A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of PRV-015 in Adult Patients With Non-Responsive Celiac Disease as an Adjunct to a Gluten-free Diet
Phase: PHASE2
Conditions: Celiac Disease
Sponsor: Provention Bio, a Sanofi Company

CONFIDENTIAL 
Protocol PRV-015-002b 
Provention Bio, Inc. 
1 
Final Version 3.0 
Clinical Study Protocol 
Protocol Title: 
A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Parallel-
Group Study to Evaluate the Efficacy and Safety of PRV-015 in Adult 
Patients with Non-Responsive Celiac Disease as an Adjunct to a 
Gluten-free Diet 
Protocol Number: 
PRV-015-002b 
Version Number: 
3.0 
Compound:   
PRV-015 
Study Phase:   
2b 
Short Title:  
Phase 2b Study of PRV-015 in Gluten-free Diet Non-responsive Celiac 
Disease 
Acronym: 
 
PROACTIVE (PROvention-Amgen Celiac protecTIVE study) 
Sponsor Name:  
Provention Bio, Inc. 
Legal Registered Address:  
55 Broad Street, 2nd Floor, Red Bank, NJ 07701 
Regulatory Agency Identifier Number(s) 
IND:   
143,549 
EudraCT:   
2020-000649-16 
Approval Date:  
24 March 2022 
NCT Number: NCT04424927

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Protocol PRV-015-002b 
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Final Version 3.0 
Sponsor Signatory: 
 
 
 
 
 
 
 
 
VP, Clinical Development 
Provention Bio, Inc.  
 
 
Date 
 
 
 
 
 
 
 
 
Medical Monitor name and contact information will be provided separately.  
 
 
 
24 March 2022

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Final Version 3.0 
Table of Contents 
1.
Protocol Summary ........................................................................................................15 
1.1. 
Synopsis ..........................................................................................................................15 
1.2. 
Schema ............................................................................................................................19 
1.3. 
Schedule of Activities (SoA) ..........................................................................................20 
2.
Introduction ...................................................................................................................23 
2.1. 
Study Rationale ...............................................................................................................23 
2.2. 
Background .....................................................................................................................23 
2.3. 
Benefit/Risk Assessment ................................................................................................24 
3.
Objectives and Endpoints ............................................................................................26 
4.
Study Design ..................................................................................................................30 
4.1. 
Overall Design ................................................................................................................30 
4.2. 
Scientific Rationale for Study Design ............................................................................31 
4.3. 
Justification for Dose ......................................................................................................31 
4.4. 
End of Study Definition ..................................................................................................32 
5.
Study Population ...........................................................................................................33 
5.1. 
Inclusion Criteria ............................................................................................................33 
5.2. 
Exclusion Criteria ...........................................................................................................34 
5.3. 
Lifestyle Considerations .................................................................................................36 
5.4. 
Screen Failures ................................................................................................................36 
6.
Study Treatment ...........................................................................................................37 
6.1. 
Study Drug Administered ...............................................................................................37 
6.2. 
Preparation/Handling/Storage/Accountability ................................................................38 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ............................................38 
6.4. 
Study Treatment Compliance .........................................................................................39 
6.5. 
Concomitant Therapy .....................................................................................................39 
6.5.1. 
Prohibited Medications ...................................................................................................39 
6.6. 
Dose Modification ..........................................................................................................39 
6.7. 
Treatment after the End of the Study ..............................................................................39 
7.
Discontinuation of Study Treatment and Subject
Discontinuation/Withdrawal........................................................................................41 
7.1. 
Discontinuation of Study Treatment ...............................................................................41 
7.1.1. 
Emergency Data Monitoring Committee Meeting .........................................................41 
7.2. 
Subject Withdrawal from the Study................................................................................42 
7.3. 
Lost to Follow-up............................................................................................................42 
8.
Study Assessments and Procedures.............................................................................43 
8.1. 
All Laboratory Tests .......................................................................................................43 
8.2. 
Efficacy Assessments .....................................................................................................46 
8.2.1. 
Celiac Disease Patient-Reported Outcome (CeD PRO) .................................................46 
8.2.2. 
Stool Frequency Question Based on BSFS .....................................................................47 
8.2.3. 
Gastrointestinal Symptom Rating Scale (GSRS) ............................................................47 
8.2.4. 
Investigator Global Assessment of Disease ....................................................................48 
8.2.5. 
PROACTIVE Dietary Questionnaire ..............................................................................48 

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8.2.6. 
Patient Global Impression of Severity and Change ........................................................48 
8.2.7. 
Esophagogastroduodenoscopy (EGD) and Histological 
Assessments ....................................................................................................................48 
8.2.8. 
Celiac Disease-Related Serology ....................................................................................49 
8.2.9. 
Gluten Stool and Urine Tests ..........................................................................................49 
8.3. 
Safety Assessments .........................................................................................................50 
8.3.1. 
Physical Examinations ....................................................................................................50 
8.3.2. 
Vital Signs .......................................................................................................................50 
8.3.3. 
Electrocardiograms .........................................................................................................50 
8.3.4. 
Clinical Safety Laboratory Assessments ........................................................................50 
8.4. 
Adverse Events and Serious Adverse Events .................................................................50 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information .....................................................................................................................51 
8.4.2. 
Method of Detecting AEs and SAEs ..............................................................................51 
8.4.3. 
Follow-up of AEs and SAEs ...........................................................................................51 
8.4.4. 
Regulatory Reporting Requirements for SAEs ...............................................................51 
8.4.5. 
Pregnancy ........................................................................................................................52 
8.4.6. 
Hospitalizations for Social Reasons or for Procedures ...................................................52 
8.4.7. 
Adverse Events of Special Interest .................................................................................52 
8.5. 
Treatment of Overdose ...................................................................................................52 
8.6. 
Pharmacokinetics and Immunogenicity ..........................................................................52 
8.7. 
Pharmacodynamics and Biomarkers ...............................................................................53 
8.8. 
Genetics ..........................................................................................................................53 
8.9. 
Quality of Life Measurements ........................................................................................53 
9. 
Statistical Considerations .............................................................................................54 
9.1. 
Statistical Hypotheses .....................................................................................................54 
9.2. 
Sample Size Determination ............................................................................................54 
9.3. 
Populations for Analyses ................................................................................................54 
9.4. 
Statistical Analyses .........................................................................................................55 
9.4.1. 
General Considerations ...................................................................................................55 
9.4.2. 
Primary Endpoint and Estimand .....................................................................................55 
9.4.3. 
Secondary Endpoints ......................................................................................................56 
9.4.4. 
Tertiary/Exploratory Endpoints ......................................................................................57 
9.4.5. 
Safety Analyses ...............................................................................................................57 
9.4.6. 
Pharmacokinetic and PK/PD Analyses ...........................................................................57 
9.5. 
Interim Analysis ..............................................................................................................58 
Internal Data Monitoring Committee .............................................................................................58 
10. 
Supporting Documentation and Operational Considerations ..................................59 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................59 
10.1.1. Regulatory and Ethical Considerations ...........................................................................59 
10.1.2. Financial Disclosure........................................................................................................59 
10.1.3. Informed Consent Process ..............................................................................................59 
10.1.4. Data Protection................................................................................................................60 
10.1.5. Committees Structure......................................................................................................60 
10.1.6. Dissemination of Clinical Study Data.............................................................................60 

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10.1.7. Data Quality Assurance ..................................................................................................61 
10.1.8. Source Documents ..........................................................................................................61 
10.1.9. Study and Site Start and Closure ....................................................................................61 
10.1.10. Publication Policy ...........................................................................................................62 
10.2. 
Appendix 2: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .........................................................63 
10.2.1. Definition of AE .............................................................................................................63 
10.2.2. Definition of SAE ...........................................................................................................64 
10.2.3. Recording and Follow-Up of AE and/or SAE ................................................................65 
10.2.4. Reporting of SAEs ..........................................................................................................67 
10.3. 
Appendix 3: Contraceptive Guidance and Collection of 
Pregnancy Information ...................................................................................................68 
10.4. 
Appendix 4: Assessment Instruments .............................................................................71 
10.4.1. Celiac Disease Patient-Reported Outcome Questionnaire ..............................................71 
10.4.2. Gastrointestinal Symptom Rating Scale .........................................................................74 
10.4.3. Stool Frequency Question ...............................................................................................75 
10.4.4. Investigator Global Assessment (IGA) ...........................................................................76 
10.4.5. Patient Global Impression of Severity (PGIS) ................................................................77 
10.4.6. Patient Global Impression of Change (PGIC) ................................................................78 
10.4.7. PROACTIVE Dietary Questionnaire ..............................................................................79 
10.4.8. Impact of Celiac Disease Symptoms Questionnaire (ICDSQ) .......................................80 
10.4.9. EQ-5D-5L .......................................................................................................................82 
10.5. 
Appendix 5: Interpretation of Hepatitis Results .............................................................84 
10.6. 
Appendix 6: Abbreviations .............................................................................................85 
11. 
References ......................................................................................................................88 
 
 
In-Text Figures 
Figure 1 
Study Schema .................................................................................................... 19 
Figure 2 
Symptom Domains in the Celiac Disease Patient-Reported Outcome 
Questionnaire 
 ........................................................................................................................... 47 

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Final Version 3.0 
Summary of Changes 
Protocol version 2.0 to 3.0 
Protocol PRV-015-002b version 2.0 (approved 01 March 2021) was amended to version 3.0 (approved 24 March 2022). Substantive 
changes to the previous version of the protocol are listed in the table below along with rationales. All changes are clearly identified in 
the track-changes version of the amendment. 
Section 
Rationale for change 
Original Text 
Revised Text 
1.1, 4.1, 5.1 
#8 
The level of tTG and DGP antibodies 
for study inclusion is revised from 
<2.0 to <3.0 times the cutoff value 
for positivity. This minor change will 
slightly expand the patient base for 
enrollment, adding potentially more 
symptomatic patients, without 
altering the target patient population. 
Low positive tTG titers may help 
identify subjects with continued 
inadvertent exposure to gluten as a 
possible cause of their symptoms. 
The allowable level, <3.0 times the 
cutoff value for positivity, is still 
well below the typical levels seen in 
celiac patients not on a GFD, which 
can be >10 times the cutoff value for 
positivity at diagnosis. 
8. Subjects must have detectable 
(above the lower limit of detection) 
serum celiac-related antibodies (at 
least one of anti-tTG IgA/IgG or 
DGP IgA/IgG). However, the titer in 
each assay must be below 2.0 times 
the diagnostic cut-off value for 
positivity of the assay in order to 
confirm that the subject is trying to 
adhere to their GFD. 
8. Subjects must have detectable 
(above the lower limit of detection) 
serum celiac-related antibodies (at 
least one of anti-tTG IgA/IgG or 
DGP IgA/IgG). However, the titer in 
each assay must be below 3.0 times 
the diagnostic cut-off value for 
positivity of the assay in order to 
confirm that the subject is trying to 
adhere to their GFD. 
1.1, 4.1, 9.2 
Although a cap of enrollment of 
subjects with VH:CD≥2 was initially 
instituted to limit the number of 
Enrollment of subjects with VH:CD 
≥2 will be capped at 32 subjects, 
Enrollment of subjects with Marsh 
score of 0 or 1 will be capped at 

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subjects with normal biopsies, which 
could affect the ability to detect 
improvements in histological 
outcomes, this criterion is revised to 
capping enrollment of subjects with 
Marsh score 0 or 1, which 
incorporates both VH:CD and IELs.  
The Marsh score better reflects the 
overall histological architecture, and 
changes from baseline in both 
VH:CD and IELs will be analyzed.  
A cap of 72 subjects, or 
approximately 33% of the planned  
total number of randomized subjects, 
will still limit those with normal 
biopsies but allow for a broader 
inspection of small bowel 
architecture using both VH:CD 
and/or IELs, thereby broadening 
subject participation. 
although fewer than 32 may be 
enrolled. 
 
 
approximately 72 subjects, although 
fewer than 72 may be enrolled. 
 
5.2 
The exclusion of IgA deficiency was 
originally instituted because of 
concerns for the effects of COVID-
19 on celiac disease at the time of 
protocol development. Because of 
the widespread availability of the 
COVID-19 vaccines and 
accumulated data that demonstrate 
no increased risks to celiac patients 
4. Selective IgA deficiency, defined 
as having undetectable levels of 
serum IgA. 
(Original text removed) 

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from COVID-19 infection, this 
exclusion criterion is removed.  
8.4.1 
The planned method for the analysis 
of delayed TEAEs in subjects who 
discontinue study treatment is 
removed and deferred to the 
Statistical Analysis Plan (SAP).  
For subjects who discontinue 
treatment but remain in the study for 
continued assessments, TEAEs 
occurring less than 105 days from 
the last dose of study drug will be 
assigned to their study treatment.  
TEAEs reported more than 105 days 
after the last received dose will be 
assigned to placebo. 
(Original text removed) 
 
 
 

CONFIDENTIAL 
Protocol PRV-015-002b 
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Final Version 3.0 
Protocol version 1.0 to 2.0 
Protocol PRV-015-002b version 1.0 (approved 29 April 2020) was amended to version 2.0 (approved 01 March 2021). Substantive 
changes to the previous version of the protocol are listed in the table below along with rationales. In addition, minor corrections and 
administrative/editorial changes and clarifications have been made throughout the document. All changes are clearly identified in the 
track-changes version of the amendment. 
Section 
Rationale for change 
Original Text 
Revised Text 
1.1, 4.1 
Correction 
Enrollment of subjects with VH:CD 
>2 will be capped at 32 subjects, 
although fewer than 32 may be 
enrolled. 
Enrollment of subjects with VH:CD 
≥2 will be capped at 32 subjects, 
although fewer than 32 may be 
enrolled. 
1.1, 4.1, 
8.2.1 
Administrative 
 
(The copyright of the CeD PRO 
[2015] is held by 9 Meters 
Biopharma and was formerly held by 
Alba Therapeutics Corporation. The 
CeD PRO is used with permission.) 
1.3, 8.1 
The antibody tests on the Day -14 
visit (Visit -2) are removed to avoid 
any delay for the Day 0 visit and the 
start of study treatment. 
See table 
See table 
1.3, 8.2.9 
All urine samples will be collected at 
each visit.  
Footnote 7. Stool gluten samples 
will be collected by the subject the 
day before each scheduled visit or 
during the visit (with a window of 3 
days before or after the visit). Urine 
gluten samples will be collected and 
Footnote 7. Stool gluten samples will 
be collected by the subject the day 
before each scheduled visit or during 
the visit (with a window of 3 days 
before or after the visit). Urine gluten 
samples will be collected at the time 
of the office visit. 

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frozen by the subject either before or 
at the time of the office visit. 
1.1, 4.1, 5.1 
#8 
The maximum levels of tTG and 
DGP antibodies for inclusion is 
revised from 1.5 to 2.0 times the 
cutoff value for positivity. This 
minor change will slightly expand 
the patient base for enrollment in this 
study, adding potentially more 
symptomatic patients without 
altering the target patient population 
in screening, as low positive titers 
help identify those subjects with 
potential continued inadvertent 
exposure to gluten as a potential 
cause of their symptoms. The change 
from 1.5 to 2.0 times is still well 
below the typical values seen without 
a GFD, as antibodies at diagnosis can 
be 10 times (or higher) the cutoff 
value for positivity. 
8. Subjects must have detectable 
(above the lower limit of detection) 
serum celiac-related antibodies (at 
least one of anti-tTG IgA/IgG or 
DGP IgA/IgG). However, the titer in 
each assay must be below 1.5 times 
the diagnostic cut-off value for 
positivity of the assay in order to 
confirm that the subject is trying to 
adhere to their GFD. 
8. Subjects must have detectable 
(above the lower limit of detection) 
serum celiac-related antibodies (at 
least one of anti-tTG IgA/IgG or 
DGP IgA/IgG). However, the titer in 
each assay must be below 2.0 times 
the diagnostic cut-off value for 
positivity of the assay in order to 
confirm that the subject is trying to 
adhere to their GFD. 
1.1, 9.5 
The DMC member composition is 
updated, as additional member(s) 
may be included to better assess 
available data during the study.  
An internal DMC will consist of a 
Physician Chair, Physician Member, 
and an independent Statistician 
separate from the study team.  
An internal DMC will be set up to 
periodically evaluate trial-related 
data. The DMC will consist of at 
least 3 independent members not 
affiliated with the study. It will be 
chaired by a physician, and other 

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Complete guidelines and evaluation 
criteria will be documented in a 
DMC Charter. 
members will include at least 1 
physician and 1 statistician. 
Complete guidelines, evaluation 
criteria, and other organizational and 
operational aspects will be 
documented in a DMC Charter. 
1.3 
The window for the baseline 
endoscopy is increased to 12 days 
prior to Visit 2 to improve 
scheduling feasibility.  
Footnote 12. The baseline EGD and 
biopsy can be performed within 7 
days before Visit 2. 
Footnote 12. The baseline EGD and 
biopsy can be performed within 12 
days before Visit 2. 
5.1 #9, 8.8 
Wording is updated to allow the 
inclusion of patients with less 
common HLA types associated with 
celiac disease. 
9. Subjects must have human 
leukocyte antigen DQ (HLA-DQ) 
typing consistent with celiac disease 
(DQ2 and/or DQ8) obtained before 
the baseline biopsy. HLA-DQ typing 
information supplied as part of the 
subject medical record is acceptable.  
 
