Peanut Sublingual Immunotherapy Induction of Clinical Tolerance of Newly Diagnosed Peanut Allergic 12 to 48 Month Old Children
Phase: PHASE2
Conditions: Peanut Hypersensitivity, Food Allergy, Food Hypersensitivity, Peanut Allergy
Sponsor: University of North Carolina, Chapel Hill

Title:  Pea n ut S u bli n g ual I m m u n ot hera p y I n d ucti o n of Cli nical T olera nce i n Ne wl y Dia g n ose d 
Pea n ut Aller gic 1 2 t o 4 8 M o nt h Ol d C hil dre n  
 
Cli nicaltrials. g o v : N C T 0 2 3 0 4 9 9 1  
 
D oc u me nt date : Marc h  1 8 , 2 0 20  
 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 2  of 5 7  
* See a p pe n di x 6 . 0 
 
P R O T O C O L  
P E A N U T S U B LI N G U A L I M M U N O T H E R A P Y  I N D U C TI O N O F 
C LI NI C A L T O L E R A N C E I N N E W L Y DI A G N O S E D P E A N U T 
A L L E R GI C 1 2 T O 4 8 M O N T H O L D C HI L D R E N  
P e a n ut S LI T a n d E arl y T ol er a n c e  I n d u cti o n  
Ve rsi o n  4. 0 M a r c h 1 8, 2 0 2 0  
I N D # 1 4 3 2 6  
T hi s cli ni c al st u d y i s s u p p o rt e d b y F o o d All e r g y R e s e a r c h a n d E d u c ati o n ( F A R E ) a n d 
c o n d u ct e d at T h e Di vi si o n of P e di at ri c All e r g y a n d I m m u n ol o g y at U N C -C h a p el Hill  
a n d T h e Di vi si o n of All e r g y a n d I m m u n ol o g y at t h e U ni v e r sit y of T e x a s S o ut h w e st e r n.  
P RI N CI P A L IN V E S TI G A T O R  [ PR O T O C O L C H AI R ] 
A.  Wesley B urks, M D  
Pr ofess or  of Pe di atrics  
T he U niversity of N ort h C ar oli n a  
C h a pel Hill , N C 2 7 5 9 9  
P h o ne: 9 1 9 -9 6 6 -4 4 2 7  
E -mail: wesle y. b ur ks @ u nc .e d u 
 
C o nfi de nti ality St ate me nt  
T his d oc u me nt is c o nfi de nti al a n d is t o be distri b ute d f or revie w o nly t o i nvesti g at ors, 
p ote nti al i nvesti g at ors, c o ns ult a nts, st u dy st aff, a n d a p plic a ble i n de pe n de nt et hics 
c o m mittees or i nstit uti o n al revie w b o ar ds.  T he c o nte nts of t his d oc u me nt s h all n ot be 
discl ose d t o ot hers wit h o ut writte n a ut h oriz ati o n fr o m Dr . B urks, u nless it is necess ary 
t o o bt ai n i nf or me d c o nse nt fr o m p ote nti al st u dy p artici p a nts. 
 
 
 
 
 
 
 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 3  of 5 7  
* See a p pe n di x 6 . 0 
 
 
 
Pr ot oc ol A p pr o v al  
 
 
 
 
 
 
 
 
Pr ot oc ol #  1 4 -0 6 4 8  
Versi o n/ Date: 4. 0 / Marc h 1 8, 2 0 2 0  
I N D: 1 4 3 2 6  
Pri nci pal I n vesti gat or:  A. Wesle y B ur ks, M D  
S h ort Title:  Pe a n ut S LI T a n d E arly T oler a nce  I n d ucti o n 
 
 
I h ave re a d pr ot oc ol # , a n d I a p pr ove it.  As t he pri nci p al i nvesti g at or, I a gree t o          c o n d uct 
t his  pr ot oc ol  acc or di n g  t o  g o o d  cli nic al  pr actices,  w hic h  are  deli ne ate d  i n  t he  I nter n ati o n al 
C o nfere nce  o n  H ar m o niz ati o n  (I C H)  of  Tec h nic al  Re q uire me nts 
f or  Re gistr ati o n  of 
P h ar m ace utic als  f or  H u m a n  Use 
“ G ui da nce  f or  I n d ustr y:  E 6  G o o d  Cli nical  Practice 
C o ns oli date d G ui da nce” ( M ay 1 9 9 6), a n d acc or di n g t o t he criteri a s pecifie d i n t his pr ot oc ol. 
 
 
   _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _                                     
   Pri nci pal I n vesti gat or ( Pri nt)                                                                 
 
 
   _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _                                    _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
   Pri nci pal I n vesti gat or ( Si g nat ure)                                                          Date  

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 4  of 5 7  
* See a p pe n di x 6 . 0 
 
S y n o psis  
Title  
Pe a n ut S u bli n g u al I m m u n ot her a py I n d ucti o n of Cli nic al T oler a nce i n Ne wly 
Di a g n ose d  Pe a n ut Aller gic  1 2 t o 4 8 m o nt h ol d  C hil dre n  
S h ort Title  
Pea n ut S LI T a n d Earl y  T olera nce  I n d ucti o n 
Cli nic al P h ase  
P hase II –  Safet y a n d Efficac y  
I N D 
1 4 3 2 6  
S p o ns or  
A.  Wesle y B ur ks, M D  
Pri nci p al I n vesti g at or  
C hair - A. Wesle y B ur ks , M D  
P artici p ati n g Site s 
U N C -C ha pel Hill  ( pri mar y), U T S o ut h wester n Me dical Ce nter (sec o n dar y) 
Accr u al O bjecti ve  
5 0  s u bjects (3 5  at pri mar y site, 1 5  at sec o n dar y site)  
Accr u al Peri o d  
3 0 m o nt hs  
St u d y Desi g n  
A pr os pecti ve, ra n d o mize d, d o u ble -bli n d, place b o c o ntr olle d st u d y t o deter mi ne t he 
efficac y of pea n ut s u bli n g ual i m m u n ot hera p y ( S LI T) i n i n d uci n g cli nical 
dese nsitizati o n  after 3 6 m o nt hs *  of treat me nt.  
St u d y D ur ati o n  
D ose escalati o n ( 5  m os); Mai nte na nce ( 3 1  m os); Wit h dra wal ( 3  m os).  
Pri m ar y E n d p oi nt  
T he pri mar y cli nical e n d p oi nt of t his trial is t o e val uate t he prese nce/a bse nce of  
cli nical dese nsitizati o n  t o pea n ut after 3 6 m o nt hs of pea n ut s u bli n g ual i m m u n ot hera p y 
( S LI T). 
Sec o n d ar y E n d p oi nts  
T he sec o n dar y cli nical efficac y e n d p oi nt of t his trial is t o e val uate t he 
prese nce/a bse nce of persiste nt cli nical t olera nce t o pea n ut 3 m o nt hs f oll o wi n g 
wit h dra wal of acti ve/ place b o S LI T.   A mec ha nistic e n d p oi nt will deter mi ne i m m u ne 
para meters of s u bjects w h o ac hie ve a state of cli nical t olera nce vers us t h ose w h o fail 
t o pr o gress be y o n d a state of dese nsitizati o n.   
I ncl usi o n Criteri a 
•  Writte n i nf or me d c o nse nt fr o m partici pa nt’s pare nt/ g uar dia n . 
•  A ge 1 2 -4 8 m o nt hs  of eit her se x, a n y race, a n y et h nicit y . 
•  1) A pea n ut aller g y w it h a c o n vi nci n g cli nical hist or y of pea n ut aller g y a n d  a 
pea n ut -s pecific I g E [ U ni C A P] >  0. 3 5  k U A / L a n d  a p ositi ve s ki n pric k test t o 
pea n ut ( >3 m m t ha n t he ne gati ve c o ntr ol) or  2) are se nsitize d t o pea n u t ( base d o n 
an  I g E [ U ni C A P] t o pea n ut of >  5 k U A/ L ) a n d  a p ositi ve s ki n pric k test t o pea n ut 
(>  3 m m t ha n t he ne gati ve c o ntr ol) a n d  n o k n o w n hist or y of i n gesti o n of pea n ut.  
•  A p ositi ve D B P C F C t o 1 0 0 0 m g of pea n ut at e nr oll me nt . 
E xcl usi o n Criteri a  
•  Hist or y of se vere a na p h yla xis t o pea n ut , defi ne d as  h y p o xia, h y p ote nsi o n, or 
ne ur ol o gic  c o m pr o mise (c ya n osis or S p O 2 < 9 2 % at a n y sta ge, h y p ote nsi o n, 
c o nf usi o n, c olla pse or  l oss of c o nsci o us ness). 
•  Partici pati o n i n a n y i nter ve nti o nal st u d y f or t he treat me nt of f o o d aller g y i n t he 
past 6 m o nt hs . 
•  K n o w n oat, w heat , or gl yceri n aller g y. 
•  E osi n o p hilic or ot her i nfla m mat or y (e. g. celiac) gastr oi ntesti nal disease . 
•  Se vere ast h ma ( 2 0 0 7 N H L BI Criteria Ste ps 5 or 6  –  A p pe n di x 2 ). 
•  I na bilit y t o disc o nti n ue a nti hista mi nes f or s ki n testi n g a n d D B P C F C s. 
•  Use of o maliz u ma b or ot her n o n -tra diti o nal f or ms of aller ge n i m m u n ot hera p y (e. g., 
oral or s u bli n g ual) or i m m u n o m o d ulat or t hera p y ( n ot i ncl u di n g c ortic oster oi d s) or 
bi ol o gic t hera p y wit hi n t he past year . 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 5  of 5 7  
* See a p pe n di x 6 . 0 
 
•  Use of b -bl oc kers ( oral), a n gi ote nsi n -c o n verti n g e nz y me ( A C E) i n hi bit ors, 
a n gi ote nsi n-rece pt or bl oc kers ( A R B) or calci u m c ha n nel bl oc kers. 
•  Si g nifica nt me dical c o n diti o n (e. g., li ver, ki d ne y, gastr oi ntesti nal, car di o vasc ular, 
he mat ol o gic, or p ul m o nar y disease) w hic h w o ul d ma ke t he s u bject u ns uita ble f or 
i n d ucti o n of f o o d reacti o ns. 
Tre at me nt Descri pti o n  
T he st u d y is a pr os pecti ve , ra n d o mize d, d o u ble-bli n d, place b o -c o ntr olle d trial base d o n 
pre vi o us e x perie nce  at D u ke U ni versit y  a n d at U N C C ha pel Hill  wit h pea n ut -aller gic 
s u bjects.  A t otal of 5 0 s u bjects at 2 sites will be e nr olle d  t o recei ve 3 6 m o nt hs *  of 
pea n ut S LI T  vers us place b o (ra n d o mize d 1 : 1 treat me nt: place b o). 
 
( * U nless affecte d b y C O VI D-1 9)  
 
T he d osi n g f or t he st u d y is o utli ne d bel o w.  
(1: 1 = f ull c o nce ntrati o n = 5 0 0 0 mc g/ ml; 1 p u m p = 0. 0 5 ml)  
 
After c o m pleti n g t he d osi n g escalati o n  p has e, s u bjects will c o nti n ue o n a dail y 
mai nte na nce d ose of 4 0 0 0 mc g of pea n ut pr otei n.  F oll o wi n g 3 6  m o nt hs *  of t otal 
treat me nt, s u bjects will u n der g o a D B P C F C t o verif y dese nsitizati o n (i.e. a n i ncrease 
i n reacti o n t hres h ol d w hile recei vi n g acti ve treat me nt).  All s u bjects will be 
dis c o nti n ue d fr o m pea n ut S LI T t hera p y after 3 6 m o nt hs of treat me nt * .  S u bjects w h o 
D ose #  
 
Pe a n ut 
Dil uti o n  
 
P u m ps  
D ose of 
Pe a n ut 
Pr otei n  
I nter v al i n 
Wee ks  
%  I ncre ase  
1  
1 :1 0 0  
1  
2. 5 mc g  
 
- 
2  
1 :1 0 0  
2  
5 mc g  
1  
1 0 0 %  
3  
1 :1 0 0  
4  
1 0 mc g  
1  
1 0 0 %  
4  
1 :1 0 0  
8  
2 0 mc g  
1  
1 0 0 %  
5  
1 :1 0  
1  
2 5 mc g  
1  
2 5 %  
6  
1 :1 0  
2  
5 0 mc g  
1  
1 0 0 %  
7  
1 :1 0  
4  
1 0 0 mc g  
1  
1 0 0 %  
8  
1 :1 0  
8  
2 0 0 mc g  
1  
1 0 0 %  
9  
1: 1  
1  
2 5 0 mc g  
2  
2 5 %  
1 0  
1: 1  
2  
5 0 0 mc g  
2  
1 0 0 %  
1 1  
1: 1  
4  
1 0 0 0 mc g  
2  
1 0 0 %  
1 2  
1: 1  
8  
2 0 0 0 mc g  
2  
1 0 0 %  
1 3  
1: 1  
1 2  
3 0 0 0 mc g  
2  
5 0 %  
1 4  
1: 1  
1 6  
4 0 0 0 mc g  
2  
3 3 %  

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 6  of 5 7  
* See a p pe n di x 6 . 0 
 
t olerate > 4 4 3 m g of pea n ut pr otei n  at t he 3 6 m o nt h *  D B P C F C  will wit h h ol d treat me nt 
f or 3 m o nt hs a n d ret ur n a n d u n der g o  a D B P C F C t o assess cli nical  t olera nce u p t o t he 
a m o u nt t olerate d at t he 3 6 m o nt h *  D B P C F C  (i.e. mai ntai ni n g a n i ncrease i n reacti o n 
t hres h ol d after disc o nti n ui n g acti ve treat me nt).  S u bjects  will be u n bli n de d  after t he 
t olera nce c halle n ge a n d will c o m plete t he st u d y. S u bjects t hat c o m plete t he  t olera nce 
D B P C F C wit h o ut s y m pt o ms will be i nstr ucte d t o i ntr o d uce pea n ut i nt o t he diet a d 
li bit u m.  S u bjects t hat fail eit her t he dese nsitizati o n or t olera nc e D B P C F C (t olerati n g < 
4 4 3 m g of pea n ut pr otei n)  or ca n n ot t olerate t he e ntire 4 4 4 3 m g of pea n ut pr otei n 
wit h o ut s y m pt o ms  will be gi ve n t he o pti o n t o ta ke a dail y pea n ut f o o d e q ui vale nt t o 
mai ntai n t he dese nsitize d state or t o strictl y a v oi d all pea n ut.  S u bjects w h o fail t he 
dese nsitizati o n D B P C F C at 3 6 m o nt hs *  will be u n bli n de d t o t heir st u d y treat me nt.  
St u d y Pr oce d ures  
T he f oll o wi n g pr oce d ures will be perf or me d  acc or di n g t o t he sc he d ule i n A p pe n di x 1:  
•  
Me dical a n d aller g y hist or y (i ncl u di n g dietar y his t or y) 
•  
P h ysical e xa mi nati o n  
•  
S ki n pric k testi n g  t o pea n ut 
•  
Bl o o d  a nal ysis f or pea n ut -s pecific i m m u n o gl o b uli ns (I m m u n oC A P)  
•  
W h ole bl o o d f or bas o p hil acti vati o n  a n d T-cell st u dies  ( U N C-C H)  
•  
Sali va c ollecti o n f or i m m u n o gl o b uli n st u dies  
•  
St o ol c ollecti o n f or  micr o bi o me a n d i m m u n o gl o b uli n st u dies  
•  
S u bli n g ual I m m u n ot hera p y ( S LI T)  
•  
D o u ble -bli n d, place b o -c o ntr olle d, f o o d c halle n ge t o pea n ut  
 
St u d y St o p pi n g R ule s 
•  
A n y deat h relate d t o pea n ut S LI T  d osi n g . 
•  
Greater t ha n 2 se vere a na p h ylactic reacti o ns relate d t o pea n ut S LI T  d osi n g at 
a n y sta ge of t he pr ot oc ol.  
•  
Greater t ha n 3 s u bjects t hat re q uire m ore t ha n 1 i ntra m usc ular i njecti o n of 
e pi ne p hri ne d uri n g d ose escalati o n or mai nte na nce d osi n g of pea n ut  st u d y 
pr o d uct.  
C O VI D -1 9  
I n Marc h of 2 0 2 0 a nati o nal e mer ge nc y was declare d o ver t he gl o bal pa n de mic 
c or o na vir us C O VI D -1 9. S ocial dista nci n g meas ures were p ut i n place i n or der t o st o p 
t he s prea d a n d miti gate i nfecti o n rates t hat w o ul d o ver w hel m h os pitals. U N C’s V ice-
C ha ncell or f or Researc h i m ple me nte d pla ns t o re d uce s u bjects c o mi n g t o ca m p us a n d 
halt n o n -esse ntial researc h. W hile t he F o o d Aller g y I nitiati ve gr o u p’s researc h was 
dee me d esse ntial  a n d all o we d t o c o nti n ue, meas ures are bei n g i m ple me nte d t o e ns ure 
safet y. 
•  
I n-pers o n f oll o w u p visits will be c o n verte d t o p h o ne visits  
•  
St u d y dr u g will be pr o vi de d direct t o patie nt as feasi ble  
•  
A ll oral  f o o d c halle n ges will be halte d  d uri n g t he U ni versities’ safet y 
meas ures d ue t o C O VI D -1 9 d ue t o t he ris k of a na p h yla xis p ossi bl y re q uiri n g 
e mer ge nc y c o de tea m res p o nse ser vices a n d/ or a n E mer ge nc y De part me nt 
( E D) visit. T his is i n a n eff ort t o re d uce a n y n o n-C O VI D b ur de n o n  U N C 
e mer ge ncy ser vices  d uri n g t his u ncertai n ti me.   
•  
S u bjects w h ose 3 6 m o nt h oral f o o d c halle n ge has bee n deferre d will c o nti n ue 
dail y d osi n g of st u d y dr u g  past t he 3 6 m o nt h ti me peri o d. T his is t o mai ntai n 
a n y p ote ntial treat me nt effect u ntil s uc h ti me t hat t he oral f o o d c halle n ge is 
resc he d ule d. 
•  
S u bjects w h ose 3 9 m o nt h oral f o o d c halle n ge has bee n deferre d will c o m plete 
t he st u d y at t hat ti me a n d be u n bli n de d t o treat me nt all ocati o n. 
 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 7  of 5 7  
* See a p pe n di x 6 . 0 
 
 
 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 8  of 5 7  
* See a p pe n di x 6 . 0 
 
T a bl e of C o nt e nt s  
1 . B A C K G R O U N D A N D R A TI O N A L E  ............................................................................... 1 0  
1.  
B A C K G R O U N D A N D R A TI O N AL E  ................................................................................................. 1 2  
1. 1  
B A C K G R O U N D  ................................................................................................................................ 1 2  
1. 2  
R A TI O N AL E  .................................................................................................................................... 1 2  
1. 3  
R A TI O N AL E F O R S EL E C TI O N OF S T U D Y P O P UL A TI O N  ............................................................................. 1 5  
1. 4  
K N O W N A N D P O T E N TI AL R I S K S A N D B E N E FI T S T O H U M A N P A R TI CI P A N T S  ................................................ 1 5  
1. 4. 1  
Ris ks  ................................................................................................................................... 1 5  
1. 4. 2  
B e n efits  .............................................................................................................................. 1 6  
2.  
O BJ E C TI V E S  ................................................................................................................................ 1 7  
2. 1  
P RI M A R Y A N D S E C O N D A R Y O BJ E C TI V E S  .............................................................................................. 1 7  
3.  
S T U D Y D E SI G N  ............................................................................................................................ 1 9  
3. 1  
S T U D Y E N D P OI N T S  .......................................................................................................................... 1 9  
3. 1. 1  
Pri m ary E n d p oi nt  ............................................................................................................... 1 9  
3. 1. 2  
S ec o n d ary E n d p oi nts  .......................................................................................................... 1 9  
3. 2  
C RI T E RI A F O R P R E M A T U R E T E R MI N A TI O N OF T H E S T U D Y : S T U D Y S T O P PI N G R UL E S  .................................... 2 0  
4.  
S EL E C TI O N A N D WI T H D R A W AL O F P A R TI CI P A N T S  ...................................................................... 2 1  
4. 1  
IN CL USI O N C RI T E RI A  ....................................................................................................................... 2 1  
4. 2  
E X CL USI O N C RI T E RI A  ....................................................................................................................... 2 1  
4. 3  
P R E M A T U R E P A R TI CI P A N T T E R MI N A TI O N F R O M T H E S T U D Y  ................................................................... 2 1  
4. 3. 1  
Crit eri a  ............................................................................................................................... 2 1  
5.  
S T U D Y M E DI C A TI O N  ................................................................................................................... 2 3  
5. 1  
F O R M UL A TI O N , P A C K A GI N G , A N D LA B ELI N G  ....................................................................................... 2 3  
5. 2  
P R E P A R A TI O N , A D MI NI S T R A TI O N , A N D D OS A G E  .................................................................................. 2 3  
5. 3  
D R U G A C C O U N T A BILI T Y  ................................................................................................................... 2 3  
5. 4  
A S S E S S M E N T OF C O M PLI A N C E WI T H S T U D Y T R E A T M E N T A N D M O NI T O RI N G  ............................................ 2 4  
5. 5  
M O DI FI C A TI O N OF S T U D Y T R E A T M E N T  ............................................................................................... 2 4  
5. 6  
C O N C O MI T A N T M E DI C A TI O NS  .......................................................................................................... 2 4  
5. 7  
P R O P H YL A C TI C M E DI C A TI O NS  ........................................................................................................... 2 4  
5. 8  
R E S C U E M E DI C A TI O NS  .................................................................................................................... 2 4  
5. 9  
P R O HI BI T E D M E DI C A TI O NS  .............................................................................................................. 2 5  
6.  
S T U D Y D E FI NI TI O N S A N D P R O C E D U R E S  ...................................................................................... 2 6  
6. 1  
S T U D Y D E FI NI TI O NS  ........................................................................................................................ 2 6  
6. 1. 1  
A n a p hyl axis  ........................................................................................................................ 2 6  
6. 1. 2  
Crit eri a f or Di a g n osis  .......................................................................................................... 2 6  
6. 1. 3  
A n a p hyl axis St a gi n g Syst e m  ............................................................................................... 2 6  
6. 2  
E N R OLL M E N T  ................................................................................................................................ 2 7  
6. 3  
S C R E E NI N G V I SI T ............................................................................................................................ 2 7  

