Conditions: Celiac Disease
Keywords: Phase 1 Double blind Multicenter
Allocation: RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 41
Healthy volunteers: no

Brief summary:
A safety study of KAN-101 in patients with celiac disease. The study has two parts:

1. Part A - first in human study in which patients receive a single dose of KAN-101
2. Part B - patients will receive three doses of either KAN-101 or placebo

Detailed description:
Study KAN-101-01 is a Phase 1, FIH study designed to evaluate the safety and tolerability of KAN-101 in patients with celiac disease on a gluten free diet (GFD).

An overview of the two parts and proposed dose groups is given below:

1. Part A (SAD): Patients will receive a single dose of KAN-101.
2. Part B (MAD): Patients will receive three doses of either KAN-101 or placebo.

Arms:
arm 1: All enrolled patients will receive one dose of KAN-101 Dose A arm 2: All enrolled patients will receive one dose of KAN-101 Dose B arm 3: All enrolled patients will receive one dose of KAN-101 Dose C arm 4: All enrolled patients will receive one dose of KAN-101 Dose D arm 5: All randomized patients will receive 3 doses of either KAN-101 Dose A or placebo arm 6: All randomized patients will receive 3 doses of either KAN-101 Dose B or placebo arm 7: All randomized patients will receive 3 doses of either KAN-101 Dose C or placebo

Interventions: intervention 1: KAN-101 intervention 2: Placebo
Intervention descriptions: intervention 1: Intravenous (IV) infusion intervention 2: Intravenous (IV) infusion

Protocol document:
Prot_000.pdf: 
Study KAN-101-01 in Celiac Disease 
 
 
 
 
        Kanyos Bio, Inc. 
KAN-101 
Final (Version 7)  
CONFIDENTIAL 
Page 1 of 65 
 
 
STUDY PROTOCOL 
KAN-101-01 
A Phase 1 Study of the Safety and Tolerability of Single and 
Multiple Doses of KAN-101 in Patients with Celiac Disease 
 
Protocol Number:
KAN-101-01 
Phase:
1 
Date of Protocol:
29 March 2021 
Version:
Version 7 
IND:
19492 
Sponsor:
Kanyos Bio, Inc. a wholly owned 
subsidiary of Anokion S.A. 
50 Hampshire St. 
Cambridge, MA 02139 
 
Not for Distribution – Do Not Copy 
This study protocol contains confidential information and is the proprietary property of 
Kanyos Bio, Inc., a wholly owned subsidiary of Anokion S.A. The protocol is for use by the 
Principal Investigator and his or her designated representatives participating in this 
investigational study. This protocol may not be copied or made available for review by an 
unauthorized person or organization without the prior written authorization of Kanyos Bio, Inc. 
 


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INVESTIGATOR APPROVAL  
I have read both the KAN-101 Investigator’s Brochure and Protocol KAN-101-01 and agree to 
the terms of this study protocol. I will conduct the study according to the procedures specified 
herein, and according to principles of Good Clinical Practice (GCP) and local regulations and 
requirements. 
 
Institution/Clinic:  
Principal Investigator 
Print Name:  
Signature:
 
Date (dd/mm/yyyy):
 
 
 
 




Study KAN-101-01 in Celiac Disease 
 
 
 
 
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CONTACT INFORMATION 
 
 
 
 
 
 
 
 
Sponsor 
Kanyos Bio, Inc. 
A wholly owned subsidiary 
of Anokion S.A. 
50 Hampshire Street 
Cambridge, MA 02139 
 
 
   
   
 
 
 
 
  
 
 
 
PPD
PPD




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 Part B – Randomized, placebo (PBO)-controlled, double-blind, multiple ascending 
dose (MAD) 
The study will be conducted in adult patients (≥ 18 years) diagnosed with CeD as 
demonstrated by intestinal histology and positive serology at the time of diagnosis, who have 
been following a gluten-free diet (GFD) for > 12 months. Eligible patients must have Human 
Leukocyte Antigen HLA-DQ2.5 genotype (HLA-DQA1*05 and HLA-DQB1*02) 
(homozygotes or heterozygotes) since the KAN0009 peptide binds to this major 
histocompatibility complex (MHC) molecule; patients positive for HLA-DQ8 (DQA1*03, 
DQB1*0302) will be excluded, since the KAN0009 peptide does not bind to this MHC 
molecule. 
Part A – SAD 
Part A employs a SAD 3+3 design, in which patients will receive a single IV infusion of 
KAN-101 on Day 1 (D1) followed by 20 days of safety monitoring, which includes 
assessment of adverse events (AEs), clinical signs and symptoms, and clinical laboratory 
values.  
All cohorts in Part A will employ sentinel dosing, whereby the first patient in each cohort will 
be dosed at least 7 days prior to the subsequent patients to monitor for the acute and subacute 
safety of KAN-101.  
The doses for Part A include 0.15 mg/kg (Cohort 1), 0.3 mg/kg (Cohort 2), 0.6 mg/kg 
(Cohort 3), and 1.2 mg/kg (Cohort 4). After the last patient within a given dose cohort has 
been followed for at least 7 days post-dose, a safety review will be performed by the SMC and 
will include review of all available safety and PK information. Dosing at the next dose level 
will only commence upon a recommendation from the SMC and agreement by the Sponsor. 
For all patients in Part A, the study will consist of a 28-day screening period, a single dose of 
KAN-101 administered on D1 followed by a 10-hour monitoring period in the clinic/hospital 
unit. Patients will be evaluated on D4 (±1), D8, and D21. In the event that patients are unable 
to return to the clinic for protocol-specified visits, alternative methods for safety assessments 
and data collection may be employed to ensure the safety of the trial participant where 
appropriate.  Blood and serum samples will be collected for PK and ADA assessments during 
the Part A.  
Please see Table 1 for the complete schedule of assessments for Part A. 
Part B - MAD 
Patients enrolled in the double-blind MAD part will be randomized 3:1 to KAN-101 or PBO 
administered IV for 3 doses. A total of 8 patients per dose cohort (6 KAN-101; 2 PBO) will be 
enrolled. All cohorts will employ sentinel dosing, whereby the first 2 patients (1 KAN-101 and 
1 PBO) in each cohort will be dosed at least 14 days prior (ie, 7 days from third and final dose) 
to the subsequent patients being dosed to monitor for the acute and subacute safety of multiple 
doses of KAN-101.   




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CONFIDENTIAL 
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The initial starting dose of KAN-101 in the Protocol version 2.0 was 1.5 mg/kg, a dose level 
consistent with an expected efficacious dose and supported by findings from the Good 
Laboratory Practice (GLP) toxicology studies.  Due to non-serious adverse events observed in 
one patient at the 1.5 mg/kg dose level, the protocol has been amended to start at the dose of 
0.15 mg/kg, 10-fold lower than the dose which induced symptoms consistent with gluten 
ingestion in celiac patients. 
Part A will use a 3+3 design to evaluate escalating single doses of KAN-101. Approximately 
12 to 24 patients are anticipated for enrollment in Part A. At any dose level, if none of the first 
3 patients experiences a dose-limiting toxicity (DLT) (defined as any ≥ Grade 3 AE assessed 
as related to KAN-101 or any Grade 2 AE assessed as related to KAN-101 not resolving 
within 14 days) then escalation to the next dose level may proceed if recommended by the 
SMC and approved by the Sponsor. If 1 of the first 3 patients experiences a DLT, the dose 
level will expand to a maximum of 6 patients if recommended by the SMC. If no DLT occurs 
among the 3 additional patients enrolled at that dose level, then escalation to the next dose 
level may proceed if recommended by the SMC and approved by the Sponsor.  
Any DLT experienced during the study will result in study pause and review by the SMC.  
Any ≥ Grade 4 AE will result in notification of the FDA in parallel with the SMC and study 
dosing and enrollment will be paused pending review by FDA.   The non-tolerated dose 
(NTD) is the dose level at which 2 or more patients experience a DLT during the dose 
escalation safety monitoring period. The maximum tolerated dose (MTD) will be defined as 
the dose level immediately below the NTD. Of note, dose escalation may not identify an NTD 
or MTD. 
Safety Monitoring Committee 
This study will utilize an SMC that will meet regularly to review all accumulated data, 
including safety and PK (when available) during dose escalation. The SMC will recommend 
all dose escalation decisions, and/or any changes to the dosing paradigm based on review of 
the received data. The SMC will also make recommendations about the dose(s) selected for 
Part B. The Sponsor will make all final decisions related to the doses and regimens examined 
in this study. 
Inclusion Criteria  
1. Adults aged 18 to 70 years inclusive    
2. Diagnosed with CeD based on positive serology (eg, tissue transglutaminase IgA 
antibody [tTG-IgA] and/or deamidated gliadin peptide IgG [DGP-IgG]) and intestinal 
histology consistent with ≥ Marsh Type II or with evidence of villous atrophy 
3. Has HLA-DQ2.5 genotype (HLA-DQA1*05 and HLA-DQB1*02) (homozygotes or 
heterozygotes) 
4. Has followed a GFD for > 12 months immediately prior to study entry 


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5. Negative or weak positive for transglutaminase (tTG) IgA and negative or weak 
positive for DGP-IgA/IgG during screening 
6. Male or female. Females of childbearing potential must use at least 2 acceptable birth 
control methods  
7. Capable of understanding and complying with protocol requirements 
8. Patient understands and has signed the informed consent form (ICF) 
Exclusion Criteria 
1. Refractory CeD 
2. Selective IgA deficiency  
3. Positive for HLA-DQ8 (DQA1*03, DQB1*0302)  
4. Previous treatment with tolerance-inducing therapies for CeD 
5. Known wheat allergy  
6. Part B only: History of hyperacute (requiring medical treatment) or prolonged 
symptoms (> 48 hours) following gluten exposure  
7. Has active inflammatory bowel disease (eg, Crohn's disease, colitis) 
8. Presence of other autoimmune disorders in addition to CeD, including but not limited 
to type 1 diabetes, rheumatoid arthritis, psoriasis, autoimmune thyroid disease, etc. 
9. Uncontrolled or significant medical conditions (including active infections or chronic 
hepatitis) which, in the opinion of the Investigator, preclude participation 
10. Patients with clinical signs and symptoms consistent with COVID-19 (eg, fever, dry 
cough, dyspnea, sore throat, and fatigue) or confirmed infection by appropriate 
laboratory test within the last 4 weeks prior to screening or on admission  
Note: Patients who experienced symptoms consistent with COVID-19 or confirmed 
infection during the screening period (ie, after signing the ICF but before dosing) may 
be rescreened after 4 weeks  
11. Patients with a prior severe course of COVID-19 requiring extracorporeal membrane 
oxygenation (ECMO) or mechanical ventilation  
12. Receipt of chronic, systemic non-biologic immunosuppressive or immunomodulatory 
therapies within the last 3 months (eg, methotrexate, sulfasalazine, or corticosteroids 
such as prednisone, etc.) 
13. Positive for HIV, HBV, or HCV 
14. Receipt of any vaccination within 4 weeks prior to first dose of study drug 
15. Receipt of biologic immunosuppressive or immunomodulatory therapies within the last 
12 months (eg, adalimumab, etanercept, certolizumab, etc.) 
16. Has any of the following laboratory parameters at Screening: 
a. Hemoglobin < 10 g/dL






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A formal statistical analysis plan (SAP) will be developed and finalized prior to study database 
lock. 
 
 
 




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3 Includes weight and height at screening only. 
4 Pregnancy test at screening must be serum; serum or urine tests are acceptable on D1 prior to dosing. 
Pregnancy test must be negative before study drug is administered. 
5 Samples/Measurements taken pre-dose (at least 5 min prior to infusion). 
6 Vital signs (pulse rate, temperature, diastolic and systolic BP). 
7 On D1 patients will be observed in the clinic/hospital unit for 10 h after initiation of IV infusion and followed 
up with by phone approximately 24 hours after dosing. 
8 PK samples to be taken pre-dose (at least 5 min prior to infusion) and the following timepoints after the end 
of infusion: 0 (+2) min, 7 (±2) min, 15 (±2) min, 30 (±5) min, 1 h (±5 min), 2 h (±5 min), 3 h (±5 min), 4 h 
(±5 min) and 6 h (±5 min). 
Abbreviations: ADA = anti-drug antibody; BB = blood pressure; CeD = celiac disease; Con Meds = concomitant 
medications; ECG = electrocardiogram; Early Term. = early termination; HBV = hepatitis B; HCV = hepatitis C; 
HIV = human immunodeficiency virus; HLA = Human Leukocyte Antigen; PK = pharmacokinetics;  
SAD = single ascending dose. 
 




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Assessments 
Screening
Treatment 
Period 
PD Assessment 
Follow-
up1 
Early 
Term.
Study Day 
-28 
1 
4 
7 
15 
21 
28 (±3) 
 
1 Phone call. 
2 ECG performed pre dose (at least 5 min before infusion), 20(±5) min after start of infusion, and 1 hour (±10 
min) post infusion     
3 All patients will be assessed via central laboratory for HLA genotype and CeD serology (eg, tTG-IgA and 
DGP-IgG) at screening to confirm eligibility. For rescreening, HLA does not need to be repeated and CeD 
serology only needs to be repeated if >3months have elapsed from last assessment. 
4 Includes weight and height at screening only. 
5 Pregnancy test at screening must be serum; serum or urine tests are acceptable predose on D1, D4, and D7. 
Pregnancy test must be negative before each dose of study drug is administered.   
6 Samples/Measurements taken pre-dose (at least 5 min prior to infusion). 
7 Vital signs (pulse rate temperature, diastolic and systolic BP). 
8 The GC will consist of patients self-administering 9 g of gluten protein PO for each of 3 days (D15 to D17), 
with the first administration in the clinic on D15. GC should be administered at approximately the same 
time each day. 
9 
 
 
  
10 On D1 patients will be observed in-clinic for 10 h from the start of IV infusion and followed up with by 
phone approximately 24 hours after dosing; on D4 and D7 (dosing days) patients will be observed for 4 h 
in clinic from the start of IV infusion. 
11 PK samples to be taken at pre-dose (at least 5 min prior to infusion) and the following timepoints after the end 
of infusion: 0 (+2) min, 7 (±2) min, 15 (±2) min, 30 (±5) min, 1 h (±5 min), 2 h (±5 min), 3 h (±5 min), 4 h 
(±5 min) and 6 h (±5 min).  
12 PK samples to be taken at pre-dose (at least 5 min prior to infusion) and the following timepoints after the end 
of infusion: 0 (+2) min, 7 (±2) min, 15 (±2) min, 30 (±5) min, 1 h (±5 min), 2 h (±5 min), and 4 h (±5 min). 
13 
 
 
14 
 
15 Collected prior to oral gluten challenge 
  
Abbreviations: ADA = anti-drug antibodies; BP = blood pressure; 
;  
CeD = celiac disease; Con Meds = concomitant medications; Early Term = early termination;  
ECG = electrocardiogram; 
; GC = gluten challenge;  
HBV = hepatitis B; HCV = hepatitis C; HIV = human immunodeficiency virus; HLA = Human Leukocyte 
Antigen; IV = intravenous; MAD = multiple ascending dose; PBMC = peripheral blood mononuclear cell;  
PBO = placebo; PD = pharmacodynamics; PK = pharmacokinetics; 
.  
 
 
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TABLE OF CONTENTS 
INVESTIGATOR APPROVAL ......................................................................................................2 
SPONSOR APPROVAL .................................................................................................................3 
CONTACT INFORMATION ..........................................................................................................4 
PROTOCOL SYNOPSIS ................................................................................................................5 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................21 
1. 
BACKGROUND ........................................................................................................24 
1.1. 
Celiac Disease .............................................................................................................24 
1.2. 
KAN-101 ....................................................................................................................24 
1.3. 
Selection of Patient Populations .................................................................................25 
1.4. 
Determination of Starting Doses and Regimen ..........................................................26 
2. 
OBJECTIVES .............................................................................................................27 
2.1. 
Primary (Part A and Part B) ........................................................................................27 
2.2. 
Secondary (Part A and Part B) ....................................................................................27 
2.3. 
Exploratory (Part B only) ...........................................................................................27 
3. 
ENDPOINTS ..............................................................................................................28 
3.1. 
Primary Endpoint (Part A and Part B) ........................................................................28 
3.2. 
Secondary Endpoint (Part A and Part B) ....................................................................28 
3.3. 
Exploratory Endpoint (Part B only) ............................................................................28 
4. 
STUDY DESIGN .......................................................................................................29 
4.1. 
PART A – Single Ascending Dose .............................................................................29 
4.2. 
PART B – Multiple Ascending Dose .........................................................................30 
4.3. 
Dosing Frequency .......................................................................................................32 
4.4. 
Blinding ......................................................................................................................32 
4.5. 
Monitoring of Adverse Events ....................................................................................33 
4.6. 
Dose-Limiting Toxicities ............................................................................................33 
4.7. 
Dose Escalation Safety Period ....................................................................................33 
4.8. 
Safety Monitoring Committee ....................................................................................34 
4.9. 
Individual and Cohort Stopping Rules .......................................................................34 
4.10. 
Treatment Discontinuation .........................................................................................34 
4.11. 
Study Withdrawal .......................................................................................................35 
5. 
STUDY POPULATION .............................................................................................36 


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5.1. 
Inclusion Criteria ........................................................................................................36 
5.2. 
Exclusion Criteria .......................................................................................................36 
6. 
STUDY PROCEDURES AND ASSESSMENTS......................................................38 
6.1. 
Screening and Treatment Procedures and Assessments .............................................38 
6.1.1. 
Informed Consent .......................................................................................................38 
6.1.2. 
Inclusion and Exclusion Criteria ................................................................................38 
6.1.3. 
Medical History, Demographics, and Celiac Disease History ...................................38 
6.1.4. 
Concomitant Medications and Procedures .................................................................38 
6.1.5. 
Incidental Gluten Exposure Assessment ....................................................................38 
6.1.6. 
Physical Examination and Vital Signs ........................................................................38 
6.1.7. 
Electrocardiogram .......................................................................................................38 
6.1.8. 
Clinical Laboratory Tests ...........................................................................................39 
6.1.9. 
KAN-101 Administration ...........................................................................................40 
6.1.10. 
 
