n dic ati o n 
I g G 4-Relate d  Disease  (I g G 4 -R D)  
S po ns or:  
Massac husetts  Ge neral  H os pital  
Co or di n ati n g 
I nvesti g at or: 
Dr. J o hn  H. St o ne, Har var d,  Massac husetts  Ge neral  H os pital  
St u dy  Ce nte r(s):  
Single  C e nter:  Massac husetts  Ge neral  H os pital  
St u dy  O bje cti ve s :  
Pri mary  O bje cti ve  
•  
T o  assess t he effect  of wee kly  s ubc uta ne o us ( S C) a d minis tra t io n  of a batace pt  
o n c o mplete  re missio n  of I g G 4-R D  
Se c o n dary  O bje cti ve s 
•  
T o  assess  t he  effect  of  a batace pt  o n  disease  res p o nse  at 4, 1 2 a nd  2 4 wee ks 
a nd c o mplete  re missio n  at 3 6  wee ks  
•  
T o  assess t he effect  of a batace pt o n ti me t o disease  re missio n (I g G 4-R D  RI  = 
0),  re missio n  rates,  nu mber  of disease  flares  per s ubject  o ver  ti me 
•  
T o  assess t he effect  of a batace pt  o n p hysicia n  glo bal assess me nt ( P G A), 
S y mpt o m Se verit y  I nde x,  a nd c u mulati ve  c ortic oster oid   d oses 
•  
T o  assess  t he  effect  of  a batace pt  o n  ser u m  i m m u no glo b uli n  le vels,  I g G 4 
s ubclass  c o nce ntratio ns,  I g E  le vels,  e osino p hils,  a nd ser u m  C 3 a nd C 4 le vels 
at 4, 1 2, 2 4 a nd 3 6 wee ks 
E x pl orat ory  O bje cti ves  
T o assess t he effect  of a batace pt  o n C D 4 + T cells  a nd B cell  s ubsets, 
s pecificall y: 
- C D 4 + c yt ot o xic  T ly mp hoc yte s 
- C D 8 + c yt ot o xic  T ly mp hoc yte s 
- C D 4 + T  follic ula r  helper  cells 
- C D 4 + perip heral  helper  T  cells 
- Plas ma blast s  
- Activate d  B  cells 
 

Brist ol  M yers  S q uib b  
Pr ot oc ol  S yno psis:  A batace pt in  I g G 4 -R D  
Clinica l  St ud y  S yno psis 
C O N FI D E N TI A L  
Pa ge 3  of 6 6  
V 3. 1: O ct 2 8, 2 0 1 8  
 
 
St u dy  D e s i g n:  
T his  is  a P hase   2, single ce nter,   pr o of  of c o nce pt clinica l trial in s ubjects wit h  
active I g G 4-R D.  A p pr o xi matel y  1 0  s ubjects  wit h  active  I g G 4 -R D  will 
be 
e nr olle d  int o  t his  st ud y.  S ubjects  will  receive  wee kly  s ubc uta ne o us  d oses  of 
a batace pt  ( 1 2 5 mg)  for 2 4 d oses.  S ubjects  w ho  are o n pre d nis o ne  at baseline  will 
be gin  a n  investi ga t or -dire cte d  c ortic oster oid  ta per  designe d  t o  disc o nti n ue 
pre d nis o ne  not  later  t ha n  8 wee ks after  t he  baseline  visit.    
I nvesti g ati o nal 
M e dici nal 
Pro d uct(s);  I M P, 
D os e  a n d  R o ute  
of 
 
D ose a nd r o ute  of a d ministrati o n:  a batace pt  ( 1 2 5 mg)  will  be give n  b y S C 
injectio n  e ver y  7 da ys for  up t o 2 4 d oses ( 2 4 wee ks). 
 
R efe re n ce 
 
N o ne  
N u m be r  of 
S u bje cts   Pl a n ne d:  
A p pr o xi mate l y  1 0 s ubjects  wit h  active  I g G 4 -R D  
Dia gnos is  a nd  Main 
Criteria  for 
I nclus io n: 
Male  a nd fe male  s ubjects  a ge 1 8 or older  w ho fulfill  t he A C R/ E U L A R  2 0 1 8 
C lassifica t io n  C riteria  for  I g G 4 -R D  wit h  a mini m u m  I g G 4 -R D  Res p o nder  I nde x 
sc ore of 2 
St u dy  D urati o n:  
After  scree ning  a nd e nr oll me nt,  eligible  s ubjects  will  receive  a n initial 
s ubc uta ne o us  d ose of a batace pt ( 1 2 5 mg)  follo we d  b y wee kly  s ubc uta ne o us  d oses 
of a batace pt  ( 1 2 5 mg)  for  a t otal  of up t o 2 4 d oses  ( 2 4 wee ks). If  s ubjects  are o n 
pre d nis o ne  at baseline,  t he y  will be gin  a n  investi ga t or -directe d  c ortic oster oid 
ta per designe d  t o disc o nti n ue  pre d nis o ne  not  later  t ha n  8 wee ks after  t he  baseline 
visit.  S ubjects  will  be follo we d  o n st ud y  for  1 2 wee ks follo wi n g  t he  last  d ose for 
a t otal  st ud y  perio d  of up t o 3 6 wee ks.  
I ncl usi o n  Crite ri a: S ubjects  w ho  meet  t he follo wi n g  criteria  will  be c o nsidere d  eligible  t o participate 
in  t he  clinica l  st ud y  if  t he y: 
1.  Are male  or fe male  1 8 years  of a ge or older  
2.  Meet t he A C R/ E U L A R  2 0 1 8 C lassifica t io n  C riteria  for  I g G 4 -R D (see 
a p pe ndix  G) 
3.  Ha ve  active  disease  base d o n a n I g G 4 -R D  RI ≥2 at scree ning  wit h  disease 
ma nife sta tio n  in  at least  o ne  or ga n  s yste m  e xcludi n g  ly mp h  no des  at 
scree ning  
4.  Ma y or ma y  not  ha ve  receive d  prior  I g G 4 -R D  t hera p y  
5.  M ust  be willi n g  t o ta per off  a ny  s yste mic  c ortic oster o id  t hera p y  wit hi n 8 
wee ks of first  d ose of  trial  dr ug.  
6.  M ust  be a ble  a nd willi n g  t o disc o ntin ue  a ny  i m mu nos up pr essi ve  a ge nt  at 
scree ning  (e. g.  met hotre xate,  myc o p he nolate  mofetil,  6-merca pt o p uri ne, 
tacr oli m us,  c yclo p hos p ha mid e  or azat hio pri ne). 
7.  N o hist or y of se vere  aller gic  reactio ns  t o mo noclo nal  a ntib o dies.    
8.  Are a ble  a nd willi n g  t o c o mplete  t he  e ntire  st ud y  per t he  st ud y  sc he d ule.  
9.  Are  willi n g  t o  fore go  ot her  for ms  of  e xperi me nta l  treat me nt  d uring  t he 
st ud y.  
1 0.  ca n pr o vide  writte n  infor me d  c o nse nt.  
 

Brist ol  M yers  S q uib b  
Pr ot oc ol  S yno psis:  A batace pt in  I g G 4 -R D  
Clinica l  St ud y  S yno psis 
C O N FI D E N TI A L  
Pa ge 4  of 6 6  
V 3. 1: O ct 2 8, 2 0 1 8  
 
 
 
E xcl usi o n  Crite ri a:  
S ubjects  w ho  meet  o ne or more  of  t he follo wi n g  criteria  will  not be c o nsidere d 
eligib le  t o participate  in  t he  clinica l  st ud y: 
 
1.  Hist or y  or e vide nce  of  a clinicall y  unsta ble/ u nc o ntr olle d  dis or der, 
c o nditio n  or  disease  (includ i n g  b ut  not  li mit e d  t o car dio p ul mo nar y, 
o nc olo gic,  re nal,  he patic,  meta b olic,  he mat olo gic  or ps yc hiatric)  ot her 
t ha n  I g G 4-R D  t hat,  in  t he  o pinio n  of t he  I nvestigat or,  w o uld  p ose a ris k 
t o patie nt  safet y  or interfere  wit h  t he  st ud y  e valuatio n,  pr oce d ures  or 
c o mpletio n.  
2.  Mali gna nc y  wit hi n  5 years  (e xce pt  s uccessfull y  treate d in  sit u  cer vical 
ca ncer,  resecte d s q ua mo us  cell  or basal  cell  carcino ma  of  t he s kin,  or 
pr ostate  ca ncer wit h  no rec urre nce  ≥3 years  follo wi n g  pr ostatect o my).  
3.  Liver  disease:  Ac ute  or c hr o nic  no n -I g G 4-related  liver  disease  dee me d 
s uffic ie nt l y  se vere  t o i mpair  t heir  a bilit y  t o  participate  in  t he  trial. 
4.  U nc o ntr olle d  disease:  e vide nce  of a not her  unc o ntr olle d  c o nditio n, 
includ i n g  dr ug  a nd  alc o hol  a b use,  w hic h  c o uld  interfere  wit h 
participatio n  in  t he  trial  acc or d ing  t o t he  pr ot oc ol. 
5.  Prese nce  of rec urre nt  or c hr o nic  infectio ns,  define d  as ≥3 infectio ns 
re q uiri n g  a nti micr o b ia ls  o ver  t he  past  6 mo nt hs  prior  t o  scree ning. 
6.  Active  infectio n  re q uirin g  hos pitalizatio n  or treat me nt  wit h  pare nteral 
a nti micr o bials  wit hin  t he  3 0 da ys prior  t o ra nd o mizat io n.  
7.  Prior  use  of  rit uxi ma b  ( or  ot her  B  cell  de pletin g  a ge nts)  wit hi n  6 mo nt hs 
of e nr oll me nt  unless  B cells  ha ve  bee n de mo nstrate d  t o ha ve 
re p o p ulate d. 
8.  Use  of  a ny  investi ga tio na l  a ge nt  wit hi n  5 half -li ve s  of  t he  a ge nt  ( or  6 
mo nt hs  if  t he  half -li fe  is  unk no w n)  prior  t o e nr oll me nt. 
9.  W hite  blo o d  cell  c o unt  < 2. 5 x 1 0 3/ µ L. 
1 0.  A bs olute  ne utr o p hil  c o unt  ( A N C) < 1. 0 x 1 0 3/ µ L. 
1 1.  I g G 4-relate d  re nal  disease  wit h  ser u m  creatini ne  > 2. 0 mg/ d L.  
1 2.  He mo glo bi n  < 1 0 g/ d L. 
1 3.  Platelet  c o unt  < 7 5 x 1 0 9/ L. 
1 4.  K no w n  p ositive  res ult  fo r  HI V  I or II a ntib o d y,  he patitis  B s urface 
a ntige n,  he patitis  B c ore a ntib o d y  or he patitis  C a ntib o d y.  
1 5.  Has receive d  live  vaccines  wit hi n  4 wee ks’ o k e nr oll me nt.  
1 6.  I na bilit y  t o  c o m munica te  relia bl y  wit h  t he  invest i gat or. 
1 7.  Patie nt  is  pre gna nt  or breast  fee din g  or pla nni n g  t o  bec o me  pre gna nt 
w hile  e nr olle d  in  t he  st ud y,  up  t o E O S visit.  
1 8.  P ositive  pre gna nc y  test  at  scree ning  or  d uring  t he  st ud y.  
1 9.  S ubjects  of  c hild beari n g  p ote ntial  w ho d o not  a gree t o use me dicall y 
acce pta ble  met ho ds  of c o ntrace ptio n.  
2 0.  K no w n  or s us p ecte d  se nsiti vit y  t o ma m malia n  cell-derive d  pr o d ucts  or 
a ny  c o mp o ne nts  of  t he  st ud y  dr ug.  
2 1.  Hist or y  of alc o hol  a nd/ or  s ubsta nce  a b use wit hi n  1 2 mo nt hs  prior  t o 
scree ning. 
2 2.  U na ble  or un willi n g  t o parta ke in  follo w -up  assess me nts  or re q uire d 
pr ot oc ol  pr oce d ures . 
 

Brist ol  M yers  S q uib b  
Pr ot oc ol  S yno psis:  A batace pt in  I g G 4 -R D  
Clinica l  St ud y  S yno psis 
C O N FI D E N TI A L  
Pa ge 5  of 6 6  
V 3. 1: O ct 2 8, 2 0 1 8  
 
 
 
St u dy  Proce d ure s :  
After  o btainin g  infor me d  c o nse nt,  all  scree ning  pr oce d ures  a nd  tests 
esta blis hi n g  eligib il it y  will  be perfor me d  o n  t he  init ia l  scree nin g  visit. 
S ubjects  deter mine d  t o be eligible  at scree nin g  will  receive  a n initial 
s ubc uta ne o us  d ose of a batace pt ( 1 2 5 mg),  w hic h  will  be c o ntinue d  wee kly 
for  a t otal  of  up t o 2 4 d oses ( 2 4 wee ks). Ster oid  t hera p y  must  be ta pere d 
off  a nd disc o ntin ue d  o ver 8 -wee k perio d  (ta per must  be c o mplete d  no 
later  t ha n  wee k 8 ). S ho uld  patie nts  be dee me d  t o ha ve w orse nin g  disease 
or faili n g  t hera p y  at 4 wee ks t he n  a trial  of ster oids  ca n be c o nsidere d.  
 
S ubjects  will  ret ur n  o n wee ks 1, 2, 4, 8, 1 2, 1 6, 2 0, a nd  2 4 w hile  o n 
treat me nt  for  t heir  injectio ns,  a nd for t he  sc he d ule d  safet y  a nd disease 
res p o nse  assess me nts.  S ubjects  will  be allo we d  t o  self-a d mi nister  t heir 
injectio ns  at ho me.  The  full  treat me nt  perio d  is  2 4 d oses give n  wee kly  for 
2 4 wee ks. S ubjects  w ho  are not  a ble t o be ta pere d off  c ortic oster oids  or 
w ho  re q uire  reinstit utio n  of  c ortic oster oid  t hera p y  at a ny  ti me  d uring  t he 
st ud y  will  be c o unte d  as  treat me nt  failures  b ut  ma y  c o ntinue  st ud y. 
S ho uld  t he  I g G 4 -R D  res p o nder  inde x  fail  t o i mpr o ve  b y 8 wee ks or w ho 
de velo p  ne w or ga n  I N V O L V E M E N T  b y wee k 4 will  be dee me d  a 
treat me nt  fail ure,  patie nt’s  will  be dee me d treat me nt  failure  a nd ca n 
be gin  c ortic oster oid  or alter nati ve  i m m u nos up pr essi ve  t hera p y  at t he 
I nvesti gat or’s  discretio n.  Those  w ho  re q uire  rit uxi ma b  or w ho re q uire 
a d ditio n  of  ot her  oral  i m mu nos up pressi ve  will  be c o unte d  as treat me nt 
failures  a nd  will  ter minate  t he  st ud y. 
 
All  s ubjects  c o mpleti n g  t he  treat me nt  perio d  will  ha ve  follo w  up  visits 
off  pr ot oc olize d  treat me nt  at 2 8 a nd 3 6 wee ks. All  A E(s)  (includi n g 
serio us  A Es  a nd deat hs)  a nd use  of c o nc o mita nt  me dicatio n  infor mati o n 
will  be c ollecte d  t hr o ugho ut  t he  st ud y  fr o m  scree nin g  t hr o ugh  st ud y 
ter minati o n.  S ubjects  de velo pin g  treat me nt-e mer ge nt  A Es  or clinica l l y 
significa nt  safet y  la b  a b nor malit ies  will  be  follo we d  until  res olutio n  or 
until  sta bilizati o n  of t he A Es/a b nor malities.  
Crite ri a  f or 
E v al uati o n: 
Dis e as e Acti vit y:  
T he  follo wi n g  disease  activit y  para meters  will  be rec or de d at sc he d ule d 
inter va ls  t hr o ugho ut  t he  st ud y: 
•  
I g G 4-R D  RI  sc ore 
•  
P hysicia n  Glo bal  Assess me nt  of  Disease  Activit y  ( Vis ual  Activit y  Sc ore)  
•  
S y mpt o m  Se verit y  I nde x 
•  
Gluc oc ortic oid  To xic it y I nde x 

Brist ol  M yers  S q uib b  
Pr ot oc ol  S yno psis:  A batace pt in  I g G 4 -R D  
Clinica l  St ud y  S yno psis 
C O N FI D E N TI A L  
Pa ge 6  of 6 6  
V 3. 1: O ct 2 8, 2 0 1 8  
 
 
 
 
S afe t y:  
T he f ollo win g  s afet y para meters will  be re c or de d at re g ular inter vals  d urin g  t he st u d y:  
•  
A d vers e  e ve nts  
•  
P h ysic al  e xa minatio ns  
•  
Vita l  sig ns (s u pine blo o d  press ure  [ B P], he art  rate [ H R], oral b o d y  te m perat ure, 
res pirat or y rate [ R R]) 
•  
Clini c al  la b orat or y  testin g  (clinic al  c he mistr y,  he mat olo g y,  s er u m 
i m m u n o glo b uli ns,  s er u m I g G4  s u bclass es, c o m ple me nts,  a n d urina lysis)  
•  
C o nc o mita nt  me dic atio ns  
 
Se r ol o gic I n dic at o rs of R es p o ns e:  
•  
I m m u n o glo b uli n le ve ls 
•  
I g G4 s u bclass es 
•  
I g E 
•  
E osin o p hil  le ve ls 
•  
C 3 a n d  C 4 le ve ls 
 
C o rre l ati v e  St u dies:  
A d ditio nal  me c ha nistic  st u dies  will  be  c o n d ucte d  t hr o u g h  t he  M G H  NI H -f u n de d 
A ut oi m m u nit y  Ce nter of E xc elle nc e f or I g G4 -R D,  w hic h has esta blis he d  tra nslatio na l 
c olla b oratio ns  bet w e e n t he  M G H  Clinic  a n d  t he  Ra g o n  I nstit ute  of  H ar var d,  M G H, 
a n d MI T (t he la b orat or y  of Dr. S hiv  Pillai).  
Briefly,  perip heral  blo o d  m o n o n ucle ar  c ells  ( P B M Cs) a n d plas ma will  be is olate d  a n d 
fr oze n fr o m e a c h s u bje ct at w e e ks  0,  1,  4,  1 2  a n d 2 4  c orres p o n din g wit h  c linic a l blo o d  
dra ws.  P B M Cs a n d  plas ma  w ill  be  st ore d  in  liq uid  nitr o ge n  f or  pres er vatio n.  T he 
f ollo win g  e x peri me nts  will  be  c arrie d  o ut  in  batc hes  of  1 0  patie nt  ti me  p oints  per 
e x peri me nt: 
1.  Flo w  c yt o metric q ua ntific atio n  of plas ma blasts,  a ctivate d B c ells,  ter minall y 
differe ntiate d  C D 4 + c yt ot o xic T c ells ( C D 4 + C T Ls), ter minally  differe ntiate d 
C D 8 + c yt ot o xic T c ells ( C D 8 + C T Ls), a ctivate d f ollic ular  helper T ( T F H) c ells 
a n d perip heral  helper T ( T P H) c ells. Ter minal  differe ntiatio n  will  be define d 
b y  t he  loss  of  C D 2 8  s urfa c e e x pressio n a n d ga in  of  C D5 7  s urfa c e e x pressio n 
wit hin  t he res pe ctive effe ct or ( C D 4 5 R A- C C R 7-) T c ell p o p ulatio n.  T hes e  c ell 
p o p ulatio ns  will  be  ass ess e d at  w e e ks  0,  1,  4,  1 2  a n d  2 4  t o  deter mine  t he 
tre at me nt effe ct o n t he a bs olute  n u m bers a n d pr o p ortio ns  of t hes e c ell t y pes. 
2.  Q ua nti fie d  c ell  p o p ulatio ns  will  be a nalyze d  f or c orrelatio n  wit h  o ne a n ot her, 
dis e as e a ctivit y,  plas ma I g G4 le vels a n d clinic al  res p o nsive ness t o  a bata c e pt.  
3.  Fr o m  5 of  t he e nr olle d s u bje cts wit h  k n o w n  e x pa nsio ns  of  t he res pe ctive c ell 
t y pe a n d  clinic al  res p o nsive ness  t o  a bata c e pt,  ter minally  differe ntiate d 
C D 4 + C T Ls,  ter minally  differe ntiate d C D 8 + C T Ls a n d a ctivate d B c ells will  be 
s orte d b y  F A C S at w e e ks 0,  1 2 a n d 2 4.  R N A will  be  is ola te d t o u n der g o  R T-
P C R a m plific a tio n of  t he T C R -β/I g H,  res pe ctively.  N e xt -Ge nerat io n 
Se q ue ncin g  will  be  us e d  t o  define  t he  diversit y  of  t he  T C R/ B C R re pert oire 
lo n git u dina lly  t o as c ertain h o w a bata c e pt ma y i m pa ct c lo na lit y.  

Brist ol  M yers  S q uib b  
Pr ot oc ol  S yno psis:  A batace pt in  I g G 4 -R D  
Clinica l  St ud y  S yno psis 
C O N FI D E N TI A L  
Pa ge 7  of 6 6  
V 3. 1: O ct 2 8, 2 0 1 8  
 
 
E n d poi nts :  
Pri mar y:  
- C o mplete  re missio n  at  3 6  wee ks.  C o mplete  re missio n  is  define d  as  a n 
I g G 4-R D  Res p o nder  I nde x  Sc ore  of  0  a nd  a  pre d nis o ne  d ose  of  0 
mg/ da y  be yo nd  wee k 4 a nd no flare  since  be ginni n g  treat me nt.  
Sec o ndar y:  
- 
Disease  res p o nse  at 4, 1 2, 2 4, a nd  3 6 wee ks. Disease  res p o nse  will  be 
define d  at 6 mo nt hs as: 1) i mpr o ve me nt  of > 1 p oint in t he I g G 4-R D  RI  
sc ore o ver  baseline;   2) no gluc oc ortic oi d  use follo wi n g  t he wee k 4 visit; 
3) no disease  flares,  as assesse d b y  t he I g G 4 -R D  RI.  Disease  flare  will 
be  define d  as  rec urre nce  of  disease  activit y  or  de mo nstratio n  of  a 
disease  e xacer batio n  s uc h  t hat  a d ditio nal  t hera p y  be yo nd  t he  tr ia l 
pr ot oc ol  is  indicate d.  
S uc h  a d ditio nal  t hera p y  
ma y  incl u d e 
gluc oc ortic oids  or alter nati ve  i m mu nos up pressi ve  a ge nts. 
- 
C o mplete  re missio n  at  3 6  wee ks.  
- 
Ti me  t o disease  re miss io n  (I g G 4 -R D  RI  =  0) 
- 
Re miss io n  rates 
- 
N u mber  of  disease  flares  per s ubject  o ver  ti me 
- 
C u mulati ve  c ortic oster oid  d oses a nd Gluc oc ortic oid  To xicit y  I nde x 
- 
P hysicia n  Glo bal  Assess me nt  ( P G A).  A  P G A  c o nsisti n g  of  a  1 0 -
ce nti meter  vis ual  a nalo g  scale  is  c ollecte d  at  eac h  patie nt  visit.  O nl y 
active  disease  (as  o p p ose d t o  da ma ge)  is c o nsidere d  in  t he  sc oring  of 
t he P G A.  
- 
S y mpt o m  Se verit y  I nde x 
- 
Ser u m   i m mu no gl o b uli n le vels, I g G 4 s ubclass c o nce ntratio ns,  I g E 
le vels, e osino p hils,  a nd ser u m  C 3 a nd C 4  le vels. 
Sec o ndar y  Safet y:  
- 
Safet y:  I ncide nce  of a d verse  e ve nts 
- 
Safet y:  I ncide nce  of c ortic os ter oid-relate d  a d verse e ve nts 
- 
C o mp osite  of  vital  signs  assess me nt  as a meas ure  of  safet y 
- 
C o mp osite  of  clinical  la b orat or y  tests assess me nt  as a meas ure  of  safet y 
 
St atistic al  M et ho ds:  
A nal ysis P o p ul ati o ns  
•  
T he  pri mar y  a nalysis  will  be a n  inte nt io n -t o-treat a nalysis  in  w hic h 
t he  pr o p ortio n of  s ubjects  ac hie vi n g  t he pri mar y  o utc o me  is  assesse d.  
Pri mary  effic ac y a nal ysis: 
T he  pri mar y  a nalysis  will  be base d o n t he pr o p ortio n  of s ubjects  ac hie vi n g  t he 
pri mar y  o utc o me.  

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 7  of 6 6  
 
 
 
2  
T A B L E O F  C O N T E N T S  
1 
TI T L E  P A G E...........................................................................................................  
S T U D Y S Y N O P SI S ................................................................................................  
2 
T A B L E O F C O N T E N T S  ........................................................................................ 
3 
I N T R O D U C TI O N A N D S T U D Y  B A C K G R O U N D..............................................  
Ba c k gr o u n d.................................................................................................  
A bata c e pt ..............................................................................................................  
I g G4-Relate d Dis e as e............................................................................................  
C urre nt Tre at me nt of I g G4 -R D a n d Ratio nal  f or Clinic al  St u d y  .......................... 
D os e  Ra tio na le  
.................................................................................................. 
P ote ntial Ris ks.......................................................................................................  
C o nclusio n  a n d Et hic al  C o nsideratio ns ................................................................. 
4 
S T U D Y O BJ E C TI V E S  ........................................................................................... 
Pri mar y O bje ctives.. ...................................................................................... 
Se c o n dar y O bje ctives....................................................................................  
E x pl orat or y  O bje ctives ................................................................................. 
5 
I N V E S TI G A TI O N A L P L A N..................................................................................  
O verall St u d y D esig n a n d Pla n...................................................................  
D es criptio n ........................................................................................................ .... 
Sc he d ule of Ass ess me nts ......................................................................................  
St u d y Ass ess me nts .......................................................................................... ...... 
Scre e nin g P erio d....................................................................................  
Tre at me nt P erio d ( 1 0 1 w e e ks) ...............................................................  
F ollo w -u p  P erio d ................................................................................... 
Dis c ussio n of St u d y D esig n........................................................................  
Ris k/ Be nefit a n d Et hic al Ass ess me nt ............................................ ........ 
Early Ter minatio n  of t he St u d y .............................................................  
Sele ctio n of St u d y P o p ulatio n  ............................................................... ..... 
I nclusio n  Criteria ................................................................................... 
E xclusio n  Criteria .................................................................. ................ 
Wit h dra w al of S u bje cts..........................................................................  
Ot her S u bje ct Restrictio ns ..................................................... ................ 
St o p pin g  Criteria f or t he Clinic al  St u d y.................................  
D os e D ela y a n d D os e M o dific atio n  in  S u bje cts W h o 
E x perie nc e T o xicit y  ...............................................................  
6 
T R E A T M E N T O F  S U BJ E C T S...............................................................................  
I de ntit y of St u d y Tre at me nt(s) ................................................................... 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 8  of 6 6  
 
 
 
A d ministratio n  of St u d y Tre at me nt(s)........................................................  
St u d y Tre at me nt P a c ka gin g a n d La bellin g.................................................  
P a c ka gin g a n d La bellin g........................................................................  
St ora ge ...................................................................................................  
S u bje ct C o m plia nc e....................................................................................  
St u d y Tre at me nt A c c o u nta bilit y,  H a n dlin g,  a n d Dis p os al .........................  
C o n c o mita nt T hera p y ................................................................................. 
Pre vio us/ C o nc o mita nt  Me dic atio n ........................................................  
C o ntra c e ptio n......................................................................................... 
7 
A S S E S S M E N T O F E F FI C A C Y  ............................................................................. 
Effic a c y V aria bles ......................................................................................  
Effic a c y Ass ess me nts .................................................................................  
I g G4-R D Res p o n der I n de x ....................................................................  
Dis e as e A ctivit y V A S............................................................................  
P h ysicia n’s G lo bal  Dis e as e A ctivit y V A S ............................. 
S u bje ct’s Glo bal  Dis e as e A ctivit y V A S.................................  
S y m pt o m  Se verit y I n de x ........................................................  
Gluc oc ortic oid  T o xicit y  I n de x ...............................................  
3 6 -Ite m S h ort F or m H e alt h S ur ve y ........................................ 
8 
A S S E S S M E N T O F  S A F E T Y..................................................................................  
La b orat or y Ass ess me nts .............................................................................  
P h ysic al E xa minatio n  .................................................................................  
Vital Sig ns ..................................................................................................  
9 
S T A TI S TI C A L E V A L U A TI O N  ............................................................................. 
Sa m ple Size a n d P o w er ..............................................................................  
A nalysis P o p ulatio n....................................................................................  
E n d p oints....................................................................................................  
Pri mar y Effic a c y E n d p oint  ................................................................. ... 
Se c o n dar y Effic a c y E n d p oints...............................................................  
Safet y E n d p oints.................................................................................. .. 
Q ualit y  of Life Ass ess me nts ..................................................................  
I n de pe n de nt D ata M o nit orin g  C o m mitte e (I D M C) ............................... 
Statistic al  Met h o ds  ..................................................................................... 
Ge neral C o nsideratio ns..........................................................................  
1 0   
DI R E C T A C C E S S T O S O U R C E D A T A/ N O T E S  ................................................. 
1 1  
Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E  ...................................... 
1 5. 1  
D ata Q ualit y Ass ura nc e  .............................................................................. 
1 5. 2  
St u d y  M o nit orin g........................................................................................  

