Clinical trial NCT03169894
Conditions: Crohn Disease Ulcerative Colitis
Sponsor: Avalo Therapeutics, Inc.
Start date: 2017-07-14; Completion date: 2021-10-12
Enrollment: 8 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a Phase 1b, open-label, dose-escalation, signal-finding, multi-center study. The study will evaluate the safety, tolerability, pharmacokinetics and short-term efficacy of MDGN-002 in adults with moderate to severe, active Crohn's disease or Ulcerative Colitis who have previously failed anti-tumor necrosis factor alpha (anti-TNFα) treatment.

Detailed description:

Arms: arm 1: MDGN-002 will be supplied in vials of 150 mg/mL. MDGN-002 will be administered by SQ injection in the abdomen every 14 days at 1 of 2 dose levels: 1.0 mg/kg or 3.0 mg/kg.
Interventions: intervention 1: MDGN-002
Intervention descriptions: intervention 1: MDGN-002 is a fully human IgG4 monoclonal antibody specific to human LIGHT.

Protocol documents:
Prot_000.pdf: 
NCT Number: NCT03169894






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3. 
REASON FOR AMENDMENT AND SUMMARY OF CHANGES 
The protocol was amended to clarify study procedures and conduct detail. Substantive changes 
include: 
• Revised the study title to reflect the expansion of the study population to include subjects 
with Ulcerative Colitis (UC) who have failed prior treatment with an anti-TNFα agent.  
• Increased the sample size to 14, adding 6 subjects with UC to the 3 mg/kg cohort. 
• Clarified that prior documentation of histological confirmation is acceptable.   
• Revised the exclusion criteria pertaining to a positive test for C. difficile infection to 
clarify that this would be exclusionary if this was reported despite an adequate course of 
treatment.  
• Revised the exclusion criteria pertaining to prior treatment with natalizumab (TysabriÒ, 
Biogen) to include a timeframe of within 5 years of Visit 1.  
• Added a new section of Inclusion and Exclusion Criteria for subjects with UC  
• Added background information on Inflammatory Bowel Disease (IBD) and UC.  
• Revised the saliva sample for genotyping to apply only to Crohn’s disease (CD) subjects. 
• Removed the reference to -14 weeks as the maximum screening period, and added that 
extensions of the screening window are allowed with approval of the medical monitor.  
• Clarified that the diary must be completed for a minimum of 7 days prior to Visit 2 and 
that Visit 2 should be scheduled >7 days (e.g., Day 8) after the initiation of the diary.  
• Revised the CDAI assessment to be collected for CD patients only. 
• Added the Modified Mayo Score for UC patients only.  
• Clarified that the washout period is the time between when the subject received their last 
dose of biologic and when they can proceed to Visit 2.  
• Added stool frequency and rectal bleeding as the information that will be captured in the 
daily diary for UC patients.  
• Added that a stable dose of 5-aminosalicylic acid (5-ASA) is allowed if taken for at least 
2 weeks prior to Visit 1. 
• Added that concomitant use of ustekinumab (Stelaraâ, Jannsen) and vedalizumab 
(Entyvioä, Takeda) is prohibited.  
• Added that treatment with tofacitinib (Xeljanzâ, Biogen) within 2 weeeks prior to Visit 1 
is exclusionary. 
• Added that use of an investigational medicine (non-biologic) within 2 weeks of Visit 1 
and/or an investigational medicine that is a biologic within 8 weeks of Visit 1 is 
exclusionary. 
• Added the definitions of primary and secondary non-responders for patients with UC.  
• Removed references to sites in Israel and Colombia.  


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• Revised statistical analyses to include UC efficacy endpoints.  
• Removed reference to an ex-US diary. 
• Updated the list of references. 
• Updated the study timelines. 
• Updated the list of abbreviations. 
 




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The total duration of participation is approximately 26 weeks. Subjects will be required to visit the 
study center up to 12 times inclusive of 1 additional follow-up safety visit. During the study, subjects 
will participate in safety and efficacy assessments as well as pharmacokinetic blood sampling; DcR3 
genotyping (CD only); measurement of LIGHT (Lymphotoxin-like, exhibits Inducible expression, 
and competes with Herpes Virus Glycoprotein D for Herpesvirus Entry Mediator, a receptor 
expressed by T lymphocytes), selected cytokines; ribonucleic acid (RNA) sequencing; flow 
cytometry of peripheral blood leukocytes; and quality of life assessment. Subjects currently receiving 
treatment with biologic therapies will be required to participate in a wash-out period, during which 
biologic treatment will be discontinued. 
Number of patients (planned):  
Approximately 14 total subjects will be enrolled as follows: 
• 
4 subjects with CD in the 1 mg/kg cohort 
• 
4 subjects with CD in the 3 mg/kg cohort 
• 
6 subjects with UC in the 3 mg/kg cohort 
Diagnosis and main criteria for inclusion:  
Inclusion criteria - Crohn’s Disease: 
1. Subject is able to speak English fluently and has provided written informed consent for this 
study. 
2. Subject is male or female, ≥18 to £75 years of age. 
3. Subject has a documented diagnosis of CD via endoscopy/colonoscopy and histological 
confirmation. Prior documentation of histological confirmation is acceptable.   
4. Subject has moderate to severe, active CD as evidenced by Simple Endoscopy Score for 
Crohn’s Disease (SES-CD) score of ³7.  
5. Subject has failed treatment with an approved therapeutic dose of an anti-TNFα monoclonal 
antibody treatment with either no initial response (primary non-responder) or an initial 
response to induction with subsequent lost response (secondary non-responder) as defined in 
the protocol.   
6. Subject can be receiving concurrent treatment with an oral corticosteroid, and/or azathioprine 
or 6-mercaptopurine (6-MP) or methotrexate (MTX) as defined in the protocol. 
7.  
8. Subject agrees to be genotyped at the DcR3 locus.  
Exclusion criteria - Crohn’s Disease: 
1. Subject has a diagnosis of ulcerative colitis (UC) or indeterminate colitis. 
2. Subject is unable to tolerate or unwilling to undergo study procedures including endoscopy 
and biopsy during the study. 
3. Subject with signs or symptoms of bowel obstruction with small bowel imaging supporting 
obstruction. 
4. Subject has short bowel syndrome as determined by the investigator. 
5. Subject has a current functional colostomy or ileostomy.  
6. Subject has had a surgical bowel resection within the past 6 months prior to screening or is 
planning any resection during the study period. 
7. Clinical suspicion of intra-abdominal abscesses exists, in the opinion of the investigator. 
8. Subject has concurrent bowel dysplasia or a history of bowel dysplasia in the 5 years prior to 
screening. 


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9. Subject has a known, active and/or positive test for C. difficile infection despite an adequate 
course of treatment.  
10. Subject has history of or current diagnosis of any cancer excluding cancers that have been 
cured by surgical excision (e.g., non melanoma skin cancers). 
11. Subject has a history of a lymphoproliferative disorder, including lymphoma, or signs and 
symptoms suggestive of lymphoproliferative disease at any time. 
12. Subject has history of or active tuberculosis (TB) infection or positive TB testing at 
screening.  
13. Subject has known concurrent viral hepatitis, or acquired immune deficiency syndrome 
(AIDS) or known human immunodeficiency virus (HIV) infection. 
14. Subject has been treated with natalizumab (TysabriÒ, Biogen) within the past 5 years. 
15. Subject who has not completed his/her primary vaccination series (particularly hepatitis B, 
varicella, measles/mumps/rubella) unless immunity is documented with blood titers. 
16. Subject has received any live attenuated vaccine, such as varicella-zoster, oral polio, or 
rubella, within 3 months prior to the baseline visit.   
17. Subject has any of the following abnormal screening laboratory test results:  
a. Clinically significant electrocardiographic (ECG) abnormalities; 
b. Aspartate transaminase (AST), alanine transaminase (ALT) or total bilirubin > ULN; 
c. Hemoglobin < 10g/dL 
d. Absolute neutrophil count < 1500 cell/mm3, or 
e. Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. 
18. Subject has abnormal vital signs during Screening (Visit 1) or prior to enrollment at the 
baseline visit (Visit 2), as defined in the protocol. 
19. Subject is pregnant or a nursing mother. 
20. Subject is sexually active and not using effective contraception as defined in the protocol. 
21. Subject has a history of drug abuse that would inhibit participation in the clinical trial. 
22. Subject has a current or recent history (within 6 months prior to screening) of significant and 
severe renal, hepatic, hematological, gastrointestinal (other than CD or conditions outlined 
above), endocrine, pulmonary, cardiac, or neurological disease.  
23. Subject has any other clinically significant mental or physical illness or infection that, in the 
opinion of the investigator, might confound the results of the study, pose additional risk to the 
subject by their participation, or prevent or impede the subject from completing the study. 
24. There is any concern on the part of the investigator regarding the subject’s safety, 
compliance, or suitability with respect to his/her participation in the study. 
Inclusion criteria - Ulcerative Colitis: 
1. Subject is able to speak English fluently and has provided written informed consent for this 
study. 
2. Subject is male or female, ≥18 to £75 years of age. 
3. Subject has received a diagnosis of UC for 90 days or greater prior to Visit 1, confirmed by 
endoscopy during the Screening Period, with exclusion of current infection, dysplasia and/or 
malignancy. Appropriate documentation of biopsy results consistent with the diagnosis of 
UC, in the opinion of the Investigator, must be available. 


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4. Subject has moderately to severely active UC, as defined by a Modified Mayo Score 
(excluding the PGA component) of 5 to 9 points at Visit 1.   
5. Subject has a Modified Mayo Endoscopic Score of ≥2 at Visit 1 as confirmed by central 
reader.  
6. Subject has a Modified Mayo Rectal Bleeding Score of ≥1 at Visit 1. 
7. Subject has failed treatment with an approved therapeutic dose of an anti-TNFα monoclonal 
antibody treatment with either no initial response (primary non-responder) or an initial 
response to induction with subsequent lost response (secondary non-responder) as defined in 
the protocol.   
8. Subject can be receiving concurrent treatment with an oral corticosteroid, and/or azathioprine 
or 6-mercaptopurine (6-MP) or methotrexate (MTX) as defined in the protocol. 
9. Subject who is currently taking 5-aminosalicylic acid (5-ASA) has been on a stable dose for 
at least 2 weeks prior to Visit 1. 
Exclusion criteria - Ulcerative Colitis: 
1. Subject has a diagnosis of CD or indeterminate colitis. 
2. Subject is unable to tolerate or unwilling to undergo study procedures including endoscopy 
and biopsy during the study. 
3. Subject with signs or symptoms of bowel obstruction with small bowel imaging supporting 
obstruction. 
4. Subject has short bowel syndrome as determined by the investigator. 
5. Subject has a current functional colostomy or ileostomy.  
6. Subject has had a surgical bowel resection within the past 6 months prior to screening or is 
planning any resection during the study period. 
7. Clinical suspicion of intra-abdominal abscesses exists, in the opinion of the investigator. 
8. Subject has concurrent bowel dysplasia or a history of bowel dysplasia in the 5 years prior to 
screening. 
9. Subject has a known, active and/or positive test for C. difficile infection despite an adequate 
course of treatment.  
10. Subject has history of or current diagnosis of any cancer excluding cancers that have been 
cured by surgical excision (e.g., non melanoma skin cancers, cervical cancer). 
11. Subject has a history of a lymphoproliferative disorder, including lymphoma, or signs and 
symptoms suggestive of lymphoproliferative disease at any time. 
12. Subject has history of or active tuberculosis (TB) infection or positive TB testing at 
screening.  
13. Subject has known concurrent viral hepatitis, or acquired immune deficiency syndrome 
(AIDS) or known human immunodeficiency virus (HIV) infection. 
14. Subject has been treated with natalizumab (TysabriÒ) within 5 years of Visit 1. 
15. Subject who has not completed his/her primary vaccination series (particularly hepatitis B, 
varicella, measles/mumps/rubella) unless immunity is documented with blood titers. 
16. Subject has received any live attenuated vaccine, such as varicella-zoster, oral polio, or 
rubella, within 3 months prior to the baseline visit.   
17. Subject has received an investigational medicine (non-biologic) within 2 weeks of Visit 1 
and/or an investigational medicine that is a biologic within 8 weeks of Visit 1. 


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18. Subject has any of the following abnormal screening laboratory test results:  
a. Clinically significant electrocardiographic (ECG) abnormalities; 
b. Aspartate transaminase (AST), alanine transaminase (ALT) or total bilirubin > ULN; 
c. Hemoglobin < 10g/dL 
d. Absolute neutrophil count < 1500 cell/mm3, or 
e. Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. 
19. Subject has abnormal vital signs during Screening (Visit 1) or prior to enrollment at the 
baseline visit (Visit 2), as defined in the protocol. 
20. Subject is pregnant or a nursing mother. 
21. Subject is sexually active and not using effective contraception as defined in the protocol. 
22. Subject has a history of drug abuse that would inhibit participation in the clinical trial. 
23. Subject has a current or recent history (within 6 months prior to screening) of significant and 
severe renal, hepatic, hematological, gastrointestinal (other than UC or conditions outlined 
above), endocrine, pulmonary, cardiac, or neurological disease.  
24. Subject has any other clinically significant mental or physical illness or infection that, in the 
opinion of the investigator, might confound the results of the study, pose additional risk to the 
subject by their participation, or prevent or impede the subject from completing the study. 
25. There is any concern on the part of the investigator regarding the subject’s safety, 
compliance, or suitability with respect to his/her participation in the study. 
Investigational product, dosage, and mode of administration:  
MDGN-002 will be supplied in vials of 150 mg/mL.  MDGN-002 will be administered by SQ 
injection in the abdomen in a zone of 4 to 10 cm from the umbilicus with the injection site rotated 
with each subsequent dose. The dose MDGN-002 will be administered every 14 days at 1 of 2 dose 
levels: 1.0 mg/kg or 3.0 mg/kg. 
Duration of treatment:  
Duration of treatment will be approximately 56 days 
Reference therapy, dosage and mode of administration:  
None 
Criteria for evaluation: 
Safety: Adverse events, clinical laboratory, and urinalysis tests, vital signs, ECGs, and physical 
examinations  
Pharmacokinetics: Sparse pharmacokinetic blood sampling  
Efficacy:  SES-CD, abdominal pain assessment, loose/watery stool frequency assessment, Modified 
Mayo Score (excluding the PGA component), stool frequency and rectal bleeding assessment, and 
CDAI (CD only)  


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Statistical methods: 
This is the first use of MDGN-002 in patients with CD or UC who have failed treatment with anti-
TNFα monoclonal antibodies. The sample size of the study is based on feasibility and not on formal 
hypothesis testing. 
Descriptive statistics will be used to summarize all safety, pharmacokinetic, efficacy, and quality of 
life variables.  Continuous variables will be summarized using N, mean and/or median, standard 
deviation, and range.  Categorical variables will be summarized using frequencies and percentages. 
Detailed descriptions of data summaries and listings will be provided in the Statistical Analysis Plan. 
 


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5. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
ABBREVIATIONS 
TABLE OF CONTENTS 
1. 
APPROVAL SIGNATURES ....................................................................................... 2 
2. 
EMERGENCY CONTACT INFORMATION ............................................................ 3 
3. 
REASON FOR AMENDMENT AND SUMMARY OF CHANGES ......................... 4 
4. 
SYNOPSIS ................................................................................................................... 6 
5. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
ABBREVIATIONS .................................................................................................... 12 
6. 
INTRODUCTION ...................................................................................................... 21 
6.1. 
Inflammatory Bowel Disease ..................................................................................... 21 
6.1.1. 
Pediatric-Onset Crohn’s Disease ................................................................................ 21 
6.1.2. 
Ulcerative Colitis ........................................................................................................ 21 
6.2. 
MDGN-002 ................................................................................................................ 22 
6.2.1. 
Description and Mechanism of Action ....................................................................... 22 
6.2.2. 
Non-Clinical Data ....................................................................................................... 22 
6.2.3. 
Clinical Data ............................................................................................................... 23 
6.3. 
Rationale for Present Study ........................................................................................ 24 
7. 
STUDY OBJECTIVES AND PURPOSE .................................................................. 25 
7.1. 
Primary Objective ....................................................................................................... 25 
7.2. 
Secondary Objectives ................................................................................................. 25 
8. 
INVESTIGATIONAL PLAN .................................................................................... 26 
8.1. 
Overall Study Design ................................................................................................. 26 
8.2. 
Study Periods .............................................................................................................. 31 
8.2.1. 
Screening Period ......................................................................................................... 31 
8.2.2. 
Open-label Treatment Period ..................................................................................... 32 
8.2.3. 
Safety Follow-up Visit ............................................................................................... 32 
8.3. 
Safety Data Review .................................................................................................... 32 
8.4. 
Data Monitoring Committee ...................................................................................... 33 
8.5. 
Individual Subject and Study Stopping Criteria ......................................................... 34 
8.5.1. 
Individual Subject Stopping Criteria .......................................................................... 34 
8.5.2. 
Study Stopping Criteria .............................................................................................. 34 
8.6. 
Study Design Rationale .............................................................................................. 35 


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8.7. 
Number of Subjects .................................................................................................... 35 
8.8. 
Treatment Assignment ............................................................................................... 36 
8.9. 
Criteria for Study Termination ................................................................................... 36 
9. 
SELECTION AND WITHDRAWAL OF SUBJECTS ............................................. 37 
9.1. 
Subject Inclusion Criteria – Crohn’s Disease ............................................................. 37 
9.2. 
Subject Exclusion Criteria – Crohn’s Disease ........................................................... 37 
9.3. 
Subject Inclusion Criteria – Ulcerative Colitis ........................................................... 39 
9.4. 
Subject Exclusion Criteria – Ulcerative Colitis ......................................................... 39 
9.5. 
Screen Failure ............................................................................................................. 41 
9.6. 
Subject Withdrawal Criteria ....................................................................................... 41 
10. 
TREATMENT OF SUBJECTS ................................................................................. 42 
10.1. 
Description of Investigational Product ....................................................................... 42 
10.2. 
Permitted and Prohibited Therapies ........................................................................... 42 
10.2.1. 
Permitted Therapies .................................................................................................... 42 
10.2.2. 
Prohibited Therapies ................................................................................................... 43 
10.2.3. 
Contraceptive Methods ............................................................................................... 43 
10.3. 
Treatment Compliance ............................................................................................... 44 
10.4. 
Randomization and Blinding ...................................................................................... 44 
10.5. 
Treatment after End of Study ..................................................................................... 44 
11. 
INVESTIGATIONAL PRODUCT MATERIALS AND MANAGEMENT ............. 45 
11.1. 
Investigational Product ............................................................................................... 45 
11.2. 
Packaging and Labeling ............................................................................................. 45 
11.2.1. 
Packaging ................................................................................................................... 45 
11.2.2. 
Labeling ...................................................................................................................... 45 
11.3. 
Storage ........................................................................................................................ 45 
11.4. 
Preparation .................................................................................................................. 46 
11.5. 
Administration ............................................................................................................ 46 
11.6. 
Accountability ............................................................................................................ 46 
11.7. 
Handling and Disposal ............................................................................................... 46 
12. 
STUDY PROCEDURES AND ASSESSMENTS ..................................................... 47 
12.1. 
Study Periods and Visits ............................................................................................ 47 
12.1.1. 
Screening (Visit 1) ...................................................................................................... 47 


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12.1.2. 
Eligibility Check/Wash-Out Period ............................................................................ 48 
12.1.3. 
Open-Label Treatment Period .................................................................................... 48 
12.1.3.1. 
Baseline Visit (Visit 2, Day 0) ................................................................................... 48 
12.1.4. 
Visit 3 (Day 7 [± 3 days]) ........................................................................................... 50 
12.1.5. 
Visit 4 (Day 14 [± 3 days]) ......................................................................................... 50 
12.1.5.1. 
Visit 5 (Day 21 [± 3 days]) ......................................................................................... 50 
12.1.5.2. 
Visit 6 (Day 28 [± 3 days]) ......................................................................................... 51 
12.1.5.3. 
Visit 7 (Day 35 [± 3 days]) ......................................................................................... 52 
12.1.5.4. 
Visit 8 (Day 42 [± 3 days]) ......................................................................................... 52 
12.1.5.5. 
Visit 9 (Day 49 [± 3 days]) ......................................................................................... 53 
12.1.5.6. 
Visit 10 (Day 56 [± 3 days]) ....................................................................................... 53 
12.1.6. 
Early Termination ....................................................................................................... 54 
12.1.7. 
Safety Follow-Up ....................................................................................................... 54 
12.1.7.1. 
Visit 11 (Day 84 [± 3 days]) ....................................................................................... 54 
12.2. 
Study Duration ........................................................................................................... 54 
12.3. 
Assessments ............................................................................................................... 54 
12.3.1. 
Safety Assessments .................................................................................................... 54 
12.3.1.1. 
Demographic/Medical History ................................................................................... 55 
12.3.1.2. 
Vital Signs .................................................................................................................. 55 
12.3.1.3. 
Physical Examination ................................................................................................. 56 
12.3.1.4. 
Electrocardiogram ...................................................................................................... 57 
12.3.1.5. 
Clinical Laboratory Assessments ............................................................................... 57 
12.3.1.6. 
Adverse Events ........................................................................................................... 61 
12.3.2. 
MDGN-002 Concentration, Pharmacokinetic and Anti-Drug Antibody 
Assessments ............................................................................................................... 67 
12.3.2.1. 
Blood Sample Collection and Analysis ...................................................................... 67 
12.3.3. 
Assessment of Efficacy .............................................................................................. 68 
12.3.3.1. 
Crohn’s Disease Activity Index ................................................................................. 68 
12.3.3.2. 
Modified Mayo Score ................................................................................................. 68 
12.3.3.3. 
Endoscopy with Biopsy and Histology ...................................................................... 69 
12.3.3.4. 
Patient-reported Assessment of Well-being, Abdominal Pain and Stool 
Frequency (Crohn’s Disease Patients) ....................................................................... 69 


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12.3.3.5. 
Patient-reported Assessment of Stool Frequency and Rectal Bleeding 
(Ulcerative Colitis Patients) ....................................................................................... 69 
12.3.4. 
Quality of Life Assessment – Inflammatory Bowel Disease Questionnaire .............. 69 
13. 
STATISTICS .............................................................................................................. 70 
13.1. 
Statistical Methods ..................................................................................................... 70 
13.1.1. 
Analysis Populations .................................................................................................. 70 
13.1.2. 
Statistical Analyses ..................................................................................................... 70 
13.2. 
Sample Size Determination ........................................................................................ 71 
14. 
STUDY CONDUCT .................................................................................................. 72 
14.1. 
Sponsor and Investigator Responsibilities ................................................................. 72 
14.1.1. 
Sponsor Responsibilities ............................................................................................ 72 
14.1.2. 
Investigator Responsibilities, Protocol Adherence and Investigator 
Agreement .................................................................................................................. 72 
14.2. 
Study Documents ....................................................................................................... 73 
14.2.1. 
Case Report Forms ..................................................................................................... 73 
14.2.2. 
Recording and Retention of Source Data and Study Documents ............................... 73 
14.2.3. 
Video Recordings ....................................................................................................... 73 
14.3. 
Data Quality Control .................................................................................................. 73 
14.3.1. 
Access to Study and Source Documents .................................................................... 73 
14.3.2. 
Data Management ....................................................................................................... 74 
14.3.3. 
Quality Assurance Audit / Inspection ........................................................................ 74 
14.4. 
Study Termination ...................................................................................................... 75 
14.5. 
Study Site Closure ...................................................................................................... 75 
14.5.1. 
Record Retention ........................................................................................................ 75 
14.5.2. 
Sample Retention ....................................................................................................... 76 
14.6. 
Changes to the Protocol .............................................................................................. 76 
14.7. 
Use of Information and Publication ........................................................................... 76 
15. 
PUBLIC POSTING OF STUDY INFORMATION .................................................. 77 
16. 
ETHICAL AND LEGAL CONSIDERATIONS ....................................................... 77 
16.1. 
Declaration of Helsinki and Good Clinical Practice .................................................. 77 
16.2. 
Subject Information and Informed Consent ............................................................... 77 
16.3. 
Institutional Review Board or Ethics Committee ....................................................... 77 
16.4. 
Financial Disclosure ................................................................................................... 78 


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16.5. 
Privacy and Confidentiality ........................................................................................ 78 
17. 
LIST OF REFERENCES ........................................................................................... 79 
18. 
APPENDICES ............................................................................................................ 82 
18.1. 
Investigator’s Agreement ........................................................................................... 83 
18.2. 
Definitions of Primary and Secondary Non-responder .............................................. 84 
 
 
 