6.1.11. 
Gluten Challenge ........................................................................................................40 
6.1.12. 
Pharmacokinetic Sampling .........................................................................................40 
6.1.13. 
 
6.1.14. 
Adverse Events ...........................................................................................................41 
6.2. 
Safety Follow-up Visit ................................................................................................41 
7. 
CONCOMITANT MEDICATIONS ..........................................................................43 
7.1. 
Prohibited Concomitant Therapies .............................................................................43 
7.2. 
Permitted Concomitant Therapies ..............................................................................43 
8. 
CONTRACEPTION AND PREGNANCY ................................................................44 
9. 
OTHER RESTRICTIONS RELATED TO COVID-19 .............................................45 
10. 
KAN-101 MATERIALS AND MANAGEMENT .....................................................46 
10.1. 
KAN-101 and Placebo ................................................................................................46 
10.2. 
Dosage and Administration ........................................................................................46 
10.3. 
Storage ........................................................................................................................46 
10.4. 
Post-Infusion Medications ..........................................................................................46 
10.5. 
Infusion-Related Reactions .........................................................................................47 
10.6. 
Drug Accountability ...................................................................................................47 
10.7. 
Assignment to Treatment ............................................................................................48 
11. 
SAFETY DATA COLLECTION, RECORDING, AND REPORTING....................49 
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11.1. 
Adverse Events ...........................................................................................................49 
11.1.1. 
Definition of an Adverse Event ..................................................................................49 
11.1.2. 
Definition of a Serious Adverse Event .......................................................................49 
11.2. 
Procedures for Recording and Reporting Adverse Events .........................................50 
11.2.1. 
Recording Adverse Events .........................................................................................50 
11.2.2. 
Relationship to KAN-101 ...........................................................................................50 
11.2.3. 
Adverse Event Severity ..............................................................................................51 
11.2.4. 
Abnormal Laboratory Values .....................................................................................51 
11.2.5. 
Medication Errors, Misuse, and Abuse of KAN-101 .................................................51 
11.2.6. 
Reporting of Serious Adverse Events .........................................................................52 
11.2.7. 
Reporting of Serious Adverse Events to Regulatory Authorities, Ethics 
Committee, and Institutional Review Board ..............................................................52 
11.2.8. 
Pregnancy and In Utero Drug Exposure .....................................................................53 
12. 
STATISTICAL METHODS .......................................................................................54 
12.1. 
Sample Size ................................................................................................................54 
12.2. 
Analysis Sets ...............................................................................................................54 
12.3. 
Background Characteristics ........................................................................................55 
12.3.1. 
Patient Disposition ......................................................................................................55 
12.3.2. 
Demographics and Baseline Characteristics ...............................................................55 
12.4. 
KAN-101 Exposure ....................................................................................................55 
12.5. 
Analysis of Patient-Reported Outcomes .....................................................................55 
12.6. 
Safety Analyses ..........................................................................................................56 
12.7. 
Adverse Events ...........................................................................................................56 
12.8. 
Clinical Laboratory Assessments ...............................................................................56 
12.9. 
Pharmacokinetic Analyses ..........................................................................................57 
12.10. 
 
13. 
STUDY ADMINISTRATION ...................................................................................60 
13.1. 
Good Clinical Practice Statement ...............................................................................60 
13.2. 
Informed Consent .......................................................................................................60 
13.3. 
Patient Confidentiality ................................................................................................60 
13.4. 
Institutional Review Board/Ethics Committee Requirements ....................................61 
13.5. 
Case Report Forms and Source Documentation .........................................................61 
13.6. 
Study Monitoring ........................................................................................................61 
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13.7. 
Quality Assurance .......................................................................................................62 
13.8. 
Study or Clinical Site Termination .............................................................................62 
13.9. 
Duration of the Study, Expected Duration of Patient Participation, and End 
of Study .......................................................................................................................62 
13.10. 
Records Retention .......................................................................................................62 
13.11. 
Publications .................................................................................................................63 
14. 
REFERENCES ...........................................................................................................64 
APPENDIX 1. COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS 
V5.0 (CTCAE) ............................................................................................................65 
 
LIST OF TABLES 
Table 1: 
Schedule of Assessments Part A (SAD) .....................................................................13 
Table 2: 
Schedule of Assessments Part B (MAD) ....................................................................15 
Table 3:  
Pharmacokinetic Parameter Definitions  ....................................................................58 
LIST OF FIGURES 
Figure 1: 
Overview Study KAN-101-01 ....................................................................................32 
 
 
 
 








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1. 
BACKGROUND 
1.1. 
Celiac Disease 
Celiac disease (CeD) is an inherited autoimmune disorder that affects the digestive process of the 
small intestine. When a patient with CeD consumes gluten, that individual’s immune system 
responds by attacking the small intestine, thereby inhibiting the absorption of nutrients. CeD can 
present with a variety of gastrointestinal (GI) symptoms, include diarrhea, bloating, flatulence 
and abdominal pain, and non-GI symptoms such as anemia and vitamin deficiencies 
(Halfdanarson 2007, Rubio-Tapia 2013). Undiagnosed and untreated CeD has been linked to the 
development of other autoimmune disorders, nutritional disorders such as osteoporosis and 
infertility, and neurological conditions (Green 2006, Green 2001).  
It has been recently estimated that 0.7% of the world-wide population has CeD, with global 
prevalence rates on the rise (Singh 2018). CeD is strongly associated with the Human Leukocyte 
Antigen (HLA)-DQA1 and HLA-DQB1 loci (HLA-1*05, HAL-DQB1*02; commonly referred to 
as HLA-DQ2.5) which is present in approximately 90% of CeD patients (Sollid 1989, Sollid 
2012). The pathology observed in CeD patients is driven by the adaptive immune response 
specific to proteins generated in the digestive system after ingestion of gluten, which results in 
autoimmune-like pathology in the small intestine (Sollid 2013). Diagnosis is typically made by a 
combination of positive immunoglobulin A (IgA) anti-tissue transglutaminase (TTG) and/or 
immunoglobulin G (IgG) anti-deamidated gliadin peptides (DGPs) and small intestinal biopsy 
demonstrating villous abnormalities while on a gluten-containing diet or following a GC 
(Halfdanarson 2007, Rubio-Tapia 2013). 
There is currently no pharmaceutical treatment approved for the management of CeD. Patients 
manage their symptoms by strict adherence to a gluten-free diet (GFD), which often presents a 
substantial logistical and financial burden (See 2015). The effectiveness of the GFD is limited 
not only by motivation, access, and expense, but by uncertainty related to potential gluten 
content of certain medications and supplements. Adherence to the strict GFD is also limited by 
the ubiquity of gluten contamination in many gluten-free foods. Several studies have shown 
incomplete histological normalization of small bowel mucosa despite a strict GFD, with 
persistent villous atrophy seen in up to 79% of treated patients (See 2015). In addition to 
adherence challenges, some patients report persistent, life-affecting symptoms despite attempting 
to adhere to the GFD. Patients with CeD who adhere to a strict GFD continue to have a heavy 
burden of care. 
Thus, there remains a strong unmet medical need for pharmacologic interventions to help 
alleviate the growing disease burden of CeD. 
1.2. 
KAN-101 
KAN-101 is composed of a synthetic liver-targeting glycopolymer that is conjugated to a 
synthetic 
peptide domain of wheat alpha gliadin (KAN0009) recognized by 
the HLA-DQ2.5 haplotype. KAN0009 does not bind to the HLA DQ8 molecule. KAN-101 is a 
liquid formulation drug product administered parenterally via an intravenous (IV) infusion.  
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KAN-101 harnesses natural tolerogenic pathways in the liver (Thomson 2010) to reprogram 
pathogenic immune cells to become tolerant toward specific antigens. KAN-101 specifically 
targets the immune cells that drive CeD and leaves the otherwise healthy components of the 
immune system intact to perform their natural, protective functions. The mechanism by which 
KAN-101 induces immunologic tolerance is mediated by 3 mechanisms:  
 Deletion of antigen-specific T cells 
 Induction of anergy/clonal exhaustion of antigen-specific T cells 
 Induction of regulatory T cells which control the antigen-specific T-cell response  
In nonclinical mouse models and a non-human primate model, administration of surrogate 
molecules of KAN-101 were effective at inducing T-cell tolerance. From these nonclinical 
models, it was concluded: 
 Three doses of surrogate molecules administered every 3 days was significantly more 
effective in inducing tolerance and improving disease outcome compared to 3 doses 
administered weekly. 
 The doses where optimal efficacy was observed for the surrogate molecules in 
nonclinical models is equivalent to 1.5 to 7.0 mg/kg of KAN-101. Doses of surrogate 
molecules equivalent to 0.3 mg/kg of KAN-101 have demonstrated effects on disease 
severity in nonclinical models. 
 T-cell tolerance induction can be observed as early as 1 week after drug 
administration in nonclinical models, supporting the observational period for the 
dosing of the sentinel patients across cohorts. 
Previous clinical studies using an adjuvant-free mix of 3 peptides were able to induce T-cell 
tolerance in patients with CeD (Goel 2017). Intradermal administration of these non-targeted 
peptides induced moderate celiac-like GI symptoms in some patients, including nausea, 
abdominal pain, and vomiting, with onset within hours of drug administration. In general, these 
symptoms are consistent with symptoms experienced by CeD patients after ingestion of gluten 
(Goel 2017).  
For more information on the nonclinical findings, please see the KAN-101 Investigator’s 
Brochure. 
Based on the nonclinical findings, Kanyos is initiating this first-in-human (FIH) study with 
KAN-101 in patients with CeD. 
1.3. 
Selection of Patient Populations 
The study population includes adults with CeD based on intestinal histology showing villous 
atrophy at the time of diagnosis and a record of positive serology (tTG-IgA and/or DGP-IgG). In 
addition, eligible patients must have HLA-DQ2.5 genotype (HLA-DQA1*05 and 
HLA-DQB1*02) (homozygotes or heterozygotes) since the KAN0009 peptide will bind this 
major histocompatibility complex (MHC) molecule. Patients who are positive for HLA-DQ8 
(DQA1*03, DQB1*0302) will be excluded, since the KAN0009 peptide will not bind to this 


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MHC molecule. Patients who are positive for both HLA-DQ2.5 and HLA-DQ8 will be excluded 
due to the presence of the HLA-DQ8 allele. 
Eligible patients are required to have maintained a self-reported GFD for at least 12 months prior 
to study enrollment, with negative (or weak positive) TTG and DGP antibodies at screening, to 
ensure proper adherence and experience with GFD during the study. Patients who have a history 
of hyperacute or prolonged symptomology (> 48 hours) following gluten exposure will be 
excluded from Part B to ensure the safety of patients exposed to the GC. Patients will remain on 
a GFD during the study with the exception of the mandated 3-day GC in Part B. 
1.4. 
Determination of Starting Doses and Regimen 
The planned doses of KAN-101 in this FIH study allow for a robust characterization of the safety 
and pharmacokinetics (PK) profile of KAN-101 encompassing the physiologically active doses 
identified in nonclinical models. The cumulative toxicology, safety pharmacology and PK data 
acquired from animal studies support dosing of KAN-101 in humans. A 4-week repeat-dose 
Good Laboratory Practice (GLP) toxicity study examining doses up to 74 mg/kg in Sprague-
Dawley rats and cynomolgus monkeys demonstrated no significant findings in either species at 
any dose of KAN-101 examined. The no-observed-adverse-effect-level (NOAEL) was 
established as 74 mg/kg (the highest dose tested) from the GLP studies in both species.   
In Part A (single ascending dose [SAD]), 4 escalating dose groups are planned: 0.15 mg/kg; 
0.3 mg/kg; 0.6 mg/kg; and 1.2 mg/kg. These doses are supported by the NOAEL and include 
doses equivalent where effects were observed in nonclinical studies. The dosing schedule 
requires that successively higher doses will only be administered after the safety, tolerability and 
available PK data of the preceding dose group have been evaluated by the Safety Monitoring 
Committee (SMC) and approved by the Sponsor. Doses may be adjusted based on the PK and 
safety findings of the preceding dose group(s).  
Part B will examine multiple doses (3) of KAN-101 and includes 3 escalating dose cohorts: 
0.15 mg/kg; 0.3 mg/kg; and 0.6 mg/kg. During Part B, the doses of KAN-101 will be 
administered every 3 days. This frequency of dosing is supported by the nonclinical experimental 
autoimmune encephalomyelitis (EAE) mouse model that demonstrated that dosing every 3 days 
was more effective than weekly dosing.  
For more information on the nonclinical findings, please see the KAN-101 Investigator’s 
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3. 
ENDPOINTS 
3.1. 
Primary Endpoint (Part A and Part B) 
 Incidence and severity of treatment-emergent adverse events (TEAEs) as assessed by 
the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 or higher 
3.2. 
Secondary Endpoint (Part A and Part B) 
 Plasma concentrations and PK parameters of KAN-101 
3.3. 
Exploratory Endpoint (Part B only) 
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4. 
STUDY DESIGN 
Study KAN-101-01 is a Phase 1, FIH study designed to evaluate the initial safety, tolerability, 
and activity of KAN-101 in patients with CeD on a GFD. An overview of the 2 parts and 
proposed dose groups is presented in Figure 1.    
4.1. 
PART A – Single Ascending Dose 
Part A employs a SAD 3+3 design, in which patients will receive a single IV infusion of 
KAN-101 on Day 1 (D1) followed by 20 days of safety monitoring, which includes assessment 
of AEs, clinical signs and symptoms, and clinical laboratory values.  
All cohorts in Part A will employ sentinel dosing, whereby the first patient in each cohort will be 
dosed at least 7 days prior to the subsequent patients to monitor for the acute and subacute safety 
of KAN-101. Based on nonclinical data, a sentinel period of 7 days should be sufficient to allow 
for complete drug clearance (>5 half-lives) and development of the immune tolerance 
mechanism.   
The doses for Part A include 0.15 mg/kg (Cohort 1), 0.3 mg/kg (Cohort 2), 0.6 mg/kg (Cohort 3), 
and 1.2 mg/kg (Cohort 4). After the last patient within a given dose cohort has been followed for 
at least 7 days post-dose, a safety review will be performed by the SMC and will include review 
of all available safety and PK information. Dosing at the next dose level will only commence 
upon a recommendation from the SMC and approval by the Sponsor. 
For all patients in Part A, the study will consist of a 28-day screening period, a single dose of 
KAN-101 administered on D1 and follow up through D21.   D1 includes a 10-hour monitoring 
period in the clinic/hospital unit and a phone call follow up approximately 24 hours after dosing.   
 If a patient is experiencing active AE(s) which require clinical monitoring at the end of 
the clinic/hospital unit monitoring period, the patient should not be discharged and should 
be followed until satisfactory resolution as determined by PI  
 If feasible, patients should be advised to have someone stay with them after discharge 
until 24 hours have elapsed after study drug administration on D1. 
 If patients do not live within 1-hour travel time of an emergency medical facility, they 
should remain in the clinic/hospital unit for the first 24 hours after study drug 
administration. 
 Patients should be instructed not to drive themselves to seek emergency medical 
treatment. 
Patients will be evaluated on D4 (±1), D8, and D21. Blood and serum samples will be collected 
for PK and anti-drug antibody (ADA) assessments during Part A. Patients in Part A may be 
replaced if they do not receive the full dose of study drug or do not complete the D8 visit, as long 
as the discontinuation was not due to a DLT assessed to be related to study drug.  In the event 
that patients are unable to return to the clinic for protocol-specified visits, alternative methods for 


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safety assessments and data collection may be employed to ensure the safety of the trial 
participant where appropriate.   
Please see Table 1 for the complete schedule of assessments for Part A. 
4.2. 
PART B – Multiple Ascending Dose 
Part B will be initiated following successful completion and SMC review of SAD Cohort 2 in 
Part A. This transition at Cohort 2 from single to multiple dosing of KAN-101 is supported by 
nonclinical models that show clearance of KAN-101 within 24 hours, and in vivo animal studies 
that did not show any drug accumulation when KAN-101 was given 3 times a week. 
Part B employs a randomized, double-blind multiple ascending dose (MAD) design, in which 3 
cohorts of patients will be assigned 3:1 to either KAN-101 or matching placebo (PBO). Patients 
in Part B will receive an IV infusion of KAN-101 or PBO on D1, D4, and D7. All cohorts in 
Part B will employ sentinel dosing, whereby the first 2 patients (1 KAN-101 and 1 PBO) in each 
cohort will be dosed at least 14 days prior to the subsequent patients (ie, 7 days following the 
third and final dose) to monitor for the acute and subacute safety of KAN-101.  
The doses for Part B include 0.15 mg/kg (Cohort 5), 0.3 mg/kg (Cohort 6), and 0.6 mg/kg 
(Cohort 7). After the last patient dosed within a given cohort has been followed for at least 
14 days, a safety review will be performed by the SMC. Initiation of the next dose cohort will 
commence upon recommendation by the SMC after review of available safety and PK data and 
approval of the Sponsor.  
For all patients in Part B, the study will consist of a screening period of up to 28 days, followed 
by 3 doses of KAN-101, each administered on D1, D4, and D7. The first dose on D1 will be 
followed by a 10-hour monitoring period in the clinic/hospital unit and a phone call follow up 
approximately 24 hours after dosing.  Subsequent doses scheduled on D4 and D7 have a 4-hour 
monitoring period in the clinic/hospital unit. 
 If a patient is experiencing active AE(s) which require clinical monitoring at the end of 
the clinic/hospital unit monitoring period, the patient should not be discharged and should 
be followed until satisfactory resolution as determined by PI  
 If feasible, patients should be advised to have someone stay with them after discharge 
until 24 hours have elapsed after study drug administration on D1. 
 If patients do not live within 1-hour travel time of an emergency medical facility, they 
should remain in the clinic/hospital unit for the first 24 hours after study drug 
administration. 
 Patients should be instructed not to drive themselves to seek emergency medical 
treatment. 
Patients will return to the clinic on D15 to initiate oral GC and on D21 for biomarker sample 
collection. Blood and serum samples will be collected for PK, PD, and ADA assessments during 
Part B of the study. Patients in Part B may be replaced if they do not receive the full 3 doses of 




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Figure 1: 
Overview Study KAN-101-01 
 
Single Ascending Dose (SAD): 3 patients will be dosed IV with KAN-101. Initiation of the next dose cohort will 
commence once all patients in a cohort reach D8 postdose, and upon acceptable safety review by SMC and 
approval from Sponsor.  
Multiple Ascending Dose (MAD): the first MAD cohort will be initiated after safety review of SAD Cohort 2. 
Patients randomized 3:1 to KAN-101 or PBO. Initiation of the next dose cohort will commence once all patients 
in a cohort reach D15 postdose, and upon acceptable safety review by SMC and approval from the Sponsor.  
All cohorts will employ sentinel dosing to allow for assessment of acute and subacute reactions prior to dosing 
additional patients in the study. 
Abbreviations: CeD = celiac disease; IV = intravenous; n = number; PBO = placebo; SMC = safety monitoring 
committee.  
4.3. 
Dosing Frequency  
In Part A, patients will receive a single IV infusion of KAN-101 on D1. 
In Part B, patients will receive a total of 3 IV infusions of either KAN-101 or PBO (double-
blind). A single IV infusion will be administered on D1, D4, and D7.   
4.4. 
Blinding 
Part A is open label. 