9. Subjects must have human 
leukocyte antigen DQ (HLA-DQ) 
typing consistent with known celiac 
disease alleles (typically DQ2 and/or 
DQ8) obtained before the baseline 
biopsy. HLA-DQ typing information 
supplied as part of the subject 
medical record is acceptable.  
 
5.4 
To clarify the consenting procedures 
for subjects undergoing rescreening. 
Randomization failures will not be 
rescreened.  
Subjects who are rescreened should 
be reconsented at the time of the 
rescreening. Subjects who have 
entered the run-in period or were 
randomization failures will not be 
rescreened. 

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8.1 
Correction to include hemoglobin 
A1C at visits designated in the 
Schedule of Activities 
 
(Visits 1, 5, 7, 9, 11, 13, 15, and 16) 
• HbA1C (subjects with diagnosed 
Type 1 or Type 2 diabetes only)  
8.2.7 
Correction and clarification. 
At each time point specified in the 
SoA (Section 1.3), at a minimum, 6 
fragments or specimens of small-
bowel tissue will be taken from the 
duodenal bulb and the second part of 
the duodenum distal to the ampulla 
(duodenum D2) by EGD and forceps 
biopsy. Biopsies should be done in 
the duodenum while avoiding 
ulcerative lesions. 
1. The first 4 specimens collected 
will be fixed in a fixative such as 
PaxGene or 10% formalin (see 
Study Manual). One of the 
specimens may be fixed in formalin 
at the site for standard pathology (if 
conducted, the information will not 
be captured in the study). Three of 
the specimens will be shipped to the 
central lab to be embedded in 
paraffin wax after orientation. The 
Central Pathologist, blinded to 
treatment assignment, will assess 
villus height (VH, in micrometers) 
and crypt depth (CD, in 
At each time point specified in the 
SoA (Section 1.3), at a minimum, 6 
biopsies or specimens of small-bowel 
tissue will be taken from the second 
part of the duodenum distal to the 
ampulla (duodenum D2) by EGD 
and endoscopic forceps biopsy. 
Ulcerative lesions should be avoided 
for all biopsies. 
1. All 6 specimens will be fixed in 
PAXgene at the site (see Central 
Laboratory Manual) and shipped to 
the Central Pathologist.   
2. The Central Pathologist, blinded to 
treatment assignment, will assess 
villus height (VH, in micrometers) 
and crypt depth (CD, in micrometers) 
and their ratio, VH:CD, using 4 
specimens.   
3. Two specimens will be placed in a 
messenger ribonucleic acid (mRNA) 
preservative for future mRNA 
analysis of inflammatory pathways 
(e.g., expression analysis of IL-15-

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micrometers) and their ratio, 
VH:CD. … 
2. The next two specimens will be 
placed in a messenger ribonucleic 
acid (mRNA) preservative for future 
mRNA analysis of inflammatory 
pathways (e.g., expression analysis 
of IL-15-related pathways to 
potentially identify predictive 
biomarkers of response to PRV-
015). 
related pathways to potentially 
identify predictive biomarkers of 
response to PRV-015). 
9.4.1 
Correction 
For the CeD PRO scores, baseline 
value is averaged over the 4-week 
placebo run-in period. 
For the CeD PRO Abdominal 
domain scores, baseline value will be 
the average of scores over the last 
week of the 4-week placebo run-in 
period immediately before 
randomization. 
9.4.4 
Clarification 
Additionally, a binary outcome will 
be derived, in which subjects are 
categorized as having worsening 
scores from baseline and those with 
no change or improvement. The 
Cochran–Mantel–Haenszel test 
(CMH) stratified by baseline median 
Marsh-Oberhuber score will be used 
to assess differences between active 
Additionally, categorical outcomes 
will be derived, in which subjects are 
categorized as having worsening 
scores, no change, or improvement 
from baseline. The Cochran–Mantel–
Haenszel test (CMH) stratified by 
baseline median Marsh-Oberhuber 
score will be used to assess 
differences between active and 

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and placebo treatments in this binary 
outcome. 
placebo treatments in these 
categorical outcomes. 
10.1.3 
Administrative 
Subjects must be informed that their 
participation is voluntary. Subjects 
will be required to sign a statement 
of informed consent that meets local 
regulatory and/or IRB/IEC 
requirements. 
Subjects must be informed that their 
participation is voluntary. Subjects or 
their legally authorized 
representatives will be required to 
sign and date a statement of informed 
consent that meets local regulatory 
and/or IRB/IEC requirements. 
10.2.4 
Clarification of procedures for SAE 
reporting 
See text 
See text 

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Final Version 3.0 
1. 
Protocol Summary 
1.1. 
Synopsis 
Protocol Title: A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group 
Study to Evaluate the Efficacy and Safety of PRV-015 in Adult Patients with Non-Responsive 
Celiac Disease as an Adjunct to a Gluten-free Diet 
Short Title: Phase 2b Study of PRV-015 in Gluten-free Diet Non-responsive Celiac Disease 
Rationale: 
Non-responsive celiac disease (NRCD) can be defined as persistent symptoms, signs, or 
laboratory abnormalities typical of celiac disease despite at least 6-12 months of treatment with a 
gluten-free diet (GFD) (Rubio-Tapia 2013). PRV-015 (also known as AMG 714), a monoclonal 
antibody (mAb) that blocks interleukin 15 (IL-15), has been shown to reduce intestinal 
inflammation and improve clinical symptoms induced by gluten consumption in celiac disease. 
PRV-015 may be effective as an adjunctive treatment to a GFD in NRCD patients. 
Objectives and Endpoints: 
Objective 
Endpoint/Estimand 
Primary 
 
• To assess the efficacy of PRV-015 in 
attenuating the symptoms of celiac 
disease in adult patients with NRCD as 
measured by the Abdominal Symptoms 
domain of the Celiac Disease Patient-
Reported Outcome (CeD PRO) 
questionnaire  
Endpoint: 
• Absolute change from baseline through 
Week 24 in abdominal symptoms as 
measured by the Abdominal Symptoms 
domain of the CeD PRO questionnaire 
Estimand: 
• The primary estimand is the difference in 
the overall mean values (averaged across 
24 weeks) of each of the 3 PRV-015 
treatment groups compared with placebo 
of the change from baseline in the 
Abdominal Symptoms domain of the 
CeD PRO questionnaire in the target 
population, regardless of compliance to 
study treatment or the occurrence of 
intercurrent events. 

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Objective 
Endpoint/Estimand 
Secondary 
 
• To assess the effect of treatment with 
PRV-015 on other measures of disease 
activity  
• To assess the safety, tolerability, and 
pharmacokinetics (PK) of PRV-015 
when administered to adult patients with 
NRCD. 
Secondary efficacy endpoints:  
• Absolute change from baseline through 
Week 24 in the Diarrhea and Loose Stool 
domain of the CeD PRO 
• Absolute change from baseline through 
Week 24 in gastrointestinal (GI) 
symptoms as assessed by the Total GI 
score (comprising the Abdominal 
Symptoms domain, the Diarrhea and 
Loose Stool domain, and the Nausea 
item) of the CeD PRO 
• Absolute change from baseline to Week 
24 in small intestinal mucosal 
inflammation, as measured by 
intraepithelial lymphocyte (IEL) density 
using immunohistochemistry (IHC) 
Safety endpoints:  
• Adverse events (AEs): treatment-
emergent adverse events (TEAEs), 
TEAEs leading to treatment 
discontinuation, and treatment-emergent 
serious adverse events (SAEs) 
• Treatment-emergent adverse events of 
special interest (AESIs) 
• Potentially clinically important (PCI) 
changes in clinical laboratory values 
(hematology, chemistry, and urinalysis), 
vital signs (blood pressure [BP], heart 
rate, temperature, respiratory rate), and 
weight 
• Immunogenicity, as assessed by the 
presence of anti-PRV-015 antibodies 
PK endpoint:  
• Serum PRV-015 trough concentrations 
(Cmin) 
See Section 9.4.2 for a description of the primary endpoint analysis.  

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Final Version 3.0 
Overall Design: 
Protocol PRV-015-002b is a Phase 2b, randomized, double-blind, placebo-controlled, parallel-
group study to evaluate the efficacy and safety of PRV-015 in adult patients with NRCD who are 
on a GFD. 
After signing informed consent form (ICF), subjects will undergo screening assessments for the 
study in a screening period of up to 28 days before Visit 1. The screening assessments will 
include the collection of demographics, medical history, and past record of the diagnosis of 
celiac disease if available. Subjects should demonstrate 1) attempted adherence to a GFD, 
confirmed by a lack of strong serological positivity (<3.0 × cutoff value for positivity), and 2) 
exposure to gluten contamination by presenting with detectable serology (above the lower limit 
of quantitation). 
After initial screening, potentially eligible subjects will enter a single-blind, placebo run-in 
period for 4 weeks, starting at Visit 1. During the run-in period, all subjects will receive 
subcutaneous (SC) injections of placebo every 2 weeks (q2w), at Visit 1 and Visit 2, in a single-
blind fashion, in which the Investigator is aware of the treatment administered but the subjects 
are not. Subjects will be asked to maintain their current GFD through the entire study and to 
complete the daily electronic diary (eDiary) for CeD PRO questionnaire as well as a stool 
frequency question (stools of Type 6 or 7 on BSFS). (The copyright of the CeD PRO [2015] is 
held by 9 Meters Biopharma and was formerly held by Alba Therapeutics Corporation. The CeD 
PRO is used with permission.) A baseline upper esophagogastroduodenoscopy (EGD) and 
biopsy will be conducted during the single-blind run-in period. The results will be used to obtain 
the villous height-to-crypt depth ratio (VH:CD) for randomization stratification. 
At the end of the 4-week single-blind, placebo run-in period, subjects will return to the study site 
for Visit 3 (Week 0/Day 1) and be re-evaluated for inclusion/exclusion criteria. Those who meet 
the entry criteria at this time will enter the 24-week double-blind treatment period (from Visit 3 
to Visit 15). At the same visit, eligible subjects will be randomized in a 1:1:1:1 ratio to receive 
100 mg, 300 mg, or 600 mg PRV-015, or matching placebo, subcutaneously (SC) every 2 weeks 
(q2w). Randomization will be stratified by VH:CD of <2 or ≥2 and by the CeD PRO Abdominal 
Symptoms domain score of <3 or ≥3 at baseline using the average of the Abdominal Symptoms 
domain scores over the last week of the placebo run-in period immediately before randomization.  
Enrollment of subjects with Marsh score of 0 or 1 will be capped at approximately 72 subjects, 
although fewer than 72 may be enrolled.  
The study drug (1 of the 3 doses of PRV-015 or placebo) will be administered SC q2w in the 
double-blind treatment period through Visit 14. Each dose will be administered in a double-blind 
fashion. The subjects’ adherence to GFD will be assessed retrospectively throughout the study 
using the stool and urine gluten tests based on the G12 antibody to interpret possible dietary 
changes or transgressions. Results will not be communicated to the subjects, who will be 
instructed to continue their baseline dietary habits throughout the study. 
Subjects will be assessed for efficacy and safety throughout the study, as indicated in the 
Schedule of Activities (SoA) (Section 1.3). Clinical assessments occur from Visit 3 through Visit 
16. Safety is also assessed at each on-site visit through the end-of-study visit (Visit 16), which 
takes place 6 weeks after the last planned dose of the study drug.  

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Final Version 3.0 
Randomized subjects will undergo a second EGD and biopsy at the end of the 24-week treatment 
period, within 7 days of Visit 15 in order to assess changes from baseline in IELs and VH:CD.  
Visits 6, 8, 10, and 12 may be conducted either at the site or remotely by certified mobile 
personnel per the Investigator’s decision. 
All subjects enrolled in the study will complete the daily eDiary for CeD PRO (at the end of the 
subject’s daily activities, when no more food will be consumed) and for the stool frequency 
question from Visit 1 through the end of the study at Visit 16, which will encompass the single-
blind placebo run-in and the double-blind treatment period and a safety follow-up period.  
Safety assessments include clinical laboratory tests, vital signs, and AE assessments. Subjects 
may undergo unscheduled visits if needed (e.g., for safety reasons). 
Disclosure Statement: This is a parallel-group treatment study with 4 treatment groups double 
blinded to subjects, investigators, and sponsor, preceded by a single-blind placebo run-in period. 
Number of Subjects: 
Approximately 220 subjects will be randomized (approximately 55 subjects per group). Subjects 
will be stratified by normal or abnormal VH:CD (i.e., ≥2 or <2) and by the CeD PRO Abdominal 
Symptoms domain score of <3 or ≥3 at baseline, using the average of the Abdominal Symptoms 
domain scores over the last week of the placebo run-in period immediately preceding 
randomization. The number of enrolled subjects with Marsh score of 0 or 1 will be capped at 
approximately 72. Withdrawn subjects will not be replaced.  
A sample size of 50 evaluable subjects within each treatment group would provide 
approximately 80% power to detect a 0.40 difference between placebo and any given active 
treatment group at the two-sided, 0.05 level of significance during the 24-week double-blind 
treatment period in the primary endpoint. See Section 9.2 for details.  
Treatment Groups and Duration: 
After the single-blind placebo run-in phase, subjects will be randomized to one of the 4 treatment 
groups in a ratio of 1:1:1:1 as follows:  
• 
PRV-015 100 mg q2w  
• 
PRV-015 300 mg q2w  
• 
PRV-015 600 mg q2w  
• 
Placebo q2w  
The duration of study participation for each subject is approximately 9 months, including 
≤4 weeks of screening period, 4 weeks of placebo run-in period, 24 weeks of double-blind 
treatment period, and 4 weeks of final safety follow-up period.  
Internal Data Monitoring Committee (DMC): 
An internal DMC will be set up to periodically evaluate trial-related data. The DMC will consist 
of at least 3 independent members not affiliated with the study. It will be chaired by a physician, 
and other members will include at least 1 physician and 1 statistician. 