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 9  of 6 6  
 
 
 
1 2  
E T HI C S  ................................................................................................................... 
I n de pe n de nt Et hics C o m mitte e/I nstit utio nal  Re vie w B oar d ...................... Go o d 
Clinic al  Pra ctic e......... ....................................................................... 
Writte n I nf or me d C o ns e nt ..........................................................................  
Pr ot oc ol A p pr o val  a n d A me n d me nt(s).......................................................  
C o nfide ntialit y  D ata Pr ote ctio n ..................................................................  
1 3  
D A T A H A N D LI N G A N D R E C O R D  K E E PI N G  ................................................... 
Cas e Re p ort F or ms/ S o urc e D ata H a n dlin g.................................................  
Rete ntio n of Ess e ntial D oc u me nts............. ................................................. 
1 4  
FI N A N CI N G A N D  I N S U R A N C E.......................................................................... 
1 5  
P U B LI C A TI O N P O LI C Y  ....................................................................................... 
1 6  
SI G N A T U R E O F I N V E S TI G A T O R  ...................................................................... 
1 7  
R E F E R E N C E LI S T  ................................................................................................. 
1 8  
A P P E N DI C E S  ......................................................................................................... 
A.  I g G4-R D Res p o n der I n de x (I g G4 -R D RI)  
B.  P h ysic ia n  Glo bal  Ass ess me nt of Dis e as e A ctivit y ( V A S)  
C.  S u bje ct’s Glo bal  Ass ess me nt of Dis e as e A ctivit y ( V A)  
D.  S F -3 6  H e alt h S ur ve y  
E.  I g G4-Relate d Dis e as e S y m pt o m  Distress I n de x  
F.  T he Gluc oc ortic oid  T o xicit y  I n de x  
G.  A C R/ E U L A R 2 0 1 8 Classific atio n  Criteria f or I g G4 - R D 
 
 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 1 0  of 
 
 
 
3  
I N T R O DU C TI O N  A N D S T U D Y  B A C K G R O U N D  
 
3. 1 A bat ace pt 
 
A batace pt  is  a selective  c osti mulati o n  mo d ulat or  t hat  c o nsists  of  a fusio n  pr otein  of hu ma n 
I g G 1  a nd  t he  e xtracell ula r  d o main  of  C T L A 4,  w hic h  inhib its  T  cell  ( T  ly mp hoc yte )  activatio n 
b y bindin g  t o C D 8 0 a nd C D 8 6 , t here b y  bloc king  interactio n  wit h  C D 2 8. This  bloc ks t he  a bilit y 
of a ntige n  prese ntin g  cells  t o deliver  t he  c o -sti mulat or y  signal  nee de d t o activate  T cells.  It is 
c urre ntl y  indicate d  for  use in  a d ult  r he u mat oid  art hritis,  j uve nile  idio pat hic  art hritis.  I t is not 
c urre ntl y  indicate d  for  use  in  I g G 4 -R D.  
 
3. 2 I g G 4- R el ate d Dis e as e  
 
I g G 4-R D  is  a c hr o nic  fibr o -infla  m mat o r y  c o nditio n  t hat  ca n  affect  virt ua ll y  e ver y  or ga n 
s yste m  includi n g  t he pa ncreas,  biliar y  tract,  salivar y  a nd  lacri mal  gla nds,  or bits,  lungs,  k id ne ys, 
me nin ges,  pit uita r y  gla nd,  pr ostate  a nd  t hyr oid  a mo ng  ot hers.  It  ma y  als o  invol ve  t he 
retr o perit o ne u m.  T his  multi-or ga n  i m m u ne -me diate d  c o nditio n  was pre vio usl y  re gar de d  as a 
gr o up  of  is olate d  single  or ga n  diseases  b ut has rece ntly  bee n rec o gnize d as  a unif yi n g  e ntit y 
linke d  b y c o m mo n  hist o pat holo gical  a nd i m m u no hist oc he mical  feat ures.  The  hist o pat holo gical 
feat ures  include  a de nse ly mp ho plas mac ytic  infiltrate  c o nsisti n g  of T cells  a nd I g G 4 +  plas ma 
cells,  st orifor m  fibr osis  a nd  o bliterat i ve  p hle bit is.  I m muno per o xidase  stainin g  of  affecte d 
tiss ues  ge nerall y  de mo nstrates  a ratio  of ≥4 0 % I g G 4/I g G +  plas ma  cells  ( Des hpa nde  et al. 
2 0 1 2). Ser u m  I g G 4  c o nce ntratio ns  are ele vate d  in  at least  5 0 -6 0 % of  cases before  t he  initiati o n 
of treat me nt  ( Wallace  et al.  2 0 1 5). 
 
T he  fre q ue nc y  of  I g G 4 -R D  is  unk no w n  in  most  c o untries  ot her  t ha n  Ja pa n,  w here  it  is 
t ho ught  t o affect  at least  8 0 0 0 individ uals  ( Uc hida  et al.  2 0 1 2). H o we ver,  beca use t his  disease 
has o nly  bee n rec o gnize d  a nd describe d  in  t he  last  1 0 years,  rec o gnitio n  of t he  disease  is 
gr o wing  in  ot her  parts  of  t he  w orld,  includ i n g  t he  U S  a nd  Eur o pe.  I g G 4 -R D  a p pears t o ha ve  a 
mo dest  pre dilectio n  for affecti n g  me n  more  ofte n  t ha n  w o me n  a nd te nds  t o afflict  mid dle -a ge d 
t o elderly  individ uals.  Alt ho u g h  I g G 4-R D  ca n affec t  a single  or ga n  at  prese ntatio n,  it  is  not 
unc o m mo n  for  patie nts  t o prese nt  wit h  or de velo p  multi -or ga n  disease.  As t he  disease 
pr o gresses,  a d ditio nal  or ga ns  de velo p  lesio ns  a nd  t he cellular  infla m matio n  c haracterizi n g  early 
disease  mo ves  t o war d a more fibr otic  sta ge, ca using  maj or  tiss ue  da ma ge,  d ysfuncti o n  a nd 
ulti mate l y  or ga n  fail ure.  
 
It is unclear  w het her  I g G 4  itself  is  invol ve d  in  t he  pat ho ge nesis  of  t he disease.  T cells 
c o mprise  t he maj or  infla m mat or y  cell  in  t his  disease.  I n fact,  t w o C D 4 + T cells  are belie ve d  t o 
pla y  cr ucial  r oles  in  t his  c o nditio n:  1) A C D 4 + c yt ot o xic  T ly mp hoc yte  bearing  S L A M F 7 o n its 
s urface,  secreting  pr ofibr otic  c yt o kines  I L-1 B a nd T G F -B 1 a nd I F N -ga m ma,  as well  as 
c yt ot o xic  molec ules  s uc h  as perforin  a nd gra nzy me  B. 2) A C D 4 + T  follic ular  helper  cell, 
k no w n  t o drive  t he  class  s witc h  wit hi n  ly mp h  no des  a nd  e xtra -no dal  ger minal  ce nters  ( Matt o o 
et al. 2 0 1 6) 
  
A d ditio nall y,  se veral  B cell  s ubsets  ha ve  rece ntly  bee n describe d  b y flo w  c yt o metr y  t o 
be ele vate d  in  t he perip heral  blo o d of  I g G 4 -R D  patie nts.  Circ ulati n g  I g G 4 +  plas ma blasts 
( C D 1 9lo w C D 3 8 + C D 2 0-C D 2 7 +)  ha ve  bee n s ho w n  t o be ele vate d  in  active  disease  as c o mpare d 
t o indivi d ua ls  wit h  ot her  diseases  a nd  nor mal  c o ntr ols,  e ve n  in  I g G 4-R D  patie nts  wit h  nor mal 
I g G 4  ser u m  le vels.  T otal plas ma blasts  ca n t herefore  be utilize d  as a dia gnostic  feat ure  of I g G 4 - 
R D ( Wallace  et al. 2 0 1 4, Matt o o et al. 2 0 1 4).  
 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 1 1  of 
 
 
 
T his  st ud y  will  e nr oll  male  a nd  fe male  s ubjects  a ge  1 8 or older  w ho  fulfil l  t he 
A C R/ E U L A R  2 0 1 8 C lassificat i o n  C riteria  for  I g G 4 -R D  wit h  a  mini m u m  I g G 4 -R D  Res p o nder 
I nde x  sc ore of  2 S ubjects  are not  re q uire d  t o ha ve  faile d  prior  t hera p y  for  t heir  disease  t o be 
eligib le  for  t his  st ud y.  
 
3. 3 C urre nt  Tre at me nt  of I g G 4- R D a n d  R ati o nale   f or  t he   Cli nic al  St u dy  
 
I g G 4-R D  is  c urre ntl y  inc ura ble.  The goals  of  treat me nt  are t o re d uce  infla m mati o n  a nd 
s welli n g  in  t he or ga ns,  pre ve nt  or re verse  (if  p ossible)  fibr osis  a nd  increase  gla nd ular  secretio n. 
A ggressi ve  treat me nt  is  warra nte d  t o pre ve nt  or ga n  failure  w he n  vital  or ga ns  are invol ve d.  F or 
e xa mple,  c hola ngitis  d ue  t o I g G 4- R D  ca n lea d t o he patic  failure,  I g G 4 -relate d  (t ype  2) 
a ut oi m m u ne  pa ncreatitis  ca n lea d  t o failure  of eit her  or b ot h t he  e nd ocrine  a nd e xocrine 
pa ncreas,  a nd I g G 4 -relate d  a ortitis  ca n  lea d t o a ne ur ys ms  a nd/ or  a ortic  dissectio n.  At t he 
prese nt  ti me,  gluc oc ortic oids  at daily  d oses of 0. 6 mg/ k g  daily  for 2 t o 4  8  wee ks follo we d  b y 
ta pering  t o lo w  d oses ( or disc o nti n ui n g  alt o get her)  o ver 3-6 mo nt hs  is  t he  first  line  of  t hera p y. 
Alt ho ug h  t his  a p pr oac h  is  effecti ve  initia ll y  in  most  patie nts,  t he  rela pse  rate up o n  ta pering  or 
disc o nti n uati o n  is high  ( K hosr os ha hi  et al. 2 0 1 5). I n a d ditio n,  t he  lo ng  ter m  use of 
gluc oc ortic oid s  in  older  p o p ulatio ns  s uc h  as t hat  affecte d  b y I g G 4 -R D  ca n  lea d t o ma ny 
unt o war d  side  effects  s uc h  as oste o p or osis,  high  blo o d  press ure  a nd dia betes. 
I m munos up pressi ve  me dicatio ns  s uc h  as azat hio pri ne,  myc o p he nolate  mofetil  a nd met hotre xate 
ha ve  bee n use d  as gluc oc ortic oi d -s pari n g  a ge nts,  wit h  no clear  indicatio n  of efficac y  ( St o ne  et 
al.  2 0 1 2, Ya ma mot o  et al.  2 0 1 4, K hosr os ha hi  et al.  2 0 1 5). A high  disease  res p o nse  rate has 
bee n o bser ve d  in  o ne  s mall  o pe n -la bel  trial  wit h  rit uxi ma b,  utilizi n g  a n  I g G 4- R D Res p o nder 
I nde x  ( RI)  as a meas ure  of disease  res p o nse  ( K hosr os ha hi  et al.  2 0 1 0, C arr ut hers  et al.  2 0 1 5). 
M ore rece ntly,  a sin gle  case re p ort fr o m  Ja pa n  has describe d  dra matic  efficac y  in  a patie nt  wit h 
mult i -or ga n  I g G 4 -R D  w hose  s y mpt o ms  a nd signs  of disease  were refract or y  t o B cell  de pletio n 
wit h  rit uxi ma b  ( Ya ma mot o  et al. 2 0 1 6). A strate gy  tar getin g  C D 4 + T cells  ma y  indee d  be 
s uccessful  in  c o ntr olli n g  I g G 4-R D.  We see k t o c o nfir m  t his  hyp ot hesis  in  a pr os pective,  single 
ce nter,  o pe n-la bel,  1 0-patie nt  pr o of- of-c o nce pt  st ud y.  S ubjects  will  receive  wee kly 
s ubc uta ne o us  d oses of a batace pt  ( 1 2 5 mg)  for 2 5 d oses. 
 
3. 4 D os e R ati o nale  
 
T h e  d ose a batace pt  1 2 5 mg  s ubc uta ne o usl y  wee kly  is  c urre ntl y  a p pr o ve d for  use in  a d ult 
r he u mat o id  art hritis,  j uve nile  idio pat hic  art hrit is 
  
3. 5 P ote nti al  Ris ks 
 
Base d o n e xperie nce  in  hu ma n  st udies  t o date a nd class  effects  of i m m u no mo d ulati n g 
me dicatio ns,  s ubjects  receivin g  S C a batace pt ma y  be at ris k  for a d verse  e ve nts.  
 
T he  follo wi n g  a d verse  effects  are base d o n a batace pt a d ministere d  intra ve no usl y  in 
patie nts  wit h  active  R A  in  place b o - c o ntr olle d  st udies  ( 1 9 5 5 patie nts  wit h  O R E N CI A, 9 8 9 wit h 
place b o).  T he s ubc uta ne o us  data is  base d o n a ra nd o mize d,  d o uble- bli nd,  d o uble -d u m m y,  no n- 
inferiorit y  st ud y  t hat  c o mpare d  t he efficac y  a nd safet y  of a batace pt  a d minister e d 
s ubc uta ne o us l y  ( S C) a nd  intra ve no us l y  (I V)  in  1 4 5 7 s ubjects  wit h  r he u mat o id  art hritis  being 
treate d  wit h  bac k gr o und  met hotre xate.  I n patie nt’s  receivin g  intra ve no us  a batace pt for  active 
R A in  place b o -c o ntr olle d  trials,  t he most  c o m mo n  a d verse  e ve nts  re p orte d  in  greater  t ha n  te n 
perce nt  of patie nts  were hea dac he,  up per res pirat or y  infectio n,  nas o p har yngitis  a nd na usea. 
A d verse  e ve nts  t hat  occ urre d  in  at least  3 % of patie nts  a nd at least  1 % more  fre q ue ntl y  in 
a batace pt-treate d  patie nts  t ha n  place b o-treate d  patie nts  were hea dac he,  nas o p har yn gitis, 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 1 2  of 
 
 
 
dizzi ness,  c o ugh,  bac k pain,  hyperte nsio n,  d ys pe psia,  urin ar y  tract infectio n,  ras h,  a nd pain  in 
e xtre mit y.  T he  most  serio us  a d verse  e ve nts  were infectio n  a nd malig na nc y.  
 
I. 
I nfectio ns 
I nfectio ns  were re p orte d in  5 4 % of  patie nts  receivi n g  a batace pt a nd 4 8 % of t hose  receivin g 
place b o.  T he  most  c o m mo n  infectio ns  were  up per  res pirat or y,  nas o p har yn gitis,  sinusitis, 
urinar y  tract  infectio n,  infl ue nza,  a nd  br o nc hitis.  Ot her  infectio ns  re p orte d  in  fe wer  t ha n  5 % of 
patie nts  were  r hinit is,  her pes  si mple x,  a nd  p ne u mo nia.  The  most  c o m mo n  serio us  infect io ns 
re p orte d were p ne u monia,  cellulitis,  urinar y  tract infectio n,  br o nc hitis,  divertic ulitis,  a nd ac ute 
p yelo ne p hr itis.  
 
II. 
Maligna nc ies  
I n place b o-c o ntr olle d  p ortio ns  of  clinica l  trials,  t he  fre q ue nc y  of  mali g na nc ie s  are si mila r  in  t he 
t w o gr o ups  wit h  1. 3 % in  t hose  receivin g  a batace pt  a nd 1. 1 % o n place b o.  H o we ver,  more cases 
of lung  ca ncer  were o bser ve d in  a batace pt -treate d  patie nts  ( 4, 0. 2 %) t ha n  place b o-treate d 
patie nts  ( 0). I n  t he c u mulati ve  a batace pt  clinic al  trials  ( place b o -c o ntr olle d  a nd unc o ntr olle d, 
o pe n- la bel)  a t otal  of  8 cases of lung  ca ncer  ( 0. 2 1 cases per 1 0 0 patie nt -years)  a nd  4 ly mp ho  ma s 
( 0. 1 0 cases per 1 0 0 patie nt- years)  were o bser ve d in  2 6 8 8 patie nts  ( 3 8 2 7 patie nt- years).  The  rate 
o bser ve d  for ly mp ho ma  is  a p pr o xi matel y  3. 5 -fold  higher  t ha n  e xpecte d  in  a n  a ge- a nd  ge nder -
matc he d  ge neral  p o p ulatio n  base d o n t he  N atio nal  C a ncer I nstit ute’s  S ur veilla nce, 
E pide mio l o g y,  a nd  E nd  Res ults  Data base.  Patie nts  wit h  R A,  partic ular l y  t hose  wit h  highl y 
active  disease,  are at a higher  ris k  for t he  de velo p me nt  of  ly mp ho ma.  Ot her  malig na nc ies 
include d  s kin,  breast, bile  d uct,  bla d der,  cer vical,  e nd o metrial,  ly mp ho ma,  mela no ma, 
myelo d ys plastic  s yndr o me,  o varia n,  pr ostate,  re nal,  t hyr oid,  a nd uterine  ca ncers.  
 
III. 
H yperse nsiti vit y  Reactio ns  
 
A na p hyla xis  was o bser ve d  in  patie nts  d ose d wit h  O R E N CI A  a d minis tere d  intra ve no us l y  in 
c o ntr olle d  a nd o pe n-la bel  clinical  trials,  a nd t he occ urre nce  was rare ( < 0. 1 %). Ot her  reactio ns 
p ote ntiall y  ass ociate d  wit h  dr ug  hyperse ns iti vit y,  s uc h  as hyp ote nsio n,  urticaria,  a nd  d ys p nea 
t hat  occ urre d  wit hi n  2 4 ho urs  of  O R E N CI A  infus io n,  were  unc o m mo n  ( < 1 %). 
 
I V. 
A d verse  Reactio ns  in  Patie nts  wit h  C O P D  
 
C O P D patie nts  treate d  wit h  O R E N CI A de velo pe d  a d verse  e ve nts  more  fre q ue ntl y  t ha n  t hose 
treate d  wit h  place b o  ( 9 7 % vs  8 8 %, res pectivel y).  Res pirat or y  dis or ders  occ urre d  more 
fre q ue ntl y  in  O R E N CI A-treate d  patie nts  c o mpare d  t o place b o-treate d  patie nts  ( 4 3 % vs 2 4 %, 
res pectivel y)  includi n g  C O P D e xacer batio n,  c o ugh,  r ho nc hi,  a nd d ys p nea.  A greater  perce nta ge 
of O R E N CI A -treate d  patie nts  de velo pe d  a serio us  a d verse  e ve nt  c o mpare d  t o place b o -treate d 
patie nts  ( 2 7 % vs  6 %), includi n g  C O P D e xacer batio n  ( 3 of 3 7 patie nts    [ 8 %]) 
a nd p ne u mo nia  ( 1 of 3 7 patie nts  [ 3 %]).  
 
V.  
I njectio n  Site  Reactio ns  in  A d ult  R A Patie nts  Treate d  wit h  S ubc uta ne o us  Ore ncia 
 
T he  o verall  fre q ue nc y  of  injectio n  site  rea ctio ns  was 2. 6 % ( 1 9/ 7 3 6) a nd 2. 5 % ( 1 8/ 7 2 1) for t he 
s ubc uta ne o us  a batace pt  gr o up  a nd t he  intra ve no us  a batace pt  gr o up  (s ubc uta ne o us  place b o), 
res pectivel y.  All  t hese  injectio n  site  reactio ns  (includi n g  he mat o ma,  pr urit us,  a nd er yt he ma) 
were mild  ( 8 3 %) t o mo d erate  ( 1 7 %) in  se verit y,  a nd no ne  necessitate d  dr ug  disc o ntin uatio n.  
 
 
 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 1 3  of 
 
 
 
VI.  
I m muno ge nic it y  in  A d ult  R A  Patie nts  Treate d  wit h  S ubc uta ne o us  O R E N CI A 
 
T he  o verall  i m m u no ge nicit y  fre q ue nc y  t o a batace pt was 1. 1 % ( 8/ 7 2 5)  a nd 2. 3 % ( 1 6/ 7 1 0) for 
t he  s ubc uta ne o us  a nd  intra ve no us  gr o ups,  res pectivel y.  There  was no c orrelatio n  of 
i m mu no ge nicit y  wit h  effects  o n p har mac o ki netics,  safet y,  or efficac y. 
 
VII.  
I m muno ge nic it y  a nd  Safet y  of  S ubc uta ne o us  O R E N CI A  A d minis tra tio n  as 
M o not hera p y  wit ho ut  a n  I ntra ve no us  Loa ding  D ose  
 
I n  a st udy  t hat  was c o nd ucte d  t o deter mine  t he  effect  of  mo not hera p y  use of  O R E N CI A o n 
i m mu no ge nic it y  follo wi n g  s ubc uta ne o us  a d minis trati o n  wit ho ut  a n  intra ve no us  loa d  in  1 0 0 R A 
patie nts,  w ho ha d not  pre vio usl y  receive d  a batace pt or ot her  C T L A 4I g,  w ho receive d  eit h er 
s ubc uta ne o us  O R E N CI A  plus  met hotre xa te  ( n = 5 1)  or  s ubc uta ne o us  O R E N CI A  mo not hera p y 
( n = 4 9).  N o patie nts  in  eit her  gr o up  de velo pe d  a nti-pr o d uct  a ntib o dies  after  4 mo nt hs  of 
treat me nt.  T he  safet y  o bser ve d  in  t his  st ud y  was  c o nsiste nt  wit h  t hat  o bser ve d  in  t he  ot her 
s ubc uta ne o us  st udies. 
 
VIII.  
I m muno ge nic it y  a nd  Safet y  of  S ubc uta ne o us  O R E N CI A  up o n  Wit hdra wa l  ( Three 
M o nt hs)  a nd Restart  of Treat me nt  
 
I n  a st ud y  c o nd ucte d  t o investi ga te  t he  effect  of  wit hdra wal  (t hree  mo nt hs)  a nd restart of 
O R E N CI A s ubc uta ne o us  treat me nt  o n  i m mu no ge nic it y  in  R A  patie nts  treate d  c o nc o mita ntl y 
wit h  met hotre xa te,  o ne  hundre d  sixt y -se ve n  patie nts  were e nr olle d  in  t he  first  3-mo nt h 
treat me nt  perio d  a nd res p o nders  ( n = 1 2 0)  were ra nd o mize d t o  eit her  s ubc uta ne o us  O R E N CI A or 
place b o  for t he  sec o nd 3 -mo nt h  perio d  ( wit hdra wal  perio d).  Patie nts  fr o m  t his  perio d  t he n 
receive d  o pe n-la bel  O R E N C I A  treat me nt  in  t he  fina l  3-mo nt h  perio d  of t he  st ud y  ( perio d  3). At 
t he  e nd of t he  wit hdra wal  perio d, 0/ 3 8 patie nts  w ho c o ntinue d  t o receive  s ubc uta ne o us 
O R E N C I A de velo pe d  a nti-pr o d uct  a ntib o dies  c o mpare d  t o 7/ 7 3 ( 9. 6 %) of patie nts  w ho  ha d 
s ubc uta ne o us  O R E N CI A  wit hdra w n  d uring  t his  perio d.  Half  of  t he  patie nts  receivin g 
s ubc uta ne o us  place b o  d uring  t he  wit hdra wa l  perio d  receive d  a  single  intra ve no us  infus io n  of 
O R E N CI A at t he start  of perio d  3 a nd half  receive d  intra ve no us  place b o.  At t he e nd of  perio d  3, 
w he n  all  patie nts  a gain  receive d  s ubc uta ne o us  O R E N CI A, t he i m m u no ge nicit y  rates were  1/ 3 8 
( 2. 6 %)  in  t he  gr o up  receivi n g  s ubc uta ne o us  O R E N CI A  t hr o ugho ut,  a nd  2/ 7 3 ( 2. 7 %) in  t he 
gr o up  t hat  ha d receive d  place b o d uring  t he  wit hdra wal  perio d.  U p o n reinitiati n g  t hera p y,  t here 
were no injectio n  reactio ns  a nd no differe nces  in  res p o nse  t o t hera p y  in  patie nts  w ho  were 
wit hdra w n  fr o m  s ubc uta ne o us  t hera p y  for  up  t o 3 mo nt hs relative  t o t hose w ho  re maine d  o n 
s ubc uta ne o us  t hera p y,  w het her  t hera p y  was  reintr o d uce d  wit h  or wit ho ut  a n  intra ve no us  loa ding 
d ose. T he  safet y  o bser ve d  in  t his  st ud y  was c o nsiste nt  wit h  t hat  o bser ve d  in  t he  ot her  st udies.  
 
3. 6 C o ncl us i o n  a n d  Et hic al  C o ns i de rati o ns 
 
T he  design  of t he  pr o p ose d trial  c o ntains  meas ures  a p pr o priate  t o t he  miti gati o n  of ris k 
fact ors  for A Es.  F urt her more,  fre q ue nt  safet y  mo nit ori n g  is a n inhere nt  part of t he  pr ot oc ol.  I n 
s u m mar y,  t he be nefits  a nd ris k  assess me nt  for  t he a p plicatio n  of  a batace pt a p pears fa vora ble 
a nd s up p ortive  for initiatio n  of  t he pr o p ose d clinical  trial.  
 