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Part B is double-blinded, such that study personnel (eg, Investigators, site coordinators) and 
patients are blinded to treatment assignments and will remain blinded throughout the study.   
Unblinded personnel include those involved in drug preparation and allocation (eg, data systems 
support and pharmacists), and the study pharmacokineticist to allow for expedited review of PK 
data prior to SMC review.   
The data for dose escalation in Part B will be presented and reviewed by the SMC in a blinded 
fashion.   
After completion of SMC review and once all patients in the cohort have completed the study, 
the sponsor study team members involved in biomarker data analysis may be unblinded to 
complete pharmacodynamic assessments. 
In the event of a medical emergency, the site may be unblinded if knowledge of the study 
treatment is necessary in order to provide appropriate urgent medical care. 
4.5. 
Monitoring of Adverse Events 
Patients will be monitored continuously for AEs while on study. AE severity will be assessed 
using the NCI CTCAE v5.0 or higher (Appendix 1).  
4.6. 
Dose-Limiting Toxicities 
Dose-limiting toxicities (DLTs) for Study KAN-101-01 include any ≥ Grade 3 AE assessed as 
related to KAN-101 or Grade 2 AE assessed as related to KAN-101 not resolving within 14 days; 
DLTs do not include those AEs attributable solely to intercurrent illness or other concomitant 
medications.  Any DLT experienced during the study will result in study pause and review by the 
SMC.  Any ≥ Grade 4 AE will result in notification of the FDA in parallel with the SMC and 
study dosing and enrollment will be paused pending review by FDA.    
4.7. 
Dose Escalation Safety Period  
In Part A, the dose escalation safety monitoring period is from the beginning of IV 
administration through D8. Any AEs that meet the above criteria but occur after the dose 
escalation safety monitoring period of Part A may be considered by the SMC in the evaluation 
for Part B dose selection.  
The dose escalation safety monitoring period in Part B is from the beginning of the first IV 
administration of KAN-101/PBO through the D15 clinic visit, prior to initiating the GC.  
The length of the monitoring periods for safety review is supported by nonclinical exposure data, 
suggesting KAN-101 will have cleared 5 half-lives, and nonclinical animal model data 
demonstrating that the tolerance induction mechanism can develop within 1 week of dosing. AEs 
and any abnormal clinical parameters, including laboratory findings, observed during this period 
will be used by the SMC to determine whether dose escalation should proceed.     
No patient with a DLT will be replaced.  


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In both parts, patients will be monitored in the clinic for 10 hours following the first IV 
administration of KAN-101/PBO. In Part B, patients will be monitored in the clinic for 4 hours 
following completion of their second and third dose.  
4.8. 
Safety Monitoring Committee 
This study will utilize an SMC that will meet regularly to review all accumulated and available 
data, including safety and PK. The SMC will be comprised of three independent medical 
reviewers, including at least 1 CeD medical expert, as voting members. Non-voting members 
will include the study medical monitor, a medical representative from the Sponsor and other 
relevant study and site staff as required to address study conduct. The SMC will recommend all 
dose escalation decisions, and/or any recommended changes to the dosing paradigm based on 
review of the received data. The SMC will also make recommendations about the dose(s) 
selected for Part B.  
4.9. 
Individual and Cohort Stopping Rules 
During the dose escalation safety monitoring period, any DLT will result in a pause in 
enrollment and a thorough review by the SMC prior to treating any additional patients.  Any ≥ 
Grade 4 AE will result in notification of the FDA in parallel with the SMC and study dosing and 
enrollment will be paused pending review by FDA.    
For Part A, if 1 of the first 3 patients experiences a DLT in a given cohort, 3 additional patients 
will be enrolled and evaluated in that cohort before dose escalation can occur if recommended by 
the SMC and only after consultation with the FDA for any ≥ Grade 4 AE. If 2 or more patients 
experience a DLT at a given dose level during the dose escalation evaluation period of Part A, 
then that dose level will be considered a non-tolerated dose (NTD), and no further escalation will 
proceed.  
If a patient experiences a DLT during the dose escalation safety monitoring period of Part B, no 
additional doses will be administered to that patient. If 1 patient experiences a DLT during the 
dose escalation safety monitoring period of Part B, the study will be paused to determine if any 
dose adjustments are needed and/or if the study should dose any additional patients.  For any ≥ 
Grade 4 AE the study would only continue after consultation with the FDA. If 2 or more patients 
experience a DLT during the dose escalation safety monitoring period of Part B, then that dose 
level will be considered an NTD, and no further escalation will proceed. 
4.10. 
Treatment Discontinuation  
Patients will be discontinued from treatment for any of the following reasons: 
 An AE that requires permanent discontinuation of study treatment* 
 Noncompliance with the protocol  
 Investigator decision  
 Patient becomes pregnant 


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 Patient death 
 Patient lost to follow-up  
 Termination of the study by the Sponsor 
 Voluntary withdrawal of consent by patient  
*AEs leading to the discontinuation of KAN-101 will be followed until resolution, resolution to baseline, or until the 
event is considered stable or chronic. 
The reason for treatment discontinuation will be documented. 
All patients will have a final Follow-Up approximately 20 days (D21±1) after the single dose of 
KAN-101 in Part A and approximately 20 days (D28±3) after the third and final dose in Part B, 
unless the patient withdraws from the study prematurely (Section 4.10). 
4.11. 
Study Withdrawal  
Patients may voluntarily withdraw from the study at any time for any reason without prejudice.  
Patients will be withdrawn from the study for any of the following reasons: 
 Investigator’s decision  
 Patient death 
Patient lost to follow-up  
Termination of the study by Sponsor 
Voluntary withdrawal of consent by patient 


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5. 
STUDY POPULATION 
5.1. 
Inclusion Criteria 
1. Adults aged 18 to 70 years inclusive    
2. Diagnosed with CeD based on positive serology (eg, tissue transglutaminase IgA 
antibody [tTG-IgA] and/or deamidated gliadin peptide IgG [DGP-IgG]) and intestinal 
histology consistent with ≥ Marsh Type II or with evidence of villous atrophy 
3. Has HLA-DQ2.5 genotype (HLA-DQA1*05 and HLA-DQB1*02) (homozygotes or 
heterozygotes) 
4. Has followed a GFD for > 12 months immediately prior to study entry 
5. Negative or weak positive for tTG IgA and negative or weak positive for DGP-IgA/IgG 
during screening 
6. Male or female.  Females of childbearing potential must use at least 2 acceptable birth 
control methods  
7. Capable of understanding and complying with protocol requirements 
8. Patient understands and has signed the informed consent form (ICF) 
5.2. 
Exclusion Criteria 
1. Refractory CeD 
2. Selective IgA deficiency  
3. Positive for HLA-DQ8 (DQA1*03, DQB1*0302)  
4. Previous treatment with tolerance-inducing therapies for CeD 
5. Known wheat allergy  
6. Part B only: History of hyperacute (requiring medical treatment) or prolonged symptoms 
(> 48 hours) following gluten exposure  
7. Has active inflammatory bowel disease (eg, Crohn's disease, colitis) 
8. Presence of other autoimmune disorders in addition to CeD, including but not limited to 
type 1 diabetes, rheumatoid arthritis, psoriasis, autoimmune thyroid disease, etc. 
9. Uncontrolled or significant medical conditions (including active infections or chronic 
hepatitis) which, in the opinion of the Investigator, preclude participation 
10. Patients with clinical signs and symptoms consistent with COVID-19 (eg, fever, dry 
cough, dyspnea, sore throat, and fatigue) or confirmed infection by appropriate laboratory 
test within the last 4 weeks prior to screening or on admission  
Note: Patients who experienced symptoms consistent with COVID-19 or confirmed 
infection during the screening period (ie, after signing the ICF but before dosing) may be 
rescreened after 4 weeks  


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11. Patients with a prior severe course of COVID-19 requiring extracorporeal membrane 
oxygenation (ECMO) or mechanical ventilation   
12. Receipt of chronic, systemic non-biologic immunosuppressive or immunomodulatory 
therapies within the last 3 months (eg, methotrexate, sulfasalazine, or corticosteroids such 
as prednisone, etc.) 
13. Positive for HIV, HBV, or HCV 
14. Receipt of any vaccination within 4 weeks prior to first dose of study drug 
15. Receipt of biologic immunosuppressive or immunomodulatory therapies within the last 
12 months (eg, adalimumab, etanercept, certolizumab, etc.) 
16. Has any of the following laboratory parameters at Screening: 
a. Hemoglobin < 10 g/dL 
b. Platelet (PLT) count < 100 x 109/L 
c. White blood cell count (WBC) outside the normal range and assessed as clinically 
significant by the Investigator 
d. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline 
phosphatase (ALP) > 1.5 x the upper limit of normal (ULN)  
e. Estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 based on the 
Cockcroft-Gault equation during screening 
17. Average alcohol consumption of > 2 drink-equivalents per day  
18. History of dermatitis herpetiformis 
19. Pregnant or breastfeeding   
 


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6. 
STUDY PROCEDURES AND ASSESSMENTS 
Time points for assessments collected throughout the study can be found in the Schedule of 
Assessments (Table 1 and Table 2). A brief description of each assessment can be found below. 
6.1. 
Screening and Treatment Procedures and Assessments  
6.1.1. 
Informed Consent 
An ICF must be signed by prospective patients prior to initiating any study-specific procedures. 
Standard of care assessments performed prior to ICF signing may fulfill study eligibility 
requirements if performed within the screening period. 
6.1.2. 
Inclusion and Exclusion Criteria 
Inclusion and exclusion criteria (Section 5) will be reviewed for each potential patient. Eligibility 
will be documented in the electronic case report form (eCRF).  
6.1.3. 
Medical History, Demographics, and Celiac Disease History 
Complete medical history will be obtained, including demographics, symptoms at diagnosis, 
disease history, and length of time on a GFD.  
6.1.4. 
Concomitant Medications and Procedures 
At screening, concomitant medications will be recorded. Assessment of any change in 
concomitant medications, or procedures since the last visit will occur at all further patient visits 
through the final Follow-Up Visit. 
6.1.5. 
Incidental Gluten Exposure Assessment 
Assessment of any incidental gluten exposure will be captured at all study visits.  
6.1.6. 
Physical Examination and Vital Signs 
A full physical examination (PE) and vital signs check will be performed at the time points 
specified in the Schedule of Assessments (Table 1 and Table 2). PEs will also be conducted as 
clinically indicated. 
The PE will include an assessment of general appearance, skin, head, neck, throat, lymph nodes, 
cardiovascular, neurological, thyroid, musculoskeletal/extremities, respiratory, abdomen, height, 
and weight (baseline only). Vital signs will include temperature, pulse rate and blood pressure 
(BP) (sitting for 5 minutes). If vital signs need to be repeated during a single visit, assessments 
should be conducted approximately 5 minutes apart.  
Any new CS abnormality from baseline should be recorded as an AE. 
6.1.7. 
Electrocardiogram  
All electrocardiograms (ECGs) will be standard resting 12-lead ECGs performed after the patient 
has been supine for at least 5 minutes.  Patients will be instructed to remain completely 


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stationary (no talking, deep breathing, sleeping or swallowing) for approximately 10 seconds 
during the ECG recording.  When possible, serial reads on dosing days should be performed by 
leaving the ECG electrode pads in place for subsequent assessments to ensure comparable ECG 
reads.  While ECGs are being acquired, patients and staff are prohibited from having devices 
(cell phones, fans, heaters and other radiofrequency signals) that emit electrical interference in 
the room. If the initial ECG at a timepoint is abnormal then the ECG should be repeated 2 
additional times (approximately 2 min apart) within 15 min of the initial ECG.   
When an ECG is scheduled at the same time of a blood collection, the ECG will be obtained 
prior to the blood collection.  ECG occurring near meals will take place prior to meals. 
All study ECGs will be evaluated by the site Investigator or qualified designee (“local reader”) 
and interpreted for safety.  The local reader will provide global interpretation of normal, 
abnormal and not clinically significant, abnormal and clinically significant, or unable to evaluate.  
Additionally, ECGs will be transmitted electronically to a central ECG core lab for cardiologist 
over read. 
ECGs will be conducted as outlined in Table 1 and Table 2. The local reader will review the 
screening ECG to confirm eligibility.  For rescreening, the ECG only needs to be repeated if >3 
months have elapsed from last assessment. 
6.1.8. 
Clinical Laboratory Tests 
The following laboratory parameters will be measured at screening and at the time points 
specified in the Schedule of Assessments (Table 1 and Table 2) and will be analyzed locally or 
centrally by a certified laboratory: 
 A serum pregnancy test during screening for all women of child-bearing potential 
(WCBP) 
 Serum or urine pregnancy testing for all WCBP prior to each dose 
 Hematology laboratory parameters include WBC count, hemoglobin, hematocrit, PLT 
count, and WBC differential  
 Blood chemistry laboratory parameters, including blood urea nitrogen, creatinine, 
glucose, AST, ALT, ALP, bilirubin (total and direct), electrolytes (sodium, chloride, 
bicarbonate, potassium), amylase, lipase, albumin, magnesium, calcium, and 
phosphorus 
 Coagulation laboratory parameters, including prothrombin time, partial 
thromboplastin time or activated partial thromboplastin time, and international 
normalized ratio 
 Complete urinalysis with qualitative analysis for protein (dipstick)  
 Human immunodeficiency virus (HIV), hepatitis B (HBV) (HBsAg, anti-HBc and 
anti-HBs), and hepatitis C (HCV) testing (screening only) 
The following laboratory tests will be performed centrally at screening as specified in the 
Schedule of Assessments (Table 1 and Table 2): 


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 HLA DQ2.5 and HLA DQ8 testing  
 Transglutaminase (tTG) and deaminated gluten peptides (DGP) IgA/IgG 
For tTG, a result of <2x ULN will be considered negative or weak positive.  For DGP, a result of 
<30 U/mL will be considered negative or weak positive. 
For re-screening, the HLA does not need to be repeated and the tTG and DGP antibody tests 
should only be repeated if >3months have elapsed from end assessment.  
Unscheduled assessments should be performed as clinically indicated. 
For any out-of-range laboratory findings during screening, repeat laboratory testing may be 
performed at the discretion of the Investigator. Abnormal laboratory findings at screening should 
be recorded as medical history only if considered CS.   
Clinical laboratory assessments should be performed prior to KAN-101/PBO infusion when 
applicable.  
Laboratory findings assessed by the Investigator as CS, including but not limited to, those 
findings resulting in a drug interruption/hold/reduction/discontinuation or medical intervention, 
should be repeated to verify the out-of-range findings, followed to a satisfactory clinical 
resolution, and reported as an AE(s) (see Section 11.1.1 for definition of an AE).  
6.1.9. 
KAN-101 Administration 
Detailed instructions on the administration of KAN-101 can be found in Section 10 . 
6.1.11. 
Gluten Challenge 
All patients enrolled in Part B of the study will undergo a GC for 3 days, from D15 to D17. 
During these 3 days, patients will self-administer 9 g of gluten protein orally (PO) once each day 
at approximately the same time every morning. The first dose of gluten will be administered in 
the clinic, and the patient will be observed for at least 6 hours to monitor for hyperacute reactions 
requiring medical treatment and collection of biomarker samples. Patient compliance will be 
recorded by the study Investigator.  
6.1.12. 
Pharmacokinetic Sampling 
PK sample collection time points are shown in Table 1 and Table 2.  
The exact date and time of each sample collection must be recorded for all collected samples. 
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Refer to the KAN-101-01 Laboratory Manual for details on processing, storage, and shipment of 
PK samples. 
6.1.14. 
Adverse Events 
All AEs should be captured on the eCRF from the time of signing of ICF through the final 
Follow-Up Visit/phone call. AEs considered at least possibly related to KAN-101 should be 
followed until resolution, return to baseline, or deemed chronic or stable.   
All serious adverse events (SAEs) will be immediately reported to the Sponsor from the time of 
signing the ICF through the Follow-Up Visit/phone call or until the patient has been deemed to 
be a screen failure. After completion of the AE reporting period (ie, through the final Follow-Up 
Visit/phone call), only SAEs attributed to KAN-101 must be reported to the Sponsor. 
See Section 11.2 for a full description of the collection and reporting of AEs during this study. 
6.2. 
Safety Follow-up Visit 
All patients in Part A will have a final Follow-Up at D21 (±1), 20 days after the single 
administration of KAN-101.  
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All patients in Part B will have a final Follow-Up phone call at D28 (±3), approximately 20 days 
after the final administration of KAN-101 on D7.  
Ongoing AEs considered at least possibly related to KAN-101 treatment should be followed until 
resolution, return to baseline, or are considered stable or chronic. 
 