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Final Version 3.0 
The DMC will receive blinded and unblinded data before each meeting. The DMC will meet at 
least quarterly. The DMC may also hold emergency meetings in the event of death regardless of 
relatedness, life-threatening events possibly related to study drug, or anaphylaxis to advise on 
continued study conduct. Relevant medical literature may also be reviewed by the committee. 
Complete guidelines, evaluation criteria, and other organizational and operational aspects will be 
documented in a DMC Charter.  
An additional series of Safety Meetings will be held between the study team, including the 
Sponsor Safety Physician, and Amgen, the holder of the global safety database. 
1.2. 
Schema 
A schema of the study procedures is presented in Figure 1. 
Figure 1 
Study Schema 
 
Abbreviations: EGD=esophagogastroduodenoscopy, q2w=every 2 weeks, SC=subcutaneous. 
100 mg PRV-015 SC q2w
300 mg PRV-015 SC q2w
600 mg PRV-015 SC q2w
Placebo SC q2w
Screening Period  
(≤28 Days)
Screening
Visit
Visit 1
(Day -28)
Visit 16 (Day197) 
Final Visit
(22-Week Randomized Treatment Period)
(4-Week 
Single-Blind 
Placebo
Run-in)
Visit 15
(Day 169) 
EGD with  
biopsy prior to  
randomization
EGD with 
biopsy 
Visit 3 
(Day 1)
Visit 14
(Day155)
Randomization
Placebo run-in
Primary 
Endpoint

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Final Version 3.0 
1.3. 
Schedule of Activities (SoA) 
 
 
Screening 
(≤28 Days) 
Single-Blind 
Run-in Period 
 
Double-Blind Randomized Treatment Period 
Follow-
up 
Visit 
Visit # 
Screen1 
1 
2 
3 
4 
5 
62 
7 
82 
9 
102 
11 
122 
13 
14 
15/ 
Early 
Term 
16 
Week 
-8 
-4 
-2 
0 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
28 
Day 
-56 
-28 
-14 
1 
15 
29 
43 
57 
71 
85 
99 
113 
127 
141 
155 
169 
197 
Window (Days) 
 
 
±2 
+2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±7 
Study Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination3 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Weight 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs4 
X 
X 
X 
XP 
X 
X 
XP 
XP 
XP 
XP 
X 
XP 
X 
X 
X 
X 
X 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood and urine samples 
for clinical lab tests5
P3 
X6
P 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
H. pylori stool test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood tests for ferritin, 
iron, TIBC, vitamins D, 
B12, folate 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
Serum pregnancy test 
(WOCBP)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
LH/FSH (non-WOCBP) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test (all 
WOCBP) 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Stool and urine gluten 
testP7 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 

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Final Version 3.0 
 
Screening 
(≤28 Days) 
Single-Blind 
Run-in Period 
 
Double-Blind Randomized Treatment Period 
Follow-
up 
Visit 
Visit # 
Screen1 
1 
2 
3 
4 
5 
62 
7 
82 
9 
102 
11 
122 
13 
14 
15/ 
Early 
Term 
16 
Week 
-8 
-4 
-2 
0 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
28 
Day 
-56 
-28 
-14 
1 
15 
29 
43 
57 
71 
85 
99 
113 
127 
141 
155 
169 
197 
Window (Days) 
 
 
±2 
+2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±7 
Randomization 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum IgA test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum for PK8 
 
 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Serum for ADA8 
 
 
 
X 
X 
X 
 
 
 
X 
 
 
 
 
X 
X 
X 
Anti-tTG and anti-DGP 
antibodies9 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Serum for biomarkers10 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Eligibility confirmation  
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study drug 
administration 
 
X11 
X11 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
EGD and biopsy 
 
 
X12 
 
 
 
 
 
 
 
 
 
 
 
 
X13 
 
Stool frequency 
question14 
 
<-------------------------------------------------------------------------------------------------------------------------------------> 
CeD PROP15 
 
<-------------------------------------------------------------------------------------------------------------------------------------> 
ICDSQ 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
EQ-5D-5L 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
Weekly diet stability 
questions 
 
<-------------------------------------------------------------------------------------------------------------------------------------> 
GSRS 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IGA 
 
X 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
PGIC16 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PGIS16 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assessment of adverse 
events17 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Final Version 3.0 
Abbreviations: ADA=anti-drug antibody; BP=blood pressure; BSFS=Bristol Stool Form Scale; CeD PRO=Celiac Disease Patient Reported Outcome; 
DGP=deamidated gliadin peptide; ECG=electrocardiogram; EGD=esophagogastroduodenoscopy; Early Term=early termination; FSH=follicle-stimulating 
hormone; GSRS=Gastrointestinal Symptom Rating Scale; HbA1C=hemoglobin A1C; HBV=hepatitis B virus; HCV=hepatitis C virus; HIV=human 
immunodeficiency virus; HLA=human leukocyte antigen; IGA=Investigator Global Assessment; LH=luteinizing hormone; PGIC=Patient Global Impression of 
Change; PGIS=Patient Global Impression of Severity; PK=pharmacokinetics; QoL=quality of life; TIBC=total iron binding capacity; tTG=tissue 
transglutaminase; WOCBP=women of childbearing potential, non-WOCBP=women not of childbearing potential. 
 
1. Testing for COVID-19 infection (including viral RNA testing for acute infection and/or antibody testing for past exposure) may be conducted if appropriate. 
2. Visits 6, 8, 10, and 12 may be conducted remotely by certified mobile healthcare personnel per Investigator’s decision.  
3. A complete physical examination is required at screening, Visit 1, Visit 15, and Visit 16. At other visits, the physical examinations are symptom directed.  
4. Vital signs (including temperature, BP, heart rate, and respiratory rate) will be measured prior to each study drug administration. Vital signs will be taken again 
30 minutes after study drug administration.  
5. Blood and urine samples will be collected for hematology, chemistry, and urinalysis. In addition, HbA1c should be measured in those subjects with diagnosis 
of Type 1 or Type 2 diabetes only. If glucose is detected in the urine, HbA1c should be tested and the subject should receive clinical evaluation for diabetes 
per standard of care. 
6. The screening blood samples include HIV, HBV, HCV, and IGRA tests. In addition, a test for HLA DQ2 and/or DQ8 typing will be performed if a previous 
report is not supplied. 
7. Stool gluten samples will be collected by the subject the day before each scheduled visit or during the visit (with a window of 3 days before or after the visit). 
Urine gluten samples will be collected at the time of the office visit.  
8. Blood samples for PK and ADA analyses should be collected before study drug administration (baseline) and at each visit before dosing (trough). The exact 
time and date of sample collection must be recorded. ADA analysis includes neutralizing antibodies (NAb).  
9. The anti-tTG and anti-DGP antibody tests at the screening visit will include both IgA and IgG. At all other visits, only anti-tTG IgA and anti-DGP IgA will be 
tested. 
10. Blood samples for biomarker analyses should be taken prior to study drug administration. The time and date of these samples must be accurately recorded.  
11. The study drug administered at Visits 1 and 2 (single-blind run-in period) is placebo for all subjects.  
12. The baseline EGD and biopsy can be performed within 12 days before Visit 2. 
13. The final EGD and biopsy can be collected within 7 days before Visit 15. A final or early termination EGD and biopsy are required for all subjects. Subjects 
with early termination should undergo the EGD and biopsy unless a medical condition precludes it, at the Investigator’s discretion.  
14. Subjects are required to answer the stool frequency question (stools of Type 6 or 7 on BSFS) daily before bedtime in the eDiary.  
15. The CeD PRO is captured daily in the eDiary after the last meal of the day before the subject goes to bed.  
16. Subjects are instructed to record PGIC and PGIS every other week in the eDiary.  
17. Treatment-emergent adverse events are collected from the first dose of the post-randomization study drug administration (Visit 3) through the final visit. 
Between signing the informed consent form and the first dose of study drug (including the single-blind run-in period), only AEs related to study procedures 
and SAEs will be recorded. 
 

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2. 
Introduction 
PRV-015, also known as AMG 714, is a monoclonal antibody (mAb) targeting interleukin (IL) 
15 (IL-15). It is being developed as an adjunct to a gluten-free diet (GFD) for the treatment of 
non-responsive celiac disease (NRCD).  
2.1. 
Study Rationale 
Approximately 50% of patients with celiac disease have continued symptoms despite at least 12 
months of treatment with a GFD. NRCD is defined by the American College of 
Gastroenterology (ACG) as persistent symptoms, signs, or laboratory abnormalities typical of 
celiac disease despite at least 6-12 months of treatment with a GFD (Rubio-Tapia 2013).  
PRV-015, a mAb that blocks IL-15, has been shown to reduce intestinal inflammation and 
improve clinical symptoms induced by gluten consumption in a previous Phase 2a gluten-
challenge study in patients with celiac disease. PRV-015 may be effective as an adjunctive 
treatment to GFD in NRCD patients. 
2.2. 
Background 
Celiac disease is a systemic autoimmune disease triggered by gluten consumption in genetically 
susceptible individuals (Green 2007). Approximately 1% of the European and North American 
population is affected by celiac disease, although many patients remain undiagnosed due to 
insufficient awareness and highly variable presentation of the disease. Currently, the only 
available management of celiac disease is lifelong total avoidance of gluten, i.e., a GFD. While 
simple in theory, maintaining a strict GFD is extremely difficult in practice because of 
occasional dietary transgressions and gluten contamination in foods purported to be gluten free. 
It has been estimated that half or more of all diagnosed patients who are following a GFD 
continue to have some disease activity, since as little as 50 mg/day of gluten exposure may 
trigger immune activation and mucosal damage (Gibert 2006, Lee 2003, Cranney 2007, Hopper 
2007, Midhagen 2003, Moreno 2017). There are significant unmet medical needs in patients with 
NRCD. 
The pro-inflammatory cytokine IL-15 has been identified as a major mediator in the 
pathophysiology of celiac disease (Gianfrani 2005, Meresse 2012). IL-15 is produced in the 
small intestine by antigen-presenting cells and epithelial cells and has been shown to be an 
essential, nonredundant factor for the activation and proliferation of intraepithelial lymphocytes 
(IELs). The IELs, primarily CD8+ cells, have been shown to destroy intestinal epithelial cells 
and cause the villous atrophy that is characteristic of celiac disease (Korneychuk 2014; Abadie 
2014). Numerous genetic variants in the IL-15 and IL-15 receptor α (IL-15Rα) genes have been 
associated with IL-15 protein expression and the risk of celiac disease (Escudero-Hernandez 
2017). In addition, IL-15 renders effector T cells resistant to inhibition by regulatory T cells, thus 
promoting the loss of tolerance to food antigens (Korneychuk 2014, Abadie 2014, DePaolo 
2011). Further, IL-15 induces an increase in enterocyte apoptosis, which in turn correlates with 
mucosal damage and villous atrophy (Di Sabatino 2006).  

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Final Version 3.0 
PRV-015, a fully human immunoglobulin (IgG1κ) mAb, binds to and inhibits the function of 
IL-15 in all of its presentations (cis, trans, soluble IL-15 bound to IL-15Rα), and blocks 
IL-15-induced T-cell proliferation (Villadsen 2003). It has also demonstrated dose-dependent 
inhibition of IL-15-induced tumor necrosis factor alpha (TNF-α) production. Thus, PRV-015 is a 
plausible candidate for the treatment of celiac disease. 
PRV-015 was previously tested in clinical trials for efficacy and safety in patients with 
rheumatoid arthritis (RA) (Baslund 2005, McInnes 2006), refractory celiac disease Type II 
(RCD-II) (Cellier 2019), and psoriasis (Lebrec 2013) and has shown acceptable safety and 
tolerability in all studies. Proof of concept was achieved in RA and RCD-II, while PRV-015 
showed no efficacy in psoriasis.  
A randomized, double-blind, placebo-controlled Phase 2a study in celiac disease was conducted, 
in which patients who were well controlled on their GFD were given a gluten challenge (2 to 4 g 
daily) while being treated with either PRV-015 (150 mg or 300 mg subcutaneous [SC] injection) 
or placebo (Lähdeaho 2019). A small number of patients in this study had NRCD, as 
demonstrated by presence of gastrointestinal mucosal damage at baseline, and did not undergo 
gluten challenge. After 12 weeks of study treatment, the primary endpoint, change from baseline 
to Week 12 in the villous height-versus-crypt depth ratio (VH:CD), was not met in the 
comparisons between placebo and either of the PRV-015 doses. However, patients in the PRV-
015 300 mg group showed better outcomes in the endpoints of change from baseline in IEL 
density, Celiac Disease Patient-Reported Outcome (CeD PRO) score, the proportion of patients 
who reported diarrhea (defined as stools of Type 6 or 7 on the Bristol Stool Form Scale [BSFS]), 
and Physician Global Assessment (Lähdeaho 2019). Subjects who did not receive gluten 
challenge also experienced nominal symptom reduction, albeit the sample size was too small for 
statistical analyses. The findings indicate that PRV-015 can attenuate the inflammatory effects 
and symptoms induced by gluten challenge. The mixed results in histology and other endpoints 
in this study may be due to limitations in the sample size, treatment duration and dosage 
administered. Hence, the current larger Phase 2b dose-ranging study will investigate the effects 
of PRV-015 with a longer duration of treatment and broader range of doses (without gluten 
challenge) in patients exposed to contaminating gluten exposure, i.e., in symptomatic NRCD 
patients as an adjunct to a GFD.  
2.3. 
Benefit/Risk Assessment 
PRV-015 (also known as AMG 714) has been studied to date in over 250 subjects, including 
healthy volunteers and adult patients with psoriasis, RA, celiac disease (with gluten challenge), 
and RCD-II. The doses studied were 150 mg and 300 mg SC every 2 weeks (q2w) for 12 weeks 
in the celiac disease study and 8 mg/kg intravenous (IV) weekly for 3 doses followed by q2w for 
4 doses (total treatment duration 10 weeks) in the RCD-II study.  

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Final Version 3.0 
Collectively, the prior safety data from earlier studies suggest an acceptable safety profile with 
the following identified adverse reactions, which, to date, have been mild and transient in nature: 
• Injection site reaction 
• Infusion site pain 
• Rash 
• Eczema 
Due to the common occurrence of injection site reactions (up to 52% in subjects receiving 
300 mg PRV-015 in the CELIM-NRCD-001 study), post-injection observation for at least 1 hour 
is required at all dosing visits.  
See the Investigator Brochure (IB) Core Safety Information for further details of the safety of 
PRV-015 injection. 
The patients to be enrolled in this Phase 2b study will have followed GFD for at least 12 months 
and, in spite of their best efforts, will have residual symptoms, evidence of anti-gluten and/or 
auto-antibody formation, and likely continued intestinal inflammation and damage. PRV-015 
may relieve symptoms and potentially reduce intestinal inflammation. The safety profile to date 
suggests that the risks associated with PRV-015 are mild and transient, and predominantly 
injection site reactions. 
In summary, PRV-015 provides an opportunity for an innovative approach to provide clinical 
benefits to patients with NRCD at a relatively low risk. 

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Final Version 3.0 
3. 
Objectives and Endpoints 
 
Objective 
Endpoint/Estimand 
Primary 
 
• To assess the efficacy of PRV-015 in 
attenuating the symptoms of celiac 
disease in adult patients with NRCD as 
measured by the Abdominal Symptoms 
domain of the Celiac Disease Patient-
Reported Outcome (CeD PRO) 
questionnaire  
Endpoint: 
• Absolute change from baseline through 
Week 24 in abdominal symptoms as 
measured by the Abdominal Symptoms 
domain of the CeD PRO questionnaire 
Estimand: 
• The primary estimand is the difference in 
the overall mean values (averaged across 
24 weeks) of each of the 3 PRV-015 
treatment groups compared with placebo 
of the change from baseline in the 
Abdominal Symptoms domain of the 
CeD PRO questionnaire in the target 
population, regardless of compliance to 
study treatment or the occurrence of 
intercurrent events. 
Secondary 
 
• To assess the effect of treatment with 
PRV-015 on other measures of disease 
activity  
• To assess the safety, tolerability, and 
pharmacokinetics (PK) of PRV-015 
when administered to adult patients with 
NRCD. 
Secondary efficacy endpoints:  
• Absolute change from baseline through 
Week 24 in the Diarrhea and Loose Stool 
domain of the CeD PRO 
• Absolute change from baseline through 
Week 24 in gastrointestinal (GI) 
symptoms as assessed by the Total GI 
score (comprising the Abdominal 
Symptoms domain, the Diarrhea and 
Loose Stool domain, and the Nausea 
item) of the CeD PRO 
• Absolute change from baseline to Week 
24 in small intestinal mucosal 
inflammation, as measured by 

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Final Version 3.0 
Objective 
Endpoint/Estimand 
intraepithelial lymphocyte (IEL) density 
using immunohistochemistry (IHC) 
Safety endpoints:  
• Adverse events (AEs): treatment-
emergent adverse events (TEAEs), 
TEAEs leading to treatment 
discontinuation, and treatment-emergent 
serious adverse events (SAEs) 
• Treatment-emergent adverse events of 
special interest (AESIs) 
• Potentially clinically important (PCI) 
changes in clinical laboratory values 
(hematology, chemistry, and urinalysis), 
vital signs (blood pressure [BP], heart 
rate, temperature, respiratory rate), and 
weight 
• Immunogenicity, as assessed by the 
presence of anti-PRV-015 antibodies 
PK endpoint:  
• Serum PRV-015 trough concentrations 
(Cmin) 
Tertiary/Exploratory 
 

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Final Version 3.0 
Objective 
Endpoint/Estimand 

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Final Version 3.0 
Objective 
Endpoint/Estimand 
 
 