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LIST OF TABLES 
Table 1 
Schedule of Assessments ............................................................................................ 27 
Table 2 
Investigational Product ............................................................................................... 45 
Table 3 
Blood Samples Taken from Each Subject .................................................................. 59 
 
 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation  
Explanation 
ADA 
anti-drug antibody 
ADL 
activities of daily living 
AE 
adverse event 
AIDS 
acquired immune deficiency syndrome 
ALT 
alanine transaminase 
Anti-TNFα 
anti-tumor necrosis factor alpha 
AST 
aspartate transaminase 
AUC  
area under the curve 
AUClast 
last observed concentration  
AUC0-¥ 
area under the sum concentration versus time curve from time zero 
to infinity 
βhCG 
beta human chorionic gonadotropin 
BP 
blood pressure 
Cmax 
maximum observed serum concentration 
CD 
Crohn’s disease 
CDAI 
Crohn’s Disease Activity Index 
CRA 
Clinical Research Associate 
CRO 
Contract Research Organization 
CRP 
C-reactive protein 
CTCAE 
Common Terminology Criteria for Adverse Events 
DcR3 
decoy receptor 3 
DMC 
Data Monitoring Committee 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
eGFR 
estimated glomerular filtration rate 
ELISA 
enzyme-linked immunosorbent assay 
EU 
European Union 
FasL 
Fas ligand 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 


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Abbreviation  
Explanation 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HVEM 
Herpes Virus Entry Mediator 
IBD 
inflammatory bowel disease 
IBD-Q 
Inflammatory Bowel Disease Questionnaire 
ICH 
International Conference on Harmonisation 
IgG4 
immunoglobulin G4 
IP 
Investigational Product 
IRB 
Institutional Review Board 
LIGHT 
Lymphotoxin-like, exhibits Inducible expression, and competes 
with Herpes Virus Glycoprotein D for Herpesvirus Entry Mediator, 
a receptor expressed by T lymphocytes 
LTβR 
lymphotoxin beta receptor 
MTX 
methotrexate 
NF-κB 
Nuclear factor kappa B 
PI 
Principal Investigator 
PK 
pharmacokinetic 
QFT 
QuantiFERON-TB Gold  
q14 
every 14 (days) 
RNA 
ribonucleic acid 
RR 
respiration rate 
SAE 
serious adverse event 
SES-CD 
Simple Endoscopy Score for Crohn’s Disease 
SOC 
system organ class 
SQ 
subcutaneous 
TB 
tuberculosis  
TEAEs 
treatment-emergent adverse events 
TL1A 
TNF-like ligand 1A 
tmax 
time to the maximum observed serum concentration 
TNF 
tumor necrosis factor 
TNFα 
tumor necrosis factor alpha 
t1/2  
Apparent terminal half-life  
UC 
ulcerative colitis 
5-ASA 
5-aminosalicylic acid 


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Abbreviation  
Explanation 
6-MP 
6-mercaptopurine 


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6. 
INTRODUCTION 
6.1. 
Inflammatory Bowel Disease 
Crohn’s Disease (CD) and ulcerative colitis (UC) are the two major phenotypes of chronic 
idiopathic inflammatory bowel disease (IBD), and they afflict over 3 million patients in the US 
(Dahlhamer et al., 2015). Both diseases carry significant risk for serious complications and the 
need for surgical interventions. The etiology of IBD involves an interplay between the immune 
system, the microbiome, and genetic factors. The immune system in the intestinal tract includes 
various epithelial cells, myeloid cells, and lymphocytes all producing a wide variety of 
molecules that mediate and regulate the inflammatory response, with imbalance of this network 
driving the pathophysiology of IBD (Abraham and Cho, 2009; Giles et al., 2018). 
6.1.1. 
Pediatric-Onset Crohn’s Disease 
The incidence of pediatric CD is rapidly increasing worldwide (Kappelman et al, 2013).  The 
treatment of pediatric CD poses several particular challenges compared to adult-onset disease.  
First, the extent of disease is more widespread among children, with pediatric CD often 
involving both the small and large intestines as well as organ systems outside the gastrointestinal 
tract (de Bie et al, 2013; Dotson et al, 2010).  As such, children tend to have a more aggressive 
disease course and many will require surgical resections (Freeman, 2014).  Second, growth 
failure is a problem unique to pediatric CD.  Without optimized treatment, the inflammatory 
burden caused by CD can result in delayed onset of puberty and shorter adult height (Sanderson, 
2014). 
The tumor necrosis factor alpha (TNFα) inhibitors infliximab and adalimumab are effective at 
inducing and maintaining remission in pediatric CD.  However, at least 12% of children with CD 
will never respond to infliximab therapy (Hyams et al, 2007).  Even among patients with initial 
response, sustained efficacy is complicated by loss of response, with nearly 50% of pediatric CD 
patients losing response to infliximab within 5 years (Assa et al, 2013).  Additionally, in 
approximately 20% of children, infusion reactions and other adverse events (AEs) require 
treatment cessation (Vahabnezhad et al, 2014).  As a result, a large percentage of pediatric CD 
patients are unable to sustain durable response with these conventional therapies.    
6.1.2. 
Ulcerative Colitis 
Anti-inflammatory agents and immunosuppressants are used as first line treatment of UC. TNFα 
inhibitors are used in the setting of first line treatment failure or intolerance to gain control of the 
disease. Unfortunately, available agents such as infliximab, adalimumab, and golimumab often 
face primary and secondary loss of response (Pouillon et al, 2016). Primary non-response rates 
for infliximab have been reported up to 30% for IBD (Ben-Horin et al, 2014), with about 50% of 
these patients requiring colectomy within 2 years (Papamichael et al, 2016). In the setting of 
rescue therapy for adult patients with severe acute UC, while 84% had an initial clinical response 
to infliximab within the first week, 54% had failed treatment and 21% required colectomy within 
14 weeks (Laharie et al, 2012). For TNFα inhibitors overall, about 30–40% of patients may fail 
to demonstrate a primary response, and about 30–40% of patients lose response over time or may 
become intolerant to TNFα inhibitors (Papamichael et al, 2015). As such there remains an unmet 








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7. 
STUDY OBJECTIVES AND PURPOSE 
7.1. 
Primary Objective 
The primary objective of this study is to evaluate the safety and tolerability of MDGN-002 
administered by SQ injection to adults with moderate to severe, active CD or UC who have 
failed prior treatment with an anti-tumor necrosis factor alpha (anti-TNFα) agent.  
7.2. 
Secondary Objectives 
The secondary objectives of this study are to: 
• Estimate plasma concentrations of MDGN-002 administered by SQ injection to adults 
with moderate to severe, active CD or UC. 
• Evaluate response to treatment with MDGN-002 administered by SQ injection to adults 
with moderate to severe, active CD or UC. 
 
 


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8. 
INVESTIGATIONAL PLAN 
8.1. 
Overall Study Design 
This is a Phase 1b, multi-center, open-label, dose-escalation, signal-finding study to evaluate the 
safety, tolerability, PK and short-term efficacy of MDGN-002 in adults with moderate to severe, 
active CD or UC who have previously failed anti-TNFα treatment. 
Four subjects with Crohn’s disease who satisfy all eligibility criteria will be enrolled in each of 
2 dose cohorts.  The first cohort will receive MDGN-002 1.0 mg/kg SQ every 14 (q14) days.  
Dose escalation will proceed after all subjects in the first cohort have been enrolled and reached 
Visit 4 (Day 14 ±3 days), the safety data from those subjects has been reviewed by the Data 
Monitoring Committee, and a decision has been made to progress to the second cohort 
(see Section 8.4).  The estimated dose escalation for the second cohort is 3.0 mg/kg SQ q14 days, 
if permitted by safety data review. After dose escalation has taken place 6 additional patients 
with UC will also be enrolled in the 3 mg/kg cohort. 
Each subject’s participation will include a screening period, which if required includes a 
wash-out period for subjects who have received biologic treatment within 12 weeks of the 
Screening Visit. With the exception of subjects requiring wash-out of the biologic certolizumab 
pegol (Cimzia), only those subjects without detectable biologic levels after 8 weeks of wash-out 
will be allowed to enter the study after confirmation of undetectable levels; all other subjects 
(including those receiving certolizumab pegol [Cimzia]) will be required to complete a full 
12-week wash-out period. The wash-out period includes the time period from the last dose 
received prior to the Screening Visit. Subjects not requiring a biologic wash-out period will be 
allowed to enter the study after review and confirmation of eligibility at screening. Screening is 
followed by an 8-week, open-label treatment period, and a safety follow-up visit approximately 
4 weeks after the last dose. The maximum study duration is 26 weeks.   
Study visits will occur at screening and on Days 0, 7, 14, 21, 28, 35, 42, 49 and 56.  The safety 
follow-up visit will occur on Day 84.  The Schedule of Assessments is shown in Table 1. 
 


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Table 1 
Schedule of Assessments 
Assessment or 
Procedure 
Screening Period 
Open-Label Treatment Period 
Safety 
Follow-
up 
Visit 1 
 
Initial 
Phone 
Contacta 
Visit for 
Testing 
Previous 
Biologics 
(if 
required) 
Wash-
out 
Phone 
Contactb 
Visit 2c 
 
 
 
 
Visit 3 
Day  
7 
 
Visit 4 
Day 
14 
 
 
 
 
Visit 5  
Day 
21 
Visit 6 
Day 
28 
Visit 7 
Day 
35 
Visit 8 
Day 
42 
 
 
 
 
Visit 9  
Day 
49 
Visit 
10 / 
ET 
Visit 
Day 
56 
Visit 11 
Day 84 
or 28 
days 
after ET 
visit 
Pre-
dose 
Day 0 
Dosing 
and 
Post-
dose 
Day 0 
Informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/ 
exclusion 
criteria review 
X 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Testing for 
Previous 
Biologics 
 
 
Xq 
 
 
 
 
 
 
 
 
 
 
 
 
Genotyping for 
DcR3 genes 
(CD only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
/ medical 
historyd 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical 
examination, 
incl. weighte 
X 
 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
Vital signs 
(BP, pulse, RR, 
T)f 
X 
 
 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
TB testingg 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
Clinical 
laboratory 
assessmentsh 
X 
 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 


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Assessment or 
Procedure 
Screening Period 
Open-Label Treatment Period 
Safety 
Follow-
up 
Visit 1 
 
Initial 
Phone 
Contacta 
Visit for 
Testing 
Previous 
Biologics 
(if 
required) 
Wash-
out 
Phone 
Contactb 
Visit 2c 
 
 
 
 
Visit 3 
Day  
7 
 
Visit 4 
Day 
14 
 
 
 
 
Visit 5  
Day 
21 
Visit 6 
Day 
28 
Visit 7 
Day 
35 
Visit 8 
Day 
42 
 
 
 
 
Visit 9  
Day 
49 
Visit 
10 / 
ET 
Visit 
Day 
56 
Visit 11 
Day 84 
or 28 
days 
after ET 
visit 
Pre-
dose 
Day 0 
Dosing 
and 
Post-
dose 
Day 0 
PK blood 
samplingi 
 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood draws 
for exploratory 
analysesj 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
X 
 
Anti-drug 
antibody 
assessment 
 
 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
X 
Urinalysis 
X 
 
 
 
X 
 
 
 
 
X 
 
 
 
X 
 
Pregnancy 
testing 
(females of 
childbearing 
potential)k 
X 
 
 
 
X 
 
 
 
 
X 
 
 
 
X 
 
Urine drug 
screenl 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Stool samplem 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
Modified Mayo 
score (UC 
only)r 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
CDAI (CD 
only) 
X 
 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
IBD-Q 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
Endoscopy 
with biopsy 
and histologyn 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 


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Assessment or 
Procedure 
Screening Period 
Open-Label Treatment Period 
Safety 
Follow-
up 
Visit 1 
 
Initial 
Phone 
Contacta 
Visit for 
Testing 
Previous 
Biologics 
(if 
required) 
Wash-
out 
Phone 
Contactb 
Visit 2c 
 
 
 
 
Visit 3 
Day  
7 
 
Visit 4 
Day 
14 
 
 
 
 
Visit 5  
Day 
21 
Visit 6 
Day 
28 
Visit 7 
Day 
35 
Visit 8 
Day 
42 
 
 
 
 
Visit 9  
Day 
49 
Visit 
10 / 
ET 
Visit 
Day 
56 
Visit 11 
Day 84 
or 28 
days 
after ET 
visit 
Pre-
dose 
Day 0 
Dosing 
and 
Post-
dose 
Day 0 
Adverse event 
monitoringo 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Provide/re-
confirm access 
to subject diary  
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Subject diary 
reviewed for 
completeness 
 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Assess 
individual 
subject 
stopping 
criteria 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
MDGN-002 
administration 
(on-site)p 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
a  Telephone visit is conducted for confirmation of eligibility. If the subject is not currently receiving biologic treatment, they will begin completing the subject diary and have visit 
2 scheduled >7 days from the diary being initiated.  The diary should be completed up to the time of the visit. 
b  Telephone visit is conducted for confirmation whether additional wash-out time is required following receipt and review of the laboratory results. If the concentration level is not 
detectable, the subject will have their visit scheduled >7 days from the time the subject started completing the diary.  If the concentration level is detectable, the subject will 
complete the full 12 week wash-out. The diary should be completed up to the time of the visit. 
c  After Day 0 (Visit 2), visits at which MDGN-002 is administered should occur every 14 ± 3 days.  These visits should be scheduled relative to Day 0 (Visit 2), which is the 
baseline visit.  
d  Medical history will include details regarding all UC/CD-related surgical procedures and hospitalizations. 
e  A complete physical examination will be performed at Visits 1, 2, 6, and 10/ET. Brief physical examinations will be done at Visits 4 and 8. Height will be measured at V2 only. 
f  Vitals will be taken pre-and post-dose on Visit 2, 4, 6 and 8. Post-dose vitals should be taken at least 60 minutes post-dose, immediately prior to discharge.  
g  TB testing will include QuantiFERON-TB Gold (QFT) blood testing or PPD skin testing. If the subject’s PPD tine skin test is ≥ 5 mm, a chest x-ray will also be employed for 
TB assessment. 


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h  Clinical laboratory assessments at Visits 1, 6, and 10/ET include: CBC with differential, hematology, serum albumin, CRP, liver panel, GGT. Anti-drug antibodies will be 
measured at Visits 2, 6 and 10. Clinical laboratory assessments at Visits 2, 4, and, 8 include hematology and serum albumin.   
i  Pre-dose PK blood samples will be obtained within 60 minutes prior to dose at Visits 2, 4, 6 and 8.  
j  Exploratory analyses will examine LIGHT, cytokines, RNA sequencing, and flow cytometry. 
k  Serum β-hCG will be conducted at Visit 1 and Urine β-hCG tests will be conducted on Visits 2, 6 and 10.  
l  Screening for amphetamines, barbiturates, benzodiazepines, cocaine, opiates, phencyclidine, cannabinoids, propoxyphene, and methadone as warranted. 
m  Stool samples will be obtained at Visits 1, 6 and 10/ET. C.difficile test will be performed only at Visit 1. Fecal calprotectin will be measured at all specified visits. 
n  Histological confirmation of disease is performed only at Visit 1. Documentation will be provided to site for confirmation or prior documentation of histological confirmation is 
acceptable. Exploratory biomarker histology will be completed for samples provided to study central laboratory provider.  
o  Adverse event monitoring begins at the time informed consent is signed. 
p  Subjects will be required to remain in the clinic for at least 60 minutes after MDGN-002 administration for adverse event monitoring. 
q  Subjects requiring wash-out will have a blood test performed at 8 weeks after the start of the wash-out period to confirm the previous biologic therapy is undetectable. If there is 
no previous biologic therapy detected, subjects will be able to continue onto Visit 2 and will not be required to complete the full 12-week wash-out. If there are detectable levels 
of the previous biologic therapy, then subjects will complete the full 12-week wash-out before proceeding to Visit 2.  For subjects receiving certolizumab pegol (Cimzia) a 
12-week wash-out is required.  
r The Modified Mayo Score includes stool frequency, rectal bleeding, and the appearance of mucosa upon endoscopy. This score will be calculated at Visit 1 and Visit 10 using the 
endoscopy score from the central reader, self reported data on stool frequency and rectal bleeding from the period prior to the subject being screened for Visit 1 and data from 
the patient diary for Visit 10. 
 BP=blood pressure; CBC=complete blood count; CDAI=Crohn’s Disease Activity Index; CRP=C-reactive protein; DcR3=decoy receptor 3; GGT=gamma-glutamyl transferase; 
ECG=electrocardiogram; ET=early termination; hCG=human chorionic gonadotropin; LIGHT=Lymphotoxin-like, exhibits Inducible expression, and competes with Herpes 
Virus Glycoprotein D for Herpesvirus Entry Mediator, a receptor expressed by T lymphocytes; PK=pharmacokinetic; PPD = purified protein derivative; RR=respiration rate; 
T=temperature; TB=tuberculosis; TNFα=tumor necrosis factor alpha.  
 


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8.2. 
Study Periods 
The study includes a screening period, an open-label treatment period, and a safety follow-up 
visit.  Each cohort will complete the study periods described below. Following a review of the 
safety data, a decision will be made whether or not to escalate to the 3 mg/kg as described in 
Section 8.4. 
8.2.1. 
Screening Period 
During the screening period, all subjects will be evaluated for their eligibility to participate in the 
study.  At Visit 1, subjects will sign the informed consent form before any study-related 
procedures or evaluations are conducted.  
Demographic information will be obtained along with medical history, including CD/UC 
diagnostic information, CD/UC-related procedures/surgeries and medication use history.  Any 
existing conditions reported at the screening visit will be recorded in the electronic case report 
form (eCRF); current medications will also be recorded on the eCRF.  Prior CD/UC therapies 
(lifetime recall) will be recorded in the eCRF with dates reflecting prior use.  All safety 
assessments will be conducted, including physical examinations (with weight measurements), 
vital signs (blood pressure, pulse, respiration rate and temperature), 12-lead ECGs, clinical 
laboratory tests, stool sample and urinalysis.  A urine drug screening test (as warranted) and 
tuberculosis (TB) testing defined as either a purified protein derivative (PPD) skin reaction test 
or QuantiFERON-TB Gold (QFT) blood test, and as required by protocol, chest x--ray, will be 
administered to all subjects.  A serum β-human chorionic gonadotropin (β-hCG) test will be 
administered to females of childbearing potential.  The CDAI and the Inflammatory Bowel 
Disease Questionnaire (IBD-Q) will be administered.  Subjects will undergo an endoscopy with 
biopsy and histology during the screening period.  Subjects with CD will be provided access to a 
study diary to record their daily assessment of well-being, abdominal pain and stool frequency 
including loose and watery stools.  Subjects with UC will be provided access to a study diary to 
record their daily assessment of their stool frequency and rectal bleeding. The diary must be 
completed for a minimum of 7 days prior to initiation of open-label treatment as described in 
Table 1.  Finally, adverse events (AEs) will be monitored. 
Subjects who are currently taking a biologic treatment or who have received biologic treatment 
within 12 weeks of the Screening Visit but who are otherwise eligible for study participation 
based on review of all screening evaluations and results will begin a wash-out period for these 
medications. Washout is the period between when the subject received their last dose of biologic 
and when they are eligible to proceed to Visit 2. With the exception of subjects requiring wash-
out of the biologic certolizumab pegol (Cimzia), a blood test will be administered to subjects 
undergoing wash-out 8 weeks after their last dose of biologic treatment to ensure that serum 
levels of any previous biologic treatments are below the level of detection. If it is confirmed that 
the levels of previous biologic treatment are undetectable, then the subject will proceed to Visit 
2.  If the test results indicate that the previous biologic treatment is detectable, the subject will be 
required to complete a full 12-week wash-out period before proceeding to Visit 2. For subjects 
receiving the biologic certolizumab pegol (Cimzia) a 12-week wash-out is required.   


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8.2.2. 
Open-label Treatment Period 
Eligible subjects will return to the clinic after the screening period (and wash-out period, if 
applicable) on Visit 2, which is Day 0 of the 8-week, open-label treatment period.  Physical 
examinations including weight and vital sign assessments, clinical laboratory tests, urinalysis, and 
the CDAI (CD only) will be performed.  A urine β-hCG test will be administered to females of 
childbearing potential.  Any AEs and concomitant medications will be recorded.  Blood will be 
drawn for PK, ADA and exploratory analyses (including LIGHT, cytokines, RNA sequencing, and 
flow cytometry).  Subjects with CD will record their daily assessment of well-being, abdominal 
pain and stool frequency including loose and watery stools daily in their study diary. Subjects with 
UC will record stool frequency and rectal bleeding daily in their study diary. Diary data will be 
reviewed for completeness during each visit. Subjects will be re-evaluated to determine whether 
they meet all inclusion criteria and do not satisfy any of the exclusion criteria.   
Eligible subjects will then be enrolled in the study and receive their first dose of MDGN-002 in 
the clinic.  Subjects will receive MDGN-002 as a SQ injection in the abdomen in a zone of 4 to 
10 cm from the umbilicus with the injection site rotated with each subsequent dose. The dose of 
MDGN-002 will be administered every 14 days (± 3 days) for 8 weeks.  Subjects will be 
monitored for AEs during the administration of each dose and for 60 minutes after dosing.  
Subjects will return to the clinic every 14 (± 3) days (Visits 4, 6, 8, and 10) after the first 
MDGN-002 dose for assessment of safety, PK, and efficacy and to receive the next dose of 
investigational product, as shown in Table 1.  Additional weekly visits between dosing visits 
(Visits 3, 5, 7, and 9) will occur at which time blood will be drawn for PK analyses, subjects will 
be provided access to a study diary for diary data collection, and AEs and concomitant 
medication use will be recorded. 
Prior to enrolling subjects in the second dose cohort, all subjects in the first cohort will have 
reached Visit 4 (Day 14 ±3 days) in the study and safety data from those subjects will be 
reviewed by the Data Monitoring Committee (DMC; as described in Section 8.4).  A 
recommendation will be provided by the DMC and a decision by the Sponsor whether subjects 
can be enrolled in the next dose cohort. 
8.2.3. 
Safety Follow-up Visit 
Approximately 28 days after the final dose, subjects will have a safety follow-up visit.  The 
safety follow-up visit will be conducted in the clinic with the subject.  Any AEs that occurred in 
the time since the subject’s last MDGN-002 dose will be recorded, along with any concomitant 
medication use.   
8.3. 
Safety Data Review  
Each investigator will review all available safety data collected at their site on a weekly basis, 
and communicate any safety concerns to the sponsor medical monitor.  The sponsor medical 
monitor will review all relevant safety findings with the coordinating principal investigator and 
DMC as needed. 
 


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Special attention will be paid to adverse drug reactions observed in the MDGN-002 preclinical 
study as well as other common adverse reactions seen with other biologic treatments which 
include: 
 
MDGN-002 preclinical observation: 
• Injection site reactions 
 
Adverse reactions observed with other biologic treatments:  
• Potential for increased infection including opportunistic infections (such as tuberculosis) 
• Hypersensitivity reactions (including anaphylaxis) 
• Immunogenicity 
• Malignancy 
• Impaired immunization 
• CD exacerbation  
8.4. 
Data Monitoring Committee  
An external, independent Data Monitoring Committee (DMC) comprising physicians, scientists 
and a biostatistician will review the study data at a meeting after all subjects in the first cohort 
have been enrolled and reached Visit 4 (Day 14 ±3 days), and after completion of the second 
cohort. Additionally, ad hoc meetings to assess individual exacerbations of CD or UC meeting 
Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or greater as defined in 
Section 8.5 may be held.  The DMC’s role is to protect the interests of the subjects in the study 
and those still to be entered in the study by reviewing information such as safety, tolerability, 
pharmacokinetic and efficacy data.  The DMC’s meeting schedule may be adjusted based on 
recommendations made by the DMC, the amount of incremental safety data, and other practical 
considerations.  The data provided to the DMC may not be monitored and will not be considered 
“clean” until the database is locked at the completion of the study. 
Possible outcomes of the DMC review can include one of the following recommendations:  
• Study can continue  
• Study can continue with modifications  
• Study is to be terminated  
Data Monitoring Committee recommendation will be documented in meeting minutes which will 
include, at a minimum: 
• List of meeting participants 
• Summary of data considered during the meeting 
• Summary of the DMC recommendation regarding further dose cohorts, including any 
concerns raised  
The sponsor is responsible for the decision to continue, modify or terminate the study. A copy of 
the DMC meeting recommendation and sponsor decision will be sent to the study sites upon 
completion and prior to administration of the next subject dose in the second cohort.  