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 9  of 5 7  
* See a p pe n di x 6 . 0 
 
6. 4  
B AS ELI N E V I SI T/ EN T R Y F O O D C H ALL E N G E  .......................................................................................... 2 7  
6. 5  
S T U D Y T R E A T M E N T V I SI T S ............................................................................................................... 2 8  
6. 6  
D O U BL E B LI N D P L A C E B O C O N T R OLL E D F O O D C H ALL E N G E ( D B P C F C) ..................................................... 3 1  
6. 7  
S KI N P RI C K T E S TI N G  ........................................................................................................................ 3 2  
6. 8  
S ALI V A C OLL E C TI O N  ........................................................................................................................ 3 2  
6. 9  
S T O OL C OLL E C TI O N  ........................................................................................................................ 3 2  
6. 1 0  
V I SI T W I N D O WS ............................................................................................................................. 3 2  
6. 1 1  
S T U D Y B LI N DI N G A N D R A N D O MI Z A TI O N P R O C E D U R E S  .......................................................................... 3 3  
6. 1 1. 1  
R e q uir e m e nts f or U n bli n di n g  ............................................................................................. 3 3  
7.  
S A F E T Y M O NI T O RI N G  ................................................................................................................. 3 4  
7. 1  
P R O C E D U R E S A N D M O NI T O RI N G  ....................................................................................................... 3 4  
7. 2  
D E FI NI TI O NS  .................................................................................................................................. 3 4  
7. 2. 1  
A dv ers e Ev e nt ( A E) or M e dic al Ev e nt  ................................................................................. 3 4  
7. 2. 2  
S eri o us A dv ers e Ev e nt ( S A E)  ............................................................................................... 3 5  
7. 2. 3  
U n ex p ect e d A dv ers e Ev e nt  ................................................................................................. 3 5  
7. 3  
T O XI CI T Y G R A DI N G  ......................................................................................................................... 3 5  
7. 3. 1  
R el ati o ns hi p t o Pr oc e d ur e D efi niti o ns  ................................................................................ 3 6  
7. 4  
A D V E R S E E V E N T S C OLL E C TI O N P R O C E D U R E S  ....................................................................................... 3 7  
7. 4. 1  
R ec or di n g a n d R e p orti n g Pr oc e d ur es  ................................................................................. 3 7  
7. 4. 2  
S A E R ec or di n g a n d R e p orti n g  ............................................................................................. 3 8  
7. 5  
S E RI O US A D V E R S E E V E N T N O TI FI C A TI O N  ............................................................................................ 3 8  
7. 5. 1  
N otifyi n g t h e F D A, I R B, a n d DS M B  ..................................................................................... 3 8  
7. 5. 2  
R e p orti n g Crit eri a  ............................................................................................................... 3 8  
8.  
M E C H A NI S TI C A S S A Y S  ................................................................................................................ 3 9  
8. 1  
B L O O D S P E CI FI C IG E,  IG G,  IG G 4,  A N D IG A  ......................................................................................... 3 9  
8. 2  
S ALI V A R Y S P E CI FI C IG G,  IG A,  IG E,  A N D S E C R E T O R Y IG A  ........................................................................ 4 0  
8. 3  
C Y T O KI N E M E AS U R E M E N T S  .............................................................................................................. 4 0  
8. 4  
T R E G AS S A Y  ..................................................................................................................................... 4 0  
8. 5  
B AS O P HIL A C TI V A TI O N AS S A Y  ............................................................................................................ 4 0  
8. 6  
S T O OL  .......................................................................................................................................... 3 8  
9.  
S T A TI S TI C AL C O N SI D E R A TI O N S  ................................................................................................... 4 2  
9. 1  
S T U D Y E N D P OI N T A S S E S S M E N T ........................................................................................................ 4 2  
9. 1. 1  
Pri m ary E n d p oi nt  ............................................................................................................... 4 2  
9. 1. 2  
S ec o n d ary E n d p oi nts  .......................................................................................................... 4 2  
9. 2  
S U BJ E C T A N D D E M O G R A P HI C D A T A  ................................................................................................... 4 2  
9. 2. 1  
B as eli n e C h ar act eristics a n d D e m o gr a p hics  ...................................................................... 4 2  
9. 2. 2  
St u dy C o m pl eti o n  ............................................................................................................... 4 3  
9. 3  
IN T E RI M A N AL Y S E S T O E NS U R E P A TI E N T S A F E T Y  .................................................................................. 4 3  
1 0.  
I D E N TI FI C A TI O N A N D A C C E S S T O S O U R C E D A T A ..................................................................... 4 4  
1 0. 1  
D A T A M A N A G E M E N T  ...................................................................................................................... 4 4  

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 1 0  of 5 7  
* See a p pe n di x 6 . 0 
 
1 0. 2  
A C C E S S T O D A T A  ............................................................................................................................ 4 4  
1 1.  
Q U ALI T Y C O N T R OL A N D Q U ALI T Y A S S U R A N C E  ....................................................................... 4 5  
1 1. 1  
D A T A H A N DLI N G  ............................................................................................................................ 4 5  
1 2.  
E T HI C AL C O N SI D E R A TI O N S A N D C O M PLI A N C E WI T H G O O D CLI NI C AL P R A C TI C E  ..................... 4 6  
1 2. 1  
S T A T E M E N T OF C O M PLI A N C E  ........................................................................................................... 4 6  
1 2. 2  
INF O R M E D C O NS E N T A N D A S S E N T ..................................................................................................... 4 6  
1 2. 3  
P RI V A C Y A N D C O NFI D E N TI ALI T Y  ........................................................................................................ 4 6  
1 3.  
R E S O U R C E S H A RI N G  ............................................................................................................... 4 7  
 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 1 1  of 5 7  
* See a p pe n di x 6 . 0 
 
Gl oss ar y of A b bre vi ati o ns  
A E  
A d verse E ve nt  
C F R  
C o de of Fe deral Re g ulati o ns  
C R F  
Case Re p ort F or m  
C T C  
C o m m o n T o xicit y Criteria  
D B P C F Cs = O F C  
D o u ble -Bli n d, Place b o -C o ntr olle d F o o d C halle n ges  
D S M B  
Data Safet y M o nit ori n g B oar d  
E C  
Et hics C o m mittee  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
G C P  
G o o d Cli nical Practice  
I C H 
I nter nati o nal C o nfere nce o n Har m o nizati o n 
I D S 
I n vesti gati o nal Dr u g Ser vice 
I N D 
I n vesti gati o nal Ne w Dr u g A p plicati o n 
I R B 
I nstit uti o nal Re vie w B oar d 
I T 
I m m u n ot hera p y 
k U/ L  
Kil o u nits per Liter  
NI AI D  
Nati o nal I nstit ute of Aller g y a n d I nfecti o us Diseases  
OI T  
Oral I m m u n ot hera p y  
P B M C  
Peri p heral Bl o o d M o n o n uclear Cells  
PI  
Pri nci pal I n vesti gat or  
S A E  
Seri o us A d verse E ve nt  
S L I T 
S u bli n g ual I m m u n ot hera p y  
S P T  
S ki n Pric k Tests  
T Re g  
T re g ulat or y cell 
U N C -C H  
U ni versit y of N ort h Car oli na at C ha pel Hill  
U T S W  
U ni versit y of Te xas S o ut h wester n  
 
 
 
 
 
 
 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 1 2  of 5 7  
* See a p pe n di x 6 . 0 
 
1.  
B A C K G R O U N D A N D R A TI O N A L E  
1. 1  
B a c k g r o u n d  
Pea n ut aller g y is o ne of t he m ost c o m m o n f o o d aller gies; m ost c hil dre n de vel o p t his aller g y earl y 
i n life, d o n ot o ut gr o w it a n d are at ris k f or se vere a n d life-e n di n g a na p h ylactic reacti o ns.  T here 
is a critical nee d f or a pr oacti ve treat me nt f or pea n ut aller g y a n d we al o n g wit h ot hers are 
de vel o pi n g s pecific t y pes of i m m u n ot hera p y t hat will act as disease -m o dif yi n g t hera pies.  
Pr os pecti ve st u dies i n dicate t hat 6 -8 % of c hil dre n less t ha n 4 years of a ge e x perie nce I g E -
me diate d f o o d aller gic reacti o ns  [1 ], a n d a rece nt s ur ve y i n t he U. S. f o u n d t hat 1. 3 % of t he 
p o p ulati o n is aller gic t o pea n uts or tree n uts [2 ].  Des pite i ncrease d rec o g niti o n a n d 
u n dersta n di n g of f o o d aller gies, f o o d -i n d uce d a na p h yla xis is t he si n gle m ost c o m m o n f or m of 
a na p h yla xis see n i n h os pital e mer ge nc y de part me nts, acc o u nt i n g f or a b o ut o ne t hir d of 
a na p h yla xis cases see n [3 ].  It is esti mate d t hat a b o ut 3 0, 0 0 0 f o o d-i n d uce d a na p h ylactic e ve nts 
are see n i n U. S. e mer ge nc y de part me nts eac h year a n d t hat a b o ut 2 0 0 of t hese are ulti matel y 
fatal; eit her pea n uts or tree n uts ca use t he maj orit y of t hese deat hs [4 , 5 ].  Pri or trials of aller g y 
i m m u n ot hera p y (I T) usi n g tra diti o nal a n d r us h aller ge n pr ot oc ols i n patie nts wit h pea n ut aller g y 
s h o we d partial rates of res p o nse b ut, u nf ort u natel y, res ulte d i n hi g h rates of a d verse reacti o ns, 
i ncl u di n g a na p h yla xis [6 , 7 ].  R ece nt brea kt hr o u g h st u dies ha ve s h o w n s uccess i n dese nsitizi n g 
pea n ut -aller gic c hil dre n t o pea n ut via oral I T ( OI T) pr ot oc ols [8 , 9 ].  O ur gr o u p was t he first t o 
s h o w e vi de nce of dese nsitizati o n a n d t olera nce t o pea n ut wit h a s u bli n g ual ( S LI T) a p pr oac h [1 0 ]. 
1. 2  
R ati o n al e  
S u bc uta ne o us aller ge n i njecti o n I T is hi g hl y effecti ve i n caref ull y selecte d patie nts wit h I g E -
me diate d res pirat or y disease a n d i nsect sti n g aller g y, a n d re prese nts t he o nl y r o uti nel y 
a d mi nistere d a nti ge n -s pecific i m m u n o m o d ulat or y treat me nt gi ve n f or i m m u n ol o gic disease of 
a n y ki n d.  I T has bee n s h o w n t o be effecti ve f or ve n o m a na p h yla xis a n d f or aller gic r hi nitis a n d 
ast h ma ca use d b y i n hala nt aller ge ns , a n d c o nfers l o n g -ter m be nefit f or at least t hree years after 
disc o nti n uati o n  [1 1 ].  I n s pite of its effecti ve ness, t here re mai ns a si g nifica nt k n o wle d ge ga p 
re gar di n g t he u n derl yi n g basis f or aller ge n I T a n d t he de vel o p me nt of e ve nt ual t olera nce [1 2 ].  
Tra diti o nal aller ge n i njecti o n I T has n ot bee n s h o w n t o be effecti ve f or t he treat me nt of f o o d 
aller g y beca use of t he si g nifica nt si de effects of t he t hera p y relate d t o s yste mic aller gic e ffects 
[6 , 7 ]. 
Alt h o u g h its use has bee n li mite d i n t he U nite d States, S LI T has bee n use d c o m m o nl y i n E ur o pe 
as a n alter nati ve t o S CI T f or aller gic r hi nitis.   It offers a n o vel mea ns of treat me nt f or f o o d 
aller g y a n d see ms well s uite d f or se veral reas o ns.   First, oral La n ger ha ns cells t hat ta ke u p 
a nti ge n wit hi n t he m o ut h ha ve bee n s h o w n t o ha ve t oler o ge nic pr o perties, p ote ntiall y acc o u nti n g 
f or t he efficac y of aer oaller ge n S LI T  [1 3 ].  Sec o n d, S LI T is easil y a d mi nistere d, es peciall y w he n 
c o m pare d wit h recei vi n g i njecti o ns, s uc h as wit h S CI T, or i n gesti n g lar ge a m o u nts of f o o d, as 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 1 3  of 5 7  
* See a p pe n di x 6 . 0 
 
wit h OI T a n d is m uc h safer.  Fi nall y, s yste mic reacti o ns ha ve bee n u nc o m m o n  [1 4 ], w hic h mi g ht 
be sec o n dar y t o t he relati vel y s mall d oses use d t o ac hie ve cli nical efficac y.  T his a p pears t o gi ve 
S LI T a fa v ora ble si de effect pr ofile, w he n c o m pare d t o ot her I T a p pr oac hes.  
T he pr o p ose d st u d y  is hi g hl y i n n o vati ve i n t he f oll o wi n g wa ys: ( 1 ) U ni q ue e m p hasis o n t he 
ne wl y dia g n ose d y o u n g pea n ut -aller gic p o p ulati o n, w h o ma y be m ore s uita ble f or t olera nce 
i n d ucti o n, (2 ) Mec ha nis ms of bas o p hil h y p ores p o nsi ve ness d uri n g t he earl y sta ges ( da ys t o 
wee ks) o f S LI T a n d later d uri n g mai nte na nce p hase of S LI T; p ossi bl y deli neati n g dese nsitizati o n 
vers us l o n g -li ve d t olera nce (I g G-me diate d or i n v ol ve me nt of S y k or b ot h), ( 3 ) Tec h n ol o g y bei n g 
use d t o i n vesti gate, f or t he first ti me, c ha n ges i n fre q ue ncies a n d p he n o t y pes of C D 4 T cells 
d uri n g t he c o urse of S LI T, a n d ( 4 ) E pit o pe s pecificities of aller ge n-s pecific I g E, G 4, a n d I g A i n 
bl o o d  a n d sali va. 
O n g oi n g St u dies  
T hr o u g h t he e n d of A pril 2 0 1 3, t here were 3 3 acti ve s u bjects a n d 9 c o m plete d s u bjects a ge d 1 - 
1 1 years i n t he first bli n de d pr ot oc ol of pea n ut S LI T ( A D o u ble-bli n de d, Place b o -c o ntr olle d 
St u d y of Pea n ut S u bli n g ual I m m u n ot hera p y i n C hil dre n, cli nicaltrials. g o v # N C T 0 0 5 9 7 7 2 7).  
T his st u d y, usi n g a pe a n ut S LI T mai nte na nce d ose of 2 m g, is place b o -c o ntr olle d t hr o u g h t he 
first 1 2 m o nt hs of t hera p y, a n d t he n a f o o d c halle n ge is perf or me d t o assess efficac y; t he i nteri m 
res ults of t his i nitial e n d p oi nt ha ve bee n p u blis he d [1 0 ], de m o nstrati n g statisticall y si g nifica nt 
dese nsitizati o n a n d i m m u ne m o d ulati o n i n t he acti ve gr o u p c o m pare d t o t he place b o gr o u p.  It 
s h o ul d be n ote d t hat t here was a wi de ra n ge of reacti o n t hres h ol ds i n t he treat me nt gr o u p 
s u g gesti n g t hat t he dese nsitizati o n effect at t he 1 2-m o nt h ti me p oi nt was o nl y partial.   T he 
pri mar y si de effect re p orte d was tra nsie nt m o ut h or or o p har y n geal itc hi n g a n d n o e pi ne p hri ne 
a n d o nl y rare di p he n h y dra mi ne was use d d uri n g h o me or o bser ve d d osi n g de m o nstrati n g t he 
safet y of t he S LI T treat me nt.  
T hese preli mi nar y res ults s h o w t hat pea n ut S LI T is ver y safe, eas y t o use, a n d ca n i n d uce cli nical 
dese nsitizati o n wit h ass ociate d i m m u n ol o gic c ha n ges i n mast cell, bas o p hil, a n d T cell res p o nses 
t o pea n ut wit hi n 1 2 m o nt hs. 
A sec o n dar y e n d p oi nt of t he st u d y was t o deter mi ne t he perce nta ge of pea n ut -aller gic patie nts 
t hat de vel o p t olera nce t o pea n ut after 3 6 m o nt hs of treat me nt as defi ne d b y passi n g a pea n ut oral 
f o o d c halle n ge 1 m o nt h after disc o nti n ui n g S LI T t hera p y.  T he first 1 2 patie nts t o reac h t his ti me 
p oi nt u n der we nt pea n ut oral f o o d c halle n ges t o d o u ble t he a m o u nt of pea n ut ( 4 4 4 3  m g) 
pre vi o usl y teste d w hile still o n treat me nt.  Si x  of t hese patie nts ( 5 0 %) s uccessf ull y c o m plete d 
t his f o o d c halle n ge a n d were c o nsi dere d f ull y dese nsitize d.  After 1 m o nt h off of t hera p y, 5 of 
t hese 6 patie nts ( 4 2 % of t otal) a gai n s uccessf ull y c o m plete d a n i de ntical pea n ut oral f o o d 
c halle n ge a n d were c o nsi dere d t olera nt.  T he 6 patie nts w h o were n ot f ull y dese nsitize d after 3 6 
m o nt hs of treat me nt all c o ns u me d m ore pea n ut t ha n at t he 1 2 -m o nt h ti me p oi nt ( me dia n 3 7 5 0 
m g; ra n ge 1 7 5 0 –  3 7 5 0 m g).  T hree  of t hese partiall y dese nsitize d patie nts o pte d t o c o nti n ue 
S LI T t hera p y.  T his u n p u blis he d data was prese nte d at t he 2 0 1 3 A A A AI a n n ual meeti n g i n 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 1 4  of 5 7  
* See a p pe n di x 6 . 0 
 
Marc h [1 5 ].  Mec ha nistic st u dies o n t his s mall c o h ort of s u bjects i n dicate d t hree ke y fact ors i n 
t he t olera nt gr o u p vers us t he n o n-t olera nt gr o u p.  First, t hese s u bjects ha d l o wer pea n ut -s pecific 
I g E at baseli ne ( me dia n t olera nt 1 4. 0 k U/ L, n o n-t olera nt 4 0. 4 k U/ L) a n d at 3 6 m o nt hs ( me dia n 
t olera nt 6. 1 8 k U/ L, n o n-t olera nt 2 0. 1 k U/ L; Sec o n d, t olera nt s u bjects ha d l o wer I g E a gai nst Ara 
h 1 a n d Ara h 2 b ot h at baseli ne a n d at 3 6 m o nt hs  [1 6 ]; T hir d, t olera nt s u bjects ha d l o wer 
bas o p hil acti vati o n i n res p o nse t o f o ur l o g -f ol d d oses of pea n ut a nti ge n i n a n e x vi v o assa y [1 7 ]. 
T hese fi n di n gs are i m p orta nt si nce it has bee n s h o w n t hat t he f o o d-s pecific I g E le vels are l o wer 
i n y o u n ger c hil dre n (see disc ussi o n bel o w) s uc h t hat t hese s u bjects ma y ha ve a hi g her li keli h o o d 
of de vel o pi n g t olera nce via S LI T t ha n t he s u bjects e val uate d a n d re p orte d at A A A AI 2 0 1 3.  
I n s u m mar y, o ur preli mi nar y data s u g gests t hat pea n ut S LI T has t he p ote ntial f or f ut ure use as a  
treat me nt t o pr otect a gai nst acci de ntal e x p os ures a n d reacti o ns i n pea n ut-aller gic c hil dre n, a 
fi n di n g wit h si g nifica nt cli nical i m pact.  I n a d diti o n, t olera nce ma y be p ossi ble i n s u bjects o n 
l o n g-ter m pea n ut S LI T wit h l o wer pea n ut-s pecific a n d pea n ut-c o m p o ne nt I g E a n d bas o p hil 
res p o nses, fi n di n gs e x pecte d i n y o u n ger, ne wl y dia g n ose d aller gic patie nts, p ossi bl y pre dicti ve 
of s uccessf ul t ole ra nce i n d ucti o n.  
E arly Life I m m u ne Res p o nses t o Pe a n ut  
T here is n o w e vi de nce fr o m m ulti ple st u dies [1 8 -2 0 ] t hat i m m u nit y t o pea n ut c o m me nces i n t he 
first year of life.  H o we ver, t he nasce nt T cell res p o nses i n t hese c hil dre n a p pear t o be wea k [2 0 ], 
re q uiri n g years t o f ull y mat ure [2 1 ]; a n d si milarl y, i n a rece nt st u d y of o ver 7 0 0 pea n ut-aller gic 
c hil dre n f oll o we d i n a tertiar y care ce nter, pea n ut -I g E le vels te n de d t o start l o w a n d i ncrease o ver 
t he first fi ve years of life bef ore reac hi n g stea d y-state [2 2 ].  T he c urre nt pr o p osal  will test S LI T 
as a n earl y i nter v e nti o n d uri n g t his de vel o p me ntal peri o d b y f oc usi n g recr uit me nt o n c hil dre n 
a ge d 1-4 years .  T his s h orte ns t he peri o d of dietar y a v oi da nce, mi ni mizes ris k of a na p h yla xis, 
a n d be gi ns treat me nt at l o wer I g E le vels, w hic h i n pre vi o us st u dies was ass ociate d wit h 
i m pr o ve d cli nical o utc o mes.  T his earl y i nter ve nti o n c o nce pt  is c urre ntl y bei n g pil ote d i n a n 
o n g oi n g st u d y of OI T f or y o u n g pea n ut -aller gic c hil dre n t hat use s t he sa me e ntr y criteria.  It has 
bee n  s h o w n t hat recr uit me nt of s uc h a y o u n g p o p ulati o n is n ot o nl y feasi ble, b ut acc o m plis hes a 
maj or g oal of t he strate g y b y esta blis hi n g a c o h ort wit h l o wer baseli ne pea n ut-s pecific I g E le vels 
t ha n i n pre vi o us st u dies [2 3 ].  I n a d diti o n, it has bee n s h o w n t hat earl y i nter ve nti o n 
i m m u n ot hera p y has a s u peri or safet y pr ofile, ver y hi g h rete nti o n rates, e nc o ura gi n g preli mi nar y 
cli nical res ults, a n d i m m u n o m o d ulat or y effects si milar t o pre vi o us trials [2 4 ].  Q ualitati vel y, it 
has bee n  o bser ve d t hat y o u n g c hil dre n are e xcelle nt st u d y partici pa nts w h o r ea dil y c o ns u me t heir 
d oses wit h o ut  t he a versi o ns t hat li mit t he partici pati o n of ol der s u bjects i n t his t y pe of 
i m m u n ot hera p y researc h.  T his is t he first pr oject t o a p pl y t hese i n n o vati ve c o nce pts t o a S LI T 
trial.  T he e xcelle nt safet y pr ofile of pea n ut S LI T ma kes it a ver y attracti ve ca n di date f or t hera p y, 
b ut t o date t he cli nical efficac y has bee n varia ble i n st u dies of ol der c hil dre n a n d a d ults.  B y 
tar geti n g y o u n g c hil dre n, we ai m t o i nterr u pt o n g oi n g aller gic pri mi n g pri or t o t he i nte nsificati o n 
of t h e I g E a n d T H 2 me m or y res p o nse, w hic h i n m ost pea n ut -aller gic c hil dre n will persist 
t hr o u g h o ut life.  I n d oi n g s o, we belie ve t hat earl y i nter ve nti o n i m m u n ot hera p y will be safer a n d 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 1 5  of 5 7  
* See a p pe n di x 6 . 0 
 
