Clinical trial NCT04549792
Conditions: Ichthyosis
Sponsor: Northwestern University
Start date: 2021-04-01; Completion date: 2024-06-26
Enrollment: 13 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The ichthyoses are a group of lifelong genetic disorders that share characteristics of generalized skin thickening, scaling and underlying cutaneous inflammation. The vast majority are orphan disorders and are associated with extremely poor quality of life related to social ostracism from altered appearance, associated itchiness and discomfort, and functional limitations from the skin disease. Among the more common "orphan" forms of ichthyosis are autosomal recessive congenital ichthyosis (ARCI; includes lamellar ichthyosis/LI and congenital ichthyosiform erythroderma/CIE), Netherton syndrome (NS) and epidermolytic ichthyosis (EI). However, there are dozens of other syndromic and non-syndromic ichthyotic disorders as well. Therapy is time-consuming for patients or parents and is supportive, focusing on clearance of the scaling. There are no therapies based on our growing understanding of what causes the disease. We have recently found marked elevations in Th17/IL-23 pathway cytokines and chemokines in the skin of individuals with ichthyosis, most similar to the inflammatory pattern of psoriasis. While the significance of the high expression of Th17/IL-23 pathway genes across all forms of ichthyosis studied to date is unknown, the high expression of genes of the Th17/IL-23 pathway in psoriasis is thought to be causative for the disease manifestations. We propose that IL-12/IL-23 -targeting therapeutics will safely suppress the inflammation and possibly the other features of ichthyosis, improving quality of life. As a proof-of-concept study, we propose to treat children (6 years of age and higher) and adults with ichthyotic disorders with ustekinumab in an open-label trial to serially assess clinical response to and safety of ustekinumab for this group of disorders.

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: Ustekinumab
Intervention descriptions: intervention 1: Each subject will receive ustekinumab at Baseline (Day 0) and Months 1, 3, 5, 7, 9, and 11. During the LTE, subjects will receive injections every 8 weeks for one year: Month 13, Month 15, Month 17, Month 19, Month 21, and Month 23. Subjects will come back in for a follow-up visit at Month 25 for an end of study visit (no drug administration).

Protocol documents:
Prot_SAP_000.pdf: 
Page 1 of 60 
 
 
    
STUDY TITLE: An Open-Label and Long-Term Extension Study to Evaluate the Efficacy 
and Safety of Ustekinumab in the Treatment of Patients with Ichthyoses.  
  
 
  
Principal Investigator/Sponsor:    
 
Amy S. Paller, M.D. 
Department of Dermatology 
Northwestern University 
676 N. St. Clair Street, Suite 1600 
 
Chicago, IL 60611 
Telephone: (312) 695-3721  
Fax: (312) 503-5900 
Email: apaller@northwestern.edu 
  
 
Date: 8 November 2022 
Version 2.0 
 
Drug and funding support provided by: Janssen Scientific Affairs, LLC  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Page 2 of 60 
 
Table of Contents 
STUDY GLOSSARY .................................................................................................................................................................... 6 
PROTOCOL SYNOPSIS ............................................................................................................................................................. 7 
Secondary objectives: ............................................................................................................................................................. 7 
1. BACKGROUND AND RATIONALE ............................................................................................................................... 13 
1.1 Disease ........................................................................................................................................................................... 13 
1.2 Clinical Hypotheses .................................................................................................................................................. 13 
1.3 Rationale for Ustekinumab Use ........................................................................................................................... 13 
1.4 Risks of Ustekinumab .............................................................................................................................................. 14 
2. STUDY ENDPOINTS .......................................................................................................................................................... 14 
2.1 Primary Endpoints .................................................................................................................................................... 14 
2.2 Secondary Objectives: ................................................................................................................................................. 15 
3. INVESTIGATIONAL PLAN .............................................................................................................................................. 15 
3.1 Study Centers .............................................................................................................................................................. 15 
3.2 Study Organization ................................................................................................................................................... 15 
3.3 Study Duration ........................................................................................................................................................... 16 
3.4 Biomarker Analyses ................................................................................................................................................. 16 
4. SUBJECT ELIGIBILITY ..................................................................................................................................................... 16 
4.1 Inclusion Criteria ............................................................................................................................................................ 16 
4.2 Exclusion criteria ........................................................................................................................................................... 17 
5. TREATMENT PROCEDURES ......................................................................................................................................... 18 
5.1 Investigational Treatment ..................................................................................................................................... 18 
5.2 Dispense and Use of Investigational Treatment ................................................................................................ 18 
5.2.1 Dispensing the Investigational Treatment .................................................................................................. 18 
5.2.2 Instructions for prescribing and taking study treatment ..................................................................... 19 
5.2.3 Prohibited treatment ........................................................................................................................................... 19 
5.3 Subject Withdrawal/Discontinuation ............................................................................................................... 20 
5.4 Study Completion and Post-study Treatment ............................................................................................... 20 
6. VISIT SCHEDULE AND ASSESSMENTS ..................................................................................................................... 21 
6.1 Screening/Baseline Visit ........................................................................................................................................ 21 
6.1.1 Consent ...................................................................................................................................................................... 21 
6.1.2 Medical and Medication History ...................................................................................................................... 21 
6.1.3 Vital Signs and Height/Weight ......................................................................................................................... 21 