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Final Version 3.0 
4. 
Study Design 
4.1. 
Overall Design 
Protocol PRV-015-002b is a Phase 2b, randomized, double-blind, placebo-controlled, parallel-
group study to evaluate the efficacy and safety of PRV-015 in adult patients with NRCD who are 
on a GFD. 
After signing informed consent form (ICF), subjects will undergo screening assessments for the 
study in a screening period of up to 28 days before Visit 1. The screening assessments will 
include the collection of demographics, medical history, and past record of the diagnosis of 
celiac disease if available. Subjects should demonstrate 1) attempted adherence to a GFD, 
confirmed by a lack of strong serological positivity (<3.0 × cutoff value for positivity), and 2) 
exposure to gluten contamination by presenting with detectable serology (above the lower limit 
of quantitation). 
After initial screening, potentially eligible subjects will enter a single-blind, placebo run-in 
period for 4 weeks, starting at Visit 1. During the run-in period, all subjects will receive 
subcutaneous (SC) injections of placebo every 2 weeks (q2w), at Visit 1 and Visit 2, in a single-
blind fashion, in which the Investigator is aware of the treatment administered but the subjects 
are not. Subjects will be asked to maintain their current GFD through the entire study and to 
complete the daily electronic diary (eDiary) for CeD PRO questionnaire as well as a stool 
frequency question (stools of Type 6 or 7 on BSFS). (The copyright of the CeD PRO [2015] is 
held by 9 Meters Biopharma and was formerly held by Alba Therapeutics Corporation. The CeD 
PRO is used with permission.) A baseline upper esophagogastroduodenoscopy (EGD) and 
biopsy will be conducted during the single-blind run-in period. The results will be used to obtain 
the VH:CD for randomization stratification. 
At the end of the 4-week single-blind, placebo run-in period, subjects will return to the study site 
for Visit 3 (Week 0/Day 1) and be re-evaluated for inclusion/exclusion criteria. Those who meet 
the entry criteria at this time will enter the 24-week double-blind treatment period (from Visit 3 
to Visit 15). At the same visit, eligible subjects will be randomized in a 1:1:1:1 ratio to receive 
100 mg, 300 mg, or 600 mg PRV-015, or matching placebo, subcutaneously (SC) every 2 weeks 
(q2w). Randomization will be stratified by VH:CD of <2 or ≥2 and by the CeD PRO Abdominal 
Symptoms domain score of <3 or ≥3 at baseline using the average of the Abdominal Symptoms 
domain scores over the last week of the placebo run-in period immediately before randomization.  
Enrollment of subjects with Marsh score of 0 or 1 will be capped at approximately 72 subjects, 
although fewer than 72 may be enrolled. 
The study drug (1 of the 3 doses of PRV-015 or placebo) will be administered SC q2w in the 
double-blind treatment period through Visit 14. Each dose will be administered in a double-blind 
fashion. The subjects’ adherence to GFD will be assessed retrospectively throughout the study 
using the stool and urine gluten tests based on the G12 antibody to interpret possible dietary 
changes or transgressions. Results will not be communicated to the subjects, who will be 
instructed to continue their baseline dietary habits throughout the study. 
Subjects will be assessed for efficacy and safety throughout the study, as indicated in the 
Schedule of Activities (SoA) (Section 1.3). Clinical assessments occur from Visit 3 through Visit 

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16. Safety is also assessed at each on-site visit through the end-of-study visit (Visit 16), which 
takes place 6 weeks after the last planned dose of the study drug.  
Randomized subjects will undergo a second EGD and biopsy at the end of the 24-week treatment 
period, within 7 days of Visit 15 in order to assess changes from baseline in IELs and VH:CD.  
Visits 6, 8, 10, and 12 may be conducted either at the site or remotely by certified mobile 
personnel per the Investigator’s decision. 
All subjects enrolled in the study will complete the daily eDiary for CeD PRO (at the end of the 
subject’s daily activities, when no more food will be consumed) and for the stool frequency 
question from Visit 1 through the end of the study at Visit 16, which will encompass the single-
blind placebo run-in and the double-blind treatment period and a safety follow-up period.  
Safety assessments include clinical laboratory tests, vital signs, and AE assessments. Subjects 
may undergo unscheduled visits if needed (e.g., for safety reasons). 
An internal Data Monitoring Committee (DMC) will monitor the study conduct (see Section 
9.5).  
4.2. 
Scientific Rationale for Study Design 
This study uses a randomized, double-blind, placebo-controlled, parallel-group design to 
evaluate the efficacy and safety of 3 dose regimens of PRV-015 in adult NRCD patients. This 
dose-ranging study design was chosen to separately compare the effects of each dose regimen 
and placebo and select a dose(s) for future development. The double-blind approach and the use 
of placebo (with matching appearance to the active treatment) are intended to minimize bias in 
the assessment and reporting of symptoms. Placebo is essential for demonstrating efficacy of a 
clinical symptom endpoint in the NRCD population, for which there are no approved 
pharmacologic therapies. Both groups will be receiving standard of care (GFD), and the study 
design will allow for a direct comparison to evaluate the effects of the active treatment.  
There is a single-blind run-in period of 4-week placebo treatment before the start of the 
randomized, double-blind treatment period. This period will allow the selection of patients who 
are truly nonresponsive to their GFD and therefore in need of adjunctive treatment.  
The primary efficacy endpoint, absolute change from baseline through Week 24 in the 
Abdominal Symptoms domain of CeD PRO, was chosen as a direct measure of changes in 
subjects’ clinical symptoms. The CeD PRO is the only fully validated symptom endpoint in 
celiac disease. In previous studies, PRV-015 has been shown to reduce the GI inflammatory 
process and symptoms. Considering the multiorgan, nonspecific symptoms associated with celiac 
disease, the Abdominal Symptoms domain, which includes GI symptoms, is expected to be the 
most sensitive domain that best reflects the manifestations of active disease and where IL-15 
blockade would most likely translate to beneficial clinical outcomes.  
4.3. 
Justification for Dose 

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4.4. 
End of Study Definition 
A subject is considered to have completed the study if he/she has completed all phases of the 
study through Visit 16 (Week 28). 
The primary completion date of the study is the date on which the last subject in the study 
provides final data for the primary efficacy assessment. 
The end of the study is defined as the date of the last assessment or data collection for the last 
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5. 
Study Population 
5.1. 
Inclusion Criteria 
Subjects must fulfill all of the following criteria at screening and, if applicable, at randomization 
(Visit 3) to be eligible for participation: 
1. Adult males or females 18 to 70 years of age, inclusive. 
2. Subjects demonstrate willingness to participate in the study and to perform all required 
procedures as documented by signed informed consent.  
3. Subjects must have a diagnosis of celiac disease by intestinal biopsy at least 12 months 
prior to screening as confirmed by medical records or written physician statement. 
4. Subjects must have reported attempting to follow a GFD for at least the 12 consecutive 
months prior to screening and must be willing to maintain their current diet for the 
duration of study participation. 
5. Subjects must have had at least one of the following symptoms at least once per week 
during the month before screening: diarrhea, loose stools, abdominal pain, abdominal 
cramping, bloating, or gas. 
6. Subjects must have a Gastrointestinal Symptom Rating Scale, Celiac Disease portion 
(CeD-GSRS) score of >2 at the screening visit. 
7. During the 4-week single-blind placebo run-in period, subjects must have a CeD PRO 
Abdominal Symptoms domain weekly average score ≥2.5 in at least 2 of the 4 weeks 
prior to the randomization visit (Visit 3) AND the CeD PRO Abdominal Symptom 
domain weekly average scores must not trend toward improvement from the initial 
weekly score (defined as continued improvement in weekly scores from week to week 
OR >50% improvement from the initial score).  
8. Subjects must have detectable (above the lower limit of detection) serum celiac-related 
antibodies (at least one of anti-tTG IgA/IgG or DGP IgA/IgG). However, the titer in each 
assay must be below 3.0 times the diagnostic cut-off value for positivity of the assay in 
order to confirm that the subject is trying to adhere to their GFD. 
9. Subjects must have human leukocyte antigen DQ (HLA-DQ) typing consistent with 
known celiac disease alleles (typically DQ2 and/or DQ8) obtained before the baseline 
biopsy. HLA-DQ typing information supplied as part of the subject medical record is 
acceptable.  
10. Body weight between 35 and 120 kg, inclusive. 
11. Female subjects must meet the following inclusion criteria: 
a. Women not of childbearing potential:  
Postmenopausal is defined as being >45 years of age with amenorrhea for at least 
18 months) or >45 years of age with amenorrhea for at least 12 months and a 
confirmatory serum follicle-stimulating hormone (FSH) level >40 IU/L with 
luteinizing hormone (LH) level >40 IU/L in women not receiving hormone 
replacement therapy; permanently sterilized (e.g., hysterectomy, bilateral 
salpingectomy, bilateral oophorectomy). Note: tubal ligation is not considered 
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b. Women of childbearing potential (WOCBP):  
i. Must have a negative serum β-human chorionic gonadotropin (β-hCG) at 
screening and a negative urine pregnancy test at randomization. 
ii. Must practice a highly effective method of birth control (<1% failure rate) 
consistent with local regulations regarding the use of birth control methods 
for subjects participating in clinical studies (see Appendix 10.3).  
iii. Must agree to use highly effective methods of birth control throughout the 
study and for 3 months after receiving the last dose of study drug.  
iv. Must agree not to donate eggs (ova, oocytes) for the purposes of assisted 
reproduction during the study and for 3 months after receiving the last 
dose of study drug. 
12. Male subjects must meet the following criterion: A man who is sexually active with a 
woman of childbearing potential and has not had a vasectomy or otherwise surgically 
sterile must agree to highly effective birth control for their female partner and must use 
condoms with spermicide during sexual intercourse, and this must continue for 3 months 
after receiving the last dose of study drug. All men must also not donate sperm during the 
study and for 3 months after receiving the last dose of study drug. 
5.2. 
Exclusion Criteria  
Subjects are excluded from the study if any of the following criteria applies at either screening 
or, if applicable, at randomization (Visit 3): 
1. Current diagnosis of any severe complication of celiac disease, such as RCD-I or RCD-II, 
enteropathy-associated T-cell lymphoma (EATL), ulcerative jejunitis, or GI perforation.  
2. Diagnosis of any chronic, active GI disease other than celiac disease, such as active, 
untreated peptic ulcer, eosinophilic esophagitis, erosive esophagitis , ulcerative colitis or 
Crohn’s disease, microscopic colitis, irritable bowel syndrome, small intestinal bacterial 
overgrowth, tropical sprue, or other GI and non-GI disorder or prior GI surgery that may, 
in the Investigator’s opinion, interfere with the assessment of symptoms of abdominal 
pain, diarrhea, or other components of celiac disease.  
3. Any known, symptomatic food allergy that, in the opinion of the Investigator, may 
interfere with the conduct or interpretation of the study. 
4. Presence of any of the following related to infection:  
a. Active acute infection with flu-like symptoms such as fever, cough, or shortness 
of breath; or active infections requiring systemic (intravenous or intramuscular) 
treatment (antibiotics, antifungal, or antiviral). 
b. Active GI infection, including H. pylori.  
c. History of tuberculosis (TB) except for successful chemoprophylaxis for positive 
TB tests. 
d. Positive Interferon Gamma Release Assay (IGRA) test at screening. Subjects with 
potential false-positive tests may have the test repeated. If chest X-ray is also 
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e. History of an opportunistic infection typical of those seen in 
immunocompromised patients (e.g., herpes zoster, systemic candida infection, or 
systemic fungal infection) within 3 years prior to screening. 
5. Any of the following laboratory test abnormalities at screening or Visit 1 (Day -28):  
a. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >3 times 
the upper limit of normal (ULN). 
b. Hemoglobin <9 g/dL (<90 g/L in SI units). 
c. Platelet count <100,000 mm3 (<100/L). 
d. White blood cell count <3,000 cells/mm3 (<3.0 ×109/L). 
e. Creatinine >1.5 mg/dL. 
f. Hemoglobin A1c (HbA1c) >9% (>90 mmol/mol) in subjects with a concurrent 
diagnosis of Type 1 or Type 2 diabetes. 
6. Use of systemic immune suppressants (including systemic or GI topical steroids) during 
the screening or single-blind placebo run-in period.  
7. Required use of a prohibited medication (see Section 6.5.1) during the screening or 
single-blind placebo run-in period. 
8. Current diagnosis or recent history of cancer within the past 5 years, except successfully 
treated basal cell or squamous cell carcinoma, cervical carcinoma-in-situ, or early-stage 
prostate cancer. 
9. Known or suspected exposure to COVID-19 infection in the 4 weeks before screening. 
10. Administration of a live vaccine within 14 days prior to randomization and the first 
administration of study drug at Visit 3.  
11. History or presence of any clinically significant disease that, in the opinion of the 
Investigator, may confound the subject’s participation and follow-up in the clinical trial 
or put the subject at unnecessary risk, including but not limited to: uncontrolled 
hypertension (BP ≥180/110 mm/Hg), unstable angina, Class II congestive heart failure or 
major fluid overload, coronary angioplasty or myocardial infarction within the past 6 
months, clinically significant arrhythmias or electrocardiogram (ECG) abnormalities, 
severe chronic pulmonary disease, or any renal, hematologic, GI, immunologic, 
dermatologic, neurologic, or psychiatric disease. 
12. History of significant substance or alcohol abuse during the 12 months prior to screening 
as obtained by medical record and/or subject report. 
13. Hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus 
(HIV) positive test results. 
14. Females who are pregnant or planning to become pregnant during the study period, or 
who are currently breastfeeding. 
15. Participation in another investigational drug or device study or treatment with an 
investigational drug within 30 days or 5 half-lives, whichever is longer, prior to 
screening. 
16. Any other reason that, in the opinion of the Investigator, may prevent the subject from 
safely participating in the study or complying with protocol requirements, including the 
endoscopies and biopsies. 

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5.3. 
Lifestyle Considerations 
Subjects are required to maintain the same diet as they have been adhering to during the entire 
study. 
Subjects are required to refrain from blood donation, illicit drug use (per applicable laws), and 
alcohol abuse (based on Investigator’s judgment) throughout the duration of the study. 
5.4. 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but do not 
enter the single-blind placebo run-in phase. Randomization failures are defined as those who 
enter the single-blind placebo run-in phase but do not meet the inclusion criteria or meet any 
exclusion criteria at Visit 3 and therefore are not randomized to a treatment group. 
A minimal set of screen failure information is required to ensure transparent reporting of screen 
failure subjects to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities. Minimal information 
includes demography, screen failure details, eligibility criteria, and any screening SAE. 
Individuals who are screen failures may be rescreened once. Rescreened subjects will be 
assigned the same subject number as for the initial screening. Subjects who are rescreened 
should be reconsented at the time of the rescreening. Subjects who have entered the run-in period 
or were randomization failures will not be rescreened. 

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6. 
Study Treatment 
Study treatment is defined as any investigational product or placebo to be administered to a study 
subject according to the study protocol. 
6.1. 
Study Drug Administered 
At each visit, each subject will receive 4 injections for a total volume of 6 mL. Depending on the 
assigned treatment group, the amount of active PRV-015 and/or placebo injected will vary as 
outlined below to administer the desired dose while maintaining the double blind.  
Name 
PRV-015 
Placebo 
Type  
Biologic  
Protein-free solution 
Unit Dose Strength(s) 
100 mg/mL with 2 mL 
deliverable volume in a 10 mL 
vial 
 
N/A 
1 ml placebo solution in 5 mL 
vials 
Dosage Levels and 
Frequency 
a. 100 mg q2w 
b. 300 mg q2w 
c. 600 mg q2w 
Placebo q2w 
Volume per Dose 
a. 1 mL active × 1 syringe,  
1 mL placebo × 1 syringe,  
2 mL placebo × 2 syringes 
b. 1 mL active × 1 syringe,  
2 mL active × 1 syringe,  
1 mL placebo × 1 syringe, 
2 mL placebo × 1 syringe 
c. 1 mL active × 2 syringes,  
2 mL active × 2 syringes  
1 mL placebo × 2 syringes 
2 mL placebo × 2 syringes 
Route of 
Administration 
SC injection 
SC injection 
Sourcing 
Provided centrally by the 
Sponsor 
Provided centrally by the 
Sponsor 

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Packaging and 
Labeling 
Provided in glass container and 
labeled according to local 
requirement 
Provided in glass container and 
labeled according to local 
requirement 
 
Duration of Study Treatment and Participation 
The duration of study participation for each subject is approximately 9 months, including ≤4 weeks 
of screening period, 4 weeks of placebo run-in period, 24 weeks of double-blind treatment period, 
and 4 weeks of final safety follow-up period. 
6.2. 
Preparation/Handling/Storage/Accountability 
PRV-015 will be supplied in a glass container and should be stored frozen at a temperature -30ºC 
(±10 ºC). Prolonged exposure to light should be avoided. The placebo solution should be stored 
refrigerated at 5 ± 3ºC.  
An unblinded pharmacist at the site will prepare 4 syringes labeled for each subject. All syringes 
will be labeled with appropriate measures to maintain the blind.  
Further guidance and information for the final disposition of unused study drugs are provided in 
the Pharmacy Manual. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
All subjects will be centrally assigned to randomized study drug (placebo or 1 of 3 doses of 
PRV-015) after the single-blind, placebo run-in period using an Interactive Voice/Web Response 
System (IVRS/IWRS). Before the study is initiated, the telephone number and call-in directions 
for the IVRS and/or the log-in information and directions for the IWRS will be provided to each 
site. 
Subjects will be randomly assigned in a 1:1:1:1 ratio, stratified by VH:CD of <2 or ≥2 (assessed 
during the placebo run-in period) and by the CeD PRO Abdominal Symptoms domain score of 
<3 or ≥3 at baseline, using the average of the Abdominal Symptoms domain scores over the last 
week of the run-in period immediately before randomization. The Investigator, Sponsor, and 
subjects will remain blinded to each subject’s assigned study drug throughout the course of the 
study. In order to maintain this blind, an otherwise uninvolved pharmacist or equivalent staff 
member will be responsible for the reconstitution and dispensation of all study drug and will 
ensure that there are no differences in time taken to dispense following randomization. 
In the event of a Quality Assurance audit, the auditor(s) will be allowed access to unblinded 
study drug records at the site(s) to verify that randomization/dispensing has been done 
accurately. 
Emergency Unblinding 
The Investigator may unblind a subject through the IVRS/IWRS at any time for an emergency 
where the treatment assignment is important for the subject’s medical care. However, if at all 
possible, it is recommended that the Investigator should consult with the Medical Monitor or 
Sponsor Medical Lead before unblinding. If the Investigator encounters difficulty in unblinding, 
the local clinical research associate can be reached for assistance. 