m ore s uccessf ul i n re pr o gra m mi n g relati vel y wea k i m m u ne res p o nses t o pea n ut , t h us i ncreasi n g 
t he li keli h o o d of t olera nce i n d ucti o n.  T hese n o vel c o nce pts e xte n d t he a d v a nces of first -
ge ner ati o n S LI T pil ot st u dies a n d pr o mise t o re defi ne t he c urre nt st a n d ar d of c are.  
1. 3  
R ati o n al e f o r S el e cti o n of St u d y P o p ul ati o n  
S u bjects bet wee n 1 2  a n d 4 8  m o nt hs of a ge  w h o ha ve bee n dia g n ose d wit h pea n ut aller g y base d 
o n a c o n vi nci n g cli nical hist or y of pea n ut aller g y a n d a n  I g E [ U ni C A P T M] t o pea n ut of > 0. 3 5 
k U A / L a n d a p ositi ve s ki n pric k test t o pea n ut ( > 3 m m t ha n t he ne gati ve c o ntr ol) or w h o are 
se nsitize d t o pea n ut ( base d o n an  I g E [ U ni C A P T M] of > 5 k UA / L a n d a p ositi ve s ki n pric k test t o 
pea n ut ( > 3 m m t ha n t he ne gati ve c o ntr ol) a n d n o k n o w n hist or y of i n gesti o n of pea n ut  will be 
e nr olle d.  T he a ge gr o u p f or st u d y was selecte d base d o n all t he pre vi o us st u dies o n a n y t y pe of 
I T f or f o o d aller g y ha vi n g s h o w n t hat t he s u bjects w h o beca me t olera nt te n de d t o be y o u n ger a n d 
ha d l o wer pea n ut I g E le vels at t he be gi n ni n g of t he st u d y.   
1. 4  
K n o w n a n d P ot e nti al Ris ks a n d B e n efits t o H u m a n P a rti ci p a nts  
1. 4. 1  Ris ks  
T he b uil d -u p a n d dail y mai nte na nce d oses of S LI T ma y ca use aller gic s y m pt o ms i ncl u di n g 
s neezi n g, r hi n orr hea, urticaria, a n gi oe de ma, fl us hi n g, flares of ecze ma, oc ular, nasal, oral a n d/ or 
t hr oat pr urit us, t hr oat ti g ht ness, na usea, v o miti n g, a b d o mi nal disc o mf ort, c o u g h, w heezi n g, 
a n d/ or s h ort ness of breat h i n a d diti o n t o se vere a na p h yla xis.  T he m ost c o m m o n s y m pt o m 
ass ociate d wit h S LI T d osi n g is or o p har y n geal itc hi n g  prese nt i n 9. 3 % of all d os es.  T o date, n o 
s u bject i n t he o n g oi n g S LI T st u d y has ha d d osi n g -relate d a na p h yla xis re q uiri n g treat me nt wit h 
e pi ne p hri ne  [1 0 ].  T he li keli h o o d of a s u bject e x perie nci n g aller gic s y m pt o ms will be lesse ne d 
b y starti n g at s mall a m o u nts of t he pea n ut pr otei n f or d osi n g per t he S LI T pr ot oc ol.   
D o u ble -bli n d, place b o -c o ntr olle d f o o d c halle n ges ( D B P C F C)  ma y i n d uce a n aller gic res p o nse  
wit h s y m pt o ms si milar t o t h ose descri be d f or S LI T d osi n g .  T he ris k of a se vere aller gic reacti o n 
is re d uce d b y c o n d ucti n g t he c halle n ge i n a m o nit ore d cli nic setti n g, i nitiati n g t he c halle n ge wit h 
a ver y s mall a m o u nt of t he f o o d, gra d uall y i ncreasi n g t he d os e, a n d st o p pi n g t he c halle n ge at t he 
first si g n of a reacti o n.  If s u bjects ha ve a n aller gic reacti o n d uri n g t he c halle n ges, t he y ma y nee d 
oral  or  i ntra m usc ular me dicati o ns.  Trai ne d pers o n nel, i ncl u di n g a p h ysicia n, as well as 
me dicati o ns a n d e q ui p me nt, w ill be i m me diatel y a vaila ble t o treat a n y reacti o n. 
Ot her ris ks i ncl u de t h ose relate d t o bl o o d dra wi n g a n d s ki n testi n g.  Bl o o d dra wi n g ma y 
a g gra vate a pre -e xisti n g a ne mic c o n diti o n, b ut t his ris k is mi ni mize d b y restricti n g t he v ol u me 
dra w n t o a ma xi m u m o f 3 ml /k g i n acc or da nce wit h U nite d States De part me nt of Healt h a n d 
H u ma n Ser vices rec o m me n dati o ns.  A d diti o nal ris ks are t h ose atte n da nt t o a n y nee dle p u nct ure, 
i ncl u di n g sli g ht br uisi n g, l ocal i nfecti o n, or t he p ossi bilit y of t he s u bject fai nti n g.  S ki n pric k 
tests ( n ot i ntra der mal) will be perf or me d b y tec h ni q ues reflecti n g ge neral sta n dar d of care a n d 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 1 6  of 5 7  
* See a p pe n di x 6 . 0 
 
ca use mi ni mal disc o mf ort (t he se nsati o n of a scratc h a n d a pr uritic, tra nsie nt hi ve ma y res ult).  
S uc h tests c o ul d t he oreticall y i n d uce a s yste mic aller gic reacti o n, b ut t his is e xcee di n gl y rare.  
1. 4. 2  B e n efits   
 
T he i m me diate be nefits f or t he s u bject i ncl u de t he p ossi bilit y of a decrease i n cli nical reacti vit y 
t o pea n ut a n d di mi nis he d aller gic reacti o n f oll o wi n g a n acci de ntal i n gesti o n of pea n ut, as well as 
t he p ossi bilit y of alteri n g t he nat ural c o urse of t he pea n ut aller g y.  A d diti o nall y, s u bjects ma y 
bec o me cli nicall y a n d i m m u n ol o gicall y t olera nt t o pea n ut, w hic h is ot her wise n ot li kel y t o 
ha p pe n.  S h o ul d t olera nce occ ur, s u bjects w o ul d ha ve t he a bilit y t o br oa de n t heir diet a n d 
e x perie nce a n i m pr o ve d q ualit y of life  wit h o ut t he restricti o ns i m p ose d b y a life-t hreate ni n g f o o d 
aller g y.  T his st u d y will als o hel p t o e x pa n d t he k n o wle d ge of f o o d aller g y i n ge neral a n d ma y 
lea d t o ne w ma na ge me nt a n d t hera pe utic pr ot oc ols f or i n di vi d uals wit h ot her f o o d aller gies. 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 1 7  of 5 7  
* See a p pe n di x 6 . 0 
 
2.  
O B J E C T I V E S  
2. 1  
P ri m a r y a n d S e c o n d a r y O bj e cti v es  
O ur ce ntr al hy p ot hesis  is t hat pea n ut S LI T as a n earl y i nter ve nti o n will i n d uce cli nical 
dese nsitizati o n  i n 8 0 % of s u bjects after 3 6  m o nt hs of t hera p y.  We will a d dress o ur h y p ot hesis 
t hr o u g h i n vesti gati o ns f oc use d o n t he f oll o wi n g o bjectives :  
O bjecti ve # 1: T o deter mi ne if 3 6  m o nt hs of pea n ut S LI T as a n earl y i nter ve nti o n i n s u bjects a ges 
1 t o 4 years i n d uces cli nical dese nsitizati o n .  
O bjecti ve # 2: T o e xa mi ne t he c ha n ge i n i m m u ne para meters ass ociate d wit h pea n ut S LI T a n d t he 
d e vel o p me nt of cli nical dese n sitizati o n.  
Pri m ary o bjective:   
T o deter mi ne if 3 6  m o nt hs of pea n ut S LI T as a n earl y i nter ve nti o n i n s u bjects a ges 1 t o 4 years 
i n d uces cli nical dese nsitizati o n .  T he pri m ary o utc o me  of t his o bjecti ve will be a statisticall y 
si g nifica nt differe nce i n c halle n ge sc ore s bet wee n  t he treat me nt gr o u p vers us t he place b o gr o u p 
d uri n g D B P C F C  perf or me d after 3 6 m o nt hs of pea n ut S LI T  (dese nsitizati o n ).  A sec o n d ary 
o utc o me  of t his o bjecti ve will be a statisticall y si g nifica nt differe nce i n t he c halle n ge sc ore  of t he 
treat me nt gr o u p vers us t he place b o gr o u p d uri n g t he D B P C F C perf or me d 3 m o nt hs after 
disc o nti n ui n g t hera p y (t olera nce). 
P ur p ose a n d ex pect ati o ns :   
T his o bjecti v e is desi g ne d t o test t he effecti ve ness of usi n g pea n ut S LI T as a n earl y i nter ve nti o n 
t o i n d uce cli nical dese nsitizati o n  i n pea n ut aller gic c hil dre n.  We e x pect t o de m o nstrate t he 
i n d ucti o n of dese nsitizati o n  b y s h o wi n g t hat s u bjects w h o ha ve c o m plete d 3 6  m o nt hs of 
treat me nt will ha ve si g nifica ntl y hi g her c halle n ge sc ores  o n D B P C F C c o m pare d t o s u bjects 
ra n d o mize d t o place b o.  Details of t his statistical a nal ysis are descri be d i n secti o n 9 bel o w.  
T he st u dies u n der O bjecti ve # 1 will deter mi ne t he efficac y of utilizi n g S LI T t o i n d uce 
dese nsitizati o n  i n y o u n g, ne wl y dia g n ose d pea n ut aller gic s u bjects.  At prese nt, strict dietar y 
a v oi da nce of f o o d aller ge ns a n d rea d y access t o self -i njecta ble e pi ne p hri ne is t he sta n dar d of care 
f or f o o d aller g y.  H o we ver, the u bi q uit y of pea n ut c o ntai ni n g f o o ds ma kes a v oi da nce diffic ult 
a n d t he p ossi bilit y of i na d verte nt i n gesti o n great.  W hile it has bee n s h o w n t hat dail y d osi n g wit h 
pea n ut S LI T res ults i n dese nsitizati o n a n d li kel y pr o vi des li mite d pr otecti o n fr o m acci de ntal 
pea n ut i n gesti o n [1 0 ], t hese res ults were q uite varia ble.  T his st u d y will de m o nstrate w het her 
pea n ut S LI T ca n ha ve a m ore r o b ust effect i n y o u n ger, ne wl y -dia g n ose d s u bjects.  T he st u d y will 
als o i n vesti gate w het her pea n ut S LI T ma y als o pr o vi de a n a ve n ue t o ca use pea n ut aller gic 
i n di vi d uals t o l ose t heir aller gic reacti vit y t o pea n uts (t olera nce).  
Sec o n d ary O bjectives:  

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 1 8  of 5 7  
* See a p pe n di x 6 . 0 
 
O bjective # 2 : T o e xa mi ne t he c ha n ge i n i m m u ne para meters ass ociate d wit h pea n ut S LI T a n d t he 
de vel o p me nt of cli nical t olera nce.  
P ur p ose a n d Ex pect ati o ns:  
T hr o u g h O bjecti ve # 2, we will see k t o u n dersta n d t he m olec ular pr ocesses b y w hic h S LI T 
affects t he i m m u ne s yste m t hr o u g h e val uati o n of i m m u ne mec ha nis ms i n relati o ns hi p t o cli nical 
fi n di n gs of dese nsitizati o n a n d t olera nce.  We will de li neate t he i m pact of pea n ut S LI T o n t he 
s u bse q ue nt cell ular a n d h u m oral res p o nses t o pea n ut pr otei n: 1) pea n ut s pecific I g E, I g G, a n d 
I g G 4 res p o nse, 2) pea n ut  s pecific bas o p hil acti vati o n, 3) mast cell res p o nses t hr o u g h s ki n pric k  
testi n g, a n d 4) s pecific T-cell c yt o ki ne res p o nses a n d T re g ulat or y cell ( TRe g ) acti vati o n.  We 
a ntici pate t hat t he effect of pea n ut S LI T will occ ur b y i n d ucti o n of T Re gs , c o n versi o n of T cells 
fr o m a n aller gic ( TH 2) t o a n o n -aller gic ( TH 1) l y m p h oc yte res p o nse ( meas ure d b y c yt o ki nes, 
a nti b o d y le vels, a n d s ki n pr ic k test size), a c ha n ge i n pea n ut-s pecific bas o p hil acti vati o n, or 
t hr o u g h a c o m bi nati o n of t he a b o ve .   
Base d o n mec ha nistic st u dies of s u bc uta ne o us i m m u n ot hera p y f or aller gic r hi nitis [1 2 ], OI T f or 
f o o d aller gies [8 ], a n d pre vi o us w or k wit h S LI T f or pea n ut aller gies [1 0 ], our e x pectati o n is t hat 
t he i m m u n o gl o b uli n res p o nse will c ha n ge o ver ti me  res ulti n g i n a decrease i n pea n ut-s pecific 
I g E a n d a n i ncrease i n pea n ut -s pecific I g G a n d I g G 4.  We a ntici pate a n i ncrease i n TRe g   s pecific 
c yt o ki nes, s uc h as I L -1 0 a n d T G F -beta, t hat will parallel earl y cli nical res p o nses a n d i n dicate 
i m m u ne de viati o n t o war d t olera nce.  T he c o n versi o n fr o m TH 2 t o T H 1 c yt o ki ne res p o nses 
w o ul d ha ve a si milar cli nical effect of ma ki n g a s u bject less se nsiti ve t o pea n uts, b ut t his w o ul d 
li kel y occ ur t hr o u g h a n alter nati ve mec ha nis m or a mec ha nis m c o m bi ni n g TRe g  acti vati o n wit h 
ot her T cell c ha n ges.  A c ha n ge i n bas o p hil acti vati o n w o ul d i n dicate t hat s u bjects w o ul d be less 
se nsiti ve t o pea n ut, a n d we a ntici pate t hat res p o nse w o ul d be i n parallel t o t he fi n di n g of cli nical 
dese nsitizati o n b ut ma y n ot i n dicate cli nical t olera nce de vel o p me nt.  O verall, we will assess 
t hese im m u ne para meters o ver ti me a n d i n c o nj u ncti o n wit h cli nical le vels of reacti vit y t o 
deter mi ne w hic h mec ha nis m(s) is rele va nt f or effecti ve pea n ut S LI T i n dese nsitizati o n a n d 
ulti matel y t olera nce.  F oll o wi n g c ha n ges i n t he i m m u ne para meters of t he place b o s u bjects will 
be t he m ost i nf or mati ve a n d ma y pr o vi de i nsi g ht i nt o s pecific i m m u ne mar kers t hat heral d t he 
l oss of dese nsitizati o n or t he de vel o p me nt of cli nical t olera nce.  
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 1 9  of 5 7  
* See a p pe n di x 6 . 0 
 
3.  
S T U D Y D E S I G N  
T his S LI T st u d y is  a ra n d o mize d, bli n de d, place b o -c o ntr olle d st u d y bas e d o n o ur pre vi o us 
e x perie nce at D u ke U ni versit y Me dical Ce nter a n d t he U ni versit y of N ort h Car oli na at C ha pel  
H ill usi n g OI T a n d S LI T i n f o o d aller gic s u bjects.  T he st u d y will e nr oll 5 0  c hil dre n a ges 1 t o 4 
years wit h pea n ut aller g y.  U p o n e nr oll me nt i nt o t he st u d y, all s u bjects will u n der g o a  q ualif yi n g  
e ntr y D B P C F C t o 1 0 0 0  m g  of pea n ut pr otei n t o c o nfir m t he dia g n osis of pea n ut aller g y  a n d 
esta blis h a baseli ne t hres h ol d le vel .  F oll o wi n g a p ositi ve D B P C F C , eac h s u bject will be 
ra n d o mize d 1: 1 t o recei ve pea n ut S LI T t hera p y vers us place b o. St u d y dr u g d osi n g will be gi n at a 
starti n g d ose of 1 p u m p of a 1:1 0 0  dil uti o n of pea n ut S LI T or place b o  (2 . 5 mc g pea n ut pr otei n  or 
place b o ).  D uri n g t he b uil d-u p p hase , w hic h lasts a p pr o xi matel y 2 0  wee ks  ( Ta ble 1), s u bjects 
will d ose dail y a n d i ncrease t he n u m ber of p u m ps e ver y 1 -2 wee ks as per t he d osi n g sc he d ule.  
S u bjects will ret ur n t o t he researc h u nit f or o bser ve d d osi n g wit h eac h c ha n ge i n st u d y dr u g 
dil uti o n  ( 1:1 0 0, 1 :1 0, 1: 1 ) a n d wit h e ver y ot her d ose i ncrease o n 1: 1  u ntil t he mai nte na nce d ose 
of 1 6  p u m ps of 1: 1  st u d y dr u g ( 40 0 0 mc g pea n ut pr otei n  or place b o ) is ac hie ve d.  S u bjects will 
t he n c o nti n ue dail y a d mi nistrati o n of t he mai nte na nce d ose a n d ret ur n e ver y 6 m o nt hs f or foll o w -
u p.  After 3 6  m o nt hs *  of treat me nt, s u bjects will u n der g o a D B P C F C t o 4 4 4 3  m g  of pea n ut 
pr otei n t o assess f or  dese nsitizati o n.  All s u bjects  will t he n disc o nti n ue pea n ut  S LI T  or place b o 
t hera p y f or 3  m o nt hs .  T h ose s u bjects w h o are a ble t o t olerate >  4 4 3 m g of pea n ut pr otei n at t he 
3 6 m o nt h *  D B P C F C will be as ke d t o  ret ur n f or a D B P C F C  at 3 9 m o nt hs *  ( or 3 m o nt hs after t he 
i nitial D B P C F C) t o t he a m o u nt of pea n ut pr otei n pre vi o usl y t olerate d at t he 3 6 m o nt h*  D B P C F C  
t o assess f or t olera nce.  All s u bjects will be u n bli n de d after t he t olera nce D B P C F C a n d will ha ve 
c o m plete d t he st u d y.   S u bjects u na ble t o t olerate >  4 4 3 m g of pea n ut pr otei n at t he 3 6 m o nt h 
D B P C F C will be  u n bli n de d a n d  gi ve n t he o pti o n t o strictl y a v oi d all pea n uts or, if a p pr o priate, 
be offere d a f o o d e q ui vale nt.    
* See C O VI D safet y meas ure i nf or mati o n i n A p pe n di x 6  
3. 1  
St u d y E n d p oi nts   
3. 1. 1  P ri m a r y E n d p oi nt  
T he pri m ary o utc o me  of t his st u d y will be a statisticall y si g nifica nt differe nce i n t he c halle n ge 
sc ore of t he treat me nt gr o u p vers us t he place b o gr o u p d uri n g D B P C F C after 3 6 m o nt hs of pea n ut 
S LI T  (dese nsitizati o n ). 
3. 1. 2  S e c o n d a r y E n d p oi nt s  
T he sec o n dar y o utc o me meas ures are as f oll o ws:  
1.  A stati sticall y si g nifica nt differe nce i n t he c halle n ge sc ore of t he treat me nt gr o u p vers us 
t he place b o gr o u p d uri n g t he D B P C F C perf or me d 3 m o nt hs after disc o nti n ui n g t hera p y  
(t olera nce). 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 2 0  of 5 7  
* See a p pe n di x 6 . 0 
 
2.  T he c ha n ge i n i m m u ne para meters o ver ti me ass ociate d wit h t he i n d ucti o n of cli nical 
dese nsitizati o n  c o m pare d t o t he fail ure t o ac hie ve cli nical dese nsitizati o n .  T hese i ncl u de 
h u m oral res p o nses, bas o p hil/effect or cell res p o nses, a n d c yt o ki ne res p o nses t o p ea n uts. 
3.  I nci de nce of all seri o us a d verse e ve nts d uri n g t he st u d y. 
 
