Conditions: Crohn Disease
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 12
Healthy volunteers: no

Brief summary:
This is a 16-week randomized controlled trial comparing a second IV weight-based induction dose at week 8 to standard 90mg subcutaneous dose at week 8, with a primary endpoint of clinical remission at week 16.

Detailed description:

Arms:
arm 1: None arm 2: None

Interventions: intervention 1: Ustekinumab intervention 2: Ustekinumab intervention 3: Ustekinumab
Intervention descriptions: intervention 1: A second IV weight-based induction dose of Stelara at week 8 intervention 2: A standard 90mg subcutaneous dose of Stelara at week 8 intervention 3: All patients will receive IV ustekinumab weight-based dose at 260mg (55kg or less), 390mg (more than 55kg to 85kg), or 520mg (more than 85kg) at time point 0

Protocol document:
Prot_SAP_000.pdf: 
 
 
Official Title: 
INDUCTION OPTIMIZATION WITH STELARA FOR CROHN’S 
DISEASE 
NCT Number: 
NCT04629196 
Study Number: 
s19-01401 
Document Type:  
Study Protocol and Statistical Analysis Plan 
Date of the 
Document: 
• 
December 18, 2022 
 
 


 
 
Page i 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 11 January 2019 
 
 
 
 
 
INDUCTION OPTIMIZATION WITH STELARA FOR CROHN’S DISEASE 
  
 
Principal Investigator 
and IND sponsor: 
 
David Hudesman, MD 
Additional Investigators: 
 
Shannon Chang, MD/NYU Langone Health, NY 
Jordan Axelrad, MD/NYU Langone Health, NY 
Raymond Cross, MD/University of Maryland, MD 
 
NYULMC Study Number: 
S19-01401 
Funding Supporter:  
Janssen Scientific Affairs, LLC 
Protocol identifier: CNTO1275CRD3009 
 
Study Product: 
Stelara (ustekinumab) 
IND Number 
155306 
Study Product Provider:  
Janssen Scientific Affairs, LLC (Janssen) 
Version: 
18DEC2022 Amendment 3.0 
 
 


Study number: S19-01401 
 
Page ii 
Version: 18 Dec 2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 11 January 2019 
 
Statement of Compliance 
 
This study will be conducted in accordance with the Code of Federal Regulations on the Protection of 
Human Subjects (45 CFR Part 46), 21 CFR Parts 50, 56, 312, and 812 as applicable, any other applicable 
US government research regulations, and institutional research policies and procedures. The International 
Conference on Harmonisation (“ICH”) Guideline for Good Clinical Practice (“GCP”) (sometimes referred to 
as “ICH-GCP” or “E6”) will be applied only to the extent that it is compatible with FDA and DHHS regulations. 
The Principal Investigator will assure that no deviation from, or changes to the protocol will take place 
without prior agreement from the sponsor and documented approval from the Institutional Review Board 
(IRB), except where necessary to eliminate an immediate hazard(s) to the trial participants. All personnel 
involved in the conduct of this study have completed Human Subjects Protection Training. 
 
 


Study number: S19-01401 
 
Page iii 
Version: 18 Dec 2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 11 January 2019 
Table of Contents 
 
STATEMENT OF COMPLIANCE ................................................................................................................. II 
LIST OF ABBREVIATIONS .......................................................................................................................... V 
PROTOCOL SUMMARY .............................................................................................................................. 6 
1 
KEY ROLES ......................................................................................................................................... 7 
2 
INTRODUCTION, BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ....................... 7 
2.1 
BACKGROUND INFORMATION AND RELEVANT LITERATURE ................................................................ 7 
2.2 
POTENTIAL RISKS & BENEFITS ........................................................................................................ 8 
2.2.1 
Known Potential Risks ............................................................................................................. 8 
3 
OBJECTIVES AND PURPOSE ......................................................................................................... 11 
3.1 
PRIMARY OBJECTIVE .................................................................................................................... 11 
3.2 
SECONDARY OBJECTIVES ............................................................................................................. 11 
4 
STUDY DESIGN AND ENDPOINTS .................................................................................................. 12 
4.1 
DESCRIPTION OF STUDY DESIGN .................................................................................................. 12 
4.2 
STUDY ENDPOINTS....................................................................................................................... 13 
4.2.1 
Primary Study Endpoints ....................................................................................................... 13 
4.2.2 
Secondary Study Endpoints .................................................................................................. 13 
4.2.3 
Exploratory Endpoints ........................................................................................................... 13 
5 
STUDY ENROLLMENT AND WITHDRAWAL .................................................................................. 14 
5.1 
INCLUSION CRITERIA .................................................................................................................... 14 
5.2 
EXCLUSION CRITERIA ................................................................................................................... 15 
5.3 
STRATEGIES FOR RECRUITMENT AND RETENTION .......................................................................... 16 
5.4 
DURATION OF STUDY PARTICIPATION ............................................................................................ 16 
5.5 
TOTAL NUMBER OF PARTICIPANTS AND SITES ................................................................................ 16 
5.6 
PARTICIPANT WITHDRAWAL OR TERMINATION ................................................................................ 16 
5.6.1 
Reasons for Withdrawal or Termination ................................................................................ 16 
5.7 
PREMATURE TERMINATION OR SUSPENSION OF STUDY .................................................................. 17 
6 
STUDY AGENT (STUDY DRUG, DEVICE, BIOLOGIC, VACCINE ETC.) AND/OR PROCEDURAL 
INTERVENTION ......................................................................................................................................... 17 
6.1.1 
Preparation ............................................................................................................................ 17 
6.1.2 
Administration of Intervention ................................................................................................ 18 
7 
STUDY PROCEDURES AND SCHEDULE ....................................................................................... 18 
7.1 
STUDY PROCEDURES/EVALUATIONS ............................................................................................. 18  
8 
ASSESSMENT OF SAFETY ............................................................................................................. 19 
8.1 
SPECIFICATION OF SAFETY PARAMETERS ...................................................................................... 19 
8.1.1 
Definition of Adverse Events (AE) ......................................................................................... 19 
8.1.2 
Definition of Serious Adverse Events (SAE) ......................................................................... 20 
8.1.3 
Definition of Unanticipated Problems (UP) ............................................................................ 21 
8.2 
CLASSIFICATION OF AN ADVERSE EVENT ....................................................................................... 21 
8.2.1 
Severity of Event ................................................................................................................... 21 
8.2.2 
Relationship to Study Agent .................................................................................................. 21 
8.2.3 
Expectedness ........................................................................................................................ 22 
8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP .................................... 22 
8.4 
REPORTING PROCEDURES – NOTIFYING THE IRB .......................................................................... 23 
8.4.1 
Adverse Event Reporting ...................................................................................................... 23 
8.4.2 
Serious Adverse Event Reporting ......................................................................................... 24 


Study number: S19-01401 
 
Page iv 
Version: 18 Dec 2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 11 January 2019 
8.5 
REPORTING PROCEDURES – NOTIFYING THE STUDY SPONSOR ...................................................... 24 
Product Quality Complaint (PQC) ...................................................................................................... 26 
9 
STATISTICAL CONSIDERATIONS .................................................................................................. 29 
9.1 
STATISTICAL HYPOTHESES ........................................................................................................... 30 
10 
ETHICS/PROTECTION OF HUMAN SUBJECTS ............................................................................. 30 
10.1 
ETHICAL STANDARD ..................................................................................................................... 30 
10.2 
INSTITUTIONAL REVIEW BOARD ..................................................................................................... 30 
10.3 
INFORMED CONSENT PROCESS .................................................................................................... 30 
10.3.1 
Consent/Assent and Other Informational Documents Provided to Participants ............... 30 
11 
DATA HANDLING AND RECORD KEEPING ................................................................................... 31 
11.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES .............................................................. 31 
12 
STUDY FINANCES ............................................................................................................................ 31 
12.1 
FUNDING SOURCE ........................................................................................................................ 31 
12.2 
COSTS TO THE PARTICIPANT ......................................................................................................... 31 
13 
STUDY ADMINISTRATION ............................................................................................................... 31 
14 
REFERENCES ................................................................................................................................... 32 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Study number: S19-01401 
 
Page v 
Version: 18 Dec 2022 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 11 January 2019 
 
List of Abbreviations 
 
AE 
Adverse Event/Adverse Experience 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CSOC 
Clinical Study Oversight Committee 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data and Safety Monitoring Board 
FFR 
Federal Financial Report 
FWA 
Federalwide Assurance 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
MOP 
Manual of Procedures 
N 
Number (typically refers to participants) 
NIH 
National Institutes of Health 
OHRP 
Office for Human Research Protections 
OHSR 
Office of Human Subjects Research 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOP 
Standard Operating Procedure 
US 
United States 
 
 


Study number: S19-01401 
 
Page 6 
Version: 18 Dec 2022 
 
 
 
Protocol Summary 
Title 
Induction Optimization with Stelara for Crohn’s Disease  
 
Brief Summary 
This is a 16-week randomized controlled trial comparing a second IV weight-
based induction dose at week 8 to standard 90mg subcutaneous dose at 
week 8, with a primary endpoint of clinical remission at week 16. 
 
Objectives 
To evaluate the efficacy of a second IV dose of ustekinumab at week 8 in 
inducing remission in “high risk” moderate to severe Crohn’s patients 
 
Endpoint 
Clinical remission at week 16: Defined as a CDAI <150 
Study Duration 
18 months 
Participant Duration 
Approximately 24 weeks 
Population 
Patients between the ages of 18 and 70 with Crohn’s Disease 
Study Sites 
NYU Langone Medical Center 
University of Maryland 
Number of participants 
88 participants expected to be enrolled across two sites 
Description of Study 
Agent/Procedure 
This is a 16-week randomized controlled trial comparing a second IV weight-
based induction dose at week 8 to standard 90mg subcutaneous dose at 
week 8, with a primary endpoint of clinical remission at week 16. 
 