Page 3 of 60 
 
6.1.4 Complete Physical Examination & Skin Examination ............................................................................. 22 
6.1.5 Safety Labs and Pregnancy Testing ................................................................................................................ 22 
6.1.6 Severity Evaluations - ISS and Ichthyosis Severity Self-Assessment ............................................... 22 
6.1.7 TEWL and Tape Strips ......................................................................................................................................... 22 
6.1.8 Microbiome Sampling .......................................................................................................................................... 23 
6.1.9  Photography .............................................................................................. Error! Bookmark not defined. 
6.1.10  Blood Samples for Biomarkers  .................................................................................................................... 23 
6.1.11  DLQI / CDLQI, IQoL-32, and IFTB ............................................................................................................... 23 
6.1.12  STIGMA Questionnaire .................................................................................................................................... 24 
6.1.13  Itch and Pain NRS/PROMIS Itch .................................................................................................................. 24 
6.2 Open Label and Long Term Extension Rollover ........................................................................................... 24 
6.2.1 Adverse Event Assessment ................................................................................................................................ 24 
6.3 Unscheduled Visits .................................................................................................................................................... 24 
6.4 Sample Collection, Preparation, Labeling and Shipment .......................................................................... 25 
6.4.1 Sample collection ................................................................................................................................................... 25 
6.4.2 Labeling and de-identifying specimens ........................................................................................................ 25 
6.4.3 Transporting specimens ..................................................................................................................................... 25 
6.4.4 Specimen management ....................................................................................................................................... 25 
7. 
SAFETY DATA COLLECTION, RECORDING AND REPORTING ................................................................... 25 
7.1 
Adverse Events .................................................................................................................................................... 25 
7.2     Follow-up of Subjects with Adverse Events ............................................................................................... 26 
7.3 
Serious Adverse Events ........................................................................................................................................ 26 
7.3.1. 
Definition of SAE ............................................................................................................................................ 26 
7.3.2. 
SAE, Adverse Events of Special Interest, and Special Reporting Situations .......................... 27 
7.4. 
Adverse Events of Special Interest .............................................................................................................. 28 
7.5. 
Pregnancy Reporting ........................................................................................................................................ 28 
7.6. 
Special Reporting Situations .......................................................................................................................... 28 
8. 
DATA REVIEW AND DATABASE MANAGEMENT ........................................................................................... 29 
8.1. 
Site Monitoring ......................................................................................................................................................... 29 
8.2. 
Data Collection .................................................................................................................................................... 30 
8.3  
Data Disclosure and Subject Confidentiality ........................................................................................... 30 
9. 
DATA ANALYSIS ........................................................................................................................................................... 30 
9.1. 
Analysis Sets ......................................................................................................................................................... 30 


Page 4 of 60 
 
9.2. 
Subject Demographics and Other Baseline Characteristics .............................................................. 30 
9.3. 
Efficacy Analyses ................................................................................................................................................ 31 
9.4 
Safety Variables ................................................................................................................................................... 31 
9.5   Sample Size Justification ...................................................................................................................................... 31 
10. 
ETHICAL CONSIDERATIONS. ............................................................................................................................. 31 
10.1. 
Informed Consent .......................................................................................................................................... 31 
10.2. 
Consent Forms ................................................................................................................................................ 31 
10.3. 
Responsibilities of the Investigator and IRB ...................................................................................... 31 
10.4. 
Publication of Study Protocol and Results .......................................................................................... 32 
11. 
PROTOCOL ADHERENCE ..................................................................................................................................... 32 
11.1. 
Protocol Amendments ................................................................................................................................. 32 
12. 
REFERENCES ............................................................................................................................................................ 32 
Appendix 1: Schedule of Assessments Flowchart .................................................................................................... 34 
Appendix 2: Ichthyosis Severity Score (ISS) .............................................................................................................. 38 
Appendix 3: DERMATOLOGY LIFE QUALITY INDEX (DLQI) ............................................................................... 42 
Appendix 4: CHILDREN'S DERMATOLOGY LIFE QUALITY INDEX (CDLQI) ................................................. 44 
Appendix 5:CHILDREN'S DERMATOLOGY LIFE QUALITY INDEX (CDLQI  Cartoon .................................. 45 
Appendix 6: NRS Itch/Pain and PROMIS Itch Scores .............................................................................................. 46 
Appendix 7: Stigma Questionnaire ................................................................................................................................. 49 
Appendix 8: Photography Protocol ................................................................................................................................ 55 
Appendix 9: Ichthyosis Severity Self-Assessment ................................................................................................... 59 
Appendix 10: Ichthyosis Financial and Time Burden ............................................................................................. 60 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Page 5 of 60 
 
INVESTIGATOR’S AGREEMENT  
I have created and read the final version of the following protocol: An Open-Label and Long-
Term Extension Study to Evaluate the Efficacy and Safety of Ustekinumab in the Treatment of 
Patients with Ichthyoses, dated 6 November 2020 where the COMPANY (Janssen Scientific 
Affairs, LLC) and SPONSOR (Dr. Amy Paller at Northwestern University) agree to abide by all 
provisions set forth therein.  
 