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8.5. 
Individual Subject and Study Stopping Criteria 
8.5.1. 
Individual Subject Stopping Criteria 
The following individual subject stopping criteria will be used during the study and will be 
assessed starting post-dose at Visit 2: 
• A subject develops a CTCAE Grade 3 or higher of the following: 
o Injection site reactions  
o Opportunistic infections (i.e. tuberculosis)  
o Hypersensitivity reactions (e.g. allergic reactions, anaphylaxis or cytokine release 
syndrome) 
o Malignancy 
o Decreased white blood cell count 
o Decrease neutrophil count 
o Decreased platelets 
o Colonic or ileal hemorrhage 
o Colonic, ileal or small intestine obstruction 
o Colonic, ileal or small intestine perforation 
o Colonic, ileal or small intestine stenosis 
• A subject will also be stopped if liver enzymes are: 
o ALT or AST >8x ULN 
o ALT or AST >5x ULN for more than 2 consecutive weeks or 
o A single subject ALT or AST >3x ULN with the appearance of fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash and or eosinophilia 
(>5%). 
Note: subjects who exhibit ALT or AST >3x ULN without appearance of any of the 
above symptoms must have repeat testing within 48-72 hours to confirm abnormality 
and determine direction (increase or decrease) from the original value. 
• A subject will be stopped if Hy’s Law is detected (i.e. ALT or AST >3x ULN and total 
bilirubin >2x ULN and no other reason can be found to explain the combination of 
increased AT and TBL, such as viral hepatitis A, B, or C; preexisting or acute liver 
disease; or another drug capable of causing the observed injury). 
 
8.5.2. 
Study Stopping Criteria 
The following study stopping criteria will be used during the study:  
• The study will be stopped if two or more subjects develop the same CTCAE Grade 3 or if 
one subject develops a CTCAE Grade 4 of the following:  
o Injection site reactions  
o Opportunistic infections (i.e. tuberculosis)  
o Hypersensitivity reactions (e.g. allergic reactions, anaphylaxis or cytokine release 
syndrome) 
o Malignancy 


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o Decreased white blood cell count 
o Decrease neutrophil count 
o Decreased platelets 
• The study will be stopped if two individual subjects develop any of the following liver 
toxicities: 
o ALT or AST >8x ULN 
o ALT or AST >5x ULN for more than consecutive 2 weeks or 
o ALT or AST >3x ULN with the appearance of fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, fever, rash and or eosinophilia (>5%). 
 
• The study will be stopped if one subject meeting Hy’s Law is detected (i.e. ALT or AST 
>3x ULN and total bilirubin >2x ULN and no other reason can be found to explain the 
combination of increased AT and TBL, such as viral hepatitis A, B, or C; preexisting or 
acute liver disease; or another drug capable of causing the observed injury). 
 
• Individual reports of exacerbations of Crohn’s disease CTCAE Grade 3 or greater, such 
as:  
o Colonic or ileal hemorrhage 
o Colonic, ileal or small intestine obstruction 
o Colonic, ileal or small intestine perforation 
o Colonic, ileal or small intestine stenosis 
 
will be reviewed by the DMC at the first available date after report to determine if modifying 
the study or stopping the study is recommended.  
8.6. 
Study Design Rationale 
This is the third study in which MDGN-002 is being administered to human subjects and the first 
study in subjects with treatment-resistant CD or treatment resistant UC.  The study is a pilot 
study using a dose-escalation design to characterize the safety and tolerability of 2 different 
doses of MDGN-002 (1.0 mg/kg and 3.0 mg/kg) in the target population.  The dose escalation 
design allows for the evaluation of safety and tolerability in small numbers of subjects before 
proceeding to the next dose level.  The open-label administration of MDGN-002 to all enrolled 
subjects minimizes the number of subjects exposed to the study procedures.  The inclusion of PK 
blood draws and efficacy assessments allows for preliminary assessments of plasma levels and 
efficacy, respectively. 
No specific hypotheses are being tested in this pilot study.  All data will be summarized using 
descriptive statistics as appropriate (see Section 13). 
8.7. 
Number of Subjects 
Four subjects with CD will be enrolled in each of the 2 planned dose cohorts for a maximum of 8 
study subjects with CD.  Additionally, 6 subjects with UC will be enrolled in the 2nd dose cohort. 
Subjects who withdraw from the study prematurely prior to a third dose may be replaced.  


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8.8. 
Treatment Assignment 
The first cohort of subjects will be assigned to the 1.0 mg/kg dose of MDGN-002.  Subjects will 
be assigned to the second dose cohort, after the DMC review of the safety data from the first 
cohort, as described in Section 8.4, provided study stopping criteria have not been met as 
described in Section 8.5.2 and a decision is made by the Sponsor that enrolment can continue. 
8.9. 
Criteria for Study Termination 
The study may be terminated at the sponsor’s discretion at any time and for any reason. 


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9. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
A screening log of potential study candidates and an enrollment log of enrolled subjects must be 
maintained at each study site. 
9.1. 
Subject Inclusion Criteria – Crohn’s Disease 
Subjects with CD must meet all of the following inclusion criteria in order to be eligible for 
enrollment in the study: 
1. Subject is able to speak English fluently and has provided written informed consent for 
this study. 
2. Subject is male or female, ≥18 to £ 75 years of age. 
3. Subject has a documented diagnosis of CD via endoscopy/colonoscopy and histological 
confirmation. Prior documentation of histological confirmation is acceptable 
4. Subject has moderate to severe, active CD as evidenced by Simple Endoscopy Score for 
Crohn’s Disease (SES-CD) score of ³7.    
5. Subject has failed treatment with an approved therapeutic dose of an anti-TNFα 
monoclonal antibody treatment with either no initial response (primary non-responder) or 
an initial response to induction with subsequent lost response (secondary non-responder) 
as defined in Appendix 18.2.   
6. Subject can be receiving concurrent treatment with an oral corticosteroid, and/or 
azathioprine or 6-mercaptopurine (6-MP) or methotrexate (MTX) as defined in 
Section 10.2.1. 
7. Subject agrees to be genotyped at the DcR3 locus.  
9.2. 
Subject Exclusion Criteria – Crohn’s Disease 
Subjects with CD who meet any of the following exclusion criteria will not be eligible for 
enrollment in the study: 
1. Subject has a diagnosis of ulcerative colitis (UC) or indeterminate colitis. 
2. Subject is unable to tolerate or unwilling to undergo study procedures including 
endoscopy and biopsy during the study. 
3. Subject with signs or symptoms of bowel obstruction with small bowel imaging 
supporting obstruction. 
4. Subject has short bowel syndrome as determined by the investigator. 
5. Subject has a current functional colostomy or ileostomy.  
6. Subject has had a surgical bowel resection within the past 6 months prior to screening or 
is planning any resection during the study period. 
7. Clinical suspicion of intra-abdominal abscesses exists, in the opinion of the investigator. 
8. Subject has concurrent bowel dysplasia or a history of bowel dysplasia in the 5 years 
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9. Subject has a known, active and/or positive test for C. difficile infection despite an 
adequate course of treatment.  
10. Subject has history of or current diagnosis of any cancer excluding cancers that have been 
cured by surgical excision (e.g., non melanoma skin cancers). 
11. Subject has a history of a lymphoproliferative disorder, including lymphoma, or signs and 
symptoms suggestive of lymphoproliferative disease at any time. 
12. Subject has history of or active TB infection or positive TB testing at screening.  
13. Subject has known concurrent viral hepatitis, or acquired immune deficiency syndrome 
(AIDS) or known human immunodeficiency virus (HIV) infection. 
14. Subject has been treated with natalizumab (TysabriÒ) within the past 5 years. 
15. Subject who has not completed his/her primary vaccination series (particularly 
hepatitis B, varicella, measles/mumps/rubella) unless immunity is documented with 
blood titers. 
16. Subject has received any live attenuated vaccine, such as varicella-zoster, oral polio, or 
rubella, within 3 months prior to the baseline visit.   
17. Subject has any of the following abnormal screening laboratory test results:  
• Clinically significant ECG abnormalities; 
• Aspartate transaminase (AST), alanine transaminase (ALT) or 
total bilirubin > ULN; 
• Hemoglobin < 10g/dL 
• Absolute neutrophil count <1500 cell/mm3, or 
• Estimated glomerular filtration rate <60 mL/min/1.73 m2. 
18. Subject has abnormal vital signs during Screening (Visit 1) or prior to enrollment at the 
baseline visit (Visit 2), as defined in Section 12.3.1.2. 
19. Subject is pregnant or a nursing mother. 
20. Subject is sexually active and not on effective contraception as defined in Section 10.2.3. 
21. Subject has a history of drug abuse that would inhibit participation in the clinical trial. 
22. Subject has a current or recent history (within 6 months prior to screening) of significant 
and severe renal, hepatic, hematological, gastrointestinal (other than CD or conditions 
outlined above), endocrine, pulmonary, cardiac, or neurological disease.  
23. Subject has any other clinically significant mental or physical illness or infection that, in 
the opinion of the investigator, might confound the results of the study, pose additional 
risk to the subject by their participation, or prevent or impede the subject from 
completing the study. 
24. There is any concern on the part of the investigator regarding the subject’s safety, 
compliance, or suitability with respect to his/her participation in the study. 


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9.3. 
Subject Inclusion Criteria – Ulcerative Colitis 
Subjects with UC must meet all of the following inclusion criteria in order to be eligible for 
enrollment in the study: 
1. Subject is able to speak English fluently and has provided written informed consent for 
this study. 
2. Subject is male or female, ≥18 to £ 75 years of age. 
3. Subject has received a diagnosis of UC for 90 days or greater prior to Visit 1, confirmed 
by endoscopy during the Screening Period. Appropriate documentation of biopsy results 
consistent with the diagnosis of UC, in the assessment of the Investigator, must be 
available. 
4. Subject has moderately to severely active UC, as defined by a Modified Mayo Score 
(excluding the PGA component) of 5 to 9 points.   
5. Subject has a Modified Mayo Endoscopic Score of ≥2 at Visit 1 as confirmed by central 
reader.  
6. Subject has a Modified Mayo Rectal Bleeding Score of ≥1 at Screening Visit 1. 
7. Subject has failed treatment with an approved therapeutic dose of an anti-TNFα 
monoclonal antibody treatment with either no initial response (primary non-responder) or 
an initial response to induction with subsequent lost response (secondary non-responder) 
as defined in Appendix 18.2.   
8. Subject can be receiving concurrent treatment with an oral corticosteroid, and/or 
azathioprine or 6-mercaptopurine (6-MP) or methotrexate (MTX) as defined in 
Section 10.2.1. 
9. Subject who is currently taking 5-aminosalicylic acid (5-ASA) has been on a stable dose 
for at least 2 weeks prior to Visit 1. 
9.4. 
Subject Exclusion Criteria – Ulcerative Colitis 
Subjects with UC who meet any of the following exclusion criteria will not be eligible for 
enrollment in the study: 
1. Subject has a diagnosis of CD or indeterminate colitis. 
2. Subject is unable to tolerate or unwilling to undergo study procedures including 
endoscopy and biopsy during the study. 
3. Subject with signs or symptoms of bowel obstruction with small bowel imaging 
supporting obstruction. 
4. Subject has short bowel syndrome as determined by the investigator. 
5. Subject has a current functional colostomy or ileostomy.  
6. Subject has had a surgical bowel resection within the past 6 months prior to screening or 
is planning any resection during the study period. 
7. Clinical suspicion of intra-abdominal abscesses exists, in the opinion of the investigator. 


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8. Subject has concurrent bowel dysplasia or a history of bowel dysplasia in the 5 years 
prior to screening. 
9. Subject has a known, active and/or positive test for C. difficile infection despite an 
adequate course of treatment.  
10. Subject has history of or current diagnosis of any cancer excluding cancers that have been 
cured by surgical excision (e.g., non melanoma skin cancers, cervical cancer). 
11. Subject has a history of a lymphoproliferative disorder, including lymphoma, or signs and 
symptoms suggestive of lymphoproliferative disease at any time. 
12. Subject has history of or active TB infection or positive TB testing at screening.  
13. Subject has known concurrent viral hepatitis, or acquired immune deficiency syndrome 
(AIDS) or known human immunodeficiency virus (HIV) infection. 
14. Subject has been treated with natalizumab (TysabriÒ, Biogen) within the past 5 years. 
15. Subject who has not completed his/her primary vaccination series (particularly 
hepatitis B, varicella, measles/mumps/rubella) unless immunity is documented with 
blood titers. 
16. Subject has received any live attenuated vaccine, such as varicella-zoster, oral polio, or 
rubella, within 3 months prior to the baseline visit.   
17. Subject has received an investigational medicine (non-biologic) within 2 weeks of Visit 1 
and/or an investigational medicine that is a biologic within 8 weeks of Visit 1. 
18. Subject has received Tofacitinib within 2 weeks of Visit 1. 
19. Subject has any of the following abnormal screening laboratory test results:  
• Clinically significant ECG abnormalities; 
• Aspartate transaminase (AST), alanine transaminase (ALT) or 
total bilirubin > ULN; 
• Hemoglobin < 10g/dL 
• Absolute neutrophil count <1500 cell/mm3, or 
• Estimated glomerular filtration rate <60 mL/min/1.73 m2. 
20. Subject has abnormal vital signs during Screening (Visit 1) or prior to enrollment at the 
baseline visit (Visit 2), as defined in Section 12.3.1.2. 
21. Subject is pregnant or a nursing mother. 
22. Subject is sexually active and not on effective contraception as defined in Section 10.2.3. 
23. Subject has a history of drug abuse that would inhibit participation in the clinical trial. 
24. Subject has a current or recent history (within 6 months prior to screening) of significant 
and severe renal, hepatic, hematological, gastrointestinal (other than CD or conditions 
outlined above), endocrine, pulmonary, cardiac, or neurological disease.  


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25. Subject has any other clinically significant mental or physical illness or infection that, in 
the opinion of the investigator, might confound the results of the study, pose additional 
risk to the subject by their participation, or prevent or impede the subject from 
completing the study. 
26. There is any concern on the part of the investigator regarding the subject’s safety, 
compliance, or suitability with respect to his/her participation in the study. 
9.5. 
Screen Failure 
Subjects who fail inclusion and/or exclusion criteria may be rescreened for the study with the 
prior approval of the Aevi Genomic Medicine, LLC medical monitor.  In the event of a 
rescreening, the first screening visit will be entered into the eCRF as the Screening Visit (Visit 1) 
and the repeat assessments entered into the eCRF as an unscheduled visit.  
9.6. 
Subject Withdrawal Criteria 
All subjects will be advised that they are free to withdraw from participation in this study at any 
time, for any reason, and without prejudice.  Every reasonable attempt should be made by the 
investigator to keep subjects in the study; however, subjects must be withdrawn from the study if 
they withdraw consent to participate.  For subjects who fail to attend scheduled visits, the 
investigator must attempt to contact them by telephone or other means to exclude the possibility 
of an AE being the cause of withdrawal.  Should this be the cause, the AE must be documented, 
reported, and followed as described in Section 12.3.1.6. 
The sponsor reserves the right to request the withdrawal of a subject due to protocol violations or 
other reasons. 
The investigator also has the right to withdraw subjects from the study at any time for lack of 
therapeutic effect that is intolerable or otherwise unacceptable to the subject, for intolerable or 
unacceptable AEs, intercurrent illness, for meeting the individual subject stopping criteria 
(Section 8.5.1), noncompliance with study procedures, administrative reasons, or in the 
investigator’s opinion, to protect the subject’s best interests. 
If a subject is withdrawn before completing the study, the reason for withdrawal and the date of 
discontinuation will be recorded on the appropriate eCRF.  Whenever possible and reasonable, 
the evaluations that were to be conducted at the completion of the open-label treatment period 
(ie, Visit 10) should be performed at the time of early termination. 
Subjects who withdraw prior to receiving the third dose of study drug may be replaced.  
All samples will be retained according to applicable rules and regulations.  Blood and biopsy 
samples may be stored and used for further analysis related to this research.  As applicable, 
saliva samples may also be used for purposes related to this research.  Samples will be given a 
unique code that will include no information that will name the subject. Any remaining DNA 
sample will be stored for future biomarker studies.  
 
 


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10. 
TREATMENT OF SUBJECTS 
10.1. 
Description of Investigational Product 
A description of the investigational product is provided in Section 11.1 
Subjects in each dose cohort will receive the investigational product as a single SQ injection in 
the abdomen in a zone of 4 to 10 cm from the umbilicus with the injection site rotated with each 
subsequent dose. The dose of MDGN-002 will be administered on Days 0, 14, 28, and 42.  After 
Day 0, injections must occur within ± 3 days of the scheduled 14-day intervals. 
Subjects in the first dose cohort will receive MDGN-002 1.0 mg/kg for the entire 8-week, 
open-label treatment period.  Data from this cohort will be reviewed by the Data Monitoring 
Committee as described in Section 8.4 before subjects in the second dose cohort can be treated.  
Eligible subjects in the second dose cohort will receive MDGN-002 3.0 mg/kg for the entire 
8-week, open-label treatment period.  Data from the second cohort will be reviewed, as described 
in Section 8.4, after all subjects have completed the treatment period and its associated 
assessments.  
Any quality issue noticed with the receipt or use of an investigational product provided by the 
sponsor (deficiency in condition, packaging, appearance, pertaining documentation, labeling, 
expiration date, etc.) should be promptly communicated to the sponsor, who will investigate. 
A potential defect in the quality of investigational product provided by the sponsor may be 
subject to initiation of a recall procedure by the sponsor.  In this case, the investigator will be 
responsible for promptly addressing any request made by the sponsor, in order to recall the 
investigational product and eliminate potential hazards. 
10.2. 
Permitted and Prohibited Therapies 
All prior lifetime CD and UC therapies as well as concomitant medications used (including 
over-the-counter medications and herbal supplements) will be recorded in the source document 
and on the appropriate eCRF. 
10.2.1. 
Permitted Therapies 
Subjects can be receiving concurrent treatment with an oral corticosteroid, and/or azathioprine, 
6-MP or MTX. Subjects may not have their dose of these medications increased during the 
study. If a dose increase of a concomitant permitted therapy is required, the subject must be 
discontinued from the study utilizing the Early Termination visit procedures. Concurrent 
treatment with an oral corticosteroid, and/or azathioprine, 6-MP, MTX or 5-ASA is defined as 
follows: 
• Oral corticosteroid – Prednisone dose not exceeding 40 mg/day, with a stable dose for at 
least 2 weeks prior to baseline. 
• Azathioprine or 6-MP – Azathioprine dose of at least 2 mg/kg/day or 6-MP dose of 1 to 
1.5 mg/kg/day rounded to the nearest available tablet formulation, or a dose that is the 
highest tolerated for the subject, in the opinion of the investigator, for at least 8 weeks 
prior to baseline with a stable dose for at least 4 weeks prior to baseline. 


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• MTX dose of 25 mg/week during study, either SQ, intramuscularly, or orally, for at least 
8 weeks prior to baseline with a stable dose for at least 4 weeks prior to baseline. 
• A stable dose of 5-ASA for at least 2 weeks prior to Visit 1 
Doses of these therapies may be decreased during the study; however, all doses must be within 
the combinations and dose ranges specified above.  These changes must be recorded on the 
concomitant medication eCRF.   
For subjects on corticosteroids at the time of study enrollment, weaning during the study may be 
done according to the rules below: 
Corticosteroid dose  
Maximum taper rate per week  
³20mg 
10mg 
10 to <20mg 
5mg 
<10mg 
2.5mg 
If a deviation from the permitted concomitant therapy combinations, dose ranges or weaning 
schedule is necessary, the subject must be withdrawn from study participation. 
10.2.2. 
Prohibited Therapies 
Concomitant use of biologic treatments during the study is prohibited including use of anakinra, 
(Kineret®, Amgen), abatacept (Orencia®, Bristol-Myers Squibb), ustekinumab (Stelara®, 
Jannsen), vedolizumab (EntyvioTM, Takeda), or tocilizumab (Actemra®, Genentech). A wash-out 
period of up to 12 weeks is required prior to study enrollment (Visit 2) and after confirmation of 
eligibility from screening procedures performed at Visit 1 for all biologic treatments received 
within 12 weeks of the Screening Visit. Treatment with tofacitinib (Xeljanz®, Pfizer) within 2 
weeks of Visit 1 or prior treatment with natalizumab (Tysabri®, Biogen) with 5 years of Visit 1 
would exclude subjects from participation. Dosing with an investigational medicine 
(non-biologic) within 2 weeks of Visit 1 and/or an investigational medicine that is a biologic 
within 8 weeks of Visit 1 would also exclude subjects from participation. 
Vaccination with live or attenuated virus 3 months prior to screening and at any time during the 
study is prohibited. 
10.2.3. 
Contraceptive Methods 
Sexually active study participants must agree to the use of effective contraceptive methods 
during the study and for the defined period after the end of study visit.  Approved methods 
require double barrier according to the following algorithm: condom plus intra-uterine device or 
condom plus hormonal contraceptive.  Should any subject be sterilized, the procedure for 
sterilization is required to have been completed more than 3 months prior to study screening 
visit. 
A sexually active male participant must use one of the above-described double barrier 
contraceptive methods during the study and for 3 months after the end-of-study visit.  A sexually 


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active female participant must use one of the above-described double barrier contraceptive 
methods during the study and for 1 month after the end-of-study visit. 
Male subjects must also have to agree not to donate sperm for the duration of the study and for 
up to 3 months after the end-of-study visit. 
 
Study participants who are abstinent at the time of study entry must agree to use the approved 
methods described in this section should they become sexually active during the study. 
10.3. 
Treatment Compliance 
Treatment with MDGN-002 will be administered by study center personnel under direct medical 
supervision, and an appropriate record will be made in the source data by the investigator or 
his/her delegate.  The investigator or designee will record the dosing information on the 
appropriate eCRF page.  It is the investigator’s responsibility to ensure that an accurate record of 
the administration of the investigational product is maintained. 
10.4. 
Randomization and Blinding 
All subjects will receive MDGN-002 in an open-label manner. 
10.5. 
Treatment after End of Study 
After successful enrollment and subsequent completion of or early termination from the study, 
each subject will be treated according to standard clinical practice. In order to support the 
subject’s transition from the clinical trial, after care medical expenses such as co-pays and out of 
pocket medical/treatment associated costs will be covered in the total amount of $5,000.00 which 
may be used up to a total 6 months post-study exit. Aftercare payments will be administered by a 
third-party vendor contracted by the Sponsor.   
 
 
 


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11. 
INVESTIGATIONAL PRODUCT MATERIALS AND 
MANAGEMENT 
11.1. 
Investigational Product 
The following table provides a description of the investigational product used in this study. 
Table 2 
Investigational Product 
Product Name: 
MDGN-002 
Dosage Form: 
150 mg/mL solution  
Unit Dose 
1.0 mg/kg or 3.0 mg/kg  
Route of Administration 
SQ injection in the abdomen in a zone of 4 to 10 cm from the 
umbilicus with the injection site rotated with each subsequent 
dose.  
Physical Description 
 
Manufacturer 
 
 
11.2. 
Packaging and Labeling 
All packaging and labeling operations will be performed by the sponsor or designee according to 
Good Manufacturing Practice and Good Clinical Practice (GCP) rules.  The investigational 
product will be sent to the study site by the sponsor or designee.  Labeling will be in the local 
language and dependent upon local regulations. 
11.2.1. 
Packaging 
MDGN-002 (150 mg/mL) vials containing nominally 2 mL will be packaged separately into 
bulk, open-labeled cartons. 
11.2.2. 
Labeling 
The vial and the carton will have affixed a label that meets the applicable regulatory 
requirements.   
The investigator will be asked to save all unused or partially used medication vials and all empty 
packaging for final disposition locally or by the sponsor.  Syringes used for dosing must be 
treated as biologic waste and disposed of properly. 
11.3. 
Storage 
All investigational product must be stored between 2° and 8°C and protected from light. 