3. 2  
C rit e ri a f o r P r e m at u r e T e r mi n ati o n of t h e St u d y: St u d y St o p pi n g R ul es  
T he st u d y will be st o p pe d a n d will u n der g o a n e x pe dite d re vie w b y t he Pri nci pal I n vesti gat or , 
I R B, a n d data safet y m o nit ori n g b oar d ( D S M B) if a n y of t he f oll o wi n g occ urs:  
•  A n y deat h relate d t o pea n ut S LI T d osi n g  
•  M ore t ha n 2 se vere a na p h ylactic reacti o n relate d t o pea n ut S LI T d osi n g at a n y sta ge of 
t he pr ot oc ol 
•  M ore t ha n 3 s u bjects w h o re q uire m ore t ha n 1 i njecti o n of i ntra m usc ular e pi ne p hri ne 
d uri n g d ose escalati o n or mai nte na nce d osi n g of t he pea n ut st u d y pr o d uct  
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 2 1  of 5 7  
* See a p pe n di x 6 . 0 
 
4.  
S E L E C T I O N A N D W
I T H D R A W A L O F P A R T I C I P A N T S  
4. 1  
I n cl usi o n C rit e ri a  
S u bjects w h o meet all  of t he f oll o wi n g criteria are eli gi ble f or e nr oll me nt as st u d y partici pa nts:  
•  Writte n i nf or me d c o nse nt fr o m partici pa nt’s pare nt/ g uar dia n . 
•  A ge 1 2 -4 8 m o nt hs of eit her se x, a n y race, a n d a n y et h nicit y. 
•  1) A pea n ut aller g y dia g n osis wit h a c o n vi nci n g cli nical hist or y of pea n ut aller g y A N D  a 
pea n ut -s pecific I g E [ U ni C A P] >  0. 3 5  k U A / L A N D  a p ositi ve s ki n pric k test t o pea n ut ( > 3 
m m t ha n t he ne gati ve c o ntr ol) O R  2 ) are se nsitize d t o pea n ut ( base d o n a n  I g E [U ni C A P] 
t o pea n ut of >  5 k U A / L) A N D  a p ositi ve s ki n pric k test t o pea n ut ( >  3 m m t ha n t he 
ne gati ve c o ntr ol) A N D  n o k n o w n hist or y of i n gesti o n of pea n ut.  
•  A p ositi ve D B P C F C t o 1 0 0 0 m g of pea n ut at e nr oll me nt. 
4. 2  
E x cl usi o n C rit e ri a  
S u bjects w h o meet a ny of t hese criteria are n ot  eli gi ble f or e nr oll me nt as st u d y partici pa nts:  
•  H ist or y of se vere a na p h yla xis t o pea n ut, defi ne d as h y p o xia, h y p ote nsi o n, or ne ur ol o gic 
c o m pr o mise (c ya n osis or S p O 2 < 9 2 % at a n y sta ge, h y p ote nsi o n, c o nf usi o n, c olla pse or 
l oss of c o nsci o us ness). 
•  Partici pati o n i n a n y i nter ve nti o nal st u d y f or t he treat me nt of f o o d aller g y i n t he past 6 
m o nt hs.  
•  K n o w n oat, w heat, or gl yceri n aller g y.  
•  E osi n o p hilic or ot her i nfla m mat or y (e. g. celiac) gastr oi ntesti nal diseas e. 
•  Se vere ast h ma ( 2 0 0 7 N H L BI Criteria Ste ps 5 or 6 –  A p pe n di x 2).  
•  I na bilit y t o disc o nti n ue a nti hista mi nes f or s ki n testi n g a n d D B P C F Cs. 
•  Use of o maliz u ma b or ot her n o n -tra diti o nal f or ms of aller ge n i m m u n ot hera p y (e. g., oral 
or s u bli n g ual) or i m m u n o m o d ulat or  t hera p y ( n ot i ncl u di n g c ortic oster oi ds) or bi ol o gic 
t hera p y wit hi n t he past year. 
•  Use of b eta-bl oc kers ( oral), a n gi ote nsi n -c o n verti n g e nz y me ( A C E) i n hi bit ors, 
a n gi ote nsi n -rece pt or bl oc kers ( A R B) or calci u m c ha n nel bl oc kers. 
•  Si g nifica nt me dical c o n diti o n ( e. g., li ver, ki d ne y, gastr oi ntesti nal, car di o vasc ular, 
he mat ol o gic, or p ul m o nar y disease) t hat w o ul d ma ke t he s u bject u ns uita ble f or i n d ucti o n 
of f o o d reacti o ns.  
4. 3  
P r e m at u r e P a rti ci p a nt T e r mi n ati o n f r o m t h e St u d y  
4. 3. 1  C rit e ri a  
N o s u bject i nitiati n g t hera p y i n t hi s trial will be re place d. 
Partici pa nts ma y be re m o ve d fr o m t his st u d y if:  

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 2 2  of 5 7  
* See a p pe n di x 6 . 0 
 
•  Si g nifica nt cli nical s y m pt o ms (res pirat or y, GI, s ki n) are e x perie nce d at h o me after ta ki n g 
t he dail y d ose of pea n ut pr otei n. 
•  T he  partici pa nt has a n acci de ntal pea n ut i n gesti o n wit h a na p h yla xis d uri n g t he st u d y. 
•  T he  partici pa nt de vel o ps  p o or c o ntr ol or persiste nt acti vati o n of sec o n dar y at o pic disease 
(e. g. at o pic der matitis , ast h ma). 
•  Circ u msta nces (e. g. c o nc urre nt ill ness, s uc h as gastr oe nteritis) re q uire misse d 
mai nte na nce d osi n g of > 1 4 c o nsec uti ve da ys (t his d oes n ot i ncl u de s u bjects i nte nti o n all y 
re m o ve d fr o m t hera p y i n pre parati o n f or t he t olera nce D B P C F C). 
•  T here is a patter n of n o n -a d here nce wit h t he h o me d osi n g pr ot oc ol ( i.e., e xcessi ve misse d 
d osi n g da ys  or misse d a p p oi nt me nts ) t hat w o ul d create a safet y iss ue warra nti n g 
disc o nti n uati o n . 
•  T he partici pa nt is s tarte d o n A R Bs, A C E i n hi bit ors, beta-bl oc kers, or ot her pr o hi bite d 
me dicati o ns a n d t here are n o alter nati ve o pti o ns pe r t he prescri bi n g p h ysicia n. 
Partici pa nts ma y pre mat urel y wit h dra w fr o m t he st u d y if: 
•  T he partici pa nt elects t o wit h dra w c o nse nt fr o m all f ut ure st u d y acti vities, i ncl u di n g 
f oll o w-u p . 
•  T he partici pa nt is “l ost t o f oll o w -u p” (i.e., n o f urt her f oll o w -u p is p o ssi ble beca use 
atte m pts t o reesta blis h c o ntact wit h t he partici pa nt ha ve faile d) . 
•  T he partici pa nt dies . 
 
 
 
 
 
 
 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 2 3  of 5 7  
* See a p pe n di x 6 . 0 
 
5.  
S T U D Y M
E D I C A T I O N  
5. 1  
F o r m ul ati o n, P a c k a gi n g, a n d L a b eli n g  
T he pea n ut S LI T st u d y dr u g will be li q ui d pea n ut e xtract ( 5 0 0 0 mc g/ ml pea n ut pr otei n)  
ma n ufact ure d b y a n d c o m merciall y p urc hase d fr o m Greer La b orat ories , I nc. i n Le n oir, N C.  T he 
place b o will c o nsist of p ure gl yceri nate d sali ne s ol uti o n wit h cara mel c ol ori n g t o matc h c ol or.  
T he pea n ut S LI T s t u d y dr u g will be deli vere d t o t he pri ma r y site la b orat or y at U N C-C H ( PI, 
B ur ks) .  It will be dil ute d as a p pr o priate ( Ta ble 1) a n d b ottle d a n d t he n be s u b mitte d t o t he 
i n vesti gati o nal dr u g ser vices (I D S) at U N C-C H  a n d U T S W res pecti vel y f or la beli n g, a n d 
distri b uti o n .  A certificate of a nal ysis f or t he pea n ut e xtract is o n file i n Dr. B ur ks’ la b orat or y.   
Gl yceri nate d sali ne s ol uti o n will be a d de d t o ma ke t he a p pro priate dil uti o ns  of b ot h t he pea n ut 
S LI T st u d y dr u g a n d place b o ( Ta ble 1).  T he pea n ut S LI T st u d y dr u g a n d place b o will be 
aliq u ote d  i nt o 3 2. 6 ml plastic vials wit h eac h p u m p dis pe nsi n g 5 0 micr oliters of st u d y dr u g.  
I n di vi d ual vials will be la bele d wit h t he s u bject I D a n d ra n d o mizati o n n u m ber, descri pti o n of 
pr o d uct, l ot n u m ber, e x pirati o n date, dil uti o n , a n d t he n u m ber of p u m ps t o be dis pe nse d dail y.  
U p o n recei vi n g t he st u d y dr u g fr o m I D S , t he st u d y c o or di nat or will verif y t hat t he dil uti o n a n d 
t he n u m ber of dail y p u m ps matc h t he partici pa nt’s c urre nt prescri pti o n.  T he s u bject’s I D a n d 
ra n d o mizati o n n u m ber will als o be c o nfir me d pri or t o gi vi n g t he vials t o t he partici pa nt or 
partici pa nt’s care pr o vi der.  
5. 2  
P r e p a r ati o n, A d mi nist r ati o n, a n d D o s a g e 
F or h o me a d m i nistrati o n t he fa mil y will be pr o vi de d wit h i n di vi d ual 3 2. 6 ml vials of t he 
a p pr o priate dil uti o n al o n g wit h i nstr ucti o ns  re gar di n g t he n u m ber of p u m ps t o dis pe nse.  
Partici pa nts will be gi ve n a n a de q uate s u p pl y f or t he i nter val bet wee n sc he d ule d visits wi t h a n 
a d diti o nal s u p pl y t o be use d i n t he e ve nt of misse d or ca ncelle d st u d y visits.  T he p u m ps are t o 
be a d mi nistere d bel o w t he t o n g ue a n d hel d i n place f or as l o n g as p ossi ble f or u p t o  2 mi n utes 
bef ore s wall o wi n g.  T he s u bjects s h o ul d ha ve n ot hi n g t o ea t or dri n k 1 5 mi n utes bef ore or  3 0 
mi n utes after d osi n g .  At least 1 2 h o urs s h o ul d pass bet wee n d oses.  F or y o u n ger s u bjects w here 
t he v ol u me of li q ui d is t o o lar ge t o be hel d u n der t he t o n g ue as a si n gle d ose, d oses ma y be s plit 
i nt o 2 d oses wit h 5 mi n utes bet wee n eac h a d mi nistrati o n.  
5. 3  
D r u g A c c o u nt a bilit y  
U n der Title 2 1 of t he C o de of Fe deral Re g ulati o ns ( 2 1 C F R § 3 1 2. 6 2) t he i n vesti gat or is re q uire d 
t o mai ntai n a de q uate rec or ds of t he dis p ositi o n of t he i n vesti gati o nal a ge nt, i ncl u di n g t he date 
a n d q uantit y of t he dr u g recei ve d, t o w h o m t he dr u g was dis pe nse d ( partici pa nt -b y -partici pa nt 
acc o u nti n g), a n d a detaile d acc o u nti n g of a n y dr u g acci de ntall y or deli beratel y destr o ye d.  

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 2 4  of 5 7  
* See a p pe n di x 6 . 0 
 
Rec or ds f or recei pt, st ora ge, use, a n d dis p ositi o n will be mai ntai ne d b y t he s t u d y site.  Eac h 
partici pa nt will ha ve a c urre nt dr u g -dis pe nsi n g l o g.  T his l o g will c o ntai n t he i de ntificati o n of 
eac h partici pa nt a n d t he date a n d q ua ntit y of dr u g dis pe nse d.  
All rec or ds re gar di n g t he dis p ositi o n of t he i n vesti gati o nal pr o d uct will be a v aila ble f or 
i ns pecti o n b y t he trial m o nit or. 
5. 4  
Ass ess m e nt of C o m pli a n c e wit h St u d y T r e at m e nt a n d M o nit o ri n g  
Fa milies will d oc u me nt dail y d osi n g of t he st u d y pr o d uct a n d a n y reacti o n fr o m h o me d osi n g 
t hr o u g h diar y l o gs.  A d diti o nall y, t he fa milies will be i ns tr ucte d t o ret ur n all e m pt y vials  as well 
as all u n use d st u d y dr u g at eac h visit. Fa milies will be pr o vi de d 2 4 -h o ur e mer ge nc y c o ntact 
i nf or mati o n. 
5. 5  
M o difi c ati o n of St u d y T r e at m e nt  
If t he s u bject is u na ble t o t olerate t he sc he d ule d d ose i ncrease d uri n g b uil d -u p , the st u d y 
c o or di nat or or PI  ma y c h o ose t o dela y or a dj ust d ose escalati o n .  O pti o ns i ncl u de le n gt he ni n g t he 
i nter val bet wee n sc he d ule d d ose i ncreases, decreasi n g t o a pre vi o usl y t olerate d d ose, or 
wit h dra wi n g fr o m t he st u d y.   
5. 6  
C o n c o mit a nt M e di c at i o ns  
All s u bjects ma y c o nti n ue t heir us ual me dicati o ns, i ncl u di n g t h ose ta ke n f or ast h ma, aller gic 
r hi nitis a n d at o pic der matitis, d uri n g t he st u d y.  H o we ver, t he y m ust be a ble t o te m p oraril y 
disc o nti n ue a nti hista mi nes ( 5 half-li ves of t he a nti hista mi ne) pri or t o s ki n pric k testi n g a n d 
D B P C F Cs .  Re g ular t o pical ster oi d use is per mitte d at t he ti me of s ki n testi n g.  Mai nte na nce 
aller ge n i m m u n ot hera p y f or e n vir o n me ntal aller gies ma y be c o nti n ue d d uri n g t he st u d y b ut 
s u bjects s h o ul d n ot start or escalate aller ge n i m m u n ot hera p y f or e n vir o n me ntal aller gies d uri n g 
t he st u d y. 
5. 7  
P r o p h yl a cti c M e di c ati o ns  
N o ne  
5. 8  
R es c u e M e di c ati o ns   
Treat me nt of i n di vi d ual aller gic reacti o ns d uri n g pea n ut S LI T t hera p y s h o ul d be wit h a n 
a nti hista mi ne a n d/ or e pi ne p hri ne, al o n g wit h I V fl ui ds, al b uter ol , ster oi ds, a n d H 2 bl oc kers as 
i n dicate d.  All s u bjects a n d/ or fa mil y me m ber m ust  ha ve a n a p pr o priate self -i njecta ble 
e pi ne p hri ne de vice a vaila ble t hr o u g h o ut t he st u d y f or e mer ge nc y use.  Pre scri pti o ns will be 
pr o vi de d f or s u bjects w h o d o n ot ha ve a n e pi ne p hri ne a ut o -i nject or.  S u bjects a n d pare nts will be 
trai ne d i n pr o per use of t he de vice a n d m ust  be a ble t o de m o nstrate pr o per tec h ni q ue.   

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 2 5  of 5 7  
* See a p pe n di x 6 . 0 
 
5. 9  
P r o hi bit e d M e di c ati o ns   
1.  O maliz u ma b ( X ol air ) 
2.  S yste mic c ortic oster oi ds of l o n ger t ha n 3 wee ks d urati o n at a n y ti me t hr o u g h o ut t he  st u d y 
3.  Beta -bl oc kers ( oral)  
4.  A n gi ote nsi n -c o n verti n g e nz y me ( A C E) i n hi bit ors  
5.  A n gi ote nsi n -rece pt or bl oc kers ( A R B) 
6.  Calci u m c ha n nel bl oc kers  
 
 
 
 
 
 
 
 
 
 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 2 6  of 5 7  
* See a p pe n di x 6 . 0 
 
6.  
S T U D Y D E F I N I T I O N S A N D P R O C E D U R E S  
6. 1  
St u d y D efi niti o ns  
6. 1. 1  A n a p h yl a xi s  
A na p h yla xis is a ge neralize d aller gic reacti o n t hat is ra pi d i n o nset a n d ma y pr o gress t o deat h.  
6. 1. 2  C rit e ri a f o r Di a g n o si s   
A na p h yla xis is li kel y w he n a n y o ne  of t he t hree f oll o wi n g sets of criteria is f ulfille d: 
1.  Ac ute o nset of a n ill ness ( mi n utes t o h o urs) wit h i n v ol ve me nt of:  
•  S ki n/ m uc osal tiss ue (e. g., ge ner alize d  hi ves, itc h or fl us h, s w olle n li ps/t o n g ue/ u v ula)   
A N D  
•  Re d uce d B P or ass ociate d s y m pt o ms (e. g., h y p ot o nia, s y nc o pe, i nc o nti ne nce)  
2.  T w o or m ore of t he f oll o wi n g t hat occ ur ra pi dl y after e x p os ure t o a li kel y aller ge n f or 
t h at s u bject ( mi n utes t o h o urs): 
•  S ki n/ m uc osal tiss ue (e. g., ge ner alize d  hi ves, itc h/fl us h, s w olle n li ps/t o n g ue/ u v ula)  
•  Air wa y c o m pr o mis e (e. g., d ys p nea, stri d or w heeze/ br o nc h os pas m, h y p o xia, re d uce d 
P E F)  
•  Re d uce d B P or ass ociate d s y m pt o ms (e. g., h y p ot o nia, s y nc o pe, i nc o nti ne nce)  
•  Persiste nt  GI s y m pt o ms (e. g., na usea, v o miti n g, cra m p y a b d o mi nal pai n)  
3.  Re d uce d B P after e x p os ure t o k n o w n aller g e n f or t hat s u bject ( mi n utes t o h o urs):  
•  I nfa nts a n d C hil dre n: l o w s yst olic B P (a ge-s pecific) or > 3 0 % dr o p i n s yst olic B P * 
•  A d ults: s yst olic B P < 9 0  m m H g or > 3 0 % dr o p fr o m t heir baseli ne  
 
*  L o w s yst olic B P f or c hil dre n is defi ne d as < 7 0 m m H g fr o m 1 m o nt h t o 1 year; less t ha n 
( 7 0 m m H g + [ 2 x a ge]) fr o m 1-1 0 years; a n d < 9 0 m m H g fr o m a ge 1 1 -1 7 years.  
 
6. 1. 3  A n a p h yl a xi s St a gi n g S y st e m  
St a gi n g S yste m of Se verit y of A n a p h yl a xis  
St a ge  
Defi ne d B y  
1. Mil d  (s ki n & s u bc uta ne o us tiss ues, 
GI, &/ or mil d res pirat or y)  
Fl us hi n g, urticaria, peri or bital or facial 
a n gi oe de ma; mil d d ys p nea, w heeze or u p per 
res pirat or y s y m pt o ms; mil d a b d o mi nal pai n 
a n d/ or e mesis  

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 2 7  of 5 7  
* See a p pe n di x 6 . 0 
 
2. M o der ate  ( mil d s y m pt o ms + feat ures 
s u g gesti n g m o derate res pirat or y, 
car di o vasc ular or GI s y m pt o ms)  
Mar ke d d ys p ha gia, h oarse ness, a n d/ or stri d or; 
S O B, w heezi n g & retracti o ns; cra m p y 
a b d o mi nal pai n, rec urre nt v o miti n g a n d/ or 
diarr hea; a n d/ or mil d dizzi ness  
3. Sever e ( h y p o xia, h y p ote nsi o n, or 
ne ur ol o gical c o m pr o mise)  
C ya n osis or S p O 2 <  9 2 % at a n y sta ge, 
h y p ote nsi o n, c o nf usi o n, c olla pse, l oss of 
c o nsci o us ness; or i nc o nti ne nce  
 
6. 2  
E n r oll m e nt  
A t otal of 5 0 c hil dre n will be e nr olle d i n t he st u d y ( 4 0  c hil dre n at U N C -C H  a n d 1 0 c hil dre n at 
U T S W ).  Acc o u nti n g f or a 1 0 % dr o p o ut rate, we a ntici pate ha vi n g 4 5  c hil dre n eli gi ble f or t he 
dese nsitizati o n D B P C F C after 3 6 m o nt hs of treat me nt . 
6. 3  
S c r e e ni n g Visit  
T he scree ni n g visit will i ncl u de t he f oll o wi n g pr oce d ur es: 
•  C o nse nt  
•  Me dical hist or y  
•  Diet a n d aller g y q uesti o n naire  
•  P h ysical e xa mi nati o n  
•  Bl o o d dra w f or pea n ut -s pecific I g E meas ure me nt a n d a d diti o nal mec ha nistic st u dies  
•  S ki n pric k testi n g t o pea n ut  
•  Sali va c ollecti o n f or i m m u n o gl o b uli n testi n g  
•  St o ol c ollecti on f or micr o bi o me a n d i m m u n o gl o b uli n st u dies 
 
6. 4  
B as eli n e Visit / E nt r y F o o d C h all e n g e 
S u bjects w h o meet eli gi bilit y criteria will ret ur n f or a baseli ne visit  wit hi n 4 wee ks of t he 
scree ni n g visit.  T his visit ma y be c o m bi ne d wit h t he scree ni n g visit i n s u bjects w h o m t he 
i n vesti gat or belie ves will q ualif y f or t he st u d y.  T his visit will i ncl u de t he f oll o wi n g pr oce d ures: 
•  P h ysical e xa mi nati o n  
•  Q ualif yi n g D B P C F C  t o 1 0 0 0 m g of pea n ut  
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 2 8  of 5 7  
* See a p pe n di x 6 . 0 
 
* Mec ha nistic bl o o d dra w ma y be re peate d d ue t o i na de q uate T a n d n o n -T cell se parati o n b ut n ot 
t o e xcee d t he less or of 3 5  m l or 3 ml / k g per bl o o d dra w wit hi n a n ei g ht ( 8) wee k peri o d.  T his 
w o ul d n ot be re peate d i n s u bjects wit h k n o w n c hr o nic a ne mia.   
6. 5  
St u d y T r e at m e nt Visits  
 
* C O VI D -1 9 S afety Me as ures  
Details o n c ha n ges t o st u d y dr u g d osi n g d urati o n, st u d y visits , la b orat or y sa m ple c ollecti o n a n d 
D B P C F Cs d ue t o t he gl o bal C O VI D -1 9 pa n de mic are descri be d i n detail i n A p pe n di x 6.  T hese 
c ha n ges are als o hi g hli g hte d t hr o u g h o ut t he f oll o wi n g secti o ns.  
D ose Esc al ati o n  
F oll o wi n g t he q ualif yi n g e ntr y D B P C F C t o pea n ut, s u bjects will ret ur n t o t he researc h u nit t o 
be gi n t he d ose escalati o n p hase of t he st u d y pr ot oc ol  ( Ta ble 1) wit hi n 7 da ys of c o m pleti n g t he 
e ntr y D B P C F C .  Acc or di n g t o t heir ra n d o mizati o n, s u bjects will a d mi nister o ne p u m p of a 1 :1 0 0 
dil uti o n of eit her pea n ut S LI T st u d y dr u g or place b o  u n der t heir t o n g ues a n d wait 2 mi n utes 
bef ore s wall o wi n g.  S u bjects will be o bser ve d f or a mi ni m u m of 3 0 mi n utes a n d t h ose wit h 
mi ni mal  (e. g.,or o p har y n geal itc hi n g) or n o  s y m pt o ms will be disc har ge d .  T he i de ntical d ose will 
be a d mi nistere d at h o me dail y f or 1 wee k.  Ta ble 1 s h o ws t he sc he d ule f or s u bse q ue nt d ose 
escalati o n, w hic h i ncl u des b ot h h o me d ose escalati o n as well as cli nic visits f or o bser ve d d ose 
escalati o n.  O bser ve d d ose escalati o n at t he researc h u nit will occ ur wit h eac h i ncrease i n st u d y 
dr u g dil uti o n a n d e ver y 4 wee ks w hile o n 1: 1 f ull c o nce ntrati o n u ntil mai nte na nce d osi n g ( 4 0 0 0 
mc g pea n ut pr otei n) is ac hie ve d.  T h ose wit h mil d s y m pt o ms re q uiri n g treat me nt d uri n g 
o bser ve d d ose escalati o n will be o bser ve d f or at least 2 h o ur s or u ntil s y m pt o ms res ol ve.   A n y 
s u bject t hat de vel o ps m o derate or se vere s y m pt o ms re q uiri n g e pi ne p hri ne will be o bser ve d f or at 
least 4 h o urs or u ntil s y m pt o ms res ol ve .  S u bse q ue nt d osi n g after a treata ble reacti o n will  be 
deter mi ne d b y t he PI usi n g his b est cli nical j u d g me nt.  O pti o ns w o ul d i ncl u de re peati n g t he 
i de ntical d ose t he f oll o wi n g da y, dela yi n g escalati o n a n d c o nti n ui n g o n t he pri or d ose f or a n 
a d diti o nal 1-2 wee ks, decreasi n g t he d ose t o t he hi g hest s y m pt o m free d ose  or a n ar bitrar y safe 
d ose , or disc o nti n ui n g d osi n g.  S u bjects will be gi ve n c o ntact n u m bers f or st u d y pers o n nel, 
i ncl u di n g e mer ge nc y c o ntact i nf or mati o n.  Fa milies will be i nstr ucte d t o c o ntact st u d y pers o n nel 
wit h a n y ne w or si g nifica nt  si de effects wit h h o me d osi n g. 
 