 
 
 
 


Study number: S19-01401 
 
Page 7 
Version: 18 Dec 2022 
 
 
 
1 Key Roles 
 
Principal Investigator:  
 
David Hudesman, MD 
Co-Director, Inflammatory Bowel Disease Center at NYU Langone Health 
Associate Professor of Medicine 
305 East 33rd Street  
New York, NY 10016 
Tel: 855-698-4232 
Fax: 212-263-3096 
 
Sub Investigator(s):  
 
Shannon Chang, MD, MBA 
Assistant Professor of Medicine 
305 East 33rd Street  
New York, NY 10016 
Tel: 855-698-4232 
Fax: 212-263-3096 
 
Jordan Axelrad, MD, MPH 
Assistant Professor of Medicine  
305 East 33rd Street  
New York, NY 10016 
Tel: 855-698-4232 
Fax: 212-263-3096 
 
Raymond Cross, MD 
Professor of Medicine 
University of Maryland  
22 S Greene St, 
Baltimore, MD 21201 
Tel: 410-706-3387 
 
2 Introduction, Background Information and Scientific Rationale 
 
2.1 Background Information and Relevant Literature 
Inflammatory bowel diseases (IBD) are comprised of two diseases: Crohn’s disease (CD) and ulcerative 
colitis (UC). Both CD and UC are driven by an aberrant immune response against intestinal flora and/or 
dietary antigens, but their pathophysiologies are quite different. The mainstay treatment of moderate to 
severe Crohn’s disease is biologic and/or immunosuppressive agents.  Despite the efficacy of anti-TNF 
agents in CD, about 30% of patients are primary non-responders, and up to 40% will lose response by the 
end of a year.  Part of this loss of response is due to lack of optimization during induction therapy.  
Furthermore, dosing strategies for anti-TNF and anti-integrin therapies have evolved overtime.  In patients 
with severe IBD (clinically and endoscopically), higher induction doses of anti-TNF are required to achieve 
remission.  In the GEMINI 1 trial with vedolizumab, steroid refractory patients responded better to every 4 
week dosing from the start compared to every 8 week dosing regimen.  Therefore, optimizing our new 
medications with novel mechanisms of action is critical for the management of CD patients. 
 


Study number: S19-01401 
 
Page 8 
Version: 18 Dec 2022 
 
 
 
Ustekinumab was FDA approved in 2016 for moderate to severe Crohn’s disease.  The UNITI induction 
trials showed a significant higher clinical response at week 6 vs placebo, 33.7 percent in TNF exposed 
patients and 55.5% in TNF naïve patients.  However, patients with elevated biomarkers, such as CRP or 
fecal calprotectin, had lower response rates compared to those with normal biomarkers.  I postulate that 
these “high risk” patients will benefit from a higher induction dose. 
2.2 Potential Risks & Benefits 
2.2.1 Known Potential Risks 
 
The following are risks associated with study drug: 
 
Risk of Ustekinumab (Stelara) 
 
The possible discomforts, side effects and risks related to Ustekinumab treatment are not all known. This 
section describes how frequently side effects occurred in subjects who were treated with Ustekinumab in 
the past.   
 
Very Common (affects more than 1 user in 10): 
 
• 
None  
 
Common (affects 1 to 10 users in 100): 
 
 
 
 
• 
Swelling, itching, hardness, bleeding, bruising and irritation where the injection is given. 
• 
Shingles (a painful rash) 
• 
Depression 
• 
Inflammation of tissue under the skin.  Signs include warmth, swelling, redness and pain 
• 
Nasal congestion 
• 
A form of psoriasis with raised bumps on the skin that are filled with pus 
• 
Allergic reactions including rash or raised, itchy bumps 
• 
Tooth infections 
• 
Acne 
• 
Feeling weak 
• 
Vaginal yeast infection 
• 
Chest infection 
 
 
 
 
• 
Infection of the throat, airway or sinus 
• 
Headache 
• 
Sore throat 
• 
Dizziness 
• 
Feeling tired 
• 
Diarrhea 
• 
Redness and pain at drug injection site 
• 
Nausea  
• 
Back, joint or muscle pain 
• 
Itchiness 
• 
Vomiting 
 
Uncommon (affects 1 to 10 users in 1,000): 


Study number: S19-01401 
 
Page 9 
Version: 18 Dec 2022 
 
 
 
Rare (affects 1 to 10 users in 10,000): 
• 
Serious allergic reactions, which could be life-threatening (including low blood pressure, trouble 
breathing, swollen face, lips, mouth and/or throat) 
• 
A form of psoriasis with redness and scaling of a much larger area of skin or entire body 
(erythrodermic psoriasis) 
• 
In rare cases, symptoms such as cough, shortness of breath, and fever may also be a sign of an 
allergic lung reaction to Ustekinumab 
• 
Inflammation of small blood vessels, which can lead to a skin rash with small red or purple bumps, 
fever or joint pain (vasculitis). 
 
 
 
Infections 
 
Ustekinumab is a drug that may change how the body fights infections. Serious infections requiring 
hospitalization for medical observation and /or treatment have been seen in Ustekinumab studies. Some of 
these infections have also been life threatening. 
 
Patients will be instructed to notify the study team should they experience any of the following while in the 
study: 
  
• 
Fever 
• 
Chills 
• 
Headache  
• 
Coughing  
• 
Congestion 
• 
Chest tightness 
• 
Shortness of breath  
• 
Flu-like symptoms  
• 
Nausea 
• 
Vomiting   
• 
Diarrhea 
• 
Increased frequency 
or 
burning 
while 
passing urine  
• 
Redness 
warmth, 
tenderness 
or 
swelling of skin or 
joint 
• 
Cold sores 
• 
New or worsening of 
pain in any location 
• 
Weight loss 
• 
Tiredness
• 
Night sweats 
 
It is unknown if Ustekinumab may stop patients from developing a fever if you do have an infection, and 
therefore hide that you have one. 
 
Fungal infections have been reported in subjects taking Ustekinumab.  Some of these fungal infections can 
be serious and involve internal organs. Patients will be instructed to notify the study team of symptoms of 
such illnesses. 
 
Subjects who receive Ustekinumab may also be at a greater risk for certain serious infections such as 
tuberculosis. Subjects will be instructed to tell their study doctor if they have ever had tuberculosis or 
anybody in their family has ever had tuberculosis or if they come in contact with someone who has 
tuberculosis. 
 
Subjects will be instructed to notify the research team if they experience the following symptoms: 
 
• 
A cough that does not go away 
• 
Coughing up blood 
• 
Shortness of breath 
• 
Fever 
• 
Night sweats 
• 
Weight loss  
 
 
 


Study number: S19-01401 
 
Page 10 
Version: 18 Dec 2022 
 
 
 
Cancer 
 
Cancers have been reported in subjects who have received Ustekinumab but it is unknown whether taking 
Ustekinumab has increased their risk for developing cancer.  Because Ustekinumab may suppress the 
immune system, it is possible that it may increase risk of developing cancer, including skin cancers. 
Subjects who have been diagnosed with psoriasis have a higher chance of developing skin cancers. 
Subjects will be instructed to notify the research team if they have any new or changing skin lesions. 
 
It is known that people who have had inflammatory diseases (such as, Crohn’s disease, Rheumatoid 
Arthritis, Ulcerative Colitis etc.) for a long time and who have had long term use of immunosuppressive 
therapies (such as, azathioprine, methotrexate etc.)  have a higher risk of developing cancer. These people 
get cancer of the lymph nodes or otherwise known as lymphoma more often than other people do.  
 
 
Infusion Reactions, Injection Site Reactions and Allergic Reactions   
 
Ustekinumab may cause an allergic reaction in some subjects. These reactions are usually mild to 
moderate.  The body might have a reaction during or shortly following an infusion of Ustekinumab into the 
vein.  This is called an infusion reaction and these reactions are usually mild to moderate.  They are 
managed by slowing the infusion or by giving you medication. The following can be symptoms of an infusion 
reaction or an allergic reaction: 
• 
Fever  
• 
Chills  
• 
Hives 
• 
Rash  
• 
Swelling  
• 
Itching  
• 
Headache  
• 
Flushing 
• 
Nausea 
• 
Light-headedness 
• 
Chest pain or tightness  
• 
Wheezing  
• 
Difficulty breathing 
             or swallowing 
• 
Decrease or increase in 
blood pressure  
• 
Anaphylaxis 
(life 
threatening 
allergic 
reaction)  
 
Serious allergic reactions have been reported in subjects taking Ustekinumab and can be life threatening.  
Signs of a serious allergic reaction include skin rash, swollen face, mouth, lips, and/or throat, and trouble 
breathing.   If this happens during the infusion, the infusion will be stopped and necessary treatment will be 
provided immediately.   
 
Delayed allergic reaction have occurred in some subjects 1-14 days after receiving some similar 
medications. Subjects will be instructed to inform the research team as soon as they experience any of the 
following reactions: fever, rash, muscle aches and joint pain 
 
Cardiac and Vascular 
 
Heart attacks and strokes have been reported in subjects who have received Ustekinumab.  It is unknown 
whether taking Ustekinumab increases the risk for developing these events.   
 
People who have psoriasis, and certain other inflammatory diseases, have a higher risk of having heart 
attacks.  Subject will be informed to seek medical attention immediately upon experience any of the 
following: 
 
• 
Chest pain or discomfort  
• 
Trouble breathing 
• 
Irregular heartbeats  
• 
Dizziness  
• 
Loss of balance  
• 
New numbness or weakness  
• 
Visual or speech changes


Study #: s19- 01401 
Version date: 17OCT2022  
Page 11 of 34 
 
 
 
 
 
 
Allergy Immunotherapy (Allergy Injections)   
  
Ustekinumab may affect response to allergy injections. Subjects will be asked to notify the research team 
of any scheduled allergy injections.  
 