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Investigators or other authorized persons (e.g., pharmacists) are responsible for storing the 
investigational product provided by the sponsor in a secure and safe place in accordance with 
local regulations, labeling specifications, institutional policies and procedures. 
Control of storage conditions for the investigational product provided by the sponsor, especially 
control of temperature (e.g., refrigerated storage) and daily temperature monitoring, and 
information on in-use stability and instructions for handling the investigational product must be 
managed according to the rules provided by the sponsor in the Pharmacy Manual. 
11.4. 
Preparation 
Preparation of syringes will be described in the Pharmacy Manual. 
11.5. 
Administration 
MDGN-002 will be administered by SQ injection in the abdomen in a zone of 4 to 10 cm from 
the umbilicus with the injection site rotated with each subsequent dose.  
11.6. 
Accountability 
The investigator must maintain adequate records showing the receipt, administration, or other 
disposition of the investigational product including the date, lot identifier, dosage, volume 
administered to each subject, and identification of subjects (subject number and initials) who 
received the investigational product.  The investigator will not supply the investigational product 
to any other location or person except those named as sub-investigators on the Form FDA 1572, 
designated study personnel, and subjects in this study.  The investigator will not dispense the 
investigational product from any study sites other than those listed on Form FDA 1572.  If any of 
the investigational product is not dispensed; is lost, stolen, spilled, unusable; or is received in a 
damaged container, this information must be documented and reported to Aevi Genomic 
Medicine and appropriate regulatory agencies, as required. 
Upon completion of the study, unused investigational product must be left in the original 
packaging for final disposition locally or by the sponsor.  Any partially used investigational 
product and all empty packaging (e.g., vials) must also be saved for final disposition locally or 
returned to the sponsor’s designee for destruction.   
11.7. 
Handling and Disposal 
Investigational product reconciliation must be performed at the site by the investigator and the 
monitoring team using treatment log forms and documented on the site’s investigational product 
inventory countersigned by the investigator and the monitoring team. 
After reconciliation authorization by the sponsor, all used, partially used, and unused vials and 
all original packaging will be disposed of locally (as required) or by the sponsor.  This process 
will be provided to the site by the sponsor’s designee.       
 


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12. 
STUDY PROCEDURES AND ASSESSMENTS  
Subjects will provide written informed consent before any study-related procedures are initiated, 
including the cessation of prohibited concomitant therapy. 
For the timing of assessments and procedures throughout the study, refer to the Schedule of 
Assessments (see Table 1).  Throughout the study, every reasonable effort should be made by 
study personnel to follow the timing of assessments and procedures in the schedule of events for 
each subject.  Visits performed after the Visit 2 baseline visit should be scheduled relative to 
Visit 2 in order to maintain 56 days of open-label treatment and administration every 14 days 
(± 3 days).  If a subject misses a study visit for any reason, the visit should be rescheduled as 
soon as possible.  Each study visit window after Visit 2 is ± 3 days. Visit procedures should be 
performed in the order shown however adjustments may be made to the order to accommodate 
site-specific requirements.  
12.1. 
Study Periods and Visits 
12.1.1. 
Screening (Visit 1)  
The subject must be screened within 14 weeks before enrollment in the study.  The following 
procedures will be performed at screening: 
1. Obtain written informed consent  
2. Review inclusion/exclusion criteria 
3. Conduct genotyping for DcR3 genes (CD only) 
4. Collect demographic information 
5. Record medical and medication history 
6. Perform a complete physical examination, including measurements of weight 
7. Collect vital signs, including systolic and diastolic blood pressures, pulse, respiration rate 
and temperature 
8. Perform 12-lead ECG 
9. Collect blood samples for clinical laboratory tests 
10. Perform QuantiFERON-TB Gold (QFT) blood test, or PPD tuberculosis skin test. If the 
subject’s PPD tine skin test is ≥ 5 mm, a confirmatory chest x-ray is required. 
11. Collect blood sample for β-hCG test (for females of childbearing potential only) 
12. Collect stool sample for C. difficile and fecal calprotectin analyses 
13. Collect urine sample for urinalysis 
14. Collect urine sample for drug testing as warranted 
15. Administer the CDAI (CD only)  
16. Administer the IBD-Q questionnaire 
17. Conduct the endoscopy with biopsy 


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18. Assess and record any AEs and concomitant medications 
19. Provide access to patient diary to record daily assessment of the following:  
a) Abdominal pain, general well-being and number of stools including loose or 
watery stool (e.g., 6 or 7 on Bristol stool form scale) and daily abdominal pain 
severity (scale of 0 to 10) for CD patients.  
b) Stool frequency and rectal bleeding for UC patients.  
20. Calculate the Modified Mayo Score (excluding the PGA component) using the 
endoscopy score from the central reader and self-reported data on stool frequency and 
rectal bleeding from the period prior to the subject being screened. 
NOTE: Stool samples may be obtained at any time during the visit.  Subjects who fail to meet 
clinical laboratory entry requirements may be re-tested as part of the screening period.  
Extensions of the screening window to accommodate clinical laboratories re-testing timeframes 
(excluding endoscopy with biopsy) are permitted as agreed with medical monitor. 
12.1.2. 
Eligibility Check/Wash-Out Period  
Each subject will receive a telephone call to confirm continued subject eligibility. For subjects 
not requiring a wash-out period the subject may return for Visit 2 once the diary has been 
completed for a minimum of 7 days immediately prior to dosing. Visit 2 should be completed no 
sooner than Day 8 from the time diary completion was initiated. Any changes in concomitant 
medication use and any newly occurring AEs since the last evaluation will be recorded.   
With the exception of subjects who most recently received the biologic certolizumab pegol 
(Cimzia), subjects requiring a wash-out will have a blood test administered 8 weeks after their 
last dose of biologic treatment to ensure that serum levels of any previous biologic treatments are 
below the level of detection. If it is confirmed that the levels of previous biologic treatment are 
undetectable and the subject has completed the diary for a minimum of 7 days immediately prior 
to dosing, the subject may return for Visit 2. Visit 2 should be completed no sooner than Day 8 
from the time diary completion was initiated. If the test results indicate that the previous biologic 
treatment is detectable, the subject will be required to complete a full 12-week wash-out period. 
For subjects receiving the biologic certolizumab pegol (Cimzia) a 12-week wash-out is required. 
The diary should be completed up to the time of the visit. Any changes in concomitant 
medication use and any newly occurring AEs since the last evaluation will be recorded. 
If the subject is not eligible, the subject should have any changes in concomitant medication use 
and any newly occurring AEs since the last evaluation recorded and should be removed from 
screening.   
12.1.3. 
Open-Label Treatment Period 
12.1.3.1. Baseline Visit (Visit 2, Day 0) 
12.1.3.1.1. Before Dosing 
Prior to administration of the first dose of investigational product on Day 0, the following 
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1. Review inclusion/exclusion criteria to confirm continued eligibility or screen failure 
status.  
NOTE: If the subject continues to be eligible for the study, the subsequent procedures 
should be performed.  If the subject is not eligible, the subject should have any changes in 
concomitant medication use and any newly occurring AEs since the last evaluation 
recorded and should be removed from screening.   
2. Perform a complete physical examination, including measurements of height and weight 
3. Collect vital signs, including systolic and diastolic blood pressures, pulse, respiration rate 
and temperature 
4. Collect blood sample for clinical laboratory tests 
5. Collect blood sample for plasma MDGN-002 concentration and PK analysis 
6. Collect blood sample for plasma ADA analysis 
7. Collect blood sample for exploratory analyses as defined in Table 1 
8. Collect urine sample for urinalysis 
9. Collect urine sample for urine β-hCG test (for females of childbearing potential only) 
10. Administer the CDAI (CD only) 
11. Administer the IBD-Q 
12. Review diary completion 
13. Assess and record concomitant medications and newly occurring AEs since the last 
evaluation 
In addition, ongoing AEs from the previous visit will be assessed and any change in their status 
will be recorded. 
12.1.3.1.2. Dosing and 60 Minutes Post-Dosing 
After completing the assessments shown in Section 12.1.3.1.1, subjects will receive MDGN-002 
by SQ injection in the abdomen in a zone of 4 to 10 cm from the umbilicus with the injection site 
rotated with each subsequent dose.  Vital sign assessments will be conducted within 60 minutes 
post-dosing. 
Subjects will remain in the clinic for 60 minutes after the investigational product has been 
administered.  During this time, the following details will be recorded: 
1. Any AEs occurring after dosing 
2. Any concomitant medications administered after dosing 
3. Assess subject response and available results against individual stopping rules criteria 
defined in Section 8.5.1.  
After completion of the post-dosing assessments, the subject may leave the clinic. 


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12.1.4. 
Visit 3 (Day 7 [± 3 days]) 
Subjects will return to the clinic on Day 7 (± 3 days), at which time the following procedures 
will be performed:  
1. Collect blood samples for plasma MDGN-002 concentration and PK analyses 
2. Assess and record any AEs and concomitant medications  
3. Review diary completion 
Assess subject response and available results against individual stopping rules criteria defined in 
Section 8.5.1.  In addition, ongoing AEs from the previous visit will be assessed and any change 
in their status will be recorded. 
12.1.5. 
Visit 4 (Day 14 [± 3 days]) 
Subjects will return to the clinic on Day 14 (± 3 days), at which time the following procedures 
will be performed prior to dosing:  
1. Perform a brief physical examination, including measurement of weight 
2. Collect vital signs, including systolic and diastolic blood pressures, pulse, respiration rate 
and temperature 
3. Collect blood sample for clinical laboratory tests 
4. Collect blood samples for plasma MDGN-002 concentration, PK and ADA analyses 
5. Administer the CDAI (CD only) 
6. Review diary completion 
7. Assess and record concomitant medication use and any newly occurring AEs since the 
last evaluation 
In addition, ongoing AEs from the previous visit will be assessed and any change in their status 
will be recorded. 
After completing these assessments, subjects will receive MDGN-002 by SQ injection in the 
abdomen in a zone of 4 to 10 cm from the umbilicus with the injection site rotated with each 
subsequent dose.  Vital sign assessments will be conducted within 60 minutes post-dosing. 
Subjects will remain in the clinic for 60 minutes after the investigational product has been 
administered.  During this time, the following details will be recorded: 
1. Any AEs occurring after dosing 
2. Any concomitant medications administered after dosing. 
After completion of the post-dosing assessments, the subject may leave the clinic. 
12.1.5.1. Visit 5 (Day 21 [± 3 days]) 
Subjects will return to the clinic on Day 21 (± 3 days), at which time the following procedures 
will be performed: 
1. Collect blood sample for plasma MDGN-002 concentration and PK analysis 


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2. Assess and record any AEs and concomitant medications  
3. Review diary completion 
4. Assess subject response and available results against individual stopping rules criteria 
defined in Section 8.5.1.   
In addition, ongoing AEs from the previous visit will be assessed and any change in their status 
will be recorded. 
12.1.5.2. Visit 6 (Day 28 [± 3 days]) 
Subjects will return to the clinic on Day 28 (± 3 days), at which time the following procedures 
will be performed prior to dosing: 
1. Perform a complete physical examination, including measurement of weight 
2. Collect vital signs, including systolic and diastolic blood pressures, pulse, respiration rate 
and temperature 
3. Perform 12-lead ECG 
4. Collect blood sample for clinical laboratory tests 
5. Collect blood samples for plasma MDGN-002 concentration, PK and ADA analyses 
6. Collect blood sample for exploratory analyses as defined in Table 1 
7. Collect stool for fecal calprotectin analysis 
8. Collect urine sample for urinalysis 
9. Collect urine sample for urine β-hCG test (for females of childbearing potential only) 
10. Administer the CDAI (CD only) 
11. Review diary completion 
12. Assess and record concomitant medication use and any newly occurring AEs since the 
last evaluation 
In addition, ongoing AEs from the previous visit will be assessed and any change in their status 
will be recorded. 
After completing these assessments, subjects will receive MDGN-002 by SQ injection in the 
abdomen in a zone of 4 to 10 cm from the umbilicus with the injection site rotated with each 
subsequent dose.  Vital sign assessments will be conducted within 60 minutes post-dosing. 
Subjects will remain in the clinic for 60 minutes after the investigational product has been 
administered.  During this time, the following details will be recorded: 
1. Any AEs occurring after dosing 
2. Any concomitant medications administered after dosing.   
NOTE: Stool samples may be obtained at any time during the visit 
3. Assess subject response and available results against individual stopping rules criteria 
defined in Section 8.5.1.   


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After completion of the post-dosing assessments, the subject may leave the clinic. 
12.1.5.3. Visit 7 (Day 35 [± 3 days]) 
Subjects will return to the clinic on Day 35 (± 3 days), at which time the following procedures 
will be performed: 
1. Collect blood sample for pharmacokinetic analysis 
2. Assess and record any AEs and concomitant medications  
3. Review diary completion 
4. Assess subject response and available results against individual stopping rules criteria 
defined in Section 8.5.1.   
In addition, ongoing AEs from the previous visit will be assessed and any change in their status 
will be recorded. 
12.1.5.4. Visit 8 (Day 42 [± 3 days]) 
Subjects will return to the clinic on Day 42 (± 3 days), at which time the following procedures 
will be performed prior to dosing: 
1. Perform a brief physical examination, including measurement weight 
2. Collect vital signs, including systolic and diastolic blood pressures, pulse, respiration rate 
and temperature 
3. Collect blood sample for clinical laboratory tests 
4. Collect blood sample for plasma MDGN-002 concentration and PK analysis 
5. Administer the CDAI 
6. Review diary completion 
7. Assess and record any AEs and concomitant medications 
In addition, ongoing AEs from the previous visit will be assessed and any change in their status 
will be recorded. 
After completing these assessments, subjects will receive MDGN-002 by SQ injection in the 
abdomen in a zone of 4 to 10 cm from the umbilicus with the injection site rotated with each 
subsequent dose.  Vital sign assessments will be conducted within 60 minutes post-dosing. 
Subjects will remain in the clinic for 60 minutes after the investigational product has been 
administered.  During this time, the following details will be recorded: 
1. Any AEs occurring after dosing 
2. Any concomitant medications administered after dosing. 
3. Assess subject response and available results against individual stopping rules criteria 
defined in Section 8.5.1.   
After completion of the post-dosing assessments, the subject may leave the clinic. 


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12.1.5.5. Visit 9 (Day 49 [± 3 days]) 
Subjects will return to the clinic on Day 49 (± 3 days), at which time the following procedures 
will be performed: 
1. Collect blood sample for plasma MDGN-002 concentration and PK analysis 
2. Assess and record any AEs and concomitant medications 
3. Review diary completion 
In addition, ongoing AEs from the previous visit will be assessed and any change in their status 
will be recorded 
12.1.5.6. Visit 10 (Day 56 [± 3 days]) 
Subjects will return to the clinic on Day 56 (± 3 days), at which time the following procedures 
will be performed: 
1. Perform a complete physical examination, including measurement of weight 
2. Collect vital signs, including systolic and diastolic blood pressures, pulse, respiration rate 
and temperature 
3. Perform 12-lead ECG 
4. Collect blood sample for clinical laboratory tests 
5. Collect blood samples for plasma MDGN-002 concentration, PK and ADA analysis 
6. Collect blood sample for exploratory analyses as defined in Table 1 
7. Collect stool for fecal calprotectin analysis 
8. Collect urine sample for urinalysis 
9. Collect urine sample for urine β-hCG test (for females of childbearing potential only) 
10. Administer the CDAI (CD only) 
11. Review diary completion 
12. Administer IBD-Q questionnaire 
13. Conduct the endoscopy and biopsy 
14. Calculate the Modified Mayo Score (excluding the PGA component) using the 
endoscopy score from the central reader and the diary data on stool frequency and rectal 
bleeding (UC only) 
15. Assess and record any AEs and concomitant medications 
16. Assess subject response and available results against individual stopping rules criteria 
defined in Section 8.5.1.   
In addition, ongoing AEs from the previous visit will be assessed and any change in their status 
will be recorded. 
NOTE: Stool samples may be obtained at any time during the visit. 


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12.1.6. 
Early Termination 
If a subject is withdrawn from the study for any reason, every effort must be made to conduct all 
Day 56 (Visit 10) procedures and assessments (see Section 12.1.5.6). 
12.1.7. 
Safety Follow-Up 
12.1.7.1. Visit 11 (Day 84 [± 3 days])  
Subjects will return to clinic 28 days (± 3 days) after Visit 10 or the early termination visit for a 
safety follow-up visit, as appropriate.  Subject will have blood collected for plasma MDGN-002 
concentration, PK and ADA analyses. Any concomitant medications and newly occurring AEs 
since the last visit will be recorded.  In addition, ongoing AEs from the previous visit will be 
assessed and any change in their status will be recorded. 
12.2. 
Study Duration 
The overall study duration is expected to be approximately 26 weeks (including up to 14 weeks 
of screening [inclusive of wash-out of up to 12 weeks, if required], 56 days of open-label 
treatment, and a follow-up visit approximately 28 days after the final dose of investigational 
product). 
The planned sequence and maximum duration of the study periods will be as follows: 
1. Screening period: approximately 2 weeks 
2. Wash-out period, if applicable: Up to 12 weeks from the subject’s last dose of biological 
treatment  
3. Open-label treatment period: 56 days (beginning on Day 0 with doses administered 
q14 days) 
4. Follow-up: 28 days after the last dose of investigational product. 
The maximum study duration for each subject is approximately 26 weeks. 
The maximum treatment duration for each subject is approximately 56 days, with SQ injections 
beginning on Day 0 and continuing every 14 (± 3) days through Day 42. 
Note:  Extensions of the screening window to accommodate clinical laboratory re-testing 
timeframes (excluding endoscopy with biopsy) are permitted as agreed with medical monitor. 
12.3. 
Assessments   
12.3.1. 
Safety Assessments 
Safety assessments will include monitoring of AEs, clinical laboratory tests, vital signs 
measurements, physical examinations (including measurement of weight) and 12-lead ECG 
parameters, as described below.  Demographic information and medical and medication histories 
will be obtained at the screening visit. 
All safety assessments are to be recorded on the appropriate eCRF. 


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The Investigator’s Brochure is the reference document for safety information pertaining to this 
study and is provided under separate cover. 
12.3.1.1. Demographic/Medical History 
Demographic information, a complete medical history (which includes surgical history), and 
medication history will be collected at the screening visit by appropriate site staff as delegated by 
the PI and reviewed and verified by a qualified licensed physician, physician’s assistant, or a 
nurse practitioner.  The medical history will be reviewed and recorded, including: 
• Date of birth 
• Sex 
• Race and ethnicity 
• Recent use of non-CD/UC medication within 30 days of Visit 1 
• CD/UC past and ongoing treatments (recall past year) 
• CD/UC-related surgical procedures and hospitalizations 
• History of respiratory, cardiovascular, renal, gastrointestinal, hepatic, endocrine, 
hematological, neurological, psychiatric, and other diseases; history of surgical 
procedures 
12.3.1.2. Vital Signs 
Vital signs, including systolic and diastolic blood pressure, pulse, and respiration rate, will be 
collected as shown in the Schedule of Assessments (see Table 1).  Vital signs must be within the 
ranges listed below during Screening (Visit 1) and prior to enrollment at Visit 2:  
• Blood Pressure: 80/50 to 140/90 mm/Hg 
• Respiratory Rate: 8-20 breaths per minute 
• Pulse: 50-120 beats per minute 
• Temperature: 97.8°F to 99.1°F (36.5°C to 37.3°C)/average 98.6°F (37°C) 
Vital signs will be taken pre- and post-dose at Visits 2, 4, 6 and 8. Pre-dose vital signs should be 
taken within 60 minutes before dosing.  Post-dose vital signs should be taken at least 60 minutes 
after dosing, prior to discharge. Additional blood pressure and pulse measurements may be 
performed, as determined by the investigator, in order to ensure appropriate monitoring of 
subject safety and accurate recording of vital sign measurements. Any changes from baseline 
deemed clinically significant by the investigator are to be recorded as AEs. 
The same method of blood pressure measurement (auscultatory or oscillometric) should be used 
and documented throughout the study for all subjects.  In addition, the conditions of vital signs 
measurements should be controlled and as consistent as possible in order to minimize variability 
of the readings.  It is advised that measurements be collected at a comfortable room temperature 
with little to no background noise, using the same (appropriately sized) cuff placed at the same 
location on the same arm.  The cuff should have a bladder length that is 80% and a width that is 
at least 40% of arm circumference (a length-to-width ratio of 2:1).  


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The subject should be asked to remove all clothing that covers the location of cuff placement. 
The subject should not have exercised or consumed caffeine, alcohol, or nicotine within 
30 minutes of collection.  The subject should be comfortably seated, with the legs uncrossed, 
with feet flat on the floor, and the back and arm supported, such that the middle of the cuff on the 
upper arm is at the level of the right atrium (the mid-point of the sternum).  The subject should 
be instructed to relax as much as possible for at least 5 minutes prior to collection.  The subject 
should remain quiet during this time and throughout the measurement. 
The bladder should be deflated (calibrated for oscillometric method or manually by auscultatory 
method) at a rate of 2-3 mmHg/sec (and the first and last audible sounds recorded as systolic and 
diastolic pressures) after at least 5 minutes of rest. 
The use of automated devices for measuring pulse is acceptable, although, when done manually, 
pulse should be measured in the brachial/radial artery for at least 30 seconds. When the timing of 
these measurements coincides with a blood collection, blood pressure and pulse should be 
obtained prior to the nominal time of the blood collection. 
12.3.1.3. Physical Examination  
A complete physical examination, including measurements of weight, will be conducted by a 
qualified licensed physician, physician’s assistant, or a nurse practitioner at the screening visit 
and at Visits 2 (Day 0), 6 (Day 28) and 10 (Day 56).  Brief physical examinations, including 
measurements of weight, will be conducted at Visits 4 (Day 14), and 8 (Day 42) (see Table 1).  
The complete physical examination will include a review of the following body systems: 
• General appearance 
• Skin 
• Head, eyes, ears, nose, and throat 
• Spine/neck/thyroid 
• Musculoskeletal 
• Respiratory 
• Cardiovascular 
• Neurological 
• Abdomen (including liver and kidneys) 
Any abnormalities or changes in intensity from baseline noted during the review of body systems 
should be documented in the medical record and reported on the appropriate eCRF.  If a new 
clinically significant abnormal finding is reported after the baseline examination, it must be 
captured as an AE and documented on the appropriate AE eCRF.  In addition, resolution of any 
abnormal findings during the study will be noted in the medical record and eCRF if clinically 
significant. 
The brief physical examination will include a review of general appearance, skin, head, eyes, 
ears, nose, and throat, abdomen, joints and perianal area at a minimum, with other systems 
reviewed as medically needed.  Measurement of weight will also be collected. 


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Subjects will remove their shoes before measurements of weight (in kg) are taken.  
12.3.1.4. Electrocardiogram  
A standard 12-lead ECG will be conducted by appropriate site staff as delegated by the PI and 
the results will be reviewed and verified by the PI or a qualified licensed physician delegated by 
the PI as shown in the Schedule of Assessments (see Table 1).  
The 12-lead ECG will be performed after the subject has been supine for approximately 
5 minutes.  All ECG recordings will be identified with the subject number, subject initials, date, 
and time of the recording and will be included in the subject’s study file. 
The subject should be asked to remove all clothing that covers the location of lead placement. 
The subject should not have exercised or consumed caffeine, alcohol, or nicotine within 
30 minutes prior to collection.  
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality.  It is important that leads are placed in the 
same positions each time in order to achieve precise ECG recordings.  One complete recording, 
including a 10-second rhythm strip, should be taken at each time point.  It should be immediately 
assessed as a valid recording and if not valid, it should be repeated.  All ECGs collected are to be 
entered in the eCRF. 
All ECGs will be performed using the equipment supplied by the site. ECG recordings will be 
collected and a copy provided to the study sponsor.  
The following parameters will be recorded on the appropriate eCRF: heart rate, PR, respiration 
rate (RR), QRS, and QT interval; corrected QT intervals using both the Bazett (QTcB) and 
Fridericia (QTcF) formulas will also be recorded. The investigator’s assessment of the ECG 
tracing as normal or abnormal must be documented, and if abnormal, his/her determination of 
whether the abnormality is clinically significant will be documented on the tracing and recorded 
in the eCRF.   
All ECG values that, in the investigator’s opinion, show clinically relevant or pathological 
changes during or after termination of the investigational product are to be discussed with the 
medical monitor and reported as AEs and followed, as described in Section 12.3.1.6.2. 
12.3.1.5. Clinical Laboratory Assessments 
12.3.1.5.1. Clinical Laboratory Tests 
Samples for the following clinical laboratory tests will be collected at the time points specified in 
the Schedule of Assessments (see Table 1).   