 
 
 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 2 9  of 5 7  
* See a p pe n di x 6 . 0 
 
 
 
 
M ai nte n a nce  d osi n g  
After c o m pleti n g t he escalati o n sc he d ule, s u bjects will c o nti n ue t o a d mi nister 1 6 p u m ps of t he 
1: 1 dil uti o n of pea n ut S LI T st u d y dr u g ( 4 0 0 0 mc g) or place b o  dail y f or a t otal of 3 6 m o nt hs.  
S u bjects will ret ur n t o t he researc h u nit e ver y 6 m o nt hs  f or a f oll o w u p visit w hic h w o ul d i ncl u de 
T a ble 1. D ose  Esc al ati o n  Sc he d ule  
 
D ose 
#  
 
Pe a n ut 
Dil uti o n  
 
P u m ps  
D ose of 
Pe a n ut 
Pr otei n  
I nter v al 
i n Wee ks 
%  I ncre ase  
 
St u d y Visit  
( O bser ve d 
d osi n g)  
1  
1 :1 0 0  
1  
2. 5 mc g  
 
- 
ü   
2  
1 :1 0 0  
2  
5 mc g  
1  
1 0 0 %  
 
3  
1 :1 0 0  
4  
1 0 mc g  
1  
1 0 0 %  
 
4  
1 :1 0 0  
8  
2 0 mc g  
1  
1 0 0 %  
 
5  
1: 1 0  
1  
2 5 mc g  
1  
2 5 %  
ü   
6  
1 :1 0  
2  
5 0 mc g  
1  
1 0 0 %  
 
7  
1 :1 0  
4  
1 0 0 mc g  
1  
1 0 0 %  
 
8  
1 :1 0  
8  
2 0 0 mc g  
1  
1 0 0 %  
 
9  
1: 1  
1  
2 5 0 mc g  
2  
2 5 %  
ü   
1 0  
1: 1  
2  
5 0 0 mc g  
2  
1 0 0 %  
 
1 1  
1: 1  
4  
1 0 0 0 mc g  
2  
1 0 0 %  
ü   
1 2  
1: 1  
8  
2 0 0 0 mc g  
2  
1 0 0 %  
 
1 3  
1: 1  
1 2  
3 0 0 0 mc g  
2  
5 0 %  
ü   
1 4  
1: 1  
1 6  
4 0 0 0 mc g  
2  
3 3 %  
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 3 0  of 5 7  
* See a p pe n di x 6 . 0 
 
vitals si g ns, a p h ysical e xa m, re vie w of s y m pt o m diaries, c ollecti o n of ol d vials a n d distri b uti o n 
of ne w vials of st u d y dr u g.  S ki n testi n g, sali va c ollecti o n a n d bl o o d m ec ha nistic st u dies  are 
sc he d ule d at e nr oll me nt, a n n uall y, a n d at t he 3 6 m o nt h dese nsitizati o n D B P C F C a n d 3 9 -m o nt h  
t olera nce D B P C F C.  S u bjects wit h ne w or si g nifica nt s y m pt o ms wit h d osi n g will ret ur n t o t he 
researc h unit  as s o o n as is reas o na bl y p ossi ble f or re vie w of t he s y m pt o ms a n d li kel y o bser ve d 
d osi n g.   * S u bjects w h ose Dese nsitizati o n D B P C F C, n or mall y sc he d ule d f or 3 6 m o nt hs, has bee n 
deferre d d ue t o t he C O VI D -1 9 safet y meas ures, will  re mai n o n mai nte na nce st u d y dr u g d osi n g 
be y o n d 3 6 m o nt hs u ntil t he ti me t hat t he Dese nsitizati o n D B P C F C is a ble t o be c o m plete d. A 
f oll o w u p visit t o re vie w safet y a n d s u bject diaries w o ul d be perf or me d i n place of t he D B P C F C 
a n d be c o m plete d re m otel y b y t ele p h o ne wit h a d diti o nal st u d y dr u g pr o vi de d direct -t o-patie nt. 
Sa m ple c ollecti o n a n d mec ha nistic st u dies sc he d ule d f or t he 3 6 m o nt h visit w o ul d be deferre d 
u ntil t he ti me of t he Dese nsitizati o n D B P C F C. F ull details of t hese c ha n ges are a vaila ble i n 
A p pe n d i x 6. 
Dese nsitiz ati o n Assess me nt by D B P C F C  
All s u bjects will u n der g o a D B P C F C t o 4 4 4 3  m g of pea n ut pr otei n after 3 6 m o nt hs of treat me nt.  
T he pr oce d ure f or t he D B P C F C is descri be d i n secti o n 6. 6.  All s u bjects will t he n disc o nti n ue 
pea n ut S LI T or place b o t hera p y.  T h ose s u bjects w h o are a ble t o t olerate >  4 4 3 m g of pea n ut 
pr otei n at t he 3 6 m o nt h D B P C F C will be as ke d t o ret ur n f or a D B P C F C at 3 9 m o nt hs , t o t he 
a m o u nt of pea n ut pr otei n pre vi o usl y t olerate d at t he 3 6 m o nt h D B P C F C t o assess f or t olera nce.  
All s u bjects will be u n bli n de d  n o s o o ner t ha n 3 6 m o nt hs ( u nless safet y u n bli n di n g is re q uire d)  at 
t heir c o m pleti o n p oi nt i n t he st u d y.  S u bjects u na ble to t olerate >  4 4 3 m g of pea n ut pr otei n at t he 
3 6 m o nt h D B P C F C will be gi ve n t he o pti o n t o strictl y a v oi d all pea n uts or, if a p pr o priate, 
alter nati ve treat me nt o pti o ns t hat ma y be a vaila ble t o t he m via researc h or F D A a p pr o ve d 
me dicati o ns .  * S u bjects w h ose D ese nsitizati o n D B P C F C w o ul d be sc he d ule d t o fall d uri n g t he 
i m ple me ntati o n of t he C O VI D-1 9 safet y meas ures w o ul d ha ve t heir D B P C F C deferre d a n d a 
f oll o w u p visit perf or me d i n its place. T he s u bject w o ul d re mai n o n mai nte na nce st u d y dr u g 
d osi n g be y o n d 3 6 m o n t hs u ntil t he safet y meas ures are lifte d a n d t he Dese nsitizati o n D B P C F C is 
a ble t o be c o m plete d.  F ull details of t hese c ha n ges are a vaila ble i n A p pe n di x 6.  
T oler a nce Assess me nt by D B P C F C  
After  disc o nti n u i n g st u d y dr u g d osi n g f or 3 m o nt hs, t h ose s u bjects w h o are a ble t o t olerate >  4 4 3 
m g of pea n ut pr otei n at t he 3 6 m o nt h D B P C F C will be as ke d t o ret ur n f or a D B P C F C at 3 9 
m o nt hs t o t he a m o u nt of pea n ut pr otei n pre vi o usl y t olerate d at t he 3 6 m o nt h D B P C F C t o assess 
f or t olera nce.   All s u bjects will be u n bli n de d after t he D B P C F C a n d t he st u d y will c o ncl u de f or 
t hese s u bjects.  S u bjects w h o c o m plete t his D B P C F C wit h o ut s y m pt o ms  at 4 4 4 3 m g of pea n ut 
pr otei n will be c o nsi dere d t olera nt a n d will be i nstr ucte d t o i ntr o d uce pea n ut i nt o t heir diet a d 
libit u m.  S u bjects w h o d o n ot pass t he D B P C F C will be gi ve n t he o pti o n t o ta ke a dail y f o o d 
e q ui vale nt of pea n ut t o mai ntai n t he dese nsitize d state or  t o strictl y a v oi d pea n ut.  * S u bjects 
w h ose T olera nce D B P C F C w o ul d be sc he d ule d t o fall d uri n g t he i m ple me nt ati o n of t he C O VI D -
1 9 safet y meas ures w o ul d ha ve t heir D B P C F C. As f urt her st u d y dr u g a v oi da nce be y o n d t his ti me 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 3 1  of 5 7  
* See a p pe n di x 6 . 0 
 
p oi nt w o ul d ha ve t he p ote ntial t o i ncrease t he ris k of reacti o n d uri n g t he D B P C F C, t he D B P C F C 
w o ul d n ot be resc he d ule d f or a later date. T he s u b ject will c o m plete t he st u d y at t hat ti me wit h a 
re m ote tele p h o ne e xit visit perf or me d t o re vie w safet y, u n bli n d t he s u bject t o treat me nt 
all ocati o n a n d re vie w st u d y c o m pleti o n i nstr ucti o ns. F ull details of t hese c ha n ges are a vaila ble i n 
A p pe n di x 6.  
6. 6  
D o u bl e  Bli n d Pl a c e b o C o nt r oll e d  F o o d C h all e n g e ( D B P C F C)  
D B P C F Cs will be c o n d ucte d at t he researc h u nit at e ntr y, 3 6  m o nt hs * , a n d at 3 9 m o nt hs *  (f or 
t h ose a ble t o t olerate >  4 4 3 m g pea n ut pr otei n  at t he 3 6 m o nt h *  c halle n ge) .  Pri or t o t he f o o d 
c halle n ge, s u bjects will be as ke d t o restrict t he use of a nti hista mi nes (s h ort acti n g, 7 2 h o urs: l o n g 
acti n g, 7 da ys), beta -a g o nists ( 1 2 h o urs), t he o p h ylli ne ( 1 2 h o urs), a n d cr o m ol y n ( 1 2 h o urs).  T he 
D B P C F C c o nsists of 2 c halle n ges.  T h e or der of t he 2 c halle n ges  will be ra n d o ml y deter mi ne d 
b y  I D S.  T he B ur ks la b will pre pare d oses a n d t he n s u b mit t he m t o t he res pecti ve I D S at U N C-
C H a n d U T S W f or  la beli n g a n d distri b ut i o n.  O ne c halle n ge will c o nsist of gra de d d oses of 
pea n ut fl o ur gi ve n e ver y 1 0 -2 0 mi n utes u p t o a c u m ulati ve d ose of 1 0 0 0 m g  (3  m g, 1 0  m g, 3 0 
m g, 1 0 0 m g, 3 0 0 m g, 5 5 7  m g)  of pea n ut pr otei n d uri n g  t he e ntr y c halle n ge a n d 4 4 4 3  m g  (3 m g , 
1 0  m g, 3 0  m g, 1 0 0  m g, 3 0 0  m g, 1 0 0 0  m g , 3 0 0 0 m g) of pea n ut pr otei n f or t he 3 6  m o nt h *  
dese nsitizati o n D B P C F C  a n d 3 9 m o nt h t olera nce D B P C F C.   T he B ur ks la b will s u p pl y I D S wit h 
la bels f or t he c halle n ge d oses t o reflect t he t otal wei g ht i n oat a n d pea n ut fl o ur ( 6 m g, 2 0 m g, 
6 0 m g, 2 0 0 m g,  6 0 0 m g, a n d 1 1 1 4 m g f or e ntr y c halle n ge a n d 6 m g, 2 0 m g, 6 0 m g, 2 0 0 m g, 6 0 0 m g, 
2 0 0 0 m g, a n d 6 0 0 0 m g f or t he 3 6 a n d 3 9 m o nt h c halle n ges).   T he d osi n g sc he d ule is base d o n 
rece nt P R A C T A L L g ui deli nes[2 5 ].  T he ot her c halle n ge w ill c o nsist of place b o i n t he f or m of 
oat fl o ur a d mi nistere d i n i de ntical gra de d d oses b y wei g ht ( 1 0 0 0 m g of pea n ut pr otei n = 2 0 0 0 m g 
of pea n ut fl o ur b y wei g ht).   T here will be a mi ni m u m 1 0 mi n ute o bser vati o n peri o d b et wee n 
d oses t o m o nit or f or s y m pt o ms.  Pri or t o eac h c halle n ge, t he patie nt will ha ve a p h ysical e xa m 
a n d f ull vital si g ns.  All f o o d c halle n ges will be perf or me d u n der p h ysicia n s u per visi o n.  T he 
c halle n ge will be a d mi nistere d b y a n urse , n urse practiti o ner, or p h ysicia n w h o is bli n de d t o t he 
testi n g material.  T he s u per visi n g i n vesti gat or will als o be bli n de d t o testi n g material.  After  t he 
i nitial c halle n ge, t he s u bject will be o bser ve d f or a mi ni m u m peri o d of 1 h o ur pri or t o starti n g t he 
sec o n d c halle n ge. T he f o o d c halle n ge s ma y be c o n d ucte d o ver t w o se parate da ys .  Reacti o ns will 
be sc ore d usi n g a F o o d C halle n ge S y m pt o m Sc ore s heet.   Fre q ue nt assess me nts wi ll be ma de f or 
s y m pt o ms affecti n g t he s ki n, gastr oi ntesti nal tract, a n d/ or res pirat or y tract.  If t he s u bject 
prese nts wit h eit her o ne maj or or t w o mi n or criteria  ( A p pe n di x 4), t he f o o d c halle n ge will be 
ter mi nate d a n d t he s u bject will be gi ve n a p pr o priate treat me nt.  F o o d c halle n ges ma y be 
ter mi nate d at t he discreti o n of a st u d y p h ysicia n f or a n y safet y st o p.  T he s u bjects w h o are 
s y m pt o matic will be o bser ve d f or a mi ni m u m of 2 h o urs after t he c halle n ges are c o m plete d 
bef ore bei n g disc har ge d fr o m t he researc h u nit. 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 3 2  of 5 7  
* See a p pe n di x 6 . 0 
 
6. 7  
S ki n P ri c k T est i n g 
Aller g y s ki n pric k testi n g t o pea n ut aller ge n will be perf or me d at e nr oll me nt, o nce yearl y , a n d at 
t he dese nsitizati o n a n d  t olera nce D B P C F Cs (if nee de d).  T he s ki n testi n g will be perf or me d 
usi n g  a Greer pic k a n d sta n dar d pea n ut e xtract 1:2 0 wt/ v ol ( Greer, I nc, Le n oir, N C) wit h a 
p ositi ve hista mi ne c o ntr ol a n d a ne gati ve sali ne c o ntr ol.  Reacti o ns will be rea d after 1 5 mi n utes 
a n d t he w heal will be o utli ne d i n i n k a n d tra nsferre d t o t he per ma ne nt r ec or d usi n g tra ns pare nt 
ta pe.  T he reacti o n size will be calc ulate d as t he mea n w heal dia meter of pea n ut less t he mea n 
w heal dia meter of t he sali ne ne gati ve c o ntr ol.  T he mea n w heal dia meter is defi ne d as t he 
avera ge of t he lar gest dia meter a n d t he c orres p o n di n g mi d p oi nt dia meter.  
6. 8  
S ali v a C oll e cti o n  
Sali va c ollecti o n will be perf or me d at e nr oll me nt, o nce yearl y, a n d at t he  dese nsitizati o n a n d  
t olera nce D B P C F Cs (if nee de d).  If t he s u bject is a ble t o s pit, sali va will be c ollecte d i n a 5 0 ml 
c o nical t u be a n d st ore d o n ice u ntil pr ocessi n g b y t he la b orat or y.  If t he s u bject is u na ble t o s pit, 
sali va ma y be c ollecte d ma n uall y usi n g a 3-5 ml s yri n ge a n d tra nsferre d t o a c ollecti o n de vice, or 
sali va ma y be c ollecte d wit h a s oft-ti p pe d cat heter attac he d t o vac u u m s ucti o n. T he c ollecti o n 
de vice f or t he s ucti o n met h o d s h o ul d be a cl ose d m uc us s peci me n tra p.   A mi ni m u m of 2 ml of 
sali va s h o ul d be c ollecte d.  All sa m ples s h o ul d be st ore d o n ice u ntil pr ocesse d b y t he 
la b orat or y.  Sali va s h o ul d be c ol lecte d pri or t o pea n ut S LI T d osi n g if p ossi ble. 
 