 


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7. 
CONCOMITANT MEDICATIONS 
7.1. 
Prohibited Concomitant Therapies  
During the study period, any additional therapies to treat CeD or other investigational agents are 
prohibited, including biologic or non-biologic immunosuppressive or immunomodulatory 
therapies. In addition, non-investigational immunosuppressive and immunomodulatory therapies 
are prohibited (eg, systemic corticosteroids). Patients should avoid the use of probiotic 
supplements during the study period. All vaccines are prohibited for at least 4 weeks prior to 
dosing and during the study period. 
7.2. 
Permitted Concomitant Therapies 
All patients are required to maintain a GFD during the study. Any other medication that is 
considered necessary for the patient’s welfare that is not expected to interfere with the evaluation 
of KAN-101 may be given at the discretion of the Investigator. In cases involving concomitant 
therapies whose predicted interference with KAN-101 is unknown to the Investigator, the 
Sponsor should be contacted for discussion. Patients being treated for IBS symptomology will be 
allowed to continue therapy (eg, dicyclomine) unless the drug is specifically prohibited 
(Section 7.1).  
Antidiarrheal (eg loperamide) or antiemetics (eg metoclopramide) may be used during the GC if 
warranted by symptomology unless the drug is specifically prohibited (Section 7.1). 
Any medication (including over the counter or prescription medications, vitamins, and/or herbal 
supplements) that the patient receives after enrollment through the last study visit must be 
recorded on the eCRF. 
 
 


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8. 
CONTRACEPTION AND PREGNANCY 
The effects of KAN-101 on conception, pregnancy, and lactation are unknown. 
At screening, all women who are not surgically sterile or postmenopausal must agree to use at 
least 2 medically acceptable methods of birth control (defined as the use of an intrauterine 
device, a barrier method with spermicide, condoms, any form of hormonal contraceptives, or 
partner sterility) for the duration of the study.  WCBP who practice complete sexual abstinence 
are NOT required to commit to use of 2 methods of birth control. Complete sexual abstinence is 
only acceptable when it is the usual/preferred lifestyle of the subject and has been so for at least 
3 months prior to Screening.  Periodic abstinence, calendar timing methods of contraception, or 
withdrawal are NOT acceptable methods of contraception. 
At screening, all men who are not sterile (biologically or surgically) must commit to the use of 1 
reliable method of birth control (e.g. condoms with spermicide, sterile partner) for the duration 
of the study. 
A serum pregnancy test will be administered during screening for all WCBP. A serum or urine 
pregnancy test will be administered to all WCBP prior to each dose of study drug and must be 
confirmed negative before administration of study drug.    


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9. 
OTHER RESTRICTIONS RELATED TO COVID-19 
Patients will be advised to adhere to local requirements for reduction of the severe acute 
respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure while ambulatory. All patients 
should be called 1 day prior to every visit for assessing COVID-19 signs and symptoms and 
asked not to attend the site if infection is suspected. In addition, patients will be asked whether 
they have had any contact with a person who has a confirmed infection. If applicable, patients 
will be referred to the local health care system. Physical distancing and person-to-person contact 
restrictions should be applied and explained to patients while staying at the study site, if required 
by local requirements. Where physical distancing is not possible, study participants will be asked 
to use face masks and/or gloves, if deemed appropriate by the Investigator and site staff and 
guided by local requirements. 
 
 


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10. 
KAN-101 MATERIALS AND MANAGEMENT 
10.1. 
KAN-101 and Placebo  
10.2. 
Dosage and Administration 
KAN-101 is provided as a frozen concentrated solution 
which will be 
diluted into 250 mL normal saline.  
Administration will be by IV infusion over approximately 30 minutes.  
For Part A, patients will receive a single IV infusion of KAN-101 only (no PBO).  
For Part B, patients will receive 3 IV infusions, each spaced 3 days apart, of a given dose of 
either KAN-101 or PBO. All doses will be prepared as outlined in the KAN-101-01 Pharmacy 
Manual by an unblinded pharmacist. 
Study treatment (KAN-101 or PBO) should be administered over 30 minutes under the 
supervision of a physician or other medically qualified study personnel experienced in the use of 
IV agents and in a facility equipped to manage medical emergencies. In the event of a Grade 3 
infusion-related reaction (IRR), the total infusion duration may be increased to 1 hour (please see 
Section 10.5 for more information). In cases where a temporary interruption is required, the total 
infusion should be completed within 24 hours of thawing the drug product. See Section 10.5 for 
detailed guidance regarding infusion administration interruptions due to infusion reactions.  
Please refer to the KAN-101 Pharmacy Manual for detailed administration instructions. 
10.3. 
Storage  
KAN-101 is supplied in vials for single use. KAN-101 is to be stored at -20°C and protected 
from light in a temperature-monitored, locked freezer. Additional details on storage conditions 
are available in the KAN-101 Pharmacy Manual. 
10.4. 
Post-Infusion Medications 
No specific post-infusion medications are required for KAN-101, but may be administered at the 
discretion of the Investigator. 
 
 
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10.5. 
Infusion-Related Reactions 
If an IRR occurs during KAN-101 administration, the following treatment recommendations are 
provided and may be modified per local treatment standards and guidelines as appropriate. 
 Grade 1 (mild): Infusion rate modification not indicated. Administer symptomatic 
treatment (eg, antihistamines, antipyretics, antiemetics) as needed. Closely monitor 
patient until resolution. Prophylaxis with diphenhydramine 50 mg (or equivalent) 
and/or acetaminophen/paracetamol 325 to 1000 mg is recommended at least 30 min 
prior to future KAN-101 infusions 
 Grade 2 (moderate): Slow infusion to ≤ 50% of the original infusion rate and treat 
symptoms with appropriate medical therapy, including but not limited to 
antihistamines, antipyretics, and analgesics. Increase monitoring of vital signs as 
medically indicated until patient is deemed stable. Prophylaxis with diphenhydramine 
50 mg (or equivalent) and/or acetaminophen/paracetamol 325 to 1000 mg is 
recommended at least 30 min prior to future KAN-101 infusions  
 Grade 3 (severe): Stop infusion and institute appropriate symptom-directed therapy, 
including but not limited to antihistamines, antipyretics, corticosteroids, 
bronchodilators, and O2. Increase monitoring of vital signs as medically indicated 
until patient is deemed stable. If the reaction has not resolved within 6 hours, the 
remainder of the infusion will not be administered and KAN-101 will be permanently 
discontinued. Following the completion or termination of a restarted infusion due to 
an IRR, all patients must be monitored until resolution of symptoms or for 2 hours in 
the absence of additional symptoms. Prophylaxis with diphenhydramine 50 mg (or 
equivalent) and/or acetaminophen/paracetamol 325 to 1000 mg is required at least 30 
min prior to future KAN-101 infusions. The next infusion should initiate at a rate of 2 
hours per dose, or 50% of the rate at which the reaction occurred. If no IRRs are 
observed within the first 30 minutes, the infusion rate may increase to the 1-hour-per-
dose rate as outlined in Section 10.2. Permanently discontinue KAN-101 upon a 
second occurrence of a Grade 3 or greater infusion reaction.  
 Grade 4 (life-threatening): Stop infusion and immediately institute appropriate 
symptom directed therapy and supportive measures as necessary, including, but not 
limited to, corticosteroids, bronchodilators, O2/respiratory support, and vasopressors. 
Hospitalization and/or intensive care unit admission may be indicated. Permanently 
discontinue treatment. 
10.6. 
Drug Accountability 
The Investigator or designee is responsible for taking an inventory of each shipment of KAN-101 
received and comparing it with the accompanying drug order form. All unused KAN-101 will be 
retained at the site. After full drug accountability and reconciliation, the Investigator will dispose 
of any KAN-101 at the clinical study site per site procedures, or if necessary, all KAN-101 will 
be returned to the Sponsor or its designee. Disposition of all KAN-101 should be documented, 
including any KAN-101 that is lost or damaged.  


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10.7. 
Assignment to Treatment 
Once a patient has met all entry criteria, the Interactive Response Technology (IRT) will be used 
to generate a distinct patient identifier. If a patient discontinues from the study, the patient 
identifier will not be reused and the patient will not be allowed to re-enter the study.  
In Part A, patients will be assigned to receive open-label KAN-101 at a dose level based on the 
next available spot in the cohort(s) currently being enrolled. 
In Part B, the first 2 eligible patients within each cohort will be randomized via IRT in a 1:1 ratio 
to receive either KAN-101 or PBO. After completion of the sentinel dosing, the remaining 
6 patients in each cohort will be randomized 5:1 to receive KAN-101 or PBO.   


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11. 
SAFETY DATA COLLECTION, RECORDING, AND 
REPORTING 
11.1. 
Adverse Events  
11.1.1. 
Definition of an Adverse Event 
An AE is defined as any untoward medical occurrence associated with the use of a drug, or with 
study participation, whether or not consider related to study treatment.  
An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of the medicinal product, 
whether or not considered related to the medicinal product.  
AEs include worsening of a pre-existing medical condition as well as CS changes from baseline 
laboratory values/conditions. Worsening of the preexisting medical condition (eg, diabetes, 
hypertension) means that it has increased in severity, frequency, and/or duration, and/or has an 
association with a significantly worse outcome. A pre-existing condition that has not worsened 
during the study is not considered an AE. 
11.1.2. 
Definition of a Serious Adverse Event  
An SAE is any untoward medical occurrence that at any dose: 
 Results in death 
 Is immediately life-threatening 
 Requires inpatient hospitalization or prolongation of existing hospitalization.  
 Elective or pre-planned treatment for a pre-existing condition that is unrelated to 
the indication under study and has not worsened since signing the ICF 
(documented as medical history on the eCRF) is not considered an SAE 
 Scheduled therapy for the target disease of the study, including admissions for 
transfusion support or convenience, is not considered an SAE 
 Results in persistent or significant disability/incapacity 
 Results in congenital anomaly/birth defect 
 Is considered an important medical event 
 If an AE does not meet 1 of the serious criteria, but the Investigator or Sponsor 
considers an event to be clinically important, the event could be classified as an 
SAE under the criterion of an ‘Important Medical Event’. Examples of such 
medical events may include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, or blood dyscrasias or convulsions that do not 
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11.2. 
Procedures for Recording and Reporting Adverse Events 
11.2.1. 
Recording Adverse Events 
Patients will be instructed to report all AEs and will be asked a general health status question at 
each study visit. All AEs and SAEs occurring in patients will be recorded in the eCRF from the 
time of signing the ICF through the Final Study Visit/phone call. An AE will be followed until it 
is resolved, has returned to baseline, or is determined to be a stable or chronic condition.  
At each protocol-required visit (including safety follow-up phone call) during the study, all AEs 
that have occurred since the previous visit must be reviewed by the Investigator. The Investigator 
must determine if the AE is serious or nonserious.  
The Investigator must assign the following AE attributes: 
 AE diagnosis or syndrome(s) if known 
 If not known at time of the report, record the signs and/or symptoms as AEs and 
provide an updated report with diagnosis when obtained 
 Dates of onset and resolution 
 Severity as defined per protocol 
 Assessment of relatedness to KAN-101/PBO 
 Action taken with each KAN-101/PBO dose as a result of the AE 
In general, an AE that is the primary cause of subsequent events should be identified by the 
primary cause (eg, for dehydration due to diarrhea, the AE would be diarrhea). However, AEs 
occurring secondary to an initiating event that are separated in time should be recorded as 
independent events (eg, for sepsis secondary to pneumonia, both events should be recorded).   
Confirmed and suspected SARS-CoV-2 infections and/or COVID-19 cases will be recorded in 
the AE eCRF.   
11.2.2. 
Relationship to KAN-101 
The Investigator must assess whether the AE may be related to KAN-101 (study drug) or any 
protocol mandated procedure, when applicable. The relationship is defined below:   
Relationship assessments that indicate the event is “Not Drug Related”: 
 None: The event is related to an etiology other than the study product administration 
(the alternative etiology must be documented in the study patient’s medical record). 
 Remote: The event is unlikely to be related to the study product and likely to be 
related to factors other than study product. 
Relationship assessments that indicate the event is “Drug Related”: 
 Possible: There is an association between the event and the administration of KAN-
101, and there is a plausible mechanism for the event to be related to the study 


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product; but there may also be alternative etiology, such as characteristics of the 
patient’s clinical status or underlying disease. 
 Probable: There is an association between the event and the administration of KAN-
101, there is a plausible mechanism for the event to be related to KAN-101, and the 
event could not be reasonably explained by known characteristics of the patient’s 
clinical status or an alternative etiology is not apparent. 
 Definite: There is an association between the event and the administration of KAN-
101, there is a plausible mechanism for the event to be related to the KAN-101 and 
causes other than KAN-101 have been ruled out and/or the event re-appeared on re-
exposure to KAN-101. 
11.2.3. 
Adverse Event Severity 
The Investigator will assess the Grade of the AE per the NCI-CTCAE v5.0 or higher 
(Appendix 1). Toxicities that are not specified in the NCI-CTCAE will be defined as follows:  
 Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated 
 Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living (ADL) 
 Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-
care ADL 
 Grade 4: Life-threatening consequences; urgent intervention indicated 
 Grade 5: Death related to AE 
Note: It is important to distinguish between SAEs and severe AEs. Severity is a measure of 
intensity, whereas seriousness is classified by the criteria based on the regulatory definitions as 
described in Section 11.1.2. 
11.2.4. 
Abnormal Laboratory Values 
The Investigator is responsible for reviewing clinical laboratory tests determining whether an 
abnormal value represents a CS change from the patient’s baseline value. In general, abnormal 
laboratory findings without clinical significance (based on the Investigator's judgment) should 
not be recorded as AEs. In general, an abnormal laboratory test result should be reported as an 
AE if the laboratory result:  
 Requires an adjustment or discontinuation of KAN-101 
 Requires treatment with or adjustment to concomitant medications 
 Is considered to be an AE by the Investigator 
11.2.5. 
Medication Errors, Misuse, and Abuse of KAN-101 
Overdose, medication error, misuse, and abuse are defined as follows: 


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 Overdose: refers to the administration of a quantity of KAN-101 given per 
administration or cumulative, which is above the maximum dose according to the 
protocol  
 Medication error: refers to an unintentional error in dispensing or administration of 
KAN-101 not in accordance with the protocol 
Off-label use: relates to situations where KAN-101 is intentionally used for medical purpose not 
in accordance with the protocol 
 Misuse: refers to situations where KAN-101 is intentionally and inappropriately not 
used in accordance with the protocol 
 Abuse: corresponds to the persistent or sporadic, intentional excessive use of KAN-
101, which is accompanied by harmful physical or psychological effects 
 Occupational exposure: refers to the exposure to KAN-101 because of one’s 
professional or non-professional occupation 
Overdoses, medication errors, abuse, or misuse will be collected as part of investigational 
medicinal product dosing information and/or as a protocol violation, as required.  
11.2.6. 
Reporting of Serious Adverse Events 
SAEs will be recorded on the appropriate eCRF and reported to the Sponsor within 24 hours of 
the Investigator’s first knowledge of the event, even if the experience does not appear to be 
related to KAN-101, from the time of signing ICF through the final Follow-Up Visit/phone call.  
The initial SAE CRF must be as complete as possible and include details of the current illness 
and SAE as well as an assessment of the relationship between the event and KAN-101. 
Additional information relating to a previously reported SAE must also be reported within 24 
hours of the Investigator’s first knowledge of information. The Investigator may also be asked, 
by the Sponsor or designee, to provide clarifications or additional information. 
If the Investigator becomes aware of an SAE considered related to KAN-101, occurring more 
than 30 days after the last dose of KAN-101, the SAE must be reported as described above.  
11.2.7. 
Reporting of Serious Adverse Events to Regulatory Authorities, Ethics 
Committee, and Institutional Review Board 
The Sponsor or designee will determine expectedness of the Sponsor’s product for each reported 
SAE based on the appropriate reference safety information per local country requirements. The 
Sponsor or designee shall notify regulatory authorities of serious, unexpected, and related AEs or 
other AEs, per local requirements.  
The Sponsor or designee shall notify the Investigator of serious, related, and unexpected AE(s) 
submitted to the regulatory agencies, per local country requirements.  
The Investigator will notify the appropriate Institutional Review Board (IRB)/Local Ethics 
Committees (LECs) of serious, related, and unexpected AE(s), or significant risks to patients, per 


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local country requirements. The Investigator must keep copies of all AE information on file, 
including correspondence with the Sponsor or IRBs/LECs. 
11.2.8. 
Pregnancy and In Utero Drug Exposure 
KAN-101 has not been evaluated in pregnant or nursing women. Thus, pregnant women or 
WCBP who are not using effective contraception are excluded from this study (see Section 8 and 
Section 6.1.8 for instructions on birth control and pregnancy testing, respectively). 
Pregnancies occurring in patients, or partners of male patients are considered immediately 
reportable events if the pregnancy occurs during the study treatment through the Safety Follow-
Up Visit after the patient’s last dose of KAN-101. If a pregnancy occurs in a patient, KAN-101 
must be discontinued immediately. The pregnant woman should be referred to an 
obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and 
counseling. 
The pregnancy must be reported to the Sponsor or designee within 24 hours of the Investigator’s 
knowledge of the pregnancy by recording it on the appropriate CRF. 
The Investigator will follow the pregnant patient until completion of the pregnancy and must 
notify the Sponsor of the pregnancy outcome within 24 hours of the Investigator’s knowledge of 
the outcome. The Investigator will provide this information by recording it on the appropriate 
CRF. This notification includes pregnancies resulting in live, “normal” births. 
If the pregnant patient experiences an SAE during pregnancy, or the outcome of the pregnancy 
meets any of the serious criteria (ie, spontaneous abortion [any congenital anomaly detected in 
an aborted fetus is to be documented], stillbirth, neonatal death, or congenital anomaly), the 
Investigator should follow the procedures for reporting SAEs (ie, report the event to the Sponsor 
or designee within 24 hours of the Investigator’s knowledge of the event). 
All neonatal deaths and congenital anomalies that occur within 30 days of birth (regardless of 
causality) should be reported as SAEs to the Sponsor or designee. In addition, any infant death or 
congenital anomaly occurring after 30 days that the Investigator suspects is related to the in-utero 
exposure to KAN-101 should also be reported to the Sponsor or designee.  