T his  st ud y  will  be perfor me d  in  t he  follo w i n g  ma nner :  
• I n  acc or da nce   wit h  G o o d  Cli nic al  Practice   ( G C P),  as  de fi ne d  by  t he  
I nte r nati o nal  C o nfe re nce   o n  H ar mo niza ti o n  (I C H),  W H O  a n d  a ny l oc al 
dire cti ves.  
• I n  c o m pli a nce   wit h  t he  prot oc ol. 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 1 4  of 
 
 
 
• T he   prot oc ol,  a ny  a me n d me nts ,  a n d  t he   s u bje ct  i nf or me d  c o ns e nt will 
re ce i ve  I ns tit uti o nal  R e vie w B o ar d/I n de pe n de nt  Et hics   C o m mitte e  
(I R B/I E C)  a p pro v al/f a v ora ble  o pi ni o n  bef ore i nitiati o n  of  t he  s t u dy.  
• Wit h  pe rs o n ne l  w ho  are  q ualifie d  by e d uc ati o n,  trai ni ng,  a n d  e x pe rie nce  t o 
pe rf or m  t he ir  re s pe cti ve  t as ks  a n d  t hat  t he   s t u dy  will  not  us e  t he   s e rvice s  of 
s t u dy  pe rs o n ne l  f or  w ho m  s a ncti o ns   ha ve  be e n  i nv o ke d  or  w he re   t he re  has  
be e n s cie n tific  mis c o n d uct  or  fra u d 
• Wit h  s i g ne d, date d  I nf or me d  C o ns e nt  fro m  e ac h of  t he  partici pa nts
 
• I nve s ti g at ors / S po ns ors   m us t  e ns ure   t hat  s u bje cts --or,  i n  t hos e sit uati o ns 
w he re   c o ns e nt c a n not  be  gi ve n by  s u bje cts ,  t he ir  le g all y acce pt a ble  
re pres e nt ati ves --are   c le arl y  a n d  f ull y  i nf or me d  a bo ut  t he   p ur pos e ,  pote nti al 
ris ks , a n d  ot he r  critic al  is s ue s  re g ar di ng  cli nic al  s t u die s  i n  w hic h  t he y 
v ol u nte e r  t o partici pate .  T he   a p pro ve d  i nf or me d  c o ns e nt f or m  will  a d he re  
t o t he   e t hic al  pri nci ple s   t hat  ha ve  t he ir  ori gi n  i n  t he D e cl arati o n  of Helsi n ki.  
• I ncl u de   re le v a nt  s afe t y i nf or mati o n  re g ar di ng  dos e /s c he d ule  of  I P  a n d  a ny 
ot he r  dr ugs / proce d ure s  
• B M S a n d  he alt h a ut horit y  t o ha ve dire ct  access t o st u dy re c or ds  B M S will 
pro vi de   t he   s t u dy  dr ug  a n d  f u n di ng  f or  t his   s t u dy.  
4  
 S T U D Y   OB J E C TI V E S  
4. 1  
Pri mary  O bje cti ves  
• T o e valuate  t he  effect  of wee kly  s ubc uta ne o us  ( S C) a d ministrati o n  of a batace pt o n 
c o mplete  re missio n  of  I g G 4 -R D  at 2 4  wee ks  
4. 2  
Se c o n dary  O bje cti ves  
• T o  e valuate t he effect  of a batace pt o n disease  res p o nse at 4, 1 2 a nd 2 4 wee ks  a nd c o mplete 
re missio n  at  3 6 wee ks  
• T o e valuate  t he  effect  of a batace pt  o n ti me  t o disease  re missio n  (I g G 4 -R D  RI  = 0), 
re missio n  rates, nu mber  of  disease  flares  per s ubject  o ver ti me 
• T o e valuate  t he  effect  of a batace pt  o n p hysicia n  glo bal  assess me nt  ( P G A),  S y mp t o m 
Se verit y  I nde x,  a nd c u mulati ve  c ortic oster oid   d oses 
• T o  e valuate  t he  effect  of  a batace pt  o n  ser u m  i m mu no gl o b uli n  le vels,  I g G 4  s ubclass 
c o nce ntratio ns, I g E le vels,  e osino p hils,  a nd  ser u m  C 3  a nd  C 4 le vels  at  4,  1 2, 2 4  a nd  3 6 
wee ks  
4. 3  
E x pl orat ory O bje cti ves  
T o e valuate  t he  effect  of a batace pt  o n C D 4 + T cells  a nd B cell  s ubsets,  s pecificall y:  
- C D 4 + c yt ot o xic  T ly mp hoc yte s 
- C D 8 + c yt ot o xic  T ly mp hoc yt es 
- C D 4 + T  follic ula r  helper  cells 
- C D 4 + perip heral  helper  T  cells 
- Plas ma blast s  
- Activate d  B  cells 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 1 5  of 
 
 
 
 
 
5  
I N V E S TI G A TI O N A L  P LA N 
O ve rall  St u dy  D e s i g n a n d  Pl a n 
D es cri pti o n  
T his  is  a  P hase  2, pr os pective,  o pe n -la bel,  single  ce nter  clinical  trial  in  s ubjects  wit h  active 
I g G 4-R D.  A p pr o xi matel y  1 0 s ubjects  wit h  active  I g G 4 -R D  will  be e nr olle d.  After  scree ni n g 
a nd e nr oll me nt,  eligib le s ubjects will  receive a n init ia l s ubc uta ne o us  d ose of a batace pt ( 1 2 5 mg) 
follo we d  b y wee kly  s ubc uta ne o us  d oses of  a batace pt ( 1 2 5 mg)  for  a t otal  of up t o 2 4 d oses ( 2 4 
wee ks). S ubjects will  be follo we d  o n st ud y  for 1 2 wee ks follo wi n g  t he last  d ose for a t otal  st ud y 
perio d  of up t o 3 6  wee ks.  
After   o btaini n g infor me d c o nse nt,  all scree ning pr oce d ures  a nd tests esta blis hi n g eligib i l i t y 
will  be  perfor me d  o n  t he  initia l  scree ning  visit.  S ubjects  deter mine d  t o  be  eligib le  at 
scree ning  will  receive  a n  init ia l  s ubc utane o us  d ose  of  a batace pt  ( 1 2 5 mg),  w hic h  will  be 
c o ntinue d  wee kly  for  a t otal  of up t o 2 4 d oses ( 2 4 wee ks). Ster oid  t hera p y  must  be ta pere d 
off  a nd disc o nti n ue d  o ver a 4 wee k perio d  (ta per  must  be c o mplete d  no later  t ha n  wee k 4). 
S ho uld  patie nts  be dee me d  t o  ha ve  w orse ning  disease  or faili n g  t hera p y  at 4 wee ks t he n  a 
trial  of ster oids  ca n be c o nsidere d.  
S ubjects  will  ret ur n  o n  wee ks  1,  2, 4,  8, 1 2,  1 6, 2 0,  a nd  2 4  w hile  o n  treat me nt  for  t heir 
injectio ns,  a nd  for t he  sc he d ule d  safet y  a nd  disease  res p o nse  assessme nts.  S ubjects  will  be 
allo we d  t o  self-a d mi nister  t heir  injectio ns  at ho me.  The  full  treat me nt  perio d  is 2 4 d oses 
give n  wee kly  for  2 4 wee ks.  S ubjects  w ho  are not  a ble  t o be ta pere d  off  c ortic oster oids  or 
w ho  re q uire  reinstit uti o n  of  c ortic oster oid  t hera p y  at  a ny  ti me  d uring  t he  st ud y  will  be 
c o unte d  as  treat me nt  failur es  b ut  ma y  c o ntinue  o n  st ud y.  S ho uld  t he  I g G 4 -R D  res p o nder 
inde x  fail  t o  i mpr o ve  b y 8 wee ks  or w ho  de velo p  ne w  or ga n  invol ve me nt  b y  wee k 4  will 
be  dee me d  a  treat me nt  failure,  patie nt’s  will   be dee me d  treat me nt failure a nd ca n  be gi n 
c ortic oster oid   or alter nati ve  i m mu nos up pr essi ve  t hera p y  at  t he  I nvestigat or’s  discreti o n. 
T hose  w ho re q uire  rit uxi ma b  or w ho re q uire  a d ditio n  of ot her oral  i m mu nos up pressi ve  will 
be c o unte d  as treat me nt  failures  a nd  will  ter minate  t he  st ud y. 
All  s ubjects  c o mpleti n g  t he  treat me nt  perio d  will  ha ve  follo w  up  visits  off  pr ot oc olize d 
treat me nt  at  2 8  a nd  3 6 wee ks.  All  A E(s)  (includi n g  serio us  A Es  a nd  deat hs)  a nd  use  of 
c o nc o mita nt  me dicatio n  infor ma t io n  will  be  c ollecte d  t hr o ugho ut  t he  st ud y  fr o m scree ni n g 
t hr o ugh  st ud y  ter mina tio n.  S ubjects  de velo pin g  treat me nt-e mer ge nt  A Es  or  clinic a l l y 
significa nt safet y la b a b nor malities will   be follo we d until res olutio n  or until sta biliza t io n of 
t he A Es/a b nor ma l it ies.  
Signs  a nd  s y mpt o m s  of  I g G 4-R D  activit y  will  be meas ure d  perio dicall y  t hr o ugho ut  t he  st ud y 
using  a mo dificati o n  of t he  I g G 4 -R D  RI ( C arr ut hers  et al. 2 0 1 2, Wallace  et al. 2 0 1 6 ). The  I g G 4-
R D  RI  is  base d o n  t he  Bir mi n g ha m  Vasc ulitis  Activit y  Sc ore  for  We ge ner’s  Gra nulo mat os is 
(St o ne  et al.  2 0 0 1 )  utilize d  for  t he  e valuatio n  a nd  lice ns ure  of  rit uxi ma b  in  A N C A-ass ociate d  
vasc ulit is   (St o ne  et al.  2 0 1 0). T he  I g G 4-R D  RI  is a n instr u me nt designe d  t o  detect  c ha nge  i n   
disease   activit y  a nd  ide ntif y  i mpr o ve  me nts   a nd  w orse nin g  in   t he  s a me   or 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 1 6  of 
 
 
 
 
differe nt  or ga n  s yste ms  a nd  has  bee n  use d  in  prior  clinica l  trials  t o  mo nit or  I g G 4 -R D  diseas e 
activit y  (K hosr os ha hi  et al. 2 0 1 0, C arr ut hers  et al. 2 0 1 5, St o ne  et al.  2 0 1 6 ). 
Assess me nts  will  include A E  assess me nt,  p hysica l e xa minat io n,  vital signs, clinica l  la b orat or y 
testing  (clinica l  c he mistr y,  he mat olo g y,  ser u m  i m mu no gl o b uli ns,  ser u m  I g G 4  s ubclass e s ,  
c o mple me nts,  a nd  urinal ys is)  a nd  c o nc o mita nt  me dicat io ns.  A d ditio na l  ser olo gic  indicat ors  of 
res p o nse  will  include  i m mu no gl o b uli n  le vels,  I g G 4  s ubclasses,  I g E,  Eosino p hil  le vels,  C 3 a nd 
C 4  le vels. 
A d ditio na l  
mec ha nis tic  st udies  
will  be  c o nd ucte d  t hr o ugh  t he  M G H  NI H -fund e d  
A ut oi m m u nit y  C e nter  of  E xcelle nce  for  I g G 4 -R D,  w hic h  has  esta blis he d  tra nslati o na l 
c olla b oratio ns  bet wee n  t he  M G H  Clinic  a nd  t he  R a go n  I nstit ute  of  Har var d,  M G H,  a nd  MI T 
(t he  la b orat or y  of  Dr.  S hiv  Pilla i). 
Briefl y,  perip heral  blo o d  mo no nuclear  cells  ( P B M Cs)  a nd  plas ma  will  be is olate d  a nd fr o ze n 
fr o m eac h s ubject at wee ks  0, 1, 4, 1 2 a nd 2 4 c orres p o ndin g wit h  clinica l  blo o d dra ws.  PB M Cs 
a nd  plas ma  will  be st ore d  in  liq uid  nitr o ge n  for  preser vatio n.  The  follo wi n g  e xperi me nts  will 
be carrie d  o ut in  batc hes  of  1 0 patie nt  ti me  p oints  per  e xperi me nt: 
1. Flo w  c yt o metric  q ua ntificatio n  of  plas ma blasts,  activate d  B  cells,  ter mina l l y 
differe nt ia te d  C D 4 +  c yt ot o xic  T  cells  ( C D 4 + C T Ls),  ter minall y  differe ntiate d  C D 8 + 
c yt ot o xic  T cells ( C D 8 + C T Ls), activate d  follic ular helper   T ( T F H) cells a nd perip her al 
helper  T  ( T P H)  cells.  Ter mina l  differe nt iat i o n  will  be  define d  b y  t he  loss  of  C D 2 8 
s urface  e xpressio n  a nd gain  of  C D 5 7 s urface  e xpressio n  wit hi n  t he  res pective  effect or 
( C D 4 5 R A-C C R 7 -) T cell  p o p ulatio n.  These  cell  p o p ulatio ns  will  be assesse d  at wee ks 
0,  1,  4,  1 2  a nd  2 4  t o  deter mine  t he  treat me nt  effect  o n  t he  a bs olute  nu mbers  a nd 
pr o p ortio ns  of t hese  c ell t ypes. 
2. Q ua ntifie d  cell  p o p ulatio ns  will  be a nalyze d  for  c orrelatio n  wit h  o ne  a not her,  disease 
activit y,  plas ma  I g G 4  le vels  a nd clinical  res p o nsive ness  t o  a batace pt.  
3. Fr o m  5 of  t he e nr olle d  s ubjects  wit h  k no w n  e xpa nsio ns  of t he  res pective  cell  t ype  a nd 
clinical  res p o nsive ness  t o  a batace pt,  ter minall y  differe ntiate d  C D 4 + C T Ls,  ter mina l l y 
differe ntiate d  C D 8 + C T Ls  a nd activate d  B cells  will  be s orte d b y F A C S at wee ks 0, 1 2 
a nd  2 4.  R N A  will  be  is olate d  t o  under go  R T-P C R  a mplificati o n  of  t he  T C R -β/I g H,  
res pectivel y.  N e xt-Ge neratio n  Se q ue ncing  will  be  use d  t o  de fine  t he  diversit y  of  t he 
T C R/ B C R  re pert oire  lo ngit udi nall y  t o ascertain  ho w  a batace pt ma y  i mpact  clo nalit y.  

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 1 7  of 
 
 
 
 
5. 1 Sc he d ule of As s ess me nts  
T he s c he d ule of ass ess me nts is pres e nte d in  ta ble  f or mat in  t he st u d y  s y n o psis  
 
St u d y P h as e  
Sc re e n
i n g  
Tre at me n
t 
VI S I T N U M B E R 
1 
2  
 
3  
 
 
4  
 
 
5  
 
 
W E E
K  
0 
1
1  
2 
3 
 
4 
5 
6 
7 
8 
9 
1 0  1 1  1 2  1 3  
1 4  
1 5  
I nf or me d c o ns e nt 
X  
X   
 
 
 
 
 
 
 
 
 
 
 
 
 
St u d y  dr u g 
d i i 
i
 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
St u d y  dr u g I nstr uctio n  
 
X   
 
 
 
 
 
 
 
 
 
 
 
 
 
Me dic a l  hist or y 2  
X 2 
X  
2  
 
X  
2  
 
 
X 2  
 
 
X 2   
 
 
P h ysic al e xa minatio n 3  
X 3 
X  
3  
 
X  
3  
 
 
X 3  
 
 
X 3   
 
 
A d vers e 
E ve nt 
4  
 
X   
 
X   
 
 
X   
 
 
X   
 
 
Re c or d c o nc o mita nt 
me dic atio ns 4  
X  
X   
 
X   
 
 
X   
 
 
X   
 
 
Vita l  sig ns 5  
X  
X   
 
X   
 
 
X   
 
 
X   
 
 
C B C w/ differe ntial, 
platelet  c o u nt  
X  
X   
 
X   
 
 
X   
 
 
X   
 
 
C o m pre he nsive 
Meta b olic P a nel ( C M P)  
X  
X   
 
X   
 
 
X   
 
 
X   
 
 
Urinalysis  a n d Urine 
pr otein/cre atinine 
 
X  
X   
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Pre g na nc y test 7  
X  
X   
 
X   
 
 
X   
 
 
X   
 
 
H Bs A g, H Bc A b, 
H C V * * N ot re q uire d  if 
c olle cte d  6 m o nt hs 
prior  t o s cre e nin g 
i i * * 
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ser u m i m m u n o glo b uli n 
le vels  (I g M, I g E,  I g G) 
X  
X   
 
 
 
 
 
 
 
 
 
 
 
 
 
Ser u m I g G s u bclass es  
X  
X   
 
X   
 
 
X   
 
 
X   
 
 
C 3 a n d C 4  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Me c ha nistic s a m ples  
X  
X   
 
X   
 
 
 
 
 
 
X   
 
 
Fa stin g  lipid  pr ofile  
X  
X  
 
 
X   
 
 
X   
  
X   
 
 
C T c hest, a b d o me n, 
pe lvis 8  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I g G4-R D RI  
X  
X   
 
X   
 
 
X   
 
 
X   
 
 
P h ysicia n  Glo bal 
A ctivit y  V A S  
X  
X   
 
X   
 
 
 
X  
 
 
 
X   
 
 
S y m pt o m  Se verit y I n de x  
X  
X   
 
X   
 
 
X   
 
 
X   
 
 
Gluc oc ortic oid 
T o xicit y  I n de x  
X  
X   
 
X   
 
 
X   
 
 
X   
 
 
S F -3 6  H e alt h S ur ve y  
X  
X   
 
X   
 
 
X   
 
 
X   
 
 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 1 8  of 
 
 
 
 
 
 
St u d y P h as e  
 
V I SI T N U M B E R 
6  
 
 
7 
 
 
 
8 
9 
1 0/ E O
S  
W E E
 
1 6  
1 7  
1 8  
1 9  
2 0  
2 1  
2 2  
2 3  
2 4  
2 8  
3 6  
I nf or me d c o ns e nt 
 
 
 
 
 
 
 
 
 
 
 
St u d y  dr u g a d ministratio n  
X  
X  
X  
X  
X  
X  
X  
X  
X   
 
Me dic a l  hist or y 2  
X  
 
 
 
X 2   
 
 
X  
X 2  
X 2  
P h ysic al e xa minatio n 3  
X  
 
 
 
X 3   
 
 
X  
X 3  
X 3  
A d vers e E ve nt ass ess me nt 4  
X   
 
 
X   
 
 
X  
X  
X  
Re c or d c o nc o mita nt  me dic atio ns 4  X   
 
 
X   
 
 
X  
X  
X  
Vita l  sig ns 5  
X   
 
 
X   
 
 
X  
X  
X  
C B C w/ differe ntial,  platelet 
 
X   
 
 
X   
 
 
X  
X  
X  
C he mistr y  P a nel  
X   
 
 
X   
 
 
X  
X  
X  
Urinalysis  a n d Urine 
pr otein/cre atinine 
i 6  
 
 
 
 
 
 
 
 
 
 
X  
Urine Pre g na nc y test 7  
X   
 
 
X   
 
 
X  
X  
X  
H Bs A g, H Bc A b, H C V 8  
 
 
 
 
 
 
 
 
 
 
 
Ser u m i m m u n o glo b uli n  le vels 
(I g M, I g E, I g G) 
 
 
 
 
 
 
 
 
X   
X  
I g G s u bclass es 
X   
 
 
X   
 
 
X   
X  
C 3 a n d C 4  
 
 
 
 
 
 
 
 
 
 
X  
Fa stin g  lipid  pr ofile  
X   
 
 
X   
 
 
X  
 
X  
Me c ha nistic s a m ples  
 
 
 
 
 
 
 
 
X   
 
I g G4-R D RI  
X   
 
 
X   
 
 
X   
X  
P h ysicia n  Glo bal  A ctivit y  V A S  
X   
 
 
X   
 
 
X   
X  
S y m pt o m  Se verit y I n de x  
X   
 
 
X   
 
 
X   
X  
Gluc oc ortic oid  T o xicit y  I n de x  
X   
 
 
X   
 
 
X   
X  
S F -3 6  H e alt h S ur ve y  
X   
 
 
X   
 
 
X   
X  
1 T he Scre e nin g visit  ( Visit  1) a n d t he Tre at me nt We e k 1 ( Visit  2) visit  c o uld  p ote ntially  be o n t he s a me 
da y  
2 I nclu des prior  hist or y  a n d tre at me nt of I g G4 - R D 
3 C o m plete  p h ysic al  e xa minatio ns  will  be  perf or me d  at  Scre e nin g,  o n  D a y  1  (c o uld 
p ote ntially  be  t he  s a me  visit)  a n d  at  E O S.  A b bre viate d,  s y m pt o m 
dire cte d  P E  will  be  perf or me d  at  all  ot her  visits.  I nclu de  heig ht  at 
s cre e nin g  o nly  a n d  w eig ht  at  visits  1,  2,  4,  8,  1 2,  1 6,  2 0,  2 4,  2 8,  a n d 
E O S.  
4 A d vers e e ve nts a n d c o nc o mita nt  me dic atio ns  t o be c olle cte d  b y site pers o n nel  via p h o ne  or e mail.  
5 S u pine  blo o d  press ure a n d he art rate, b o d y  te m perat ure, res pirat or y rate. Vital sig n 
ass ess me nts will  be ma de i m me diately  prior  t o inje ctio n.  
6 Urinalysis  a n d urine  pr otein/cre atinine  ratios,  at s cre e nin g or bas eline  a n d E O S, 
a n d at e a c h st u d y visit  if  re nal in v olve me nt  
7 Pre g na nc y test o nly  f or w o me n of c hild -be arin g  p ote ntial  ( urine)  
7 If t he patie nt  has a d oc u me nte d ne gative  res ult wit hin  6 0  da ys bef ore t he first d os e 
of a bata c e pt, t his ite m ma y be o mitte d  
8 All  patie nts  will  ne e d t o ha ve a s cre e nin g C T c hest, a b d o me n a n d pelvis  wit h  he a d 
a nd/ or or bits  if  t here is he a d a n d ne c k or e xtra oc ular m us cle 
in v olve me nt.  If a b n or mal,  it  will  be re pe ate d at a p pr o xi mately  6 
m o nt hs  or e arlier bas e d o n dis e as e a ctivit y.  
* N ot re q uire d  if c olle cte d  6 m o nt hs  prior  t o s cre e nin g visit  

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 1 9  of 
 
 
 
 
5. 2 St u dy  Ass ess me nts  
 
Scree ning  Visit  
T he  follo wi n g  pr oce d ures  will  be perfor me d:  
1.  
O btain  writte n  infor me d  c o nse nt  after  c o nse nt  prese ntatio n  
2.  
O btain  Me dical  hist or y  
a) I ncludi n g  de mo gra p hics 
b)  I ncludi n g  hist or y  of  I g G 4-R D  
3.  
P hysical  e xa mina t io n  
4.  
Rec or d c o nc o mita nt  me dicatio n  
5.  
Vital  sign s  includ i n g;  B P, P, R,  T,  weight,  a nd  height. 
a. 
Weight  will  be meas ure d  wit h  o uter wear  a nd s hoes  re mo ve d  
b.  
Height  will  be  meas ure d  wit h  s hoes  re mo ve d  (scree nin g  visit  o nly)  
c. 
Blo o d  press ure  a nd  p ulse  rate o btaine d  after  t he s ubject  has bee n 
s upine  ≥ 5 minutes 
6.  
A d verse  E ve nt  mo nit or i n g  (fr o m  ti me  of  st ud y  dr ug  a d ministrati o n)  
7.  
La b orat or y  tests:  
a. 
C B C wit h  cell  differe ntial  a nd platelets  
b.  
C he mistr y  pa nel  
c. 
Urinal ysis  a nd urine  pr otein/creati ni ne  ratio  
d.  
Urine  pre gna nc y  test  ( o nly  for  w o ma n  of  c hild  bearing  a ge)  
e. 
He patitis  B a nd  C tests  ( not  re q uire d  if  c ollecte d  3 0 da ys  prior  t o 
scree ning  visit) 
f. 
Ser u m  I m muno glo b uli n  le vels  (I g M,  I g E,  I g G)  
g.  
Ser u m  I g G 4  s ubclasses  
h.  
C o mple me nt  le vels  
i. 
Fasting  lipid  pr ofile  
j. 
Mec ha nistic  sa mples  will  be c ollecte d  fr o m  s ubject  at wee ks 0, 1, 
4, 1 2 a nd 2 4 st udies)  
8.  
I ma gin g  tests:  C T c hest,  a b d o me n,  pelvis 
9.  
P hysicia n  re p orte d  o utc o mes  
a. 
I g G 4  Res p o nder  I nde x  (I g G 4-R D  RI)  
b.  
P hysicia n  Glo bal  Activit y  V A S  
1 0.  
Patie nt  re p orte d  o utc o mes  
a. 
S y mpt o m  Se verit y  I nde x  
b.  
Gluc oc ortic oid  To xicit y  I nde x  
c. 
S F -3 6 Healt h  S ur ve y  
d.  
Patie nt  Glo ba l  Activit y  V A S 
 
Baseline  Visit :  Visit  2 ( wee k  1)  
 
T he  scree ning  ( visit  1) a nd  baseline  visit  ( visit  2) c o uld  p ote ntiall y  be c o mbine d  a nd c o mplete d 
o n t he  sa me da y  
T he  follo wi n g  pr oce d ures  will  be perfor me d:  
1.  
Verify  eligib i lit y  criteria.  
2.  
Re vie w  ge neral  me dic al  a nd  I g G 4  hist or y 
3.  
Brief  p hysical  e xa mina t io n  
4.  
Rec or d c o nc o mita nt  me dicatio n  
5.  
Vital  signs  includ i n g;  B P, P, R,  T,  weight,  a nd  height.  

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 2 0  of 
 
 
 
a. 
Weight  will  be meas ure d  wit h  o uter wear  a nd s hoes 
re mo ve d 
b.  
Blo o d  press ure  a nd  p ulse  rate o btaine d  after  t he s ubject 
has bee n s upine  ≥ 5 minutes 
6.  
A d verse  E ve nt  mo nit or i n g  
7.  
La b orat or y  tests:  
a. 
C B C wit h  cell  differe ntial  a nd platelets  
b.  
C he mistr y  pa nel  
c. 
Urinal ysis  a nd urine  pr otein/creati ni ne  ratio  
d.  
Urine  pre gna nc y  test  ( o nly  for  w o ma n  of  c hild  bearing 
a ge) 
e. 
Ser u m  I m muno glo b uli n  le vels  (I g M ,  I g E,  I g G) 
f. 
Ser u m  I g G 4  s ubclasses  
g.  
Fasting  lipid  pr ofile  
h.  
Mec ha nistic  sa mples  will  be c ollecte d  fr o m  s ubject  at 
wee ks 0, 1, 4, 1 2 a nd 2 4 st udies) 
8.  
Patie nt -re p orte d  o utc o mes: 
a. 
S y mpt o m  Se verit y  I nde x  
b.  
Gluc oc ortic oid  To xicit y  I nde x  
c. 
S F -3 6 Healt h  S ur ve y  
d.  
Patie nt  Glo b al  Activit y  V A S  
9.  
P hysicia n -re p orte d  o utc o mes 
a. 
Gluc oc ortic oid  To xicit y  I nde x  
b.  
P hysicia n  glo bal  activit y  V A S  
c. 
I g G 4-R D  RI  
1 0.  
St ud y  dr ug  a d minis tra tio n  a nd  teac hin g  
1 1.  
St ud y  me dicatio n  dis pe nse  
 
Visit  3 ( wee k 4)- visit  1 0 ( wee k 3 6)  
 
Patie nts  will  ha ve  visits  at Wee ks 4, 8, 1 2, a nd t he n  e ver y  4 wee ks per t he  sc he d ule  of 
assess me nts  s ho w n  in  Ta ble  1  
1.  Brief  p hysical  e xa m  includ i n g  vital  signs  ( F ull  p hysical  e xa m  at E O S)  
2.  Assess me nt  of signs  a nd s y mpt o ms  of I g G 4 -R D  
3.  C o nc o mita nt  Me dicatio ns  re vie w  
4.  A d verse  E ve nts  Assess me nts  
5.  Asses s me nt  of  signs  a nd  s y mpt o ms  of  I g G 4-R D  activit y  
6.  A batace pt  a d ministratio n  ( baseline,  w 4, w 1 2, w 2 0, w 2 8, w 3 6, w 4 4)  
7.  La b orat or y  tests  (t o be dra w n  before  st ud y  pr o d uct  a d ministr atio n).  See sc he d ule  of 
e ve nts.  
i. Mec ha nistic  sa mples  will  be c ollecte d  fr o m  s ubject at wee ks 0, 1, 4, 1 2 
a nd 2 4 st udies) 
8.  Patie nt -re p orte d  o utc o mes  ( per sc he d ule  of  e ve nts,  ta ble  1) 
9.  P hysicia n  re p orte d  o utc o mes  ( per sc he d ule  of e ve nts,  ta ble  1)  
1 0.  St ud y  me dicatio n  acc o unta bilit y  a nd dis pe nse  
 
Safet y  follo w  up  visit  (if  nee de d)  
D uring  t he  safet y  follo w  up t he follo wi n g  pr oce d ures  will  be c o mplete d  
1.  Vital  signs  a nd  P hysical  e xa m  
2.  C o nc o mita nt  Me dicatio ns  re vie w  

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 2 1  of 
 
 
 
3.  A d verse  E ve nts  Assess me nts  
4.  Assess me nt  of signs  a nd s y mpt o ms  of I g G 4 -R D  
 
5. 3 Disc ussio n  of  St ud y  Design  
 
N o t hera pies  for  I g G 4 -R D  ha ve  bee n a p pr o ve d  b y  re gulat or y  a ut horities  a nd  t hus  t here  are no 
esta blis he d  st ud y  designs  for  t his  disease  indicatio n.  This  st ud y  design  is  c o nsiste nt  wit h  t he 
foc us  of t his  trial  o n pr o of- of-c o nce pt  a nd mec ha nistic  st udies  a nd  will  be s uita ble  t o ac hie ve 
t his  goal  base d o n t he  strict  pri mar y  o utc o me  criteria.  There  is  no c o ntr ol  gr o up  in  t his  pr o of  of 
c o nce pt  st ud y.  T he  design  will  be a ble  t o assess w het her  a batace pt ca n  ha ve  a n effect  o n disease 
res p o nse  as has  bee n s ho w n  in  a prior  case re p ort as disc usse d  a b o ve.  The  design  of  t his  trial  is 
a p pr o priate  t o o ur  c urre nt  understa ndi n g  of t he  p ote ntial  r ole  of a batace pt in  I g G 4 -R D,  w hic h  is 
prese ntly  t o o li mite d  t o j ustif y  a ra nd o mize d  trial.   S ho uld  patie nts  fail  t o res p o nd  t o t he  st ud y 
dr ug  a batace pt  or s ho uld  t he y de velo p  e nd -or ga n  ma nife sta t io ns,  t he y  will  be a ble  t o o btain 
sta ndar d  of  care gluc oc ortic oi d  treat me nt. 
 
A was ho ut  perio d  is b uilt  int o  t he st ud y  pr ot oc ol.  Exclusio n  criteria  include  t he prior  use  of 
rit uxi ma b  ( or  ot her  B cell  de pleting  a ge nts)  wit hi n  6 mo nt hs  of  e nr oll me nt  unless  B  cells  ha ve 
bee n  de mo nstrate d  t o  ha ve  re p o p ulate d  or t he  use  of  a ny  investi ga tio na l  a ge nt  wit hi n  5 half -
lives  of  t he  a ge nt  ( or 6 mo nt hs  if  t he  half-life  is unk no w n)  prior  t o e nr oll me nt.  This  s ho uld  be 
s uffic ie nt  in  ide ntif yi n g  any  a d verse  effects  d ue t o t he  investi gati o nal  pr o d uct  a batace pt. 
H o we ver,  patie nt’s  ma y  ha ve  bee n  o n  gluc oc ortic o ids  d uring  trial  e ntr y,  b ut  must  be willi n g  t o 
ta per off  of gluc oc ortic oid s  wit hi n 4  8 wee ks of be ginni n g  a batace pt. This  is  necessar y  in  or der 
to s uffic ie nt l y recr uit  patie nts  for  t he  st ud y. 
 