6. 9  
St o ol C oll e cti o n  
St o ol c ollecti o n will be perf or me d at e nr oll me nt, o nce yearl y, a n d at t he dese nsitizati o n a n d 
t olera nce D B P C F Cs (if nee de d).  If t he s u bject is i n dia pers, pare nts will be gi ve n s u p plies a n d 
will be i nstr ucte d o n h o w t o c ollect a st o ol sa m ple fr o m h o me.  F or t oilet trai ne d c hil dre n, 
pare nts will be gi ve n s u p plies a n d i nstr ucti o ns as t o h o w t o c ollect a st o ol sa m ple fr o m h o me.  
6. 1 0  Visit Wi n d o ws  
D osi n g sc he d ule s h o ul d be a d here d t o strictl y.  T w o d a ys bef ore or se ve n da ys after a pla n ne d 
d osi n g visit is a n acce pta ble wi n d o w wit h c o nti n ue d dail y d osi n g of t he c urre nt d ose le vel.  
St u d y visits f or sc he d ule d bl o o d dra ws or D B P C F C s h o ul d ta ke place wit hi n 2 wee ks of t he 
sc he d ule d visit.  T h ose w h o are u na ble t o c o m pl y wit h t he d osi n g sc he d ule ris k re m o val fr o m t he 
st u d y. 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 3 3  of 5 7  
* See a p pe n di x 6 . 0 
 
6. 1 1  St u d y Bli n di n g  a n d R a n d o mi z ati o n  P r o c e d u r es  
S u bjects w h o fail t he q ualif yi n g e ntr y D B P C F C t o 1 0 0 0 m g of pea n ut pr otei n will be 
ra n d o mize d i n a 1 : 1 rati o usi n g bl oc k ra n d o mizati o n t o recei ve eit her pea n ut S LI T ( n = 2 5 ) or 
place b o ( n = 2 5 ).  S u bjects , st u d y c o or di nat ors, a n d t he pri mar y i n vesti gat or will re mai n bli n de d  
u ntil s u bjects are u n bli n de d after t he  3 6 m o nt h *  or  3 9 m o nt h *  D B P C F C s de pe n di n g o n c halle n ge 
eli gi bilit y. A ll D B P C F C s will als o be ra n d o mize d .  T he data ma na ge me nt gr o u p f or t he st u d y 
will perf or m all ra n d o mizati o n.  
6. 1 1. 1  R e q ui r e m e nt s f o r U n bli n di n g  
If a cli nicall y si g nifica nt e ve nt occ urs  d uri n g t he st u d y , i m me diate me dical atte nti o n will be 
pr o vi de d irres pecti ve of t he treat me nt assi g n me nt.  Bli n di n g will be br o ke n as dee me d necessar y 
f or t he care of t he s u bject.  A n y pre mat ure u n bli n di n g will re q uire a f ull writte n acc o u nt b y t he 
pri mar y i n vesti gat or  of t he e ve nt(s) t hat necessitate d t he u n bli n di n g of t he st u d y dr u g  f or a n 
i n di vi d ual partici pa nt.  T his acc o u nt will be se nt t o t he s p o ns or/lea d i n vesti gat or, I R B, D S M B , 
a n d F D A. 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 3 4  of 5 7  
* See a p pe n di x 6 . 0 
 
7.  
S A F E T Y M
O N I T O R I N G  
T his secti o n defi nes t he t y pes of a d verse e ve nts t hat s h o ul d be re p orte d a n d o utli nes t he 
pr oce d ures f or a p pr o priatel y c ollecti n g, gra di n g, rec or di n g a n d re p orti n g t he m.  
7. 1  
P r o c e d u r es a n d M o nit o ri n g  
All u ne x pecte d seri o us a d verse e ve nts relate d t o t he e x peri me ntal pr oce d ures will be re p orte d t o 
t he I R B, D S M B, a n d F D A i n a ma n ner c o nsiste nt wit h 2 1 C F R 3 1 2. 3 2.   All ot her a d verse e ve nts 
relate d t o t he e x peri me ntal pr oce d ures will als o be re p orte d t o t he I R B a n d D S M B i n a n 
e x pe dite d ma n ner if t he y are Gra de 3 a n d a b o ve i n se verit y.   Partici pa nt deat hs are re p orta ble 
wit hi n 2 4 h o urs.  T he e x pe dite d re p ort se nt t o ot her or ga nizati o ns ca n be c o pie d t o t he D S M B.  
T he i n vesti gat or will c o nti n ue t o f oll o w or o btai n d oc u me ntati o n of t he res ol uti o n c o urse of s uc h 
a n e ve nt.  A c o p y of t he a n n ual re p ort of a d verse e ve n ts s u b mitte d t o t he I R B will be c o pie d t o 
t he D S M B.  Reacti o ns t o d osi n g of t he st u d y pr o d uct will be rec or de d o n a d osi n g l o g a n d will 
n ot be re p orte d se paratel y as a d verse e ve nts.  A n y reacti o n t hat meets t he criteria f or a seri o us 
a d verse e ve nt will be re p orte d b ot h o n t he d osi n g l o g a n d o n a n a d verse e ve nt case re p ort f or m. 
7. 2  
D efi niti o ns  
7. 2. 1  A d v e rs e E v e nt ( A E)  o r M e di c al E v e nt  
A n a d verse e ve nt is a ne w, u n desira ble me dical e ve nt or occ urre nce or w orse ni n g of a n e xisti n g 
c o n diti o n (i ncl u di n g a n a b n or mal la b ora t or y fi n di n g) i n a s u bject t hat occ urs d uri n g treat me nt 
a n d t hr o u g h o ut t he st u d y, w het her or n ot it is c o nsi dere d t o be st u d y relate d.  A d verse e ve nts or 
me dical e ve nts a n d t o xicities are treat me nt e mer ge nt si g ns a n d s y m pt o ms.   
T his i ncl u des t he f oll o wi n g : 
•  A Es n ot pre vi o usl y o bser ve d i n t he patie nt t hat e mer ge d uri n g t he pr ot oc ol -s pecifie d A E 
re p orti n g peri o d, i ncl u di n g si g ns or s y m pt o ms ass ociate d wit h pea n ut aller g y t hat were 
n ot prese nt pri or t o t he A E re p orti n g peri o d . 
•  C o m plicati o ns t hat occ ur as a res ult of pr ot oc ol -ma n date d i nter ve nti o ns (e. g.,  i n vasi ve 
pr oce d ures s uc h as bi o psies) . 
•  If a p plica ble, A Es t hat occ ur pri or t o assi g n me nt of st u d y treat me nt ass ociate d wit h 
me dicati o n was h o ut, treat me nt r u n -i n, or ot her pr ot oc ol-ma n date d i nter ve nti o n . 
•  Pree xis ti n g me dical c o n diti o ns ( ot her t ha n t he c o n diti o n bei n g st u die d) j u d ge d b y t he 
i n vesti gat or t o ha ve w orse ne d i n se verit y or fre q ue nc y or c ha n ge d i n c haracter d uri n g t he 
pr ot oc ol -s pecifie d A E re p orti n g peri o d. 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 3 5  of 5 7  
* See a p pe n di x 6 . 0 
 
P ote ntial a d verse reacti o ns see n i n s u bjects tr eate d wit h pea n ut S LI T a n d s u bjects u n der g oi n g 
D B P C F C i ncl u de t he f oll o wi n g: s ki n ma nifestati o ns s uc h as pr urit us, urticaria, or a n gi oe de ma; 
res pirat or y s y m pt o ms s uc h as w heezi n g, c o u g hi n g, nasal c o n gesti o n/r hi n orr hea, c o u g h a n d 
h oarse ness; a n d gastr oi ntes ti nal s y m pt o ms s uc h as v o miti n g, diarr hea, or a b d o mi nal pai n.  
A na p h yla xis is a p ote ntial ris k i n v ol vi n g a n y of t he a b o ve s y m pt o ms pl us h y p ote nsi o n a n d 
circ ulat or y c olla pse.  
7. 2. 2  S e ri o us A d v e rs e E v e nt ( S A E)  
A seri o us a d verse e ve nt is defi ne d as a n y a d verse t hera p y e x perie nce occ urri n g at a n y d ose t hat 
s u g gests a si g nifica nt hazar d, c o ntrai n dicati o n, si de effect, or preca uti o n will be defi ne d as a n 
S A E.  T his i ncl u des, b ut ma y n ot be li mite d t o a n y of t he f oll o wi n g e ve nts: ( T his ter mi n ol o g y is 
fr o m Secti o n B. 2 o n t he F D A Me d Watc h f or m.  F or a c o p y of t he c urre nt Me d Watc h F or m 3 5 0 0, 
see t he list of P D F f or ms o n t he We b at: 
htt p:// w w w.f da. g o v/ o pac o m/ m orec h oices/f daf or ms/c der. ht ml ) 
1.  Deat h: A deat h occ urri n g d uri n g t he st u d y, or w hic h c o mes t o t he atte nti o n of t he 
i n vesti gat or d uri n g t he pr ot oc ol-defi ne d f oll o w -u p after t he c o m pleti o n of t hera p y 
w het her or n ot c o nsi dere d treat me nt relate d, m ust be re p orte d. 
2.  Life -t hreate ni n g: A n y a d verse t hera p y e x perie nce t hat places t he s u bject or s u bjects, i n 
t he vie w of t he i n vesti gat or, at i m me diate ris k of deat h fr o m t he reacti o n as it occ urre d 
(i.e., it d oes n ot i ncl u de a reacti o n t hat, ha d it occ urre d i n a m ore seri o us f or m, mi g ht 
ha ve ca use d deat h).  
3.  I n-patie nt h os pitalizati o ns or pr ol o n gati o n of e xisti n g h os pitalizati o n.  
4.  Persiste nt or si g nifica nt disa bilit y or i nca pacit y.  
5.  C o n ge nital a n o mal y/ birt h defect.  
6.  A n e ve nt t hat re q uire d i nter ve nti o n t o  pre ve nt per ma ne nt i m pair me nt or da ma ge.  
7. 2. 3  U n e x p e ct e d A d v e rs e E v e nt  
A n a d verse e ve nt is c o nsi dere d “ u ne x pecte d” w he n its nat ure (s pecificit y) or se verit y is n ot 
c o nsiste nt wit h a p plica ble pr o d uct i nf or mati o n, s uc h as safet y i nf or mati o n pr o vi de d i n t he 
pr ot oc ol or c o nse nt.  
7. 3  
T o xi cit y G r a di n g  
T he ter ms “se vere” a n d “seri o us” are n ot s y n o n y m o us.  Se verit y refers t o t he i nte nsit y of a n A E 
(as i n mil d, m o derate, or se vere pai n); t he e ve nt itself ma y be of relati vel y mi n or me dical 
si g nifica nce (s uc h as se vere hea dac he).  “ Seri o us” is a re g ulat or y defi niti o n a n d is base d o n 
patie nt or e ve nt o utc o me or acti o n criteria us uall y ass ociate d wit h e ve nts t hat p ose a t hreat t o a 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
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F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 3 6  of 5 7  
* See a p pe n di x 6 . 0 
 
patie nt’s life or vital f u ncti o ns.  Seri o us ness ( n ot se verit y) ser ves as t he g ui de f or defi ni n g 
re gulat or y re p orti n g o bli gati o ns.   
T o xicit y gra des are assi g ne d b y t he st u d y site t o i n dicate t he se verit y of a d verse e x perie nces a n d 
t o xicities usi n g t he N CI-C T C A E versi o n 4 . 0.  T o xicit y gra di n g f or aller gic reacti o ns i ncl u di n g 
a na p h yla xis is m o difie d fr o m t he N CI-C T C A E s yste m t o be m ore a p pr o priate f or t his st u d y 
p o p ulati o n, a n d is dis pla ye d i n A p pe n di x 2.  T he N CI -C T C A E has bee n re vie we d s pecificall y f or 
t his pr ot oc ol a n d is ot her wise a p pr o priate f or t his st u d y p o p ulati o n.  T he p ur p ose of usi n g t he 
N CI -C T C A E s yste m is t o pr o vi de sta n dar d la n g ua ge t o descri be t o xicities a n d t o facilitate 
ta b ulati o n a n d a nal ysis of t he data a n d assess me nt of t he cli nical si g nifica nce of treat me nt-
relate d t o xicities. 
A d verse e ve nts n ot i ncl u de d i n t he C T C A E listi n g s h o ul d be r ec or de d a n d gra de d 1 -5 acc or di n g 
t o t he Ge neral Gra de Defi niti o n pr o vi de d bel o w: 
Gr a de 1  
Mil d  
Tra nsie nt or mil d disc o mf orts ( < 4 8 h o urs), n o or mi ni mal  
me dical i nter ve nti o n/t hera p y re q uire d, h os pitalizati o n n ot 
necessar y ( n o n -prescri pti o n or si n gle -use pre scri pti o n 
t hera p y ma y be e m pl o ye d t o relie ve s y m pt o ms, e. g., as piri n 
f or si m ple hea dac he, aceta mi n o p he n f or p ost-s ur gical pai n). 
Gr a de 2  
M o der ate  
Mil d t o m o derate li mitati o n i n acti vit y s o me assista nce ma y 
be nee de d; n o or mi ni mal i nter ve nti o n/t hera p y re q uire d, 
h os pitalizati o n p ossi ble.  
Gr a de 3  
Se vere  
Mar ke d li mitati o n i n acti vit y, s o me assista nce us uall y 
re q uire d; me dical i nter ve nti o n/t hera p y re q uire d, 
h os pitalizati o n p ossi ble.  
Gr a de 4  
Life -
t hre ate ni n g 
E xtre me li mitati o n i n acti v it y, si g nifica nt assista nce 
re q uire d; si g nifica nt me dical/t hera p y i nter ve nti o n re q uire d, 
h os pitalizati o n or h os pice care pr o ba ble.  
Gr a de 5  
De at h  
Deat h.  
 
7. 3. 1  R el ati o ns hi p t o P r o c e d u r e D efi niti o ns  
Ass oci ate d:  T here is a reas o na ble p ossi bilit y t hat t he A E ma y ha ve bee n ca use d b y t he test 
pr o d uct a n d/ or pr oce d ure.  T his defi niti o n a p plies t o t h ose a d verse e ve nts t hat are c o nsi dere d 
defi nitel y, pr o ba bl y or p ossi bl y relate d t o t he pr oce d ure.  
1.  Defi nitel y rel ate d:  A n  A E t hat f oll o ws a te m p oral se q ue nce fr o m a d mi nistrati o n of t he 
test pr o d uct a n d/ or pr oce d ure; f oll o ws a k n o w n res p o nse patter n t o t he test article a n d/ or 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 3 7  of 5 7  
* See a p pe n di x 6 . 0 
 
pr oce d ure; a n d, w he n a p pr o priate t o t he pr ot oc ol, is c o nfir me d b y i m pr o ve me nt after 
st o p pi n g t he test pr o d uct ( p ositi ve rec halle n ge: a n d b y rea p peara nce of t he reacti o n after 
re peat e x p os ure [ p ositi ve rec halle n ge]); a n d ca n n ot be reas o na bl y e x plai ne d b y k n o w n 
c haracteristics of t he s u bject’s cli nical state or b y ot her t hera pies.  
2.  Pr o b a bl y rel ate d:  A n A E t h at f oll o ws a reas o na ble te m p oral se q ue nce fr o m 
a d mi nistrati o n of t he test pr o d uct a n d/ or pr oce d ure; f oll o ws a k n o w n res p o nse patter n t o 
t he test pr o d uct a n d/ or pr oce d ure, is c o nfir me d b y i m pr o ve me nt after rec halle n ge; a n d 
ca n n ot be reas o na bl y e x plai ne d b y t he k n o w n c haracteristics of t he partici pa nt’s cli nical 
state or ot her t hera pies. 
3.  P ossi bl y rel ate d:  A n A E t hat f oll o ws a reas o na ble te m p oral; se q ue nce fr o m 
a d mi nistrati o n of t he test pr o d uct a n d/ or pr oce d ure a n d f oll o ws a k n o w n res p o nse patter n 
t o t he test pr o d uct a n d/ or pr oce d ure, b ut c o ul d ha ve bee n pr o d uce d b y t he partici pa nt’s 
cli nical state or b y ot her t hera pies.  
 
N ot ass oci ate d:  A n A E f or w hic h s ufficie nt i nf or mati o n e xists t o i n dicate t hat t he eti ol o g y is n ot 
relate d t o t he test pr o d uct a n d/ or t hera py.  
1.  U nrel ate d : A n A E t hat d oes n ot f oll o w a reas o na ble te m p oral se q ue nce after 
a d mi nistrati o n of t he test pr o d uct a n d/ or pr oce d ure a n d m ost li kel y is e x plai ne d b y t he 
partici pa nt’s cli nical disease state or b y ot her t hera pies.  I n a d diti o n, a ne gati ve 
rec halle n ge t o t he test article a n d/ or pr oce d ure w o ul d s u p p ort a n u nrelate d relati o ns hi p. 
F or a d diti o nal i nf or mati o n a n d a pri nta ble versi o n of t he N CI -C T C A E ma n ual, c o ns ult t he N CI -
C T C A E we bsite, htt p:/ /cte p.ca ncer. g o v/re p orti n g/ctc. ht ml. 
7. 4  
A d v e rs e E v e nts C oll e cti o n P r o c e d u r es  
T he Pri nci pal I n vesti gat or a n d C o -I n vesti gat or are res p o nsi ble f or c ollecti n g a n d rec or di n g all 
cli nical data.  As t hese res ults are c ollecte d, all t o xicities a n d a d verse e ve nts will  be i de ntifie d 
a n d re p orte d t o t he pri nci pal i n vesti gat or.  A d verse e ve nts will be re p orte d as descri be d a b o ve.  
T he Pri nci pal I n vesti gat or will deter mi ne relati o ns hi p of t he e ve nt t o t he st u d y i nter ve nti o n a n d 
deci de c o urse of acti o n f or t he st u d y partici pa nt.  
7. 4. 1  R e c o r di n g a n d R e p o rti n g P r o c e d u r es  
M o nit ori n g of t he pri mar y site ( U N C -C H) will be c o n d ucte d via I nter nal A u dits wit h a Researc h 
Safet y A d v ocate o n t he D S M B.  T he pri mar y site ( U N C -C H) will be res p o nsi ble f or m o nit ori n g 
of t he sec o n dar y site ( U T S W).  Details of t his m o nit ori n g are i n c o nti n ui n g de vel o p me nt.  
M o nit ori n g will occ ur se mi -a n n uall y a n d y earl y re p orts will be ma de t o t he pr o per I nstit uti o nal 
C o m mittee s, as re q uire d.  All a d verse e ve nts will be ke pt i n a file b y n u merical i de ntifier. 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 3 8  of 5 7  
* See a p pe n di x 6 . 0 
 
7. 4. 2  S A E R e c o r di n g a n d R e p o rti n g  
Seri o us a d verse e ve nts will be rec or de d o n t he a p pr o priate case re p ort f or ms.  
7. 5  
S e ri o us A d v e rs e E v e nt N otifi c ati o n  
T he researc h staff will n otif y  t he s p o ns or/ pri nci pal i n vesti gat or of a n y seri o us a d verse e ve nt 
i m me diatel y u p o n lear ni n g a b o ut t he e ve nt. 
7. 5. 1  N otif yi n g t h e F D A, I R B, a n d D S M B  
T he s p o ns or will pr o vi de t he D S M B  wit h listi n gs of all S A Es o n a n o n g oi n g basis.  F urt her m ore, 
t he s p o ns or will i nfor m t he F D A, I R B, a n d D S M B of e x pe dite d re p orts of S A Es.  
7. 5. 2  R e p o rti n g C rit e ri a  
T he i n vesti gat or will e ns ure t he ti mel y disse mi nati o n of all A E i nf or mati o n, i ncl u di n g e x pe dite d 
re p orts, t o t he I R B i n acc or da nce wit h a p plica ble l ocal re g ulati o ns a n d g ui deli nes. 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 3 9  of 5 7  
* See a p pe n di x 6 . 0 
 
8.  
M
E C H A N I S T I C A S S A Y S  
F ull c o m ple me ntar y st u dies will be perf or me d o n sa m ples fr o m t he U N C -C H site t o meas ure 
cell ular a n d h u m oral i m m u ne res p o nses at baseli ne a n d l o n git u di nall y.   T hese assa ys ha ve bee n 
selecte d base d o n h y p ot hesize d mec ha nis ms of cli nical t olera nce i n d ucti o n.  Mec ha nistic st u dies 
o n sa m ples fr o m t he U T S W site will be li mite d t o s ki n pric k testi n g, bl o o d i m m u n o gl o b uli ns, 
a n d sali var y i m m u n o gl o b uli ns.  T he bl o o d a n d sali var y st u dies will be s hi p pe d t o U N C-C H a n d 
pr ocesse d b y t he B ur ks la b orat or y.  
Earl y data de m o nstrates t hat dese nsitizati o n wit h pea n ut S LI T alters b ot h h u m oral a n d cell ular 
para meters  [1 0 ].  We a ntici pate t hat pea n ut S LI T will i n d uce cli nical dese nsitizati o n a n d 
t olera nce b y eit her ( 1) a c o n versi o n fr o m a TH 2 t o T H 1 i m m u ne res p o nse or ( 2) t he i n d ucti o n of 
T R e gs  or ( 3) a c o m bi nati o n of b ot h.  S u bjects will be f oll o we d f or c ha n ges i n i m m u n ol o gic 
para meters fr o m baseli ne a n d a n n uall y  f or t he d urati o n of t he st u d y.  A fi nal bl o o d dra w will be 
perf or me d at t he ti me of t h e t olera nce D B P C F C after disc o nti n ui n g pea n ut S LI T or place b o 
t hera p y f or 3 m o nt hs.  I m m u n ol o gic assa ys will f oc us o n pea n ut  s pecific para meters i ncl u di n g: 
1) bas o p hil acti vati o n a n d s ki n pric k testi n g; 2) h u m oral st u dies - s pecific I g E, I g G, I g G 4, a n d 
I g A i n bl o o d a n d sali va; a n d 3) cell ular st u dies –  T re g acti vati o n a n d T cell-sti m ulate d c yt o ki ne 
pr o d ucti o n.   
Briefl y, P B M C’s will be is olate d fr o m bl o o d dra w n at yearl y ti me p oi nts a n d c ult ure d wit h cr u de 
pea n ut e xtract ( C P E)  [2 6 ], teta n us t o xi n, a n d C o n A t o assess cell ular pr oliferati o n res p o nses.  A 
c o ntr ol pr oliferati o n assa y usi n g n o nsti m ulate d cells will al s o be perf or me d.  I n a d diti o n, c ult ures 
will be set u p t o assess c yt o ki ne pr o d ucti o n b y P B M C’s after sti m ulati o n wit h C P E, teta n us 
t o xi n, C o n A a n d c o ntr ol.  C ult ure s u per nata nts will be a nal yze d yearl y  f or t he le vels of t he 
f oll o wi n g c yt o ki nes: I F N-g, I L-4 , I L-5, I L -1 0, I L -1 3, T G F -b  a n d T N F-a .  Usi n g fl o w c yt o metr y, 
we will deter mi ne t he prese nce of T R e gs  i n t he bl o o d sa m ple eac h year .  Bas o p hil st u dies will be 
perf or me d a n n uall y t o e xa mi ne acti vati o n mar kers.  Sali var y a n d bl o o d  pea n ut s pecific a nti b o d y 
le vels, i ncl u di n g I g E, I g G, I g G 4, a n d I g A will be assesse d a n n uall y. 
8. 1  
Bl o o d  s p e cifi c I g E, I g G, I g G 4, a n d I g A  
Aller ge n i m m u n ot hera p y has bee n s h o w n t o i n d uce a nti ge n -s pecific h u m oral res p o nses.  T he 
bala nce of is ot y pic res p o nse ma y pla y a r ole i n aller ge n se nsiti vit y (e. g., a n i ncrease of I g G/ 
I g E).  Bl o o d will be c ollecte d  at baseli ne, a n n uall y, a n d at t he t olerance D B P C F C (if nee de d) . 
Pea n ut -s pecific I g E, I g G, I g G 4, a n d I g A le vels will be meas ure d usi n g t he P ha dia I m m u n o C A P 
1 0 0 i nstr u me nt ( U p psala, S we de n) acc or di n g t o t he ma n ufact urer’s i nstr ucti o ns.   