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12. 
STATISTICAL METHODS 
Details of the statistical methods for this study will be documented in a Statistical Analysis Plan 
(SAP). When there is a difference between the final approved SAP and the protocol, the methods 
described in the final SAP will prevail. 
Statistical methods will be primarily descriptive in nature. No hypothesis will be formally tested. 
For Part A, the data will be listed by dose group. For Part B, summary statistics will be provided 
by dose group. Categorical variables will be summarized using numbers and percentages. 
Continuous variables will be summarized by total number (n), mean, standard deviation (StD), 
median, and range (minimum and maximum).  
Part A and Part B PK will be analyzed separately and together where appropriate. 
12.1. 
Sample Size  
In Part A, the number of patients enrolled into a cohort will be based on safety and tolerability, 
and will employ a traditional 3+3 design. Under this model, Part A may enroll between 12 and 
24 patients across 4 dose cohorts, depending upon what toxicities are observed. No formal 
hypothesis testing is planned for Part A. The PK data obtained in Part A will be combined with 
the PK data obtained following first dose of KAN-101 in Part B. 
In Part B, the total sample size of 24 patients (n=18 KAN-101; n=6 PBO) across 3 dose cohorts 
was chosen to allow for a comparison of safety, PK, and PD between KAN-101 and PBO. A 
sample size of 6 active patients per cohort in Part B allows for an 0.80 power to detect a 
treatment-related AE occurring at an event rate of 0.25.   
12.2. 
Analysis Sets 
The main analysis sets are defined in this section. Additional analysis sets may be defined in the 
SAP.  
 The All-Treated Analysis Set is defined as all patients who received any amount of 
study drug with treatment group based on the dose level received. This analysis set 
will be the primary analysis set for all safety endpoints.  
 The PK Analysis Set will include all enrolled patients who received at least one dose 
of KAN-101 and have at least one measurement. This analysis set will be used for the 
analysis of PK parameters as further defined in the protocol.  
 
 
 
 
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12.3. 
Background Characteristics  
12.3.1. 
Patient Disposition 
The number and percentage of patients in each disposition category (eg, enrolled, included in 
each Analysis Set, discontinuing treatment, and discontinuing study, with a breakdown of the 
reasons for discontinuation) will be summarized by dose level and cohort. 
For each part of the study, the All-Treated Analysis Set will be used as the basis for percentages, 
as appropriate. 
12.3.2. 
Demographics and Baseline Characteristics 
The following demographics and baseline characteristics will be summarized by treatment group 
and cohort for the All-Treated Analysis Set: sex, race, age, years since CeD diagnosis, and years 
on GFD. Additional parameters may be provided in the SAP.  
12.4. 
KAN-101 Exposure  
The summary statistics of exposure will be tabulated by study part and by dose group. In the 
summary, the following will be included: 
 the cumulative number of days of exposure 
 the number of IV infusions completed  
 the relative dose intensity  
All variables are predefined:  
 The relative dose intensity is defined as the percentage of the planned treatments 
completed. It is the ratio of the cumulative actual dose (mg) and cumulative planned 
dose (mg) times 100. In this definition, 
 the cumulative actual dose (mg) is the sum of the actual doses (mg) that the patient 
receives during the study  
 the cumulative planned dose (mg) is the cumulative number of days of exposure 
times the planned dose level (mg)  
All analyses within this section will be based on the All-Treated Set unless otherwise specified. 
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12.6. 
Safety Analyses  
The Dose-Escalation Safety Analysis Set will be used to evaluate safety within the dose-
escalation phase of Part A and Part B. The number and type of AEs experienced by patients will 
be summarized for each dose level, accompanied by a by-patient listing of potentially dose-
limiting AEs events. This analysis will include all DLTs between D1 to D8 for Part A and all 
DLTs between D1 to D15 for Part B, which are the time periods that constitute the safety 
monitoring period for dose-escalation.   
All-Treated Analysis Set will be used to evaluate all other safety endpoints. The number and type 
of AEs experienced by patients will be summarized for each dose level, accompanied by a by-
patient listing of all AEs. The listing will include the description, severity, and relationship of the 
events to KAN-101.  
For Part A and Part B, safety data, including vital signs, ECGs, laboratory test results, PEs, and 
AEs will be summarized by dose and assessment time points, as appropriate. 
12.7. 
Adverse Events 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) v22.0 
(MedDRA March 2019) or higher and will be graded according to the NCI-CTCAE v5.0 or 
higher (Appendix 1).  
Summaries of AEs will include TEAEs. A TEAE is an AE that emerges or worsens in the period 
from the first dose of study treatment to the final Follow-Up Visit/phone call after the last dose 
of KAN-101 or PBO. 
For Part A and Part B, AEs will be summarized overall and by dose group.   
TEAEs will be summarized by the frequency within MedDRA system organ class and 
preferred term. Separate tabulations will also be provided for TEAEs related to study drug, 
TEAEs that led to treatment discontinuation, TEAEs that led to death, and TEAEs ≥ Grade 3 in 
severity. Treatment-emergent SAEs and SAEs related to study drug will also be tabulated.  
Detailed information of AEs will be included in a listing. 
12.8. 
Clinical Laboratory Assessments 
All statistical analyses of laboratory values will be performed using International System units. 
All statistical analyses will be by dose group. 
Summary statistics for laboratory values including change from baseline will be tabulated for 
scheduled visits. Shifts in Grade from baseline to the maximum post-baseline (including 
unscheduled) grade will be summarized by number and percentage of patients within each 
category. Abnormality of laboratory data will be listed for patients with ≥ Grade 3 in severity. 
A listing of individual patient hematology, serum chemistry, and coagulation values outside the 
reference ranges will be provided. This listing will include data from scheduled and unscheduled 
timepoints. 


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12.9. 
Pharmacokinetic Analyses 
Blood samples will be collected for measurement of KAN-101, as specified in Table 1 and 
Table 2. The timing of sampling may be altered based on the emerging PK data. The adjustment 
of the PK sampling schedule is not considered to be a substantial amendment so long as the total 
number of plasma PK samples and the total blood volume to be collected from each participant 
will not change. Any adjusted sampling time points will be documented appropriately. 
Instructions for the collection and handling of biological samples will be provided by the 
Sponsor. The actual date and time of PK blood sampling will be recorded by the Investigator or 
designee in the CRF, as appropriate. 
For the final analysis, PK parameters of KAN-101 will be determined from the plasma 
concentration-time data. Parameters will be calculated by noncompartmental modeling methods, 
using Phoenix WinNonlin 8.0 or higher, using actual sampling times where relevant. The 
parameters that will be calculated are defined in Table 3, and will be calculated for single or 
multiple dosing of KAN-101, as appropriate. Not all listed parameters may be calculable, and 
additional parameters may be calculated, if needed, to fully characterize the available data.  
 
 


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Table 3:  
Pharmacokinetic Parameter Definitions  
Parameter 
Definition 
Cmax  
Maximum observed plasma concentration 
Tmax  
Time to first occurrence of maximum observed plasma concentration 
Ctrough 
Pre-dose plasma concentration 
AUC72  
Area under the plasma concentration-time curve from time 0 to 72 hours post-dose 
AUClast 
Area under the plasma concentration-time curve from time 0 to the last measurable time 
point 
AUCinf  
Area under the plasma concentration-time curve extrapolated to infinity 
AUCtau 
Area under the plasma concentration-time curve over the dosing interval 
t1/2  
Terminal elimination half-life 
CL/F 
Apparent oral clearance  
Vz/F 
Apparent volume of distribution after a single dose  
Racc,AUC 
Accumulation ratio based on AUC  
Racc,Cmax  
Accumulation ratio based on Cmax   
Statistical evaluations of PK data will include dose proportionality assessment using Cmax, 
AUClast, and AUCinf.   
For cohort by cohort PK analysis, not all PK parameters may be calculated, and 
noncompartmental analysis done may be done using nominal times. 
Additional details on the PK analyses will be provided in a PK analysis plan.   
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13. 
STUDY ADMINISTRATION 
13.1. 
Good Clinical Practice Statement 
This study is to be performed in accordance with the protocol, the Declaration of Helsinki, the 
International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good 
Clinical Practice (GCP), and all applicable local regulatory requirements. 
13.2. 
Informed Consent 
The Sponsor or designee will provide a sample patient ICF for modification, as appropriate, by 
the Investigator. The ICF must include all elements required by ICH and GCP and must adhere 
to the IRB/ Independent Ethics Committee (IEC) requirements and the ethical principles that 
have their origin in the Declaration of Helsinki. 
The Investigator or designee will explain the nature of the study, its purpose and associated 
procedures, the expected duration, and the potential risks involved to the patient prior to 
enrollment. The Investigator or designee will obtain written, informed consent. The patient will 
have ample time and opportunity to ask questions and will be informed about the right to 
withdraw from the study at any time without any disadvantage and without having to provide a 
reason for this decision. Following the discussion regarding the study, a patient will be asked if 
he/she is willing to sign and personally date a statement of informed consent. Only if the patient 
voluntarily agrees to sign the informed consent statement and has done so, may he/she enter the 
study. A copy of the signed and dated ICF will be provided to the patient. The signed ICF is to 
remain in the Investigator’s file, per local country requirements. 
The ICF and any other written information provided to the patients will be revised whenever 
important new information becomes available that may be relevant to the patient’s consent, or if 
there is an amendment to the protocol which necessitates a change to the content of the patient’s 
informed consent. The Investigator will inform the patients of changes in a timely manner and 
will ask the patients to confirm continuation of their participation in the study by their signature 
on the revised ICF (if applicable). Any written ICF and written information must receive the 
approval/favorable opinion of the IRB/IEC in advance of use. Any additional approvals from the 
initial ICF should be forwarded to the Sponsor. 
13.3. 
Patient Confidentiality 
The written ICF will explain that study data will be stored in a database, maintaining 
confidentiality in accordance with national data legislation. All data processed by the Sponsor or 
its representative(s) will be identified by patient number and study code. 
The written ICF will also explain that for data verification purposes, authorized representatives 
of the Sponsor, a regulatory authority, and an IRB/IEC may require direct access to parts of the 
hospital or clinic records relevant to the study that include patient medical history. 
The Investigator must ensure that patient anonymity is maintained. On the eCRFs or other 
documents submitted to the Sponsor, patients should not be identified by their names, but by 


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their assigned patient number and study code. Documents not for submission to the Sponsor, 
such as signed ICF, should be maintained in strict confidence by the Investigator. 
13.4. 
Institutional Review Board/Ethics Committee Requirements  
The final study protocol, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an IRB/IEC at each clinical study site. The Principle Investigator 
(PI) must submit written approval from the IRB to the Sponsor before he or she can enroll any 
patient into the study. 
The PI is responsible for informing the IRB/IEC of any amendment to the protocol. In addition, 
the IRB/IEC must approve all advertising used to recruit patients for the study. The protocol 
must be reapproved by the IRB/IEC annually or as required by the IRB, regulations, and 
guidelines. 
Progress reports and notifications of SAEs will be provided to the IRB/IEC according to 
regulations and guidelines. 
13.5. 
Case Report Forms and Source Documentation  
eCRFs will be provided for the recording of all data. The PI/Sub-Investigator or designee will 
record data from all observations, tests, and assessments specified in the protocol on the eCRFs 
provided by the Sponsor. 
13.6. 
Study Monitoring  
Before the first patient signs the ICF to participate in the study, the Sponsor or designee will visit 
the study site to: 
 Determine the adequacy of the facilities 
 Discuss with the Investigator(s) (and other personnel involved with the study) their 
responsibilities related to the protocol and the responsibilities of the Sponsor or 
designee 
 Confirm that the Investigator(s) (and other personnel involved with the study) have 
not invoked sanctions or demonstrated any scientific misconduct or fraud 
During the conduct of the study, the Sponsor or designee will maintain regular contact and visits 
to the clinical study site to: 
 Provide information and support the Investigator 
 Confirm that the facilities remain acceptable 
 Confirm that the study team is adhering to the protocol, data are being accurately 
recorded in the eCRFs, and the investigational product is being properly maintained 
and accountability records are current 
 Perform source data verification with access to all original clinical records for each 
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13.7. 
Quality Assurance  
In compliance with GCP and regulatory requirements, the Sponsor, a third party on behalf of the 
Sponsor, and regulatory agencies or IRB/IECs may conduct quality assurance audits at any time 
during or following a study. The Investigator must agree to allow auditors direct access to all 
study-related documents, including source documents, and must agree to allocate his/her time 
and the time of the study staff to the auditors in order to discuss findings and issues. 
Monitoring visits at site will be limited to a minimum required as deemed appropriate during the 
COVID-19 pandemic. 
13.8. 
Study or Clinical Site Termination 
The Sponsor, or designee, reserves the right to terminate the study or a clinical study site at any 
time. Conditions that may warrant termination of the study include, but are not limited to: 
 Discovery of an unexpected, serious, or unacceptable risk to patients enrolled in the 
study 
 Decision on the part of the Sponsor to suspend or discontinue testing the study 
treatment 
Conditions that may warrant termination of a study site include, but are not limited to: 
 Failure of the Investigator to comply with GCP 
 Submission of knowingly false information from the clinical study site to the Sponsor 
or regulatory authorities 
 Insufficient adherence to protocol requirements 
If terminating the study, the Sponsor and the Investigator(s) will assure that adequate 
consideration is given to the protection of the patients’ interests. 
13.9. 
Duration of the Study, Expected Duration of Patient Participation, 
and End of Study 
The study is planned to initiate enrollment in January 2020 with the last study visit in June 2021. 
In Part A of the study, enrolled patients will receive a single IV infusion of KAN-101 on D1 and 
will be monitored through D21. Thus, the total length of patient participation, which includes 
screening, is approximately 49 days. 
In Part B of the study, enrolled patients will receive 3 IV infusions of KAN-101, each on D1, D4, 
and D7, with a final follow-up phone call on D28. Thus the total length of patient participation, 
which includes screening, is approximately 56 days. 
13.10. 
Records Retention  
All correspondence related to this clinical study should be kept in appropriate study files. 
Records of patients, source documents, eCRFs, KAN-101 inventory, IRB, and Sponsor or 


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designee correspondence pertaining to this study must be kept on file. All study documents must 
be kept secured for a period of 2 years after a marketing application is approved for KAN-101, or 
for 2 years after the last shipment and delivery of KAN-101 for investigational use on study, or 
as long as required by local regulations, whichever is longer. There may be other circumstances 
for which the Sponsor is required to maintain study records and, therefore, the Sponsor should be 
contacted prior to removing or relocating study records for any reason. 
13.11. 
Publications 
Publication by the clinical study site(s) of any data from this study must be carried out in 
accordance with the Clinical Trial Agreement. 


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14. 
REFERENCES 
Goel G, King T, Daveson AJ, et al. Epitope-specific immunotherapy targeting CD4-positive T 
cells in coeliac disease: two randomised, double-blind, placebo-controlled phase 1 studies. 
Lancet Gastroenterol Hepatol. 2017 Jul;2(7):479-93. 
Green PH, Jabri B. Celiac disease. Annu Rev Med. 2006;57:207-21. 
Green PHR, Stavropoulos SN, Panagi SG, et al. Characteristics of adult celiac disease in the 
USA: results of a national survey. Am J Gastroenterol. 2001 Jan;96(1):126-31. 
Halfdanarson TR, Litzow MR, Murray JA. Hematologic manifestations of celiac disease. Blood. 
2007 Jan 15;109(2):412-21. 
Rubio-Tapia A, Hill ID, Kelly CP, et al. ACG clinical guidelines: diagnosis and management of 
celiac disease. Am J Gastroenterol. 2013 May;108(5):656-76; quiz 77. 
See JA, Kaukinen K, Makharia GK, et al. Practical insights into gluten-free diets. Nat Rev 
Gastroenterol Hepatol. 2015 Oct;12(10):580-91. 
Singh P, Arora A, Strand TA, et al. Global Prevalence of Celiac Disease: Systematic Review and 
Meta-analysis. Clin Gastroenterol Hepatol. 2018 Jun;16(6):823-36 e2. 
Sollid LM, Jabri B. Triggers and drivers of autoimmunity: lessons from coeliac disease. Nat Rev 
Immunol. 2013 Apr;13(4):294-302. 
Sollid LM, Markussen G, Ek J, et al. Evidence for a primary association of celiac disease to a 
particular HLA-DQ alpha/beta heterodimer. J Exp Med. 1989 Jan 1;169(1):345-50. 
Sollid LM, Qiao SW, Anderson RP, et al. Nomenclature and listing of celiac disease relevant 
gluten T-cell epitopes restricted by HLA-DQ molecules. Immunogenetics. 2012 Jun;64(6):455-
60. 
Thomson AW, Knolle PA. Antigen-presenting cell function in the tolerogenic liver environment. 
Nat Rev Immunol. 2010 Nov;10(11):753-66. 
 