T he  investi gati o nal  me dicatio n  a batace pt  is d ose d wee kly  b y s ubc uta ne o us  r o ute  w hic h  is 
c o nsiste nt  wit h  its  p har mac o kinetic  a nd p har mac o d y na mic  pr ofile.  It is  a p pr o ve d for  t he 
treat me nt  of  r he u mat oid  art hritis  at  t his  d osing  inter va l.  These  me dicatio ns  ma y  be c o ntinue d 
indefi nitel y  for c o ntr ol  of t he  disease  a nd a ny  effect  s ho uld  be seen  wit hi n  2 4 wee ks of 
treat me nt. 
 
5. 4 Early  Ter minati o n  of  t he  St ud y  
 
If  t he I nvesti gat or  or t he  S p o ns or bec o mes  a ware of  c o nditio ns  or  e ve nts  t hat  s uggest  a p ossible 
hazar d  t o s ubjects  if  t he  clinical  st ud y  c o ntinues,  t he n  t he clinical  st ud y  ma y  be ter minate d  after 
a p pr o priate  c o ns ultatio n  a mo ng  t he invol ve d  parties.  The  clinic al  st ud y  ma y  be ter minate d  at 
t he  S p o ns or’s  discretion  als o  in  t he  a bse nce  of  s uc h  a findi n g.  
C o nditio ns  t hat  ma y  warra nt  ter minati o n  of  t he  clinica l  st ud y  include,  b ut  are not  li mite d  t o:  
• 
T he  disc o ver y  of a n  une xpecte d,  rele va nt,  or unacce pta ble  ris k  t o t he 
s ubjects  e nr olle d  in  t he  clinica l  st ud y; 
• 
Failure  t o e nr oll  s ubjects  at t he  re q uire d  rate;  
• 
A decisio n  of t he  S p o ns or t o s us pe nd  or disc o ntin ue  de velo p me nt  of t he 
I M P. 
 
S ho uld  t he  st ud y  be ter minate d, a nd/ or  t he  site  close d  for w hate ver  reas o n,  all  d oc u me ntatio n 
pertaini n g  t o t he  st ud y  a nd  I M P must  be ret ur ne d  t o t he  S p o ns or. A ny  actio ns  re q uire d  for 
assessing  or maintai ni n g  st ud y  s ubject  safet y  will  c o ntinue  as re q uire d,  des pite  ter minatio n  of 
t he  st ud y  b y  t he  S p o ns or. 
 
E nd - of-St ud y  is  define d  as c o mpletio n  of  t he  End - of-St ud y  Visit  o n Wee k 3 6.  
 
 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 2 2  of 
 
 
 
 
5. 5 Selec tio n  of St ud y  P o p ulatio n 
 
Male  a nd fe male  s ubjects  w ho  meet  t he A C R/ E U L A R  2 0 1 8 Classificatio n  Criteria  for  I g G 4 - 
R D A N D active  disease  ( define d  b y I g G 4 -R D  RI ≥2 at scree ning  wit h  disease  ma nifestati o n  in 
at  least  o ne  or ga n  s yste m  e xcludi n g  ly mp h  no des  at  s cree ning).  S ubjects  are not  re q uire d  t o 
ha ve  faile d  prior  t hera p y  for t heir  disease  t o be eligible  for t his  st ud y.  
 
I nclus io n  C riteria 
S ubjects  w ho  meet  t he follo wi n g  criteria  will  be c o nsidere d  eligible  t o participate  in  t he clinical 
st ud y  if  t he y: 
2.  
Are  ma le  or fe male  1 8 years  of a ge or older 
3.  
Meet t he A C R/ E U L A R  2 0 1 8 Classificatio n  Criteria  for  I g G 4 -R D  (see 
a p pe ndix) 
4.  
Ha ve  active  disease  base d o n a n I g G 4 -R D  RI ≥2 at scree ning  wit h  disease 
ma nife sta tio n  in  at least  o ne  or ga n  s yste m  e xcludi n g  ly mp h  no des  at 
scree ning 
5.  
Ma y or ma y  not  ha ve  receive d  prior  I g G 4 -R D  t hera p y  
6.  
M ust  be willi n g  t o ta per off  a ny  s yste mic  c ortic oster oid  t hera p y  wit hi n 
4   8 
wee ks of first  d ose of  trial  dr ug.  
7.  
M ust  be a ble  a nd willi n g  t o disc o ntin ue  a ny  i m mu nos up pr essi ve  a ge nt  at 
scree ning  (e. g.  met hotre xate,  myc o p he nolate  mofetil,  6-merca pt o p uri ne, 
tacr oli m us,  c yclo p hos p ha mid e  or azat hio pri ne). 
8.  
N o hist or y  of se vere  aller gic  reactio ns  t o mo noclo nal  a ntib o dies.  
9.  
Are a ble  a nd willi n g  t o c o mplete  t he  e ntire  st ud y  acc or ding  t o t he st ud y 
sc he d ule. 
1 0.  
Are wil li n g  t o  fore go  ot her  for ms  of  e xperi me nta l  treat me nt  d uring  t he  st ud y. 
1 1.  
Are a ble  t o pr o vide  writte n  infor me d  c o nse nt.  
 
E xclus io n  C riteria  
S ubjects  w ho  meet  o ne or more  of  t he follo wi n g  criteria  will  not be c o nsidere d  eligible  t o 
participate  in  t he  clinical st ud y: 
1.  Hist or y  or e vide nce  of a clinicall y  unsta ble/ u nc o ntr olle d  dis or der,  c o nditio n  or diseas e 
(includi n g  b ut  not  li mite d  t o  car dio p ul mo nar y,  o nc olo gic,  re nal,  he patic,  meta b olic, 
he mat olo gic  or  ps yc hiatric)  ot her  t ha n  I g G 4 -R D  t hat,  in  t he  o pinio n  of  t he  
I nvesti gat or,  w o uld  p ose a ris k  t o patie nt  safet y  or interfere  wit h  t he st ud y  e valuati o n, 
pr oce d ures  or c o mpletio n.  
2.  Maligna nc y  wit hin  5 years (e xce pt s uccessfull y  treate d in sit u  cer vical  ca ncer, resecte d 
s q ua mo us cell  or basal cell carcino ma  of t he s kin,  or pr ostate  ca ncer wit h  no  rec urre nc e 
≥3 years  follo wi n g pr ostatect o my).  
3.  Liver  disease:  Ac ute  or c hr o nic  no n -I g G 4-relate d  liver  disease  dee me d s ufficie ntl y 
se vere  t o i mpair  t heir  a bilit y  t o  participate  in  t he trial. 
4.  U nc o ntr olle d  disease:  e vide nce  of a not he r  unc o ntr o lle d  c o nditio n,  includ i n g  dr ug 
a nd alc o hol a b use,  w hic h  c o uld interfere wit h  participatio n in t he trial acc or ding t o t he 
pr ot oc ol. 
5.  Prese nce  of rec urre nt  or c hr o nic  infectio ns,  define d  as ≥3 infectio ns  re q uirin g 
a nti micr o bials  o ver t he  past 6 mo nths  prior  t o  scree nin g. 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 2 3  of 
 
 
 
6.  Active  infectio n  re q uirin g  hos pitalizatio n  or treat me nt  wit h  pare nteral  a nti micr o bials 
wit hi n  t he 3 0 da ys  prior  t o  ra nd o miza t io n. 
7.  Prior  use  of  rit uxi ma b  ( or  ot her  B  cell  de pletin g  a ge nts)  wit hi n  6 mo nt hs  of 
e nr oll me nt  unless  B  cells ha ve  bee n de mo nstrate d  t o ha ve  re p o p ulate d. 
8.  Use  of  a ny  investi ga tio na l  a ge nt  wit hi n  5 half -li ve s  of  t he  a ge nt  ( or  6 mo nt hs  if  t he 
half- life  is  unk no w n)  prior  t o e nr oll me nt.  
9.  W hite  blo o d  cell  c o unt  < 2. 5 x 1 0 3 / µ L. 
1 0.  A bs olute  ne utr o p hil  c o unt  ( A N C) < 1. 0 x 1 0 3 / µ L. 
1 1.  I g G 4-relate d  re nal  disease  wit h  ser u m  creatini ne  > 2. 0 mg/ d L.  
1 2.  He mo glo bi n  < 1 0 g/ d L.  
1 3.  Platelet  c o unt  < 7 5 x  1 09 / L. 
1 4.  K no w n  p ositive  res ult  for  HI V  I or II  a ntib o d y,  he patitis  B  s urface  a ntige n,  he patitis 
B c ore a ntib o d y  or he patitis  C  a ntib o d y. 
1 5.  Has receive d  live  vaccines  wit hi n  4 wee ks o k  e nr oll me nt.  
1 6.  I na bilit y  t o  c o m munica te  relia bl y  wit h  t he investi ga t or. 
1 7.  Patie nt  is  pre gna nt  or breast  fee ding,  or pla nni n g  t o bec o me pre gna nt  w hile  e nr olle d 
in  t he  st ud y,  up  t o E O S visit.  
1 8.  P ositive  pre gna nc y  test at scree ning or  d uring  t he  st ud y. 
1 9.  S ubjects  of  c hild beari n g  p ote ntial  w ho d o not  a gree t o use me dicall y  acce pta ble 
met ho ds  of  c o ntrace ptio n.  
2 0.  K no w n  or s us pecte d se nsiti vit y t o ma m ma lia n  cell-derive d   pr o d ucts  or a ny 
c o mp o ne nts  of  t he st ud y dr ug.  
2 1.  Hist or y  of alc o hol  a nd/ or s ubsta nce  a b use  wit hi n  1 2 mo nt hs  prior  t o scree ning. 
2 2.  U na ble  or un willi n g  t o parta ke in  follo w -up  assess me nts  or re q uire d  pr ot oc ol 
pr oce d ures.  
5. 6 Wit hdra wal  of S ubjects 
S ubjects  are e nc o ura ge d  t o c o mplete  all  st ud y  e valuatio ns.  H o we ver,  t he y  ma y  wit hdra w  fr o m 
t he  st ud y  at  a ny  ti me  a nd  for  a ny  reas o n.  Ever y  effort  will  be ma de  t o  deter mine  w hy  a n y 
s ubject wit hdra ws  fr o m t he st ud y pre mat urel y.  All  s ubjects w ho  wit hdra w  fr o m t he st ud y wit h 
a n o ngoin g  A E must  be follo we d  until  t he  e ve nt  is  res olve d  or dee me d  st a ble.  At t he  ti me  t hat 
a  s ubject  wit hdra ws  pre mat urel y  for  a ny  reas o n,  all  assess me nts  as  liste d  for  t he  E O S  visit 
s ho uld  be perfor me d.  If  a s ubject  wit hdra ws  pre mat urel y  after  d osing,  all  data t o be c ollect e d 
prior  t o  disc har ge  fr o m  t he  clinica l  site  will  be  c ollecte d  at  t he  ti me  of  pre mat ur e 
disc o nti n uati o n   or at t he sc he d ule d e nd- of-st ud y visit.  S ubject  participat io n ma y   be ter mina t e d  
prior  t o c o mpleti n g  t he st ud y  a nd t he  reas o n rec or de d as  follo ws : 
1.  A d verse  e ve nt 
2.  Pr ot oc ol violat io n 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 2 4  of 
 
 
 
3.  L oss t o  F ollo w -up  
4.  S ubj ect  wit hdre w c o nse nt 
5.  I nvesti gat or  wit hdre w  s ubject  t o give  resc ue  t hera p y  ot her  t ha n ster oids 
6.  Ot her  
A c o mpre he nsi ve  effort  must  be ma de  t o deter mine  t he  reas o n(s)  w hy  a s ubject  fails  t o ret ur n 
for  t he  necessar y  visits  or  is  disc o ntin ue d  fr o m  t he  st ud y.  If t he  s ubject  is  unreac ha ble  b y 
tele p ho ne,  a re gistere d  letter,  at mini m u m,  s ho uld  be se nt  t o t he  s ubject  re q uesting  hi m/ her  t o 
c o ntact  t he  st ud y  site.  
S ubjects  wit hdra w n  d ue  t o  A Es  c o nsidere d  t o  ha ve  a p ossible  relatio ns hi p  t o st ud y  dr ug  will 
not  be re place d.  S ubjects  wit hdra w n  for  a no n -dr ug  relate d  reas o n  will  be re place d  if  dee me d 
necessar y  b y  t he  S p o ns or.  T he  decisio n  re gar ding  t he  re place me nt  of  s ubjects  will  be 
d oc u me nte d.  
If  a  s ubject  wit hdra ws  pre mat urel y,  all  assess me nts  as  liste d  for  t he  E O S  visit s ho uld  be 
perfor me d  a nd rec or de d o n a n unsc he d ule d  visit  e C R F  pa ge.  I n a d ditio n, t he s ubject s ho uld be 
sc he d ule d  for  a  follo w-up  visit  4  wee ks  fr o m  t he  ti me  of  t he  last  injectio n  of  st ud y  dr ug,  at 
w hic h  ti me  all  assess me nts  as liste d  for  t he  E O S visit  s ho u ld  be perfor me d. 
5. 7 Ot he r  S u bje ct  R e s tricti o ns  
S ubjects  must  ha ve  signe d  a nd  date d a n  I R B/I E C -a p pr o ve d  writte n  infor me d  c o nse nt  for m  i n 
acc or da nce  wit h  re gulat or y a nd instit uti o na l guideli nes   before t he perfor ma nce   of a ny pr ot oc ol-  
relate d  pr oce d ures.  Pris o ners  or s ubjects  w ho  are c o mp uls or y  detaine d  will  not  be eligible  t o 
participate.  
5. 8 St o p pi ng  Crite ri a  f or  t he  Cli nic al  St u dy  
Participatio n  for  a ny  indivi d ual  s ubject  will  be  st o p pe d  if  t he  s ubject  e xperie nces  a  p ossibl y 
dr ug-relate d  S A E  or a p ossibly  dr ug-relate d  significa nt  no n-serio us  A E,  w hic h  in  t he  o pini o n 
of  t he  PI or  S p o ns or’s  me dical  re prese ntati ve,  warra nts  disc o nti n uati o n  of  t he  s ubject  in  t he 
st ud y  in  t he  interest  of t hat  s ubject’s  well-bei n g.  Disc o nti n uatio n  of  t he s ubject  fr o m  t he st ud y 
wil l  be disc usse d  wit h  t he S p o ns or. 
T he  I nvestigat or  will  ma ke  all  a p pr o priate  safet y  assess me nts  o n  a n  o ngoing  basis.  The 
S p o ns or’s  me dical  re prese ntati ve  will  re vie w  individ ua l  safet y  infor ma t io n  as  it  bec o me s  
a vaila b le  t hr o ugho ut  t he  st ud y.  
A n  I D M C  will  be  use d  t o e valuate  interi m  safet y  a nd  efficac y  res ults  a nd  t o deter mine  if  t he 
trial  s ho uld  be st o p pe d early.  All  unbli nde d  a nalyses  for  I D M C re vie w  will  be pre pare d b y  a n 
inde pe nde nt  Data  C o or dinatin g  C e nter  (I D C C). Me mbers  of t he  I D M C will  be e xter nal  t o t he  
S p o ns or’s  st ud y  tea m  a nd  will  follo w  a  c harter  t hat  o utli nes  t heir  r oles  a nd  res p o nsibilitie s. 
Prior  t o  t he  pla nne d  interi m  a nalyses  of  t he  pri mar y  e nd p oint,  t he  I D M C  will  meet 
a p pr o xi matel y  t wice  a nnuall y  t o re vie w  safet y.  

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 2 5  of 
 
 
 
 
6. T R E A T M E N T  O F  S U B J E C T S    
6 . 1 I de ntit y  of St u dy  Tre at me nt(s) 
O R E N CI A (a batace pt)  is  a s oluble  fusio n  pr otein  t hat  c o nsists  of  t he e xtracell ular  d o main  of  
hu ma n  c yt ot o xic  T -ly mp hoc yte-ass ociate d  a ntige n  4  ( C T L A-4)  linke d  t o  t he  mo difie d  Fc 
( hinge,  C H 2, a nd  C H 3 d o mains)  p ortio n  of  huma n  i m mu no glo b uli n  G 1  (I g G 1).  A batace pt  is 
pr o d uce d  b y  rec o mbina nt  D N A  tec hnolo g y  in  a  ma m malia n  cell  e xpressio n  s yste m.  The 
a p pare nt  molec ular  weight  of a batace pt is  9 2 kilo dalt o ns.  
 
O R E N C I A  s olutio n  for  s ubc uta ne o us  a d minis tra t io n  is  s up plie d  as a steril e,  preser vative -free, 
clear,  c olorless  t o  pale -yello w  s olutio n  wit h  a  p H  of  6. 8  t o  7. 4.  Eac h  single  d ose  of 
s ubc uta ne o us injectio n  pr o vides  1 2 5 mg  a batace pt,  dibasic   s o diu m  p hos p hate a nhydr o us  ( 0. 8 3 8 
mg),  mo no basic  s o diu m  p hos p hate  mo no hydrat e  ( 0. 2 8 6 mg), p olo xa mer  1 8 8 ( 8 mg),  s ucr os e 
( 1 7 0  mg),  a nd  q ua ntit y  s uffic ie nt  t o  1  m L  wit h  water  for  injectio n.  U nlike  t he  intra ve n o us  
for mulati o n,  O R E N CI A  s olutio n  for  s ubc uta ne o us  a d ministrati o n  c o ntains  no malt ose.  
A ctive  s u bsta nc e:  a bata c e pt 
Teste d  in dic atio n:  I g G4 - R D 
Stre n gt h:  1 2 5. 0  m g/s yrin ge  
D os a ge f or m:  prefille d  glass s yrin ge 
R o ute of a d ministratio n:  S C inje ctio n  
T he d osin g  a n d s c he d ule are s u p p orte d b y  P has e I or later res e arc h.  
 
6. 2  A d mi nistrati o n  of St u dy  Tre at me nt(s)  
All  s u bjects  will  receive  a batace pt.  
6. 3 Tre at me nt   Prot oc ol 
•A batace pt ( Ore ncia):  O ne  1 2 5 mg/ m L  single -d ose  prefille d  glass  s yringe  will  be a d minis t e r e d  
b y  s ubc uta ne o us  ( S C)  injectio n  wee kly  b y  t he  pati e nts  or care givers.  Patie nts  a nd  care gi vers 
will  be traine d  o n  ho w  t o a d minis ter  t he  me dicatio n  b y  t he  st ud y  investi gat o rs  or a  designa t e d  
st ud y  staff  me mber  d uring  baseline  a nd  wee k 1 visits.  A batace pt  interr upti o ns  or wit hdra w a ls 
will  be as per t he c urre nt  U. S. pr o d uct  insert  ( See Attac he d  Pac ka ge I nsert).  
•Pre d nis o ne  ta per :  S ubjects  w ho  are  o n  pre d nis o ne  at  baseline  will  be gin  a n  investi gat o r-
directe d  c ortic oster oid  ta per designe d  t o disc o ntin ue  pre d nis o ne  not later  t ha n  8 wee ks after  t he 
baseline  visit.    
6. 4 St u dy  Tre at me nt  P ac k a gi ng  a n d  L a belli ng  
O R E N CI A (a batace pt)  injectio n  s olutio n  for  s ubc uta ne o us  a d ministrati o n  is s up plie d  eit her  as 
a single-d ose  dis p osa ble  prefille d  glass  s yringe  wit h  Ultra Safe  Passive  nee dle guar d  wit h  fla n ge 
e xte nders  or as a single-d ose  dis p osa ble  prefille d  glass  s yrin ge  wit h  fla nge  e xte nder.  The  Type 
I glass  s yringe  has  a  c oate d  st o p per  a nd  fixe d  stainless-steel  nee dle  ( 5  be vel,  2 9- ga uge  t hi n 
wall,  ½ -inc h  nee dle)  c o vere d wit h  a rigid  nee dle  s hield.  The  prefille d  s yrin ge  pr o vides  1 2 5 m g 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 2 6  of 
 
 
 
of a batace pt  in  1 m L  a nd  is pr o vide d  in  t he follo wi n g  pac ka ges:  
• 
N D C 0 0 0 3- 2 1 8 8- 1 1: pac k of  4 s yringes  wit h  a passive  nee dle  safet y  guar d  
• 
N D C 0 0 0 3- 2 1 8 8- 3 1: pac k of  4 s yringes  wit ho ut  a passive  nee dle  safet y  guar d  
6. 5 St ora ge 
O R E N CI A  s olutio n  s up p lie d  in  a prefille d  s yringe  s ho uld  be refrigerate d  at 2 C t o 8 C ( 3 6 F t o 
4 6 F). T he  me dicatio ns  s ho uld  not  be use d be yo nd  t he  e xpiratio n  date o n t he  prefille d  s yringe.  
It s ho uld  be pr otecte d fr o m  light  b y st oring  in  t he origi nal  pac ka ge until  ti me  of use. The prefille d 
s yringe  s ho uld  not be allo we d  t o freeze. 
 
T he  I nvestigat or /I ns tit uti o n  is  res p o nsible  for  t he  follo wi n g.  
o  I nvesti gati o nal  pr o d uct  is  t o be st ore d  in  a sec ure  area acc or ding  t o local  re gulat i o ns 
a nd  st ore d  under  t he  a p pr o priate  e nvir o n me ntal  c o nd itio ns  (te mperat ure,  light,  a nd  
hu midit y).  If  mar kete d  pr o d uct  is  use d,  it  s ho uld  be  st ore d  in  acc or da nce  wit h  t he 
pac ka ge  insert, S u m mar y   of Pr o d uct C haracteristics  ( S m P C), U nite d  States  prescri bi n g 
infor mat i o n  ( U S PI),  or si mila r guida nce.  
o  T he  investi ga t io nal  pr o d uct  will  be  dis pe nse d  o nly  t o  st ud y  s ubjects  a nd  o nly  fr o m 
official  st ud y  sites  b y a ut horize d  pers o nnel,  as dictate d  b y local  re gulatio ns 
o  C urre nt  dis p ositio n  rec or d  of  I P (s up plie d  b y B M S)  is  t o be maintai ne d  at eac h  st u d y 
site  w here  st ud y  dr ug  is  inve nt or ie d  a nd dis pe nse d  
o  Pr oce d ures  for  pr o per  dis p osal  ha ve  bee n  esta blis he d  acc or ding  t o  a p plica ble 
re gulatio ns,  guideli nes,  a nd  instit utio na l pr oce d ures  
6. 6 S u bje ct  C o m pli a nce  
D osing  will  be perfor me d  b y traine d,  q ualifie d  pers o nnel  designate d  b y  t he  PI.  The  date  a nd 
ti me  of d osing will   be d oc u me nte d   o n eac h d osing da y.  C o m me nts  will   be rec or de d if t here are 
a ny  de viatio ns  fr o m  t he  pla nne d  d osing pr oce d ures.  
6. 7 St u dy  Tre at me nt  Acc o u nt a bilit y,  H a n dli ng,  a n d  Dis pos al  
T he  I nvesti gat or  or designee  is  res p o nsible  for  maintai ni n g  acc urate  acc o unta bilit y  rec or ds of 
t he  I M Ps t hr o ugho ut  t he  clinica l  st ud y.  The  dr ug  acc o unta bilit y  lo g  includes  infor  mati o n  s uc h 
as a mo unt  dis pe nse d  a nd  a mo unt  ret ur ne d  t o t he  p har mac y  (if  a ny).  
All  dis pe nsi n g  a nd  acc o unta bilit y  re c or ds  will  be a vaila ble  for  S p o ns or  re vie w  after  data base 
loc k. T he  site p har macist  ( or designee  under  t he directio n  of t he p har macist)  will  dis pe nse  I M P 
for  eac h s ubject  acc or ding  t o t he pr ot oc ol  a nd p har mac y  ma nual,  if a p plica ble.  
After  receivi n g  S p o ns or  a p pr o val  in  writin g,  t he  site  is  res p o nsible  for  eit her  ret ur ni n g  all 
unuse d  or partiall y  use d I M P t o t he  S p o ns or  or designate d  t hir d  part y  or for  t he  destr uctio n  of 
t he  I M P acc or ding  t o locally  c o mplia nt  pr oce d ures. 
6. 8 C o nc o mit a nt  T he ra py  
Pre vio us/ C o nc o mita nt  Me dicatio n  
C o nc urre nt  a d ministr atio n  of  a T N F a nta go nist  wit h  a batace pt  has bee n ass ociate d  wit h  a n 
increase d  ris k  of  serio us  infectio ns  a nd no signific a nt  a d ditio nal  efficac y  o ver use of  t he T N F 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 2 7  of 
 
 
 
a nta go nists  alo ne.  C o nc urre nt  t hera p y  wit h  a batace pt a nd  T N F a nta go nis ts  is  not 
rec o m me nde d.  
 
Dis all o we d  pre vi o us or  c o nc o mit a nt  me dic ati o ns:  
• Prior  use of  rit uxi ma b  ( or ot her B cell  de pletin g  a ge nts)  wit hi n  6 mo nt hs  of e nr oll me nt 
unless  B cells  ha ve  bee n de mo nstrate d  t o ha ve   re p o p ulate d. 
• Use  of  a ny  investi g a tio na l  a ge nt  wit hi n  5 half-li ve s  of  t he  a ge nt  ( or  6 mo nt hs  if  t he  half- 
life  is  unk no w n)  prior  t o e nr oll me nt 
• Receive d  live  vaccines  wit hi n  4 wee ks of  e nr oll me nt.  
 
Fro m  A bat ace pt  P ac k a ge I ns e rt (s e cti o n 5. 1): C o nc o mit a nt  Us e wit h  T N F A nt a g o nists  
•  I n  c o ntr olle d  clinica l  trials  in  patie nts  wit h  a d ult  R A,  patie nts  receivi n g  c o nc o mita nt 
O R E N CI A a nd T N F a nta go nist  t hera p y  e xperie nce d  more  infectio ns  ( 6 3 %) a nd serio us 
infectio ns  ( 4. 4 %) c o mpare d  t o patie nts  treate d  wit h  o nly  T N F a nta go nists  ( 4 3 % a nd 
0. 8 %, res pectivel y)  [see A d verse  Reactio ns  ( 6. 1) fr o m  pac ka ge insert].  These  trials 
faile d  t o de mo nstrate  a n i mp orta nt  e nha nce me nt  of efficac y  wit h  c o nc o mita nt 
a d ministr atio n  of  O R E N CI A  wit h  T N F  a nta go nist;  t herefore,  c o nc urre nt  t hera p y  wit h 
O R E N CI A  a nd  a T N F  a nta go nist  is  not  rec o m me nde d.  W hile  tra nsit io ni n g  fr o m  T N F 
a nta go nist  t hera p y  t o O R E N CI A t hera p y,  patie nts  s ho uld  be mo nit ore d  for signs  of 
infect io n. 
o  E nbrel  (eta nerce pt)  
o  Kineret  (a na kinra)  
o  C i mzia  (cert oliz u ma b  pe gol)  
o  H u mira  (a dali m u ma b )  
o  Rit uxa n  (rit uxi ma b )  
o  Acte m ra  (t ociliz u ma b) 
o  Re mica de  (infli xi ma b)  
o  Si mp o n  ( goli m u ma b)  
•  
D e ta ils  of  a ll prior  a n d c o nc o mita nt me dic atio n  m ust  be  re c or de d at st u d y e ntr y (i. e., at t he first 
visit)  inclu din g  prior  tre at me nt f or I g G4 -R D, prior I g G4 -R D c linic a l  tria l  pa rtic ipa tio n  a n d prio r 
m o n oclo nal  a ntib o d y  us e. All  t hera pies ( pres criptio n  or o ver -t he-c o u nter me dic atio ns,  inclu di n g 
vita mins  a n d her bal s u p ple me nts) differe nt fr o m t he st u d y dr u g m ust be re c or de d. A n y me dicin a l 
pr o d uct,  pres cribe d or O T C,  inclu din g  her bal  a n d ot her  n o n -tra ditio nal  re me dies,  is  c o nsidere d 
a  c o nc o mita nt  me dic atio n.  A n y  c ha n ges  in  c o nc o mita nt  me dic atio n  m ust  be re c or de d  at e a c h 
visit. If t he c ha n ge influe nc es  t he s u bje ct’s eligibilit y  t o c o ntin ue  in  t he st u d y,  t he S p o ns or  m ust 
be  inf or me d.  C o nc o mita nt  me dic atio n  us e ma y  be  w arra nte d f or  t he  tre at me nt of  A Es.  I n t he 
interest of  s u bje ct s afet y a n d a c c e pta ble  sta n dar ds of  me dic al  c are  t he  I n vestigat or  will  be 
per mitte d  t o pres cribe tre at me nt(s) at his/ her dis cretio n.  All  tre at me nts m ust be  re c or de d in t he 
s u bje cts’ c as e  re p ort f or m ( C R F); me dic atio n,  d os e,  tre at me nt d uratio n  a n d  in dic atio n. 
•  
T he  inf or matio n c olle cte d f or e a c h c o nc o mita nt me dic atio n  inclu des, at a mini m u m,  start date, 
e n d date or o n g oin g,  d os e a n d u nit,  fre q ue nc y, r o ute of a d ministratio n  a n d  in dic a tion.  