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6.4. 
 Study Treatment Compliance 
When subjects are dosed, they will receive the study drug directly from the Investigator or 
designee, under medical supervision. The date and time of each dose administered will be 
recorded in the source documents and recorded in the case report form (CRF). The dose of study 
intervention and study subject identification will be confirmed at the time of study drug 
preparation by a member of the unblinded study site staff. 
6.5. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements, or other specific categories of interest) that the subject is receiving at 
the time of screening or receives during the study must be recorded along with: 
• Reason for use 
• Dates of administration, including start and end dates 
• Dosage information, including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy.  
6.5.1. 
Prohibited Medications 
The following medications are not allowed during the study (unless otherwise noted):  
• Systemic or intestinal immune suppressants, including steroids. Inhaled or nasal steroids 
for respiratory diseases such as asthma and allergic rhinitis as well as topical steroids 
(except intestinal) are permitted.  
• Oral pharmaceutical presentations (e.g., capsules) of probiotic supplements. Probiotics in 
foods (e.g., yogurt) are acceptable. 
• Chronic or continuous oral and IV antibiotics (>2 weeks use). Topical antibiotic use is 
allowed. 
• Systemic antiviral medications 
• Systemic antifungal medications 
• Live vaccines (within 14 days before Visit 3) 
• Investigational drugs or devices 
Note: After screening, use of any of these medications may be permitted if they are required for 
treatment of an AE, if the Investigator believes it is necessary. The use of any of these 
medications should be documented as a protocol deviation, even if they are used to treat AEs. 
The Investigator should inform the Medical Monitor of such use as early as possible. 
6.6. 
Dose Modification 
Subjects should receive the dose regimen as assigned through randomization. No dose 
modification during the double-blind treatment period is allowed. Patients who meet the criteria 
for study treatment discontinuation should follow the instructions in Section 7.1.  
6.7. 
Treatment after the End of the Study 

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7. 
Discontinuation of Study Treatment and Subject 
Discontinuation/Withdrawal 
Discontinuation of study treatment or withdrawal from the study will be noted in the subject’s 
record. 
7.1. 
Discontinuation of Study Treatment 
In rare instances, it may be necessary for a subject to permanently discontinue (definitive 
discontinuation) study treatment. If a subject discontinues study drug administration after 
randomization (Visit 3), the subject will be encouraged to return for all subsequent on-site visits 
as listed in the SoA (i.e., Visits 4, 5, 7, 9, 11, 13, 14, 15, and 16). If the discontinued subject 
chooses to not return for on-site visits, study personnel should make every effort to conduct the 
Early Termination (ET) visit and ask the subject to return 6 weeks after the last dose of the study 
drug for the final safety follow-up visit (see Section 1.3). If a subject discontinues study drug 
administration before randomization, no further assessments will be conducted.  
The reasons for permanent discontinuation of study treatment at any time during the study 
include but are not limited to the following: 
• Safety reasons, either at the discretion of the Investigator or at the subject’s request.  
o In particular, subjects can be discontinued from study treatment if they develop 
severe complications of celiac disease that require intensive treatment (e.g., RCD-
I or RCD-II, jejunitis, perforation). 
o Malignancy 
o Active TB 
o A serious opportunistic infection 
o Pregnancy (female subjects) 
o Anaphylaxis or severe hypersensitivity reactions after the initial injection(s) 
• Significant protocol violations (e.g., noncompliance with study procedures), at the 
discretion of the Sponsor 
• The use of prohibited therapy that may interfere with the study assessment and analysis 
(Section 6.5.1). The Investigator is required to report all such information on the CRF 
and decide, upon discussion with the Sponsor, whether the subject is to be discontinued 
from study treatment.  
7.1.1. 
Emergency Data Monitoring Committee Meeting  
The DMC will hold an emergency meeting if any of the following occur:  
• Death of a subject  
• Anaphylactic reaction in any subject 
• A life-threatening AE in any subject that is considered by the investigator to be possibly 
related to study drug 
The DMC would review unblinded safety information to determine whether any change in study 
conduct should occur.  

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7.2. 
Subject Withdrawal from the Study 
A subject may withdraw from the study at any time at his/her own request. If possible, the early 
termination assessments listed for Visit 15 (Week 24) in the SoA (Section 1.3) should be 
conducted before the withdrawal, including EGD with biopsy, unless the withdrawal occurs 
before randomization.  
A subject who withdraws consent from the study will be permanently discontinued both from the 
study drug and from any further assessments.  
If the subject withdraws consent for disclosure of future information, the sponsor may retain and 
continue to use any data collected before such a withdrawal of consent. 
If a subject withdraws from the study, he/she may request destruction of any samples taken and 
not yet tested, and the Investigator must document this in the site study records. 
7.3. 
Lost to Follow-up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. The site should attempt to contact the 
subject at least 3 times and document all such attempts before determining the subject has been 
lost to follow-up.  

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8. 
Study Assessments and Procedures 
8.1. 
All Laboratory Tests 
The maximum amount of blood collected from each subject over the duration of the study is 
expected not to exceed 400 mL over a period of approximately 9 months. This estimation does 
not include repeat or unscheduled samples, which may be taken for safety reasons or for 
technical issues with collected samples. 
All laboratory tests to be conducted at in-office visits are listed as follows.  
Screening Visit (within 28 days before Visit 1) 
• Chemistry: calcium, ALT, AST, albumin, total and direct bilirubin, sodium, potassium, 
blood urea nitrogen (BUN), creatinine, chloride, CO2, glucose, total protein, alkaline 
phosphatase (ALP) (if ALP is >3 x ULN, test 5’nucleotidase or GGT), magnesium, 
phosphorus 
• Complete blood count (CBC): hemoglobin, hematocrit, platelets, white blood cell count 
(WBC) with differential, red blood cell count (RBC), mean corpuscular volume (MCV), 
mean corpuscular hemoglobin concentration (MCHC), mean cell hemoglobin (MCH) 
• Urinalysis (dipstick and microscopic) 
• HbA1C (subjects with diagnosed Type 1 or Type 2 diabetes only) 
• HLA DQ2/8 (as needed) 
• Testing for HIV, HBV and HCV for exclusion as follows: 
- HIV: positive antibody to p24 antigen (Ab-p24Ag) for human immunodeficiency 
virus (HIV) 1 or 2 confirmed by positive HIV 1/2 Western blot  
- HBV: HBsAg, anti-HBc total (IgM and IgG) confirmed by positive HBV DNA, anti-
HBs  
- HCV: HCV antibody confirmed by positive HCV RNA  
• IGRA 
• H. pylori stool test 
• Serum pregnancy test (all WOCBP only) 
• FSH/LH for women with suspected menopause (i.e., not surgical menopause) 
• Serum IgA 
• Anti-tTG IgA and IgG, anti-DGP IgA and IgG 
Visit 1 (Single-blind run-in Week -4) 
• Chemistry (same tests as screening) 
• CBC (same tests as screening) 
• HbA1C (subjects with diagnosed Type 1 or Type 2 diabetes only)  
• Urinalysis (same tests as screening) 
• Stool and urine gluten tests 
• Urine pregnancy (WOCBP only) 
Visit 2 (Single-blind run-in Week -2) 
• Stool and urine gluten tests 

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• Urine pregnancy (WOCBP only) 
Visit 3 (Week 0/Day 1) 
• Chemistry (same tests as screening) 
• CBC (same tests as screening) 
• Urinalysis (same tests as screening) 
• Stool and urine gluten tests 
• Urine pregnancy test (WOCBP only) 
• Anti-tTG IgA, anti-DGP IgA  
• Ferritin, iron, TIBC, vitamins D, B12, folate 
• Serum biomarkers (e.g., IL-15) 
• Trough concentration of PRV-015 
• ADA  
Visit 4 (Week 2/Day 15) 
• Stool and urine gluten tests 
• Trough concentration of PRV-015 
• ADA  
Visit 5 (Week 4/Day 29) 
• Chemistry (same tests as screening) 
• CBC (same tests as screening) 
• HbA1C (subjects with diagnosed Type 1 or Type 2 diabetes only)  
• Urinalysis (same tests as screening) 
• Stool and urine gluten tests 
• Urine pregnancy test (WOCBP only) 
• Anti-tTG IgA, anti-DGP IgA  
• Serum biomarkers (e.g., IL-15) 
• Trough concentration of PRV-015 
• ADA 
Visit 7 (Week 8/Day 57) 
• Chemistry (same tests as screening) 
• CBC (same tests as screening) 
• Urinalysis (same tests as screening) 
• HbA1C (subjects with diagnosed Type 1 or Type 2 diabetes only) 
• Stool and urine gluten tests 
• Urine pregnancy test (WOCBP only) 
• Anti-tTG IgA, anti-DGP IgA  
• Serum biomarkers (e.g., IL-15) 
• Trough concentration of PRV-015 
Visit 9 (Week 12/Day 85) 
• Chemistry (same tests as screening) 

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• CBC (same tests as screening) 
• HbA1C (subjects with diagnosed Type 1 or Type 2 diabetes only) 
• Urinalysis (same tests as screening) 
• Stool and urine gluten tests 
• Urine pregnancy test (WOCBP only) 
• Anti-tTG IgA, anti-DGP IgA  
• Ferritin, iron, TIBC, vitamins D, B12, folate 
• Serum biomarkers (e.g., IL-15) 
• Trough concentration of PRV-015 
• ADA 
Visit 11 (Week 16/Day 113) 
• Chemistry (same tests as screening) 
• CBC (same tests as screening) 
• HbA1C (subjects with diagnosed Type 1 or Type 2 diabetes only) 
• Urinalysis (same tests as screening) 
• Stool and urine gluten tests 
• Urine pregnancy test (WOCBP only) 
• Anti-tTG IgA, anti-DGP IgA  
• Serum biomarkers (e.g., IL-15) 
• Trough concentration of PRV-015 
Visit 13 (Week 20/Day 141) 
• Chemistry (same tests as screening) 
• CBC (same tests as screening) 
• HbA1C (subjects with diagnosed Type 1 or Type 2 diabetes only) 
• Urinalysis (same tests as screening) 
• Stool and urine gluten tests 
• Urine pregnancy test (WOCBP only) 
• Anti-tTG IgA, anti-DGP IgA  
• Serum biomarkers (e.g., IL-15) 
• Trough concentration of PRV-015 
Visit 14 (Week 22/Day 155)  
• Trough concentration of PRV-015 
• ADA 
Visit 15 (Week 24/Day 169) or Early Termination 
• Chemistry (same tests as screening) 
• CBC (same tests as screening) 
• HbA1C (subjects with diagnosed Type 1 or Type 2 diabetes only) 
• Urinalysis (same tests as screening) 
• Stool and urine gluten tests 

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• Urine pregnancy test (WOCBP only) 
• Anti-tTG IgA, anti-DGP IgA  
• Ferritin, iron, TIBC, vitamins D, B12, folate 
• Serum biomarkers (e.g., IL-15) 
• Trough concentration of PRV-015  
• ADA 
Visit 16 (Week 28/Day 197) 
• Chemistry (same tests as screening) 
• CBC (same tests as screening) 
• HbA1C (subjects with diagnosed Type 1 or Type 2 diabetes only) 
• Urinalysis (same tests as screening) 
• Stool and urine gluten tests 
• Urine pregnancy test (WOCBP only) 
• Anti-tTG IgA, anti-DGP IgA  
• Serum biomarkers (e.g., IL-15) 
• Trough concentration of PRV-015  
• ADA 
8.2. 
Efficacy Assessments 
8.2.1. 
Celiac Disease Patient-Reported Outcome (CeD PRO) 
Subjects will assess their symptoms daily in the CeD PRO using the eDiary throughout the study. 
This questionnaire was specifically developed and validated to assess symptom severity in 
clinical trials of celiac disease (Leffler 2015) and is accepted by Health Authorities as a 
registrational endpoint for marketing authorization. The symptom domains within the CeD PRO 
are illustrated in Figure 2. 
Items in the questionnaire were formulated based on one-on-one interviews with patients with 
celiac disease, thus they reflect the symptoms that patients consider part of their celiac disease 
experience. The questionnaire is designed as a self-administered daily diary to be completed at 
the same time each day and requires less than 10 minutes to complete. It includes 9 items asking 
participants about the severity of celiac disease symptoms they may experience each day. 
Participants are asked to rate their symptom severity on an 11-point (0 to 10) scale; from “not 
experiencing the symptom” to “the worst possible symptom experience”. Symptoms include 
abdominal cramping, abdominal pain, bloating, gas, diarrhea, loose stool, nausea, headache, and 
tiredness. 
The Abdominal Symptoms domain refers to questions regarding abdominal pain, abdominal 
cramping, bloating, or gas in the CeD PRO questionnaire.  
Analyses will be performed on all individual domain scores and weekly worst symptom domain 
scores in the GI domains (Abdominal Symptoms and Diarrhea/Loose Stool domains) and Total 
GI score (Abdominal Symptoms Domain + Diarrhea/Loose Stool Domain + Nausea item). The 
Total GI score will be assessed with and without inclusion of the Nausea item.  

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The copyright of the CeD PRO [2015] is held by 9 Meters Biopharma and was formerly held by 
Alba Therapeutics Corporation. The CeD PRO is used with permission. 
Figure 2 
Symptom Domains in the Celiac Disease Patient-Reported Outcome 
Questionnaire 
 
See Appendix 10.4 for the instrument.  
8.2.2. 
Stool Frequency Question Based on BSFS 
The BSFS is a pictorial aid to help subjects identify the shape and consistency of their stools 
during the study (Riegler 2001). The subject will be asked to record the number of stools that 
have a consistency of Type 6 or 7 (loose stool or entirely liquid) at bedtime daily in the eDiary. 
On the days in which the subject experiences no such stool (BSFS Type 6 or 7), the subject 
should record 0 in the eDiary instead of leaving it blank.  
See Appendix 10.4 for the instrument.  
8.2.3. 
Gastrointestinal Symptom Rating Scale (GSRS) 
The GSRS is a 15-question, 7-point-scale questionnaire used to assess 5 dimensions of GI 
syndromes: diarrhea, indigestion, constipation, abdominal pain, and reflux (Svedlund 1988). The 
recall period is 1 week before the assessment. While not specific for celiac disease, the GSRS is 
widely used in gastroenterology and has been used in several clinical trials of experimental 
medications in celiac disease (Kelly 2013; Lähdeaho 2011; Leffler 2015).  