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Hematology 
Hemoglobin, hematocrit, red blood cell count, red blood cell indices, 
mean corpuscular hemoglobin, mean corpuscular hemoglobin 
concentration, mean corpuscular volume, platelet count (or estimate), and 
white blood cell count including differential 
Serum chemistry 
Albumin, total bilirubin, total protein, calcium, alkaline phosphatase, 
alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl 
transferase, blood urea nitrogen, creatinine, creatine kinase, glucose, 
sodium, potassium, chloride, bicarbonate, lactate dehydrogenase, uric 
acid, eGFR, and C-reactive protein 
Other 
ADAs; LIGHT, cytokines (e.g. IL-1 beta, IL-6, IL-8, and TNF-alpha, and 
other exploratory cytokines), flow cytometry analysis of peripheral blood 
leukocytes and RNA sequencing 
Fecal chemistry 
Fecal calprotectin, C. difficile 
Urinalysis 
pH, specific gravity, hemoglobin, white blood cells, red blood cells, 
glucose, casts, protein, ketones, epithelial cells, crystals, mucous threads, 
bacteria, yeast, color, and appearance 
Serum & Urine 
β-hCG test 
For women of childbearing potential only 
Urine drug screen 
(screening visit 
only as warranted) 
Amphetamines, barbiturates, benzodiazepines, cocaine, opiates, 
phencyclidine, cannabinoids, propoxyphene and methadone. 
Testing for 
previous biologics 
(for subjects 
requiring wash-
out) 
Commercial test to detect the serum concentrations of four of the 
common biologic drugs and biosimilars (infliximab [Remicade], 
infliximad-adba [Renflexis], infliximab-dyyb [Inflectra], adalimumab 
[Humira], adalimumab-adbm [Cyltezo], adalimumab-atto [Amjevita] 
vedolizumab [Entyvio] and ustekinumab [Stelara]).   
Note: Testing is not required for certolizumab pego1 (Cimzia) as 
there is no commercially available test to determine serum 
concentration.  
Laboratory specimens will be collected and analyzed at the laboratories specified in the study 
Laboratory Manual(s) or guidelines.  
12.3.1.5.2. Sampled Blood Volume 
The sampled blood volume to be taken from each subject is shown in Table 3.  (See 
Section 12.3.2.1 for details regarding pharmacokinetic blood sampling.) 


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Table 3 
Blood Samples Taken from Each Subject 
Assessment 
Sample Volume 
(mL) 
Number of 
Samples 
Total Volume 
(mL) 
Safety 
Hematology 
2.0 
6 
12.0 
 
Clinical chemistry 
3.5 
6 
21.0 
MDGN-002 concentration and PK analysis 
(Pre-dose Day 0) 
2.0 
2 
4.0 
MDGN-002 concentration and PK analysis 
2.0 
9 
18.0 
Anti-drug Antibodies (ADA) 
2.0 
5 
10.0 
Flow Cytometry 
3.0 
3 
9.0 
RNA sequencing 
2.5 
3 
7.5 
Cytokines 
3.5 
3 
10.5 
LIGHT 
2.0 
3 
6.0 
Testing for previous biologics 
6.0 
1 
6.0 
Total mL 
-- 
-- 
104.0  
12.3.1.5.3. Tuberculosis (TB) testing 
  
All subjects will be screened for tuberculosis using QuantiFERON-TB Gold (QFT) blood test, or 
tuberculin skin reaction test (PPD skin test) at screening. If the subject’s PPD tine skin test is 
≥ 5 mm, a chest x-ray is required to be performed to rule out active or latent pulmonary TB 
infection. Subjects will be excluded from the study if they have active or latent TB as 
demonstrated by any of the following:  
• A positive QFT test result or a positive PPD skin test reaction ³10 mm.  
• Chest x-ray in which active or latent pulmonary TB cannot be ruled out.  
12.3.1.5.4. Genotyping for Decoy Receptor 3 
For patients with CD, 2 mL of saliva for genotyping will be collected in a designated collection 
vehicle according to the manufacturer’s instructions. 
Deoxyribonucleic acid (DNA) is isolated from the saliva samples from each study subject and 
then evaluated for genetic alteration in TNFRSF6B encoding for the protein DcR3 or alterations 
in at least one DcR3 network gene.  All genotyping will be performed in a CLIA certified 
laboratory specified in the laboratory manual(s) and guidance(s). Any remaining DNA samples 
will be stored for future biomarker studies. 
12.3.1.5.5. LIGHT, Cytokines, RNA Sequencing and Flow Cytometry Exploratory Analyses 
Blood samples will be collected for exploratory analyses. Exploratory analyses may include but 
are not limited to of LIGHT biomarker, cytokines (e.g. IL-1 beta, IL-6, IL-8,TNF-alpha, and 
other exploratory cytokines), ribonucleic acid (RNA) sequencing; flow cytometry of peripheral 
blood leukocytes at visits specified in Table 1. Exploratory biomarker analyses will be performed 
at the laboratories specified in the laboratory manual(s) and guidance(s). 


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12.3.1.5.6. Testing for Previous Biologics 
An adequate wash-out period is required to avoid the potential for confounding the effects 
related to dosing with MDGN-002 following the prior use of other biologics. In order to allow 
for a shorter wash-out period, commercial tests available to identify the serum concentrations of 
biologics will be utilized. With the exception of Cimzia, a blood test will be administered to 
subjects undergoing wash-out 8 weeks after their last dose of biologic treatment to ensure that 
serum levels of any previous biologic treatments are below the level of detection. If the serum 
concentration of biologic treatment is undetectable (i.e., below the level of quantification) 
according to the respective, CLIA-validated commercial test, then the subject is deemed to have 
completed the wash-out period and will be able to proceed to Visit 2. If biologic treatment is 
detected, then the subject will complete a full 12-week wash-out period prior to proceeding to 
Visit 2. For subjects receiving the biologic certolizumab pegol (Cimzia) a 12-week wash-out is 
required. 
12.3.1.5.7. Specimen Handling Requirements 
The transmission of infectious agents may occur through contact with contaminated needles, 
blood or blood products and/or laboratory specimens.  Consequently, appropriate blood, body 
fluid and specimen precautions should be employed by all study personnel involved in the 
collection and handling of specimens in both the clinic and laboratory settings.  Refer to current 
recommendations of the appropriate authorities. 
In addition to appropriate handling of subject samples, specific regulations exist regarding the 
shipment of biologic samples.  Procedures and regulations for the packaging and shipping of 
infectious samples are outlined in the study Laboratory Manual(s).  The investigator is 
responsible for ensuring that all study samples that are to be transported to another location are 
appropriately packed and shipped according to the applicable regulations. 
12.3.1.5.8. Evaluation of Laboratory Values 
The normal ranges of values for the clinical safety laboratory assessments will be provided by 
the responsible laboratory and submitted to Aevi Genomic Medicine, LLC prior to the beginning 
of the study.  They will be regarded as the reference ranges upon which clinical decisions will be 
made. 
If a laboratory value is out of the reference range, it is not necessarily clinically relevant, with the 
exception of those defined as exclusionary per Section 9.2.  The investigator must evaluate the 
out-of-range values and record his/her assessment of their clinical relevance in the appropriate 
eCRF. 
All laboratory values which, in the investigator’s opinion, show clinically relevant or 
pathological changes during or after termination of the treatment are to be discussed with the 
medical monitor and reported as AEs and followed, as described in Section 12.3.1.6.2. 


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12.3.1.6. Adverse Events   
12.3.1.6.1. Adverse Event Collection 
The investigator is responsible for the detection and documentation of events meeting the criteria 
and definitions of an AE (Section 12.3.1.6.2) or SAE (Section 12.3.1.6.6) described below.  At 
each visit, the subject will be allowed time to spontaneously report any issues since the last visit 
or evaluation.  At each visit, the investigator will then monitor, ask about, and/or evaluate AEs 
using non-leading questions, such as: 
• “How are you feeling?” 
• “Have you experienced any issues since your last visit?” 
• “Have you taken any new medications since your last visit?” 
Any clinically relevant observations made during each visit will also be considered AEs.  
12.3.1.6.2. Definition of Adverse Events, Period of Observation and Recording of Adverse 
Events 
An AE is defined as any untoward medical occurrence in a clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
the product.  An AE can therefore be any unfavorable and unintended sign (including a new, 
clinically important abnormal laboratory finding), symptom, or disease, temporally associated 
with the product, whether or not related to the product. 
All AEs are collected from the time of the informed consent is signed until the final safety 
follow-up visit (described in Section 8.2.3).  This includes events occurring during the screening 
phase of the study, regardless of whether investigational product is administered.  Where 
possible, a diagnosis rather than a list of symptoms should be recorded.  If a diagnosis has not 
been made, then each symptom should be listed individually.  All AEs should be captured on the 
appropriate AE eCRF and in source documents.  In addition to AEs, unexpected benefits outside 
the investigational product indication should also be captured in the source documents and AE 
eCRF.  
All AEs must be followed to closure (ie, the subject’s health has returned to his/her baseline 
status or all variables have returned to normal), regardless of whether the subject is still 
participating in the study.  Closure indicates that an outcome is reached, stabilization is achieved 
(the investigator does not expect any further improvement or worsening of the event), or the 
event is otherwise explained.  When appropriate, medical tests and examinations are performed 
so that resolution of an event(s) can be documented. 
12.3.1.6.3. Severity of Adverse Events 
The severity of AEs must be recorded during the course of the event, including the start and stop 
dates for each change in severity.  An event that changes in severity should be captured as a new 
event.  Worsening of pre-treatment events after initiation of the investigational product must be 
recorded as new AEs.  For example, if the subject experiences mild, intermittent headaches prior 
to dosing with investigational product and the headache intensity increases to moderate after the 


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first dose of investigational product, a new AE of moderate intermittent headaches is to be 
recorded in the source documents and eCRF.   
The medical assessment of clinical severity of an AE will be determined using the definitions 
outlined in Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 (Published 
May 28, 2009 with Version 4.0.3 on June 14, 2010 by the US Department of Health and Human 
Services, National Institutes of Health, National Cancer Institute): 
Grade 1  
Mild; asymptomatic or mild symptoms; or clinical or diagnostic 
observations only; or intervention not indicated 
Grade 2 
Moderate; or minimal, local or non-invasive intervention 
indicated; or limiting age-appropriate instrumental activities of 
daily living (ADL) 
Grade 3 
Severe or medically significant but not immediately life-
threatening; or hospitalization or prolongation of hospitalization 
indicated; or disabling; or limiting self-care ADL. 
Grade 4 
Life-threatening consequences; or urgent intervention indicated. 
Grade 5 
Death related to AE 
It is important to distinguish between severe AEs and SAEs.  Severity is a classification of 
intensity whereas an SAE is an AE that meets serious criteria as described in 
Section 12.3.1.6.6.2. 
Please refer to the above-referenced CTCAE document for full description of CTCAE terms and 
instrumental and self-care ADLs.  
12.3.1.6.4. Relationship Categorization 
A physician/investigator must make the assessment of relationship to the investigational product 
for each AE.  The investigator should decide whether, in his or her medical judgment, there is a 
reasonable possibility that the event may have been caused by the investigational product.  If 
there is no valid reason for suggesting a relationship, then the AE should be classified as “not 
related.”  Otherwise, the AE should be categorized according to the guidelines below.  The 
causality assessment must be documented in the source document and the eCRF. 


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Not related 
Exposure to Investigational Product (IP) has not occurred; 
OR 
The administration of IP and the occurrence of the AE are not 
reasonably related in time; 
OR  
The AE is considered likely to be related to an etiology other 
than the use of the IP; that is, there are no facts/evidence or 
arguments to suggest a causal relationship to the IP. 
Possibly related 
The administration of the IP and the occurrence of the AE are 
reasonably related in time  
AND 
The AE could not be explained equally well by factors or causes 
other than exposure to IP. 
Probably related 
The administration of IP and the occurrence of the AE are 
reasonably related in time  
AND 
The AE is more likely explained by exposure to IP than by other 
factors or causes. 
IP=investigational product 
12.3.1.6.5. Outcome at the Time of Last Observation 
The outcome of an AE at the time of last observation will be classified as: 
• Recovered/resolved 
• Recovered/resolved with sequelae 
• Recovering/resolving 
• Not recovered/not resolved 
• Fatal (see Section 12.3.1.6.6.5) 
• Unknown 
12.3.1.6.6. Serious Adverse Events 
12.3.1.6.6.1. Reporting of Serious Adverse Events 
Initial and follow-up SAE reports must be completed by the investigator and sent to the sponsor 
and the CRO within 24 hours of the first awareness of a SAE.   
The investigator must complete, sign and date the appropriate SAE form and verify the accuracy 
of the information against corresponding source documents.  No source documents are to be sent 


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with the SAE form.  This SAE information (form) is to be sent to the CRO pharmacovigilance 
department, with a copy to the Aevi Genomic Medicine medical monitor by e-mail or fax at one 
of the methods noted below. For questions on SAE reporting, please call the drug safety helpline 
noted below. 
 
 
 
 
 
 
12.3.1.6.6.2. Definition of Serious Adverse Event 
An SAE is any untoward medical occurrence, whether considered to be related to the 
investigational product or not, that at any dose: 
• Results in death 
• Is life-threatening  
NOTE:  The term “life-threatening” in the definition of “serious” refers to an event in 
which the subject was at risk of death at the time of the event; it does not refer to an event 
which hypothetically might have caused death if it were more severe. 
• Requires inpatient hospitalization or prolongation of existing hospitalization  
NOTE:  Inpatient hospitalization is defined as 24 hours in a hospital or an overnight stay. 
An elective hospital admission to treat a condition present before exposure to the test 
drug, or a hospital admission for a diagnostic evaluation of an AE, does not qualify the 
condition or event as an SAE.  Further, an overnight stay in the hospital that is only due 
to transportation, organization, or accommodation problems and without medical 
background does not need to be considered an SAE. 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly  
NOTE:  A congenital anomaly in an infant born to a mother who was exposed to the IP 
during pregnancy is an SAE.  However, a newly diagnosed pregnancy in a subject that 
has received an IP is not considered an SAE unless it is suspected that the IP(s) interacted 
with a contraceptive method and led to the pregnancy. 
• Is an important medical event  
NOTE:  Medical and scientific judgment should be exercised in deciding whether it is 
appropriate to consider other situations serious, such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the subject or may require intervention to prevent one of the other outcomes 
listed in the definition above.  Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions 
that do not result in hospitalization, or development of drug dependency or drug abuse. 






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Abuse 
Persistent or sporadic intentional intake of IP when used for a non-
medical purpose (for example, to get high, for potential 
psychoactive effects) in a manner that would be detrimental to the 
individual and/or society 
Misuse 
Intentional use of IP other than as directed or indicated at any dose. 
This includes where IP is not used as directed at the dose prescribed 
in the protocol.  
Overdose 
Intentional or unintentional intake of a dose of IP exceeding the 
dose prescribed to the subject as part of the study. 
Medication error 
Error made in prescribing, dispensing, administration and/or use of 
IP.  A medication error is reportable to the sponsor or its designee if 
it involves: 
• Administration and/or use of an unassigned treatment (for 
example, incorrect IP kit used by subject) 
• Administration and/or use of expired IP 
IP=investigational product 
NOTE: An abuse, misuse, overdose or medication error event can meet more than 1 category. 
Missing doses are not considered medication error events and do not need to be reported.   
12.3.1.6.8. Reporting to Regulatory Agency, Institutional Review Board and Site 
The sponsor or its designee is responsible for notifying the relevant regulatory authorities of 
related, unexpected SAEs. 
In addition, the sponsor or its designee is responsible for notifying active sites of all related, 
unexpected SAEs occurring during all interventional studies across the development program.  
The investigator is responsible for notifying the local IRB or the relevant local regulatory 
authority of all SAEs that occur at his/her site, as required. 
12.3.2. 
MDGN-002 Concentration, Pharmacokinetic and Anti-Drug Antibody 
Assessments 
The name and address of the bioanalytical laboratory for this study is defined in the Laboratory 
Manual(s) and guidance(s). 
Pharmacokinetics will be calculated from the plasma concentrations of MDGN-002.  
12.3.2.1. Blood Sample Collection and Analysis 
Blood samples will be collected within 60 minutes prior to the administration of MDGN-002 on 
Days 0, 14, 28 and 42 (Visits 2, 4, 6, and 8 respectively) and at any time on Days 7, 21, 35, 49, 
56, and 84 (Visits 3, 5, 7, 9, 10, and 11) and processed to plasma (see laboratory manual).  Time 
of PK samples will be recorded in the electronic CRF. A total of 1.0mL plasma (0.5 mL per PK 
and ADA sample) will be collected from each subject to measure plasma concentrations of 


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MDGN-002 or ADA samples.  Pharmacokinetic and ADA samples will be processed according 
to the methods and directions set forward in the Laboratory Manual(s) and guidance(s). 
Pharmacokinetic and ADA plasma sample analysis will be performed by laboratory defined in 
the Laboratory Manual(s) and guidance(s), according to their SOPs using a validated enzyme-
linked immunosorbent assay (ELISA).  Assay and analysis details will be described in the 
method validation and bioanalytical information. 
12.3.3. 
Assessment of Efficacy 
12.3.3.1. Crohn’s Disease Activity Index 
The CDAI will be completed by a qualified licensed physician, physician’s assistant, or a nurse 
practitioner at the times shown in the Schedule of Assessments (see Table 1). Site personnel 
conducting the CDAI should use the following link to derive individual and total scores: 
https://www.thecalculator.co/health/Crohn’s-Disease-Activity-Index-(CDAI)-Calculator-
1035.html, with standard weights calculated as follows:  
• Standard weight for men = (height in m)2 x 22.1 
• Standard weight for women = (height in m)2 x 20.8 
Information on abdominal pain and frequency of loose and watery stools should be taken from 
subject diary information (see Section 12.3.3.4). The same individual should complete the CDAI 
for a given subject throughout the study, whenever possible.   
The CDAI was developed by the National Cooperative Crohn’s Disease Study group and 
published in 1976 by Best et al (1976) to determine variables that best predicted disease activity.  
A total of 8 items were identified (abdominal pain, number of liquid stools, general well-being, 
extraintestinal complication, use of antidiarrheal drugs, abdominal mass, hematocrit, and body 
weight).  Each item is scored on individual parameter criteria.  Total CDAI scores can range 
from 0 to approximately 600 with higher scores indicating more active disease.  The CDAI has 
been the most frequently used efficacy scale for interventional trials in CD (Sostegni et al, 2003). 
12.3.3.2. Modified Mayo Score 
The Modified Mayo Score (excluding the PGA component) includes stool frequency, rectal 
bleeding, and the appearance of mucosa upon endoscopy. Stool frequency will be based on a 
scale of 0 to 3 (0 = normal, 1 = 1 to 2 stools/day > normal, 2 = 3 to 4 stools/day > normal, 3 = > 
4 stools/day > normal).  Rectal bleeding will be based on a scale of 0 to 3 (0 = none, 1 = streaks 
of blood, 2 = obvious blood, 3 = blood alone passed).  Appearance of mucosa upon endoscopy 
will be based on a scale of 0 to 3 (0 = normal, 1 = mild friability, 2 = moderate friability, 3 = 
exudation, spontaneous bleeding). The score consists of the sum of all 3 criteria and can range 
from 0 to 9, with higher scores indicating more severe disease. This score will be calculated at 
Visit 1 and Visit 10 using the endoscopy score from the central reader, self-reported data on stool 
frequency and rectal bleeding from the period prior to the subject being screened for Visit 1 and 
data from the patient diary for Visit 10. 
 


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12.3.3.3. Endoscopy with Biopsy and Histology 
All subjects who enroll in the study will undergo an endoscopy with biopsy at screening and 
again at Day 56 (Visit 10) or at early termination.  Screening endoscopies may be performed 
either as a stand-alone endoscopy for purposes of this protocol or as a clinically-required 
endoscopy, provided consenting procedures for this study were completed prior to endoscopy.  
Endoscopy evaluation for patients with CD will use the SES-CD.  The SES-CD is a simple, easy-
to-use endoscopic scoring system developed specifically for CD.  It assesses 4 variables: size of 
ulcers, percentage of ulcerated surface, percentage of affected surface and the presence of 
narrowing across 4 categories per variable on a scale of 0 to 3 (Daperno et al 2004).   
Endoscopic evaluation for patients with UC will use the Mayo Endoscopy Score.  The Mayo 
Endoscopy Score is a simple, easy-to-use scoring system in order to evaluate ulcerative colitis 
stage, based only on endoscopic exploration.   
Biopsies taken at screening will be assessed for histological confirmation of disease.  Each 
subject will have screening and Visit 10/ET biopsy samples retained for evaluation of 
exploratory parameters (which may include but is not limited to DcR3, LIGHT, HVEM and 
LTβR) which may occur after trial completion.  Further information on endoscopic transmission 
to the central reader and assessment can be found in the endoscopy manual. Information on 
biopsy collection requirements for exploratory parameters are found in the study sample 
guidelines. 
12.3.3.4. Patient-reported Assessment of Well-being, Abdominal Pain and Stool 
Frequency (Crohn’s Disease Patients) 
All CD subjects who enroll in the study will be required to report their daily assessment of well-
being, abdominal pain and stool frequency including loose and/or watery stools via a diary 
(electronic or hard copy). Abdominal pain will be assessed on a scale of 0 to 3 with higher values 
indicating greater pain severity.  The stool frequency including number of loose and/or watery 
stools per day, equivalent to a score of a 6 or 7 on the Bristol Stool Scale, will be recorded.  
Loose stools are described as fluffy pieces with ragged edges, a mushy stool.  Watery stools are 
described as watery, no solid pieces (O’Donnell et al, 1990).   
12.3.3.5. Patient-reported Assessment of Stool Frequency and Rectal Bleeding (Ulcerative 
Colitis Patients) 
All UC subjects who enroll in the study will be required to report their daily assessment of stool 
frequency and rectal bleeding via a diary.  Stool frequency is to be recorded as an increase from 
“normal” where normal is the subject’s bowel movement pattern when healthy, ideally prior to 
UC diagnosis or for a 24 hour period during a period of disease remission. 
12.3.4. 
Quality of Life Assessment – Inflammatory Bowel Disease Questionnaire 
The IBD-Q is a 32 item questionnaire validated to measure quality of life in CD and UC.  The 
IBD-Q assesses the dimensions of bowel function, emotional status, systemic symptoms and 
social function (Guyatt G, 1989).  The IBD-Q will be completed by all subjects at screening 
(Visit 1),  before dosing (Visit 2), and at the end of the open-label treatment period or early 
termination (Visit 10/ET) (see Table 1).   


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13. 
STATISTICS 
Detailed descriptions of data summaries and listings will be provided in the Statistical Analysis 
Plan, which will be finalized prior to database lock.  The sections below provide a summary of 
the planned statistical methods. 
13.1. 
Statistical Methods 
Pharmacokinetic, efficacy and quality of life data will be summarized with traditional descriptive 
statistics.  Continuous variables will be summarized with N, mean, standard deviation, and range.  
Categorical variables will be summarized by frequencies and percentages. 
No formal inferential analyses are planned. 
13.1.1. 
Analysis Populations 
The Safety Population will include all subjects who are enrolled in the study and receive any 
amount of investigational product.  The Pharmacokinetic Population will include all subjects 
who received their assigned dose of MDGN-002 and for whom MDGN-002 plasma 
concentration data are available.  The Efficacy Population will include all subjects who have a 
baseline and at least 1 post-baseline efficacy score.   
13.1.2. 
Statistical Analyses 
Analyses of efficacy will focus on the Efficacy Population.  Results of endpoints (e.g., CDAI, 
SES-CD, abdominal pain and loose/watery stool frequency and IBD-Q (CD only; Modified 
Mayo Score, stool frequency, rectal bleading, endoscopic appearance, and IBD-Q (UC only) will 
be summarized by visit for each cohort, both as raw scores and the change from baseline value.  
For CD, the CDAI individual and total scores will be derived programmatically using recorded 
data from patient diary, responses to CDAI questions, laboratory tests, and physical exam results. 
For UC, the Modified Mayo Score individual and total scores will be derived programmatically 
using recorded data from patient diary and endoscopy results. Quantitative endoscopy and biopsy 
results will also be summarized for both the Baseline and End of study visits.  
Analyses of safety data will be focused on the Safety Population (as defined in Section 13.1.1). 
Safety variables include treatment-emergent AEs (TEAEs), clinical laboratory results, vital signs 
measurements, ECG results, and physical examination findings. 
Adverse events will be coded using Medical Dictionary for Regulatory Affairs (MedDRA).  
TEAEs are defined as any AE having first onset or worsening in severity after the first 
administration of IP.  TEAEs will be classified by system organ class (SOC) and preferred term 
and summarized by the number of subjects reporting each event for each cohort and overall.   
For clinical laboratory tests, descriptive summaries of actual (absolute) values and change from 
baseline values will be presented by cohort for each study visit.   
Vital signs (systolic and diastolic blood pressure, pulse, and respiratory rate) and ECG results 
will be summarized by visit and cohort using appropriate descriptive statistics.   
Data in this open-label study will be monitored continually and may be analyzed at any time. 


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13.2. 
Sample Size Determination 
This is the first use of MDGN-002 in the intended population of patients with CD or UC resistant 
to anti-TNFα monoclonal antibodies.  The sample size of the study was based on feasibility. 
 