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 2 8  of 
 
 
 
6. 9  C o ntr ac e pti o n  
•  
W o me n  of  c hild be arin g  p ote ntial  m ust  ha ve a ne gative  pre g na nc y  test d urin g  s cre e nin g  a n d  at 
bas eline  ( D a y 1)  a n d  m ust  us e 1 hig hly  effe ctive met h o d  of birt h  c o ntr ol  d urin g  t he  st u d y  a n d 
f or  3  m o nt hs  f ollo win g  t he  last  d os e  of  a bata c e pt. Hig hly  effe ctive  met h o ds  of  birt h  c o ntr ol 
inclu de  h or m o nal  birt h  c o ntr ol,  intra uterine  de vic es (I U Ds),  or  a n y  barrier  met h o ds  (s p o n ges, 
fe male c o n d o ms) us e d b y t he w o ma n in  a d ditio n  t o c o ntra c e ptio n us e d b y t heir male part ner s uc h 
as a vas e ct o m y or a c o nd o m  s u p ple me nte d  wit h s per micide.  
•  
W o me n of n o n -c hild be arin g  p ote ntial  m ust ha ve a d oc u me nte d re as o n (i. e., p ost me n o pa us al  b y 
hist or y  wit h  n o  me ns es f or  o ne ye ar a n d c o nfir me d  b y  F S H [ usin g  loc al  refere nc e ra n ges], O R 
hist or y  of  h ystere ct o m y,  O R  hist or y  of bilateral  t u bal  ligatio n,  O R  hist or y  of  bilatera l 
o o p h ore ct o m y).  
•  
Male s u bje cts of c hild be arin g  p ote ntial  m ust  be willin g  t o pra ctic e a hig hly  effe ctive met h o d  of 
birt h  c o ntr ol  f or  t he  d uratio n  of  t he  st u d y  a n d  c o ntin uin g  f or  3  m o nt hs  after t he  last  d os e  of  
a bata c e pt.  Hig hly  effe ctive  met h o ds  of  birt h  c o ntr ol  inclu de  a  vas e ct o m y  or  a  c o n d o m  in 
c o m binatio n  wit h  barrier met h o ds,  h or m o nal  birt h  c o ntr ol  or I U D us e d b y  t he w o ma n.  
 
6. 1 0 Tre at me nt  C o m pli a nce   
 
Patie nts  will  be as ke d t o maintai n  diaries  t o rec or d me dicatio n  ta ke n at ho me.  These  diaries 
will  be re vie we d  b y t he c o or dinat ors  at eac h visit  t o assess c o mplia nce.  
 
7.  A S S E S S M E N T O F E F FI C A C Y  
7. 1  Effic ac y  Vari a ble s  
Efficac y  will  be  meas ure d  b y  t he  a bilit y  of  a batace pt  t o  s ustain  t he  disease  i mpr o ve me nt. 
Disease  activit y  will  be  follo we d  using  t he  follo wi n g  assess me nts  t o  be  rec or de d  b y  st ud y 
investi gat o rs : 
• 
I g G 4-R D  RI will  be t he  pri mar y  efficac y  varia ble  
• 
T he  follo w i n g  assess me nts  will  als o  be  o btaine d: 
• 
P hysicia n  Glo bal  Assess me nt  of  Disease  Activit y  ( Vis ual  Acti vit y Sc ore)  
• 
S ubject’s  Glo bal  Disease  Activit y  V A S  
• 
S y mpt o m  Se verit y  I nde x 
• 
Gluc oc ortic o id  T o xicit y  I nde x 
• 
S F -3 6 Healt h S ur ve y  
7. 2  Effic ac y As s ess me nts  
T he  follo wi n g  efficac y  assess me nts  will  be perfor me d  acc or ding  t o t he  ti me  p oints  define d  in 
t he  Sc he d ule  of Assess me nts  ( Ta ble  1).  
• I g G 4-R D R e s po n de r  I n de x 
Disease  activit y will   be meas ure d  per  sc he d ule  of assess me nts.   F or deter minati o n   of t he I g G 4-  
R D  res p o nder inde x as describe d  in t he sc he d ules  of assess me nts (I g G 4-R D  RI),  t he follo wi n g 
criteria  will  be  use d ( mo difie d  after  C arr ut hers  et al.  2 0 1 2):  Or ga n  site,  s y mpt o matic,  ur ge nt 
disease  (as per I g G 4 -R D  RI)  o ver  t he  pre vio us  2 8  da ys.  
T he  origina l  I g G 4 -R D  RI  has  bee n  mo difie d  t o includ e  t he  full  s pectr u m  of  or ga ns  affect e d 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 2 9  of 
 
 
 
most  fre q ue ntl y  b y  I g G 4 -R D  a nd  t o  eli m i nat e  ser u m  I g G 4  c o nce ntratio ns  as  part  of  t he 
instr u me nt.  I n  a d ditio n,  a n  assess me nt  of  da ma ge  ca use d  b y I g G 4-R D  in  eac h  affecte d  or ga n 
is  include d.  A sa mple  assess me nt  for m  is  include d  in A p pe ndix.  
• P hysici a n  Gl o bal  Dis e as e Acti vit y  V A S  
T he  p hysicia n’s   o verall assess me nt  of t he s ubject’s c urre nt disease  activit y will   be rec or de d o n 
a 1 0 0 m m  linear  horizo nt al  V A S,  w here  t he  left  ha nd  e xtre me  of  t he  line  is  c o nsidere d  “ Ver y 
G o o d”  (s y mpt o m  free  a nd  no  I g G 4 -R D  s y mpt o ms)  a nd  t he  right -ha nd  e xtre me  is  c o nsider e d  
“ Ver y  Ba d”  ( ma xi m u m  I g G 4 -R D  activit y).  
Details  o n t he  efficac y  assess me nts  ca n be fo und  in A p pe ndix.  
• S u bje ct’s  Gl o bal  Dis e as e Acti vit y  V A S  
T he  s ubject’s  o verall  assess me nt  of t he  s ubject’s  c urre nt  disease  activit y  will  be rec or de d o n a 
1 0 0  m m  linear  horiz o ntal  V A S,  w here  t he  left  ha nd  e xtre me  of  t he  line  is  c o nsidere d  “ Ver y 
G o o d”  (s y mpt o m  free  a nd  no  I g G 4 -R D  s y mpt o ms)  a nd  t he  right  ha nd  e xtre me  is  c o nsider e d  
“ Ver y  Ba d”  ( ma xi m u m  I g G 4 -R D  activit y).  
• S y m pt o m  Se ve rit y  I n de x 
T he  S y mpt o m  Se verit y  I nde x  is  a  no vel  instr u me nt  for  assessing  patie nt-re p orte d  diseas e 
se verit y. It has  not  yet  bee n  validate d  in  a  lo ngit ud i na l  st ud y  of  patie nts  wit h  I g G 4 -R D  b ut  is  
base d  o n  si milar  instr u me nts  use d  in  ot her  c o nditio ns  like  dia betes  mellit us,  hyperte ns io n,  a nd 
be nign  pr osta te  hypertr o p h y.  T he  instr u me nt  q ueries  patie nts  o n  s y mpt o ms  t hat  ca n  be 
ass ociate d  wit h  differe nt  ma nifestatio ns  of  I g G 4 -R D.  F or  eac h  or ga n,  t he  patie nt  sc ores  t he 
se verit y  of his/ her  s y mpt o ms a nd a t otal sc ore is t he n derive d.  I n a d ditio n t o helpin g assess t he  
efficac y  of treat me nt, data  c ollecte d  t hr o ugh t he use  of t his instr u me nt in t his trial will   be use d  
t o assess  t he  valid it y  of  t he instr u me nt. 
• Gl uc oc ortic oi d  T o xicit y  I n de x 
T he  gluc oc ortic oi d  t o xicit y  inde x  is  a  c o mpre he nsi ve  assess me nt  of  t he  c ha nge 
i n 
gluc oc ortic oid  t o xicit y  o ver  ti mes.  It  fact ors  in  a  nu mber  of  varia bles  includi n g  b o d y  mass 
inde x,  gluc ose  t olera nce,  blo o d press ure,  lipids,  b o ne  de nsit y,  ster oid  myo pat hy,  s kin  t o xicit y, 
ne ur o ps yc hiatric  t o xicit y,  infectio n,  a nd  e nd ocrine  (a dre nal  ins uffic ie nc y),  gastr ointes ti na l,  
musc ulos k e le ta l,  a nd  oc ular  t o xicit ies.  
• 3 6- Ite m S hort  F or m  He alt h S urve y  
T he  S F - 3 6 is  a set of  ge neric,  c o here nt,  a nd  easily  a d minister e d  q ualit y- of-life  meas ures.  It has  
bee n use d in  ma ny  diseases  t o assess t he  s ubject’s  per s pective  of  t he effect  t hat  t he disease  pla ys 
in  t heir  activit ies  of  daily  life. T hese  meas ures  rely  up o n  patie nt  self -re p orti n g  a nd are no w wi d el y 
utilize d

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 3 0  of 
 
 
 
 
 
7. 3 P O S T - S T U D Y  A C C E S S  & A D V E R S E  E V E N T 
R E P O R TI N G I N F O R M A TI O N F O R 
I N T E R V E N TI O N A L  P R O T O C O L S 
 
At t he  e nd of t he  st ud y  perio d,  Brist ol-M yer s  S q uib b  C o mpa ny  will  not  c o ntinue  t o  s up pl y 
st ud y dr ug t o s ubjects/i n vesti gat ors unless  t he S p o ns or-I nvesti ga t or c ho oses t o e xte nd t heir 
st ud y.  T he  investi gat or  is  res p o nsible  t o  e ns ure  t hat  t he  s ubject  receives  a p pr o priat e 
sta ndar d  of care or ot her   a p pr o priate treat me nt in t he inde pe nde nt me dical  j ud ge me nt  of t he  
I nvesti gat or  t o  treat  t he  c o nditio n  under st ud y. 
• All  Serio us  A d verse  E ve nts  ( S A Es)  t hat  occ ur  follo wi n g  t he s ubject’s  writte n  c o nse nt  t o 
participate  in  t he  s t ud y  t hr o ugh  3 0 da ys  of disc o nti n uati o n  of d osing  must  be re p orte d  t o 
B M S  W orld wide Safet y,  w het her  relate d  or not  relate d t o st ud y dr ug.  If a p plica ble,  S A Es 
must  be  c ollecte d  t hat  relate  t o  a ny  later  pr ot oc ol -s pecifie d  pr oce d ure  (e g,  a follo w - u p 
s kin  bio ps y). 
• F ollo wi n g  t he  s ubject’s  writte n  c o nse nt  t o  participate  in  t he  st ud y,  all  S A Es,  w het her 
relate d  or not  relate d t o st ud y dr ug,  are c ollecte d,  includ i n g t hose t ho ught t o be ass ociate d 
wit h  pr ot oc ol -s pecifie d  pr oce d ures.  The  investi gat or  s ho uld  re p ort  a ny S A E  occ urri n g 
after  t hese  afore me ntio ne d  ti me  perio ds,  w hic h  is  belie ve d  t o be relate d  t o st ud y  dr ug  or 
pr ot oc ol- s pecifie d pr oce d ure.  
• A n  S A E  re p ort  s ho uld  be  c o mplete d  for  a ny  e ve nt  w here  d o ubt  e xists  re gar ding  its  
serio us ness; 
• If  t he  investi ga t or  belie ves  t hat  a n  S A E  is  not  relate d  t o  st ud y  dr ug,  b ut  is  p ote ntiall y 
relate d  t o  t he  c o nditio ns  of  t he  st ud y  (s uc h  as  wit hdra wal  of  pre vio us  t hera p y  or  a 
c o mplicati o n  of  a st ud y  pr oce d ure),  t he  relatio ns hi p  s ho uld  be s pecifie d  in  t he  narrati ve 
sectio n  of  t he S A E Re p ort F or m.  
• If  t he  B M S  safet y  a d dress  is  not  include d  in  t he  pr ot oc ol  d oc u me nt  (e g,  multice nt er 
st udies  w here  e ve nts  are re p orte d  ce ntrall y),  t he  pr oce d ure  for  safet y  re p orting  must  be 
re vie we d/a p pr o ve d  b y  t he  B M S  Pr ot oc ol  Ma na ger.  Pr oce d ures  for  s uc h  re porting  mus t  
be re vie we d  a nd a p pr o ve d b y B M S prior  t o st ud y  activatio n.  
A n  a p pr o priate  S A E  for m  (e. g. e x - U S = CI O M S for m  or U S A = Me d watc h  for m)  will  be use d 
t o re p ort  S A Es t o B M S. 
o  T he  CI O M S for m  is a vaila ble  at:  htt p:// w w w.ci o ms.c h/i nde x. p hp/cio ms -for m-i 
o  T he  Me d Watc h  for m  is  a vaila ble  at: Me d Watc h  3 5 0 0  F or m  
• F or st udies  wit h  lo ng -ter m  follo w-up  perio d s  in  w hic h  safet y  data are being  re p orte d, 
include  t he  ti min g  of  S A E c ollectio n.  
• T he  S p o ns or  will  rec o ncile  t he clinical  data base S A E cases (case le vel  o nly)  tra ns mitt e d 
t o  B M S  Glo bal  P har mac o vi gila nce  (W orld wide. Safet y @ b ms .c o m).  Fre q ue nc y  of 
rec o nciliatio n  s ho uld  be  e ver y  3  mo nt hs  a nd  prior  t o  t he  data base  loc k  or  final  data 
s u m mar y.  B M S  G P V & E  will  e mail,  up o n  re q uest  fr o m  t he  I nvesti gat or,  t he  G P V & E 
rec o nciliatio n  
re p ort.  
Re q uests  
for  
rec o nciliati o n  
s ho uld  
be  
se nt  
t o 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 3 1  of 
 
 
 
ae p b usiness pr ocess @ b ms.c o m.  The  data  ele me nts  liste d  o n  t he  G P V & E  rec o nciliat i o n 
re p ort will  be use d for  case ide ntific atio n  p ur p oses.  If  t he I nvesti gat or  deter mines  a case 
was  not  tra ns mitte d  t o B M S  G P V & E,  t he  case  s ho uld  be  se nt  i m me diatel y  t o  B M S.I n 
acc or da nce  wit h  local  re gulatio ns,  B M S  will  notify  investi gat ors  of  all  re p orte d  S A Es 
t hat  are  s us pecte d  (relate d  t o  t he  investi gati o nal  pr o d uct)  a nd  une xpecte d  (ie,  not 
pre vio usl y  describe d  in  t he  I B).  A n  e ve nt  meeting  t hese  criteria  is  ter me d  a  S us pecte d, 
U ne xpecte d  Serio us  A d verse  Reactio n  ( S U S A R). I nvestiga t or notifica t io n  of t hese e ve nts  
will  be in  t he  for m  of  a  S U S A R  Re p ort. 
o  Ot her  i mp orta nt  findi n gs  w hic h  ma y  be re p orte d  b y  B M S as  a n  Expe dite d  Safet y 
Re p ort ( E S R) include : increase d fre q ue nc y  of a clinica ll y signif ica nt e xpecte d  S A E,  
a n S A E  c o nsidere d  ass ociate d  wit h  st ud y  pr oce d ures  t hat  c o uld  mo dify  t he  c o nd uct 
of t he st ud y, lac k of efficac y t hat  p oses signific a nt hazar d  t o st ud y s ubjects, clinica l l y 
significa nt  safet y  find i n g  fr o m  a  no ncli nical  (e g,  a ni mal)  st ud y,  i mp orta nt  safet y 
rec o m me ndati o ns  fr o m  a  st ud y  data  mo nit ori n g  c o m mittee,  or  s p o ns or  decisio n  t o 
e nd or te mp oraril y  halt  a clinical  st ud y  for  safet y reas o ns. 
o  U p o n receivi n g a n E S R  fr o m B M S,  t he investi ga t or must  re vie w a nd retain t he E S R 
wit h  t he I B. W here re q uire d  b y local  re gulatio ns  or w he n  t here  is  a ce ntral  I R B/I E C 
for  t he  st ud y,  t he  s p o ns or  will  s ub mit  t he  E S R  t o  t he  a p pr o priate  I R B/I E C.  T he 
investi gat or  a nd I R B/I E C  will  deter mine  if  t he  infor me d  c o nse nt  re q uires  re visio n. 
T he in vestigat or  s h o uld  als o  c o m ply  wit h  t he I R B/I E C pr oc e d ures f or re p ortin g  a n y ot her 
s afet y inf or matio n. 
o  I n  a d ditio n  t o  t he  S p o ns or  I n vestigat or’s  res p o nsibilit y  t o  re p ort  e ve nts t o  t heir loc a l  H A, 
s us pe cte d s erio us a d vers e re a ctio ns ( w het her e x pe cte d or u ne x pe cte d) s hall  be  re p orte d b y 
B M S  t o  t he  rele va nt  c o m pete nt  he alt h  a ut h orities  in  all  c o nc er ne d c o u ntries  a c c or din g  t o 
loc al  re g ulatio ns  (eit her as e x pe dite d  a n d/ or in  a g gre gate re p orts). 
S A Es,  w het her relate d  or n ot  relate d  t o st u d y  dr u g,  a n d pre g na ncies  m ust  be re p orte d  t o  B M S  wit hin 
2 4  h o urs \ 1 B usiness D a y of be c o min g  a w are of t he e ve nt. S A Es m ust  be re c or de d o n  eit her CI O M S, 
Me d Watc h, or a p pr o ve d  site S A Ef or m.  
Pre g na ncies m ust be re p orte d a n d s u b mitte d  t o B M S o n a n y of t he f ollo win g  f or m(s):  
1.  Me d Wa tc h or, CI O M S or  
2.  B M S Pre g na nc y S ur veilla nc e  F or m  or , 
3.  A p pr o ve d site S A E  f or m 
S A E E m ail A d dre s s :  W orld wide. Safet y @ B M S. c o m  
S A E F acsi mile  N u m be r:  + 1 6 0 9 -8 1 8 -3 8 0 4  
If o nly  li mite d  inf or ma tio n  is  initia lly  a va ila ble ,  f ollo w -u p  re p orts are re q uire d. ( N ote: F ollo w - u p S A E 
re p orts s h o uld  inclu de  t he s a me in vestigat or  ter m(s) initially  re p orte d.) 
If a n o n g oin g  S A E c ha n ges in  its  inte nsit y  or relatio ns hip  t o st u d y dr u g  or if ne w inf or matio n  be c o mes 
a vaila ble,  a f ollo w-u p  S A E  re p ort s h o uld be  s e nt wit hin  2 4  h o urs  \ 1 B usiness  D a y  t o  B M S usin g  t he 
s a me pr oc e d ure us e d f or tra ns mittin g  t he initial  S A E re p ort. 
All  S A Es s h o uld  be f ollo w e d  t o res olutio n  or sta bilizatio n.  
 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 3 2  of 
 
 
 
D E FI NI TI O N S  
T he pr ot oc ol  m ust inclu de  a definitio n  f or  Serio us A d vers e E ve nts ( S A E) . 
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 dverse E ve nt ( S A E) is  a ny  unt o war d  me dical  occ urre nce  t hat  at a ny  d ose: 
• res ults  in deat h 
• is  life-t hre ate ni n g  ( define d  as a n e ve nt  in  w hic h  t he  participa nt  was at ris k  of deat h  at t he 
ti me  of t he  e ve nt;  it  d oes  not  refer  t o  a n  e ve nt  w hic h  hyp ot hetica ll y  might  ha ve  ca use d  
deat h  if  it  were more  se vere) 
• re q uires  inpatie nt  hos pitali zati o n  or  ca uses  pr olo ngatio n  of  e xistin g  hos pitalizati o n ( see 
N O T E belo w) 
• res ults  in  persiste nt  or significa nt  disa bilit y/i nc a pacit y 
• is  a c o nge nita l  a no mal y/ b irt h defect  
• is  a n i mp orta nt  me dical  e ve nt  ( define d  as a me dical  e ve nt(s)  t hat  ma y  not be i m me diat e l y 
life-t hr eate ni n g  or res ult  in  deat h or hos pitalizatio n  b ut,  base d up o n  a p pr o priate  me dic al 
a nd  scie ntific  j ud g me nt,  ma y  je o par dize  t he  s ubject  or  ma y  re q uire  inter ve nti o n  [e g, 
me dical,  s ur gical]  t o pre ve nt  o ne  of  t he  ot her  serio us  o utc o mes  liste d  in  t he  definit i o n 
a b o ve.)  E xa mples  of  s uc h  e ve nts  inclu de,  b ut  are not  li mite d  t o, inte nsi ve  treat me nt  i n 
a n  e mer ge nc y  r o o m or  at  ho me  for  aller gic  br o nc hos pas m;  blo o d  d yscrasias  or 
c o nvuls io ns  t hat  d o  not  res ult  in hos pitalizatio n.)  
• S us pecte d  tra ns missi o n  of  a n  infectio us  a ge nt  (e g,  pat ho ge nic  or  no npat ho ge nic)  via  t he 
st ud y  dr ug  is  a n S A E.  
Alt ho ug h  pre gna nc y,  o ver d ose,  p ote n tial  dr ug-ind uce d  liver  inj ur y  ( DI LI),  a nd  ca ncer  are not 
al wa ys  serio us  b y  re gulat or y  definiti o n,  t hese  e ve nts  must  be ha ndle d  as S A Es.  
A ny  c o mp o ne nt  of  a  st ud y  e nd p oint  t hat  is  c o nsidere d  relate d  t o  st ud y  t hera p y  s ho uld  be 
re p orte d as a n S A E  (e g, deat h is a n e nd p oint, if deat h occ urre d  d ue  t o a na p hyla xis,  a na p hyla x is  
must  be  re p orte d). 
N O T E :  ( PI deter mines  if  t his  infor matio n  re gar din g  hos pitalizati o ns  are c o nsidere d  S A Es  a nd 
s ho uld  be include d  in  t he  pr ot oc ol.  T his  is  s up ple me nta l  infor ma t io n  t hat  is  inc l ude d  in  B M S-
s p o ns ore d  trials) 
T he  follo wi n g  hos pitalizatio ns  are not  c o nsidere d  S A Es in  B M S clinical  st udies:  
• a visit  t o t he e mer ge nc y  r o o m or ot her  hos pital de part me nt   < 2 4 ho urs,  t hat d oes not  res ult 
in  a d missio n  ( unless  c o nsidere d  a n  i mp orta nt  me dical or life -t hreate ni n g e ve nt) 
• elective  s ur ger y,  pla nne d  prior  t o signi n g c o nse nt 
• a d missio ns  as per pr ot oc ol  for  a pla nne d  me dical/s ur gical   pr oce d ure 
• r o utine  healt h  assess me nt  re q uiri n g  a d missio n  for  baseline/tr e nd i n g  of  healt h  stat us  (e g,  
r o utine  c olo nosc o p y) 
• Me dical/s ur gical  a d missio n ot her  t ha n t o re me d y ill healt h a nd pla nne d   prior t o e ntr y int o  
t he  st ud y.  A p pr o priate  d oc u me ntatio n  is re q uire d  in  t hese cases. 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 3 3  of 
 
 
 
• A d missio n  e nc o untere d  for  a not her  life  circ u msta nce  t hat  carries  no  bearing  o n  healt h 
stat us  a nd  req uires  no  me dical/s ur gical  inter ve ntio n  (e g,  lac k  of  ho usin g,  ec o no mic 
ina de q uac y,  care giver  res pite,  fa mil y  circ u msta nces,  a d ministrati ve reas o n). 
• A d missio n  for  a d ministratio n  of  a ntica ncer  t hera p y  in  t he  a bse nce  of  a ny  ot her  S A Es 
(a p plies  t o o nc olo gy pr o t oc ols) 
 
A D V E R S E  E V E N T S  
A n  A d verse  E ve nt  ( A E) is define d  as a ny ne w  unt o war d  me dical  occ urre nce   or w orse ning   of a 
pree xisti n g  me dical  c o nditio n  in  a  clinica l  invest i ga t io n  participa nt  a d minis tere d  st ud y  dr u g 
a nd  t hat  d oes  not  necessaril y  ha ve  a  ca usal  rela tio ns hip  wit h  t his  treat me nt.  A n  A E  ca n 
t herefore  be a ny unfa vora b le  a nd uninte nde d  sign (s uc h as a n a b nor mal  la b orat or y  findi n g), 
s y mpt o m,  or disease  te mp orall y  ass ociate d  wit h  t he  use  of investi gati o nal  pr o d uct,  w het her  or 
not c o nsidere d  relate d  t o t he investi ga tio na l  pr o d uct.  
T he  ca usal relatio ns hi p t o st ud y dr ug is deter mine d   b y a p hysicia n a nd s ho uld  be use d  t o assess 
all  a d verse  e ve nts  ( A E).  T he  cas ual  relatio ns hip  ca n be o ne of t he  follo wi n g: 
Relate d:  T here  is  a reas o na ble  ca usal  relatio ns hip  bet wee n  st ud y  dr ug  a d minis tra tio n  a nd  t he  
A E.  
N ot relate d:  T here  is  not  a reas o na ble  ca usal  relatio ns hip  bet wee n  st ud y  dr ug  a d ministra t i o n 
a nd  t he  A E.  
T he  ter m  "reas o na ble  ca usal  relatio ns hip "  mea ns  t here  is  e vide nce  t o  s uggest  a  ca usal 
relatio ns hi p. 
A d verse  e ve n ts  ca n  be  s p o nta ne o usl y  re p orte d  or  elicite d  d uring  o pe n-e nde d  q uestio ni n g, 
e xa mina t io n,   or e valuatio n  of a s ubject. (I n or der t o pre ve nt  re p orting bias,  s ubjects s ho uld not 
be q uestio ne d  re gar din g  t he s pecific  occ urre nce  of  o ne or more  A Es.)  
N O N S E RI O U S A D V E R S E  E V E N T  
• N o n- serio us  A d verse  E ve nts  ( A E)  are  t o be pr o vide d  t o B M S  in  a ggre gate  via  interi m 
or final  st ud y  re p orts  as s pecifie d  in  t he  a gree me nt  or, if  a re gulat or y  re q uire me nt  [e g, 
I N D U S trial]  as part of  a n a nnual  re p orting re q uire me nt. 
• N o n- serio us  AE infor mati o n  s ho uld  als o be c ollecte d  fr o m  t he start  of a place b o lea d - i n 
perio d  or  ot her  o bser vatio nal  perio d  inte nde d  t o  esta blis h  a  baseline  stat us  for  t he 
s ubjects. 
A n o n- seri o us a dverse eve nt is  a n A E not  classifie d  as serio us. 
N o n- s e ri o us A dve rs e Eve nt  C olle cti o n  a n d  R e porti ng  
T he  c ollectio n  of no n -serio us  A E  infor ma tio n  s ho uld  be gin  at initia tio n  of  st ud y  dr ug.  All  no n-
serio us a d verse e ve nts ( not o nly t hose dee me d  t o  be treat me nt-relate d) s ho uld  be c ollect e d 
c o ntinuo us l y d uring t he treat me nt  perio d a nd for a mini m u m   of 3 0 da ys  follo wi n g t he last  d ose 
of st ud y treat me nt. 
N o n-serio us  A Es  s ho uld  be follo we d  t o res olutio n  or sta bilizati o n,  or re p orte d as S A Es if  t he y 
bec o me  serio us.  F ollo w -up  is  als o  re q uire d  for  no n -serio us  A Es  t hat  ca use  interr upti o n or 
disc o nti n uati o n   of st ud y dr ug a nd for t hose prese nt  at t he e nd of st ud y treat me nt as a p pr o priate. 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 3 4  of 
 
 
 