 
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APPENDIX 1. COMMON TERMINOLOGY CRITERIA FOR ADVERSE 
EVENTS V5.0 (CTCAE) 
CTCAE Terms  
An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medical treatment or procedure that 
may or may not be considered related to the medical treatment or procedure. An AE is a term 
that is a unique representation of a specific event used for medical documentation and scientific 
analyses. Each CTCAE v5.0 term is a MedDRA Lowest Level Term. 
Definitions  
A brief definition is provided to clarify the meaning of each AE term.  
Grades  
Grade refers to the severity of the AE. The CTCAE displays Grades 1 through Grade 5 with 
unique clinical descriptions of severity for each AE based on this general guideline:  
 Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated  
Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental ADL*  
Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
selfcare ADL**  
Grade 4: Life-threatening consequences; urgent intervention indicated  
Grade 5: Death related to AE 
A Semi-colon indicates ‘or’ within the description of the grade.  
A single dash (-) indicates a grade is not available. 
Not all Grades are appropriate for all AEs. Therefore, some AEs are listed with fewer than 5 
options for Grade selection. Grade 5 (Death) is not appropriate for some AEs and therefore is not 
an option.  
Activities of Daily Living (ADL)  
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the 
telephone, managing money, etc.  
**Selfcare ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden. 
Publish date 27 November 2017 
https://ctep.cancer.gov/protocolDevelopment/electronic applications/ctc.htm#ctc 50 
  


Protocol Amendment 1, Version 2 (27 January 2020) 
• Updated language regarding pausing and stopping criteria to include reporting any ≥ Grade 4 
AE to FDA prior to dosing any additional subjects. This has been modified to reflect FDA 
feedback. 
• Updated language defining the Safety Monitoring Committee to reflect FDA feedback on the 
independence of the SMC review 
9.8.1.2 Protocol Amendment 2, Version 3 (4 March 2020) 
• Clarified and expanded observations from nonclinical models 
• Updated Language to clarify and expand acceptable forms of birth control for WCBP 
• Modified Dose Levels 
o A subject received a single dose of 1.5 mg/kg KAN-101 and experienced symptoms 
consistent with the ingestion of gluten. Due to these events, Anokion decided to lower 
the doses explored in the KAN-101-01 study. 
o The doses for Part A: 
• 
Original planned doses: 1.5 mg/kg (Cohort 1), 3.75 mg/kg (Cohort 2), 7.5 
mg/kg (Cohort 3), and 15 mg/kg (Cohort 4) 
• 
New planned doses: 0.15 mg/kg (Cohort 1), 0.3 mg/kg (Cohort 2), 0.6 mg/kg 
(Cohort 3), and 1.2 mg/kg (Cohort 4) 
o Doses for Part B: 
• 
Original planned doses: 1.5 mg/kg (Cohort 5), 3.75 mg/kg (Cohort 6), and 
7.5 mg/kg (Cohort 7) 
• 
New planned doses: 0.15 mg/kg (Cohort 5), 0.3 mg/kg (Cohort 6), and 0.6 
mg/kg (Cohort 7) 
• Updated Starting Dose and Dose escalation section of the synopsis to reflect new starting dose 
and included explanation for reduction 
Protocol Amendment 3, Version 4 (28 April 2020) 
 
 
Protocol Amendment 4, Version 5 (14 September 2020) 
• COVID updates/modifications added 
• Window for SAD study visit D4 provided (±1 day) 
• Removal of PK sample on SAD D4 – due to short plasma half-life of KAN-101 (less than 20 
minutes) the drug will clear 5 half-lives within the 6 hours of sampling on D1, therefore the D4 
sample is not required to establish the clearance of KAN-101 
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• 
 
Protocol Amendment 5, Version 6 (6 January 2021) 
• Upon consultation with the FDA, the length of time for in-clinic/hospital unit observation on 
D1 has been reduced from 24 hours to 10 hours to reduce patients COVID-19 exposure risk. 
• Language has been added to allow for replacement of patients who do not receive full dose(s) 
of study drug as long as they do not discontinue due to a DLT assessed as related to study drug 
• Statistical language has been updated to align with SAP 
• Inclusion criteria #5 has been updated to allow enrollment patients with negative or weak 
positive tTG-IgA (defined as > 2 x ULN) 
• Exclusion Criteria #12 has been modified to clarify that systemic non-biologic 
immunosuppressive or immunomodulatory therapies within the last 3 months should be 
exclusionary 
• Clarified that for rescreening that: 
o HLA testing does not need repeating 
o CeD serology only needs to be repeated if > 3 months have elapsed from last 
assessment 
 
o ECG only needs to be repeated if > 3 months have elapsed from last assessment 
• 
 
• Clarified blinding language to include that after completion of SMC review and once all 
patients in the cohort have completed the study, the Sponsor study team may be unblinded to 
perform biomarker analysis 
Protocol Amendment 6, Version 7 (29 March 2021) 
• To enhance patient safety in KAN-101-01 study, safety ECG assessments added on certain 
dosing days pre-dose, during infusion and post-dose 
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ANOKION 
KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 1 of 52 
TITLE PAGE 
 
 
 
 
 
ANOKION 
KAN-101-01 
A Phase 1 Study of the Safety and Tolerability of Single and Multiple Doses of KAN-101 
in Patients with Celiac Disease  
 
 
Statistical Analysis Plan 
 
 
Version: 3.0 
 
 
 
 
 
Dated: 12-Nov-2021 
 
 
 
 
 
 
 
 
 
 
 
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ANOKION 
KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 2 of 52 
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ANOKION 
KAN-101-01                                                                                                                       Statistical Analysis Plan 
TP-GDO-WW-016-08                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
Related to:  SOP-GDO-WW-019                                                                                                         Page 3 of 52 
SPONSOR SIGNATURE PAGE 
 
 
 
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ANOKION 
KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 4 of 52 
TABLE OF CONTENTS 
TITLE PAGE ............................................................................................................................. 1 
 
SPONSOR SIGNATURE PAGE .............................................................................................. 3 
TABLE OF CONTENTS ........................................................................................................... 4 
REVISION HISTORY............................................................................................................... 8 
LIST OF ABBREVIATIONS .................................................................................................... 9 
1 
INTRODUCTION .......................................................................................................... 13 
2 
STUDY OBJECTIVES .................................................................................................. 13 
2.1 
Primary Objective (Part A and Part B) ........................................................................... 13 
2.2 
Secondary Objective (Part A and Part B) ....................................................................... 13 
2.3 
Exploratory Objectives (Part B only) ............................................................................. 13 
3 
INVESTIGATIONAL PLAN ........................................................................................ 13 
3.1 
Overall Study Design and Plan ....................................................................................... 13 
3.2 
Sample Size .................................................................................................................... 15 
3.3 
Assignment to Cohort ..................................................................................................... 15 
3.4 
Endpoints ........................................................................................................................ 15 
3.4.1 
Primary Endpoints (Part A and Part B) ..................................................................... 15 
3.4.2 
Secondary Endpoints (Part A and Part B) ................................................................. 15 
3.4.3 
 
3.5 
Assessments .................................................................................................................... 15 
3.5.1 
Safety Assessments .................................................................................................... 15 
3.5.1.1 Adverse Events (AE) ................................................................................................. 16 
3.5.1.2 Other Safety Assessments .......................................................................................... 17 
3.5.1.2.1 Clinical Laboratory Evaluation .............................................................. 17 
3.5.1.2.2 Physical Examination ............................................................................. 18 
3.5.1.2.3 Vital Signs .............................................................................................. 18 
3.5.1.2.4 ECG ........................................................................................................ 18 
3.5.1.2.5 Prior and Concomitant Medications and Procedures ............................. 18 
3.5.1.2.6 Incidental Gluten Exposure .................................................................... 19 
3.5.1.2.7 Medications for Infusion Reactions ....................................................... 19 
3.5.1.2.8 Study Drug Administration .................................................................... 19 
3.5.2 
Pharmacokinetic Assessments ................................................................................... 19 
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ANOKION 
KAN-101-01                                                                                                                       Statistical Analysis Plan 
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REVISION HISTORY 
Version No. 
Effective Date 
Summary of Change(s) 
Final 1.0 
[12 Apr 21] 
New document 
2.0 
03 Nov 2021 
Minor: few words/sentences were added for below.  
1. Covid related data collection: section 3.5.1.1 and 
4.8.1.  
2. ADA related screening titer information added 
section 3.5.3. 
3. Protocol deviation: section 4.7.   
4. Laboratory: section 4.8.2. 
5. Part A tables and few Part A and B tables were 
added for CSR 
6. Added condition for analysis if the dose level 
received is unknown 
7. Similar information PK sentences and peptide data 
were removed as were not applicable 
Major:  
1. 
 
3.0 
12 Nov 2021 
Minor: 
1. PK sections (3.5.2, 4.3.2, 4.4.4, 4.9) were updated 
to include the necessary PK parameters to be 
consistent with the shells.  
2. Not applicable abbreviations were removed from 
‘List of Abbreviations’  
 
 
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ANOKION 
KAN-101-01                                                                                                                       Statistical Analysis Plan 
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                                                                                                         Page 13 of 52 
1 
INTRODUCTION 
Study KAN-101-01 is a two-part, multicenter Phase 1, First-In-Human (FIH) study designed 
to evaluate the initial safety, tolerability, and activity of KAN-101 in patients with celiac 
disease (CeD) on a gluten-free diet (GFD). The two parts include: Part A – FIH single 
ascending dose (SAD) and Part B – Randomized, placebo (PBO)-controlled, double-blind, 
multiple ascending dose (MAD).  
The initial starting dose of KAN-101 in KAN-101-01 Protocol version 2.0 was 1.5 mg/kg, a 
dose level consistent with an expected efficacious dose and supported by findings from the 
Good Laboratory Practice (GLP) toxicology studies. Due to non-serious adverse events 
consistent with gluten ingestion in celiac patients observed in only one patient at the 1.5 mg/kg 
dose level, the protocol was amended to start at the dose of 0.15 mg/kg, 10-fold lower than the 
dose which induced symptoms. 
This Statistical Analysis Plan (SAP) details the statistical methodology to be used in analyzing 
study data and provides information on Tables, Listings and Figures (TLFs). It describes the 
study endpoints, variables and populations, derived variables, anticipated data transformations 
and manipulations, and other details of the analyses not provided in the Clinical Study Protocol 
(CSP).  
The analyses described are based on the clinical study protocol for study number KAN-101-01 
Version 7.0 (29 Mar 2021) and Blank CRF Casebook (eCRF) Version 5.0 (23 April 2021). 
This SAP was developed in accordance with ICH E9 guideline. All decisions regarding 
statistical analysis, as defined in this SAP document, will be made prior to study database lock 
(DBL) and describes the statistical analysis as it is foreseen when the study is being planned. 
The reader of this SAP should also read the clinical protocol, and other relevant documents for 
details on the planned conduct of this study.  
2 
STUDY OBJECTIVES 
2.1 
Primary Objective (Part A and Part B) 
• Assess the safety and tolerability of escalating doses of KAN-101 in patients with CeD. 
2.2 
Secondary Objective (Part A and Part B) 
• Assess the pharmacokinetic (PK) of KAN-101 after single and multiple doses of KAN-101 
in patients with CeD. 
2.3 
Exploratory Objectives (Part B only) 
3 
INVESTIGATIONAL PLAN 
3.1 
Overall Study Design and Plan 
Study KAN-101-01 is a Phase 1, FIH study designed to evaluate the initial safety, tolerability, 
and activity of KAN-101 in patients with CeD on a GFD. As this is the first instance of KAN-
101 administration to humans, safety, tolerability and PK will be evaluated in an escalating 
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ANOKION 
KAN-101-01                                                                                                                       Statistical Analysis Plan 
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                                                                                                         Page 16 of 52 
a final Follow-Up at D21 (±1), 20 days after the single administration of KAN-101. All patients 
in Part B will have a final Follow-Up phone call at D28 (±3), approximately 20 days after the 
final administration of KAN-101 on D7.  
3.5.1.1 Adverse Events (AE) 
All AEs from the time of signing of Informed Consent Form (ICF) through the final Follow-
Up Visit/phone call will be collected. Adverse events will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA) Version 23.1 (MedDRA Sep 2020) or higher. 
Ongoing AEs considered at least possibly related to KAN-101 treatment should be followed 
until resolution, return to baseline, or are considered stable or chronic. 
AE: 
An AE is defined as any untoward medical occurrence associated with the use of a drug, or 
with study participation, whether or not consider related to study treatment.  
TEAE: 
TEAEs are defined as AEs that emerge or worsen in the period from the first dose of study 
treatment to the final Follow-Up Visit/phone call after the last dose study drug.  
The incidence and severity of TEAEs as assessed by the CTCAE v5.0 or higher is considered 
the primary endpoint. TEAEs that occur before and after gluten challenge will also be examined 
separately and defined as in section 4.8.1. 
DLT: 
A dose-limiting toxicity (DLT) for Study KAN-101-01 is defined as any ≥ Grade 3 AE assessed 
as related to KAN-101 or Grade 2 AE assessed as related to KAN-101 not resolving within 14 
days. DLTs do not include those AEs attributable solely to intercurrent illness or other 
concomitant medications.  
AE Severity: 
The National Cancer Institute Common Toxicity Criteria Adverse Event (NCI-CTCAE) 
version 5.0 or higher will be used to grade the severity of all AEs, whether or not they are 
considered related to KAN-101. Toxicities that are not specified in the NCI-CTCAE will be 
defined as follows:  
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
• Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (ADL) 
• Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL 
• Grade 4: Life-threatening consequences; urgent intervention indicated 
• Grade 5: Death related to AE  
AE Causality: 
Relationship to the study drug for all AEs will be assessed as “drug related” (Possible, 
Probable, Definite) or “not drug related” (None, Remote). 
Impact of COVID-19:  
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ANOKION 
KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
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Pandemic related Impact of COVID-19 data will be assessed, detailing the category of impact 
(example: Missed Visit, Missed Assessment, Early termination, Screen Failure, Adverse Event, 
Withdrawal of consent, Death, Replacement subject) based on data collection. 
3.5.1.2 Other Safety Assessments 
Additionally, safety will be also be examined by the following assessments:  
• Clinical laboratory evaluations  
• Physical examination 
• Vital signs  
• Prior and concomitant medications and procedures  
• Incidental gluten exposure 
• Medications for infusion reactions 
• Study drug administration 
3.5.1.2.1 Clinical Laboratory Evaluation 
All statistical analyses of laboratory values will be performed using International System units. 
The Clinical laboratory parameters and tests to be analyzed locally or centrally by a certified 
laboratory with corresponding laboratory normal ranges are: 
• Serum Chemistry: Blood urea nitrogen, creatinine, glucose, aspartate aminotransferase 
(AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin (total and 
direct), electrolytes (sodium, chloride, bicarbonate, potassium), amylase, lipase, albumin, 
magnesium, calcium, and phosphorus 
• Hematology: White blood cell (WBC) count, hemoglobin, hematocrit, Platelet (PLT) 
count, and WBC differential 
• Coagulation: Prothrombin time, partial thromboplastin time or activated partial 
thromboplastin time, and international normalized ratio 
• Complete urinalysis with qualitative analysis for protein (dipstick) 
• Virus Serology: Human immunodeficiency virus (HIV), hepatitis B (HBV) (HBsAg, anti-
HBc and anti-HBs), and hepatitis C (HCV) testing (Screening only) 
• Serum pregnancy test will be performed at screening for women of child-bearing potential 
(WCBP). Serum or urine pregnancy testing for all WCBP will be performed prior to each 
dose. 
The following laboratory tests will be performed centrally at Screening only: 
• HLA DQ2.5 and HLA DQ8 testing  
• Transglutaminase (tTG) and deaminated gluten peptides (DGP) IgA/IgG 
For tTG, a result of <2xULN will be considered negative or weak positive.  For DGP, a result 
of <30 U/mL will be considered negative or weak positive. 
For re-screening, the HLA does not need to be repeated and the tTG and DGP antibody tests 
should only be repeated if >3months have elapsed from end assessment.  
Unscheduled assessments should be performed as clinically indicated. For any out-of-range 
laboratory findings during screening, repeat laboratory testing may be performed at the 
discretion of the Investigator. Abnormal laboratory findings at screening should be recorded as 
medical history only if considered clinically significant (CS). 
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Investigators will assess whether the values outside the clinical reference range are clinically 
significant and these will be reported as abnormal NCS or abnormal CS.  
• Clinically significant abnormal laboratory values will be recorded by the Investigator as 
AEs.  
• The abnormal values will be flagged with ‘LOW’ for values below the lower limit of the 
local clinical reference range and ‘HIGH’ for values above the upper limit of the local 
clinical reference range and included in the listings. 
3.5.1.2.2 Physical Examination 
The physical exam (PE) will be conducted at Screening and as clinically indicated, including 
for early terminated subjects. The PE includes an assessment of general appearance, skin, head, 
neck, throat, lymph nodes, cardiovascular, neurological, thyroid, musculoskeletal / extremities, 
respiratory, abdomen, height (screening only) and weight (screening only).  
3.5.1.2.3 Vital Signs 
Vital signs will include temperature, pulse rate and blood pressure (BP) (sitting for 5 minutes). 
If vital signs need to be repeated during a single visit, assessments should be conducted 
approximately 5 minutes apart.  
Any new CS change from baseline should be recorded as an AE. 
3.5.1.2.4 ECG 
All electrocardiograms (ECGs) will be standard resting 12-lead ECGs performed after the 
patient has been supine for at least 5 minutes. ECG data will be presented. 
3.5.1.2.5 Prior and Concomitant Medications and Procedures 
At screening, concomitant medications will be recorded. Assessment of any change in 
concomitant medications, or procedures since the last visit will occur at all further patient visits 
through the final Follow-Up Visit. Concomitant medications will be coded using the World 
Health Organization Drug Dictionary drug (WHO Drug Global Sep 2019) and will be presented 
by WHO-DD Anatomical Therapeutic Chemical (ATC) therapeutic Level 4 classification and 
preferred term (PT). Below rules will be applied to decide if the medications and procedures 
are prior, concomitant or both. 
• Medications that start and stop prior to the first dose of study medication will be classified 
as prior only.  
• If a medication starts before the date of first dose of study medication and stops on or after 
the date of first dose of study medication, then the medication will be classified as both 
prior and concomitant.  
• Medications will be classified as concomitant only if they have a start date on or after the 
first dose of study medication.  
• If medication start and/or stop dates are missing or partial, the dates will be imputed (section 
4.4.3.2).  
o Medications will be assumed to be concomitant only, unless there is clear evidence 
(through comparison of partial dates) to suggest that the medication started prior to 
the single dose of study medication.  
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o If there is clear evidence to suggest that the medication started prior to the single 
dose of study medication, the medication will be assumed to be both prior and 
concomitant, unless there is clear evidence to suggest that the medication stopped 
prior to the single dose of study medication. 
o If there is clear evidence to suggest that the medication stopped prior to the single 
dose of study medication, the medication will be assumed to be prior only. 
3.5.1.2.6 Incidental Gluten Exposure 
Assessment (date and source) of any incidental gluten exposure will be captured at all study 
visits.  
3.5.1.2.7 Medications for Infusion Reactions  
Details of medications to treat infusion reactions will be collected at all study visits.  
3.5.1.2.8 Study Drug Administration 
Weight of the IV bag/line, dates and times will be captured for each infusion of the study drug. 
Study drug infusion details will also include whether the infusion was interrupted or re-started 
along with the reasons for the interruption (for more administration instructions refer KAN-
101-01 Pharmacy Manual). 
3.5.2 Pharmacokinetic Assessments 
For the secondary endpoint, blood samples will be collected for measurement of KAN-101, as 
specified in Appendix 6.1 Table 8 (Part A) and Table 9 (Part B). The timing of sampling may 
be altered based on the emerging PK data, and appropriately documented in database. PK 
concentrations data along with dosing data will be used to determine the PK parameters.  
PK parameters will be calculated relative to start of the infusion (approximate duration 30 
minutes), hence nominal time will be calculated in hours relative to start of infusion (in ADPC) 
for PK parameter summarization and determination of deviations from actual time of sample 
collection, e.g. end of infusion sample, 0 (+2) min, will be considered 0.5 h sample, 7 (±2) min 
will be considered 0.62 h sample etc.  
For Part A, PK parameters as outlined in Table 1 will be determined for KAN-101 following 
single dose administration.  
For Part B, PK parameters as outlined in Table 2 will be determined for KAN-101 following 
multiple dose administration. 
For non-compartmental analysis, actual sampling times relative to dosing rather than nominal 
times will be used in the calculation of all derived pharmacokinetic parameters, except when 
parameters are calculated for safety/dose escalation meetings when nominal times may be used 
to calculate PK parameters. 
Table 1: Pharmacokinetic Parameters after Single Dose Administration (Part A) and 
after First Dose Administration (Part B) 
Parameter 
Definition 
Method of Determination 
Cmax  
Maximum observed plasma 
concentration 
Obtained directly from the concentration-time data 
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Parameter 
Definition 
Method of Determination 
DNCmax 
Dose-normalized Cmax 
Obtained by dividing Cmax by total dose administered in mg 
(scheduled dose will be used e.g. if dose level is 0.3 mg/kg 
and is subject weight is 50 kg, then dose administered will 
be 15 mg, DNCmax will be Cmax divided by 15. 
tmax  
Time to first occurrence of 
Cmax 
Obtained directly from the concentration-time data 
λz 
Terminal elimination rate 
constant 
Terminal phase rate constant calculated by linear regression 
of the log-linear concentration-time curve. Only those data 
points judged to describe the terminal log-linear decline will 
be used in the regression.  
• 
A minimum number of three data points in the terminal 
phase will be used in calculating λz with the line of 
regression starting at any post-Cmax data point (Cmax 
should not be part of the regression slope) and including 
Clast, tlast. 
• 
The adjusted correlation coefficient (R2 adjusted) in 
general should be greater than 0.90. Any value less than 
0.90 may be used at the PK Scientist’s best knowledge 
and judgment. 
• 
An appropriate number of decimal places should be used 
for λz to enable the reported value of t½ to be calculated. 
t1/2  
Terminal elimination half-
life 
Loge(2)/ λz 
AUC0-t 
AUC from time zero to the 
last quantifiable 
concentration 
The linear-log trapezoidal method will be employed to 
calculate AUCs. The linear method will be used for all 
incremental trapezoids arising from increasing 
concentrations and the logarithmic trapezoidal method will 
be used for those arising from decreasing concentrations.  
AUC0-t=
 t
0
dt
t
C
)
(
. 
DNAUC0-t 
Dose normalized AUC0-t 
Obtained by dividing AUC0-t by total dose administered in 
mg (scheduled dose will be used e.g. if dose level is 0.3 
mg/kg and is subject weight is 50 kg, then dose 
administered will be 15 mg, DNAUC0-t will be AUC0-t 
divided by 15. 
AUC0-inf 
AUC from time zero 
extrapolated to infinity 
AUC0-inf =
 t
0
dt
t
C
)
(
＋