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14. 
STUDY CONDUCT 
Steps to ensure the accuracy and reliability of data include the selection of a qualified 
investigator and appropriate study site, review of protocol procedures with the investigator and 
associated personnel prior to the study, periodic monitoring visits, and meticulous data 
management. 
14.1. 
Sponsor and Investigator Responsibilities 
14.1.1. 
Sponsor Responsibilities 
The sponsor is obligated to conduct the study in accordance with strict ethical principles 
(Section 16).  The sponsor reserves the right to withdraw a subject from the study (Section 9.6), 
to terminate participation of a study site at any time (Section 14.5), and/or to discontinue the 
study (Section14.4). 
Aevi Genomic Medicine agrees to provide the investigator with sufficient material and support 
to permit the investigator to conduct the study according to the study protocol. 
14.1.2. 
Investigator Responsibilities, Protocol Adherence and Investigator Agreement 
By signing the Investigator’s Agreement (Appendix 18.1), the investigator indicates that she/he 
has carefully read the protocol, fully understands the requirements, and agrees to adhere to the 
study procedures as detailed in this protocol.  The investigator is responsible for enrolling only 
those subjects who have met the protocol eligibility criteria. 
The investigator also agrees to conduct this study in accordance with all laws, regulations, and 
guidelines of the pertinent regulatory authorities, including and in accordance with the 
International Conference on Harmonisation (ICH) Guidance for Industry E6 GCP and in 
agreement with the Declaration of Helsinki.  While delegation of certain aspects of the study to 
subinvestigators and study coordinators is appropriate, the investigator will remain personally 
accountable for closely overseeing the study and for ensuring compliance with the protocol and 
all applicable regulations and guidelines.  The investigator is responsible for maintaining a list of 
all persons that have been delegated study-related responsibilities (e.g., subinvestigators and 
study coordinators) and their specific study-related duties.  
The investigator should ensure that all persons who have been delegated study-related 
responsibilities are adequately qualified and informed about the protocol, investigational 
products, and their specific duties within the context of the study.  The investigator is responsible 
for providing Aevi Genomic Medicine with documentation of the qualifications, GCP training, 
and research experience for themselves and their staff as required by the sponsor and the relevant 
governing authorities. 
According to local laws and regulations, the investigator, sponsor or sponsor designee will 
communicate with the IRB to ensure accurate and timely information is provided throughout the 
study. 


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14.2. 
Study Documents 
All documentation and material provided by Aevi Genomic Medicine for this study are to be 
retained in a secure location and treated as confidential material. 
14.2.1. 
Case Report Forms 
By signing the Investigator’s Agreement (Appendix 18.1), the investigator agrees to maintain 
accurate eCRFs and source documentation as part of the case histories for all subjects who sign 
an Informed Consent Form. 
Case report forms are considered confidential documents and should be handled and stored 
accordingly.  The sponsor or its designee will provide the necessary training on the use of the 
specific eCRFs used during the study to ensure that the study information is captured accurately 
and appropriately. 
To ensure data accuracy, eCRF data for individual subject visits should be completed as soon as 
possible after the visit.  All requested information must be entered in the eCRF according to the 
completion guidelines provided by the sponsor or its designee.  All data will have separate 
source documentation; no data will be recorded directly into the eCRF.  
The eCRFs will be signed by the investigator or a subinvestigator to whom this authority has 
been delegated.  These signatures serve to attest that the information contained in the eCRF is 
accurate and true. 
14.2.2. 
Recording and Retention of Source Data and Study Documents 
All study information must be recorded in the subject’s medical records.  
Data recorded in the eCRF must be supported by corresponding source documentation.  
Examples of acceptable source documentation include, but are not limited to, hospital records, 
clinic and office charts, laboratory reports and notes, and recorded data from automated 
instruments, memoranda, and pharmacy dispensing records. 
14.2.3. 
Video Recordings 
The endoscopic examinations will be recorded to allow for central reading and scoring of 
CD/UC in study participants.  These recordings will be stored at a vendor designated by the 
Sponsor on a secure computer server and will not be labeled with any information that allows 
direct identification of the subject. 
14.3. 
Data Quality Control 
Aevi Genomic Medicine and its designees will perform quality control checks on this clinical 
study. 
14.3.1. 
Access to Study and Source Documents 
Aevi Genomic Medicine and/or designee will conduct site visits to monitor the study and ensure 
compliance with the protocol, GCP, and applicable regulations and guidelines.  The consent form 
includes a statement by which the subject agrees to the monitor/auditor from the sponsor or its 
representatives, national or local authorities, or the IRB, having access to the source data (for 






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investigator’s notice, and the sponsor shall have a further opportunity to retain such materials at 
the sponsor’s expense. 
14.5.2. 
Sample Retention 
All samples will be retained according to applicable Standard Operating Procedures and 
regulations.  Blood and biopsy samples may be stored and used for further analysis related to this 
research.  
Saliva samples may be used for purposes related to this research.  Samples will be given a unique 
code that will include no information that will identify the subject.  They will be stored securely 
at locations defined in the Laboratory Manual(s) and guidance(s).  Clinical information will be 
held at a separate location. 
14.6. 
Changes to the Protocol 
This protocol cannot be altered or changed except through a formal protocol amendment, which 
requires the written approval of Aevi Genomic Medicine, LLC.  The protocol amendment must 
be signed by the investigator and approved by the IRB before it may be implemented.  Protocol 
amendments will be filed with the appropriate regulatory agency(ies) having jurisdiction over the 
conduct of the study. 
14.7. 
Use of Information and Publication 
All information concerning MDGN-002, Aevi Genomic Medicine’ operations, patent 
applications, formulas, manufacturing processes, basic scientific data, and formulation 
information supplied by Aevi Genomic Medicine or designee to the investigator and not 
previously published, is considered confidential and remains the sole property of Aevi Genomic 
Medicine.  Case report forms also remain the property of Aevi Genomic Medicine.  The 
investigator agrees to use this information for purposes of study execution through finalization. 
The information developed in this study will be used by Aevi Genomic Medicine in connection 
with the continued development of MDGN-002 and thus may be disclosed as required to other 
clinical investigators or government regulatory agencies. 
The information generated by this study is the property of Aevi Genomic Medicine.  Publication 
or other public presentation of MDGN-002 data resulting from this study requires prior review 
and written approval of Aevi Genomic Medicine.  Abstracts, manuscripts, and presentation 
materials should be provided to Aevi Genomic Medicine for review at least 30 days prior to the 
relevant submission deadline.  
It is agreed that the results of the study will not be submitted for presentation, abstract, poster 
exhibition or publication by the investigator until Aevi Genomic Medicine has reviewed and 
commented on such a presentation or manuscript for publication. 
 
 


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15. 
PUBLIC POSTING OF STUDY INFORMATION 
Aevi Genomic Medicine is responsible for posting appropriate study information on applicable 
websites. Information included in clinical study registries may include participating investigator 
information (e.g., site name, investigator name, site location, site contact information). 
16. 
ETHICAL AND LEGAL CONSIDERATIONS 
16.1. 
Declaration of Helsinki and Good Clinical Practice 
This study will be conducted in compliance with the ICH Guidance for Industry E6 GCP 
(including archiving of essential study documents), the Declaration of Helsinki, and the 
applicable regulations of the country in which the study is conducted. 
16.2. 
Subject Information and Informed Consent 
It is the responsibility of the investigator to ensure that written informed consent is obtained from 
the subject before any activity or procedure is undertaken that is not part of routine care, 
including screening assessments.  All consent documentation must be in accordance with 
applicable regulations and GCP.  Each subject is requested to sign and date the subject informed 
consent form or a certified translation, if applicable, after the subject has received and read (or 
been read) the written subject information and received an explanation of what the study 
involves, including but not limited to: the objectives, potential benefits and risks, 
inconveniences, and the subject’s rights and responsibilities. A copy of the informed consent 
documentation (such as a complete set of subject information sheets and fully executed signature 
pages) must be given to the subject. This document may require translation into local language.  
Signed consent forms must remain in each subject’s study file and must be available for 
verification at any time.  
The PI provides the sponsor with a copy of the consent form which was reviewed by the IRB and 
which received favorable opinion/approval.  A copy of the IRB’s written favorable 
opinion/approval of these documents must be provided to the sponsor, prior to the start of the 
study unless it is agreed to and documented (abiding by regulatory guidelines and national 
requirements) prior to the study start that another party (such as the sponsor or coordinating PI) 
is responsible for this action.  If the IRB requires modification of the sample subject information 
and consent document provided by the sponsor, the documentation supporting this requirement 
must be provided to the sponsor. 
16.3. 
Institutional Review Board or Ethics Committee 
A properly constituted, valid IRB according to local laws and regulations must review and 
approve the protocol, the investigator’s informed consent document, and related subject 
information and any other study materials requiring review (such as recruitment information) 
before the start of the study. 
Until written approval by the IRB has been received by the investigator, no subject may undergo 
any study procedure solely for determining eligibility for this study.  Investigational product will 
not be released until the sponsor or its designee has received written IRB approval. 


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Prior to implementing changes in the study, the sponsor and the IRB must approve and provide 
documentation of favorable opinion/approval of any revisions to informed consent documents 
and amendments to the protocol unless there is a subject safety issue.  
Depending on location (outside the European Union [EU] or inside EU) the IRB will be apprised 
of the progress of the study and of any changes made to the protocol at least yearly.  This may be 
done by the investigator (outside EU and in some cases, inside EU) or the sponsor (in some cases 
inside EU).  These updates include information on any serious or significant AEs.  
Upon study completion, the investigator will provide the IRB with a final report/summary as 
required. 
16.4. 
Financial Disclosure 
The investigator is required to disclose any financial arrangement during the study and for 1 year 
after where the outcome of the study could be influenced by the value of the compensation for 
conducting the study, or other payments the investigator received from the sponsor.  The 
following information is collected:  any significant payments from sponsor or subsidiaries such 
as grant to fund ongoing research, compensation in the form of equipment, retainer for ongoing 
consulting or honoraria; any proprietary interest in the investigational product; any significant 
equity interest in the sponsor or subsidiaries as defined in 21 CFR 54 (b) (1998). 
16.5. 
Privacy and Confidentiality 
All US-based sites and laboratories or entities providing support for this study, must, where 
applicable, comply with the Health Insurance Portability and Accountability Act (HIPAA) of 
1996.  A site that is not a covered entity as defined by HIPAA must provide documentation of 
this fact to the sponsor/contract research organization.  
The confidentiality of records that may be able to identify subjects will be protected in 
accordance with applicable laws, regulations and guidelines.  
After subjects have consented to participate in a study, the sponsor and/or its representatives 
reviews their medical records and data collected as part of the study.  These records and data 
may be reviewed by others including the monitor/auditor from the sponsor or its representatives, 
national or local authorities, or the IRB which gave the approval for the study, third parties with 
whom the sponsor may develop, register or market the investigational product.  The sponsor and 
its representatives will take all reasonable precautions in accordance with applicable laws, 
regulations, and guidelines to maintain the confidentiality of subjects’ identities.  
Subjects are assigned a unique identifying number; however, the initials and date of birth may 
also be collected and used to assist the sponsor to verify the accuracy of data.  
The results of the studies, containing the subjects’ unique identifying numbers, relevant medical 
records and possibly initials and dates of birth, will be recorded.  They may be transferred to and 
used in other countries which may not afford the same level of protection that applies within the 
countries where the study is conducted.  The purpose of such transfer would include supporting 
regulatory submissions, to conduct new data analyses, to publish or present the study results or to 
answer questions asked by regulatory or health authorities. 


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17. 
LIST OF REFERENCES 
Assa A, Hartman C, Weiss B, et al.  Long-term outcome of tumor necrosis factor alpha 
antagonist’s treatment in pediatric Crohn’s disease.  J Crohns Colitis.  2013;7:369–76 
Ben-Horin S, Kopylov U, Chowers Y. Optimizing anti-TNF treatments in inflammatory bowel 
disease. Autoimmun Rev. 2014 Jan;13(1):24-30. doi: 10.1016/j.autrev.2013.06.002. Epub 2013 
Jun 19. PMID: 23792214. 
Best WR, Becktel JM, Singleton JW, Kern F, Jr. Development of a Crohn’s disease activity 
index. National Cooperative Crohn’s Disease Study. Gastroenterol. 1976;70:439-44. 
Clara Abraham and Judy H. Cho, Inflammatory Bowel Disease, N Engl J Med 2009; 361:2066-
2078, DOI: 10.1056/NEJMra0804647 
de Bie CI, Paerregaard A, Kolacek S, et al.  Disease phenotype at diagnosis in pediatric Crohn’s 
disease: 5-year analyses of the EUROKIDS Registry.  Inflamm Bowel Dis. 2013;19:378–385. 
Giles DA, Zahner S, Krause P, Van Der Gracht E, Riffelmacher T, Morris V, Tumanov A, and 
Kronenberg M, The Tumor Necrosis Factor Superfamily Members TNFSF14 (LIGHT), 
Lymphotoxin β and Lymphotoxin β Receptor Interact to Regulate Intestinal Inflammation, 
Front. Immunol., 22 November 2018 | https://doi.org/10.3389/fimmu.2018.02585 
Cardinale CJ, Wei Z, Panossian S, Wang F, Kim CE, Mentch FD et al.  Targeted resequencing 
identifies defective variants of decoy receptor 3 in pediatric-onset inflammatory bowel disease.  
Genes Immun. 2013. Oct;14(7):447-52 
Cohavy O, Zhou J, Ware CF, et al.  LIGHT is constitutively expressed on T and NK cells in the 
human gut and can be induced by CD2-mediated signaling.  J Immunol.  2005:174:646-53. 
Cohavy O, Zhou J, Granger SW, et al. LIGHT expression by mucosal T cells may regulate 
IFN-gamma expression in the intestine.  J. Immunol.  2004;173(1):251-8. 
Dahlhamer JM, Zammitti EP, Ward BW, Wheaton AG, Croft JB. Prevalence of Inflammatory 
Bowel Disease Among Adults Aged ≥18 Years — United States, 2015. MMWR Morb Mortal 
Wkly Rep 2016;65:1166–1169.  
Daperno M, D’Haens G, Van Assche G et al.  Development and validation of a new, simplified 
endoscopic activity score for Crohn’s disease: the SES-CD.  Gastroinest Endosc. 2004 Oct; 
60(4):505-12.  
Dotson J, Hyams J, Markowitz J, Leleiko N, Mack DR, et al.  Extraintestinal manifestations of 
pediatric inflammatory bowel disease and their relation to disease type and severity.  J Pediatr 
Gastroenterol Nutr. 2010;51(2):140-45. 
Freeman HJ.  Natural history and long-term clinical course of Crohn’s disease. World J 
Gastroenterol. 2014;20:31–36. 
Funke B, Autschbach F, Kim S, Lasitschka F, Strauch U, Rogler G et al.  Functional 
characterisation of decoy receptor 3 in Crohn's disease.  Gut.  2009.  Apr;58(4):483-91. 
Granger SW, Butrovich KD, Houshmand P, Edwards WR, Ware CF.  Genomic characterization 
of light reveals linkage to an immune response locus on chromosome 19p13.3 and distinct 
isoforms generated by alternate splicing or proteolysis.  J Immunol.  2001;167:5122-28. 


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Guyatt G, Mitchell A, Irvine EJ et al. A new measure of health status for clinical trials in 
inflammatory bowel disease.  Gastroenterol. 1989;96:804-10.  
Hyams J , Crandall W, Kugathasan S, et al.  REACH Study Group. Induction and maintenance 
infliximab therapy for the treatment of moderate-to-severe Crohn’s disease in children. 
Gastroenterology.  2007;132:863–73. 
Kappelman MD, Moore KR, Allen JK, Cook SF.  Recent trends in the prevalence of Crohn’s 
disease and ulcerative colitis in a commercially insured US population.  Dig Dis Sci. 
2013;58(2):519-25. 
Laharie D, Bourreille A, Branche J, Allez M, Bouhnik Y, Filippi J, Zerbib F, Savoye G, Nachury 
M, Moreau J, Delchier JC, Cosnes J, Ricart E, Dewit O, Lopez-Sanroman A, Dupas JL, 
Carbonnel F, Bommelaer G, Coffin B, Roblin X, Van Assche G, Esteve M, Färkkilä M, Gisbert 
JP, Marteau P, Nahon S, de Vos M, Franchimont D, Mary JY, Colombel JF, Lémann M; Groupe 
d'Etudes Thérapeutiques des Affections Inflammatoires Digestives. Ciclosporin versus infliximab 
in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label 
randomised controlled trial. Lancet. 2012 Dec 1;380(9857):1909-15. doi: 10.1016/S0140-
6736(12)61084-8. Epub 2012 Oct 10. PMID: 23063316. 
National Cancer Institute, Common Terminology Criteria for Adverse Events v4.0  
NCI, NIH, DHHS. May 28, 2009, v4.0.3 June 14, 2010.  
O’Donnell LJD, Virjee J, Heaton KW. Detection of pseudodiarrhoea by simple clinical 
assessment of intestinal transit rate. Br Med J. 1990; 300: 439-40.  
Papamichael K., Rivals-Lerebours O, Billiet T, Vande Casteele N., Gils A., Ferrante M, Van 
Assche G, Rutgeerts PJ, Mantzaris GJ, Peyrin-Biroulet L, and Vermeire S, Long-Term Outcome 
of Patients with Ulcerative Colitis and Primary Non-response to Infliximab, Journal of Crohn's 
and Colitis, Volume 10, Issue 9, September 2016, Pages 1015–1023, 
https://doi.org/10.1093/ecco-jcc/jjw067 
Papamichael K., Vande Casteele N., Gils A., Tops S., Hauenstein S., Singh S., Princen F., Van 
Assche G, Rutgeerts P, Vermeire S, and Ferrante M., Long-Term Outcome of Patients With 
Crohn's Disease Who Discontinued Infliximab Therapy Upon Clinical Remission, Clinical 
Gastroenterology and Hepatology, 2015, 13  (6) , pp. 1103-1110. 
Pouillon L, Bossuyt P, Peyrin-Biroulet L. Considerations, challenges and future of anti-TNF 
therapy in treating inflammatory bowel disease. Expert Opin Biol Ther. 2016;16:1277–1290 
Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, McLeon RS, et al.  Genome wide search in 
Canadian families with inflammatory bowel disease reveals two novel susceptibility loci.  
Am J Hum Genet.  2000;66:1863-70. 
Sanderson IR.  Growth problems in children with IBD.  Nat Rev Gastroenterol Hepatol. 
2014;11(14):601-10. 
Sostegni R, Daperno M, Scaglione N, Lavagna A et al. Review: Crohn’s disease: monitoring 
disease activity.  Aliment Pharmacolo Ther. 2003: 17 (Suppl. 2) 11-17.  


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Vahabnezhad E, Rabizadeh S, Dubinsky MC.  A 10-year, single tertiary care center experience 
on the durability of infliximab in pediatric inflammatory bowel disease.  Inflamm Bowel Dis. 
2014;20:606–13. 
Wang J, Anders RA, Wang Y, et al.  The critical role of LIGHT in promoting intestinal 
inflammation and Crohn’s disease.  J Immunol.  2005:174;8173-82. 
Ware, CF.  Network Communications: Lymphotoxins, LIGHT and TNF.  Annual Rev Immunol. 
2005;23:787-819. 
Yu KY, Kwon B, Ni J, Zhai Y, Ebner R, Kwon BS .  A newly identified member of tumor 
necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis.  J Biol Chem. 
1999.  274(20):13733–6. 
 


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18. 
APPENDICES 


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18.1. 
Investigator’s Agreement 
 
PROTOCOL NUMBER: 
MDGN-002-CD-101 
PROTOCOL TITLE: 
Phase Ib Escalating Dose, Open-Label, Signal-Finding Study to 
Evaluate the Safety, Tolerability, and Short-Term Efficacy of the 
Anti-Light Monoclonal Antibody MDGN-002 in Adults with 
Moderate to Severe Active Crohn’s Disease (CD) or Ulcerative 
Colitis (UC) who have Failed Prior Treatment with an Anti-TNFα  
 
FINAL PROTOCOL: 
 
Version 11.0, 23 July 2021 
 
I have read this protocol and agree to conduct this clinical trial as outlined herein.  I will ensure 
that all subinvestigators and other study staff members have read and understand all aspects of 
this protocol. I agree to cooperate fully with Aevi Genomic Medicine, LLC. and their designees 
during the study.  I will adhere to all FDA, ICH, and other applicable regulations and guidelines 
regarding clinical trials on an investigational product during and after study completion. 
 
Principal Investigator: 
 
 
Printed Name: 
 
 
 
 
 
 
 
 
Signature: 
 
 
 
 
 
 
 
 
Date: 
 
 
 
 
 


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18.2. 
Definitions of Primary and Secondary Non-responder 
 
1. Primary non-responder – Crohn’s Disease 
 
A primary non-responder is defined as a subject for whom treatment with infliximab, 
adalimumab, or certolizumab pegol produced an inadequate initial response.  Inadequate initial 
response symptom details must occur ³ 2 weeks after the last dose of induction therapy.  The 
algorithm for defining inadequate initial response is shown below.  Subjects categorized as 
primary non-responders must meet both parts of the algorithm.  Documentation required includes 
dates and doses of failed induction therapy and lack of response details around disease activity 
recorded by a treating clinician.  
 
Algorithm for inadequate initial response to current or prior therapy with infliximab, 
adalimumab, or certolizumab pegol: 
 
Subject has received induction doses of either: 
• infliximab (2 or 3 doses of ³ 5 mg/kg), OR 
• adalimumab (dose of 160 mg followed by a dose of ³ 80 mg or, dose of 80 mg 
followed by a dose of ³ 40 mg), OR 
• certolizumab pegol (2 or 3 doses of ³ 400 mg). 
 
AND 
 
Subject did not initially respond to these induction doses as documented by the presence of 
at least 1 of the following signs or symptoms related to Crohn’s disease activity:  
 
• lack of improvement or worsening in stool frequency 
• lack of improvement or worsening in daily abdominal pain 
• occurrence, lack of improvement, or worsening of fever associated with Crohn’s 
disease 
• recurring drainage from a previously non-draining fistula or development of a new 
draining fistula 
• lack of improvement or worsening in rectal bleeding 
• initiation or increase in antidiarrheal medication 
 
2. Secondary non-responder – Crohn’s Disease 
 
A secondary non-responder is defined as a subject for whom treatment with infliximab, 
adalimumab, or certolizumab pegol produced an initial response followed by a loss of response.  
Loss of response details must occur ³ 2 weeks after last dose of maintenance therapy.  The 
algorithm for defining loss of response is shown below.  Subjects categorized as secondary non-
responders must meet both parts of the algorithm.  Documentation required includes dates and 


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doses of induction and maintenance, initial response and subsequent loss of response including 
details around disease activity recorded by a treating clinician.  
 
Algorithm for loss of response to prior therapy with infliximab, adalimumab, or 
certolizumab pegol: 
 
Subject responded to induction therapy at doses described above and received at least 
2 maintenance doses of: 
• infliximab (³ 5 mg/kg), OR 
• adalimumab (dose ³ 40 mg or, if failed as a pediatric dose of ³ 20 mg), OR 
• certolizumab pegol (³ 400 mg) 
 
AND 
 
Subject did not respond to these maintenance doses as documented by the presence of at 
least 1 of the following signs or symptoms related to Crohn’s disease activity.  
 
• worsening in stool frequency 
• worsening in daily abdominal pain 
• occurrence, or worsening of fever associated with Crohn’s disease 
• recurring drainage from a previously non-draining fistula or development of a new 
draining fistula 
• worsening in rectal bleeding 
• initiation or increase in antidiarrheal medication 
 
3. Primary non-responder – Ulcerative Colitis 
 
A primary non-responder is defined as a subject for whom treatment with infliximab, 
adalimumab, certolizumab pegol or golimumab produced an inadequate initial response.  
Inadequate initial response symptom details must occur ³ 2 weeks after the last dose of induction 
therapy.  The algorithm for defining inadequate initial response is shown below.  Subjects 
categorized as primary non-responders must meet both parts of the algorithm.  Documentation 
required includes dates and doses of failed induction therapy and lack of response details around 
disease activity recorded by a treating clinician.  
 
Algorithm for inadequate initial response to current or prior therapy with infliximab, 
adalimumab, certolizumab pegol or golimumab in patients with UC: 
 
Subject has received induction doses of either: 
• infliximab (2 or 3 doses of ³ 5 mg/kg), OR 
• adalimumab (dose of 160 mg followed by a dose of ³ 80 mg or, dose of 80 mg 
followed by a dose of ³ 40 mg), OR 
• certolizumab pegol (2 or 3 doses of ³ 400 mg), OR 
• golimumab (dose of 100 mg every 4 weeks). 