L a borat ory  Test A b nor malities  
All  la b orat or y  test res ults  ca pt ure d  as part of t he st ud y  s ho uld  be rec or de d follo wi n g 
instit uti o na l  pr oce d ures.  Test  res ults t hat  c o nstit ute  S A Es  s ho uld  be d oc u me nte d  a nd re p orte d 
t o B M S as s uc h. 
T he  follo wi n g  la b orat or y  a b nor malities  s ho uld  be d oc u me nte d  a nd re p orte d  a p pr o priately:  
• a ny  la b orat or y  test res ult  t hat  is clinicall y  significa nt  or meets  t he  definitio n  of a n  S A E  
• 
a n y la b orat or y  a b n or malit y  t hat re q uire d  t he participa nt  t o ha ve st u d y  dr u g dis c o ntin ue d  or 
interr u pte d 
• 
a n y la b orat or y a b n or malit y t hat re q uire d t he s u bje ct t o re c eive s pe c ific c orre ctive  t hera p y. 
It is e x pe cte d t hat w here ver  p ossible,  t he c linic a l rat her t ha n la b orat or y ter m w o uld  be  us e d  b y  t he 
re p ortin g  in vestigat or  (e g, a ne mia  vers us lo w he m o glo bin value).  
P ote nti al D r u g I n d uc e d Li v e r I nj ur y ( DI LI)  
P ote ntial  dr u g in d uc e d  liver  injur y  is define d  as:  
1)  A T ( A L T or A S T) ele vatio n  > 3 ti mes u p per li mit  of n or mal  (U L N)  
A N D  
2)  T otal  bilir u bin  > 2 ti mes U L N, wit h o ut  initial  fin din gs  of c h olestasis (ele vate d s er u m alkaline  
p h os p hatas e)  
A N D  
3)  N o ot her i m me diately  a p pare nt p ossible  c a us es of A T ele vatio n  a n d h y per bilir u bi ne mia, 
inclu din g,  b ut n ot  li mite d  t o,  viral  he patitis, pre -e xistin g  c hr o nic  or a c ute liver  dis e as e, or t he 
a d ministratio n  of ot her dr u g(s) k n o w n  t o be  he pat ot o xic.  
W here ver p ossible,  ti mely  c o nfir matio n  of initial  liver -relate d  la b orat or y  a b n or malities s h o uld  oc c ur 
prior  t o t he re p ortin g  of a p ote ntial  DI LI e v e nt. All  oc c urre nc es of p ote ntial  DI LIs, me etin g  t he 
define d criteria, m ust be re p orte d as  S A Es.  
Pre g n a nc y  
If, f ollo win g initia tio n of  t he in vestigatio nal pr o d uct,  it is s u bs e q ue ntly dis c o vere d  t hat a st u d y 
participa nt  is  pre g na nt or ma y ha ve be e n pre g na nt  at t he ti me  of in vestigatio nal  pr o d uct e x p os ure, 
inclu din g d urin g  at le ast 5 ha lf -live s after pr o d uct  a d ministratio n, t he in vestigatio nal  pr o d uct  will  be 
per ma ne ntly  dis c o ntin ue d  in  a n a p pr o priate  ma n ner (e g, d os e ta perin g  if ne c ess ar y f or  participa nt).  
T he  in vestigat or m ust  i m me dia te ly n otif y  W orld wide. Safet y @ b ms. c o m  of  t his e ve nt via  eit her t he 
CI O M S, Me d Watc h or a p pr o priate Pre g na nc y S ur veilla nc e  F or m in  a c c or da nc e wit h S A E re p ortin g  
pr oc e d ures.  
Pr ot oc o l-re q uire d  pr oc e d ures f or st u d y dis c o ntin uatio n  a n d f ollo w-u p  m ust be perf or me d o n  t he 
participa nt.  
F ollo w -u p  inf or matio n re gar din g t he c o urs e  of  t he pre g na nc y,  inclu din g perinatal a n d ne o natal 
o utc o me a n d,  w here a p plic a ble,  offs prin g  inf or matio n  m ust be re p orte d o n t he CI O M S, Me d Watc h, 
B M S Pre g na nc y S ur veilla nc e  F or m, o r a p pr o ve d site S A E f or m. A B M S Pre g na nc y S ur veilla nc e 
F or m ma y be pr o vide d  u p o n  re q uest. 
A n y pre g na nc y t hat oc c urs in  a fe male part ner of a male  st u d y participa nt  s h o uld  be re p orte d t o  B M S.  
I nf or matio n o n  t his pre g na nc y  will  be  c olle cte d o n  t he Pre g na nc y  S ur ve illa nc e  F or m. I n or der f or 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 3 5  of 
 
 
 
S p o ns or or designee  t o c ollect  a ny  pre gna nc y  s ur veilla nce  infor mati o n  fr o m  t he fe male 
part ner,  t he  fe male  part ner  must  sign  a n infor me d  c o nse nt  for m  for  discl os ure  of  t his 
infor mat i o n. 
O ve r dos e 
A n  o ver d ose is  define d  as t he  accide ntal  or inte ntio nal  a d ministratio n  of a ny  d ose of a  pr o d uct 
t hat  is  c o nsidere d  b ot h e xcessive  a nd me dicall y  i mp orta nt.  All  occ urre nces  of  o ver d ose must 
be re p orte d as a n  S A E.  
Ot he r  S af et y C o nsi de rati o ns 
A ny  significa nt  w orse nin g  note d  d uring  interi m  or  final  p hysical  e xa mi nati o ns, 
electr ocar dio gra ms,  X-ra ys, a nd a ny  ot her  p ote ntial  safet y  assess me nts,  w het her  or not t hese 
pr oce d ures  are re q uire d  b y t he  pr ot oc ol,  s ho uld  als o  be rec or de d as a no n-serio us  or serio us 
A E, as a p pr o priate,  a nd re p orte d acc or dingl y.  
L a borat ory  Ass ess me nts  
T he  follo wi n g  la b orat or y  varia bles  will  be deter mine d  as o utline d  belo w:  
He mat ol o g y :  T he  follo w i n g  he mat olo g y  para meters  will  be assesse d:  he mo glo b i n, he mat ocr it, 
re d blo o d cell  c o unt,  w hite  blo o d  cell  c o unt  wit h  differe ntial  ( % a nd derive d  a bs olute  values), 
mea n  c or p usc ular  volu me,  mea n  c or p usc ular  he mo glo bi n,  mea n  c or p usc ular  he mo gl o b i n 
c o nce ntratio n,  a nd a bs olute  platelet  c o unt. 
Cli nic al  c o m pre he ns i ve   met a bolic test ( C M P) : The   follo wi n g clinica l c he mistr y para meters 
will  be  assesse d  per  sc he d ule  of  assess me nt:  T otal  pr otein,  s o diu m,  p otassiu m,  calci u m, 
c hloride,  bicar b o nate  ( H C O 3 ), alb u mi n,  gluc ose,  blo o d  urea  nitr o ge n  ( B U N),  creatini ne,  t otal 
bilir ub i n,  
alka line  
p hos p hatase  ( A P),  as partate  a minotra nsferas e  
( A S T),  ala ni n e 
a minotra nsferase  ( A L T),  a nd  he mo glo bi n  A 1 C. He mo glo bi n  A 1 C will  be use d  as a s urr o gat e 
for  pa ncreatic  e nd ocrine functio n. A  fasting  lipid  pa nel  a nd  H b A 1c  will  be perfor me d  d uri n g 
t he  G TI assess me nt  visits. 
I m m u no gl o b uli n:  Ser u m  I g M,  I g G,  a nd  I g E  will  be  assesse d  per  sc he d ule  of  assess me nt. 
Ser u m  I g G s ubclasses  will  be meas ure d  per sc he d ule  of  assess me nt 
C o m ple me nt  le vels: C 3 a nd C 4 le vels  will  be assesse d per sc he d ule  of  assess me nt  
Uri nal ysis a nd  Urine  pr otein/creati ni ne  ratio:  The  follo wi n g  urinal ysis  para meters  will  be 
assesse d  per  sc he d ule  of  assess me nt:  p H,  gluc ose,  ket o nes,  s pecific  gra vit y,  nitrite,  pr otei n, 
bilir ubi n,  ur o bili no ge n,  le uk oc ytes  a nd  blo o d.  Micr osc o pic  urinal ysis  will  be  per for me d  if 
clinicall y  indicate d.  
Se rol o g y :  H Bs A g,  H Bc A b,  a nd  H C V  A b  will  be  perfor me d  at  Scree ning.  N ot  re q uire d  if 
c ollecte d  6 mo nt hs  prior  t o scree nin g  visit. 
Uri ne   Pre g na nc y  Te s t :  Urine  pre gna nc y  testing  will  be  perfor me d  in  fe male  s ubjects  of 
c hild bearin g  a ge (if  not  s ur gicall y  sterilize d)  
M e c ha nistic s a m ples: C orrel ati ve  St u dies  
Perip heral   blo o d mo no nuc lea r  cells ( P B M Cs) a nd plas ma  will   be is olate d a nd fr oze n fr o m eac h 
s ubject  at wee ks  0, 1, 4, 1 2 a nd  2 4 c orres p o nding  wit h  clinical  blo o d  dra ws.  Flo w  c yto metr y 
lo o king  at T cells  will  be assesse d  at wee ks  0, 1, 4, 1 2 a nd 2 4. Fr o m  5 of  t he  e nr olle d  s ubjects 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 3 6  of 
 
 
 
wit h  k no w n  e xpa nsio ns  of  t he  res pective  cell  t ype  a nd  clinical  res p o nsive ness  t o  a batace pt, 
ter minall y  differe ntiate d  C D 4 + C T Ls,  ter minall y  differe ntiat ed  C D 8 + C T Ls  a nd  activate d  B 
cells  will  be s orte d b y F A C S at wee ks 0, 1 2 a nd 2 4. 
Bl o o d  R e q uire  me nts :  
Blo o d  will  be c ollecte d  for  clinica l  la b orat or y  testing  as  o utline d  belo w: 
He mat olo g y:  Blo o d  ( 3 m L)  will  be c ollecte d  int o  a la ve nder- t o p  ( E D T A)  t ube. 
C he mis tr y:  Blo o d  ( 5. 0 m L)  will  be c ollecte d  int o  a ser u m  gel  ( S S T) t ube. 
He patitis  ser olo gies ( H Bs A g, H Bc A b,  H C V A b):   Blo o d ( 4. 0 m L)  will   be c ollecte d  int o  a ser u m 
gel  ( S S T)  t ube.  I m muno gl o b uli ns  (I g G,  I g M,  I g E,  I g G4 )  a nd C o mple me nt  C 3 a nd  C 4: Blo o d  ( 5 
m L)  will  b e c ollecte d  int o  a ser u m  gel  ( S T T)  t ube.  
Flo w  C yt o metr y  B  C ell  a nd  C D 1 9 R O:  Blo o d  ( 3. 0 m L)  will  be c ollecte d  int o  a la ve nder -t o p 
t ube  a nd blo o d ( 5. 0 m L)  will  be c ollecte d  in  a C yt o-C he x  B C T glass  strec k C E mar ke d  t ube.  
Plas ma blast  a nd  C D 4 +  C T L  Assess me nt: Blo o d  ( 5. 0  m L)  will  be  c ollecte d  in  a  C yt o -C he x 
B C T glass  strec k C E mar ke d  t ube.  
L a borat ory  V al ues O utsi de  N or mal  R a nge:  
A ny  value  o utside  t he  nor mal  ra nge  will  be  fla gge d  for  t he  atte ntio n  of  t he  I nvesti gat o r  or 
designee  at  t he  site.  T he  I nvesti gat or  or d esignee  will  indicate  w het her  or not  t he  value  is  of 
clinica l significa nce.  La b orat or y values  t hat are clinica ll y significa nt a nd t hat are not  e xplai ne d 
b y  t he  s ubject’s  underlyi n g  disease  or  me dicatio ns  s ho uld  be  e ntere d  as  A Es  a nd  t he 
relatio ns hi p  t o  st ud y  dr ug  assigne d.  A  la b orat or y  value  of  clinica ll y  significa nce  t ypica ll y 
re q uires  a dia gnost ic   or t hera pe utic inter ve nti o n ot her  t ha n re peating t he test. A d ditio nal testi n g 
d uring  t he  st ud y  ma y  be  d o ne  if  me dicall y  indicate d.  The  st ud y  s ubject  will  be fol lo we d  until 
t he  test(s)  has ( ha ve)  nor malize d  or sta bilize d. 
P hysic al  E x a mi nati o n  
C o mplete  p hysical  e xa minatio ns  will  be perfor me d  at Scree ning,  o n  Da y  1 (c o uld  p ote ntiall y 
be t he sa me visit)  a nd at E O S.  A b bre viate d  P Es  will   be directe d   t o war ds t he s y mpt o ms  of I g G 4- 
R D t hat  were pre vio usl y  define d  a nd will  be perfor me d  at all  ot her  visits.  
T he  p hysical  e xa minati o n  includes  a n  assess me nt  of  ge neral  a p peara nce  a nd  a  re vie w  of 
s yste ms  ( der mat olo gic,  hea d,  e yes,  ears,  nose,  mo ut h/t hr oat/ nec k,  t hyr oid,  ly mp h  no d es, 
res pirat or y,  car dio vasc ular,  gastr ointesti nal,  e xtre mities,  musc ulos keletal,  ne ur olo gic,  a nd 
ps yc hiatric  s yste ms).  
Vit al  Si g ns  
Vital  signs  will  be  assesse d  at  Scree ning  ( Visit  1)  a nd  at  eac h  visit  t o  t he  PI’s  office.  The 
follo w i n g  vital  signs  will  be meas ure d: 
• Blo o d  press ure  (s yst olic  a nd diast olic  [ m m H g]); 
• Heart  rate ( beats per minute  [ b p m]); 
• B o d y  te mperat ure  (° C); 
• Res pirat or y  rate ( breat hs  per  minute).  
 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 3 7  of 
 
 
 
 
 
8.  S T A TI S TI C A L  E V A L U A TI O N  
 
8. 1 A nal ysis P o p ul ati o n 
 
T he definitio ns  of st u d y p o p ulatio ns  are as f ol lo ws: 
• 
Effic a c y  P o p ulatio n:  All  s u bje cts. T his  p o p ulatio n  will  be  us e d  f or t he pri mar y effic a c y 
a nalysis a n d ot her effic a c y a nalys es e xc e pt w here ot her wis e  n ote d.  
• 
Safet y  P o p ulatio n:  All  s u bje cts tre ate d wit h  a bata c e pt.  T his  p o p ulatio n  will  be  us e d  f or 
s afety a nalys es.  
• 
P atie nt  Re p orte d  O utc o me  P o p ulatio n   ( P R O): All  ra n d o mize d s u bje cts w h o  ha ve  a n o n - 
missin g  ba s e line  a n d at le ast o ne  p ost -ba s e line  P R O ass ess me nt.  S u bje cts  in t his s u bs et 
will  be  a nalyze d  a c c or din g  t o  t heir  ra n d o mize d  tre at me nt  assig n me nt,  re gar dless  of 
tre at me nt re c eive d, e xc e pt w here ot her wis e n ote d.  
• 
P har ma c o kinetic P o p ulatio n:  S u bje cts wit h  at le ast o ne q ua ntifia ble  tr o u g h  c o nc e ntratio n 
re s ult will  be inc lu de d  in  t his p o p ulatio n.  
• 
P har ma c o d y na mic P o p ulatio n:  S u bje cts wit h a q ua ntifia ble  bas eli ne  a n d at le ast o ne p ost -
bas eline  ass a y res ult will  be inclu de d  in  t his  p o p ulatio n.  
• 
O pe n -la bel P o p ulatio n:  S u bje cts  wit h  c o ntrain dic atio ns  t o or  w h o  ref us e gluc oc ortic oi d 
t hera p y ma y e nter a n o pe n-la bel  st u d y  a n d re c eive X m A b 5 8 7 1  if  t he y ot her wis e me et all 
ot her  inclusio n  a n d  e xclusio n  criteria.  T hes e s u bje cts  will  f ollo w  t he  s a me  s c he d ule of 
ass ess me nts, b ut s afet y a n d effic a c y will  be re p orte d s e parately. 
• 
C o ntin uin g  Gluc ortic oid  P o p ulatio n:  S u bje cts  w h o  c o ntin ue  o n  st u d y  after  a n 
u ns uc c essf ul gluc oc ortic o id ta per or  w h o  c o ntin ue  after re c eivin g gluc oc ortic oid  res c ue 
t hera p y f ollo win g  a s uc c essf ul ta per. 
8. 2 E n d p oi nts  
Pri m ar y  Effic ac y  E n d p oi nt  
T he pri mar y  e n d p oint  is  c o m plete  re missio n  at 2 4  w e e ks. C o m plete  re missio n  is  define d  as a n I g G4 -
R D  Res p o n der  I n de x  Sc ore  of  0  a n d  a  pre d nis o ne  d os e  of  0  m g/ da y  a n d  n o  flare  sinc e  be gin ni n g 
tre at me nt. 
Se c o n d ar y Effic ac y  E n d p oi nts  
•  
Dis e as e res p o ns e at 4, 1 2,  2 4,  a n d 3 6 w e e ks. Dis e as e res p o ns e will be define d  at 6 m o nt hs as: 1) 
i m pr o ve me nt  of > 1  p oint  in  t he  I g G4 -R D  RI  s c ore o ver  bas eline;  2)  n o  gluc oc ortic oid  use 
f ollo win g  t he w e e k 4  visit;  3)  n o  dis e as e flares,  as ass ess e d b y t he I g G4-R D RI. Dis e as e flare 
will  be define d as re c urre nc e of dis e as e a ctivit y or de m o nstratio n of a dis e as e e xa c er batio n s uc h 
t hat  a d ditio nal  t hera p y  be y o n d  t he  trial  pr ot oc ol  is  in dic ate d.  S uc h  a d ditio nal  t hera p y  ma y 
inclu de  gluc oc ortic oids  or alter native i m m u n os u p pressive a ge nts.  
•  
C o m plete  re missio n  at 3 6  w e e ks.  
•  
Ti me  t o dis e as e re missio n  (I g G4 -R D RI =  0)  
•  
Re missio n  rates 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 3 8  of 
 
 
 
 
•  
N u m ber of dis e as e flares  per s u bje ct  o ver  ti me 
•  
C u m ulative  c ortic oster oid  d os es a n d Gluc oc ortic oid  T o xicit y  I n de x 
•  
P h ysicia n  Glo bal  Ass ess me nt ( P G A). A P G A c o nsistin g  of a 1 0 -c e nti meter vis ual  a nalo g s c ale 
is c olle cte d at e a c h patie nt visit.  O nly a ctive dis e as e (as o p p os e d t o da ma ge) is c o nsidere d in t he 
s c orin g  of t he P G A.  
•  
S y m pt o m  Se verit y  I n de x 
•  
Ser u m i m m u n o glo b ulin  le vels,  I g G4 s u bclass c o nc e ntratio ns,  I g E le vels,  e osin o p hils,  a n d s er u m 
C 3 a n d  C 4 
S afe t y E n d p oi nts  
Safet y a nalys es will  be perf or me d usin g  all tre ate d s u bje cts.  
•  
T he  n u m ber  a n d perc e nt of s u bje cts e x perie ncin g  a tre at me nt -e mer ge nt a d vers e e ve nt will  be 
ta b ulate d  f or e a c h c o de d Me d D R A s yste m-or ga n class a n d preferre d ter m. Tre at me nt -e mer ge nt 
a d vers e e ve nts will  als o be ta b ulate d a c c or din g  t o inte nsit y  a n d c a us alit y.  
•  
All   SA Es,  dis c o ntin uatio ns  d ue  t o A E,  or  de at hs  oc c urrin g  d urin g  t he c o urs e  of  t he tria l  will  be 
pres e nte d in  s u bje ct  listin gs. 
•  
T he n u m ber  a n d perc e nt of s u bje cts e x perie ncin g  a gluc oc ortic oid -relate d  A E will  be ta b ulate d 
f or  e a c h c o de d  Me d D R A s yste m-or ga n clas s a n d preferre d ter m. Tre at me nt-e mer ge nt a d verse 
e ve nts will  als o be ta b ulate d  a c c or din g t o  inte nsit y  a n d c a us alit y.  
•  
Clinic al  la b orat or y  tests ( o bs er ve d  values) will  be s u m marize d  des criptively  in  ta b ular  f or mat. 
S hift  ta bles  will  be  pres e nte d f or s ele ct l a b orat or y  para meters. I n  t he  s u bje ct  listin gs, values  
o utside  of  t he la b orat or y’s refere nc e li mits will  be  ide ntifie d, alo n g wit h  t he  I n vestigat or’s 
ass ess me nt of clinic al  sig nific a nc e.  A list  of all  n or mal  la b orat or y  ra n ges will  als o  be pr o vide d.  
Clinic a l ly  sig nific a nt  la b orat or y  test a b n or malities  t hat w ere c o nsidere d A Es b y t he I n vestigat or 
will  be pres e nte d in  t he A E  listin gs. 
•  
Vital  sig ns ( B P, p uls e,  te m perat ure) will  be s u m marize d  ( o bs er ve d a n d c ha n ge fr o m bas eline)  at 
e a c h visit vital  sig ns are c olle c te d usin g  des criptive  statistics a n d s u bje ct listin gs. 
•  
C o nc o mita nt  Me dic atio ns  will  be s u m marize d  b y t he n u m ber  a n d perc e nta ge of s u bje cts in  e a c h 
t hera pe utic class a n d preferre d ter m as c o de d usin g  t he W H O Dr u g dictio nar y. 
P h ysic al E xa minatio ns  will  be pre s e nte d in  s u bje ct listin gs. 
8. 3 Q u alit y of Life As s ess me nts  
Q ualit y  of  life  ass ess me nts will  inclu de  t he  P h ysicia n  Glo bal  Dis e as e A ctivit y  Ass ess me nt Vis ual 
A nalo g ue Sc ale ( P h G A V A S), t he P atie nt Glo bal  Dis e as e A ctivit y Ass ess me nt V A S ( Pt G A V A S), t he 
S y m pt o m  Se verit y  I n de x a n d t he 3 6 -ite m  s h ort f or m he alt h  s ur ve y ( S F-3 6). U nless ot her wis e s pe cifie d, 
t he  Q O L a nalys es  will  inclu de  all  ra n d o mize d  s u bje cts  w h o  ha ve a n o n-missin g  bas eline  a n d at le ast 
o ne p ost -bas eline Q O L ass ess me nt. S u bje cts in t his  s u bs et 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 3 9  of 
 
 
 
 
w ill  be a nalyze d a c c or din g t o t heir ra n d o mize d  tre at me nt assig n me nt, re gar dless of tre at me nt re c eive d. 
T he  perc e nta ge  of  participa nts  ra n d o mize d  t o  e a c h  tre at me nt  gr o u p  w h o  c o m plete  t he  Q O L 
q uestio n naires  at e a c h ass ess me nt p oint  after bas eline (i. e., Q O L c o m pletio n rates) will  be c alc ulate d 
a n d c o m pare d. If sig nific a nt  differe nc es in Q O L c o m pletio n  rates are o bs er ve d, a d ditio nal  a nalys es ma y 
be perf or me d t o e valuate t he p ote ntial  f or re p ortin g  bias es.  
F or  e a c h  Q O L  e n d p oint,  des criptive  statistics  will  be  pr es e nte d f or  re c or de d values  at  e a c h  visit, 
inclu din g  me a n,  sta n dar d de viatio n,  me dia n,  mini m u m,  ma xi m u m,  c ha n ge fr o m bas eline a n d  perc e nt 
c ha n ge fr o m bas eline.  
8. 4 St atis tic al M et h o ds Ge ne r al 
C o ns i de r ati o ns  
S u m mar y  statistics  will  be pres e nte d b y  w a y of n,  me a n,  sta n dar d de viatio n  ( S D),  me dia n,  mini m u m 
a n d ma xi m u m  f or c o ntin u o us  varia bles a n d b y w a y of gr o u p fre q ue ncies a n d perc e nta ges  f or c ate g oric al 
varia bles.  P erc e nta ges  will  be  c alc ulate d usin g  t he t otal s u bje cts per  ar m  in  t he  pla n ne d  a nalysis  
p o p ulatio n,  u nless s pe cifie d  ot her wis e.  
F or  listin gs,  in  t he c as es w here a s u bje ct’s re c or d has be e n c o ntin ue d  t o t he  ne xt pa ge,  a n a p pr o priate 
ide ntific atio n  (e. g., t he s u bje ct I D n u m ber)  m ust be pres e nte d at t he be gin nin g  of t hat pa ge. 
U nless ot her wis e s pe cifie d ,  in  s u m mar y  ta bles  of  c o ntin u o us  varia bles,  t he  mini m u m  a n d  ma xi m u m 
values will  be dis pla ye d  t o t he s a me n u m ber of de ci mal  pla c es as t he ra w data, t he me a n a n d me dia n 
will  be pres e nte d t o o ne e xtra de ci mal  pla c e c o m pare d t o t he ra w data, a n d t he sta n dar d de viatio n  will 
be dis pla ye d  t o  t w o e xtra de ci mal  pla c es c o m pare d t o t he ra w  data. W here ver p ossible,  data will  be 
de ci mal alig ne d.  
U nless  ot her wis e  s pe cifie d fre q ue nc y ta b ulatio ns will  be  pres e nte d  b y  n u m ber  a n d perc e nta ge, w here 
t he perc e nta ge is pres e nted in  bra c kets t o 1 de ci mal pla c e.  
P- values, if a p plic a ble,  will  be pres e nte d t o 3 de ci mal pla c es. If a p -value  is less t ha n 0. 0 5 b ut is  gre ater  
t ha n or  e q ual t o 0. 0 1,  t he n a n asteris k ( *) will  be  a d de d ne xt  t o t his value.  If a p-va lue  is  le ss t ha n 0. 0 1  
b ut  is gre ater  t ha n or  e q ual t o 0. 0 0 1,  t he n t w o asteris ks  ( * *) will  be  a d de d ne xt t o  t his  value. Finally,  if 
t he p-value  is  less  t ha n 0. 0 0 1  t he n t hre e asteris ks  ( * * *)  will  be a d de d ne xt  t o t his value  a n d it will  be  
pres e nte d  as  < 0. 0 0 1.  If t he r o u n de d re s ult is a value  of  1. 0 0 0,  it  will  be dis pla ye d  a s > 0. 9 9 9.  
 
9  DI R E C T A C C E S S  T O  S O U R C E  D A T A/ N O T E S  
T he  I nvestiga t or will  e ns ure t he acc urac y,  c o mplete ness,  a nd ti meli ness  of t he data  re p orte d t o 
t he S p o ns or. Data  c ollectio n pr ocesses  a nd pr oce d ures  will   be re vie we d  and  validate d  t o e ns ur e  
c o mplete ness,  acc urac y,  relia bilit y,  a nd  c o nsiste nc y.  
 
T he  I nvestiga t or  or designee  will  pre pare  a nd mainta i n  a de q uate a nd acc urate st ud y  d oc u me nts 
( me dical rec or ds, E C Gs,  A E  a nd c o nc o mita nt me dicatio n  re p orting, ra w data  c ollectio n for ms ,  
etc.)  designe d  t o  rec or d  all  o bser vatio ns  a nd  ot her  pertine nt  data  for  eac h  s ubject  receivi n g 
I M P. 
 
T he  I nvesti gat or  will  allo w  S p o ns or  re prese ntatives,  c o ntract  designees,  a ut horize d  re gulat or y 
a ut horit y ins pect ors, a nd t he I nstit ut io na l Re vie w  B oa r d (I R B)/ I nde pe nde nt Et hics  C o m mit t e e  
(I E C) t o ha ve  direct  access t o all  d oc u me nts  pertaini n g  t o t he st ud y. 
 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 4 0  of 
 
 
 
 
1 0  Q U A LI T Y  C O N T R O L  A N D Q U A LI T Y  A S S U R A N C E 
D at a Q ualit y  As s ura nce  
T he  I nvesti gat or  must  pre pare a nd  maintai n  a de q uate  a nd  acc urate  rec or ds  of  all  o bse r vati o ns 
a nd  ot her  data  pertine nt  t o  t he  clinical  st ud y  for  eac h  st ud y  participa nt.  Fre q ue nt 
c o m municati o n  bet wee n  t he  clinical  site  a nd t he  S p o ns or  is  esse ntial  t o e ns ure  t hat  t he  safet y 
of  t he  st ud y  is  mo nit ore d  a de q uately.  The  I nvesti gat or  will  ma ke  all  a p pr o priate  safet y 
assess me nts  o n  a n  o ngoing  basis.  T he  S p o ns or’s  me dical  re prese ntative  ma y  re vie w  safet y 
infor  mati o n  as it  bec o mes  a vaila ble  t hr o ugho ut  t he  st ud y. 
All  as pects  of  t he  st ud y  will  be  carefull y  mo nit ore d  wit h  res pect  t o  G C P  a nd  S O Ps  for 
c o mplia nce  wit h  a p plica ble  go ver n me nt  re gulat io ns. 
 
T he  st ud y  ma y  be  a udite d  t o  assess  a d here nce  t o  t he  Clinical  St ud y  Pr ot oc ol.  The 
I nvesti gat or/i n vesti gati o nal  site  will  per mit  st ud y-relate d  mo nit ori n g,  a udits,  I R B/I E C  re vie w 
a nd  re gulat or y  ins pectio ns  b y  pr o vidin g  direct  access t o s o urce  data/ d oc u me nts.  Direct  access 
includes per missio n t o e xa mine,  a nalyze,  verif y,  a nd re pr o d uce a ny rec or ds a nd re p orts t hat are 
i mp orta nt  t o t he e valuatio n  of a clinical st ud y. 
 
D uring  t he  c o nd uct  of  t he  st ud y,  pr ocess -relate d a udits  ma y  be  perfor me d  as well.  A n  a udit 
certificate  will  be pr o vide d  in  t he  final  st ud y  re p ort  o utli ni n g  t he  a udit  perfor me d  a nd  ot her 
relate d  activities. 
 