t
dt
t
C
)
(
= AUC0-t＋Clast/λz , 
where Clast is last observed quantifiable concentration. 
DNAUC0-inf 
Dose normalized AUC0-inf 
Obtained by dividing AUC0-inf by total dose administered 
in mg (scheduled dose will be used e.g. if dose level is 0.3 
mg/kg and is subject weight is 50 kg, then dose 
administered will be 15 mg, DNAUC0-inf will be AUC0-inf 
divided by 15. 
%AUCex 
Percentage of AUC(0-inf) 
obtained by extrapolation 
(1－[AUC0-t/AUC0-inf])×100 
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Parameter 
Definition 
Method of Determination 
CL 
Clearance following 
intravenous administration 
dose/AUC0-inf 
Vz 
Volume of distribution 
during terminal phase 
CL/F/λz 
Table 2: Pharmacokinetic Parameters on Day 7 after Multiple Dose Administration (Part 
B) 
Parameter 
Definition 
Method of Determination 
Cmax 
Maximum observed 
concentration  
Obtained directly from the concentration-time data 
DNCmax 
Dose normalized Cmax 
Obtained by dividing Cmax by total dose administered in 
mg (scheduled dose will be used e.g. if dose level is 0.3 
mg/kg and is subject weight is 50 kg, then dose 
administered will be 15 mg, DNCmax will be Cmax divided 
by 15. 
Cmin 
Minimum observed 
concentration  
Obtained directly from the concentration-time data 
tmax 
Time corresponding to 
occurrence of Cmax  
Obtained directly from the concentration-time data 
λz  
Terminal elimination rate 
constant  
Terminal phase rate constant calculated by linear 
regression of the log-linear concentration-time curve. 
Only those data points judged to describe the terminal log-
linear decline will be used in the regression.  
A minimum number of three data points in the terminal 
phase will be used in calculating λz  with the line of 
regression starting at any post- Cmax data point (Cmax 
should not be part of the regression slope) and include 
Clast, tlast.  
The adjusted correlation coefficient (R2 adj) in general 
should be greater than 0.90. Any value less than 0.90 may 
be used at the PK Scientist’s best knowledge and 
judgment.  
An appropriate number of decimal places should be used 
for λz to enable the reported value of t½ to be calculated. 
t½ 
 Terminal elimination half-
life  
Loge(2)/ λz 
AUC0-t 
AUC from time zero to the 
last quantifiable 
concentration 
The linear-log trapezoidal method will be employed to 
calculate AUCs. The linear method will be used for all 
incremental trapezoids arising from increasing 
concentrations and the logarithmic trapezoidal method 
will be used for those arising from decreasing 
concentrations.  
AUC0-t=
 t
0
dt
t
C
)
(
. 
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
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3.5.5.5 GC (Part B only) Administration 
Dates and times will be captured for GC administration on D15, D16, and D17. Patient 
compliance will be recorded by the study Investigator.  
4 
STATISTICAL METHODS 
The following treatment groups will be considered for reporting for each part, except for PK 
reporting: 
Part A (SAD) 
• KAN-101 0.15 mg/kg 
• KAN-101 0.30 mg/kg 
• KAN-101 0.60 mg/kg 
• KAN-101 1.20 mg/kg 
• KAN-101 1.5 mg/kg 
• Pooled KAN-101 
Part B (MAD) 
• Pooled Placebo 
• KAN-101 0.15 mg/kg 
• KAN-101 0.30 mg/kg 
• KAN-101 0.60 mg/kg 
• Pooled KAN-101 
All summary tables will be presented for Part A and Part B separately (unless otherwise 
specified). Also, summary tables will be presented for Part A and Part B combined for the same 
dose level treatment group for the following: 
• PK data: PK concentrations and parameters for Day 1 in 0.15, 0.30, and 0.60 mg/kg 
dose levels will be summarized using descriptive statistics  
• Disposition, analysis population, demographics, baseline celiac disease, ADA, and 
Treatment-Emergent Serious Adverse Events (TESAEs). 
Listings will be presented for subjects from Part A and Part B to display the collected data of 
clinical and statistical importance. All by-subject listings will include part, treatment group, 
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center, and subject ID for enrolled subjects. All TLFs will be analyzed by dose level received 
and not by cohort number. 
The principal of ‘As Treated’ (as dose level received) will be applied to the subject treatment 
data. If there are randomization or cohort assignment errors they will still be analyzed in the 
treatment group of the dose level they received. If the actual dose level received is unknown 
then the subject will be analyzed under the planned dose level, however for PK TFLs, the 
concentrations and parameters from such subject/s will be listed  and flagged in the Listings, 
but excluded from summary tables and statistical analysis, since these are not 
pharmacokinetically meaningful if the dose is unknown.   
4.1 
Data Quality Assurance 
All TLFs data to be included in the report will be independently checked for consistency, 
integrity and in accordance with standard Parexel procedures. Datasets will be prepared using 
headings from Clinical Data Interchange Consortium (CDISC) Study Data Tabulation Model 
(SDTM) implementation for human clinical trials and Analysis Dataset Model. 
4.2 
Changes in the SAP Compared to the Study Protocol 
No changes. 
4.3 
General Presentation Considerations and Descriptive Statistics 
No formal statistical hypotheses or inferential statistics will be performed in this study. For 
Part A and Part B, summary statistics and listings will be provided by dose. 
All by-visit summaries will be based on the nominal day/time per Appendix 6.1 Table 8 (Part 
A) and Table 9 (Part B) as recorded on the eCRF. 
Study day will be calculated relative to the date of first dose, ‘Study Day’ = Assessment Date 
– First Dose Date + 1. 
4.3.1 Non-PK Tables, Listings and Figures 
• ‘Baseline’ is defined as the last available pre-treatment assessment, including any 
unscheduled assessment. Every effort will be made to ensure that accurate baseline 
information is collected. Subjects will not be excluded from any of the analysis populations 
due to missing baseline. However, if a subject is missing baseline information, they will 
have a missing change from baseline result. 
• Continuous data will be summarized in terms of the number of observations (n), mean 
(arithmetic), standard deviation (SD), median, and range (minimum and maximum), unless 
otherwise stated.  
• The minimum and maximum will be reported to the same number of decimal places as the 
raw data recorded in the database.  The mean and median will be reported to one more 
decimal place than the raw data recorded in the database.  The SD will be reported to two 
more decimal places than the raw data recorded in the database.  In general, the maximum 
number of decimal places reported shall be four for any summary statistic. 
• Categorical data will be summarized in terms of the number of subjects providing data at 
the relevant time point (n), frequency counts and percentages.  
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• Percentages will be rounded to the nearest one decimal place. Percentages will not be 
presented for zero counts.  Percentages will generally be calculated using the number of 
subjects in a group (n) as the denominator, otherwise the method will be noted in a footnote.  
• Unscheduled and early termination visits may not be summarized in the tables but will be 
presented in the listings.  
4.3.2 PK Tables, Listings and Figures 
The following rules will be followed with regards to the number of decimal places and 
presentation of data in the tables and listings for PK concentration data:  
• 
Source data shall be used in all derived PK concentrations without prior rounding.  
• 
The mean, SD, geometric mean and median will be tabulated to same significant digit 
compared to the source data, but with a maximum of four significant digits.  
• 
Minimum and maximum values will be tabulated to the same precision as the source data, 
but with a maximum of four significant digits.  
• 
Geometric coefficient of variation (geometric CV%) and arithmetic coefficient of variation 
(CV%) will be presented to one decimal place.  
The following rules will be followed with regards to the number of decimal places and 
presentation of data in the tables and listings for PK parameters:  
• 
Individual PK parameters will be presented to three significant digits, with the exception 
of tmax, which will be presented to three decimal places.  
• 
Parameters derived directly from source data (e.g. Cmax) shall be reported with the same 
precision as the source data (if this is not four significant digits).  
• 
The mean, geometric mean, median and SD values will be reported to three significant 
digits, all other descriptive statistics will also be reported to three significant digits except 
for CV% and geometric CV% which will be presented to one decimal place.  
• 
For tmax, the minimum and maximum will be presented to three decimals places and all 
other descriptive statistics will be presented to three decimal places.  
• 
Estimates and confidence intervals in the form of percentages will be presented to two 
decimal places.  
4.4 
Analysis and Data Handling Conventions 
4.4.1 Multi-center Studies 
The term ‘Center’ will be used to define each investigator site. The data from all study centers 
(approximately 5 to 12 US sites) will be pooled together for analyses and summary statistics.  
4.4.2 Adjustments for Covariates 
No adjustments for covariates are planned for the study. 
4.4.3 Handling of Dropouts or Missing Data 
All missing or partial data will be presented in the patient data listing, as they are recorded on 
the eCRF. Patients lost to follow-up or withdrawn will be included in statistical analyses up to 
the point of their last evaluation.  
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4.4.3.1 Missing Start and Stop Dates/Time for Adverse Events 
Due diligence will be done to obtain accurate AE information. If all planned methods to obtain 
accurate time AE information have failed, missing and partial AE onset and end dates will be 
imputed. Imputed dates will be flagged in the individual supportive subject listings. Unless 
otherwise specified, the following conventions will be used: 
Missing and Partial AE onset dates: 
• If onset date is completely missing, then onset date is set to date of first dose. 
• If onset year is present and  
- month and day are missing: 
▪ If onset year = year of first dose, then set onset date to date of first dose. 
▪ If onset year < year of first dose, then set onset month and day to December 
31st. 
▪ If onset year > year of first dose, then set onset month and day to January 1st. 
- month is missing: 
▪ If onset year = year of first dose, then set onset date to date of first dose. 
▪ If onset year < year of first dose, then set onset month to December. 
▪ If onset year > year of first dose, then set onset month to January. 
• If onset month and year are present and day is missing: 
- If onset year = year of first dose and 
▪ onset month = month of first dose then set onset date to date of first dose. 
▪ onset month < month of first dose then set onset date to last day of month. 
▪ onset month > month of first dose then set onset date to 1st day of month. 
- If onset year < year of first dose, then set onset date to last day of month. 
- If onset year > year of first dose, then set onset date to 1st day of month. 
• For all other cases, set onset date to date of first dose. 
Missing and Partial AE end dates: 
• If end date is completely missing, end date is not imputed and the AE is flagged as 
“ongoing”. 
• If year is present and  
- month and day are missing: 
▪ If year = year of last dose, then set end date to the date of last dose. 
▪ If year < year of last dose, then set end month and day to December 31st. 
▪ If year > year of last dose, then set end month and day to January 1st. 
- month is missing: 
▪ If year = year of last dose, then set end date to date of last dose. 
▪ If year < year of last dose, then set end month to December. 
▪ If year > year of last dose, then set end month to January. 
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• If month and year are present and day is missing: 
- If year = year of last dose and 
▪ month = month of last dose then set day to day of last dose. 
▪ month < month of last dose then set day to last day of month. 
▪ month > month of last dose then set day to 1st day of month. 
- If year < year of last dose, then set end date to last day of the month. 
- If year > year of last dose, then set end date to 1st day of month. 
• For all other cases, set end date to date of last dose. 
• Screen failures are collected in EDC and will be a part of SDTM. Screen failure data 
are not analyzed and will not be included in the ADaM except for demographics 
(ADSL) and inclusion/exclusion criteria (ADIE).  
Any AEs with incomplete start and end dates/times will be treated as follows: 
• Adverse events with unknown start and/or end times (but where the date is known) will 
be imputed with a time of 00:00 h for the tabulations but will be shown as NK: NK in 
the listings (where NK = Not Known). 
4.4.3.2 Missing Start and Stop Dates for Prior and Concomitant Medication 
For the purpose of inclusion in prior and/or concomitant medication tables, incomplete 
medication starts and stop dates will be imputed as follows: 
• If year and month are present and day is missing, then set day to first day of month for 
start date and set day to last day of month for end date.  
• If year and day are present and month is missing, then set month to January for start 
date, and set month to December for end date.  
• If year is present and month and day are missing, then set month and day to January 1 
for start date and set month and day to December 31 for end date.  
• Completely missing date will not be imputed. 
The partial dates will be provided as such in the subject data listings (with the imputed dates). 
When imputing a start date, the programmer will ensure that the new imputed date is sensible 
i.e. it is before the end date of prior and concomitant medications. 
4.4.3.3 
 