 
Other Risks 
 
Two cases of a very rare disease of the brain, posterior reversible encephalopathy syndrome (PRES), also 
known as Reversible Posterior Leukoencephalopathy Syndrome (RPLS), were reported in clinical studies 
with Ustekinumab. PRES is generally reversible and is not caused by an infection. It is unknown whether 
taking Ustekinumab increases the risk of developing PRES/RPLS.  The research team will follow subjects 
closely for the following signs and symptoms: 
 
• 
Headache 
 
• 
Seizures 
• 
Confusion 
• 
Loss of eyesight 
3 Objectives and Purpose 
The primary aim of this IIS is to evaluate whether a second IV weight-based induction dose at week 8 will 
improve clinical remission rates in “high risk” moderate to severe Crohn’s disease patient population at 
week 16. 
 
A “high risk” patient is defined as a patient with moderate to severe CD with a CDAI between 220 and 450 
and either a CRP > 8mg/L and/or a fecal calprotectin > 250ug/g, who at week 8, the CDAI does not drop 
by more than 100 points (clinical response), unless CDAI <150, (clinical remission), or at week 6 either the 
CRP does not drop below 5mg/L or fecal calprotectin does not decrease by 50%. 
3.1 Primary Objective 
To evaluate the efficacy of a second IV dose of ustekinumab at week 8 to induce remission in “high risk” 
moderate to severe Crohn’s patients. 
3.2 Secondary Objectives  
1. To evaluate the safety of a second IV dose of ustekinumab at week 8 in “high risk” moderate to 
severe Crohn’s patients. 
 
2. To evaluate the efficacy of a second IV dose of ustekinumab at week 8 in clinical response in “high 
risk” moderate to severe Crohn’s patients. 
 
3. To evaluate the efficacy of a second IV dose of ustekinumab at week 8 in health-related quality of 
life. 
 
4. To evaluate the pharmacodynamics of a second IV dose of ustekinumab in moderate to severe 
Crohn’s disease patients, including C-reactive protein (CRP) and fecal calprotectin. 
 
5. To evaluate the endoscopic response and endoscopic remission of a second IV dose of 
ustekinumab at week 8 in “high risk” moderate to severe Crohn’s patients. 
 


Study number: S19-01401 
 
Page 12 
Version: 18 Dec 2022 
 
 
 
4 Study Design and Endpoints 
4.1 Description of Study Design 
 
This is a 16-week randomized, controlled trial comparing a second IV weight-based induction dose at week 
8 to standard 90mg subcutaneous dose at week 8, with a primary endpoint of clinical remission at week 16. 
 
A total of 88 patients are to be enrolled, 18 years or older, with moderate to severe Crohn’s disease based 
on a CDAI between 220 and 450, and either a CRP > 8mg/L and/or a fecal calprotectin > 250ug/g. 
 
All patients will receive IV ustekinumab weight-based dose at 260mg (55kg or less), 390mg (more than 
55kg to 85kg), or 520mg (more than 85kg) at time point 0.  At week 6, clinical and biochemical response 
will be assessed using CRP, and fecal calprotectin.   
 
Patients will be randomized to a second weight based IV dose or standard 90mg subcutaneous dose at 
week 8 if:  
• 
Week 8 CDAI (based on CDAI score calculated from previous 7 days) does not drop by more than 
100 points from Week 0 (and is >150) 
OR 
• 
Week 8 CDAI (based on CDAI score calculated from previous 7 days) does drop by 100 points 
from Week 0 (but is >150) but subject does not have a biomarker response.  
Biomarker response at week 6 is defined as a CRP < 5mg/l, or a fecal calprotectin drops by at least 50%, 
or is less than 150 ug/g.  Patients will be stratified based on lack of clinical response and lack of biomarker 
response. According to literature, a normal CRP is <5mg/L.  For fecal calprotectin, based on the literature 
findings, over 250 ug/g suggests active inflammation.  From 150-250 ug/g, it is less clear if there is still 
active inflammation.  Less than 150 ug/g indicates the ability to rule out active inflammation.   
 
 
All other subjects (e.g., attaining remission and those attaining biomarker response with clinical response) 
will not be randomized.  These patients will continue to the standard 90 mg SC q8wk dosing and receive 
standard of care. 
 
Outside of the randomization to IV vs SubQ dosing at week 8, the management will follow standards of 
care.   
 
Given that this is an unblinded study, randomization will be done by study coordinators through the 
TrialMasters platform. Study coordinators will communicate the randomization assignment to the NYU 
Investigational Pharmacy via email. 
 
The Investigators agree that CDAI is a subjective marker of disease.  In an effort to mitigate the issue of 
subjectivity, randomized subjects will include those who do not have a drop in more objective biomarkers 
of disease including CRP and fecal calprotectin. 
 
Steroid Taper: 
Use of prednisone or budesonide and any tapering of these drugs will be at the discretion of the provider, 
consistent with standard of care. 
 
If the provider assesses that the patient’s disease has progressed based on CDAI or any other clinical or 
laboratory parameter, the provider may make any necessary medication changes as he or she sees fit.  If 
prednisone is increased or another biologic/immunosuppressant is added, then the patient will be withdrawn 
from the study. Subjects withdrawn from the study will be called every three months for one year from the 
date of last intervention During this call, adverse events will be collected and reported to investigators.  
 
 


Study number: S19-01401 
 
Page 13 
Version: 18 Dec 2022 
 
 
 
4.2 Study Endpoints 
4.2.1 Primary Study Endpoints 
Clinical remission at week 16: Defined as a CDAI <150 
4.2.2 Secondary Study Endpoints 
Major Secondary Endpoints:  
 
1. Clinical response at week 16: Defined as a drop in CDAI by at least 100 points between week 0 
and week 16, or a CDAI < 150 
2. Composite clinical and biomarker response at week 16: Defined as a drop in CDAI by at least 100 
points from week 0 to week 16, or a CDAI < 150, and a biomarker response from week 0 to week 
16 
3. Composite clinical and biomarker remission at week 16: Defined as a CDAI < 150 and a CRP 
<5mg/l or a fecal calprotectin <150 ug/g 
4. Change in CDAI from week 0 to week 16 
5. Improvement in health-related quality of life at week 16: Increase in SIBDQ by at least 9 points 
between week 0 and week 16 
6. Biomarker response:  
-Drop in CRP and fecal calprotectin at week 0 and week 16 
-Normalization of CRP defined as CRP < 5mg/L at week 0 and 16 (in patients with baseline 
elevation of CRP) 
-Normalization of fecal calprotectin defined as <150ug/g at week 0 and 16 (in patient with baseline 
elevation of fecal calprotectin) 
 
7. Endoscopic response at month 6: Defined as a >/= 50% reduction from baseline in SES-CD score 
8. Endoscopic remission at month 6: Defined as SES-CD score </=2 (The secondary endpoints of 
endoscopic response and endoscopic remission will be assessed in patients that had a 
colonoscopy within 3 months of the screening visit and a colonoscopy between 4-8 months after 
starting the study). 
 
Other Secondary Endpoints Include:  
 
9. Clinical response between week 8 and week 16: Defined as a drop in CDAI by at least 100 points 
between week 8 and week 16 
10. Composite clinical and biomarker response between week 6/8 and week 16: Defined as a drop in 
CDAI by at least 100 points from week 8 to week 16 and a biomarker response from week 6 to 
week 16  
11. Drop in CRP and/or fecal calprotectin between week 6 and week 16 in patients with baseline 
biomarker elevation 
12. Steroid free clinical remission 
13. Clinical remission based on past biologic failure status 
14. Clinical response based on past biologic failure status 
 
4.2.3 Exploratory Endpoints 
PK testing will be done to look at the week 8 levels associated with subsequent response as well as possibly 
examine week 16 PK for subjects who have received the second IV dose. PK samples will be stored at 
NYU Langone for the time-being however they may be sent to Janssen at a future date (for which protocol 
will be amended). When/if PK samples are   transferred to Janssen, they will be sent via courier designated 
by Janssen R&D to the Janssen R&D - Biologics Development Sciences labs located in Spring House, PA, 
U.S.A for analysis by Janssen researchers. PK samples will be labeled with a subject number to help protect 
the subject's privacy. The Janssen scientists doing the research will not know the identity of the study 


Study number: S19-01401 
 
Page 14 
Version: 18 Dec 2022 
 
 
 
subject. Once testing is complete and if any samples remain, they will be returned to NYU Langone Medical 
Center in New York, NY, U.S.A. 
 
The samples collected from patients entering into this IIS will be deidentified upon completion of this IIS.  
The only identifiers that will be kept includes, age, gender, disease and date of collection. 
 
Subjects enrolled in this trial at NYU Langone will also be approached about participating in a separate 
biobanking protocol entitled, “Mucosal immune profiling in patients with inflammatory bowel disease” (s12-
01137).- The purpose of this research study is to create a database of information from medical records of 
patients with and without Inflammatory Bowel Disease. However, co-enrollment in study s12-01137 is not 
a requirement for eligibility into this study (s19-01401). Should a patient choose to consent to this additional 
study, blood, stool, and biopsy samples will be collected in accordance with the timepoints under the s12-
01137 protocol, which are in accordance with the subject’s standard of care visits.  
  
The collection of biospecimens under the protocol, “Mucosal immune profiling in patients with inflammatory 
bowel disease” (s12-01137) will allow for post hoc analyses focusing on predictors of response 
(translational) and therapeutic drug monitoring in this study. Samples will be stored and analyzed at NYU 
Langone.  Samples obtained under study s12-01337 will not be shared with Janssen R&D. 
 