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 4 0  of 5 7  
* See a p pe n di x 6 . 0 
 
8. 2  
S ali v a r y s p e cifi c I g G , I gA , I g E, a n d S e c r et o r y I g A 
We will u tilize E LI S A assa ys t o e val uate h ost a nti b o d y res p o nses t o Ara h 2 a n d w h ole pea n ut 
e xtract i n sali va sa m ples c ollecte d at t he desi g nate d ti me p oi nts f or bl o o d  c ollecti o n ( baseli ne, 
a n n uall y, a n d at t he t olera nce D B P C F C ).  Ara h 2 is t he maj or aller ge n f o u n d i n pea n ut.  Ot hers 
ha ve use d sali va t o meas ure aller ge n -s pecific S-I g A res p o nses i n aller gic c hil dre n as well as 
a nti ge n-s pecific S-I g A i n d uce d i n res p o nse t o oral i m m u nizati o n wit h K L H ( ke y h ole li m pet 
he m oc ya ni n) or a c h olera vacci ne.  Sali va sa m ples will be teste d at a n i nitial dil uti o n of 1: 4 
f oll o we d b y serial 2-f ol d dil uti o ns u ntil we are a ble t o deter mi ne a n e n d p oi nt titer.  A n e n d p oi nt 
titer will be calc ulate d as t he last sa m ple dil uti o n t hat has a n E LI S A rea di ng (fl u oresce nt relati ve 
li g ht u nits) 3-f ol d great t ha n t he R L U of t he sa me sa m ple teste d a gai nst E LI S A plates t hat are 
n ot c oate d wit h a nti ge n.  O nce t he a nti ge n -s pecific e n d p oi nt titers are calc ulate d, we will 
q ua ntitate t he t otal c o nce ntrati o n ( mc g / ml) of I g G, I gA , I gE , secret or y-I g A i n eac h sali va sa m ple 
a n d re p ort t he a nti ge n -s pecific res p o nses as a “titer/mc g  of t otal a nti b o d y”.  
8. 3  
C yt o ki n e m e as u r e m e nts  
Is olate d P B M Cs  fr o m baseli ne a n d 1 2, 2 4, 3 6, a n d 3 9 m o nt h ti me  p oi nts  will be  c ult ure d i n 
R P MI 1 6 4 0 c o ntai ni n g 1 0 % fetal b o vi ne ser u m, 1 % pe nicilli n/stre pt o m yci n, a n d 1 % gl uta mi ne.  
Cells will be c ult ure d i n 2 4 well plates ( 4 x 1 0 6/ well/ ml) i n t he prese nce or a bse nce of C P E (2 0 0  
mc g / ml), teta n us t o xi n ( 5 mc g / ml), or C o n A (5  mc g / ml).  S u per nata nts will be c ollecte d after 7 2 
hrs of c ult ure a n d ali q u ots will be st ore d at – 8 0 °C u ntil a nal yze d.  I F N -g, I L-4, I L-5, I L -1 3, I L -
1 0, T G F -b , a n d T N F-a  le vels will be deter mi ne d eit her b y E LI S A acc or di n g t o t he 
ma n ufact urer’s i nstr ucti o ns  ( R & D s yste ms, Mi n nea p olis) or b y a C yt o ki ne Bea d Arra y ( B D).  
T he sti m ulate d cells will be c ollecte d t o is olate R N A w hic h will be use d t o meas ure G A T A-3, T -
bet, F o x p 3, a n d TH 2 c yt o ki nes b y q P C R.  
8. 4  
T R e g  ass a y  
Is olate d P B M Cs fr o m baseli ne a n d 1 2, 2 4, 3 6, a n d 3 9  m o nt h  ti me p oi nts will be c ult ure d wit h 
C P E ( 2 0 0 mc g/ ml) or me dia al o ne a n d i nc u bate d f or 7 da ys.  Cells will be s urface stai ne d f or 
C D 4 a n d C D 2 5, t he n i ntracell ularl y stai ne d f or F o x P 3.  T he prese nce of T Re gs  will be assesse d b y 
fl o w c yt o metr y ( C D 2 5 +/ C D 4 +/ F o x p3 +).  
8. 5  
B as o p hil a cti v ati o n ass a y  
W h ole bl o o d fr o m baseli ne a n d 1 2, 2 4, 3 6, a n d 3 9  m o nt h ti me p oi nts will be di vi de d a n d 
sti m ulate d i n t he prese nce of I L-3 wit h se veral dil uti o ns of pea n ut a nti ge n ( 1 0 0 mc g/ ml, 1 0 -1 
mc g/ ml, 1 0 -2 mc g/ ml, 1 0 -3 mc g/ ml), a nti -I g E ( 1 mc g/ ml), a n d me dia al o ne.  After 3 0 mi n utes 
i nc u bati o n, R B Cs will be l yse d a n d le u k oc ytes will be fi xe d a n d st ore d fr oze n f or batc h m A b 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 4 1  of 5 7  
* See a p pe n di x 6 . 0 
 
stai ni n g a n d fl o w c yt o metric a nal ysis of acti vati o n mar kers.  Bas o p hils will be i de ntifie d as 
C D 1 2 3 +  C D 2 0 3c +  li n- ( CD 3, C D 1 4, C D 1 9, C D 4 1) e ve nts a n d acti vati o n will be assesse d b y 
C D 2 0 3c ( E N P P 3) a n d C D 6 3 ( L A M P -3), w hic h are mar kers f or piece meal a n d classical 
de gra n ulati o n, res pecti vel y.  
8. 6  
St o ol  Ass a y   
St o ol ma y be use d f or micr o bi o me st u dies t o i de ntif y i n di vi d ual strai ns of bacteria f o u n d i n t he 
st o ol.  T hese st u dies c o ul d all o w t he researc hers t o ma ke ass ociati o ns of g ut fl ora t o cli nical 
dese nsitizati o n a n d t olera nce o utc o mes.   A d diti o nall y, st o ol e xtracts ma y be a nal yze d f or I g A, 
I g A 2, secret or y-I g A, or ot her i m m u n o gl o b uli ns.   T hese st u dies c o ul d all o w t he researc hers t o 
i de ntif y c ha n ges d uri n g t he c o urse of t he st u d y t o cli nical o utc o mes, w hic h are n ot p ossi ble fr o m 
peri p heral bl o o d sa m ples . 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 4 2  of 5 7  
* See a p pe n di x 6 . 0 
 
9.  
S T A T I S T I C A L C O N S I D E R A T I O N S  
9. 1  
St u d y E n d p oi nt Ass ess m e nt  
9. 1. 1  P ri m a r y E n d p oi nt  
T he pri mar y e n d p oi nt is defi ne d i n Secti o n 3. 1. 1 .  Data will be a nal yze d i n a n i nte nti o n -t o-treat 
a p pr oac h.  L o gistic re gressi o n  will be utilize d t o c o m pare t he D B P C F C c halle n ge sc ores  of 
s u bjects o n pea n ut S LI T after 3 6 m o nt hs *  vers us t h e c halle n ge sc ores of s u bjects  o n place b o 
after 3 6 m o nt hs * .  Details of t his a nal ysis are descri be d i n 2 0 1 2 P R A C T A L L c o nse ns us re p ort 
o n sta n dar dizi n g oral f o o d c halle n ges [2 5 ].  I n s h ort, c halle n ge res ults will be sc ore d base d o n 
t he # of d ose wit hi n t he c halle n ge s uccessf ull y i n geste d.  A n e xtre me val ue hazar d f u ncti o n will 
be calc ulate d a n d l o gistic re gressi o n use d t o create a discrete ti me s ur vi val a nal ysis.  
Sa m ple size was calc ulate d f or 9 0 % p o wer of detecti n g a p -val ue of 0. 0 5 c o nsi deri n g 1 : 1 
treat me nt: place b o ra n d o mizati o n a n d esti mati n g an  8 0 % pass rate f or t h ose ra n d o mize d t o pea n ut 
S LI T  vers us a 2 0 % pass rate f or t h ose ra n d o mize d t o place b o .  A dj usti n g f or a n esti mate d 2 0 % 
dr o p o ut rat e res ults i n a mi ni m u m re q uire d sa m ple size of 5 0 s u bjects.  
9. 1. 2  S e c o n d a r y E n d p oi nts  
T he sec o n dar y e n d p oi nts are defi ne d i n Secti o n 3. 1. 2.   C o m paris o n of t he c halle n ge sc ores of 
s u bjects o n pea n ut S LI T vers us o n place b o passi n g t he t olera nce D B P C F C 3  m o nt hs after 
disc o nti n ui n g  treat me nt will be perf or me d usi n g l o gistic re gressi o n i n a si milar fas hi o n as t he 
pri mar y e n d p oi nt .  C o m paris o n of  s ki n pric k testi n g a n d mec ha nistic data (i m m u n o gl o b uli ns, 
bas o p hil reacti vit y, c yt o ki nes, a n d T R e gs ) bet wee n t h ose o n pea n ut S LI T vers us t h ose o n place b o 
will be perf or me d usi n g a t w o-sa m ple t-test ( S A S 9.3 , S A S, C ha pel Hill, N C) wit h a p-val ue < 
0. 0 5 c o nsi dere d si g n ifica nt.  
9. 2  
S u bj e ct a n d D e m o g r a p hi c D at a  
9. 2. 1  B as eli n e C h a r a ct e risti cs a n d D e m o g r a p hi cs  
S u m mar y descri pti ve statistics f or baseli ne a n d de m o gra p hic c haracteristics will be pr o vi de d f or 
all e nr olle d partici pa nts.  De m o gra p hic data will i ncl u de a ge, race, se x, b o d y  wei g ht, a n d hei g ht; 
t hese data will be prese nte d i n t he f oll o wi n g ma n ner: 
•  C o nti n u o us data (i.e., a ge, b o d y wei g ht, a n d hei g ht) will be s u m marize d descri pti vel y b y 
mea n, sta n dar d de viati o n, me dia n, a n d ra n ge.   
•  Cate g orical data (i.e., se x a n d race) will be  prese nte d as e n u merati o ns a n d perce nta ges.   
Statistical prese ntati o n f or baseli ne a n d de m o gra p hic c haracteristics ma y be f urt her s u m marize d 
b y treat me nt gr o u p, baseli ne pea n ut -s pecific I g E, a n d q ualif yi n g e ntr y D B P C F C.  Statistical 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 4 3  of 5 7  
* See a p pe n di x 6 . 0 
 
c o m paris o n of t he t hes e gr o u ps will be perf or me d b y Fis her’s e xact test ( S A S 9. 3 , S A S, C ha pel 
Hill, N C)  
9. 2. 2  St u d y C o m pl eti o n  
T he perce nt a ge of partici pa nts w h o c o m plete t he st u d y, l osses t o f oll o w -u p, ti mes t o l ost t o 
f oll o w-u p, a n d reas o ns f or disc o nti n uati o n (e. g., a d verse e ve nts) will be prese nte d.  Statistical 
prese ntati o n of st u d y c o m pleti o n will be f urt her prese nte d via a nal ysis of t he sec o n dar y 
e n d p oi nts s u m marize d.  
9. 3  
I nt e ri m A n al ys es t o E ns u r e P ati e nt S af et y  
All e x pe dite d a d verse e ve nt re p orts will be re vie we d b y t he D S M B i n its c o n ve ne d meeti n gs.  
T he a n n ual s u m mar y of all a d verse e ve nts a n d a n y a u dit re p orts will be re vie we d a n n uall y b y t he 
D S M B . 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 4 4  of 5 7  
* See a p pe n di x 6 . 0 
 
1 0.  
I D E N T I F I C A T I O N A N D A C C E S S T O S O U R C E D A T A  
1 0. 1  D at a M a n a g e m e nt  
All rec or ds ge nerate d d uri n g t he visits will be st ore d b ot h i n a n electr o nic data base t hr o u g h t he 
data ma na ge me nt c o m pa n y a n d t he i n di vi d ual s u bject’s researc h st u d y bi n der.  S pecifics o n t he 
mec ha nis m of data ma na ge me nt a n d m o nit ori n g of t he sec o n dar y site’s ( U T S W) data are i n 
c o nti n ui n g de vel o p me nt.  T he s u bject’s i nf or mati o n will be  accessi ble o nl y t o t he i n vesti gat or or 
his desi g nate d c ollea g ues b y i n di vi d ual pass w or d or direct vie wi n g of t he researc h rec or d . 
1 0. 2  A c c ess t o D at a  
T he s u bject’s i nf or mati o n is accessi ble o nl y t o t he i n vesti gat or or his desi g nate d c ollea g ues b y 
i n di vi d ual pass w or d or direct vie wi n g of t he researc h rec or d.  T he researc h rec or ds will be ke pt 
i n a l oc ke d cl oset i n t he i n vesti gat or’s office s uite.  T he i n vesti gat or is re q uire d b y la w 
( 2 1 C F R 3 1 2. 6 2) t o kee p acc urate case rec or ds u ntil t he y o u n gest s u bject reac hes 2 1 years of a ge 
a n d or f or 6 years after t he i n vesti gati o n is disc o nti n ue d ( w hic he ver is l o n ger) a n d rec or d 
o bser vati o ns t o ass ure t he safe c o n d uct of t he st u d y . 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 4 5  of 5 7  
* See a p pe n di x 6 . 0 
 
1 1.  
Q U A L I T Y C O N T R O L A N D Q U A L I T Y A S S U R A N C E  
T he s p o ns or/i n vesti gat or is re q uire d t o kee p acc urate rec or ds t o e ns ure t hat t he c o n d uct of t he 
st u d y is f ull y d oc u me nte d.   
T he s p o ns or/i n vesti gat or is res p o nsi ble f or re g ularl y re vie wi n g t he c o n d uct of t he trial, f or 
verif yi n g a d here nce t o t he pr ot oc ol, a n d f or c o nfir mi n g t he c o m plete ness, c o nsiste nc y, a n d 
acc urac y of all d oc u me nte d data.   S pecific o n t he m o nit ori n g of t he sec o n dar y site ( U T S W) are 
i n c o nti n ui n g de vel o p me nt. 
1 1. 1  D at a H a n dli n g  
T he i n vesti gat or is re q uire d t o e ns ure t hat all C R Fs are le gi bl y c o m plete d f or e ver y partici pa nt 
e ntere d i n t he trial.   
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 4 6  of 5 7  
* See a p pe n di x 6 . 0 
 
1 2.  
E T H I C A L C O N S I D E R A T I O N S A N D C O M P L I A N C E W I T H G O O D 
C L I N I C A L P R A C T I C E  
1 2. 1  St at e m e nt of C o m pli a n c e  
T his st u d y will be c o n d ucte d usi n g g o o d cli nical practice ( G C P), as deli neate d i n G ui d a nce f or 
I n d ustry: E 6 G o od Cli nic al Pr actice C o ns oli d ate d G ui d a nce , a n d acc or di n g t o t he criteria 
s pecifie d i n t his st u d y pr ot oc ol.  Bef ore st u d y i nitiati o n, t he pr ot oc ol a n d t he i nf or me d c o nse nt 
d oc u me nts will be re vie we d a n d a p pr o ve d b y a n a p pr o priate E C or I R B.  A n y a me n d me nts t o t he 
pr ot oc ol or t o t he c o nse nt materials m ust als o be a p pr o ve d bef ore t he y are i m ple me nte d.  
1 2. 2  I nf o r m e d C o ns e nt a n d Ass e nt  
T he i nf or me d c o nse nt f or m is a mea ns of pr o vi di n g i nf or mati o n a b o ut t he st u d y t o a pr os pecti ve 
partici pa nt’s pare nt/ g uar dia n a n d all o ws f or a n i nf or me d decisi o n a b o ut partici pati o n i n t he 
st u d y.  Si nce all s u bjects will be < 1 8 years ol d, pare nts/le gal g uar dia ns will be as ke d t o rea d, 
si g n, a n d date a c o nse nt f or m bef ore e nteri n g t he st u d y, ta ki n g st u d y dr u g, or u n der g oi n g a n y 
st u d y-s pecific pr oce d ures.  C hil dre n will si g n asse nt as a p pr o priate.  C o nse nt materials f or 
s u bjects or pare nts/ g uar dia ns w h o d o n ot s pea k or rea d E n glis h will be tra nslate d i nt o t he 
a p pr o priate la n g ua ge.  T he i nf or me d c o nse nt f or m will be re vise d w he ne ver t he pr ot oc ol is 
a me n de d wit h a st u d y desi g n c ha n ge.  A c o p y of t he i nf or me d c o nse nt will be gi ve n t o a 
pr os pecti ve pare nt/ g uar dia n f or re vie w.  A st u d y  p h ysicia n  or n urse c o or di nat or , i n t he prese nce 
of a wit ness, will re vie w t he c o nse nt a n d a ns wer q uesti o ns.  T he  pr os pecti ve s u bject or 
pare nt/ g uar dia n will be t ol d t hat bei n g i n t he st u d y is v ol u ntar y a n d t hat he or s he ma y wit h dra w 
his/ her c hil d fr o m t he st u d y at a n y ti me, f or a n y reas o n . 
1 2. 3  P ri v a c y a n d C o nfi d e nti alit y  
A partici pa nt’s pri vac y a n d c o nfi de ntialit y will be res pecte d t hr o u g h o ut t he st u d y.  Eac h 
partici pa nt will be assi g ne d a se q ue ntial i de ntificati o n n u m ber a n d t hese n u m bers rat her t ha n 
na mes will be use d t o c ollect, st ore, a n d re p ort partici pa nt i nf or mati o n . 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 4 7  of 5 7  
* See a p pe n di x 6 . 0 
 
1 3.  
R E S O U R C E S H A R I N G  
S u bject i nf or mati o n will o nl y be s hare d usi n g t he u ni q ue s u bject i de ntificati o n n u m ber.  All 
ot her i de ntifiers of t he s u bject will be re m o ve d pri or t o t he release of t he i nf or mati o n.  If t he 
res ults of t he trial are p u blis he d, t he partici pa nt’s i de ntit y will re main c o nfi de ntial.  St u d y 
rec or ds will be retai ne d u ntil t he s u bject reac hes a ge 2 1.  At t hat p oi nt, a n y data n ot i n t he 
me dical rec or d will be destr o ye d.   
 
 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 4 8  of 5 7  
* See a p pe n di x 6 . 0 
 
Fi g ure 1 . St u d y Desi g n O ver vie w 
 
 
 
 
 
 
                                                                     
 
 
 
 
 
 
 
 
D B P C F C 
4 4 4 3 m g  
Scree ni n g 
Visit  
Visit -1  
R a n d o mizati o n 
1: 1  
Pea n ut       
n = 2 5  
Place b o 
n = 2 5  
 St u dies : i m m u ne 
st u dies +/- s ki n tests 
 
Assess t olera nce 3 
m o nt hs after 
disc o nti n ui n g 
t hera p y ( 1o o utc o m e)  
Assess 
dese nsitizati o n after 
3 6 m o nt hs of 
t hera p y ( 2o o utc o m e)  
6 m o  
1 2 m o  
1 8 m o  
2 4 m o  
3 0 m o  
* 3 6 m o  
* 3 9 m o  
D B P C F C 
4 4 4 3 m g  
D B P C F C 
1 0 0 0 m g  
* See A p pe n di x 6 re gar di n g c ha n ges i n st u d y visit 
ti me p oi nts d ue t o t he C O VI D -1 9 safet y meas ures  

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 4 9  of 5 7  
* See a p pe n di x 6 . 0 
 
A p pe n di x 1. Sc he d ule of E ve nts  
 
Scr e e ni n g  
Visit  
B as eli n e  
Visit  
I niti al 
D osi n g  
D os e Esc al ati o n  
* D es e nsitiz ati o n 
D B P C F C  
* T ol er a nc e 
D B P C F C  
Visit  #  
-1  
0  
1  
2  
3  
4  
5  
6  
7  
8  
9  
1 0  
1 1  
1 2  
M o nt h  
-1  
0  
0  
1  
2  
3  
4  
6  
1 2  
1 8  
2 4  
3 0  
3 6  
3 9  
I nf or m e d C o ns e nt  
X  
X  
X  
 
 
 
 
 
 
 
 
 
 
X  
R evi e w I ncl usi o n/ Excl usi o n 
Crit eri a  
X  
X  
X  
 
 
 
 
 
 
 
 
 
 
 
R a n d o miz ati o n ( 1 : 1) 
 
 
X  
 
 
 
 
 
 
 
 
 
 
 
D e m o gr a p hic I nf or m ati o n  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
M e dic al/ S ur gic al Hist or y  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
Di et a n d All er gy Ass ess m e nt  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
C o nc o mit a nt M e dic ati o ns  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Vit al Si g ns  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
C o m pr e h e nsiv e P hysic al 
Ex a m  
X  
X  
 
 
 
 
 
 
 
 
 
 
X  
X  
Bri ef P h ysic al Ex a m  
 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
 
S ki n Pric k T est  
X  
 
 
 
 
 
 
 
X  
 
X  
 
X  
X  
Bl o o d dr a w f or M ec h a nistic 
St u di es  
X  
 
 
 
 
 
 
 
X  
 
X  
 
X  
X  
St o ol C oll ecti o n  
X  
 
 
 
 
 
 
 
X  
 
X  
 
X  
 
S ali v a c oll ecti o n  
X  
 
 
 
 
 
 
 
X  
 
X  
 
X  
X  
D B P C F C  
 
X  
 
 
 
 
 
 
 
 
 
 
X  
X  
O bs erv e d SLI T D osi n g  
 
 
X  
X  
X  
X  
X  
 
 
 
 
 
 
 
Dis p e ns e St u d y M e dic ati o n  
 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
 
Ass ess C o m pli a nc e  
 
 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
R ec or d A Es  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
* See A p pe n di x 6 re gar di n g c ha n ges i n st u d y visit ti me p oi nts d ue t o t he C O VI D -1 9 safet y meas ures  
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 5 0  of 5 7  
* See a p pe n di x 6 . 0 
 
A p pe n di x 2. E v al u ati o n of Ast h m a  
T he e val uati o n of ast h ma se verit y will be assesse d usi n g t he N H L BI classificati o n as descri be d i n t he ta ble bel o w.  
Cl assific ati o n  
S y m pt o ms  
Ni g htti me 
a w a ke ni n gs  
L u n g F u ncti o n  
I nterfere nce wit h 
n or m al acti vit y  
S h ort acti n g bet a -a g o nist 
use  
I nter mitte nt 
( Ste p 1) 
• 
<  2 da ys per wee k  
<  2 x / m o nt h  
•  
N or mal F E V 1 bet wee n 
e xacer bati o ns  
•  
F E V 1> 8 0 % pre dicte d  
•  
F E V 1/ F V C n or mal * 
•  
N o ne  
•  
< 2 x / m o nt h  
Mil d Persiste nt  
( Ste p 2) 
• 
> 2 da ys per wee k b ut 
n ot dail y  
 