 
4.4.4 Concentrations Below the Limit of Quantification (BLQ) 
For PK data, all concentrations that are BLQ will be labeled as “BLQ” in the concentration 
data listings (Footnote describing the BLQ value will be added to the listing).  
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
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For summary: For concentration summary tables and mean concentration time plots, all BLQs 
will be considered zero, and the number of BLQs and non-BLQs at each scheduled time point 
will be reported.  
For individual data: For non-compartmental PK analysis, all below the limit of quantification 
(BLQ) values pre-dose to the first dose, and prior to the first quantifiable concentration will be 
substituted by zeros. BLQ values between non-BLQ concentrations will be considered missing 
before the calculation of the PK variables. Terminal BLQ values will be considered missing. 
4.4.5 Adjustment for Multiplicity 
No formal multiple statistical analyses are planned.  Hence no adjustments for multiplicity are 
required. 
4.4.6 Interim Analyses 
No formal interim analyses are planned. 
4.4.7 Unblinding  
Part A is open-label. 
Part B is double-blinded, such that study personnel (e.g., Investigators, site coordinators) and 
patients are blinded to treatment assignments and will remain blinded throughout the study.  
Unblinded personnel include those involved in drug preparation and allocation (e.g., data 
systems support and pharmacists), and the study pharmacokineticist to allow for expedited 
review of PK data prior to SMC review.   
The data for dose escalation in Part B will be presented and reviewed by the SMC in a blinded 
fashion. If required SMC will be unblinded as per SMC Charter and Blinded Maintenance Plan 
for Part B.  
After completion of SMC review and once all patients in the cohort have completed the study, 
the sponsor study team members involved in biomarker data analysis may be unblinded to 
complete pharmacodynamic assessments as per Protocol section 4.4. 
4.4.8 Final Analysis   
The final analysis of the study data will be conducted once the last remaining patient has 
completed the study or is withdrawn from the study prior to completion, all data have been 
entered into the database, all data issues resolved, the protocol deviations have been addressed, 
and the database has been locked and released. 
4.5 
Software 
All report outputs (tables, figures and listings) will be produced using SAS® version 9.4 or a 
later version in a secure and validated environment [1].  
Non-compartmental PK analyses will be produced using Phoenix® WinNonLin (WNL) version 
[8.0] or a later version in a secure and validated environment [1]. 
All report outputs will be provided to the Sponsor in RTF and PDF format. Outputs will be 
printed in 8pt font size and Courier New font type. 
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• Agree on the assignment of each subject to the appropriate analysis sets of the study, if 
applicable. 
• Identify any major/minor protocol deviation to finalize the analyses set. 
Results and decisions made during the meeting will be summarized in BDRM minutes which 
will be signed off by Parexel representatives and the Sponsor.  
The PKAS is decided at the PK data review meeting if needed, which occurs after the unblinded 
PK concentration data is received. For final analysis, the PK TLFs will be generated on the PK 
dataset created after data unblinding for Part B.  
Parexel Protocol Deviation tool will be used to document the deviations.  
4.8 
Safety Evaluation 
All safety summaries and analyses will be on ATAS.  
4.8.1 Adverse Events 
For Part A (SAD) and Part B (MAD) separately, the following AE summaries will be provided 
for the number of subjects reporting at least one AE by treatment group using the ATAS:  
• An overall summary of TEAE will include the number of subjects with any TEAEs, drug-
related TEAEs, ≥ Grade 3 TEAEs, TESAEs,  TEAEs leading to discontinuation (treatment 
and study); 
• Before and after GC, overall summary of TEAE will include the number of subjects with 
any TEAEs, drug-related TEAEs, ≥ Grade 3 TEAEs, treatment-emergent serious AEs 
(TESAEs), TEAEs leading to discontinuation (treatment and study); (this table is for Part 
B only); 
• A summary of the number and percentage of subjects reporting a TEAE by system organ 
class (SOC) and PT; 
• 
A summary of the number and percentage of subjects reporting a TEAE by causality, SOC 
and PT; 
• 
A summary of the number and percentage of subjects reporting a TEAE by severity, SOC 
and PT. 
AE summaries will be ordered in terms of decreasing frequency for SOC, and PT within SOC, 
in the Total group, and then alphabetically for SOC, and PT within SOC.  
For each subject and each AE, the worst severity recorded will be attributed and used in the 
by-severity summaries. Similarly, the worst causality (most related to treatment) will be 
attributed and used in the by-causality summaries. 
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 32 of 52 
A summary of TESAE will be presented for Part A and B combined. 
For Part A and Part B, by-subject listings of AEs will be presented by study part and treatment 
group for the following listings: 
• All DLT events 
• All TEAEs 
• All SAEs 
• All TESAEs 
• TEAEs Leading to Study Discontinuation  
• TEAEs Leading to Permanent Discontinuation of Study Drug 
The following information will be included in the listings: verbatim (reported term), PT, SOC, 
AE onset date (and time), AE end date (and time), AE duration, relationship to study drug, AE 
outcome, severity and SAE indicator flag.  If available, confirmed and suspected SARS-CoV-
2 infections and/or COVID-19 cases will be recorded in the AE eCRF and data will be 
presented. 
Pandemic related Impact of COVID-19 will be presented in listing, detailing the category of 
impact (example: Missed Visit, Missed Assessment, Early termination, Screen Failure, 
Adverse Event, Withdrawal of consent, Death, Replacement subject) based on data availability. 
4.8.2 Clinical Laboratory Evaluation 
For Part A (SAD) and Part B (MAD) separately, the following clinical laboratory summaries 
will be provided for serum chemistry, hematology, coagulation and urinalysis (specific gravity 
and pH only). 
• Continuous descriptive statistics of observed values and change from baseline by study 
visit; 
• Summary tables by reference range indicator; 
• Shift summary tables by reference range indicator 
Unscheduled and early termination visits may not be summarized in the tables but will be 
presented in the listings.  
The following by-subject laboratory listings (values and change from baseline if applicable) 
will be provided by study part and treatment group using the enrolled subjects:  
• Serum Chemistry 
• Hematology 
• Coagulation 
• Urinalysis 
• Virus Serology (screening only) 
• Serum and Urine Pregnancy test 
• HLA DQ2.5 and HLA DQ8 testing (screening only) 
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
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• Transglutaminase and deaminated gluten peptides IgA/IgG (screening only) 
• Lab abnormality experiencing ≥ Grade 3 in Severity. 
Toxicity, in reflection of safety laboratory results will be graded locally according to NCI-
CTCAE v5.0 or higher and included in listings. If any laboratory value falls above or below 
the upper or lower level of quantification, the value of the upper or lower level of quantification 
will be used. 
Protocol doesn’t require Urine micro analysis under the microscope for urinalysis, leukocyte 
count, erythrocyte count, epithelial cell count and bacterial count. So, these parameters will be 
shown in the listings only. 
There are tests with multiple standard units. “Standard-Unit” per test/subject will be taken into 
consideration in deriving the baseline. Post-baseline records will not have a ‘Change’ value if 
the unit doesn’t match with baseline record unit for that subject and test. 
4.8.3 Physical Examination, Vital Signs and ECG 
For Part A (SAD) and Part B (MAD) separately, categorical and continuous descriptive 
statistics of observed values and change from baseline will be presented for: 
• Each vital sign measurement by scheduled study visit and change from baseline. 
• Each physical examination measurement by scheduled study visit(Normal, Abnormal, Not 
done). 
• Each ECG measurement by scheduled study visit (Normal, Abnormal Non-Clinically 
Significant (ANCS), Abnormal Clinically Significant (ACS))  
The following by-subject listings will be provided by study part and treatment group on 
enrolled subjects: 
• Vital Signs (values and change from baseline) 
• Physical Examination (screening and as clinically indicated) 
• ECG 
4.8.4 Prior and Concomitant Medications and Procedures 
All prior and concomitant medications including dose, form, route of administration, frequency 
and indication will be provided in a by-subject listing for each study part and treatment group 
for prior and concomitant medications by ATC Levels and PT on enrolled subjects. 
For Part A (SAD) and Part B (MAD) separately, summary tables will be provided by treatment 
group for prior and concomitant medications by ATC Levels and PT on ATAS. 
4.8.5 Incidental Gluten Exposure 
A by-subject listing will be provided by study part and treatment group for any incidental gluten 
exposure (Yes/No) on enrolled subjects. Number of times the subjects is exposed to gluten 
within the study period will be calculated.   
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 34 of 52 
4.8.6 Medications for Infusion Reactions  
A by-subject listing will be provided by study part and treatment group for any medications to 
treat infusion reactions by ATC levels and PT on enrolled subjects. 
4.8.7 Study Drug Administration and Compliance   
A by-subject listing for study drug administration and compliance will be provided by study 
part and treatment group on enrolled subjects. 
4.8.8 Gluten Challenge Compliance 
Patient compliance with GC will be listed as well as number of GC completed (Part B only). 
For Part B (MAD), by-subject listings for the GC compliance will be provided on enrolled 
subjects. 
4.9 
Pharmacokinetics 
All pharmacokinetic summaries and analyses will be on PKAS. 
4.9.1 Pharmacokinetic Concentrations 
Plasma concentrations for KAN-101 will be summarized by treatment group, day of dose, and 
nominal protocol timepoint for PKAS in Part A (SAD) and Part B (MAD) separately, 
Additionally, PK concentrations for Day 1 in 0.15, 0.30, and 0.60 mg/kg dose levels in Part A 
and B will be combined to summarize by treatment group, day of dose, and nominal protocol 
timepoint using descriptive statistics.  
A by-subject listing for plasma concentration data for KAN-101-01, will be listed by study 
part, treatment group, subject, day and time of sampling for PKAS. Listings will include 
nominal and protocol time, actual sampling time relative to start and end of infusion, actual 
infusion duration, scheduled infusion duration (30 minutes) and difference between scheduled 
and actual infusion duration. 
Following will be presented for Part A and Part B: 
• Linear mean (+/- SD) plasma concentration-time profiles for KAN-101 by Day of dose 
(all doses on one plot)  
• Semilogarithmic mean (+/- SD) plasma concentration-time profiles for KAN-101by 
Day of dose (all doses on one plot) 
• Linear individual concentration-time combined profiles for KAN-101 by Day of dose 
(all subjects on same dose on one plot) 
• Semilogarithmic individual concentration-time combined profiles for KAN-101 by Day 
of dose (all subjects on same dose on one plot) 
• Linear individual concentration-time profiles for KAN-101 (separate plot for each 
subject) 
• Semilogarithmic individual concentration-time profiles for KAN-101 (separate plot for 
each subject) 
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 35 of 52 
4.9.2 Pharmacokinetic Parameters 
PK parameters for KAN-101 will be summarized by study part, treatment group and day of 
dose For Part A and Part B separately, using the PKAS.  
Additionally, Part A and B parameters will be pooled for the first (Day 1) dose for doses 
common in Parts A and B for summary tables and plots.  
• Descriptive statistics for calculated PK parameters will include n, arithmetic mean, SD, 
%CV, geometric mean, geometric CV% (calculated as: geometric CV% =SQRT(es²-
1)*100; where s is the standard deviation of the log-transformed values), median, minimum 
and maximum values.  
• For tmax, only median, minimum and maximum values will be presented.  
• 
λz or Lambdaz dependent PK parameters, i.e. λz, AUC0-inf, CL, Vz will not be summarized 
if r2adj is <0.90 , and/or span of the terminal phase is <1.3 times the half-life and/or the 
%extrapolation to calculate AUC0-inf is >30%, unless otherwise determined by the PK 
scientist. Such parameters will be flagged in parameters listing, and if flagged parameters 
are not used for calculation of descriptive summaries, it will be footnoted in the PK 
parameters listing.  
A by-subject listings for PK parameters and dose-normalized PK parameters for KAN-101-01 
will be listed by study part and treatment group, subject and day of dose using the PKAS.  
4.9.2.1 Assessment of Dose Proportionality 
No formal dose proportionality assessment will be performed. Informal assessment of dose 
proportionality will be done using Box plots for Cmax and AUCs and corresponding dose-
normalized parameters by Part A, Part B, and combined parts A and B for the common doses.  
4.10 Immunogenicity 
For Part A (SAD) and Part B (MAD) (separately and combined), immunogenicity summaries 
will be provided by treatment group on ATAS. Subjects with any ADA positive samples, 
screening (ADA status) and confirmatory assay (titer and ADA status) results will be included. 
The results for 3-Tiers will be displayed. If the sample is ADA-positive then the reactivity to 
the 
 will be included.  
A by-subject listing of immunogenicity will be provided by study part and treatment group on 
enrolled subjects. 
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 36 of 52 
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 37 of 52 
4.12 Disposition of Subjects and Screen Failures 
A clear accounting of the disposition of all subjects who enter the study will be provided, from 
screening to end of study participation. Number and percentage of subjects screened, 
enrolled/randomized, subjects completed treatment, subjects discontinued from the study and 
discontinuation reasons (including reasons for early withdrawal). 
For Part A and Part B (separately and combined), summary tables will be provided by treatment 
group for subject disposition on enrolled subjects.  
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 39 of 52 
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 40 of 52 
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 41 of 52 
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 42 of 52 
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 43 of 52 
5 
REFERENCES 
[1] SAS® Version 9.4 of the SAS System for Personal Computers. Copyright © 2002-2003. 
SAS Institute Inc. SAS and all other SAS Institute Inc. product or service names are 
registered trademarks or trademarks of SAS Institute Inc., Cary, NC, USA. 
[2] Phoenix®WinNonlin® Professional Software Version 8.0. https://www.certara.com 
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 45 of 52 
Assessment 
Screening 
Study Period 
Early 
Term. 
Study Day 
-28 
1 
4 (±1) 
8 
D21 
(±1) 
 
6. Vital signs (pulse rate, temperature, diastolic and systolic BP). 
7. On D1 patients will be observed in the clinic/hospital unit for 10 h after initiation of IV infusion and 
followed up with by phone approximately 24 hours after dosing. 
8. PK samples to be taken pre-dose (at least 5 min prior to infusion) and the following timepoints after the 
end of infusion: 0 (+2) min, 7 (±2) min, 15 (±2) min, 30 (±5) min, 1 h (±5) min), 2 h (±5 min), 3 h (±5 
min), 4 h (±5 min), 6 h (±5 min).  
Abbreviations: ADA = anti-drug antibodies; BP = blood pressure; CeD = celiac disease; Con Meds = 
concomitant medications; ECG = electrocardiogram; Early Term. = early termination; HBV = hepatitis B; 
HCV = hepatitis C; HIV = human immunodeficiency virus; HLA = Human Leukocyte Antigen; PK = 
pharmacokinetics; SAD = single ascending dose. 
 
 
 
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 47 of 52 
Assessments 
Screening 
Treatment 
Period 
PD Assessment 
Follow-
up1 
Early 
Term. 
Study Day 
-28 
1 
4 
7 
15 
21 
28 (±3) 
 
1. Phone call. 
2. ECG performed pre dose (at least 5 min before infusion), 20(±5) min after start of infusion, and 1 hour (±10 
min) post infusion.   
3. All patients will be assessed via central laboratory for HLA genotype and CeD serology (eg, tTG-IgA and 
DGP IgG) at screening to confirm eligibility. For rescreening, HLA does not need to be repeated and CeD 
serology only needs to be repeated if >3months have elapsed from last assessment. 
4. Includes weight and height at screening only. 
5. Pregnancy test at screening must be serum; serum or urine tests are acceptable predose on D1, D4, and D7. 
Pregnancy test must be negative before each dose of study drug is administered. 
6. Samples/Measurements taken pre-dose (at least 5 min prior to infusion). 
7. Vital signs (pulse rate, temperature, diastolic and systolic BP). 
8. The GC will consist of patients self-administering 9 g of gluten protein PO for each of 3 days (D15 to D17), 
with the first administration in the clinic on D15. GC should be administered at approximately the same 
time each day. 
9. 
 
 
 
10. On D1 patients will be observed in-clinic for 10 h from the start of IV infusion and followed up with by 
phone approximately 24 hours after dosing; on D4 and D7 (dosing days) patients will be observed for 4 h 
in clinic from the start of IV infusion. 
11. PK samples to be taken at pre-dose (at least 5 min prior to infusion) and the following timepoints after the 
end of infusion: 0 (+2) min, 7 (±2) min, 15 (±2) min, 30 (±5) min, 1 h (±5 min), 2 h (±5 min), 3 h (±5 min), 
4 h (±5 min), 6 h (±5 min). 
12. PK samples to be taken at pre-dose (at least 5 min prior to infusion) and the following timepoints after the 
end of infusion :0 (+2) min, 7 (±2) min, 15 (±2) min, 30 (±5) min, 1 h (±5 min), 2 h (±5 min), and 4 h (±5 
min). 
13. 
 
 
14. 
 
15. Collected prior to oral gluten challenge. 
Abbreviations: ADA = anti-drug antibodies; BP = blood pressure; 
 CeD 
= celiac disease; Con Meds = concomitant medications; Early Term = early termination; ECG = 
electrocardiogram; 
 GC = gluten challenge; HBV = hepatitis 
B; HCV = hepatitis C; HIV = human immunodeficiency virus; HLA = Human Leukocyte Antigen; IV = 
intravenous; MAD = multiple ascending dose; 
 PBO = placebo; PD 
= pharmacodynamics; PK = pharmacokinetics; 
 
 
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 48 of 52 
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 49 of 52 
 
 
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 50 of 52 
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 51 of 52 
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KAN-101-01                                                                                                                       Statistical Analysis Plan 
                        CONFIDENTIAL                              Project Document Version No. 3.0 
Effective Date:  26 Nov 19                                             Project Document Effective Date: Date of last signature 
                                                                                                         Page 52 of 52 
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