 
 
5 Study Enrollment and Withdrawal 
5.1 Inclusion Criteria 
1. Males or females between the ages of 18 and 70 
2. History of Crohn’s disease for at least 3 months confirmed by colonoscopy and/or cross sectional 
imaging reviewed by the PI 
3. Moderate to Severe Crohn’s disease defined as a CDAI between 220 and 450 at Week 0.  
4. Either a CRP >8mg/L or a fecal calprotectin > 250ug/g within 4 weeks of starting ustekinumab 
5. Stable Concomitant medications (prior to first dose of ustekinumab) 
a. Stable dose of 6-MP, azathioprine, or methotrexate for at least 4 weeks 
b. Stable dose of oral mesalamine for at least 2 weeks 
c. Stable dose of prednisone of 20mg or less or budesonide 9mg daily for at least 2 weeks 
6. If subject is a female, before randomization she must be: 
a. Postmenopausal, defined as 
a. ≥ 45 years of age with amenorrhea for at least 18 months, 
OR  
b. ≥ 45 years of age with amenorrhea for at least 6 months and a 
serum FSH level > 40 IU/mL 
 
OR 
 
b. Of childbearing potential, in which case she must satisfy at least one of the below: 
a. Surgically sterile (has had a hysterectomy or bilateral 
oophorectomy, tubal ligation, or otherwise be incapable of 
pregnancy), or 
b. If heterosexually active, practicing a highly effective method of 
birth control, including hormonal prescription oral contraceptives, 
contraceptive injections, contraceptive patch, intrauterine device, 
double-barrier method (eg, condoms, diaphragm, or cervical cap, 
with spermicidal foam, cream, film, gel or suppository), or male 
partner sterilization, consistent with local regulations regarding 


Study number: S19-01401 
 
Page 15 
Version: 18 Dec 2022 
 
 
 
use of birth control methods for subjects participating in clinical 
trials, for a period of 16 weeks after the last administration of 
study agent, 
OR  
c. Not heterosexually active. 
Note: If a woman participant’s childbearing potential changes after start of the study (e.g., a pre-
menarchal woman experiences menarche) or if women of childbearing potential who are not 
heterosexually active at screening become heterosexually active, they must agree to utilize a highly 
effective method of birth control, as described above. 
 
7. Female participants of childbearing potential (menstrual and not surgically sterile), must have a 
negative  urine pregnancy test at Week 0 (prior to randomization) and agree not to donate eggs 
(ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 16 
weeks after the last administration of study agent. 
8. Male participants who are not surgically sterilized and are heterosexually active with a woman of 
childbearing potential, must agree to use a barrier method of contraception (e.g., condom with 
spermicidal foam/gel/film/cream/suppository) and to not donate sperm during the study and for 16 
weeks after last receiving study agent. Note that barrier methods must also be used in all male 
subjects sexually active with pregnant partners for at least 16 weeks after last study agent 
administration. 
5.2 Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
1. Past Stelara or anti-IL 23 use.   
2. Active infection.   
3. Has any known malignancy or has a history of malignancy (except for basal cell carcinoma; 
squamous cell carcinoma in situ of the skin; or cervical carcinoma in situ that has been treated 
with no evidence of recurrence; or squamous cell carcinoma of the skin that has been treated 
with no evidence of recurrence within 5 years prior to screening). 
4. Indeterminate colitis.   
5. Active perianal fistula as the primary symptom.   
6. Fibrostenotic disease with primarily obstructive symptoms.  
7. Hospitalization within the past 2 weeks. 
8. Bowel resection within the past 4 weeks. 
9. Subtotal colectomy. 
10. Permanent Ileostomy.  
11. Known infection with human immunodeficiency virus (HIV).  
12. Has a concomitant diagnosis or any history of congestive heart failure or demyelinating disease. 
13. Has current signs or symptoms, or a history of severe, progressive, or uncontrolled renal, hepatic, 
hematologic, endocrine, pulmonary, cardiac, neurologic, systemic lupus erythematosus, or 
psychiatric diseases. 
14. Has a transplanted organ (except for corneal transplant performed > 3 months prior to screening). 
15. Has a history of lymphoproliferative disease including lymphoma, or signs and symptoms 
suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or 
location (e.g., nodes in the posterior triangle of the neck, supraclavicular, epitrochlear, or 
paraaortic areas), or splenomegaly. 
16. Has previously undergone allergy immunotherapy for prevention of anaphylactic reactions. 
17. Is unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of 
easy access to veins. 
18. Has known allergies, hypersensitivity, or intolerance to ustekinumab or excipients (refer to the 
ustekinumab prescribing information). 


Study number: S19-01401 
 
Page 16 
Version: 18 Dec 2022 
 
 
 
19. Has a clinically significant substance abuse problem (eg, drugs or alcohol) at screening or during 
the previous 12 months prior to baseline. 
20. Any biologic or small molecule therapy within 4 weeks of start of ustekinumab.   
21. Known infection or symptoms of active tuberculosis including Positive quantiferon gold within the 
last 1 year that is not being treated and followed by Infectious Disease.   
22. Known Hepatitis B infection or unknown Hepatitis B history including no documentation of 
immunity (vaccination history or positive HepB surface antibody test). Tests positive for HBV 
surface antigen (HBsAg), regardless of the results of other hepatitis B tests. Subjects who test 
positive only for core antibody (anti-HBc) must undergo further testing for hepatitis B DNA acid 
(HBV DNA test). If the HBV DNA test is positive, the subject is not eligible for this study. If the 
HBV DNA test is negative, the subject is eligible for this study. In the event the HBV DNA test 
cannot be performed, the subject is not eligible for this study.  
23. Change in dose of 6-MP, methotrexate, or azathioprine within one month of the start of 
ustekinumab. 
24. Change in prednisone or budesonide dose within 2 weeks of start of ustekinumab 
25. Change in mesalamine dosage within 2 weeks of start of ustekinumab 
26. Has a stool culture or other examination positive for an enteric pathogen, including Clostridium 
difficile toxin, in the last 4 months unless a repeat examination is negative and there are no signs 
of ongoing infection with that pathogen 
27. Has received a Bacillus Calmette–Guérin (BCG) vaccination within 12 months or any other live 
bacterial or live viral vaccination within 2 weeks of baseline. 
28. Have immune deficiency syndrome (e.g., severe combined immunodeficiency syndrome, T-cell 
deficiency syndromes, B-cell deficiency syndromes, and chronic granulomatous disease). 
29. Known infection with Hepatitis C (HCV) without a history of clearance or successful treatment. 
Successful treatment is defined as being negative for HCV RNA at least 24 weeks after 
completing antiviral treatment.  
5.3 Strategies for Recruitment and Retention 
Patients will be enrolled by the study coordinator or investigators directly during routine office visits or 
prior to scheduled colonoscopy procedures. Patients will not be contacted 
outside of routine clinical interactions. No additional procedures will be performed 
specifically for the purposes of this study. Informed consent for participation in the study will 
be obtained in parallel with consent for the colonoscopy procedure. 
5.4 Duration of Study Participation 
Patients will be enrolled at both NYU and University of Maryland, under Dr. Raymond Cross.  Each subject 
will be enrolled for approximately 32 weeks.  We expect enrollment to be complete within 18 months. 
 
5.5 Potential Benefits  
Participants may or may not benefit directly from participating in this study. Those who do experience 
benefits from the study may see an improvement in symptoms related to Crohn’s disease. Ultimately, the 
information gained from this study will help the scientific community’s understand of Crohn’s Disease. Total 
Number of Participants and Sites. 
 
A total of 88 participants will be recruited at NYU Langone and University of Maryland sites.  
5.6 Participant Withdrawal or Termination 
5.6.1 Reasons for Withdrawal or Termination 
 


Study number: S19-01401 
 
Page 17 
Version: 18 Dec 2022 
 
 
 
Participants are free to withdraw from participation in the study at any time upon request. An investigator 
may terminate participation in the study if: 
• 
Any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
participant 
• 
The participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
• 
Participant fails to complete study 
• 
Patients who experience disease progression and are in need of an addition or increase of 
prednisone or another biologic/immunosuppressant will be withdrawn from the study.  
 
Subjects withdrawn from the study will be called every three months for one year from the date of the last 
dose of the study intervention. During this call, adverse events will be collected and reported to 
investigators.  
5.7 Premature Termination or Suspension of Study 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be provided 
by the suspending or terminating party to Janssen Scientific Affairs LLC. If the study is prematurely 
terminated or suspended, the PI will promptly inform the IRB and will provide the reason(s) for the 
termination or suspension. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant stopping 
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, data quality are addressed and 
satisfy the sponsor, IRB and/or FDA. 
 
6 Study Agent (Study drug, device, biologic, vaccine etc.) and/or 
Procedural Intervention  
6.1.1 Preparation 
 
The study drug will be provided by Janssen Scientific Affairs, LLC and prepared at the Investigational 
pharmacy located at: 
 
160 East 34th Street, Room 610 
New York, NY 10016 
 
And  
 
22. S. Greene St 
Rm N9E14 
Baltimore MD 21201 
 
 


Study number: S19-01401 
 
Page 18 
Version: 18 Dec 2022 
 
 
 
6.1.2 Administration of Intervention 
Study drug will be administered by qualified individuals at respective study sites.  
 
7 Study Procedures and Schedule 
7.1 Study Procedures/Evaluations 
 
Visit Schedule and Events: (All visits are standard of care except for week 8 randomization to IV or SQ 
ustekinumab.  The only medication requested from Janssen will be the week 8 IV ustekinumab dose).  
 
1. Screening (4 week window period) 
a. Informed consent will be obtained prior to any study procedures. 
b. Review of medical records – confirm diagnosis 
c. Inclusion and exclusion criteria to be reviewed. 
d. Routine labs and stool studies ordered including fecal calprotectin and CRP (about 1 
teaspoon of blood). Fecal calprotectin and CRP results collected prior to consent may be 
used if the results are within 4 weeks of the scheduled Week 0 visit.  
e. Patients to be given CDAI worksheets to record data that will be used to calculate CDAI 
score at Week 0. A 3 day CDAI recall may also be calculated at Week 0.  
 
* Please note: If unable to approach patient prior to Week 0 Visit, patient may be consented at 
Week 0 and a 3 day CDAI recall worksheet may be used.   
 