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AND 
 
Subject did not initially respond to these induction doses as documented by the presence of 
at least 1 of the following signs or symptoms related to UC activity:  
 
• lack of improvement of stool frequency 
• lack of improvement of rectal bleeding 
• initiation or increase in antidiarrheal medication 
 
4. Secondary non-responder – Ulcerative Colitis 
 
A secondary non-responder is defined as a subject for whom treatment with infliximab, 
adalimumab, certolizumab pegol, or golimumab produced an initial response followed by a loss 
of response.  Loss of response details must occur ³ 2 weeks after last dose of maintenance 
therapy.  The algorithm for defining loss of response is shown below.  Subjects categorized as 
secondary non-responders must meet both parts of the algorithm.  Documentation required 
includes dates and doses of induction and maintenance, initial response and subsequent loss of 
response including details around disease activity recorded by a treating clinician.  
 
Algorithm for loss of response to prior therapy with infliximab, adalimumab, certolizumab 
pegol, or golimumab: 
 
Subject responded to induction therapy at doses described above and received at least 
2 maintenance doses of: 
• infliximab (dose of 5 mg/kg), OR 
• adalimumab (dose of 40 mg or, if failed as a pediatric dose of 20 mg), OR 
• certolizumab pegol (dose of 400 mg) OR 
• golimumab (dose of 100 mg every 4 weeks) 
 

SAP_001.pdf: 
Avalo Therapeutics, Inc. 
Statistical Analysis Plan Version 1.0 
MDGN-002-CD-101 
05OCT2021 
STATISTICAL ANALYSIS PLAN 
Phase Ib Escalating Dose, Open-Label, Signal-Finding Study to 
Evaluate the Safety, Tolerability, and Short-Term Efficacy of the Anti-
Light Monoclonal Antibody MDGN-002 in Adults with Moderate to 
Severe Active Crohn’s Disease (CD) or Ulcerative Colitis (UC) who have 
Failed Prior Treatment with an Anti-TNFα Agent 
PROTOCOL NO. MDGN-002-CD-101 
Protocol Version 11.0 (23JUL2021) 
SPONSORED BY 
Avalo Therapeutics, Inc. 
(formerly known as Cerecor, Inc.,  
Aevi Genomic Medicine, LLC,  
Aevi Genomic Medicine, Inc., and 
Medgenics, Inc.) 
1500 Liberty Ridge Drive, Suite 321 
Wayne, PA 19087 
NCT03169894


Avalo Therapeutics, Inc. 
Statistical Analysis Plan Version 1.0 
MDGN-002-CD-101 
05OCT2021 
 
 
 


Avalo Therapeutics, Inc. 
Statistical Analysis Plan Version 1.0 
MDGN-002-CD-101 
05OCT2021 
 
 
REVISION HISTORY 
 
Table 1 SAP Version History Summary 
SAP 
Version 
Approval 
Date 
Change 
Rationale 
1.0 
05OCT2021 
Not Applicable 
Original version 
 
 


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ABBREVIATIONS 
 
ABBREVIATION DEFINITION OR DESCRIPTION 
ADA 
Anti-drug Antibodies 
AE 
Adverse Event 
ATC 
Anatomical Therapeutic Chemical 
BMI 
Body Mass Index 
CD 
Crohn’s Disease 
CDAI 
Crohn’s Disease Activity Index 
CM 
Concomitant Medication 
CRF 
Case Report Form 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
ET 
Early Termination 
FAS 
Full Analysis Set 
GI 
Gastrointestinal 
IBD-Q 
Inflammatory Bowel Disease Questionnaire 
ICH 
International Council for Harmonisation 
LLOQ 
Lower Limit of Quantification 
MedDRA 
Medical Dictionary for Regulatory Activities 
PK 
Pharmacokinetic 
PT 
Preferred Term 
SAP 
Statistical Analysis Plan 
SES-CD 
Simple Endoscopy Score for Crohn’s Disease 
SOC 
System Organ Class 
SQ 
Subcutaneous 
TEAE 
Treatment-emergent Adverse Event 
TNFα 
Tumor Necrosis Factor Alpha 
UC 
Ulcerative Colitis 
WHO 
World Health Organization 


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TABLE OF CONTENTS 
 
TABLE OF CONTENTS ......................................................................................................................... 5 
1. 
INTRODUCTION ................................................................................................................. 7 
1.1            STUDY OBJECTIVES ......................................................................................................... 7 
1.1.1  Primary Objective ......................................................................................................... 7 
1.1.2  Secondary Objectives .................................................................................................... 7 
2. 
STUDY DESIGN AND PROCEDURES ............................................................................. 8 
3. 
DETERMINATION OF SAMPLE SIZE ........................................................................... 8 
4. 
STUDY ASSESSMENTS ..................................................................................................... 8 
4.1            CROHN’S DISEASE ACTIVITY INDEX (CROHN’S DISEASE PATIENTS) .................................. 8 
4.2            MODIFIED MAYO SCORE (ULCERATIVE COLITIS PATIENTS) .............................................. 10 
4.3            ENDOSCOPY WITH BIOPSY AND HISTOLOGY ......................................................................... 10 
4.4            PATIENT-REPORTED ASSESSMENT OF ABDOMINAL PAIN AND STOOL FREQUENCY (CROHN’S 
DISEASE PATIENTS) .............................................................................................................................. 11 
4.5            PATIENT-REPORTED ASSESSMENT OF STOOL FREQUENCY AND RECTAL BLEEDING 
(ULCERATIVE COLITIS PATIENTS) ....................................................................................................... 12 
4.6            QUALITY OF LIFE ASSESSMENT – INFLAMMATORY BOWEL DISEASE QUESTIONNAIRE ..... 12 
5. 
GENERAL ANALYSIS AND REPORTING CONSIDERATIONS ................................ 12 
5.1            BASELINE AND CHANGE FROM BASELINE MEASUREMENTS ................................................ 13 
5.2            STUDY DAY CALCULATION .................................................................................................... 13 
5.3            NUMBER OF DAYS SUBJECT ON STUDY DRUG ....................................................................... 14 
5.4            LAST DOSE DATE ................................................................................................................... 14 
5.5            ADJUSTMENTS FOR COVARIATES .......................................................................................... 14 
5.6            STUDY HYPOTHESES .............................................................................................................. 14 
5.7            HANDLING OF MISSING DATA ............................................................................................... 14 
5.8            ASSESSMENT TIME WINDOWING ........................................................................................... 15 
5.9            POOLING OF INVESTIGATOR SITES ........................................................................................ 16 
5.10          ADJUSTMENTS FOR MULTIPLICITY ....................................................................................... 16 
5.11          EXAMINATION OF SUBGROUPS .............................................................................................. 16 
6. 
SUBJECT SUMMARIES ..................................................................................................... 16 
6.1            ANALYSIS DATASETS .............................................................................................................. 16 
6.1.1  Full Analysis Set ........................................................................................................... 16 
6.1.2  Safety Analysis Set ....................................................................................................... 16 
6.1.3  Pharmacokinetic Analysis Set ....................................................................................... 16 
6.2            PATIENT DISPOSITION ............................................................................................................ 16 
6.3            DEMOGRAPHIC AND BASELINE CHARACTERISTICS .............................................................. 17 
6.3.1  Demographic and Baseline Characteristics ................................................................... 17 
6.3.2  Baseline Disease Status/Disease History ...................................................................... 17 
6.3.3  Medical History ............................................................................................................. 17 
6.3.4  Prior and Concomitant Medications .............................................................................. 17 
6.4            PROTOCOL DEVIATIONS ........................................................................................................ 17 
7. 
MEASUREMENTS OF TREATMENT EXPOSURE AND COMPLIANCE ................. 18 
8. 
EFFICACY EVALUATION ................................................................................................ 18 
8.1            EFFICACY ENDPOINT(S) ......................................................................................................... 18 
8.1.1  Primary Efficacy Endpoints .......................................................................................... 18 


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8.1.2  Secondary Efficacy Endpoint(s) .................................................................................... 18 
8.2            EFFICACY ANALYSIS .............................................................................................................. 19 
8.2.1  Primary Efficacy Analyses ............................................................................................ 19 
8.2.2  Supportive and Sensitivity Analyses of the Primary Endpoint ..................................... 19 
8.2.3  Secondary Efficacy Analyses ........................................................................................ 19 
9. 
SAFETY EVALUATIONS ................................................................................................... 21 
9.1            OVERVIEW OF SAFETY ANALYSIS METHODS ........................................................................ 21 
9.2            ADVERSE EVENTS ................................................................................................................... 21 
9.3            CLINICAL LABORATORY EVALUATIONS ............................................................................... 22 
9.4            VITAL SIGNS ........................................................................................................................... 22 
9.5            PHYSICAL EXAMINATION ....................................................................................................... 22 
9.6            ECG EXAMINATION ............................................................................................................... 22 
9.7            PREGNANCY TEST .................................................................................................................. 22 
10. 
PK ANALYSIS ...................................................................................................................... 23 
11. 
ADA ANALYSIS ................................................................................................................... 23 
12. 
INTERIM ANALYSIS ......................................................................................................... 23 
13. 
DATA MONITORING COMMITTEE .............................................................................. 23 
14. 
CHANGES TO THE ANALYSES PLANNED IN THE PROTOCOL ............................ 23 
15. 
TABLE OF CONTENTS FOR APPENDICES .................................................................. 24 
15.1            TABLES ................................................................................................................................. 24 
15.2            LISTINGS ............................................................................................................................... 24 
16. 
REFERENCES ...................................................................................................................... 26 


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1. INTRODUCTION 
This statistical analysis plan (SAP) describes the planned analysis and reporting for Avalo 
Therapeutics, Inc. protocol number MDGN-002-CD-101, version 11.0, dated 23Jul2021: 
“Phase Ib Escalating Dose, Open-Label, Signal-Finding Study to Evaluate the Safety, 
Tolerability, and Short-Term Efficacy of the Anti-Light Monoclonal Antibody MDGN-002 
in Adults with Moderate to Severe Active Crohn’s Disease (CD) or Ulcerative Colitis (UC) 
who have Failed Prior Treatment with an Anti-TNFα Agent”.  
This SAP will be signed off, at a minimum, before the final database lock and contains 
detailed information to aid in the performance of the statistical analysis and reporting of the 
study data for use in the final clinical study report (CSR). This SAP is being written with due 
consideration of the recommendations outlined in the most recent International Council for 
Harmonisation (ICH) E9 Guideline entitled Guidance for Industry: Statistical Principles for 
Clinical Trials, the most recent ICH E3 Guideline and the Guidance for Industry: Structure 
and Content of Clinical Study Reports. 
This SAP describes the data that will be analyzed and the subject characteristics, safety, and 
efficacy assessments that will be evaluated. This SAP provides details of the specific 
statistical methods that will be used. If additional analyses are performed after database lock 
to supplement the planned analyses described in this SAP, they will be clearly identified as 
post-hoc in the CSR.  
In addition to the study protocol, the case report form (CRF) was reviewed in preparation of 
this SAP.  
The reader of this SAP is encouraged to also read the study protocol for details on the 
planned conduct of this study. Operational aspects related to collection and timing of planned 
clinical assessments are not repeated in this SAP unless relevant to the planned analysis. 
Although methods applicable to pharmacokinetic (PK) data may be mentioned in this 
document, further PK analysis will be described in a separate document as needed. 
1.1            STUDY OBJECTIVES 
1.1.1  Primary Objective 
The primary objective of this study is to evaluate the safety and tolerability of MDGN-002 
administered by subcutaneous (SQ) injection to adults with moderate to severe, active CD or 
UC who have failed prior treatment with an anti-TNFα agent. 
1.1.2  Secondary Objectives 
• Estimate plasma concentrations of MDGN-002 administered by SQ injection to adults 
with moderate to severe, active CD or UC. 


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• Evaluate response to treatment with MDGN-002 administered by SQ injection to 
adults with moderate to severe, active CD or UC. 
2. STUDY DESIGN AND PROCEDURES 
This is a Phase 1b, open-label, dose-escalation, signal-finding, multi-center study to evaluate 
the safety, tolerability, pharmacokinetics, and short-term efficacy of MDGN-002 in adults 
with moderate to severe, active CD or UC who have previously failed anti-TNFα treatment. 
The study is a pilot study using a dose-escalation design to characterize the safety and 
tolerability of 2 different doses of MDGN-002 (1.0 mg/kg and 3.0 mg/kg) in the CD 
population, and 3.0 mg/kg in the UC population. All subjects will receive a total of 4 doses of 
MDGN-002 by SQ injection at 14-day intervals. The study will consist of a screening period, 
an open-label treatment period and a safety follow-up visit. 
In this document, MDGN-002 will be referred to as “study drug” regardless of dosage, and 
“cohort” will refer to 1.0 mg/kg (Cohort 1) or 3.0 mg/kg (Cohort 2) as described above.  
The following study visits will be performed:  
• Visit 1 (Screening). This period may be up to 14 weeks, inclusive of a washout period 
for subjects who have received a biologic treatment within 12 weeks of Visit 1. The 
amount of time required is determined based on the subject’s last dose of the 
medication and may be up to 12 weeks.  
• Visit 2 (Pre-/Post-Dose Day 0);  
• Visit 3 (Day 7);  
• Visit 4 (Pre-/Post-Dose Day 14);  
• Visit 5 (Day 21);  
• Visit 6 (Pre-/Post-Dose Day 28);  
• Visit 7 (Day 35);  
• Visit 8 (Pre-/Post-Dose Day 42);  
• Visit 9 (Day 49);  
• Visit 10 (Day 56/Early Termination (ET));  
• Visit 11 (Day 84 or 28 days after ET).  
3. DETERMINATION OF SAMPLE SIZE 
This is the first use of MDGN-002 in the intended population of patients with CD or UC who 
have failed prior treatment with an anti-TNFα agent. The sample size of the study was based 
on feasibility. 
4. STUDY ASSESSMENTS 
4.1            CROHN’S DISEASE ACTIVITY INDEX (CROHN’S DISEASE PATIENTS) 
The Crohn’s Disease Activity Index (CDAI) consists of the following 8 items: abdominal 
pain, number of liquid stools, general well-being, extraintestinal complication, use of 
antidiarrheal drugs, abdominal mass, hematocrit, and body weight. Information on abdominal 


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pain, general well-being, and frequency of loose and watery stools will be taken from a daily 
diary completed by the subject. 
 
Total CDAI scores can range from 0 to approximately 600 with higher scores indicating 
more active disease. Disease severity as measured by CDAI is categorized as: 
Remission (<150), Mildly active disease (150 - 219); Moderately active disease (220 - 450); 
Severe disease (> 450). 
 
Item and total scores, as outlined below, will be derived programmatically for Visit 1 
(Screening), Visits 2 (Day 0), 4 (Day 14), 6 (Day 28), 8 (Day 42), and Visit 10 (Day 56/ET).  
 
The CDAI total score consists of 8 item scores: 
1) The liquid stools score is calculated as the sum of the number of loose/watery stools 
values recorded for the 7 days prior to the visit; 
2) The abdominal pain score is calculated as the sum of the abdominal pain values recorded 
for the 7 days prior to the visit.  Abdominal pain severity (graded from 0 - 3 with higher 
values indicating greater severity) summed over the previous 7 days, where 0 = “None”, 
1 = “Mild”, 2 = “Moderate”, 3 = “Severe”; 
3) The general well-being score is calculated as the sum of the general well-being values 
recorded for the 7 days prior to the visit. General well-being is graded from 0 - 4 with 
higher values indicating a poorer condition of health, where 0 = “Generally well”, 1 = 
“Slightly under par”, 2 = “Poor”, 3 = “Very poor”, 4 = “Terrible”;  
4) The extraintestinal complications score is calculated as the number of complications 
present (0 to 6) from the following list: 
• Arthritis/arthralgia 
• Iritis/uveitis  
• Skin/mouth lesions 
• Peri-anal disease 
• Other fistula 
• Fever >37.8 °C, >100 °F (in the last week); 
5) Taking medication for symptomatic relief from diarrhea (0 = No, 1 = Yes); 
6) Presence of an abdominal mass (0 = None, 2 = Questionable, 5 = Definite); 
7) Hematocrit score is calculated as follows, adding to or subtracting from total score 
according to sign: 
• 47 minus hematocrit value for males 
• 42 minus hematocrit value for females; 


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8) Weight percentage difference from standard weight, is calculated by 100 x (1 – (current 
weight / standard weight)) where the standard weight is defined as height in m2 x 22.1 for 
males and height in m2 x 20.8 for females. Values > 0 and indicate the subject is below 
standard weight; values < 0 indicate that the subject is over standard weight. 
The CDAI total score is calculated as the weighted sum to the above 8 scores as follows: 
CDAI =             2 x (Item 1)  +  5 x (Item 2)  +  7 x (Item 3)  +  20 x (Item 4) +  
30 x (Item 5)  +  10 x (Item 6)  +  6 x (Item 7)  +  1 x (Item 8) 
Please refer to section 5.7 for handling missing data. 
4.2            MODIFIED MAYO SCORE (ULCERATIVE COLITIS PATIENTS) 
The Modified Mayo Score (excluding the Physician’s Global Assessment [PGA] component) 
includes stool frequency, rectal bleeding, and the appearance of mucosa upon endoscopy. 
Stool frequency is based on a scale of 0 to 3 (0 = “normal”, 1 = “1 to 2 stools/day > normal”, 
2 = “3 to 4 stools/day > normal”, 3 = “> 4 stools/day > normal”). Rectal bleeding will be 
based on a scale of 0 to 3 (0 = “none”, 1 = “streaks of blood”, 2 = “obvious blood”, 3 = 
“blood alone passed”). Appearance of mucosa upon endoscopy will be based on a scale of 0 
to 3 (0 = “normal”, 1 = “mild friability”, 2 = “moderate friability”, 3 = “exudation, 
spontaneous bleeding”). The score consists of the sum of all 3 criteria and can range from 0 
to 9, with higher scores indicating more severe disease. This score will be derived 
programmatically for Visit 1 and Visit 10 using the Modified Mayo Endoscopic score from 
the central reader and self-reported data on stool frequency and rectal bleeding from 7 days 
prior to Visit 1 (Screening) and Visit 10 (Day 56/ET). 
4.3            ENDOSCOPY WITH BIOPSY AND HISTOLOGY 
All subjects who enroll in the study will undergo an endoscopy with biopsy at screening and 
again at Visit 10 (Day 56) or at early termination.  
 
Endoscopy evaluation for patients with CD will use the Simple Endoscopy Score for Crohn’s 
Disease (SES-CD). The SES-CD is assessed through endoscopic review of 5 predefined 
gastrointestinal (GI) segments (ileum; right colon; transverse colon; left colon; rectum).  For 
each segment, 4 endoscopic variables are assessed (presence of ulcers, ulcerated surface, 
affected surface, and presence of narrowing).  Each variable is scored from 0 to 3 with higher 
scores indicating more severe symptoms as defined below (Daperno et al 2004). 
  
 
SES-CD Score 
Variable 
0 
1 
2 
3 
Size of ulcers 
None 
Aphthous ulcers   
(0.1–<0.5 cm) 
Large ulcers  
(0.5–2 cm) 
Very large ulcers  
(> 2 cm) 
Ulcerated 
surface 
None 
< 10% 
10–30% 
> 30% 


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Affected 
surface 
Unaffected 
segment 
< 50% 
50–75% 
> 75% 
Presence of 
narrowing 
None 
Single, can be passed 
Multiple, can be 
passed 
Cannot be passed 
For each variable, the total score is calculated as the sum across all segments of the GI tract. 
The SES-CD total score, ranging from 0-60, is calculated as the sum of all variable total 
scores with a higher score indicating more severe endoscopic activity as shown (Moskovitz 
et al 2007). 
SES-CD Score 
Severity Category 
0-2 
Remission 
3-6 
Mild endoscopic activity 
7-15 
Moderate endoscopic 
activity 
>15 
Severe endoscopic activity 
 
Endoscopic evaluation for patients with UC will use the Modified Mayo Endoscopic Score. 
Appearance of mucosa (friability) upon endoscopy will be based on a scale of 0 to 3 
(0 = “normal”, 1 = “mild friability”, 2 = “moderate friability”, 3 = “exudation, spontaneous 
bleeding”). 
4.4            PATIENT-REPORTED ASSESSMENT OF ABDOMINAL PAIN AND 
STOOL FREQUENCY (CROHN’S DISEASE PATIENTS) 
All CD subjects who enroll in the study will be required to report their daily assessment of 
abdominal pain, general well-being and stool frequency including loose and/or watery stools 
via an electronic diary. Derived 7-day interval average scores, explained in Section 5.8 for 
Time Windowing, will be provided that correspond to all visits from Visit 1 (Screening) to 
Visit 10 (Day 56/ET). 
 
Abdominal pain will be assessed on a scale of 0 to 3 with higher values indicating greater 
pain severity: 0 = “None”, 1 = “Mild”, 2 = “Moderate”, 3 = “Severe”. 
 
The stool frequency including number of loose and/or watery stools per day, equivalent to a 
score of a 6 or 7 on the Bristol Stool Scale, will be recorded.  
 
General well-being will be assessed on a scale of 0 to 4 with higher values indicating a 
poorer condition of health: 0 = “Generally well”, 1 = “Slightly under par”, 2 = “Poor”, 3 = 
“Very poor”, 4 = “Terrible”. 


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4.5            PATIENT-REPORTED ASSESSMENT OF STOOL FREQUENCY AND 
RECTAL BLEEDING (ULCERATIVE COLITIS PATIENTS) 
All UC subjects who enroll in the study will be required to report their daily assessment of 
stool frequency and rectal bleeding via an electronic diary. Derived 7-day interval average 
scores, explained in Section 5.8 for Time Windowing, will be provided that correspond to all 
visits from 1 (Screening) to 10 (Day 56/ET). 
 
Stool frequency will be based on a scale of 0 to 3 (0 = “normal”, 1 = “1 to 2 stools/day > 
normal”, 2 = “3 to 4 stools/day > normal”, 3 = “> 4 stools/day > normal”). Normal is defined 
as the patient’s bowel movement pattern during a period of remission where remission means 
that their symptoms of UC resolve, they feel well, and their UC is not interfering with daily 
activities. If the subject has not achieved remission, then normal is their bowel movement 
pattern when healthy prior to being diagnosed with Ulcerative Colitis. 
 
Rectal bleeding is to be reflective of the most severe bleeding of the day and will be based on 
a scale of 0 to 3 (0 = “none”, 1 = “streaks of blood”, 2 = “obvious blood”, 3 = “blood alone 
passed”). If the subject had no stools in a day, then “None” would be selected.    
4.6            QUALITY OF LIFE ASSESSMENT – INFLAMMATORY BOWEL 
DISEASE QUESTIONNAIRE 
The IBD-Q is a 32-item questionnaire validated to measure quality of life in CD and UC 
subjects. The IBD-Q will be completed by all subjects at screening (Visit 1), before dosing 
(Visit 2), and at the end of the open-label treatment period or early termination (Visit 10/ET). 
The IBD-Q assesses the dimensions of bowel function, emotional status, systemic symptoms, 
and social function (Guyatt G, 1989).  
Each of the 32 items is scored on a 1 to 7 scale, where higher scores represent a more 
positive response. The mapping of questionnaire items to each domain is given in the table 
below. 
 
Domain Name 
Questionnaire items 
Bowel symptoms 
1, 5, 9, 13, 17, 20, 22, 24, 26, 29 
Systemic symptoms 
2, 6, 10, 14, 18 
Emotional status 
3, 7, 11, 15, 19, 21, 23, 25, 27, 30, 31, 32 
Social functioning 
4, 8, 12, 16, 28 
Each domain score is calculated as the sum of the items in that domain. The IBD-Q total 
score is calculated as the sum of all 32 items in the questionnaire, ranging from 32 to 224. 
5. GENERAL ANALYSIS AND REPORTING CONSIDERATIONS 
Descriptive statistics will be used to summarize all safety, pharmacokinetic, efficacy, and 
quality of life variables. 


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Continuous data will be summarized using descriptive statistics: n, mean, standard deviation, 
median, minimum, and maximum unless otherwise noted. The mean and median will be 
rounded to one decimal place greater that in the raw data; the standard deviation will be 
rounded to two decimal places greater than in the raw data; the minimum and maximum will 
be reported to the same number of decimal places as present in the raw data. These will be 
referred to as “continuous summaries” in this document. 
Categorical variables will be summarized using frequency counts and percentages.  When 
count data are presented, the percentage for zero counts will be suppressed to draw attention 
to the non-zero counts.  Unless otherwise noted the denominator for all percentages within 
the analysis set of interest will be the number of subjects by disease and cohort as shown 
below: 
 
Frequency counts will be presented as whole numbers and percentages will be rounded to 
one decimal place. These will be referred to as “categorical summaries” in this document. 
5.1            BASELINE AND CHANGE FROM BASELINE MEASUREMENTS 
The baseline measurement will be defined as the last non-missing assessment on the day of 
or prior to first study dose administration (includes all data up to the first dose 
administration). 
Change from baseline will be calculated as: 
• (value at analysis visit – baseline value) 
A positive change signifies an increase in the measurement while a negative change signifies 
a decrease. 
5.2            STUDY DAY CALCULATION 
Study Day defined: 
• for dates on or after date of first dose administration: (analysis date – date of first 
dose administration) + 1. 
• for dates prior to date of first dose administration: (analysis date – date of first dose 
administration). 