1 1  E T HI C S  
1 1. 1 I n de pe n de nt  Et hics   C o m mitte e /I ns tit uti o na l  R e vie w B o ar d  
Prior  t o t he  start of  t he st u d y,  t he  investi gat o r  is  res p o nsible  for  e ns urin g  t hat  t he  pr ot oc ol  a nd  
c o nse nt  for m  ha ve  bee n re vie we d  a nd a p pr o ve d  b y a rele va nt  I E C/I R B.  The  I E C/I R B  s hall  be 
a p pr o priately  c o nstit ute d  a nd  perfor m  its  functio ns  in  acc or da nce  wit h  F D A  I C H  G C P  a nd 
local  re quire me nts  as a p plica ble.  
T he  I E C/I R B  s hall  a p pr o ve  all  pr ot oc ol  a me nd me nts  (e xce pt  for  lo gistical  or  a d ministr at i v e 
c ha nges),  writte n  infor me d  c o nse nt  d oc u me nts  a nd  d oc u me nt  up dates,  s ubject  recr uit me nt 
pr oce d ures  (e. g.,  a d vertise me nts),  writte n  infor mati o n  t o  be  pr o vide d  t o  t he  s ubjects, 
investi gat or's  Br oc hure,  a vaila ble  safet y  infor matio n,  infor matio n  a b o ut  pa y me nt  a nd 
c o mpe nsatio n  a vaila ble  t o s ubjects,  t he investi gat or's  c urric ul u m  vitae  a nd/ or ot her  e vide nce  of  
q ualificati o ns  a nd a ny ot her  d oc u me nts   re q ueste d   b y t he I E C/I R B a nd Re gulat or y  A ut hor it y 
( C o mpete nt  A ut horit y)  as a p plica ble.  
1 1. 2 G o o d Cli nic al  Practice 
T he  pr oce d ures  set o ut  in  t his  clinical  st ud y  pr ot oc ol  are  designe d  t o e ns ure  t hat  t he  S p o ns or 
a nd  t he  I nvestiga t or  a bide  b y  t he  princip les  of t he  I C H  guideli nes  o n  G C P  as  o utli ne d  i n 
C P M P/I C H/ 1 3 5/ 9 5 a nd t he Declaratio n   of Helsink i  ( Versio n  2 0 0 8). The  clinica l st ud y als o will 
be carrie d  o ut  in kee ping wit h  natio na l a nd local le gal re q uire me nts (in acc or da nce wit h  U nit e d  
States I nvesti gati o nal  N e w Dr ug  [I N D] re gulatio ns  [ 2 1 C F R Parts 5 0, 5 6 a nd  3 1 2]). 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 4 1  of 
 
 
 
T he  I nvesti gat o r  will  be  res p o nsible  for  t he  care  of  t he  s ubjects  t hr o ugho ut  t he  st ud y.  If  t he  
I nvesti gat or  is  not  prese nt  at  t he  st ud y  site,  he/s he  will  lea ve  instr ucti o ns  for  t he  staff  a nd  a 
tele p ho ne  nu mber  w here  he/s he  ca n be reac he d.  
1 1. 3 Writte n  I nf or me d  C o ns e nt 
Before  eac h s ubject  is e nr olle d  in  t he clinical  st ud y,  writte n  infor me d  c o nse nt  will  be  o btaine d 
fr o m t he s ubject acc or ding t o t he re gulat or y a nd le gal re q uire me nts  of t he participati n g c o untr y.  
As  part  of  t his  pr oce d ure,  t he  I nvesti gat or  must  e xplain  orally  a nd  in  writin g  t he  nat ure ,  
d uratio n,  a nd  p ur p ose  of  t he  st ud y,  a nd  t he  actio n  of  t he  dr ug  in  s uc h  a  ma nner  t hat  t he  st ud y 
s ubject  is  a ware  of  t he  p ote ntial  ris ks,  inc o nve nie nces,  or  A Es  t hat  ma y  occ ur.  The  s ubject 
s ho uld  be  infor me d  t hat  he/s he  is  free  t o  wit hdra w  fr o m  t he  st ud y  at  a ny  ti me.  He/ S he  will 
receive all infor ma t io n t hat is re q uire d  b y fe deral re gulatio ns a nd I C H guideli ne s.  The  Princi p a l 
I nvesti gat or  or  designee  will  pr o vide  t he  S p o ns or  wit h  a c o p y  of  t he  I R B/I E C -a p pr o ve d  I C F 
prior  t o t he start  of t he  st ud y. 
T he  infor  me d  c o nse nt  d oc u me nt  must  be  signe d  a nd  date d;  o ne  c o p y  will  be  give n  t o  t he  
s ubject,  a nd  t he  I nvesti gat or  will  retain  a  c o p y  as  part  of  t he  clinical  st ud y  rec o r ds.  The 
I nvesti gat or  will  not  underta ke  a ny  investi ga tio n  s pecifica ll y  re q uire d  for  t he  clinica l  st ud y 
until  writte n  c o nse nt  has  bee n  o btaine d.  The  ter ms  of  t he  c o nse nt  a nd  w he n  it  was  o btaine d 
must  als o  be d oc u me nte d.  
If  a  pr ot oc ol  a me nd me nt  is  re q uire d, t he n  t he  infor me d  c o nse nt  d oc u me nt  ma y  nee d  t o  be 
re vise d  t o reflect  t he  c ha nges  t o t he  pr ot oc ol.  If  t he  infor me d  c o nse nt  d oc u me nt  is  re vise d,  it 
must  be  re vie we d  a nd  a p pr o ve d  b y  t he  res p o nsible  I R B/I E C  a nd  signe d  b y  all  s ubjects 
s ubse q ue ntl y  e nr olle d  in t he  clinical  st ud y  as  well  as  t hose  c urre ntly  e nr olle d  in  t he  clinic a l 
st ud y. 
1 1. 4 Prot oc ol  A p pro v al  a n d  A me n d me nt(s) 
Before  t he  start  of  t he clinical  st ud y,  t he  clinical  st ud y  pr ot oc ol  a nd  ot her  rele va nt  d oc u me nts 
will  be a p pr o ve d  b y  t he  I R B/I E C,  in  acc or da nce  wit h  local  le gal  re q uire me nts.  The  S p o ns or 
must  e ns ure  t hat  all  et hical  a nd  le gal  re q uire me nts  ha ve  bee n  met  before  t he  first  s ubject  is 
e nr olle d  in  t he  clinica l  st ud y.  
T his  pr ot oc ol  is  t o be follo we d  e xactly.  A ny  de viatio ns  s ho uld  be a gree d  b y  b ot h t he  S p o ns or 
a nd t he  I nvestigat or,  wit h  t he  a p pr o priate  writte n  a nd a p pr o ve d  pr ot oc ol  a me nd me nts  ma de  t o 
reflect t he c ha nges a gree d  up o n.   Pr ot oc ol a me nd me nts must   be release d  b y t he res p o nsible staff 
a nd  receive  I R B/I E C  a p pr o val  prior  t o i mple me ntati o n  (as a p pr o priate).  W here  t he  de viati o n 
occ urs  for  t he  well-bei n g  of  t he  s ubject,  t he  S p o ns or  must  be  infor me d  of  t he  actio n  a gree d 
up o n.  
A d ministrati ve  c ha nges  ma y  be ma de  wit ho ut  t he  nee d for  a for mal  a me nd me nt  b ut  will  als o 
be me ntio ne d  in  t he  inte grate d  clin ica l  st ud y  re p ort.  All  a me nd me nts  will  be  distrib ute d  t o  a ll 
st ud y  pr ot oc ol  recipie nts,  wit h  a p pr o priate  instr uctio ns. 
1 1. 5 C o nfi de nti alit y  D at a Prote cti o n 

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 4 2  of 
 
 
 
All  clinical  st ud y  findi n gs  a nd  d oc u me nts  will  be re gar de d  as  c o nfide ntial.  St ud y  d oc u me nts 
( pr ot oc ols, I Bs a nd  ot her  material)  will  be st ore d  a p pr o priately  t o e ns ure  t heir  c o nfide ntialit y. 
T he  I nvesti ga t or  a nd  me mbers  of  his/ her  researc h  tea m  (incl ud i n g  t he  I R B/I E C)  must  not 
disclose  s uc h infor ma t io n wit ho ut   prior writte n   a p pr o val fr o m t he S p o ns or, e xcept t o t he e xte nt 
necessar y  t o  o btain  infor me d  c o nse nt  fr o m  s ubjects  w ho  wis h  t o participate  in  t he  trial  or t o 
c o mply  wit h  re gulat or y re q uire me nts. 
T he a no ny mit y  of participati n g  s ubjects must  be maintai ne d.  S ubjects will  be s pecifie d  o n st ud y 
d oc u me nts  b y  t heir  s ubject  nu mber,  init ia l  or  birt h  date, not  b y  na me.  D oc u me nts  t hat  ide ntif y 
t he  s ubject  (e. g., t he  signe d  infor me d  c o nse nt  d oc u me nt)  must  be maintai ne d  in  c o nfide nce  b y 
t he  I nvestiga t or. 
 
1 2  D A T A H A N D LI N G A N D R E C O R D K E E PI N G  
1 2. 1 C as e R e port F or ms/ S o urce  D a t a H a n dli ng  
T he  investi gat or  must  maintai n  s o urce  d oc u me nts,  s uc h  as la b orat or y  re p orts,  X -ra ys,  E C Gs, 
c o ns ultatio n  re p orts,  a nd c o mplete  me dical  hist or y  a nd p hysical  e xa minatio n  re p orts.  
1 2. 2 R ete nti o n of Ess e nti al D oc u me nts 
T he  s p o ns ors  must  retain  all  s t ud y  rec or ds  a nd  s o urce  d oc u me nts  for  t he  ma xi m u m  perio d 
re q uire d  b y  a p plica ble  re gulatio ns  a nd  guideli nes  or  instit uti o n  pr oce d ures,  or  for  t he  perio d 
s pecifie d  b y a gree me nt  wit h  B M S, w hic he ver  is  lo nger. 
 
1 3  P U B LI C A TI O N  P O LI C Y  
B y  signi n g  t he  clinica l  st ud y  pr ot oc ol,  t he  I nvestiga t or  a grees  wit h  t he  use  of  res ults  of  t he  
clinica l  st ud y  for  t he  p ur p oses  of  natio na l  a nd  inter nati o na l  re gistratio n,  p ublicatio n  a nd 
infor mati o n  for  me dical  a nd  p har mace utical  pr ofessio nals.  If  necessar y,  t he  c o mpete nt 
a ut horit ie s  will  be  notifie d  of  t he  I nvesti gat or’s  na me,  a d dress,  q ualificati o ns  a nd  e xte nt  of 
invol ve me nt.  A n  I nvesti gat or  s hall  not  p ublis h  a ny  data  ( p oster,  a bstract,  pa per, etc.)  wit h o ut 
ha vin g  c o ns ulte d  wit h  t he  S p o ns or  in  a d va nce.  

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 4 3  of 
 
 
 
 
 
1 4  
SI G N A T U R E O F  I N V E S TI G A T O R 
I agre e t o c o n d uct t he st u d y o utline d a b o ve in a c c or da nc e wit h t he ter ms a n d c o n ditio ns of  t he pr ot oc ol, 
I C H g uidelines  o n  G C P  a n d wit h  a p plic a ble  re g ulat or y re q uire me nts. All  inf or matio n  pertainin g  t o  t he 
st u d y s hall  be tre ate d in  a c o nfide ntial ma n ner.  
 
 
 
 
 
2 8 O ct o ber 2 0 1 8  
 
Dr. J o h n H St o ne,  M. D., M. P. H 
P rinc ipa l  I n vestigat or 
 
D ate ( da y/ m o nt h/ ye ar)  

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 4 4  of 
 
 
 
 
1 5  
R E F E R E N C E  LI S T  
A bata c e pt P a c ka ge I ns ert. htt ps:// pa c ka geins erts. b ms. c o m/ pi/ pi_ ore ncia. p df.  
 
A n ders o n P. K. a n d Gill  R. D. C o x’s re gressio n m o del  f or c o u ntin g  pr oc e ss es: a lar ge s a m ple st u d y. 
A n nals of Statistics  1 9 8 2;  1 0:1 1 0 0 -1 1 2 0.  
 
Br o w nlie  RJ, La wlor K E, Nie derer H A, C utler AJ, Xia n g  Z, Clat w ort h y  M R et al. 2 0 0 8. Distinct  c ell -
s pe cific c o ntr ol  of a ut oi m m u nit y  a n d infe ctio n  b y Fc g RII b. J E x p Me d 2 0 5:8 8 3- 8 9 5.  
 
Carr ut hers M N, St o ne J H, D es h pa n de V, K h osr os ha hi  A. 2 0 1 2.  D e velo p me nt of a n I g G4 - R D 
res p o n der I n de x.  I nt J R he u m V olu me  2 0 1 2,  Article I D 2 5 9 4 0 8,  7 pa ges. 
 
Carr ut hers M N, T o pa zia n  M D, K h osr os ha hi  A, et al. 2 0 1 5. Rit u xi ma b  f or I g G4 -relate d dis e as e: a 
pr os pe ctive,  o pe n -la be l  tria l.  A n n R he u m  Dis 0:1-7,  d oi:1 0. 1 1 3 6/a n nr he u m dis - 2 0 1 4 -2 0 6 6 0 5.  
 
Car vajal Ale gria G, P oc har d P, P ers J O, C or ne c D. C o uld a bata c e pt dire ctly tar get e x pa n de d 
plas ma blasts  in  I g G4 -relate d dis e as e ? A n n R he u m Dis. 2 0 1 6  N o v; 7 5( 1 1):e 7 3. 
 
 
Cr o wle y J E, Sta da nlic k  J E, Ca m bier J C, Ca ncr o M P. 2 0 0 9. Fc g RII B sig nals  in hibit  B L y S sig nalin g 
a n d B C R-me diate d B L y S re c e pt or u p -re g ulatio n.  Blo o d  1 1 3:1 4 6 4-1 4 7 3.  
 
D es h pa n de V, Ze n Y, C ha n J K C, et al. 2 0 1 2.  C o ns e ns us state me nt o n t he pat h olo g y  of I g G4 - relate d 
dis e as e. M o der n P at h olo g y  2 5:1 1 8 1-1 1 9 2.  
 
H ort o n H M, Ber nett MJ, P o n g E, P eip p M,  K ar ki S, C h u S Y,  Ric har ds J O, V ostiar I, J o yc e P F, Re p p 
R, D esjarlais J R, Z h u k o vs k y  E A. 2 0 0 8.  P ote nt in  vitr o  a n d in  viv o  a ctivit y  of a n Fc e n gine ere d a nti -
C D 1 9 m o n oclo nal  a ntib o d y  a gainst ly m p h o ma  a n d le u ke mia.  Ca nc er Res. 6 8:8 0 4 9 -8 0 5 7.  
 
H ort o n H M, C h u S Y, Ortiz  E C, P o n g E, Ce mers ki S,  Le u n g I W et al. 2 0 1 1. A ntib o d y 
me diate d c oe n ga ge me nt of Fc g RII b a n d B c ell re c e pt or c o m ple x  s u p press es h u m oral 
i m m u nit y  in  s yste mic lu p us  er yt he matos us. J I m m u n ol  1 8 6:4 2 2 3 -4 2 3 3.  
 
I nter natio nal  C o nfere nc e  o n  H ar m o nis atio n  of  Te c h nic al  Re q uire me nts  f or  Re gistratio n  of 
P har ma c e utic als f or  H u ma n  Us e. I C H  H ar m o nis e d  Tripartite  Guideline,  E 6:  Guideline  f or  Go o d 
Clinic al  Pra ctic e ( C P M P/I C H/ 1 3 5/ 9 5), J a n uar y 1 9 9 7.  
 
K a mis a w a T, F u nata N, H a yas hi Y et al. 2 0 0 3. A ne w clinic o pat h olo gic al  e ntit y  of I g G4 - relate d 
a ut oi m m u ne  dis e as e.  J Gastr oe nter ol 3 8:9 8 2-9 8 4.  
 
K a mis a w a T, Ze n Y, Pillai  S, St o ne  J H. 2 0 1 4. I g G4 -relate d dis e as e. La nc et 
htt p:// d x. d oi. or g/ 1 0. 1 0 1 6/ S 0 1 4 0 -6 7 3 6  ( 1 4) 6 0 7 2 0-0.  
 
K h osr os ha hi  A, Bloc h  D B, D es h pa n de V, St o ne J H. 2 0 1 0. Rit u xi ma b  t hera p y le a ds t o ra pid de cline 
of s er u m I g G4  le vels  a n d pr o m pt  clinic al  i m pr o ve me nt  in  I g G4 -relate d dis e as e. 
Art hri tis  R he u mat ol  6 2:1 7 5 5-1 7 6 2.  

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 4 5  of 
 
 
 
 
K h osr os ha hi  A, Walla c e Z S, Cr o w e J L, A ka miz u  T,  A z u mi  A, Carr ut hers M N, C hari S, D ella - T orre 
E, Fr ullo ni  L, Got o H, H art P, K a mis a w a T, K a w a S, K a w a n o M, Ki m M H, K o da ma Y, K u b ota K, 
Lerc h M M, L o hr  M, Mas a ki Y, Mats ui S,  Mi m ori  T, N a ka m ura, N a ka za w a T, O hara A, O ka za ki K, 
R y u J H, Sa e ki T, Sc hleinitz  N, S hi mats u  A, S hi m os e ga w a T, Ta ka has hi H, Ta ka hira M, Ta na ka A, 
T o pa zia n  M,  U me hara H, We bster GJ, Witzig  T, Y a ma m ot o M, Z ha n g  W, C hiba T,  a n d St o ne J H. 
2 0 1 5.  I nter natio nal  C o ns e ns u s Guida nc e  State me nt o n t he Ma na ge me nt a n d Tre at me nt of I g G4-
Relate d Dis e as e. Art hritis  R he u mat ol  6 7:1 6 8 8 -1 6 9 9.  
 
Mats u ba yas hi H, F ur u ka w a H, Ma e da A, Mats u na ga K et al. 2 0 0 9.  Us ef ulness of p ositr o n 
e missio n  t o m o gra p h y  in  t he e valuatio n  of distrib utio n  a n d a ctivit y  of s yste mic lesio ns ass ociate d 
wit h  a ut oi m m u ne  pa ncre atitis. P a ncre at olo g y 9:6 9 4 -6 9 9.  
 
Matt o o H, Ma haja n V S, D ella T orre E, Se kiga mi  Y, Walla c e Z S, Carr ut hers M, D ella T orre E, 
St o ne J H, Pillai  S. 2 0 1 4.  D e n o v o olig oclo nal  e x pa nsio ns  of circ ulatin g  plas ma blasts  in  a ctive a n d 
rela psin g  I g G4-relate d  dis e as e. J o ur nal  of Aller g y  & Clinic al  I m m u n olo g y  1 3 4( 3):6 7 9-8 7.  
 
Matt o o H, Ma haja n V, Ma e hara T, D es h pa n de V, D ella -T orre E, Walla c e Z, K ulik o va  M, Drijvers J, 
Carr ut hers M,  St o ne J R, St o ne J H, Pillai  S.  Clo nal  e x pa nsio n  of  C D 4( +) c yt ot o xic  T ly m p h oc ytes  in 
patie nts wit h  I g G4 -relate d  dis e as e.  J Aller g y  Clin  I m m u n ol.  2 0 1 6  Se p; 1 3 8( 3):8 2 5-8 3 8.  
 
Mc Ga ha T L, S orre ntin o  B, Ra vetc h J V. 2 0 0 5. Rest oratio n  of t olera nc e in  lu p us  b y  tar gete d 
in hibit or y  re c e pt or e x pressio n. Scie nc e 3 0 7:5 9 0-3.  
 
Mc H or ne y C A, Ware J E, L u J F R, S her b o ur ne  C D. 1 9 9 4. T he M O S 3 6 -ite m  s h ort-f or m  he alt h 
s ur ve y ( S F-3 6):  III. Tests of data q ualit y,  s c alin g  ass u m ptio ns,  a n d relia bilit y  a cr oss divers e 
patie nt  gr o u ps. Me dic al  Care 3 2:4 0 -6 6.  
 
Me e ker T C, Miller  R A, Lin k  M P, Bin dl  J, War n ke R, Le v y R. 1 9 8 4.  A u niq ue  h u ma n B 
ly m p h oc yte  a ntige n  define d b y  a m o n oclo nal  a ntib o d y.  H y brid o ma  3( 4):3 0 5-3 2 0.  
 
N a dler L M, A n ders o n K C, Marti  G,  Bates M, P ar k E, D ale y J F, et al. 1 9 8 3.  B 4, a h u ma n B 
ly m p h oc yte-ass ocia te d  a ntige n  e x press e d o n n or mal,  mit o ge n-a ctivate d,  a n d malig na nt  B 
ly m p h oc ytes.  J I m m u n ol  1 3 1:2 4 4-2 5 0.  
 
Ni m merja h n  F, Ra vetc h J V. 2 0 0 8. Fc g re c e pt ors as re g ulat ors of i m m u ne  res p o ns es. N at Re v 
I m m u n ol  8:3 4-4 7.  
 
Reff M E, Car ner K, C ha m bers K S, C hin n P C, Le o nar d J E, Ra a b R, N e w ma n R A, H a n na N, 
A n ders o n D R. 1 9 9 4. D e pletio n  of B Cells  I n Viv o  b y a C hi meric  M o us e H u ma n M o n oclo nal 
A ntib o d y  t o C D 2 0. Blo o d  8 3:4 3 5 -4 4 5.  
 
Sa m ps o n H A, M u n oz -F urlo n g  A, Ca m p bell  R L, A d kins o n  N F, B oc k S A, Bra n u m A, et al. 2 0 0 6. 
Se c o n d s y m p osiu m  o n  t he definitio n  a n d ma na ge me nt of a na p h yla xis:  S u m mar y  re p ort — Se c o n d 
N atio nal  I nstit ute  of Aller g y  a n d I nfe ctio us  Dis e as e/ F o o d Aller g y  a n d A na p h yla xis  N et w or k 
s y m p osiu m.  J Aller g y  Clin  I m m u n ol  1 1 7:3 9 1-7.  
 
S mit h  K G, Clat w ort h y  M R. 2 0 1 0.  Fc ga m ma RII B in  a ut oi m m u nit y  a n d infe ctio n: 
e v olutio nar y  a n d t hera pe utic i m plic atio ns.  N at ure Re v I m m u n ol  1 0:3 2 8 -3 4 3.  

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 4 6  of 
 
 
 
 
 
St o ne J H, H off ma n G S,  Mer kel  P A, Min  YI, U hlfelder M L,  H ell ma n n  D B, S pe c ks U, Alle n  N B, 
S piera R F, Cala bres e L H, Wigle y  F M, D a vis J C, Maide n N, V a le nte R M, Niles J L, F ye K H, 
Mc C u ne J W, St. Clair  E W, L u q ma ni  R A. 2 0 0 1.  A dis e as e -s pe cific a ctivit y  in de x  f or We ge ner’s 
gra n ulo mat osis:  M o dific atio n  of t he Bir min g ha m  V as c ulitis  A ctivit y  Sc ore.  
I nter natio nal  N et w or k f or t he St u d y  of t he S yste mic  V as c ulitides (I N S S Y S). Art hritis 
R he u mat ol  4 4:  9 1 2 -9 2 0.  
 
St o ne J H, Mer kel P A, S piera R et al. 2 0 1 0. Rit u xi ma b  vers us c yclo p h os p ha mide  f or A N C A - 
ass ociate d vas c ulitis.  N EJ M 3 6 3:2 2 1-2 3 2.  
 
St o ne J H, Ze n Y, D es h pa n de V. 2 0 1 2.  I g G4 -relate d dis e as e. N E n gl  J Me d 3 6 6:5 3 9-5 5 1.  
 
Taras e n k o T, D e a n J A, B olla n d  S. 2 0 0 7.  Fc g RII B as a m o d ulat or  of a ut oi m m u ne  dis e as e 
s us c e ptibilit y.  A ut oi m m u nit y  4 0:4 0 9-1 7.  
 
U c hida K, Mas a m u ne A, S hi m os e ga w a T, O ka za ki.  2 0 1 2. Pre vale nc e of I g G4 -relate d dis e as e in 
J a pa n bas e d o n natio n wide  s ur ve y in  2 0 0 9.  I nt J R he u m V olu me,  Article I D 3 5 8 3 7 1,  5 pa ges.  
 
U niz o n y  S H, D as g u pta B,  Fis hele va E,  R o w ell  L, Sc hett G,  S piera  R, Z w erina J, H arari O, a n d 
St o ne J H. 2 0 1 3. D esig n  of t he t ociliz u ma b  in  gia nt  c ell  arteritis  trial. I nt J of R he u m. V olu me 
2 0 1 3,  Article I D 9 1 2 5 6 2,  1 0 pa ges.  
 
va n Eltere n,  P. H. 1 9 6 0. " O n t he c o m binatio n  of in de pe n de nt  t w o -s a m ple tests of Wilc o x o n,"  B ulletin 
of t he I nter natio nal  Statistic al  I nstit ute,  3 7,  3 5 1 -3 6 1.  
 
Walla c e Z S, Matt o o H, Carr ut hers M et al. 2 0 1 4. Plas ma blasts as a bio mar ker f or I g G4 - relate d 
dis e as e, in de pe n de nt  of s er u m I g G4 c o nc e ntratio ns. A n n R he u m Dis  
d oi:  1 0. 1 1 3 6/a n nr he u m dis -2 0 1 4 -2 0 5 2 3 3  [ E p u b a he a d of print].  
 
Walla c e  Z S,  D es h pa n de V,  Matt o o  H,  Ma haja n V S,  K ulik o va  M,  Pillai  S,  St o ne  J H. 2 0 1 5.  I g G4 -
relate d dis e as e: Bas eline clinic al  a n d la b orat or y fe at ures in 1 2 5 s u bje cts wit h bio ps y- pr o ve n dis e as e. 
Art hritis  R he u mat ol  6 7:2 4 6 6 -2 4 7 5.  
 
Walla c e Z S, K h osr os ha hi  A, Carr ut hers M, P er u gin o  C, C h oi  H, et al. 2 0 1 6.  A n I nter natio nal,  M ulti -
S pe cialt y  V alidatio n  St u d y  of t he I g G4 -Relate d  Dis e as e Res p o n der I n de x. Art hritis  R he u mat ol. 2 0 1 6; 
6 8 (s u p pl  1 0),  A bstra ct 9 4 1.  
 
Ware J E, S her b o ur ne  C D. 1 9 9 2. T he M O S 3 6 -ite m  s h ort-f or m  he alt h s ur ve y ( S F-3 6). 
Me dic al  Care 3 0:4 7 3 -4 8 3.  
 
We c hsler M E, A k ut h ota  P, J a y ne D, K h o ur y  P, Klio n  A, La n gf or d C A, et al. 2 0 1 7.  Me p oliz u ma b 
or pla c e b o f or e osin o p hilic  gra n ulo mat osis  wit h p olya n giitis.  N E n gl  J Me d. 3 7 6:1 9 2 1 -1 9 3 2.  
 
W M A D e cla ratio n of H elsin ki  ( 1 8t h W M A Ge neral Ass e m bly  1 9 6 4),  re vis e d at 5 9t h W orld 
Me dic al  Ass ociatio n  Ge neral Ass e m bly Se o ul,  O ct o ber 2 0 0 8.  

Brist ol  M yers S q uib b  Pr ot oc ol: 
A batace pt  in  I g G 4 -R D  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Pa ge 4 7  of 
 
 
 
 
Y a ma m ot o M, Ta ka has hi H, S hin o m ura  Y. 2 0 1 4.  Me c ha nis ms a n d ass ess me nt of I g G4 - relate d 
dis e as e: less o ns f or t he r he u mat olo gist.  N at Re v R he u mat ol  1 0:1 4 8 -1 5 9.  
 
Y a ma m ot o M, Ta ka has hi H, Ta ka n o K, S hi miz u  Y, Sa k urai  N, S uz u ki  C, N ais hir o  Y, Y aji ma  H, 
A w a ka w a T, Hi mi T, N a kas e H. Effic a c y of a bata c e pt f or I g G4 -relate d dis e as e o ver 8 m o nt hs.  A n n 
R he u m Dis. 2 0 1 6  A u g; 7 5( 8):1 5 7 6 -8.  