2. Week 0 (5 day window period): 
a. Urine pregnancy testing for women of childbearing potential 
b. Standard of care history and physical exam 
c. Calculate CDAI measurement using the 7 day CDAI worksheet given to patient at Screening 
Visit. Alternatively, can also use a 3 day CDAI recall worksheet for those consented at Week 
0.  
d. Inclusion and exclusion criteria to be reviewed. 
e. SIBDQ measurement 
f. 
Standard safety assessments* 
g. Standard labs – CRP (about 1 teaspoon of blood) 
h. Ustekinumab infusion 
i. 
Patients to be given CDAI worksheets to record data that will be used to calculate CDAI 
score at Week 6 
 
3. Week 6: (5 day window period) 
a. Standard of care history and physical exam 
b. Calculate CDAI measurement 
c. SIBDQ measurement 
d. Standard safety assessment* 
e. Standard labs – CRP(about 1 teaspoon of blood) 
f. 
Fecal calprotectin 
g. Patients to be given CDAI worksheets to record data that will be used to calculate CDAI 
score at Week 8 
 
4. Week 8: (within 5  day window period) 
a. Pregnancy testing for women of childbearing potential 
b. Standard safety assessment* 
c. Calculate CDAI measurement 
d. SIBDQ measurement 
e. Standard labs ( about 1 teaspoon of blood) 
f. 
Serum samples for PK (less than 1 teaspoon of blood)  


Study number: S19-01401 
 
Page 19 
Version: 18 Dec 2022 
 
 
 
g. “High risk” patients randomized to weight based IV ustekinumab versus SQ ustekinumab 
(randomization to be done by investigational pharmacy, study is not blinded). Patients 
randomized to receive the second weight based IV dose of ustekinumab, will have their vital 
signs obtained 30 minutes after the start of the second infusion, and twice after the end of 
infusion at 30 minute intervals. In addition, patients are to be monitored for adverse events 
during and for at least 1 hour after the end of the second IV infusion. 
 
5. Week 10: Follow-Up Call: A member of the research team will call patient to assess for any adverse 
events.  
 
6. Week 16: (within 5 day period):  
a. Pregnancy testing for women of childbearing potentialPrimary endpoint – CDAI 
measurement 
b. Standard history and physical exam 
c. Standard safety assessment* 
d. SIBDQ measurement 
e. Standard labs including CRP (about 1 teaspoon of blood) 
f. 
Serum samples for PK (less than 1 teaspoon of blood)  
g. Fecal calprotectin 
h. SQ ustekinumab administration 
 
7. Week 24: (Within 5 day period) – Long term follow up:  
a. Standard history and physical exam- Standard of Care 
b. CDAI measurement 
c. SIBDQ measurement 
d. Standard safety assessment*- Standard of Care 
e. Standard labs including CRP (about 1 teaspoon of blood)- Standard of Care 
 
8. Week 24 Colonoscopy Visit (within 8 weeks): Standard of Care 
a. SES-CD measurement 
 
* A Standard Safety Assessment will be conducting by an IRB approved member of the research 
team. This assessment is to collect information from the subject regarding any adverse events that 
may have occurred since last call/ visit.  
 
Blood samples are collected at six time points (Screening, Week 0, 6, 8, 16, and 24). Over the course of 
the study, about 6.5 teaspoons of blood are drawn from each subject.  
 
8 Assessment of Safety 
8.1 Specification of Safety Parameters  
8.1.1 Definition of Adverse Events (AE) 
Adverse Event (AE) 
An adverse event is any untoward medical occurrence in a clinical study subject administered a medicinal 
(investigational or non-investigational) product. An adverse event does not necessarily have a causal 
relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign 
(including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational or non- investigational) product, whether or not related to that medicinal (investigational or 
non-investigational) product. (Definition per International Conference on Harmonization [ICH]) 
This includes any occurrence that is new in onset or aggravated in severity or frequency from the 
baseline condition, or abnormal results of diagnostic procedures, including laboratory test abnormalities. 


Study number: S19-01401 
 
Page 20 
Version: 18 Dec 2022 
 
 
 
 
Adverse Events of Special Interest (AESI)  
Adverse events of special interest are events that the COMPANY is actively monitoring as a result of a 
previously identified signal (even if non-serious).  
 
In addition to the usual expedited reporting of all “serious” adverse events (per ICH criteria), the following 
AEs of special interest must also be reported to Janssen in an expedited fashion, i.e., per SAE reporting 
timelines, even when not serious (AE does not meet any of the ICH serious AE criteria): 
• 
All malignancies  
• 
All cases of active tuberculosis (TB)  
• 
Anaphylactic reactions  
• 
Serum sickness-like reactions 
 
Special consideration should be given to reporting adverse events that are opportunistic infections and 
clinically significant as serious adverse events based on the “otherwise medically significant” criteria for 
seriousness, when they do not meet other Serious AE ICH criteria (eg hospitalization). 
 
8.1.2 Definition of Serious Adverse Events (SAE) 
Serious Adverse Event (SAE) 
A serious adverse event based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for 
Human Use is any untoward medical occurrence that at any dose: 
 
• 
Results in death 
• 
Is life-threatening 
(The subject was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe.) 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
Results in persistent or significant disability/incapacity 
• 
Is a congenital anomaly/birth defect 
• 
Is a suspected transmission of any infectious agent via a medicinal product 
• 
Is medically important* 
 
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
also appropriate in other situations, such as important medical events that may not be 
immediately life threatening or result in death or hospitalization but may jeopardize the subject or 
may require intervention to prevent one of the other outcomes listed in the definition above. 
These should usually be considered serious. 
 
NOTE: DEATH FOR ANY REASON SHOULD BE REPORTED AS A SERIOUS ADVERSE EVENT. 
 
Hospitalization 
For reports of hospitalization, it is the sign, symptom or diagnosis which led to the hospitalization that is the serious 
event for which details must be provided. 
 
Any event requiring hospitalization or prolongation of hospitalization that occurs during the study must be reported 
as a serious adverse event, except hospitalizations for the following: 
• 
Hospitalizations not intended to treat an acute illness or adverse event (e.g., social reasons such 
as pending placement in long-term care facility) 
• 
Surgery or procedure planned before entry into the study. [Note: Hospitalizations that were 
planned before the start of data collection and where the underlying condition for which the 
hospitalization was planned has not worsened will not be considered serious adverse 
events. Any adverse event that results in a prolongation of the originally planned 
hospitalization is to be reported as a new serious adverse event.] 


Study number: S19-01401 
 
Page 21 
Version: 18 Dec 2022 
 
 
 
 
Life-Threatening Conditions 
The cause of death of a subject in a study within 30 days of the last dose of study drug, whether or not the 
event is expected or associated with the study drug, is considered a serious adverse event. 
 
Disease progression should not be recorded as an adverse event or serious adverse event term; instead, 
signs and symptoms of clinical sequelae resulting from disease progression/lack of efficacy will be reported 
if they fulfill the serious adverse event definition. 
 
8.1.3 Definition of Unanticipated Problems (UP) 
 
Unanticipated Problems Involving Risk to Subjects or Others 
Any incident, experience, or outcome that meets all of the following criteria:  
• Unexpected in nature, severity, or frequency (i.e. not described in study-related documents such 
as the IRB-approved protocol or consent form, the investigators brochure, etc.) 
• Related or possibly related to participation in the research (i.e. possibly related means there is a 
reasonable possibility that the incident experience, or outcome may have been caused by the 
procedures involved in the research) 
• Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
 
An adverse event is considered unlisted if the nature or severity is not consistent with the applicable 
product reference safety information. For a medicinal product(s) with a marketing authorization, the 
expectedness of an adverse event will be determined by whether or not it is listed in the applicable 
product information.  
 
For Stelara (ustekinumab), the link to the package insert is: 
 
                  http://www.stelarahcp.com/pdf/PrescribingInformation.pdf  
8.2 Classification of an Adverse Event 
8.2.1 Severity of Event 
 
The following guidelines will be used to describe severity of Adverse Event. 
 
• Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities. 
• Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or incapacitating. 
 
8.2.2 Relationship to Study Agent 
 
All AEs must have their relationship to study agent assessed. The following guidelines will be used: 
 
• Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test 


Study number: S19-01401 
 
Page 22 
Version: 18 Dec 2022 
 
 
 
result, occurs in a plausible time relationship to drug administration and cannot be explained by 
concurrent disease or other drugs or chemicals. The response to withdrawal of the drug 
(dechallenge) should be clinically plausible. The event must be pharmacologically or 
phenomenologically definitive, with use of a satisfactory rechallenge procedure if necessary. 
• Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within a 
reasonable time after administration of the drug, is unlikely to be attributed to concurrent disease 
or other drugs or chemicals, and follows a clinically reasonable response on withdrawal 
(dechallenge). Rechallenge information is not required to fulfill this definition. 
• Possibly Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the trial medication). However, other 
factors may have contributed to the event (e.g., the participant’s clinical condition, other 
concomitant events). Although an AE may rate only as “possibly related” soon after discovery, it 
can be flagged as requiring more information and later be upgraded to “probably related” or 
“definitely related,” as appropriate. 
• Unlikely to be related – A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to drug administration makes a causal relationship improbable (e.g., the 
event did not occur within a reasonable time after administration of the trial medication) and in 
which other drugs or chemicals or underlying disease provides plausible explanations (e.g., the 
participant’s clinical condition, other concomitant treatments). 
• Not Related – The AE is completely independent of study drug administration, and/or evidence 
exists that the event is definitely related to another etiology. There must be an alternative, 
definitive etiology documented by the clinician. 
 
8.2.3 Expectedness 
 
At NYU Langone, Dr. Hudesman will be responsible for determining whether an AE is expected or 
unexpected. Dr. Cross will determine whether an AE is expected or unexpected at the University of 
Maryland site. An AE will be considered unexpected if the nature, severity, or frequency of the event is 
not consistent with the risk information previously described for the study agent. 
 