3 -4 x / m o nt h  
•  
F E V 1 >  8 0 % pre dicte d  
•  
F E V 1/ F V C n or mal * 
•  
Mi n or 
li mitati o n 
•  
3 -4 x / m o nt h  
M o derate Persiste nt  
( Ste p 3 or 4) 
• 
Dail y  
> 1 x / wee k b ut 
n ot ni g htl y  
•  
F E V 1 > 6 0 % b ut < 8 0 % 
pre dicte d  
•  
F E V 1/ F V C re d uce d 
5 % *  
•  
S o me li mitati o n  
•  
> 1 x / wee k b ut n ot 
ni g htl y  
Se vere Persiste nt  
( Ste p 5 or 6) 
• 
T hr o u g h o ut t he da y  
Ofte n 7 x / wee k 
•  
F E V 1< 6 0 % pre dicte d  
•  
F E V 1/ F V C re d uce d 
> 5 % *  
•  
E xtre mel y 
li mite d 
•  
Ofte n 7 x / wee k  
* N or mal F E V 1/ F V C: 8 -1 9 yr = 8 5 %; 2 0 -3 9 yrs = 8 0 %

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 5 1  of 5 7  
* See a p pe n di x 6 . 0 
 
A p pe n di x 3 . Aller gic Re acti o n a n d T o xicit y Gr a di n g 
C urre nt N CI -C T C A E gra di n g s yste m f or aller gic reacti o ns.  
Gra de 1 - Mil d  
Gra de 2 - M o derate  Gra de 3 –  Se vere  
Gra de 4 –  Life -
t hreate ni n g  
Gra de 5 - 
Deat h  
Tra nsie nt fl us hi n g 
or ras h,  
dr u g fe ver < 3 8 
de grees C ( < 1 0 0. 4 
de grees F); 
i nter ve nti o n n ot 
i n dicate d  
I nter ve nti o n or 
i nf usi o n  
i nterr u pti o n 
i n dicate d;  
res p o n ds pr o m ptl y 
t o  
s y m pt o matic 
treat me nt (e. g., 
a nti hista mi nes, 
N S AI D S, 
narc otics); 
pr o p h ylactic 
me dicati o ns 
i n dicate d f or < = 2 4 
h rs  
Pr ol o n ge d (e. g., n ot 
ra pi dl y  
res p o nsi ve t o 
s y m pt o matic  
me dicati o n a n d/ or brief  
i nterr u pti o n of i nf usi o n);  
rec urre nce of s y m pt o ms  
f oll o wi n g i nitial 
i m pr o ve me nt;  
h os pitalizati o n i n dicate d 
f or  
cli nical se q uelae (e. g., 
re nal  
i m pair me nt, p ul m o nar y  
i nfiltrates)  
Life -t hreate ni n g  
c o nse q ue nces; ur ge nt 
i nter ve nti o n i n dicate d  
Deat h  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 5 2  of 5 7  
* See a p pe n di x 6 . 0 
 
T he N CI -C T C A E ta ble will be re place d wit h t he St u d y s pecific gra di n g s yste m f or aller gic reacti o ns as 
dis pla ye d bel o w.   
Gra de 1 - Mil d  
Gra de 2 - M o derate  
Gra de 3 - Se vere  
Gra de 4 - Life 
t hreate ni n g 
Gra de 5 - 
Deat h  
Tra nsie nt or mil d 
disc o mf orts ( < 4 8 
h o urs), n o or 
mi ni mal  me dical 
i nter ve nti o n/t hera p y 
re q uire d. T hese 
s y m pt o ms ma y 
i ncl u de pr urit us, 
s welli n g or ras h, 
a b d o mi nal 
disc o mf ort or ot her 
tra nsie nt s y m pt o ms. 
S y m pt o ms t hat 
pr o d uce mil d t o 
m o derate li mitati o n i n 
acti vit y s o me 
assista nce ma y be 
nee de d; n o or mi ni mal 
i nter ve nti o n/t hera p y is 
re q uire d. 
H os pitalizati o n is 
p ossi ble. T hese 
s y m pt o ms ma y i ncl u de 
persiste nt hi ves, 
w heezi n g wit h o ut 
d ys p nea, a b d o mi nal 
disc o mf ort/ i ncrease d 
v o miti n g or ot her 
s y m pt o ms 
Mar ke d li mitati o n i n 
acti vit y, s o me 
assista nce us uall y 
re q uire d; me dical 
i nter ve nti o n/t hera p y 
re q uire d, 
h os pitalizati o n is 
p ossi ble S y m pt o ms 
ma y i ncl u de 
Br o nc h os pas m wit h 
d ys p nea, se vere 
a b d o mi nal pai n, t hr oat 
ti g ht ness wit h 
h oarse ness, tra nsie nt 
h y p ote nsi o n a m o n g 
ot hers. Pare nteral 
me dicati o n(s) are 
us uall y i n dicate d.  
E xtre me li mitati o n 
i n acti vit y, 
si g nifica nt 
assista nce re q uire d; 
si g nifica nt 
me dical/t hera p y. 
I nter ve nti o n is 
re q uire d; 
h os pita lizati o n is 
pr o ba ble. S y m pt o ms 
ma y i ncl u de 
persiste nt 
h y p ote nsi o n a n d/ or 
h y p o xia wit h 
res ulta nt decrease d 
le vel of 
c o nsci o us ness 
ass ociate d wit h 
c olla pse a n d/ or 
i nc o nti ne nce or 
ot her life t hreate ni n g 
s y m pt o ms. 
Deat h  
 
 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 5 3  of 5 7  
* See a p pe n di x 6 . 0 
 
A p pe n di x 4. Criteri a f or deter mi ni n g t he o utc o me of a n Or al F o o d C h alle n ge  
Maj or Criteria  
•  C o nfl ue nt er yt he mat o us pr uritic ras h  
•  Res pirat or y si g ns (at least o ne of t he f oll o wi n g: w heezi n g, i na bilit y t o s pea k, 
stri d or, d ys p h o nia, a p h o nia) 
•  > 3 urticarial lesi o ns  
•  > 1 site of a n gi oe de ma  
•  > 2  disti nct e pis o des of v o miti n g  
•  H y pt ote nsi o n f or a ge n ot ass ociate d wit h vas o va gal e pis o de  
•  E vi de nce of se vere a b d o mi nal pai n t hat persists f or > 5 mi n utes  
Mi n or Criteria  
•  1 -2 urticarial lesi o ns  
•  Si n gle e pis o de of v o miti n g  
•  Diarr hea  
•  N ota ble distresse d beca use of na usea a n d / or a b d o mi nal pai n wit h decrease d 
acti vit y 
•  Dr y hac ki n g c o u g h lasti n g > 3 mi n utes  
•  C o m plai nt of t hr oat ti g ht ness a n d/ or pr uritis pl us > 3 e pis o des of t hr oat cleari n g  
•  Persiste nt r u b bi n g of n ose or e yes t hat lasts f or >  5 mi n utes  
•  Persiste nt r hi n orr hea t hat lasts f or > 5 mi n utes  
•  C o nti n u o us har d scratc hi n g t hat lasts f or >  3 mi n utes  
•  Disti nct c ha n ge i n affect; w hi ni n g, cr yi n g a n d/ or cli n gi n g t o pare nt  
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 5 4  of 5 7  
* See a p pe n di x 6 . 0 
 
A p pe n di x 5 . Refere nces 
1.  
Sa m ps o n, H. A., U p d ate o n f o o d aller gy.  J Aller g y Cli n I m m u n ol, 2 0 0 4. 1 1 3 ( 5): p. 8 0 5-1 9; q uiz 
8 2 0.  
2.  
Sic herer, S. H., et al., U S prev ale nce of self -re p orte d pe a n ut, tree n ut, a n d ses a me aller gy: 1 1-
ye ar f oll o w-u p.  J Aller g y Cli n I m m u n ol, 2 0 1 0. 1 2 5 ( 6): p. 1 3 2 2-6.  
3.  
de Sil va, I. L., et al., P ae di atric a n a p hyl axis: a 5 ye ar retr os pective revie w.  Aller g y, 2 0 0 8. 6 3 ( 8): 
p. 1 0 7 1 -6.  
4.  
B oc k, S. A., A. M u n oz -F url o n g, a n d H. A. Sa m ps o n, F urt her f at alities c a use d by a n a p hyl acti c 
re acti o ns t o f o o d, 2 0 0 1-2 0 0 6.  J Aller g y Cli n I m m u n ol, 2 0 0 7. 1 1 9 ( 4): p. 1 0 1 6-8.  
5.  
B oc k, S. A., A. M u n oz -F url o n g, a n d H. A. Sa m ps o n, F at alities d ue t o a n a p hyl actic re acti o ns t o 
f o o ds. J Aller g y Cli n I m m u n ol, 2 0 0 1. 1 0 7 ( 1): p. 1 9 1-3.  
6.  
Nels o n, H. S., et al., Tre at me nt of a n a p hyl actic se nsitivity t o pe a n uts by i m m u n ot her a py wit h 
i njecti o ns of a q ue o us pe a n ut extr act. J Aller g y Cli n I m m u n ol, 1 9 9 7. 9 9 ( 6 Pt 1): p. 7 4 4-5 1.  
7.  
O p pe n hei mer, J.J., et al., Tre at me nt of pe a n ut aller gy wit h r us h i m m u n ot her a py.  J Aller g y Cli n 
I m m u n ol, 1 9 9 2. 9 0 ( 2): p. 2 5 6-6 2.  
8.  
J o nes, S. M., et al., Cli nic al effic acy a n d i m m u ne re g ul ati o n wit h pe a n ut or al i m m u n ot her a py.  
J o ur nal of Aller g y a n d Cli nical I m m u n ol o g y, 2 0 0 9. 1 2 4 ( 2): p. 2 9 2-3 0 0.e 9 7.  
9.  
Vars h ne y, P., et al., A r a n d o mize d c o ntr olle d st u dy of pe a n ut or al i m m u n ot her a py: cli nic al 
dese nsitiz ati o n a n d m o d ul ati o n of t he aller gic res p o nse.  J Aller g y Cli n I m m u n ol, 2 0 1 1. 1 2 7 ( 3): p. 
6 5 4 -6 0.  
1 0.  
Ki m, E. H., et al., S u bli n g u al i m m u n ot her a py f or pe a n ut aller gy: cli nic al a n d i m m u n ol o gic 
evi de nce of dese nsitiz ati o n.  J Aller g y Cli n I m m u n ol, 2 0 1 1. 1 2 7 ( 3): p. 6 4 0-6 e 1.  
1 1.  
Lerc h, E. a n d U. R. M uller, L o n g -ter m pr otecti o n after st o p pi n g ve n o m i m m u n ot her a py: res ults of 
re-sti n gs i n 2 0 0 p atie nts. J Aller g y Cli n I m m u n ol, 1 9 9 8. 1 0 1 ( 5): p. 6 0 6-1 2.  
1 2.  
A k dis, C. A. a n d M. A k dis, Mec h a nis ms of aller ge n -s pecific i m m u n ot her a py. J Aller g y Cli n 
I m m u n ol, 2 0 1 1. 1 2 7 ( 1): p. 1 8-2 7; q uiz 2 8 -9.  
1 3.  
Alla m, J. P., et al., P hl p 5 res or pti o n i n h u m a n or al m uc os a le a ds t o d ose -de pe n de nt a n d ti me -
de pe n de nt aller ge n bi n di n g by or al m uc os al L a n ger h a ns cells, atte n u ates t heir m at ur ati o n, a n d 
e n h a nces t heir mi gr at ory a n d T G F -bet a 1 a n d I L -1 0 -pr o d uci n g pr o perties.  J Aller g y Cli n 
I m m u n ol, 2 0 1 0. 1 2 6 ( 3): p. 6 3 8-4 5 e 1.  
1 4.  
C o x, L. S., et al., S u bli n g u al i m m u n ot her a py: a c o m pre he nsive revie w.  J Aller g y Cli n I m m u n ol, 
2 0 0 6. 1 1 7 ( 5): p. 1 0 2 1-3 5.  
1 5.  
Ki m, E. H., et al., T oler a nce I n d ucti o n i n a n I nteri m A n alysis of Pe a n ut S u bli n g u al 
I m m u n ot her a py. J Aller g y Cli n I m m u n ol, 2 0 1 3. 1 3 1 ( 2): p. A B 1 3 0. 
1 6.  
B ur k, C., et al., C h a n ges i n I g E a n d I g G 4 I n dic ative of Dese nsitiz ati o n Are Ass oci ate d wit h Ar a h 
1 a n d 2, b ut N ot Ar a h 3, 8, a n d 9, i n S u bjects O n S u bli n g u al I m m u n ot her a py f or Pe a n ut Aller gy.  
J Aller g y Cli n I m m u n ol, 2 0 1 3. 1 3 1 ( 2): p. A B 3 3 0. 
1 7.  
K ulis, M. D., et al., Devel o p me nt of T oler a nce F oll o w i n g Pe a n ut I m m u n ot her a py Is Ass oci ate d 
wit h B as o p hil Hy p ores p o nsive ness a n d L o w Pe a n ut -I g E:I g G 4 R ati o. J Aller g y Cli n I m m u n ol, 
2 0 1 3. 1 3 1 ( 2): p. A B 1 3 1. 
1 8.  
Gree n, T. D., et al., Cli nic al c h ar acteristics of pe a n ut -aller gic c hil dre n: rece nt c h a n ges.  
Pe diatrics , 2 0 0 7. 1 2 0 ( 6): p. 1 3 0 4-1 0.  
1 9.  
Os b or ne, N.J., et al., Prev ale nce of c h alle n ge -pr ove n I g E -me di ate d f o o d aller gy usi n g 
p o p ul ati o n -b ase d s a m pli n g a n d pre deter mi ne d c h alle n ge criteri a i n i nf a nts.  J Aller g y Cli n 
I m m u n ol, 2 0 1 1. 1 2 7 ( 3): p. 6 6 8-7 6 e 1 -2.  
2 0.  
Sic herer, S. H., et al., I m m u n ol o gic fe at ures of i nf a nts wit h milk or e g g aller gy e nr olle d i n a n 
o bserv ati o n al st u dy ( C o ns orti u m of F o o d Aller gy Rese arc h) of f o o d aller gy.  J Aller g y Cli n 
I m m u n ol, 2 0 1 0. 1 2 5 ( 5): p. 1 0 7 7-1 0 8 3 e 8.  

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 5 5  of 5 7  
* See a p pe n di x 6 . 0 
 
2 1.  
R o we, J., et al., Pre n at al  vers us p ost n at al se nsitiz ati o n t o e nvir o n me nt al aller ge ns i n a hi g h -risk 
birt h c o h ort.  J Aller g y Cli n I m m u n ol, 2 0 0 7. 1 1 9 ( 5): p. 1 1 6 4-7 3.  
2 2.  
Ne u ma n -S u ns hi ne, D. L., et al., T he n at ur al hist ory of persiste nt pe a n ut aller gy.  A n n Aller g y 
Ast h ma I m m u n ol, 2 0 1 2.  1 0 8 ( 5): p. 3 2 6-3 3 1 e 3.  
2 3.  
Vic ker y, B., et al., E arly i nterve nti o n wit h or al i m m u n ot her a py is a pr o misi n g str ate gy f or t he 
tre at me nt of pe a n ut aller gy. J Aller g y Cli n I m m u n ol, 2 0 1 2. 1 2 9 : p. A B 2 7. 
2 4.  
Vic ker y, B., et al., L o w -d ose or al i m m u n ot her a py as a n e arly i nterve nti o n str ate gy f or pe a n ut 
aller gy.  J Aller g y Cli n I m m u n ol, 2 0 1 3. 1 3 1 : p. A B 1 3 0. 
2 5.  
Sa m ps o n, H. A., et al., St a n d ar dizi n g d o u ble -bli n d, pl ace b o -c o ntr olle d or al f o o d c h alle n ges: 
A meric a n Ac a de my of Aller gy, Ast h m a & I m m u n ol o gy -E ur o pe a n Ac a de my o f Aller gy a n d 
Cli nic al I m m u n ol o gy P R A C T A L L c o nse ns us re p ort.  J Aller g y Cli n I m m u n ol, 2 0 1 2. 1 3 0 ( 6): p. 
1 2 6 0 -7 4.  
 
 
 

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 5 6  of 5 7  
* See a p pe n di x 6 . 0 
 
A p pe n di x 6. 0  C O VI D -1 9 S afet y Me as ures  
I n Marc h of 2 0 2 0, State a n d Nati o nal e mer ge ncies were declare d o ver t he gl o bal pa n de mic 
c or o na vir us C O VI D -1 9.  U N C -C H  instit ute d  safet y meas ures ( o utli ne d here: 
htt ps:// w w w. u nc.e d u/c or o na vir us/  ) i n a n eff ort t o sl o w t he s prea d of t he vir us a n d hel p ste m t he 
fl o w of patie nts nee di n g access t o the e mer ge nc y res p o nse ser vices a n d t he e mer ge nc y 
de part me nt at U N C H os pitals.  Staff recei ve d g ui da nce f or s ocial dista nci n g a n d re m ote w or ki n g.  
St u de nts were e nc o ura ge d t o re mai n off ca m p us.  Meas ures were create d t o desi g nate esse ntial 
pers o nal as well as halt all n o n -esse ntial a n d i n pers o n visits.  M ost ca m p us b uil di n gs were als o 
s h ut d o w n.  Tele me dici ne meas ures were i m ple me nte d t o scree n patie nts pri or t o i n-pers o n 
treat me nt. C O VI D-1 9 testi n g l ocati o ns were als o create d utilizi n g U N C me dical staff.   
I n li g ht of t he c urre nt sit uati o n, ca m p us researc h als o recei ve d g ui da nce fr o m t he office of Vice 
C ha ncell or of Researc h ( o utli ne d here:  htt ps://researc h. u nc.e d u/c o vi d -1 9/  ) restricti n g all n o n-
esse ntial cli nical researc h acti vities . As a p hase 2 b st u d y, t he c urre nt st u d y has bee n all o we d t o 
c o nti n ue, h o we ver  t he direct or f or t he F o o d Aller g y I nitiati ve ( F AI) at U N C, Dr. E d wi n Ki m, has 
deci de d t o halt all oral f o o d c halle n ges d uri n g t he i m ple me ntati o n of safet y meas ures at U N C -
C H d ue t o t he C O VI D -1 9 pa n de mic .  D B P C F C’s carr y a ris k of a na p h yla xis t hat o n occasi o n 
c o ul d re q uire me dical s u p p ort fr o m t he U N C c o de bl ue e mer ge nc y res p o nse tea m or care wit hi n 
t he U N C e mer ge nc y de part me nt .  Utilizati o n of t hese ser vices as a res ult of cli nical trial 
p ur p oses has bee n dee me d i na p pr o priate d uri n g t he o n g oi n g pa n de mic a n d als o c o ul d p ose a ris k 
of e x p os ure t o t he vir us f or t he st u d y s u bject. As s uc h, a n y  3 6 m o nt h Dese nsitizati o n D B P C F C 
will be p ost p o ne d w hile  t he safet y meas ures s urr o u n di n g C O VI D -1 9 are i n place.  S u bjects w h o 
c h o ose t o re mai n i n t he st u d y will c o nti n ue o n st u d y dr u g at t he mai nte na nce d ose le vel be y o n d 
t he ori gi nall y pla n ne d 3 6 m o nt hs u ntil s uc h ti me t hat t he Dese nsitizati o n D B P C F C is c o n d ucte d.  
. T his will hel p pr otect o ur s u bjects fr o m e x p os ure t o t he C O VI D -1 9 vir us a n d hel p wit h 
meas ures t o re d uce b ur de n o n t he U N C E D.  
S u bjects w h o are sc he d ule d t o u n der g o t he 3 9 m o nt h T olera nce D B P C F C w hile t he C O VI D -1 9 
safet y meas ures are i n place will ha ve t heir D B P C F C ca ncelle d. A d diti o nal ti me off of st u d y 
dr u g t hera p y w o ul d p ote ntiall y i ncrease t he ris k of aller gic reacti o n d uri n g t he D B P C F C a n d 
w o ul d n ot be acce pta ble.  
F or s u bjects w h ose Dese nsitizati o n D B P C F C is p ost p o ne d, a f oll o w -u p visit t o re vie w safet y a n d 
s u bject d osi n g diaries w o ul d be c o n d ucte d. T his visit w o ul d be c o n d ucte d re m otel y b y tele p h o ne. 
A d di ti o nal st u d y dr u g w o ul d be se nt direct-t o-patie nt as necessar y t o c o nti n ue o n mai nte na nce 
d osi n g. La b sa m ple c ollecti o n a n d mec ha nistic st u dies w o ul d be deferre d a n d be c o m plete d at 
t he ti me t hat t he Dese nsitizati o n D B P C F C is c o m plete d. T he T olera nce D B P C FC w o ul d be 
c o m plete d 3 m o nt hs after t he Dese nsitizati o n D B P C F C is c o m plete d as descri be d i n secti o n 6. 5.  

I R B Pr ot oc ol# 1 4 -0 6 4 8  
C O N FI D E N TI A L  
 
F A R E Pea n ut S LI T a n d Earl y T olera nce I n d ucti o n  
 
 
 
V ersi o n 4. 0  
M arc h 1 8, 2 0 2 0  
Pa ge 5 7  of 5 7  
* See a p pe n di x 6 . 0 
 
F or s u bjects w h ose T olera nce D B P C F C is ca ncele d, a n e xit visit w o ul d be c o n d ucte d t o re vie w 
safet y. T he s u bject w o ul d be u n bli n de d t o treat me nt all ocati o n a n d e n d of st u d y i nstr ucti o ns 
w o ul d be re vie we d wit h t he s u bject.  
As t he sit uati o n is c ha n gi n g dail y, we are u na ble t o pr o vi de a ti me fra me f or e xte nsi o n.  We h o pe 
t o li mit t he n u m ber of s u bjects w h o will nee d t o utilize t his o pti o n a n d preser ve t he e nd p oi nt data 
para meters.  Pre vi o us S LI T st u dies ha ve n ot s h o w n a n y a d diti o nal ris k wit h pea n ut S LI T d osi n g 
be y o n d 3 years u p t o a t otal of 5 years of d osi n g.