Pa ge 5 8  of 6 6  
Brist ol  M yers  S q uib b  
Pr ot oc ol  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
1 7  
A P P E N DI C E S 
Effic ac y  Ass ess me nts  
A. I g G 4-R D R e s po n de r  I n de x  (I g G 4 -R D RI)
T he  I g G 4 -R D  RI  is  a  t o ol  designe d  t o  detect  c ha nge  in  disease  activit y  a nd  ide ntif y 
i mpr o ve me nt s a nd w orse ning  in t he sa me or differe nt  or ga n s yste ms ( mo difie d after C arr ut her s ,  
2 0 1 2). 
At eac h assess me nt,  t he p hysicia n  e nters  a 0 -3 sc ore after  t he  or ga n/site  liste d  wit h; 
0 = N or mal  or res olve d 
1 = I mpr o ve d  b ut  still  prese nt 
2 = N e w  or rec urre nt disease  activit y w hile  s ubject is off treat me nt,  or unc ha nge d  fr o m pre vio us 
visit *  
3 = W orse ne d  or ne w  disease  ma nife statio n  des pite  treat me nt 
* U nc ha nge d  fr o m  pre vio us  visit  will  ofte n  refer  t o disease  ma nifestati o ns  t hat  re q uire  follo w -
up i ma gi n g  t o assess acc urately.
T he  sec o nd c olu mn  is  use d t o rec or d s y mpt o matic  disease;  yes = Y,  no = N.
T he  t hir d  c olu mn  rec or ds w het her  t here  is ur ge nt  disease  in  t hat  site;  yes = Y,  no = N.
Da ma ge  in  t he  or ga n/site  is  rec or de d  in  t he  fo urt h  c olu mn;  yes = Y,  no = N.
T he  fift h  c olu mn  rec or ds  w het her  da ma ge  in  t he  or ga n/site  is  s y mpt o matic ;  yes = Y,  no = N.  
P hysicia n   Glo bal Assess me nt   of disease  activit y is de note d  o n a 1 0 0 m m  line as c o vere d  belo w. 

Pa ge 5 9  of 6 6  
Brist ol  M yers  S q uib b  
Pr ot oc ol  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
I g G 4-R D R e s p o n d er I n d e x ( V er si o n 2 5 J ul y 2 0 1 6)  
S c ori n g R ul e s  
S c ori n g  r ef er s  t o m a nif e st ati o n s  of  di s e a s e  a cti vit y pr e s e nt  i n  t h e l a st 2 8  d a y s 
S c ori n g:  0  
N or m al  or r e s ol v e d 
I m pr o ve d  b ut  still pr e s e nt 
N e w  / R e c urr e n c e  w hil e  p ati e nt  i s off  tr e at m e nt or  u n c h a n g e d  fr o m pr e vi o u s  
vi sit*  
W or s e n e d  or n e w  di s e a s e  m a nif e st ati o n  d e s pit e  tr e at m e nt  
* U n c h a n g e d  fr o m  pr e vi o u s  vi sit will  oft e n  r ef er  t o di s e a s e  m a nif e st ati o n s  t h at
r e q uir e f oll o w-u p  i m a gi n g  t o a s s e s s a c c ur at el y
D efi niti o n s  
Or g a n/ Sit e  s c or e: T h e  o ver all  l e vel  of  I g G 4 -R D a cti vit y wit hi n  a s p e cifi c  or g a n  s y st e m  
S y m pt o m ati c:  I s t h e di s e a s e  m a nif e st ati o n  i n a p arti c ul ar  or g a n  s y st e m  s y m pt o m ati c ?  ( Y = 
y e s; N =  n o)  
Ur g e nt  di s e a s e: Di s e a s e  t h at r e q uir e s  tr e at m e nt  i m m e di at el y t o pr e ve nt  s eri o u s or g a n 
d y sf u n cti o n  ( Y = y e s; N = n o)  ( Pr e s e n c e  of ur g e nt  di s e a s e wit hi n  a n or g a n  l e a d s  t o 
D O U B LI N G of t h at or g a n  s y st e m s c or e ) 
D a m a g e:  Or g a n  d y sf u n cti o n  t h at h a s  o c c urr e d  a s  a r es ult  of  I g G 4-R D  a n d  i s c o n si d er e d 
p er m a n e nt  ( Y =  y e s;  N  =  n o)  

Pa ge 6 0  of 6 6  
Brist ol  M yers  S q uib b  
Pr ot oc ol  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
 
 
 
 
 
T otal  activit y  sc ore is calc ulate d  as give n  in  t he  lo wer  left  ha nd  c or ner  = 
S u m  of  or ga n  sc ores  (a ny  t hat  are ur ge nt  are  multip lie d  b y  2).  

Pa ge 6 1  of 6 6  
Brist ol  M yers  S q uib b  
Pr ot oc ol  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
Gl o b a l A sse ssm e nt  o f Di se a se Acti vit y  ( V A S) 
B. P hysici a n’s  Gl o bal  Ass ess me nt of Dis e as e Acti vit y ( 1 0 0 m m- V A S)
Place  a mar k  o n t he line  belo w  t o indicate  disease  activit y  (inde pe nde nt  of  t he s ubject’s  self - 
assess me nt): 
V A S P h y si ci a n Gl o b al  A s s e s s m e nt of  Di s e a s e  A cti v ity = 
m m  
C. S u bje ct’s Gl o bal Ass ess me nt of Dis e as e  Acti vit y  ( V A S)
S u bje ct’s  Gl o bal  Ass ess me nt of Dis e as e Acti vit y ( 1 0 0  m m -V A S)  
Pla ce  a mar k  o n t he line  belo w  t o indicate  disease  activit y: 
V A S S u bj e ct  Gl o b al  A s s e s s m e nt of  Di s e a s e  A cti v ity = 
m m  
Ver y  G o o d  
Ver y  Ba d  
Ver y  G o o d  
Ver y  Ba d  

Pa ge 6 2  of 6 6  
Brist ol  M yers  S q uib b  
Pr ot oc ol  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
D. S F -3 6 He alt h S urve y
S F -3 6 is  a  set  of  ge neric,  c o here nt,  a nd  easily  a d ministere d  q ualit y -of-life  meas ures.  Thes e 
meas ures  rely  up o n  patie nt  self -re p orti n g  a nd  are no w  widely utilize d  for  r o utine  mo nit or i n g 
a nd assess me nt  of care o utc o mes  in  a d ult  patie nts.  The  3 6 -Ite m Healt h  S ur ve y  was de velo pe d 
at R A N D as part of t he  Me dical  O utc o mes  St ud y  ( Ware et al.  1 9 9 2, Mc H or ne y  et al. 1 9 9 4).  
3 6 -Ite m S h o rt F o r m S ur ve y I nstr u me nt ( S F-3 6) 
R A N D 3 6 -Ite m He alt h S ur ve y 1. 0 Q uesti o n n aire Ite ms 
C ho ose o ne o ptio n  for  eac h q uestio nnaire  ite m. 
1. I n ge neral,  w o uld  yo u  sa y  yo ur  healt h  is:
1 - E xcelle nt
2 - Ver y  go o d
3 - G o o d
4  - Fair
5  – P o or
2. C o mpare d  t o o ne y ear  a go,  ho w  w o uld  yo u  rate  yo ur  healt h  in  ge neral  no w?
1 - M uc h  better  no w  t ha n  o ne  year  a go
2 - S o me w hat  better no w  t ha n  o ne  year a go
3 - A b o ut  t he  sa me
4 - S o me w hat  w orse no w  t ha n  o ne year  a go
5 - M uc h  w orse  no w  t ha n  o ne  year  a go
T he  follo w i n g  ite ms are a b o ut  activitie s  yo u  might  d o d uring  a t ypical  da y.  D oes  yo ur  healt h 
no w  li mit  yo u  in  t hese  activities?  If  s o, ho w  muc h?  
3. Vigor o us  activities,  s uc h  as r unni n g,  lifti n g  hea vy  o bjects,  participati n g  in  stre nuo us  s p orts
1) Yes,  li mit e d  a lot   2) Yes,  li mite d  a litt le   3) N o, not  li mite d  at all 
4. M o derate activities,  s uc h  as mo vin g  a ta ble,  p us hin g  a vac uu m  clea ner,  b o wling,  or pla yin g
golf
1) Yes,  li mite d  a lot   2) Yes,  li mite d  a little   3) N o, not  li mite d  at  all 
5. Lifti n g  or  carr ying  gr oceries
1) Yes,  li mite d  a lot   2) Yes,  li mite d  a little   3) N o, not  li mite d  at  all 

Pa ge 6 3  of 6 6  
Brist ol  M yers  S q uib b  
Pr ot oc ol  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
6. C li mbi n g  se veral  flig ht s  of  stairs
1) Yes,  li mite d  a lot   2) Yes,  li mite d  a little   3) N o, not  li mite d  at  all 
7. C li mbi n g  o ne  flig ht   of stairs
1) Yes,  li mite d  a lot   2) Yes,  li mite d  a little   3) N o, not  li mite d  at  all 
8. Be nding,  k neelin g,  or  st o o ping
1) Yes,  li mite d  a lot   2) Yes,  li mite d  a little   3) N o, not  li mite d  at  all 
9. Walking  more  t ha n  a  mile
1) Yes,  li mite d  a lot   2) Yes,  li mite d  a little   3) N o, not  li mite d  at all 
1 0. Walking  se veral   bloc ks
1) Yes,  li mit e d  a lot   2) Yes,  li mite d  a litt le   3) N o, not  li mite d  at  all  
1 1. Walking  o ne  bloc k
1) Yes,  li mit e d  a lot   2) Yes,  li mite d  a litt le   3) N o, not  li mite d  at  all  
1 2. Bat hin g  or dressing  yo urself
1) Yes,  li mit e d  a lot   2) Yes,  li mite d  a litt le   3) N o, not  li mite d  at  all 
D uring  t he  past 4 wee ks, ha ve  yo u  ha d a ny  of  t he follo wi n g  pr o ble ms  wit h  yo ur  w or k or ot her 
re gular  daily  activities  as a res ult  of yo ur  p hysical  healt h? 
1 3. C ut  d o w n  t he  a mo unt  of  ti me  yo u  s pe nt  o n  w or k  or ot her  activities
1) Yes  2) N o
1 4. Acc o mplis he d  less  t ha n  yo u  w o uld  like
1) Yes  2) N o
1 5. Were li mite d  in  t he  kind  of  w or k or ot her  activities
1) Yes  2) N o
1 6. Ha d diffic ult y  perfor mi n g  t he  w or k or ot her  activities  (for  e xa mple,  it  t o o k e xtra  effort)
1) Yes  2) N o
D uring t he  past 4 wee ks, ha ve  yo u  ha d  a ny  of t he  follo wi n g  pr o ble ms  wit h  yo ur  w or k or ot her 
re gular  daily  activities  as  a  res ult  of  a ny  e motio nal  pr o ble ms  (s uc h  as  feelin g  de presse d  or 
a nxio us)? 
1 7. C ut  d o w n  t he  a mo unt  of  ti me  yo u  s pe nt  o n  w or k  or ot her  activities
1) Yes  2) N o
1 8. Acc o mplis he d  less  t ha n  yo u  w o uld  like

Pa ge 6 4  of 6 6  
Brist ol  M yers  S q uib b  
Pr ot oc ol  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
1) Yes  2) N o  
1 9. Did n't  d o w or k or ot her activities  as carefull y  as us ual
1) Yes  2) N o
2 0. D uring  t he  past  4 wee ks,  t o w hat  e xte nt  has  yo ur  p hysical  healt h  or e motio na l  pr o ble ms
interfere d  wit h  yo ur nor mal  s ocial  activit ies  wit h  fa mil y,  frie nds,  neighb ors,  or  gr o ups?
1 - N ot at  all 
2 - Slight l y
3 - M o derately
4 - Q uite  a bit
5 - E xtre mel y
2 1. H o w  muc h  b o dily  pain  ha ve  yo u  ha d  d uring  t he  past  4  wee ks?
1 - N o ne
2 - Ver y  mild
3 - Mild
4  - M o derate
5  - Se vere
6  - Ver y  se vere
2 2. D uring  t he  past  4 wee ks,  ho w  muc h  did  pain  interfere  wit h  yo ur  nor mal  w or k  (includ i n g
b ot h w or k o utside  t he ho me  a nd  ho use w or k)?
1 - N ot at  all 
2 - A  little  bit
3 - M o derately
4 - Q uite  a bit
5 - E xtre mel y
T hese  q uestio ns  are a b o ut  ho w  yo u  feel  a nd  ho w  t hings  ha ve  bee n  wit h  yo u  d uring  t he  past  4 
wee ks. F or eac h  q uestio n,  please  give  t he  o ne  a ns wer  t hat  c o mes  closest  t o t he  wa y  yo u  ha ve 
bee n feeli n g.  
H o w muc h  of t he  ti me  d uring  t he past 4 wee ks...  

Pa ge 6 5  of 6 6  
Brist ol  M yers  S q uib b  
Pr ot oc ol  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
 
 
 
2 3.  Did  yo u  feel  full  of  pe p? 
1) All  of  t he  ti me  2) M ost  of  t he  ti me  3) A  go o d  bit  of  t he  ti me  4) S o me  of  t he  ti me  5) A  little   
of t he  ti me   6) N o ne of  t he  ti me 
2 4.  Ha ve  yo u  bee n  a ver y  ner vo us   pers o n? 
1) All  of  t he  ti me  2) M ost  of  t he  ti me  3) A  go o d  bit  of  t he  ti me  4) S o me  of  t he  ti me  5) A  little   
of t he  ti me   6) N o ne of  t he  ti me 
2 5.  Ha ve  yo u  felt  s o d o w n  in  t he  d u mps  t hat  not hin g  c o uld  c heer  yo u  up?  
1) All  of  t he  ti me  2) M ost  of  t he  ti me  3) A  go o d  bit  of  t he  ti me  4) S o me  of  t he  ti me  5) A  little   
of t he  ti me   6) N o ne of  t he  ti me 
2 6.  Ha ve  yo u  felt  cal m  a nd  peaceful?  
1) All  of  t he  ti me  2) M ost  of  t he  ti me  3) A  go o d  bit  of  t he  ti me  4) S o me  of  t he  ti me  5) A  little   
of t he  ti me   6) N o ne of  t he  ti me 
2 7.  Did  yo u  ha ve  a lot  of  e ner gy? 
1) All  of  t he  ti me  2) M ost  of  t he  ti me  3) A  go o d  bit  of  t he  ti me  4) S o me  of  t he  ti me  5) A  little    
of t he  ti me   6) N o ne of  t he  ti me 
2 8.  Ha ve  yo u  felt  d o w nhearte d  a nd  blue?  
1) All  of  t he  ti me  2) M ost  of  t he  ti me  3) A  go o d  bit  of  t he  ti me  4) S o me  of  t he  ti me  5) A  little   
of t he  ti me   6) N o ne of  t he  ti me 
2 9.  Did  yo u  feel  w or n  o ut?  
1) All  of  t he  ti me  2) M ost  of  t he  ti me  3) A  go o d  bit  of  t he  ti me  4) S o me  of  t he  ti me  5) A  little   
of t he  ti me   6) N o ne of  t he  ti me 
3 0.  Ha ve  yo u  bee n a ha p p y   pers o n? 
1) All  of  t he  ti me  2) M ost  of  t he  ti me  3) A  go o d  bit  of  t he  ti me  4) S o me  of  t he  ti me  5) A  little   
of t he  ti me   6) N o ne of  t he  ti me 
3 1.  Did  yo u  feel   tire d? 
1) All  of  t he  ti me  2) M ost  of  t he  ti me  3) A  go o d  bit  of  t he  ti me  4) S o me  of  t he  ti me  5) A  little   
of t he  ti me   6) N o ne of  t he  ti me 
 
 
3 2.  D uring  t he  past  4 wee ks,  ho w  muc h  of  t he  ti me  has  yo ur  p hysical  healt h  or  e motio na l 
pr o ble ms  interfere d  wit h  yo ur  s ocial  ac tivit ie s  (like  visit i n g  wit h  frie nds,  relatives, etc.)? 
1  - All  of  t he  ti me 
2  - M ost of t he ti me   3 
- S o me  of  t he  ti me  4 - 
A  little  of  t he  ti me 

Pa ge 6 6  of 6 6  
Brist ol  M yers  S q uib b  
Pr ot oc ol  
C O N FI D E N TI A L  
Fe br uar y  2 0 1 8  
 
 
 
5 - N o ne  of  t he  ti me  
 
 
H o w T R U E  or F A L S E  is  eac h of  t he follo wi n g  state me nts  for  yo u.  
3 3.  I see m  t o get sic k  a little  easier  t ha n  ot her   pe o ple 
1) Definitel y  tr ue   2) M ostly  tr ue   3) D o n't  k no w   4) M ostly  false   5) Definitel y  false 
3 4.  I a m  as healt hy  as  a nyb o d y  I k no w 
1) Definitel y  tr ue   2) M ostly  tr ue   3) D o n't  k no w   4) M ostly  false   5) Definitel y  false 
3 5.  I e xpect  my  healt h  t o get w orse  
1) Definitel y  tr ue   2) M ostly  tr ue   3) D o n't  k no w   4) M ostly  false   5) Definitel y  false 
3 6.  M y  healt h  is  e xcelle nt 
1) Definitel y  tr ue   2) M ostly  tr ue   3) D o n't  k no w  4) M ostly  false   5) Definitel y false 

1  
 
D at e  
 
Pill ai  I D  
 
 
 
 
E.  I g G 4-R el at e d  Dis e as e  S y m pt o m  Distr ess I n d ex  
 
 
 
S ur v e y  I nstr ucti o ns 
 
1.  T his s h o ul d r efl ect a n y s y m pt o ms y o u m ay h av e ex p eri e nc e d o v er t h e l ast 3 0 d ays. F or e ac h  s y m pt o m, c h o os e h o w  oft e n, if at all,  
y o u ex p eri e nc e   t h e s y m pt o m. 
2.  If  pr es e nt,  c h o os e h o w  m uc h t h e s y m pt o m c a us es  y o u distr ess.  
3.  Of all t h e s y m pt o ms y o u i d e ntify o n t his s ur v ey, c h o os e u p t o t hr e e w hic h y o u w o ul d s ay ar e t h e m ost b ot h ers o m e, s ev er e, or 
i m p ort a nt t o y o u. R a n k t h es e t hr e e b y m ar ki n g a 1 f or t h e m ost i m p ort a nt, 2 as t h e n ext m ost i m p orta nt, a n d 3 as t h e l e ast 
i m p ort a nt of t h es e  t hr e e. 
4.  D o n ot c alc ul at e  t h e sc or e.  T his  will b e d o n e  b y y o ur  p h ysici a n.  
 
Ex a m pl e:  
 
 
1.) Fr e q u e nc y 
( C h ec k o n e) 
2.) H o w m uc h distr ess d o es t h e s y m pt o m c a us e 
y o u ?   ( C h ec k o n e)  
Sc or e  
S y m pt o m  
N e v er  
 
 
( 0) 
A f e w 
d a ys a 
m o nt h 
( 1) 
A f e w 
d a ys a 
w e e k 
( 2) 
E v er y 
D a y  
 
( 3) 
N o n e  
 
 
( 0) 
A littl e bit 
( 1) 
S o m e - 
w h at  
 
( 2) 
Q uit e a 
bit  
 
( 3) 
V er y 
m uc h  
 
( 4) 
 
S w elli n g of s ali v ar y gl a n ds 
u n d er  or si d e of t h e j a w  
 
 
 
X  
 
 
X  
 
 
8  
Dr y m o ut h  
X  
 
 
 
 
 
 
 
 
 
S w elli n g  ar o u n d  t h e ey es  
X  
 
 
 
 
 
 
 
 
 
C h a n g e  i n visi o n  
 
 
X  
 
 
X  
 
 
 
3  

2  
 
I g G 4-R el at e d Dis e as e S y m pt o m Distr ess I n d e x  
 
 
 
 
Fr e q u e nc y  
( C h ec k o n e) 
H o w m uc h   distr ess d o es t h e s y m pt o mc a us e y o u ?  
( C h ec k o n e) 
Sc or e  
S y m pt o m  
N e v er  
 
 
 
( 0) 
A f e w 
d ays a 
m o nt h  
 
( 1) 
A f e w 
d ays a 
w e e k  
 
( 2) 
E v er y 
D ay  
 
 
( 3) 
N o n e  
 
 
 
( 0) 
A littl e 
bit  
 
 
( 1) 
S o m e - 
w h at  
 
 
( 2) 
Q uit e a 
bit  
 
 
( 3) 
V er y 
m uc h  
 
 
( 4) 
 
S ali v ar y Gl a n ds  
 
 
 
 
 
 
 
 
 
 
S w elli ng of s ali v ary gl a n ds u n d er  or 
si d e of t h e j a w 
 
 
 
 
 
 
 
 
 
 
Dry m o ut h  
 
 
 
 
 
 
 
 
 
 
Or bit ( E y e Ar e a)  
 
 
 
 
 
 
 
 
 
 
S w elli ng ar o u n d   t h e e y es  
 
 
 
 
 
 
 
 
 
 
C h a ng e i n visi o n  
 
 
 
 
 
 
 
 
 
 
Dry e y es  
 
 
 
 
 
 
 
 
 
 
Ot h er H e a d a n d N ec k  
 
 
 
 
 
 
 
 
 
 
Si n us c o ng esti o n/ dis c h arg e  
 
 
 
 
 
 
 
 
 
 
Si n us p ai n 
 
 
 
 
 
 
 
 
 
 
L oss of s e ns e of s mell  
 
 
 
 
 
 
 
 
 
 
C h est  
 
 
 
 
 
 
 
 
 
 
S h ort n ess   of br e at h  
 
 
 
 
 
 
 
 
 
 
C o ug h  
 
 
 
 
 
 
 
 
 
 
A b d o m e n  
 
 
 
 
 
 
 
 
 
 
P ai n i n t h e  a b d o me n  
 
 
 
 
 
 
 
 
 
 
L oss of a p p etit e 
 
 
 
 
 
 
 
 
 
 
N a us e a a n d/ or  v o miti ng  
 
 
 
 
 
 
 
 
 
 
L o os e st o ol a n d/ or  di arr h e a  
 
 
 
 
 
 
 
 
 
 

3  
 
 
Fr e q u e nc y 
( C h ec k o n e) 
H o w m uc h  distr ess d o es t h e s y m pt o mc a us e y o u ? 
( C h ec k o n e) 
Sc or e  
S y m pt o m  
N e v er  
 
 
( 0) 
A f e w 
d ays a 
m o nt h 
( 1) 
A f e w 
d ays a 
w e e k 
( 2) 
E v er y 
D ay  
 
( 3) 
N o n e  
 
 
( 0) 
A littl e 
bit  
 
( 1) 
S o m e - 
w h at  
 
( 2) 
Q uit e a 
bit  
 
( 3) 
V er y 
m uc h  
 
( 4) 
 
G e nit o uri n ar y ( m al e o nl y)  
 
 
 
 
 
 
 
 
 
 
P ai n i n t h e  gr oi n  
 
 
 
 
 
 
 
 
 
 
Diffic ulty st arti ng a uri n ary 
str e a m 
 
 
 
 
 
 
 
 
 
 
Uri n ati ng fr e q u e ntl y  
 
 
 
 
 
 
 
 
 
 
W a ki ng u p at ni g ht t o uri n at e  
 
 
 
 
 
 
 
 
 
 
S ki n a n d E xtr e miti es  
 
 
 
 
 
 
 
 
 
 
Y ell o wi ng of t h e s ki n 
 
 
 
 
 
 
 
 
 
 
S w elli ng of t h e l o w er l e gs  
 
 
 
 
 
 
 
 
 
 
Ot h er S y m pt o ms  
 
 
 
 
 
 
 
 
 
 
1.  
 
 
 
 
 
 
 
 
 
 
2.  
 
 
 
 
 
 
 
 
 
 
3.  
 
 
 
 
 
 
 
 
 
 
T ot al Sc or es  
 
 
 
 
 
 
 
 
 
 
Of all   t h e s y m pt o ms  list e d a b o v e,  w hic h t hr e e d o y o u  c o nsi d er  t o b e t h e m ost  b ot h ers o m e, s e v er e, or  i m p ort a nt  t o y o u ? 
1.  
 
2.  
 
3.  

4  
 
P ati e nt S ur v e y (S u bj ect  s h o ul d c o m pl et e  t his  f or m) 
 
 
I nstr ucti o ns:  Pl e as e r at e y o ur o v er all  h e alt h  r el at e d  t o y o ur I g G 4 -R el at e d  Dis e as e i n t h e p ast w e ek  b y s el ecti n g  a  
w h ol e n u m b er  b el o w, usi n g t h e f oll o wi n g sc al e:  1 = Extr e m el y  P o or a n d 1 0 =  Exc ell e nt . 
 
* H e alt h  pr o bl e ms  d u e t o a  dis e as e ot h er t h a n  I g G 4 -r el at e d  Dis e as e s h o ul d  n ot b e c o nsi d er e d  i n t his ev al u ati o n. 
  P A R TI CI P A N T  GL O B AL  A S S E S S M E N T  
 
T o d ay's  D at e:  |   
|  
|  - |   
|   
|  - |   
|   
|  
| _    |  ( M M-D D -Y Y Y Y)  
  O n a sc al e  of 1- 1 0, H o w w as y o ur o v er all  h e alt h i n t h e l ast  w e e k ?  
 
( Extr e m el y  P o or) 1  2 3 4 5 6 7  8 9 1 0  ( Exc ell e nt)  

F . T he  Gl uc oc ortic oi d  T o xicit y  I n de x  
c he c k if pre s e nt  
C o m p osite G TI  
Ite m Wei g ht 
S pe cific List  
B o dy  mas s  i n de x  
 
 
I mpr o ve me nt  in  B MI 
- 8 
Maj or increase  in 
B MI  
 
N o c ha nge  in  B MI  
0  
 
 
M o derate increase  in 
B MI  
2 1 
 
 
Maj or increase  in 
B MI  
3 6 
 
Gl uc os e t ole ra nce  
 
I mpr o ve me nt  in 
gluc ose  t olera nce  
- 8 
 
Dia betic  retino pat h y  
 
N o c ha nge  in  gluc ose 
t olera nce 
0 
 
Dia betic  ne p hr o pat hy  
 
W orse ning  of 
gluc ose  t olera nce  
3 2 
 
Dia betic  ne ur o pat hy  
 
W orse ning  of  
gluc ose  t olera nce 
des pite  treat me nt  
 
4 4 
 
Bl o o d  pre s s ure  
 
I mpr o ve me nt  in 
blo o d press ure  
- 1 0 
H yperte nsi ve  
e mer ge nc y 
 
 
N o c ha nge  in  blo o d 
press ure  
 
0 
P osterior  re versible 
e nce p halo pat h y 
s yndr o me 
 
W orse ning 
hyperte ns io n  
1 9 
 
 
W orse ning 
hyperte ns io n  des pite 
treat me nt 
 
4 4 
 
Li pi ds  
 
I mpr o ve me nt  in 
lipids 
- 9 
 
 
N o c ha nge  in  lipids 
0  
 
 
W orse ning  hyperlip id 
e mia 
1 0 
 
 
W orse ning  hyperlip id 
e mia  des pite 
treat me nt 
 
3 0 
 
B o ne  de ns it y  
 
I mpr o ve me nt  in  b o ne 
de nsit y 
- 1 
Maj or decrease in 
b o ne de nsit y 

 
N o c ha nge  in  b o ne 
de nsit y 
0 
I ns uffic ie nc y 
fract ure 
 
Decrease  in  b o ne 
de nsit y 
2 9 
 
Ste roi d  my o pat hy  
 
 
N o ster oid  myo pat hy  
0 
Se vere  
ster oid  myo pat hy 
 
Mild  
ster oid  myo pat hy 
9 
 
 
M o derate  
ster oid  myo pat hy  or 
greater  
 
6 3 
 
S ki n t o xicit y  
 
N o s kin  t o xicit y  
0  
Se vere  s kin  t o xicit y  
 
Mild  s kin  t o xicit y  
8  
 
 
M o derate s kin 
t o xicit y  or greater 
2 6 
 
N e uro ps yc hi atric  t o xicit y  
 
N o ne ur o ps yc hiatric 
s y mpt o ms 
0 
 
Ps yc hosis  
 
Mild 
ne ur o ps yc hia tr ic 
s y mpt o ms 
 
1 1 
 
 
G G -ind uce d  viole nce 
 
M o derate 
ne ur o ps yc hia tr ic 
s y mpt o ms  or greater 
 
7 4 
Ot her se vere 
ne ur o ps yc hia tr ic 
s y mpt o ms 
I nfe cti o n 
 
N o significa nt 
infect io n 
0 
 
Gra de 4 infectio n  
 
Oral/ va gi nal  ca ndidia 
sis  or unc o mplicate d 
zoster 
 
1 9 
 
 
Gra de 5 infectio n  
 
Gra de 3 infectio n  or  
greater  
9 3 
 
E n docri ne  
 
 
 
A dre nal  
ins ufficie nc y 
G astroi ntesti nal  
 
 
 
Perforatio n  
 
 
 
Pe ptic  ulcer  disease  
M us c ul os kelet al  
 
 
 
A vasc ular  necr osis  
 
 
 
Te nd o n  r upt ure  
Oc ul ar  

C e ntral  ser o us  
retino pat h y 
I ntra oc ular  press ure 
ele vatio n 
P osterior  s ubca ps ular  
cataract 
T ot al  
-3 6 t o 4 3 9