8.3 Time Period and Frequency for Event Assessment and Follow-Up 
 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits and 
interviews of a study participant presenting for medical care, or upon review by a study monitor. All AEs 
including local and systemic reactions not meeting the criteria for SAEs will be captured on the 
appropriate RF. Information to be collected includes event description, time of onset, clinician’s 
assessment of severity, relationship to study product (assessed only by those with the training and 
authority to make a diagnosis), and time of resolution/stabilization of the event. All AEs occurring while on 
study must be documented appropriately regardless of relationship. All AEs will be followed to adequate 
resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any time 
during the study, it will be recorded as an AE. UPs will be recorded in the data collection system 
throughout the study. 
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. AEs characterized as intermittent require documentation of 
onset and duration of each episode. 
 
The PI will record all reportable events with start dates occurring any time after informed consent is 
obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation. At 


Study number: S19-01401 
 
Page 23 
Version: 18 Dec 2022 
 
 
 
each study visit, the investigator will inquire about the occurrence of AE/SAEs since the last visit. Events 
will be followed for outcome information until resolution or stabilization.  
 
 
8.4 Reporting Procedures – Notifying the IRB  
 
Data Safety Monitoring Plan 
 
The principal investigator (David Hudesman) will be responsible for systematic oversight of the study and 
will convene a data safety monitoring board (DSMB) comprised of Dr. Hudesman and the following 
investigators from NYULH and University of Maryland: 
1.Raymond K. Cross, D, MS, AGAF, FACG is a professor of medicine, Division of Gastroenterology and 
Hepatology at the University of Maryland, Baltimore. He is also director of the Inflammatory Bowel Disease 
Program at the University of Maryland School of Medicine and is co-director of the Digestive Health Center 
at the University of Maryland Medical Center.  
2. Shannon Chang, MD, MBA is Associate Professor at the Department of Medicine, Division of 
Gastroenterology at NYU Grossman School of Medicine. Dr. Chang specializes in Inflammatory Bowel 
Diseases and serves as the Clinical Director of the IBD Center, NYU Langone.  
 
3. Jordan Axelrad, MD, MPH is and Assistant Professor at the Department of Medicine, Division of 
Gastroenterology at NYU Grossman School of Medicine. Dr. Axelrad specializes in Inflammatory Bowel 
Diseases at the IBD Center, NYU Langone.  
 
 
The DSMB will conduct a quarterly review of accumulated data and safety information which includes 
adverse events and study deviations, to ensure proper conduct of protocol, compliance, data accuracy and 
integrity, and subject safety. Dr. Hudesman is the Medical Director for Inflammatory Bowel Disease Center 
at NYU Langone Health. He also has several years of experience conducting many clinical trials at his 
practice.  
 
Adverse events will be reported by the patient throughout the study and recorded by the investigator. 
The investigator and coordinator will review and train the University of Maryland investigators and 
coordinators on the protocol and follow up on a monthly basis. All safety data finding will be disseminated 
to the University of Maryland through secure email. An annual progress report will summarize the findings 
of these safety reviews and tabulate all AEs. This will be submitted to the IRB as part of the 
Annual/Continuing Review submission. 
 
The PI will follow all rules and regulations listed in Janssen’s Interventional IIS COMPANY Requirements 
for Safety Data Collection and Reporting. 
 
8.4.1 Adverse Event Reporting 
 
Non-Serious AEs 
 
All adverse events that do not fit the criteria of Reportable New Information will be considered a non-serious 
adverse event. A list of adverse events will be maintained in each subject’s binder and will be reported to 
the IRB with the annual continuing review. 
 
All non-serious adverse events should be reported to COMPANY according to the timeframe outlined in the 
Research Funding Agreement section entitled Reporting of Data. 


Study number: S19-01401 
 
Page 24 
Version: 18 Dec 2022 
 
 
 
8.4.2 Serious Adverse Event Reporting 
SAE’s at NYU Langone Medical Center that meet the institution criteria for Reportable New Information 
will be reported to the IRB and Janssen Scientific Affairs, LLC within 24 hours of the PI or Sub-I becoming 
aware of the event. 
 
Any SAEs at the University of Maryland will be reported to NYU within 24 hours and NYU will then report 
that SAE to the NYU IRB and Janssen Scientific Affairs, LLC immediately.  If needed the investigator and 
coordinator will travel to the University of Maryland.  
8.5 Reporting Procedures – Notifying the Study Sponsor 
Overview  
 
As the sponsor of the Study, INSTITUTION and PRINCIPAL INVESTIGATOR shall be solely responsible 
for complying, within the required timelines, any safety reporting obligation to competent Health Authorities, 
IRB/ECs and any participating (co or sub) investigators, as defined in applicable laws and regulations.  For 
the purposes of this EXHIBIT, safety data includes adverse events, product quality complaints (PQCs), and 
special situations including pregnancies. 
 
The INSTITUTION and PRINCIPAL INVESTIGATOR will provide safety information to the COMPANY on 
adverse events, special situations including pregnancies and product quality complaints as defined within 
this EXHIBIT. 
 
The INSTITUTION and the PRINCIPAL INVESTIGATOR) will transmit all SAEs, Adverse Events of 
Special Interest and special situations following exposure to a Janssen product under study in a form 
provided by the COMPANY in accordance with transmission methods listed in this exhibit, in English 
within 24-hours of becoming aware of the event(s). 
 
In the event the study is blinded, the PRINCIPAL INVESTIGATOR will submit an unblinded SAE or 
pregnancy exposure report to COMPANY. 
 
All follow-up information for serious adverse events that are not resolved at the end of the study or by the 
time of patient withdrawal must be reported directly by the PRINCIPAL INVESTIGATOR, within 24 hours 
becoming aware, to the COMPANY using the COMPANY’s Serious Adverse Event Report  
 
All available clinical information relevant to the evaluation of a related SAE, Adverse Events of Special 
Interest serious ADR or special situation is required. 
 
The INSTITUTION and/or PRINCIPAL INVESTIGATOR is responsible for ensuring that these cases are 
complete and if not are promptly followed-up. A safety report is not considered complete until all clinical 
details needed to interpret the case are received. Reporting of follow-up information should follow the 
same timeline as initial reports. 
 
Copies of any and all relevant extraordinary (not including routine initial or follow-up ICSR submission) 
correspondences with regulatory authorities and ethics committees regarding any and all serious adverse 
events, irrespective of association with the Janssen Product under study, are to be provided to the 
COMPANY using a transmission method listed in this exhibit within 24 hours of such report or 
correspondence being sent to applicable health authorities. 
 
 
Management of Safety Data: 
 
This Study has been designated as an interventional study.  As such, all adverse events for Janssen 
Medicinal Products regardless of causality and special situations excluding those from subjects not exposed 
to a Janssen Medicinal Product and product quality complaints with or without an adverse event as 
described in this Exhibit will be reported from the time a subject has signed and dated an Informed Consent 


Study number: S19-01401 
 
Page 25 
Version: 18 Dec 2022 
 
 
 
Form (ICF) until completion of the subject’s last study-related procedure (which may include contact for 
follow-up safety).  Serious adverse events will be reported for 30 after the last dose of study drug. 
 
For the purposes of this study, the Janssen medicinal product is: 
                        Stelara (ustekinumab) 
 
 
Procedures for Reporting Safety Data and Product Quality Complaints (PQCs) for Janssen Medicinal 
Products to the COMPANY 
All adverse events and special situations, whether serious or non-serious, related or not related, following 
exposure to a Janssen medicinal product are to be documented by the investigator and recorded in the 
CRF and in the subject’s source records. Investigators must record in the CRF their opinion concerning the 
relationship of the adverse event to a Janssen medicinal product.  
All (serious and non-serious) adverse events reported for a Janssen medicinal product should be 
followed-up in accordance with clinical practice. 
 
SAEs, Adverse Events of Special Interest and Special Reporting Situations 
All serious adverse events that have not resolved by the end of the study, or that have not resolved upon 
discontinuation of the subject's participation in the study, must be followed until any of the following occurs: 
• 
The event resolves 
• 
The event stabilizes 
• 
The event returns to baseline, if a baseline value/status is available 
• 
The event can be attributed to agents other than the study drug or to factors unrelated to study 
conduct 
• 
It becomes unlikely that any additional information can be obtained (subject or health care 
practitioner refusal to provide additional information, lost to follow-up after demonstration of due 
diligence with follow-up efforts) 
 
The INSTITUTION and the PRINCIPAL INVESTIGATOR) will transmit all SAEs, Adverse Events of Special 
Interest and special situations following exposure to a Janssen product under study in a form provided by 
the COMPANY in accordance with transmission methods listed in this exhibit, in English within 24-hours 
of becoming aware of the event(s). 
 
In the event the study is blinded, the PRINCIPAL INVESTIGATOR will submit an unblinded SAE or 
pregnancy exposure report to COMPANY. 
 
All follow-up information for serious adverse events that are not resolved at the end of the study or by the 
time of patient withdrawal must be reported directly by the PRINCIPAL INVESTIGATOR, within 24 hours 
becoming aware, to the COMPANY using the COMPANY’s Serious Adverse Event Report  
 
All available clinical information relevant to the evaluation of a related SAE, Adverse Events of Special 
Interest serious ADR or special situation is required. 
 
• 
The INSTITUTION and/or PRINCIPAL INVESTIGATOR is responsible for ensuring that these 
cases are complete and if not are promptly followed-up. A safety report is not considered 
complete until all clinical details needed to interpret the case are received. Reporting of follow-
up information should follow the same timeline as initial reports. 
 
• 
Copies of any and all relevant extraordinary (not including routine initial or follow-up ICSR 
submission) correspondences with regulatory authorities and ethics committees regarding any 
and all serious adverse events, irrespective of association with the Janssen Product under 
study, are to be provided to the COMPANY using a transmission method listed in this exhibit 
within 24 hours of such report or correspondence being sent to applicable health 
authorities. 