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5.3            NUMBER OF DAYS EXPOSED TO STUDY DRUG 
Based upon the pharmacokinetics of the drug (t1/2 of 18.0 to 27.0 days), each dose will count as 14 
days of exposure to investigational product. Therefore, days of exposure to study drug will be 
calculated as: 
• (last dose date – first dose date + 14). 
5.4            LAST DOSE DATE 
The last dose date is defined for subjects who either completed, or ET’d from, the study (i.e., 
have an ET visit), as the last dose administration date. 
5.5            ADJUSTMENTS FOR COVARIATES 
Not applicable due to the use of descriptive statistics only. 
5.6            STUDY HYPOTHESES 
No specific hypotheses are being tested in this pilot study. All data will be summarized using 
descriptive statistics only. 
5.7            HANDLING OF MISSING DATA 
All efforts will be made to minimize missing data.  
CD patient diary data (total stools, loose/watery stools, abdominal pain, and general well-
being) used in calculating the CDAI total score will handle missing data as follows: in cases 
where at least 4 days of data are non-missing for a given 7-day interval leading up to the visit 
date, the average of the non-missing values for all days in the 7-day interval will be imputed 
for missing diary days. If less than 4 days of data are non-missing, then the 7-day interval 
will be set to missing (Henao M.P., et al, 2015). To maintain consistency, the same approach 
of needing at least 4 days of non-missing data for imputation will also be used for UC patient 
diary data (stool frequency, rectal bleeding). 
Missing laboratory data will not be imputed, unless otherwise stated. 
All medications with partial or missing dates recorded on the concomitant medication 
electronic case report form (eCRF) page will be considered concomitant unless a partial stop 
date clearly indicates it was stopped before the first dose of study treatment.  Start and stop 
dates will be imputed when partial dates are present as needed to determine concomitant 
medications.   


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Table 2: 
Table of Imputation Rules for Missing AE and Medication Date Times  
Missing Date 
Portion 
Prior to 
Treatment 
Same as 
Treatment Start 
Date 
After Treatment Start 
Date 
Day 
Month and Year < 
Month and Year of first 
treatment: 
 
Start Day = 1 
Stop Day = last day of 
the month reported 
Month and Year = 
Month and Year of 
first treatment: 
 
Start Day = Day of 
first treatment  
Stop Day = last 
day of the month 
Month and Year > 
Month and Year of first 
treatment: 
 
Start Day = 1  
Stop Day= last day of 
the month 
Day and Month 
Define Day as 
above, then: 
Year < Year of first 
treatment: 
 
Start Month = January 
 
Stop Month = Dec 
Year = Year of 
first treatment: 
 
Start Month = 
Month of first 
treatment 
Stop Month = Dec 
Year > Year of first 
treatment: 
 
Start Month = January 
Stop Month = Dec 
Day, Month, and 
Year 
 
To be conservative, completely missing start dates will be set to the 
date of first treatment, completely missing end dates will be set to the 
date of last contact. 
Time 
Missing start times will be imputed as 00:01 (or the start time of the 
first dose administration if AE occurred on the date of first dose 
administration) 
Missing stop times will be imputed as 23:59  
 
After following these imputation rules, if the start date/time is imputed as a date after the end 
date/time, the start date/time will be set to the end date/time to provide a positive duration for 
the event or medication. No imputation will be done for subjects who did not receive the 
study drug.   
Missing assessments for study medication relationship or severity for AEs starting on or after 
first dose administration will be analysed as related or Grade 3 respectively.  
No other imputation is planned for safety data. 
5.8            ASSESSMENT TIME WINDOWING 
Most safety and efficacy assessment summaries will be based on the nominal 
protocol-specified assessment times. Thus, if the protocol specified Visit 3 (Day 7) visit 
occurs on study Day 8, it will still be summarized as a Visit 3 (Day 7), acknowledging that 
all visits after Visit 2 (Day 0) have a time window of ±3 days.  
The only exception is for daily diary data. The CD diary collects abdominal pain score, 
frequency of loose/watery stools, frequency of total stools, and general well-being, while the 
UC diary collects stool frequency and rectal bleeding. These will have 7-day interval 


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averages calculated, corresponding to the 7 days leading up to weekly visit dates. For 
screening data, the 7-day intervals will be relative to the date of first dose. 
 
Unscheduled visits prior to first dose might be considered as the baseline value while post-
baseline unscheduled visits will be listed only. Unscheduled visits are possible for biologic 
washout, clinical laboratory assessment, ECG, physical exam, pregnancy test, and vital signs. 
5.9            POOLING OF INVESTIGATOR SITES 
Not applicable. 
5.10          ADJUSTMENTS FOR MULTIPLICITY 
Not applicable due to the use of descriptive statistics only. 
5.11          EXAMINATION OF SUBGROUPS 
Not applicable. 
6. SUBJECT SUMMARIES 
6.1            ANALYSIS DATASETS 
6.1.1  Full Analysis Set 
The Full Analysis Set (FAS) will include subjects who receive at least one dose of study drug 
and have a baseline and at least one post-baseline value for any efficacy variable. As a result, 
dosed subjects will be included in the summarization of data in the FAS population for any 
efficacy variable for which they have data. 
6.1.2  Safety Analysis Set 
The Safety Analysis Set will include all subjects who are enrolled and receive at least one 
dose of study drug. 
6.1.3  Pharmacokinetic Analysis Set 
The Pharmacokinetic (PK) Analysis Set will include all subjects who receive at least one 
dose of study drug and for whom plasma concentration data are available, minimally at 
baseline and one post-baseline visit. 
6.2            PATIENT DISPOSITION 
The number and percentage of subjects in each of the following groups will be presented in a 
by-subject listing and summarized by disease and cohort: 
• Subjects screened  
• Subjects screen failed 
• Subjects enrolled 


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• Subjects included in each analysis set 
• Subjects who have completed treatment (defined as receiving four doses)  
• Subjects who have completed study (defined as completing the follow-up visit)  
• Subjects who have discontinued from the study including the reasons for 
discontinuation 
Enrolled subjects are those who are not a screen failure. 
6.3            DEMOGRAPHIC AND BASELINE CHARACTERISTICS 
6.3.1  Demographic and Baseline Characteristics 
Demographic variables will include age, sex, race, and ethnicity. Baseline characteristics 
include height (cm), weight (kg), body mass index (BMI; kg/m2), and time since diagnosis 
(</=10 years vs >10 years). Demographics and baseline characteristics will be presented in a 
by-subject listing and summarized by disease and cohort using the safety analysis set. 
6.3.2  Baseline Disease Status/Disease History 
Crohn’s Disease and Ulcerative Colitis history will be presented in by-subject listings using 
the safety analysis set. 
6.3.3  Medical History 
Medical history conditions will be collected at screening. The number of subjects with any 
medical history will be presented in a by-subject listing using the safety analysis set. 
6.3.4  Prior and Concomitant Medications 
Prior medications are those received prior to the start of the study drug administration. Any 
medication that stops on or after the start of the first study drug administration or with 
missing stop dates is considered a concomitant medication. A medication can be both prior 
and concomitant (e.g., a medication that started before first dose and is ongoing at the end of 
the study).   
 
Prior and concomitant medications will be coded using World Health Organization Drug 
Dictionary Anatomical Therapeutic Chemical (WHO/ATC) classification index version 
2020-03-01, ATC Level 3. The number and percentage of subjects who take prior and 
concomitant medications will be summarized by drug class and preferred term, disease and 
cohort for the safety analysis set.  
 
All medications captured in CRFs will also be presented in a by-subject listing. 
6.4            PROTOCOL DEVIATIONS 
Protocol deviations will be collected in a tracker and presented in a by-subject listing 
including description, category/type, and importance (Important or Not Important) as 
determined by Avalo prior to database lock. Important deviations will be summarized by 
disease and cohort by category/type for the safety analysis set. 


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7. MEASUREMENTS OF TREATMENT EXPOSURE AND COMPLIANCE 
Because study medication is administered at the study center by trained study personnel, 
compliance with respect to study medication will not be calculated. The total number of 
doses/injections and number of days exposed to study drug (defined in Section 5.3) will be 
summarized by disease and cohort for the safety analysis set. A listing of study drug 
administration and exposure data will be provided. 
8. EFFICACY EVALUATION 
8.1            EFFICACY ENDPOINT(S) 
8.1.1  Primary Efficacy Endpoints 
CD subjects only: 
• Change from baseline in SES-CD total score at Visit 10 (Day 56/ET) 
UC subjects only: 
• Change from baseline in Modified Endoscopic Score at Visit 10 (Day 56/ET) 
8.1.2  Secondary Efficacy Endpoint(s) 
CD subjects only: 
• Change from baseline in CDAI item and total scores at Visits 4 (Day 14), 6 (Day 28), 
and 8 (Day 42) 
• Change from baseline in number of total stools for 7-day interval averages from Visit 
3 (Day 7) to Visit 10 (Day 56/ET) 
• Change from baseline in number of loose/watery stools for 7-day interval averages 
from Visit 3 (Day 7) to Visit 10 (Day 56/ET) 
• Change from baseline in abdominal pain score for 7-day interval averages from Visit 
3 (Day 7) to Visit 10 (Day 56/ET) 
• Change from baseline in general well-being for 7-day interval averages from Visit 3 
(Day 7) to Visit 10 (Day 56/ET) 
UC subjects only: 
• Change from baseline in stool frequency for 7-day interval averages from Visit 3 
(Day 7) to Visit 10 (Day 56/ET) 
• Change from baseline in rectal bleeding for 7-day interval averages from Visit 3 (Day 
7) to Visit 10 (Day 56/ET) 


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• Change from baseline in Modified Mayo Score at Visit 10 (Day 56/ET) 
Both CD and UC subjects: 
• Change from baseline in IBD-Q total score at Visit 10 (Day 56/ET) 
8.2            EFFICACY ANALYSIS 
The efficacy analyses will be conducted using the full analysis set as defined in Section 6.1, 
unless otherwise stated. 
The efficacy endpoints mentioned in section 8.1 are described in detail in section 4. 
No statistical tests will be generated. Only descriptive statistics will be presented. 
8.2.1  Primary Efficacy Analyses 
SES-CD (CD subjects only) 
The SES-CD total score and the variable scores will be summarized by cohort and visit using 
continuous and categorical disease severity summaries; the change from baseline for each 
post-baseline visit will also be summarized. 
SES-CD total score and the variable scores will be presented in a listing. 
Modified Endoscopic Score (UC subjects only) 
Mean Modified Endoscopic Score will be summarized for baseline and Visit 10 (Day 56/ET) 
using continuous summaries; the change from baseline will also be summarized.  
Modified Endoscopic Score will be presented in a listing. 
8.2.2  Supportive and Sensitivity Analyses of the Primary Endpoint 
 
Not applicable. 
8.2.3  Secondary Efficacy Analyses 
 
CD subjects only: 
CDAI 
The CDAI item and total scores will be summarized by cohort and visit using continuous 
summaries; the change from baseline for each post-baseline visit will also be summarized. 
Disease severity as defined by the CDAI total score will be summarized by cohort and visit 
using categorical summaries: Remission (<150); Mild (150 - 219); Moderate (220 - 450); 
Severe (> 450). 


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The CDAI total score and each of the 8 item scores will be presented in a listing. Listings 
will also be provided for daily diary data, as well as non-diary item data and CDAI related 
questions. 
Abdominal Pain, Frequency of Loose Stools, and Total Stools 
Mean abdominal pain score, frequency of loose stools, total stools, and general well-being 
will be summarized for baseline and post-baseline visits by cohort and 7-day interval 
averages (corresponding to weekly visit dates) using continuous summaries; the change from 
baseline for each post-baseline visit will also be summarized.  
Since these endpoints are collected in the CD subject diary, they will be presented together in 
one listing. 
UC subjects only: 
Stool Frequency and Rectal Bleeding 
Mean stool frequency and rectal bleeding will be summarized for baseline and post-baseline 
visits by 7-day interval averages (corresponding to weekly visit dates) using continuous 
summaries; the change from baseline for each post-baseline visit will also be summarized.  
Since these endpoints are collected in the UC subject diary, they will be presented together in 
one listing. 
Modified Mayo Score 
The Modified Mayo Score will be summarized by visit using continuous summaries; the 
change from baseline for each post-baseline visit will also be summarized. 
 
The Modified Mayo Score and each of the 3 criteria will be presented in a listing.  
Both CD and UC subjects: 
IBD-Q 
The IBD-Q total score and the domain scores (Bowel; Systemic; Emotional; and Social) will 
be summarized by disease, cohort, and visit using continuous summaries; the change from 
baseline to Visit 10/ET will also be summarized. 
IBD-Q data will be presented in a listing. 


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9. SAFETY EVALUATIONS 
9.1            OVERVIEW OF SAFETY ANALYSIS METHODS 
The safety analyses will be conducted using the safety analysis set as defined in Section 6.1, 
unless otherwise stated. 
9.2            ADVERSE EVENTS 
Any untoward medical event that occurs after signing the informed consent form (ICF) is 
considered to be an adverse event (AE). Adverse events recorded between the time of 
signature of informed consent until the first dose administration will be considered baseline 
signs and/or symptoms.  
A treatment-emergent adverse event (TEAE) is an adverse event with onset on or after the 
first dose administration date or an adverse event present before the first dose administration 
date that worsens (i.e., increases in severity) on or after the first dose administration date. 
TEAEs will be summarized from the first dose administration date through: 
• the Safety Follow-Up/Visit 11 for subjects who completed the study or 
• 28 days after the last dose administration date for subjects who discontinued 
prematurely from the study. 
Verbatim terms used by investigators to identify AEs in the CRFs will be coded to the 
appropriate preferred term (PT) and system organ class (SOC) using a standardized coding 
dictionary (MedDRA Version 23.0 April 2020). All coding will be reviewed prior to 
database lock. All recorded AEs will be listed, but only TEAEs will be summarized. 
Adverse events will be classified according to severity (CTCAE Grades 1-5) and relationship 
to study drug (not related, possibly related, or probably related).  For summary tables, a 
“related” adverse event is one judged to be possibly related or probably related to study drug.  
The following adverse event categories will be summarized by disease and cohort:  
• Overall TEAEs 
• TEAEs related to study drug 
• TEAEs leading to discontinuation 
• Serious AEs 
• Severe TEAEs (Grade 3 or higher) 
The number of subjects with AEs will be further summarized by SOC and PT (TEAEs, as 
well as related TEAEs), by PT only, and by SOC, PT and severity. Sorting will be in 
descending order of frequency.  
If a patient has multiple occurrences of a TEAE within the same SOC and PT, only the most 
related or most severe will be included in the summaries.  


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Separate listings for all AEs, serious AEs, and AEs leading to discontinuation will be 
generated. 
9.3            CLINICAL LABORATORY EVALUATIONS 
Clinical laboratory tests (hematology, serum chemistry, fecal chemistry, and LIGHT [serum 
and tissue]) will be summarized from baseline through Visit 10/ET by visit. For each 
individual lab test value, the observed value and change from baseline will be summarized by 
disease and cohort.  
 
All results, along with urinalysis and other laboratory tests, will be listed. 
 
Other laboratory tests include cytokines (e.g. IL-1 beta, IL-6, IL-8, and TNF-alpha, and other 
exploratory cytokines), flow cytometry analysis of peripheral blood leukocytes, and RNA 
sequencing. 
9.4            VITAL SIGNS 
Vital signs results including systolic and diastolic blood pressure (mmHg), pulse rate 
(beats/min), respiratory rate (breaths/min), and body temperature (C) will be listed for 
individual subjects. These will be collected at Visits 1 (Screening), 2 (Day 0), 4 (Day 14), 6 
(Day 28), 8 (Day 42), 10/ET (Day 56). 
 
Summary statistics, including change from baseline, will be determined for each measure, 
and will be summarized by disease, cohort and by visit and time point (pre-/post-dose). 
9.5            PHYSICAL EXAMINATION 
A complete physical examination including all major body systems will be performed at 
Visits 1 (Screening), 2 (Day 0), 6 (Day 28), and 10/ET (Day 56). In addition, a brief physical 
exam will be performed at Visits 4 (Day 14) and 8 (Day 42).  
 
Physical examination results will be listed for individual subjects. 
9.6            ECG EXAMINATION 
ECG examination will be assessed at Visits 1 (Screening), 6 (Day 28), and 10/ET (Day 56). 
 
Observed values and changes from baseline for ECG parameters, including abnormal results 
and significance, will be displayed by disease, cohort, and time point. All ECG data will be 
listed, including shifts from normal at baseline to abnormal post-baseline. 
9.7            PREGNANCY TEST 
Pregnancy tests (for female subjects of childbearing potential) will be performed at Visits 1 
(Screening), 2 (Day 0), 6 (Day 28), and 10/ET (Day 56).  
 


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Urine test results will be presented on the urinalysis listing while serum test results will be 
presented on the serum chemistry listing. Each test result will be defined to be “negative” or 
“positive”. 
10. PK ANALYSIS 
PK concentration data will be presented in a by-subject listing and summarized by disease, 
cohort and visit using continuous summaries for the PK analysis set. Continuous summaries 
will include arithmetic as well as geometric statistics: n, mean, standard deviation, coefficient 
of variation, median, minimum, maximum, geometric mean, geometric standard deviation, 
and geometric coefficient of variation.  
Plasma concentrations that are reported as lower limit of quantification (LLOQ) will be set to 
0 (zero) for reporting and summary statistics, except for geometric mean and error, for which 
only nonzero data is included. 
11. ADA ANALYSIS 
Anti-drug Antibodies (ADA) data will be collected at Visits 2 (Day 0), 4 (Day 14), 6 (Day 
28), 10 (Day 56/ET), and 11 (Day 84 or 28 days after ET). Screening result, confirmation 
result, and titration result using the safety analysis set will be presented in a by-subject 
listing.  
12. INTERIM ANALYSIS 
No interim analyses will be performed. 
13. DATA MONITORING COMMITTEE 
An external, independent Data Monitoring Committee (DMC) comprising physicians, 
scientists and a biostatistician will review the study data at separate meetings after enrollment 
in the first and second cohorts, respectively.  
The DMC’s role is to protect the interests of the subjects in the study and those still to be 
entered in the study by reviewing information such as safety, tolerability, pharmacokinetic 
and efficacy data.  
Additional details will be outlined in the DMC charter. 
14. CHANGES TO THE ANALYSES PLANNED IN THE PROTOCOL 
Not applicable. 


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15. TABLE OF CONTENTS FOR APPENDICES 
15.1            TABLES 
Table Number 
Analysis 
Set 
Title  
14.1.1 
All 
Subjects 
Patient Disposition 
14.1.2 
Safety 
Important Protocol Deviations 
14.1.3 
Safety 
Demographics and Baseline Characteristics 
14.1.4 
Safety 
Prior Medications by ATC Class and Preferred Term 
14.1.5 
Safety 
Concomitant Medications by ATC Class and 
Preferred Term 
14.1.6 
PK 
Pharmacokinetic Concentration 
14.2.1 
FAS 
Simple Endoscopy Score for Crohn’s Disease 
(SES-CD) 
14.2.2 
FAS 
Modified Mayo Score for Ulcerative Colitis 
14.2.3 
FAS 
Ulcerative Colitis Subject Diary 
14.2.4 
FAS 
Crohn’s Disease Activity Index (CDAI) Item and 
Total Scores 
14.2.5 
FAS 
Crohn’s Disease Subject Diary 
14.2.6 
FAS 
Inflammatory Bowel Disease Questionnaire (IBD-Q) 
14.3.1 
Safety 
Study Drug Exposure 
14.3.2.1 
Safety 
Overall Summary of Treatment Emergent Adverse 
Events 
14.3.2.2 
Safety 
Treatment Emergent Adverse Events by System 
Organ Class and Preferred Term 
14.3.2.3 
Safety 
Study Drug Related Treatment Emergent Adverse 
Events by System Organ Class and Preferred Term 
14.3.2.4 
Safety 
Treatment Emergent Adverse Events by Preferred 
Term 
14.3.2.5 
Safety 
Treatment Emergent Adverse Events by System 
Organ Class, Preferred Term, and Severity 
14.3.3.1 
Safety 
Hematology Parameters 
14.3.3.2 
Safety 
Chemistry Parameters 
14.3.3.3 
Safety 
Fecal Chemistry Parameters 
14.3.4.1 
Safety 
Soluble LIGHT Levels 
14.3.4.2 
Safety 
Tissue LIGHT Levels 
14.3.5 
Safety 
Vital Signs 
14.3.6 
Safety 
Electrocardiogram (ECG) 
 
15.2            LISTINGS 
Listing Number 
Analysis 
Set 
Title  


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16.2.1.1 
All Subjects Subject Disposition 
16.2.2.1 
All Subjects Subjects Not Meeting Inclusion / Meeting 
Exclusion Criteria 
16.2.2.2 
All Subjects Protocol Deviations 
16.2.3 
All Subjects Study Populations 
16.2.4.1 
Safety 
Demographics and Baseline Characteristics 
16.2.4.2.1 
Safety 
Medical History 
16.2.4.2.2 
Safety 
Crohn’s Disease History 
16.2.4.2.3 
Safety 
Ulcerative Colitis History 
16.2.4.3 
Safety 
Prior and Concomitant Medications 
16.2.5.1 
Safety 
Drug Administration and Accountability 
16.2.5.2 
PK 
Pharmacokinetic Sample Collection and 
Concentration 
16.2.5.3 
Safety 
Anti-drug Antibodies (ADA) 
16.2.6.1.1 
FAS 
Quantitative Endoscopy (SES-CD) and Biopsy – 
Part 1 
16.2.6.1.2 
FAS 
Quantitative Endoscopy (SES-CD) and Biopsy – 
Part 2 
16.2.6.2.1 
FAS 
Modified Mayo Score for Ulcerative Colitis 
16.2.6.2.2 
FAS 
Ulcerative Colitis Subject Diary 
16.2.6.3.1 
FAS 
Crohn’s Disease Activity Index (CDAI) Scores 
16.2.6.3.2 
FAS 
Crohn’s Disease Subject Diary 
16.2.6.3.3 
FAS 
Crohn’s Disease Activity Index (CDAI) Non-
Diary Item Data and Related Questions 
16.2.6.4 
FAS 
Inflammatory Bowel Disease Questionnaire 
(IBD-Q) 
16.2.7.1 
Safety 
Adverse Events 
16.2.7.2 
Safety 
Serious Adverse Events 
16.2.7.3 
Safety 
Adverse Events Leading to Discontinuation 
16.2.8.1 
Safety 
Hematology Laboratory Results 
16.2.8.2 
Safety 
Serum Chemistry Laboratory Results 
16.2.8.3 
Safety 
Fecal Chemistry Laboratory Results 
16.2.8.4 
Safety 
Urinalysis Laboratory Results 
16.2.8.5 
Safety 
LIGHT and Confirmatory Disease Biopsy 
Results 
16.2.8.6 
Safety 
Other Laboratory Results 
16.2.9.1 
Safety 
Vital Sign Measurements 
16.2.9.2 
Safety 
Physical Examination 
16.2.9.3 
Safety 
12-Lead Electrocardiogram (ECG)  


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Daperno M, D’Haens G, Van Assche G et al. Development and validation of a new, 
simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastroinest 
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Guyatt G, Mitchell A, Irvine EJ et al. A new measure of health status for clinical trials in 
inflammatory bowel disease. Gastroenterol. 1989;96:804-10. 
 
Henao, M.P., Bewtra M., Osterman M.T., et al [2015]. Measurement of Inflammatory 
Bowel Disease Symptoms: Reliability of an Abbreviated Approach to Data Collection. 
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Moskovitz, David N., et al. Defining and validating cut-offs for the simple endoscopic 
score for Crohn's disease. Gastroenterol. 2007;132.4:A173-A173. 
 
Sostegni R, Daperno M, Scaglione N, Lavagna A et al. Review: Crohn’s disease: 
monitoring disease activity. Aliment Pharmacolo Ther. 2003: 17 (Suppl. 2) 11-17