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See Appendix 10.4 for the instrument.  
8.2.4. 
Investigator Global Assessment of Disease 
The IGA is a 5-point Likert scale designed for use by the Investigator or qualified sub-
investigator to assess the subject’s clinical disease activity at each specified time point. The same 
assessor should be used at each specified time point if possible.  
See Appendix 10.4 for the instrument. 
8.2.5. 
PROACTIVE Dietary Questionnaire 
The PROACTIVE Dietary Questionnaire (See Appendix 10.4) is a two-question instrument to 
assess potential inadvertent exposure to gluten. The questionnaire will be completed on a weekly 
basis (every Monday) to assess dietary habits during the previous week. 
8.2.6. 
Patient Global Impression of Severity and Change 
In the current study, data collected from the PGIS and PGIC instruments will assist in future 
analyses of clinically meaningful change for the Abdominal Symptoms domain of the CeD PRO.  
8.2.6.1. 
Patient Global Impression of Severity (PGIS) 
Subjects will be asked to complete the PGIS every 2 weeks in the eDiary, from the evening of 
eDiary dispensation at Visit 1 (Day -28) through the end of the study.  
Subjects will be asked to assess the severity of their symptoms as follows: 
“Please choose the response that best describes the severity of your celiac disease over 
the past 7 days (check one response): None, Mild, Moderate, Severe, Very Severe.” 
8.2.6.2. 
Patient Global Impression of Change (PGIC) 
Subjects will be asked to complete the PGIC every 2 weeks in the eDiary, beginning 2 weeks 
after the first dose of study drug administration at Visit 1.  
Subjects will be asked to compare their symptoms to those before treatment as follows: 
“Please choose the response below that best describes the overall change in your celiac 
disease symptoms since you started taking the study medication: Much better, A little 
better, No change, A little worse, Much worse.”  
8.2.7. 
Esophagogastroduodenoscopy (EGD) and Histological Assessments 
At each time point specified in the SoA (Section 1.3), at a minimum, 6 biopsies or specimens of 
small-bowel tissue will be taken from the second part of the duodenum distal to the ampulla 
(duodenum D2) by EGD and endoscopic forceps biopsy. Ulcerative lesions should be avoided 
for all biopsies. The biopsies should be opaque and not translucent or stringy. Poor specimens 
should be replaced. The location and macroscopic appearance of the tissue will be noted in the 
source documents. The potential presence of any observable lesion such as ulcerative jejunitis 
will also be captured. When necessary, samples will be re-oriented and sectioned again until they 
are of good quality. The procedures will be described in a Study or Laboratory Manual or a 
similar document. The biopsies or specimens will be prioritized as follows: 

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1. All 6 specimens will be fixed in PAXgene at the site (see Central Laboratory Manual) 
and shipped to the Central Pathologist.   
2. The Central Pathologist, blinded to treatment assignment, will assess villus height (VH, 
in micrometers) and crypt depth (CD, in micrometers) and their ratio, VH:CD, using 4 
specimens. Further, the Marsh-Oberhuber histology score will be given (M0, M1, M2, 
M3a, M3b, or M3c) and the density of CD3-positive IELs (cells/100 epithelial cells) will 
be assessed. Histology analysis will be performed following standard operating 
procedures for fixed biopsy specimen orientation, paraffin embedding, cutting, staining, 
and scanning for whole slide virtual microscopy. Standard operating procedures will also 
be followed for biopsy morphometry readings using validated methods (Taavela 2013). If 
it is not feasible to measure at least 3 villus-crypt units for a subject's given biopsies, even 
after re-cutting, the results will be considered not evaluable. 
3. Two specimens will be placed in a messenger ribonucleic acid (mRNA) preservative for 
future mRNA analysis of inflammatory pathways (e.g., expression analysis of IL-15-
related pathways to potentially identify predictive biomarkers of response to PRV-015).  
Every effort will be made to collect at least all 6 specimens, but if this number cannot be 
reached, the specimens will be allocated in the order indicated above. Sites may collect a 
maximum of 2 additional duodenal biopsy fragments for local clinical and/or research purposes. 
Additional biopsies of unexpected abnormalities or diseases that are excluded from the study 
may also be taken and processed locally.  
8.2.8. 
Celiac Disease-Related Serology 
Anti-tTG auto-antibodies, while not very responsive to modest dietary transgressions, constitute 
a specific tool to assess disease activity in response to large amounts of gluten over a period of 
time of at least 8-12 weeks (Lähdeaho 2011; Kelly 2013). Blood samples will be collected at the 
specified visits to determine the levels of serum anti-tTG antibodies (see Section 1.3). Anti-tTG 
IgA and IgG are analyzed in blood at screening and in serum thereafter using enzyme-linked 
immunosorbent assay (ELISA). 
Anti-DGP antibodies are more responsive than anti-tTG to gluten consumption and have been 
detected in some celiac patients who are negative for anti-tTG due to the different kinetics 
between the antibodies and the possibility of IgA deficiency and a false negative anti-tTG IgA. 
Thus, anti-DGP IgG is a sensitive antibody to measure celiac disease activity (Brusca 2015). 
Blood samples will be collected to analyze serum anti-DGP antibodies (IgA) by ELISA at 
specified visits (see Section 1.3). 
8.2.9. 
Gluten Stool and Urine Tests 
The G12 antibody-based stool and urine gluten tests are validated assays used to assess patient 
compliance with gluten challenge and to measure possible gluten contamination in research 
studies. The assay detects and quantifies gluten consumption by measuring gluten immunogenic 
peptides in stool (Comino 2012) and urine (Moreno 2015). 
Subjects are instructed to collect a stool sample approximately every 2 weeks, before each 
scheduled visit and bring it to the site or provide the sample during the visit if possible. If this is 
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For at-home visits, samples are not collected. Urine sample for gluten testing will be collected 
during the office visit.  
8.3. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA. 
8.3.1. 
Physical Examinations 
A complete physical examination, required at screening, Visit 1, Visit 15, and Visit 16, will 
include, at a minimum, assessments of the head, eyes, ears, nose and throat, cardiovascular, 
respiratory, gastrointestinal and neurologic systems and skin, extremities, and lymph nodes. A 
brief physical examination at other specified visits (Section 1.3) will include, at a minimum, 
assessments of the skin, lungs, cardiovascular system, abdomen (liver and spleen), and areas of 
previously noted abnormalities.  
Height will be measured and recorded at screening. Weight will be measured at all physical 
examinations. 
8.3.2. 
Vital Signs 
Vital signs include BP, respiratory rate, heart rate, and body temperature (axillary or oral).  
Measurements of BP and heart rate will be assessed supine or sitting, after the subject has rested 
for at least 5 minutes in a quiet setting without distractions. 
The investigator will note if vital signs are normal or abnormal and, if abnormal, whether they 
are clinically significant or not.  
Cut-off values considered to be potentially clinically important (PCI) will be outlined in the 
Statistical Analysis Plan (SAP). 
8.3.3. 
Electrocardiograms 
Single 12-lead ECG will be obtained at screening for study eligibility. The Investigator should 
note whether it is normal, abnormal not clinically significant, or abnormal clinically significant.  
8.3.4. 
Clinical Safety Laboratory Assessments 
Clinical safety laboratory tests are among the overall laboratory tests listed in Section 8.1.  
The Investigator must review the laboratory report, document this review, and determine whether 
any clinically relevant changes occurring during the study should be classified as an AE or not. 
Cut-off values for PCI laboratory abnormalities will be outlined in the SAP and Laboratory 
Manual.    
8.4. 
Adverse Events and Serious Adverse Events 
All AEs will be reported by the subject. 
The Investigator and any qualified designees are responsible for detecting, documenting, and 
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responsible for following up AEs that are serious, considered related to the study drug or study 
procedures, or that caused the subject to discontinue the study drug (see Section 7). 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs and SAEs will be collected from the signing of the ICF through the final visit (Visit 16) 
as specified in the SoA (Section 1.3). 
TEAEs will be collected from the first post-randomization dose of the study drug administration 
at Visit 3 through the final visit (Visit 16) as specified in the SoA (Section 1.3). The AEs and 
SAEs reported during the screening and single-blind placebo run-in periods will be reported 
separately from the TEAEs.  
All SAEs will be recorded and reported to the sponsor or designee immediately upon observing 
or learning of the event and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 10.2. Information about the SAE should be as complete as possible and include 
causality. The Investigator will submit any updated SAE data to the sponsor within 24 hours of it 
being available. 
8.4.2. 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 10.2. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the subject is the preferred method to inquire about 
AE occurrences. 
8.4.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs and AESIs (as defined in Section 8.4.7) will be followed 
until resolution, stabilization, the event is otherwise explained, or the subject is lost to follow-up 
(as defined in Section 7.3). Further information on follow-up procedures is provided in Appendix 
10.2. 
8.4.4. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the Investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of subjects and the safety of a study 
drug under clinical investigation are met.  
The Investigator is required to submit via email or facsimile the SAE form to the CRO, including 
a summary of relevant information, a diagnosis or symptom summary, and the Investigator’s 
assessment of its relationship to study drug, within 24 hours. Follow-up information should be 
provided as it becomes available. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study drug under clinical investigation. The sponsor 
will comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees (IEC), 
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Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSAR) according to local regulatory requirements and sponsor policy and forwarded to 
Investigators as necessary. 
An Investigator who receives an Investigator Safety Report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the sponsor will review and then file 
it along with the study binder and will notify the IRB/IEC, if appropriate according to local 
requirements. 
8.4.5. 
Pregnancy 
All pregnancies in female subjects and female partners of male subjects that occur after 
randomization and the start of study drug administration will be collected through the final visit 
and up to 3 months after the last dose of the study drug, whichever is later.  
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of learning 
of the pregnancy and should follow the procedures outlined in Appendix 10.3. 
The pregnancy should be followed until delivery or termination of the pregnancy. Abnormal 
pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital anomalies, 
ectopic pregnancy) are considered SAEs. 
8.4.6. 
Hospitalizations for Social Reasons or for Procedures 
Hospitalization for social reasons or for procedures that do not generally require hospitalization 
such as for endoscopy, will not be considered as AEs.  
8.4.7. 
Adverse Events of Special Interest  
The treatment-emergent AESIs to be collected are severe opportunistic infections and 
hypersensitivity reactions of at least moderate severity.  
8.5. 
Treatment of Overdose 
Overdose (a dose above the highest dose specified in this protocol) is not expected in this study 
since the drug is administered by study personnel. No doses of PRV-015 above 600 mg or 
8 mg/kg have been previously administered. The effects above these doses are unknown, and no 
antidote is available.  
8.6. 
Pharmacokinetics and Immunogenicity 
Blood samples will be collected at Visit 3 before the first post-randomization dose of study drug 
administration (baseline) and before the dose is given at each subsequent visit indicated in the 
SoA. Samples will be analyzed for serum trough concentration of PRV-015 (Cmin) and ADA, as 
well as neutralizing antibodies (NAb), using validated assays.  
Drug concentration information will not be reported to investigative sites or blinded personnel 
until the study is unblinded.  

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8.7. 
Pharmacodynamics and Biomarkers 
Pharmacodynamic biomarkers to be explored in the study include, but are not limited to, the 
following parameters:  
• Biomarkers of disease activity (such as serum IL-15)   
• Anti-tTG IgA  
• Anti-DGP IgA  
• Other exploratory biomarkers 
8.8. 
Genetics 
Celiac genetic markers (typically HLA DQ2 and DQ8) will be assessed at screening for inclusion 
(Section 5.1), if the subject has not already been tested and the results available in the medical 
record. If a subject has previously obtained a test for HLA, the result will be recorded in the 
eCRF. 
8.9. 
Quality of Life Measurements 
The study personnel will evaluate subjects’ quality of life using the ICDSQ questionnaire at 
study visits specified in the SoA (Section 1.3). The ICDSQ questionnaire (https://eprovide.mapi-
trust.org/instruments/impact-of-celiac-disease-symptoms-questionnaire-c) is an instrument 
developed by Alvine Therapeutics to assess the impact of celiac disease symptoms on patients’ 
quality of life (Acaster 2011).  
In addition, EQ-5D-5L will be administered to subjects at the same visits as ICDSQ. The EQ-
5D-5L is a 6-item, self-administered generic measure of health status and consists of two parts: a 
descriptive system and a visual analog scale (VAS). (https://euroqol.org/wp-
content/uploads/2019/09/EQ-5D-5L-English-User-Guide_version-3.0-Sept-2019-secured.pdf)  
ICDSQ and EQ-5D-5L are included in Appendix 10.4.  

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9. 
Statistical Considerations 
9.1. 
Statistical Hypotheses 
The hypothesis of this study is that one or more dose groups of PRV-015 is effective in 
attenuating the symptoms of celiac disease compared with placebo in adult subjects with celiac 
disease who are symptomatic despite being on a GFD for at least 12 months. 
9.2. 
Sample Size Determination 
A proposed sample size of approximately 50 evaluable subjects within each treatment group 
would provide approximately 80% power to detect a 0.40 difference from placebo to any given 
active treatment group at the two-sided, 0.05 level of significance in the primary endpoint, 
change through Week 24 in the Abdominal Symptoms domain score in CeD PRO. These 
calculations are based on the assumption of a 
 within-subject standard deviation (SD), as 
derived in the CELIM-NRCD-001 trial using the mixed effect modeling for repeated measures 
(MMRM) analyses. An approximate 
 difference in the overall least squares (LS) means 
through 16 weeks in the treatment period was observed between the active (300 mg) and placebo 
groups. The overall estimate through 16 weeks was observed to be 
 for placebo versus 
 
for the 300 mg treatment group. Of note, the estimated difference at week 16 was 
; however, 
the more conservative overall difference of 
 was used in the calculation of sample size. The 
results and their ranking are exploratory in nature, and the selection of endpoints and dose for 
confirmatory studies will be based on the totality of evidence. As such, these calculations are not 
adjusted for multiplicity. 
Approximately 220 subjects will be randomized at a ratio of 1:1:1:1 to PRV-015 100 mg, 
300 mg, 600 mg, or placebo (approximately 55 subjects per group). Subjects will be stratified by 
normal or abnormal VH:CD (i.e., <2 or ≥2) and by the CeD PRO Abdominal Symptoms domain 
score of <3 or ≥3 at baseline using the average of the Abdominal Symptoms domain scores over 
the last week of the single-blind placebo run-in period immediately before randomization. The 
number of subjects with Marsh score of 0 or 1 will be capped at approximately 72. Withdrawn 
subjects will not be replaced. 
9.3. 
Populations for Analyses 
The following populations are defined as follows: 
Population 
Description 
Intent to treat (ITT) 
All randomized subjects. Subjects will be analyzed according to 
the treatment they are randomly assigned, regardless of the 
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Population 
Description 
Per protocol (PP) 
All subjects in the ITT population except those who have major 
protocol violations. Major protocol violations are defined as 
protocol deviations serious enough that are considered likely to 
affect the interpretation of the study results. These subjects will 
be identified prior to unblinding of the study and will be 
documented in the subject classification document. Subjects who 
withdraw due to lack of response or worsening of disease will be 
included in the PP analysis. 
Safety 
All randomized subjects who take at least 1 dose of the study 
drug post-randomization. Subjects will be analyzed according to 
the treatment they actually receive. In addition, safety results 
reported in the 4-week placebo run-in period will be reported 
separately from the active treatment period. 
9.4. 
Statistical Analyses 
The SAP will be finalized prior to unblinding and will include a detailed description of the 
statistical analyses, data derivation rules and handling of missing data.  
Any differences between the protocol and the SAP will be documented in the SAP. Final 
statistical analyses will be based on the SAP.  
9.4.1. General Considerations 
All continuous endpoints and respective changes from baseline (absolute and percent) will be 
summarized (N, means, medians, SD, coefficients of variation [CV%], minimum and 
maximum). Rates or proportions will be tabulated by frequency of occurrence (count) and 
percent. All summaries will be by treatment and collection time. 
Baseline values will be derived from observations collected in the placebo run-in period. For the 
CeD PRO Abdominal domain scores, baseline value will be the average of scores over the last 
week of the 4-week placebo run-in period immediately before randomization. 
9.4.2. 
Primary Endpoint and Estimand 
The primary endpoint is the change from baseline through Week 24 in the score of the 
Abdominal Symptoms domain of CeD PRO questionnaire, compared between the 3 PRV-015 
dose groups and the placebo group.  
The primary estimand is the difference in the overall mean values (averaged across 24 weeks) of 
each of the 3 PRV-015 treatment groups compared with placebo of the change from baseline in 
the Abdominal Symptoms domain of the CeD PRO questionnaire in the target population, 
regardless of compliance with study treatment or the occurrence of intercurrent events. 
The primary endpoint will be tested for each of the 3 dose levels of PRV-015, 100 mg, 300 mg, 
or 600 mg against placebo, separately as follows: 
H10: µPRV015 (600mg) = µPlacebo         

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against the alternative  
H11: µPRV015 (600mg) ≠ µPlacebo,  
H20: µPRV015 (300mg) = µPlacebo  
against the alternative  
H21: µPRV015 (300mg) ≠ µPlacebo, and 
H30: µPRV015 (100mg) = µPlacebo  
against the alternative  
H31: µPRV015 (100mg) ≠ µPlacebo  
The primary efficacy endpoint will be summarized along with respective absolute and percent 
changes from baseline.  
The primary efficacy endpoint (CeD PRO Abdominal Symptoms domain score) will be analyzed 
using linear mixed effect modeling for repeated measures (MMRM) with treatment, week, and 
week by treatment as fixed effects, the continuous baseline Abdominal Symptoms domain and 
VH:CD as covariates, and subject as a random effect.  
Baseline Abdominal Symptoms domain score is defined as the average of the daily scores for the 
last week of assessment in the placebo run-in period. Baseline VH:CD is the measure from 
endoscopic biopsies performed during the placebo run-in period. 
The base-model variance-covariance structure for the repeated measures data will be 
unstructured (UN). An autoregressive variance-covariance structure of order 1 [AR(1)] will be 
tested against the UN variance-covariance structure using likelihood ratio tests. An overall 
estimate of treatment effect as well as treatment differences will be provided along with the 
respective 95% confidence intervals (CIs). By-week estimates will be provided as well. All tests 
of statistical significance will be at two-sided, 0.05 level of significance. As the MMRM analysis 
assumes that data are missing at random, sensitivity analyses will be performed to assess affects 
from departure of this assumption. 
The primary analyses will be conducted on the ITT population. Secondary analyses of the 
primary endpoint will be conducted on the PP population. Subgroup analyses of the primary 
endpoint will be conducted for each level of both stratification factors and for subjects showing 
at least 2 positive results from the stool or urine gluten tests post baseline, as well as those with 0 
or 1 positive tests. 
9.4.3. 
Secondary Endpoints 
The secondary efficacy endpoints (Section 3) will be analyzed using the ITT and PP populations, 
as well as the subgroups described for the primary endpoint. This includes changes from baseline 
through Week 24 in the Diarrhea and Loose Stool Domain score and the Total GI score. 
Analyses will be performed on the IEL density (measured by IHC). The analyses will be 
comparable to the primary endpoint analysis and will be described in detail in the SAP.  