Study number: S19-01401 
 
Page 26 
Version: 18 Dec 2022 
 
 
 
 
Non-Serious AEs 
All non-serious adverse events should be reported to COMPANY according to the timeframe outlined in the 
Research Funding Agreement section entitled Reporting of Data. 
 
Pregnancy 
 
All initial reports of pregnancy must be reported to the COMPANY by the PRINCIPAL INVESTIGATOR 
within 24 hours of becoming aware of the event using the Serious Adverse Event Form. Abnormal 
pregnancy outcomes (e.g. spontaneous abortion, fetal death, stillbirth, congenital anomaly, ectopic 
pregnancy) are considered serious adverse events and must be reported using the Serious Adverse Event 
Form.  
 
Any subject who becomes pregnant during the study must discontinue further study treatment. 
 
Because the effect of the Janssen medicinal product on sperm is unknown, pregnancies in partners of male 
subjects exposed to a Janssen medicinal product will be reported by the PRINCIPAL INVESTIGATOR 
within 24 hours of their knowledge of the event using the Serious Adverse Event Form.  Depending on local 
legislation this may require prior consent of the partner. 
 
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the infant will 
be required. 
 
Product Quality Complaint (PQC) 
A product quality compliant is defined as any suspicion of a product defect related to a potential quality 
issue during manufacturing, packaging, release testing, stability monitoring, dose preparation, storage or 
distribution of the product, or delivery system.  Not all PQCs involve a subject.  Lot and batch numbers are 
of high significance and need to be collected whenever available. 
 
Examples of PQC include but not limited to: 
• 
Functional Problem: e.g., altered delivery rate in a controlled release product 
• 
Physical Defect:  e.g. abnormal odor, broken or crushed tablets/capsules 
• 
Potential Dosing Device Malfunction: e.g., autoinjector button not working, needle 
detaching from syringe 
• 
Suspected Contamination 
• 
Suspected Counterfeit 
 
PQC Reporting 
 
A PQC may have an impact on the safety and efficacy of the product. Timely, accurate, and complete 
reporting and analysis of PQC information from studies are crucial for the protection of patients, 
investigators, and the COMPANY, and are mandated by regulatory agencies worldwide. The COMPANY 
has established procedures in conformity with regulatory requirements worldwide to ensure appropriate 
reporting of PQC information. Lot and/or Batch #s shall be collected or any reports failure of expected 
pharmacological action (i.e., lack of effect). The product should be quarantined immediately and if possible, 
take a picture. 
 
All initial PQCs involving a Janssen medicinal product under study must be reported to the COMPANY by 
the PRINCIPAL INVESTIGATOR within 24 hours after being made aware of the event. The Janssen 
contact will provide additional information/form to be completed. 
 
If the defect for a Janssen medicinal product under study is combined with either a serious adverse event 
or non-serious adverse event, the PRINCIPAL INVESTIGATOR must report the PQC to the COMPANY 


Study number: S19-01401 
 
Page 27 
Version: 18 Dec 2022 
 
 
 
according to the serious adverse event reporting timelines.  A sample of the suspected product should be 
maintained for further investigation if requested by the COMPANY. 
 
 
Special Reporting Situations:  
 
Safety events of interest for a Janssen medicinal product that require expediting reporting and/or 
safety evaluation include, but are not limited to: 
• 
Drug exposure during pregnancy (maternal and paternal) 
• 
Overdose of a Janssen medicinal product  
• 
Exposure to a Janssen medicinal product from breastfeeding  
• 
Suspected abuse/misuse of a Janssen medicinal product 
• 
Inadvertent or accidental exposure to a Janssen medicinal product  
• 
Any failure of expected pharmacological action (i.e., lack of effect) of a Janssen medicinal 
product 
• 
Medication error involving a Janssen medicinal product (with or without patient exposure to 
the Janssen medicinal product, e.g., name confusion) 
• 
Suspected transmission of any infectious agent via administration of a medicinal product 
• 
Unexpected therapeutic or clinical benefit from use of a Janssen medicinal product 
 
These safety events may not meet the definition of an adverse event; however, from a COMPANY 
perspective, they are treated in the same manner as adverse events. Special situations should be 
recorded on the Adverse Event page of the CRF. 
 
Any special situation that meets the criteria of a serious adverse event should be recorded on a Serious 
Adverse Event Report Form and be reported to the COMPANY within 24 hours of becoming aware 
of the event. 
 
Maintenance of Safety Information 
 
All safety data should be maintained in a clinical database in a retrievable format. The INSTITUTION and 
PRINCIPAL INVESTIGATOR shall provide all adverse events, both serious and non-serious, in report 
format. However, in certain circumstances more frequent provision of safety data may be necessary, e.g. 
to fulfill a regulatory request, and as such the data shall be made available within a reasonable timeframe 
at the COMPANY’s request. 
 
Individual Case Safety Report (ICSR) 
 
A valid ICSR must contain the four minimum criteria required to meet regulatory reporting requirements. 
• 
an identifiable subject (but not disclosing personal information such as the subject’s name, initials or 
address) 
• 
an identifiable reporter (investigational site) 
• 
a Janssen medicinal product 
• 
an adverse event, outcome, or certain special situations 
 
The minimum information required is: 
• 
suspected Janssen medicinal product (doses, indication) 
• 
date of therapy (start and end date, if available) 
• 
batch or lot number, if available 
• 
subject details (subject ID and country) 
• 
gender 
• 
age at AE onset 
• 
reporter ID 


Study number: S19-01401 
 
Page 28 
Version: 18 Dec 2022 
 
 
 
• 
adverse event detail (AE verbatim in English), onset date, relatedness, causality, action taken, 
outcome, (if available) 
• 
Janssen protocol ID 
 
Transmission Methods 
The following methods are acceptable for transmission of safety information to the COMPANY: 
• 
Electronically via Janssen SECURE Email service (preferred) IIS-BIO-VIRO-GCO@its.jnj.com 
• 
For business continuity purposes, if SECURE Email is non-functional: 
Facsimile (fax), receipt of which is evidenced in a successful fax transmission report to 1-866-451-0371 
• 
Telephone (if fax is non-functional). 
 
The contact information and process information provided by the COMPANY will be used.  
 
Contacting COMPANY Regarding Safety 
The names (and corresponding contact information) of the individuals who should be contacted regarding 
safety issues will be provided separately by the COMPANY. 
 
SAEs Listing 
At a minimum, on a quarterly basis and at the end of the Study, COMPANY will provide to the INSTITUTION 
and/or PRINCIPAL INVESTIGATOR, a listing of all SAEs reported to the COMPANY.  SPONSOR and/or 
PRINCIPAL INVESTIGATOR will review this listing and will resolve any discrepancies with the data 
provided by the COMPANY 
 
Dissemination of Safety Information from COMPANY to INSTITUTION/PRINCIPAL INVESTIGATORS 
PRINCIPAL INVESTIGATOR will be responsible for submitting Serious Unexpected Serious Adverse 
Reaction (SUSAR) reports for the Study Product to INSTITUTION’s IRB in accordance with Federal 
regulations 21 CFR 312.66.  The PRINCIPAL INVESTIGATOR will provide a copy of each SUSAR report 
to sub-investigators where the study design is either a multi-center or cooperative study. 
 
COMPANY agrees to provide to the PRINCIPAL INVESTIGATOR SUSAR reports for the Janssen 
Medicinal Product as they become available until all subjects in the Protocol have completed their last Study 
visit according to the Protocol (i.e. Last Subject Last Visit has occurred).  
 
Suspected Unexpected Serious Adverse Reaction (SUSAR) – An adverse drug reaction (ADR) that is both 
serious and unexpected (per the reference safety information [RSI]) that based on the opinion of the 
investigator or sponsor, is felt to have a reasonable suspected causal relationship to a medicinal product.  
 
Final Study Report 
The INSTITUTION/PRINCIPAL INVESTIGATOR will prepare a final report including a complete and full 
summary of all adverse events, special situations and pregnancy reports according to the timeframe 
outlined in the agreement. 
 
 
8.6 Reporting Procedures – Notifying the FDA  
 
The following describes the IND safety reporting requirements by timeline for reporting and associated 
type of event: 
 
• 
Reporting any unexpected fatal or life-threatening suspected adverse reactions to this 
Division of Gastroenterology, Office of Immunology and Inflammation at the Center for Drug 
Evaluation and Research no later than 7 calendar days after initial receipt of the information. 
 
• 
All 7-day reports will be submitted electronically in eCTD format via the FDA Electronic 
Submissions Gateway (ESG).  


Study number: S19-01401 
 
Page 29 
Version: 18 Dec 2022 
 
 
 
 
• 
Reporting any (1) serious, unexpected suspected adverse reactions, (2) findings from other 
clinical, animal, or in-vitro studies that suggest significant human risk, and (3) a clinically 
important increase in the rate of a serious suspected adverse reaction to this Division 
Gastroenterology, Office of Immunology and Inflammation at the Center for Drug Evaluation 
and Research and to all investigators no later than 15 calendar days after determining that 
the information qualifies for reporting. Given the IND is in eCTD format, submissions of 15-
day reports to FDA will be made electronically in eCTD format via the ESG.  
 
• 
Submitting annual progress reports within 60 days of the anniversary of the date that the IND 
became active (the date clinical studies were permitted to begin). 
 
 
SUBMISSION REQUIREMENTS 
 
The IND number will be listed above at the top of the first page of any communications concerning this 
application. 
 
Electronic submissions: 
 
Future amendments, that are in eCTD format, will be submitted electronically via the FDA CDER NextGen 
Portal.  
 