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9.4.4. 
Tertiary/Exploratory Endpoints 
9.4.5. 
Safety Analyses 
The Safety population will be used for all safety analyses. The safety variables, including AEs 
(coded using the Medical Dictionary for Regulatory Activities [MedDRA]) will be tabulated by 
actual treatment received. TEAEs, TEAEs leading to withdrawal, treatment-emergent SAEs, and 
AESIs will be tabulated by MedDRA system organ class and preferred term. PCI laboratory tests 
and vital signs will be tabulated and listed by visit. Additionally, AEs and SAEs will be tabulated 
separately for subjects enrolled in the 4-week placebo run-in period. 
9.4.6. 
Pharmacokinetic and PK/PD Analyses  
The geometric means and geometric CV% of PRV-015 minimum concentrations (Cmin) will be 
reported by treatment group and time point in addition to N, mean, SD, min, and max. In 

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addition, dose proportionality, achievement of steady-state, and accumulation ratio based on Cmin 
will be assessed. Associations of Cmin with biomarkers of disease activity and other clinical 
endpoints may be explored. Dose proportionality will be analyzed using a power model, and 
potential PK/PD associations will mainly be assessed graphically and, if warranted, further 
elucidated with linear or nonlinear modeling techniques. 
Additionally, absolute and changes from baseline in gluten-induced serum antibodies (anti-tTG 
and anti-DGP antibodies) will be listed and summarized by treatment group and collection visit. 
Relationships to dose and PK may be explored. 
9.5. 
Interim Analysis  
No formal interim analysis is planned for this study. An internal DMC will evaluate risk-benefit 
continually during the study and may recommend changes to study conduct.  
Internal Data Monitoring Committee 
An internal DMC will be set up to periodically evaluate trial-related data. The DMC will consist 
of at least 3 independent members not affiliated with the study. It will be chaired by a physician, 
and other members will include at least 1 physician and 1 statistician.  The DMC will receive 
blinded and unblinded data before each meeting. The DMC will meet at least quarterly. The 
DMC may also hold emergency meetings in the event of death regardless of relatedness, life-
threatening events possibly related to study drug, or anaphylaxis to advise on continued study 
conduct. Relevant medical literature may also be reviewed by the committee. 
Complete guidelines, evaluation criteria, and other organizational and operational aspects will be 
documented in a DMC Charter.  
An additional series of Safety Meetings will be held between the study team, including the 
Sponsor Safety Physician, and Amgen, the holder of the global safety database. 

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10. 
Supporting Documentation and Operational Considerations 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines 
• Applicable ICH Good Clinical Practice (GCP) Guidelines 
• Applicable laws and regulations 
The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., advertisements) 
must be submitted to an IRB/IEC by the Investigator and reviewed and approved by the IRB/IEC 
before the study is initiated. 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study subjects. 
The Investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC 
• Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
• Providing oversight of the conduct of the study at the site and adherence to local and 
other applicable regulatory requirements 
10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
10.1.3. 
Informed Consent Process 
The Investigator or his/her designee will explain the nature of the study to the subject or his/her 
legally authorized representative and answer all questions regarding the study. 
Subjects must be informed that their participation is voluntary. Subjects or their legally 
authorized representatives will be required to sign and date a statement of informed consent that 
meets local regulatory and/or IRB/IEC requirements.  

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The medical record must include a statement that written informed consent was obtained before 
the subject was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
Subjects must be re-consented to the most current version of the ICF(s) during their participation 
in the study. 
A copy of the ICF(s) must be provided to the subject or the subject’s legally authorized 
representative. 
The ICF will contain a separate section that addresses the use of remaining mandatory samples 
for optional exploratory research. The Investigator or authorized designee will explain to each 
subject the objectives of the exploratory research. Subjects will be told that they are free to 
refuse to participate and may withdraw their consent at any time and for any reason during the 
storage period. A separate signature will be required to document a subject's agreement to allow 
any remaining specimens to be used for exploratory research. Subjects who decline to participate 
in this optional research will not provide this separate signature. 
10.1.4. 
Data Protection 
Subjects will be assigned a unique identifier by the sponsor. Any subject records or datasets that 
are transferred to the sponsor will contain the identifier only; subject names or any information 
that would make the subject identifiable will not be transferred. 
The subject must be informed that his/her personal study-related data will be used by the sponsor 
in accordance with local data protection law. The level of disclosure must also be explained to 
the subject who will be required to give consent for their data to be used as described in the 
informed consent  
The subject must be informed that his/her medical records may be examined by Clinical Quality 
Assurance auditors or other authorized personnel appointed by the sponsor, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 
The Investigator is responsible for ensuring that subject confidentiality is maintained for any 
documents submitted to the sponsor. 
10.1.5. 
Committees Structure 
A Safety Committee, consisting of the CRO Medical Monitor, Sponsor Medical Lead, Sponsor 
Safety Physician, and Pharmacovigilance Physician from the holder of the Global Safety 
Database, will be formed to provide oversight during the study. Other study team members may 
be included in the committee as well. Meetings with minutes will be held at least quarterly to 
assess the cumulative blinded safety tables and listings and to review relevant safety information 
of PRV-015 as it becomes available from other studies in other indications. Relevant medical 
literature may also be reviewed by the committee. 
10.1.6. 
Dissemination of Clinical Study Data 
The study information will be posted on www.ClinicalTrials.gov and EudraCT. The disclosure 
of study results will be compliant with regulatory requirements. 

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10.1.7. 
Data Quality Assurance 
All relevant study data will be recorded, as appropriate, in the CRF unless transmitted to the 
sponsor or designee electronically (e.g., laboratory data). The Investigator is responsible for 
verifying that data entries are accurate and correct by electronically signing the CRF at intervals 
determined by the Sponsor. 
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
Monitoring details describing strategy (e.g., risk-based initiatives in operations and quality such 
as Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), methods, 
responsibilities and requirements, including handling of noncompliance issues and monitoring 
techniques (central, remote, or on-site monitoring), are provided in the Monitoring Plan. 
The sponsor or designee is responsible for the data management of this study, including quality 
checking of the data. 
The sponsor assumes accountability for actions delegated to other individuals (e.g., CRO). 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of subjects are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and any other study agreements, 
ICH GCP, and all applicable regulatory requirements. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator for 25 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be transferred to 
another location or party without written notification to the sponsor. 
10.1.8. 
Source Documents 
Source documents provide evidence for the existence of the subject and substantiate the integrity 
of the data collected. Source documents are filed at the Investigator’s site. 
Data reported in the CRF that are transcribed from source documents must be consistent with the 
source documents or the discrepancies must be explained. The Investigator may need to request 
previous medical records or transfer records, depending on the study. Also, current medical 
records must be available. 
Definition of what constitutes source data can be found in the study Monitoring Plan. 
10.1.9. 
Study and Site Start and Closure 
The sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 

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The Sponsor may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or Investigator may include but are 
not limited to: 
• 
Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate recruitment of subjects by the Investigator 
• 
Discontinuation of further study drug development 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
Investigators, the IECs/IRBs, the regulatory authorities, and any CRO used in the study of the 
reason for termination or suspension, as specified by the applicable regulatory requirements. The 
Investigator shall promptly inform the subject and should assure appropriate subject therapy 
and/or follow-up 
10.1.10. 
Publication Policy 
The results of this study may be published or presented at scientific meetings.  
Authorship of any publications resulting from this study will be determined on the basis of the 
Uniform Requirement for Manuscripts Submitted to Biomedical Journals International 
Committee of Medical Journal Editors (ICMJE) Recommendations for the Conduct of Reporting, 
Editing, and Publications of Scholarly Work in Medical Journals, which states: 
Authorship credit is to be based on:  (1) substantial contributions to conception and design, 
acquisition of data, or analysis and interpretation of data; (2) drafting the article or revising it 
critically for important intellectual content; (3) final approval of the version to be published; and 
(4) agreement to be accountable for all aspects of the work in ensuring that questions related to 
the accuracy or integrity of any part of the work are appropriately investigated and resolved. 
Authors need to meet conditions 1, 2, 3, and 4. 
When a large, multicenter group has conducted the work, the group is to identify the individuals 
who accept direct responsibility for the manuscript. These individuals must fully meet the criteria 
for authorship defined above. 
Acquisition of funding, collection of data, or general supervision of the research group, alone, 
does not justify authorship. 
All persons designated as authors must qualify for authorship, and all those who qualify are to be 
listed. 
Each author must have participated sufficiently in the work to take public responsibility for 
appropriate portions of the content. 
All publications (e.g., manuscripts, abstracts, oral/slide presentations, book chapters) based on 
this study must be submitted to the Sponsor for review, according to the applicable Clinical Trial 
Agreement.  
 
 

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10.2. 
Appendix 2: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.2.1. 
Definition of AE 
AE Definition 
• An AE is any untoward medical occurrence in a patient or clinical study subject, 
temporally associated with the use of study drug, whether or not considered related to 
the study drug. 
• NOTE: An AE can therefore be any unfavorable and unintended sign (including a 
clinically significant abnormal laboratory finding), symptom, or disease (new or 
exacerbated) temporally associated with the use of study drug. 
• A treatment-emergent AE (TEAE) is defined as an AE that occurs from the first dose 
of post-randomization study drug administration through the end of the study.  
 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the Investigator (i.e., not related to progression of 
underlying disease). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study drug administration even though it 
may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study drug 
or a concomitant medication. Overdose per se will not be reported as an AE/SAE 
unless it is an intentional overdose taken with possible suicidal/self-harming intent. 
Such overdoses should be reported regardless of sequelae. 
• The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be 
reported as AE or SAE if they fulfil the definition of an AE or SAE. Also, “lack of 
efficacy” or “failure of expected pharmacological action” also constitutes an AE or 
SAE. 
 

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Events NOT Meeting the AE Definition 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
Investigator to be more severe than expected for the subject’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the subject’s 
condition. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
10.2.2. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (e.g., hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the subject 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the subject has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE should be considered serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE. 

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d. Results in persistent disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g., sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect 
f. 
Other situations: 
• Medical or scientific judgment should be exercised in deciding whether SAE reporting 
is appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
subject or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These events should usually be considered 
serious. 
• 
Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse. 
10.2.3. 
Recording and Follow-Up of AE and/or SAE 
AE and SAE Recording 
• When an AE/SAE occurs, it is the responsibility of the Investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics 
reports) related to the event. 
• The Investigator will then record all relevant AE/SAE information in the CRF. 
• It is not acceptable for the Investigator to send photocopies of the subject’s medical 
records to the CRO in lieu of completion of the AE/SAE CRF page. 
• There may be instances when copies of medical records for certain cases are requested 
by the CRO. In this case, all subject identifiers, with the exception of the subject 
number, will be redacted on the copies of the medical records before submission to the 
CRO. 
• The Investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE. 

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Assessment of Intensity 
The Investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to 1 of the following categories:  
• Mild: An event that is easily tolerated by the subject, causing minimal discomfort and 
not interfering with everyday activities. 
• Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities. 
• Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with a SAE. Severe is a category utilized for rating the 
intensity of an event; and both AEs and SAEs can be assessed as severe. 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe. 
 
Assessment of Causality 
• The Investigator is obligated to assess the relationship between study drug and each 
occurrence of each AE/SAE. 
• A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out. 
• The Investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study drug administration 
will be considered and investigated. 
• The Investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment. 
• For each AE/SAE, the Investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the Investigator has 
minimal information to include in the initial report to the CRO. However, it is very 
important that the Investigator always make an assessment of causality for every event 
before the initial transmission of the SAE data to the CRO. 
• The Investigator may change his/her opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality assessment. 
• The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
 

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Follow-up of AEs and SAEs 
• The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated to elucidate the nature and/or 
causality of the AE or SAE as fully as possible. This may include additional laboratory 
tests or investigations, histopathological examinations, or consultation with other 
health care professionals. 
• If a subject dies during participation in the study or within 3 months of the last dose, 
the Investigator will provide the Sponsor with a copy of the death certificate, 
hospitalization records and any post-mortem findings including histopathology where 
available  
• New or updated information will be recorded in the originally completed CRF. 
• The Investigator will submit any updated SAE data to the CRO within 24 hours of 
receipt of the information. 
10.2.4. 
Reporting of SAEs 
SAE Reporting via Paper CRF 
Within 24 hours of identifying an SAE, the Investigator must obtain an SAE Report Form, 
complete the form, and transmit it via email or FAX to the designated Pharmacovigilance 
contact. The SAE Report Form must contain all information required for CIOMS reporting. It 
should contain a check box for initial or follow-up reporting. 
Minimum information to be documented on the SAE report form: 
• Protocol number 
• Name and contact phone number of the Principal Investigator 
• Participant number and year of birth 
• SAE (preliminary diagnosis and SAE criterion), date of event onset, date of last study 
drug administration, brief narrative including current status of subject 
Investigator causality assessment MUST be provided 
• Concomitant medication information and treatments provided 
• Relevant laboratory/diagnostic test results and other relevant information 
Follow-up information should be provided with the same form with the Follow-up box 
checked. 
SAE Reporting via eCRF 
After transmitting the SAE report form, the eCRF should be completed for the SAE. This 
should be updated as the SAE is updated. 
 
 
 

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10.3. 
Appendix 3: Contraceptive Guidance and Collection of Pregnancy 
Information 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study drug, additional evaluation should be considered. 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (e.g., Mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry. 
Note: Documentation can come from the site personnel’s: review of the subject’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female: 
• Surgical menopause is the result of removal of uterus with/without the ovaries 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
• A high follicle stimulating hormone (FSH) level in the postmenopausal range may be 
used to confirm a postmenopausal state in women not using hormonal contraception or 
hormonal replacement therapy (HRT). However, in the absence of 12 months of 
amenorrhea, a single FSH measurement is insufficient. Females on HRT and whose 
menopausal status is in doubt will be required to use one of the non-estrogen hormonal 
highly effective contraception methods if they wish to continue their HRT during the 
study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal 
status before study enrollment. 
Contraception Guidance: 
Female subjects and female partners with childbearing potential of male subjects must use a 
highly effective birth control method according to the Clinical Trials Facilitation and 
Coordination Group (CTFG) guidance. 

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Highly effective methods 
Methods that can achieve a failure rate of less than 1% per year when used consistently and 
correctly are considered as highly effective birth control methods, including: 
• combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation: 
o oral 
o intravaginal 
o transdermal 
• progestogen-only hormonal contraception associated with inhibition of ovulation: 
o oral 
o injectable 
o implantable 
• intrauterine device  
• intrauterine hormone-releasing system 
• bilateral tubal occlusion 
• vasectomized partner 
• sexual abstinence 
Notes: Vasectomized partner is a highly effective birth control method provided that partner is 
the sole sexual partner of the WOCBP trial participant and that the vasectomized partner has 
received medical assessment of the surgical success. 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatments. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical 
trial and the preferred and usual lifestyle of the subject. 
A man who is sexually active with a woman of childbearing potential and has not had a 
vasectomy or otherwise surgically sterile must agree to use highly effective birth control for their 
female partner and must use condoms with spermicide during sexual intercourse, and this must 
continue for 3 months after receiving the last dose of study drug. All men must also not donate 
sperm during the study and for 3 months after receiving the last dose of study drug.  
Collection of Pregnancy Information 
Male subjects with partners who become pregnant 
• The Investigator will attempt to collect pregnancy information on any male subject’s 
female partner who becomes pregnant while the male subject is in this study.  
• After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the Investigator will record pregnancy information on the appropriate form and 
submit it to the sponsor within 24 hours of learning of the partner’s pregnancy. The 
female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to the sponsor. 
Generally, the follow-up will be no longer than 6 to 8 weeks following the estimated 

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delivery date. Any termination of the pregnancy will be reported regardless of fetal status 
(presence or absence of anomalies) or indication for the procedure.  
Female subjects who become pregnant 
• 
The Investigator will collect pregnancy information on any female subject who becomes 
pregnant while participating in this study. The initial information will be recorded on the 
appropriate form and submitted to the sponsor within 24 hours of learning of a subject's 
pregnancy. A separate informed consent is required to collect the pregnancy-related 
information.  
• 
The subject will be followed to determine the outcome of the pregnancy. The Investigator 
will collect follow-up information on the subject and the neonate and the information will 
be forwarded to the sponsor. Generally, follow-up will not be required for longer than 6 
to 8 weeks beyond the estimated delivery date. Any termination of pregnancy will be 
reported, regardless of fetal status (presence or absence of anomalies) or indication for 
the procedure. 
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be reported 
as an AE or SAE.  
• 
A spontaneous abortion (occurring at <22 weeks gestational age) or still birth (occurring 
at >22 weeks gestational age) is always considered to be an SAE and will be reported as 
such.  
• 
Any post-study pregnancy-related SAE considered reasonably related to the study drug 
by the Investigator will be reported to the sponsor as described in Section 8.4.4. While 
the Investigator is not obligated to actively seek this information in former study subjects, 
he or she may learn of an SAE through spontaneous reporting. 
Any female subject who becomes pregnant while participating in the study will discontinue 
study drug administration and be withdrawn from the study.  
 

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10.4. 
Appendix 4: Assessment Instruments 
10.4.1. 
Celiac Disease Patient-Reported Outcome Questionnaire 
An electronic version of the CeD PRO will be administered in PRV-015-002b. Instructions, 
items, and response scales of the CeD PRO are presented in this Appendix. 
Celiac Disease Patient-Reported Outcome Questionnaire 
Instructions:  These questions ask about how you feel each day. Please complete the daily diary 
every evening, at approximately the same time.  
 
1. Thinking about your worst experience in the past 24 hours, how severe was each of the 
following symptoms?  On the following screens, please tap a number to indicate how 
you felt. 
 
 
a. How severe was your abdominal cramping? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
No 
abdominal 
cramping 
 
 
 
 
 
 
 
 
 
Worst possible 
abdominal 
cramping  
 
b. How severe was your abdominal pain? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
No 
abdominal 
pain 
 
 
 
 
 
 
 
 
 
Worst possible 
abdominal pain  
 
 
 

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c. How severe was your bloating? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
No  
bloating 
 
 
 
 
 
 
 
 
 
Worst possible 
bloating 
 
 
d. How severe was your diarrhea? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
No  
diarrhea 
 
 
 
 
 
 
 
 
 
Worst possible 
diarrhea 
 
e. How severe was your gas (flatulence)? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
No  
gas 
 
 
 
 
 
 
 
 
 
Worst possible 
gas 
 
f. How severe was your loose stool? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
No  
loose stool 
 
 
 
 
 
 
 
 
 
Worst possible 
loose stool 
 
 
 

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g. How severe was your nausea? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
No  
vomiting 
 
 
 
 
 
 
 
 
 
Worst possible 
vomiting 
 
h. How severe was your headache(s)? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
No  
headache(s) 
 
 
 
 
 
 
 
 
 
Worst possible 
headache(s) 
 
 
i. How severe was your tiredness? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
No  
tiredness 
 
 
 
 
 
 
 
 
 
Worst possible 
tiredness 
 
The copyright of the CeD PRO [2015] is held by 9 Meters Biopharma and was formerly held by 
Alba Therapeutics Corporation. The CeD PRO is used with permission.  
 

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10.4.2. 
Gastrointestinal Symptom Rating Scale 
 
 

THE GASTROINTESTINAL SYMPTOM RATING SCALE 
(GSRS) 
 
 
 
Please read this first: 
 
 
This survey contains questions about how you have been feeling and what  
 
it has been like DURING THE PAST WEEK. Mark the choice that best  
 
applies to you and your situation with an “X” in the box. 
 
 
 
1. 
Have you been bothered by PAIN OR DISCOMFORT IN YOUR UPPER  
 
ABDOMEN OR THE PIT OF YOUR STOMACH during the past week? 
 
 
 
No discomfort at all 
 
 
Minor discomfort 
 
 
Mild discomfort 
 
 
Moderate discomfort 
 
 
Moderately severe discomfort 
 
 
Severe discomfort 
 
 
Very severe discomfort 
 
 
2. 
Have you been bothered by HEARTBURN during the past week? (By heartburn we 
 
mean an unpleasant stinging or burning sensation in the chest.) 
 
 
 
No discomfort at all 
 
 
Minor discomfort 
 
 
Mild discomfort 
 
 
Moderate discomfort 
 
 
Moderately severe discomfort 
 
 
Severe discomfort 
 
 
Very severe discomfort 
Copyright © AstraZeneca 2005 
All rights reserved. 
https://www.astrazeneca.com/patient-reported-outcomes.html 

3. 
Have you been bothered by ACID REFLUX during the past week? (By acid reflux we  
 
mean the sensation of regurgitating small quantities of acid or flow of sour or bitter  
 
fluid from the stomach up to the throat.) 
 
 
 
No discomfort at all 
 
 
Minor discomfort 
 
 
Mild discomfort 
 
 
Moderate discomfort 
 
 
Moderately severe discomfort 
 
 
Severe discomfort 
 
 
Very severe discomfort 
 
 
4. 
Have you been bothered by HUNGER PAINS in the stomach during the past week? 
 
(This hollow feeling in the stomach is associated with the need to eat between 
 
meals.) 
 
 
 
No discomfort at all 
 
 
Minor discomfort 
 
 
Mild discomfort 
 
 
Moderate discomfort 
 
 
Moderately severe discomfort 
 
 
Severe discomfort 
 
 
Very severe discomfort 
 
 
5. 
Have you been bothered by NAUSEA during the past week? (By nausea we mean a 
 
feeling of wanting to throw up or vomit.) 
 
 
 
No discomfort at all 
 
 
Minor discomfort 
 
 
Mild discomfort 
 
 
Moderate discomfort 
 
 
Moderately severe discomfort 
 
 
Severe discomfort 
 
 
Very severe discomfort 
Copyright © AstraZeneca 2005 
All rights reserved. 
https://www.astrazeneca.com/patient-reported-outcomes.html 

6. 
Have you been bothered by RUMBLING in your stomach during the past week? 
 
(Rumbling refers to vibrations or noise in the stomach.) 
 
 
 
No discomfort at all 
 
 
Minor discomfort 
 
 
Mild discomfort 
 
 
Moderate discomfort 
 
 
Moderately severe discomfort 
 
 
Severe discomfort 
 
 
Very severe discomfort 
 
 
7. 
Has your stomach felt BLOATED during the past week? (Feeling bloated refers to 
 
swelling often associated with a sensation of gas or air in the stomach.) 
 
 
 
No discomfort at all 
 
 
Minor discomfort 
 
 
Mild discomfort 
 
 
Moderate discomfort 
 
 
Moderately severe discomfort 
 
 
Severe discomfort 
 
 
Very severe discomfort 
 
 
8. 
Have you been bothered by BURPING during the past week? (Burping refers to 
 
bringing up air or gas from the stomach via the mouth, often associated with easing  
 
a bloated feeling.) 
 
 
 
No discomfort at all 
 
 
Minor discomfort 
 
 
Mild discomfort 
 
 
Moderate discomfort 
 
 
Moderately severe discomfort 
 
 
Severe discomfort 
 
 
Very severe discomfort 
 
Copyright © AstraZeneca 2005 
All rights reserved. 
https://www.astrazeneca.com/patient-reported-outcomes.html 

9. 
Have you been bothered by PASSING GAS OR FLATUS during the past week? 
 
(Passing gas or flatus refers to the need to release air or gas from the bowel,  
 
often associated with easing a bloated feeling.) 
 
 
 
No discomfort at all 
 
 
Minor discomfort 
 
 
Mild discomfort 
 
 
Moderate discomfort 
 
 
Moderately severe discomfort 
 
 
Severe discomfort 
 
 
Very severe discomfort 
 
 
10. Have you been bothered by CONSTIPATION during the past week? (Constipation 
 
refers  to a reduced ability to empty the bowels.) 
 
 
 
No discomfort at all 
 
 
Minor discomfort 
 
 
Mild discomfort 
 
 
Moderate discomfort 
 
 
Moderately severe discomfort 
 
 
Severe discomfort 
 
 
Very severe discomfort 
 
 
11. Have you been bothered by DIARRHEA during the past week? (Diarrhea refers to 
 
a too frequent emptying of the bowels.) 
 
 
 
No discomfort at all 
 
 
Minor discomfort 
 
 
Mild discomfort 
 
 
Moderate discomfort 
 
 
Moderately severe discomfort 
 
 
Severe discomfort 
 
 
Very severe discomfort 
Copyright © AstraZeneca 2005 
All rights reserved. 
https://www.astrazeneca.com/patient-reported-outcomes.html 

12. Have you been bothered by LOOSE STOOLS during the past week? (If your stools 
 
(motions) have been alternately hard and loose, this question only refers to the 
 
extent you have been bothered by the stools being loose.) 
 
 
 
No discomfort at all 
 
 
Minor discomfort 
 
 
Mild discomfort 
 
 
Moderate discomfort 
 
 
Moderately severe discomfort 
 
 
Severe discomfort 
 
 
Very severe discomfort 
 
 
13. Have you been bothered by HARD STOOLS during the past week? (If your stools 
 
(motions) have been alternately hard and loose, this question only refers to the 
 
extent you have been bothered by the stools being hard.) 
 
 
 
No discomfort at all 
 
 
Minor discomfort 
 
 
Mild discomfort 
 
 
Moderate discomfort 
 
 
Moderately severe discomfort 
 
 
Severe discomfort 
 
 
Very severe discomfort 
 
 
14. Have you been bothered by an URGENT NEED TO HAVE A BOWEL MOVEMENT 
 
during the past week? (This urgent need to go to the toilet is often associated with  
 
a feeling that you are not in full control.) 
 
 
 
No discomfort at all 
 
 
Minor discomfort 
 
 
Mild discomfort 
 
 
Moderate discomfort 
 
 
Moderately severe discomfort 
 
 
Severe discomfort 
 
 
Very severe discomfort 
Copyright © AstraZeneca 2005 
All rights reserved. 
https://www.astrazeneca.com/patient-reported-outcomes.html 

15. When going to the toilet during the past week, have you had the SENSATION OF 
 
NOT COMPLETELY EMPTYING THE BOWELS? (This feeling of incomplete 
 
emptying means that you still feel a need to pass more stool despite having 
 
exerted yourself to do so.) 
 
 
 
No discomfort at all 
 
 
Minor discomfort 
 
 
Mild discomfort 
 
 
Moderate discomfort 
 
 
Moderately severe discomfort 
 
 
Severe discomfort 
 
 
Very severe discomfort 
 
 
 
 
 
PLEASE CHECK THAT ALL QUESTIONS HAVE BEEN ANSWERED! 
 
THANK YOU FOR YOUR CO-OPERATION. 
Copyright © AstraZeneca 2005 
All rights reserved. 
https://www.astrazeneca.com/patient-reported-outcomes.html 

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10.4.3. 
Stool Frequency Question 
 
In the past 24 hours, how many stools did you have that had a consistency that are Type 6 or 7 on 
the chart (Bristol Stool Form Scale) below?  
 
 
 
 
 

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10.4.4. 
Investigator Global Assessment (IGA) 
 
Based on the information available, choose the box that best represents the subject’s current overall 
disease activity: 
 
□ 
Inactive Disease 
 
□ 
Mild Disease 
 
□ 
Moderate Disease 
 
□ 
Severe Disease 
 
□ 
Very Severe Disease                
 
 
 

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10.4.5. 
Patient Global Impression of Severity (PGIS) 
Please choose the response that best describes the severity of your celiac disease over the past 7 
days (check one response):  
o None 
o Mild 
o Moderate 
o Severe 
o Very Severe 
 

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10.4.6. 
Patient Global Impression of Change (PGIC) 
Please choose the response below that best describes the overall change in your celiac disease 
symptoms since you started taking the study medication:  
o Much better  
o A little better 
o No change  
o A little worse  
o Much worse 
 

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10.4.7. 
PROACTIVE Dietary Questionnaire 
The following questions ask about your dietary activities as they relate to your celiac disease 
during the past 7 days. 
During the past 7 days:  
 
1. How many days did you consume a meal prepared outside of your home? 
0  
1  
2  
3  
4  
5  
6  
7  
 
 
2. How many days do you think you consumed gluten? 
0  
1  
2  
3  
4  
5  
6  
7  
 
 

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Impact of Celiac Disease Symptoms Questionnaire (ICDSQ) 
 
   

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10.4.9. 
EQ-5D-5L 
 

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10.5. 
Appendix 5: Interpretation of Hepatitis Results 
Subjects must undergo screening for hepatitis B virus (HBV). At a minimum, this includes 
testing for HBsAg (HBV surface antigen), anti-HBs (HBV surface antibody), and anti-HBc total 
(HBV core antibody total (IgM and IgG)):  
1. Subjects who test negative for all HBV screening tests (i.e., HBsAg-, anti-HBc-, and 
anti-HBs) are eligible for this study. 
2. Subjects who test positive for HBsAg are not eligible for this study, regardless of the 
results of other hepatitis B tests. 
3. Subjects who test negative for HBsAg and test negative for anti-HBc and positive for 
anti-HBs are eligible for this study. 
4. Subjects who test positive for anti-HBc and anti-HBs are not eligible for this study unless 
HBV DNA test is negative. If the HBV DNA test cannot be performed, the subject is not 
eligible. 
5. Subjects who test positive for anti-HBc must undergo further HBV DNA test. If the HBV 
DNA test is positive, the subject is not eligible for this study. If the HBV DNA test is 
negative, the subject is eligible. In the event the HBV DNA test cannot be performed, the 
subject is not eligible. 
 
 
Hepatitis B test result 
Eligibility Action 
Hepatitis B surface 
antigen 
(HBsAg) 
Hepatitis B surface 
antibody 
(anti-HBs) 
Hepatitis B 
core antibody 
(anti-HBc 
total) 
Exclude 
+ 
− or + 
− or + 
Include 
− 
− 
− 
− 
+ 
− 
Require HBV DNA 
testing* 
− 
− or + 
+ 
* If HBV DNA is detectable, exclude from the trial. If HBV DNA testing cannot be performed, exclude from the trial.  
 
 

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10.6. 
Appendix 6: Abbreviations 
 
Abbreviation or Specialist Term 
Explanation 
ACG 
American College of Gastroenterology 
ADA 
anti-drug antibody 
AE 
adverse event 
AESI 
adverse event of special interest 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance  
AST 
aspartate aminotransferase 
β-hCG 
β-human chorionic gonadotropin 
BP 
blood pressure 
BSFS 
Bristol Stool Form Scale 
BUN 
blood urea nitrogen 
CBC 
complete blood count 
CeD PRO 
Celiac Disease Patient-Reported Outcome 
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
Cmin 
trough concentration 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
case report form 
CRO 
contract research organization 
CV% 
coefficient of variation 
DGP 
deamidated gluten peptide 
DMC 
Data Monitoring Committee 
EATL 
enteropathy-associated T-cell lymphoma 
ECG 
electrocardiogram 
eDiary 
electronic diary 
EGD 
esophagogastroduodenoscopy 
ELISA 
enzyme-linked immunosorbent assay 
ET 
early termination 
FSH 
follicle-stimulating hormone 

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Abbreviation or Specialist Term 
Explanation 
GCP 
Good Clinical Practice 
GFD 
gluten-free diet 
GGT 
gamma-glutamyl transpeptidase 
GI 
gastrointestinal 
GSRS 
Gastrointestinal Symptom Rating Scale 
HbA1c 
hemoglobin A1c 
HEENT 
head, eyes, ears, nose, throat 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HLA 
human leukocyte antigen 
IB 
Investigator’s Brochure 
ICDSQ 
Impact of Celiac Disease Symptoms Questionnaire 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IEL 
intraepithelial lymphocytes 
Ig 
immunoglobulin 
IGA 
Investigator Global Assessment 
IGRA 
Interferon Gamma Release Assay 
IHC 
immunohistochemistry 
IL 
interleukin 
IL-15Rα 
interleukin 15 receptor alpha unit 
IRB 
Institutional Review Board 
ITT 
intent to treat 
IV 
intravenous(ly) 
IVRS 
interactive voice response system 
IWRS 
interactive web response system 
LH 
luteinizing hormone 
mAb 
monoclonal antibody 
MCH 
mean cell hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 

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Abbreviation or Specialist Term 
Explanation 
MCV 
mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
mixed effect modeling for repeated measures 
mRNA 
messenger ribonucleic acid 
NAb 
neutralizing antibody 
NRCD 
non-responsive celiac disease 
PCI 
potentially clinically important 
PD 
pharmacodynamic(s) 
PGIC 
Patient Global Impression of Change 
PGIS 
Patient Global Impression of Severity 
PK 
pharmacokinetic(s) 
PP 
per protocol 
q2w 
every 2 weeks 
QoL 
quality of life 
RA 
rheumatoid arthritis 
RBC 
red blood cell count 
RCD-II 
refractory celiac disease Type II 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous(ly) 
SD 
standard deviation 
SoA 
schedule of activities 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TB 
tuberculosis 
TEAE 
treatment-emergent adverse events 
TNFα 
tumor necrosis factor alpha 
tTG 
tissue transglutaminase 
ULN 
upper limit of normal 
VH:CD 
villous height-to-crypt depth ratio 
WBC 
white blood cell count 
WOCBP 
women of childbearing potential 

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