Paper submissions: 
 
If submitting in paper, each submission to this IND will be provided in triplicate (original plus two copies). 
Include three originals of all illustrations that do not reproduce well. FDA will also accept submissions on 
certain physical media (e.g. CDs, DVDs (up to 6 pieces), external hard drives); a printed copy of the cover 
letter will be included with submissions on electronic media. All submissions, electronic or paper, 
including those sent by overnight mail or courier, will be sent to the following address: 
 
Food and Drug Administration 
Center for Drug Evaluation and Research 
Central Document Room 
5901-B Ammendale Road 
Beltsville, MD 20705-1266 
 
All regulatory documents submitted in paper will be three-hole punched on the left side of the page and 
bound. The left margin will be at least three-fourths of an inch to assure text is not obscured in the 
fastened area. Standard paper size (8-1/2 by 11 inches) will be used; however, it may occasionally be 
necessary to use individual pages larger than standard paper size. Non-standard, large pages will be 
folded and mounted to allow the page to be opened for review without disassembling the jacket and 
refolded without damage when the volume is shelved.  
 
Future amendments to the IND will be sent electronically through the FDA Electronic Submissions 
Gateway (ESG) which is the central transmission point for sending information electronically to the FDA 
and enables the secure submission of regulatory information for review.  
 
 
 
 
9 Statistical Considerations 
We expect a 20% clinical remission rate in the subcutaneous group and a 50% clinical remission rate in 
the IV group.  Based on supplementary appendix from the UNITI trials and post hoc analysis, we expect 


Study number: S19-01401 
 
Page 30 
Version: 18 Dec 2022 
 
 
 
that 75 percent of the patients starting ustekinumab therapy will get randomized (CDAI will not drop by 
100 points or CRP will not drop below 5mg/l or calprotectin will not drop by 50% at week 6). This yields an 
estimated enrollment ratio of 0.6 (IV group to subcutaneous group). Under these assumptions a sample 
size of 80 total participants is needed to achieve a power of 1- β=0.80 for a two-sided statistical level of 
α=0.05. Given an estimated 10% drop out rate, we plan to enroll 88 patients into the study.  
 
Descriptive statistics (eg, mean, median, standard deviation) will be used to summarize continuous 
variables. Frequencies and percentages will be used to summarize categorical variables. The primary 
efficacy endpoint, clinical remission at week 16, and other binary secondary outcomes will be analyzed 
using a two-sided, Cochran-Mantel-Haenszel chi-squared test. The Fisher exact test will be used for 
treatment comparisons in rare events. Secondary continuous response parameters will be compared 
using an analysis of variance (ANOVA) or covariance (ANCOVA). All statistical testing will be performed 
at the α=0.05 (2-sided) level.  Nominal p-values will be displayed for all treatment comparisons. 
 
9.1 Statistical Hypotheses 
A second IV dose of ustekinumab at week 8 is superior to standard 90mg sq dosing at week 8 to induce 
clinical remission at week 16 in “high risk” moderate to severe Crohn’s disease patients. 
 
10 Ethics/Protection of Human Subjects 
10.1 Ethical Standard 
 
The investigator will ensure that this study is conducted in full conformity with Regulations for the 
Protection of Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 
and/or the ICH E6. 
10.2 Institutional Review Board 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form must be 
obtained before any participant is enrolled. Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study. All changes to the consent form 
will be IRB approved; a determination will be made regarding whether previously consented participants 
need to be re-consented. 
10.3 Informed Consent Process 
Consent and Other Informational Documents Provided to Participants. This study will first be introduced 
to eligible subjects by the PI or Sub-I. PI/Sub-I and an available coordinator will review the consent form 
with the patient. Patients will be given ample time to review the consent form, and the coordinator or 
investigator will be available to answer any questions the patient may have. Consenting may occur in 
office during the patient’s regularly scheduled clinic visit, with additional time given to patients if required. 
An IRB approved personnel will sign consent with the subject. The consent process will be documented 
and signed by the PI/Sub-I, and the documentation will be kept in the patient’s study binder. 
 
A copy of the signed informed consent document will be stored in the subject’s research record. The 
consent process, including the name of the individual obtaining consent, will be thoroughly documented in 
the subject’s research record. Any alteration to the standard consent process (e.g. use of a translator, 
consent document presented orally, etc.) and the justification for such alteration will likewise be 
documented.  
 


Study number: S19-01401 
 
Page 31 
Version: 18 Dec 2022 
 
 
 
11 Data Handling and Record Keeping 
11.1 Data Collection and Management Responsibilities 
NYU Langone Medical Center will serve as the Data Coordinating Site for this trial. Pertinent data 
collected at the University of Maryland will be de-identified and sent to NYU Langone Medical Center for 
analyses via TrialMaster.  
 
Careful data monitoring and quality control will be maintained with all possible precautions taken to 
protect the confidentiality of study subjects. All study staff delegated to enter data into the selected 
electronic database will have their own login information and passwords. All information with patient 
identifiers will be coded using study IDs. Data will be collected and stored in an encrypted database such 
as TrialMaster. Patient information with identifiers will be under lock-and-key with access only to the PI 
and study co-coordinator at each respective site. No participant will be identified from published reports 
and correspondence between investigators will not include patient names. All information will be reviewed 
in a private location and only by study staff delegated to review records. 
 
 
12 Study Finances 
12.1 Funding Source 
Janssen Scientific Affairs, LLC will provide Stelara for patients randomized to the second IV arm at no 
additional cost to patients.  
12.2 Costs to the Participant 
 Participants will not be reimbursed for taking part in this study.  
13 Study Administration 
Dr. Hudesman is the Principal Investigator of this study. NYU Langone Medical Center will serve as the 
Primary and the Data Coordinating Site for this study. All interim data findings and study related 
modifications will be relayed to other site(s) via email detailing the changes that need to be made. These 
changes will need to be approved by each site(s) respective IRB(s).  
 
Dr. Cross will be the lead Investigator at the University of Maryland. The University of Maryland IRB will 
provide approval of study before any study related procedures take place.  
 


Study number: S19-01401 
 
Page 32 
Version: 18 Dec 2022 
 
 
 
14 References 
1.  Strober, W. et al. Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. 
Gastroenterology. 2010;140(6):1756-67.  
 
2.  Kaser, A. et al. Inflammatory bowel disease. Annu Rev Immunol.28:573-621. 
 
3.  Mayer, L. Evolving paradigms in the pathogenesis of IBD. J Gastroenterol.45(1):9-16.  
 
4.  Rutgeerts, P. et al. Infliximab for induction and maintenance therapy in ulcerative colitis. N Engl J Med. 
2005 Dec 8;353(23):2462-76. 
 
5.  Sandborn, WJ. et al. Adalimumab induces and maintains clinical remission in moderate-severe 
ulcerative colitis. Gastroenterology. 2012 Feb;142(2):257-65. 
 
6.  Sandborn, WJ. et al. Subcutaneous golimumab induces clinical response and remission in moderate-
severe ulcerative colitis. Gastroenterology. 2014 Jan;146(1):85-95. 
 
7.  Feagan, BG. et al. Vedolizumab as induction and maintenance therapy in ulcerative colitis. N Engl J 
Med. 2013 Aug 22;369(8):699-710. 
 
8.  Sandborn, WJ. et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J 
Med. 2017 May 4;376(18):1723-1736. 
 
9.  Maloy KJ, Powrie F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. 
Nature.474(7351):298-306. 
 
10. Littman DR, Rudensky AY. Th17 and regulatory T cells in mediating and restraining inflammation. 
Cell.140(6):845-58.  
 
11. Trifari S, Spits H. IL-22-producing CD4+ T cells: middle-men between the immune system and its 
environment. European journal of immunology. 2010;40(9):2369-71.  
 
12. Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in 
inflammation. Immunity. 2008;28(4):454-67. 
 
13. Sonnenberg GF, Fouser LA, Artis D. Border patrol: regulation of immunity, inflammation and tissue 
homeostasis at barrier surfaces by IL-22. Nature immunology.12(5):383-90.  
 
14. Leung JM, Davenport M, Wolff MJ, Wiens KE, Abidi WM, Poles MA, et al. IL-22-producing CD4+ cells 
are depleted in actively inflamed colitis tissue. Mucosal Immunol. 2013.  
 
15. Davenport M, Poles J, Leung JM, Wolff MJ, Abidi WM, Ullman T, et al. Metabolic Alterations to the 
Mucosal Microbiota in Inflammatory Bowel Disease. Inflamm Bowel Dis. 2014.  
 
16. Tang MS, Poles J, Leung JM, Wolff MJ, Davenport M, Lee SC, et al. Inferred metagenomic 
comparison of mucosal and fecal microbiota from individuals undergoing routine screening colonoscopy 
reveals similar differences observed during active inflammation. Gut Microbes. 2015;6(1):48-56. 
 
17.  Bowcutt R, Malter LB, Chen LA, Wolff MJ, Robertson I, Rifkin DB, et al. Isolation and cytokine 
analysis of lamina propria lymphocytes from mucosal biopsies of the human colon. Journal of 
immunological methods. 2015.  
 
18. Loke P, Favre D, Hunt PW, Leung JM, Kanwar B, Martin JN, et al. Correlating cellular and molecular 
signatures of mucosal immunity that distinguish HIV controllers from noncontrollers. Blood. 
2010;115(15):e20- 32.  


Study number: S19-01401 
 
Page 33 
Version: 18 Dec 2022 
 
 
 
19. Lehmann FS, Burri E, Beglinger C. The role and utility of faecal markers in inflammatory bowel 
disease. Therap Adv Gastroenterol. 2015;8(1):23-36. doi:10.1177/1756283X14553384  
 
20. Assessment of disease activity in ulcerative colitis by faecal calprotectin, a novel granulocyte marker 
protein. Røseth AG, Aadland E, Jahnsen J, Raknerud N 
Digestion. 1997; 58(2):176-80. 
 
21. Normalization of faecal calprotectin: a predictor of mucosal healing in patients with inflammatory 
bowel disease. Røseth AG, Aadland E, Grzyb K 
Scand J Gastroenterol. 2004 Oct; 39(10):1017-20. 
  
 


Study #: s19- 01401 
Version date: 17OCT2022  
Page 34 of 34