 
I agree to comply with the current International Conference on Harmonisation Guideline for Good 
Clinical Practice relating to the conduct of the clinical study.  
 
I also agree that persons debarred from conducting or working on clinical studies by any court or 
regulatory agency will not be allowed to conduct or work on this study.  
 
I have received and reviewed the STELARA® (ustekinumab) Prescribing Information (version 
November 2019). 
 
I agree that the study is ethical.  
 
I agree to conduct the study as outlined and in accordance with all applicable regulations guidelines.  
 
I agree to maintain the confidentiality of all information received or developed in connection with this 
protocol.  
 
This document contains confidential information, which must not be disclosed to anyone other than the 
recipient study staff and members of the Institutional Review Board. I agree to ensure that this 
information will not be used for any purpose other than the evaluation or conduct of the clinical 
investigation without the prior written consent of all Principal Investigators.  
 
 
____________________________________________                             _________________  
Signature of Investigator  
 
 
 
 
 
 
Date  
 
____________________________________________  
Printed Name of Investigator 


Page 6 of 60 
 
STUDY GLOSSARY 
 
Abbreviation/Term 
Definition/Explanation 
AE   
   
   
Adverse Event(s) 
CDLQI  
 
Children’s Dermatology Life Quality Index 
CIE 
 
 
Congenital Ichthyosiform Erythroderma  
CIL   
   
 
Coded Identifier List 
DLQI  
 
Dermatology Life Quality Index 
DCC 
 
 
Data Coordinating Center  
DSMB  
 
Data Safety Monitoring Board 
EI 
 
 
Epidermolytic Ichthyosis 
FDA 
 
 
Food and Drug Administration 
ISS 
 
 
Ichthyosis Severity Score 
ISS-E  
 
Erythema subscore of Ichthyosis Severity Score 
ISS-S  
 
Scaling subscore of Ichthyosis Severity Score  
IFTB 
 
 
Ichthyosis Financial and Time Burden 
IP 
 
 
Investigational Product 
IRB   
   
 
Institutional Review Board 
ITT 
 
 
Intention-to-treat 
LI 
 
 
Lamellar Ichthyosis  
NRS 
 
 
Numerical Rating Scale 
NS 
 
 
Netherton Syndrome  
PASI 
 
 
Psoriasis Area Severity Index 
SAE 
 
 
Serious Adverse Event 
TEWL  
 
Transepidermal water loss 
 
 


Page 7 of 60 
 
PROTOCOL SYNOPSIS  
Title: An Open-Label and Long-Term Extension Study to Evaluate the Efficacy and Safety of 
Ustekinumab in the Treatment of Patients with Ichthyoses 
 
Investigation Type: Drug 
 
Study Type: Open Label 
 
Purpose and Rationale: The ichthyoses are a group of lifelong genetic disorders that share 
characteristics of generalized skin thickening, scaling and underlying cutaneous inflammation. The vast 
majority are orphan disorders and are associated with extremely poor quality of life related to social 
ostracism from altered appearance, associated itchiness and discomfort, and functional limitations from 
the skin disease. Among the more common “orphan” forms of ichthyosis are autosomal recessive 
congenital ichthyosis (ARCI; includes lamellar ichthyosis/LI and congenital ichthyosiform 
erythroderma/CIE), Netherton syndrome (NS) and epidermolytic ichthyosis (EI). However, there are 
dozens of other syndromic and non-syndromic ichthyotic disorders as well. Therapy is time-consuming 
for patients or parents and is supportive, focusing on clearance of the scaling. There are no therapies 
based on our growing understanding of what causes the disease. We have recently found marked 
elevations in Th17/IL-23 pathway cytokines and chemokines in the skin of individuals with ichthyosis, 
most similar to the inflammatory pattern of psoriasis. While the significance of the high expression of 
Th17/IL-23 pathway genes across all forms of ichthyosis studied to date is unknown, the high expression 
of genes of the Th17/IL-23 pathway in psoriasis is thought to be causative for the disease manifestations. 
We propose that IL-12/IL-23 -targeting therapeutics will safely suppress the inflammation and possibly 
the other features of ichthyosis, improving quality of life. As a proof-of-concept study, we propose to 
treat children (6 years of age and higher) and adults with ichthyotic disorders with ustekinumab in an 
open-label trial to serially assess clinical response to and safety of ustekinumab for this group of 
disorders.  
 
Co-primary objectives:  
• 
To evaluate the efficacy of ustekinumab for ichthyosis, as measured by an at least 50% reduction 
in severity (using the Ichthyosis Severity Score (ISS) measure) at 7 months after initiation of 
study drug (Visit 6) 
• 
To evaluate the safety of ustekinumab for ichthyosis, based on occurrence of bacterial and fungal 
infections  
 
Secondary objectives:  
• 
To evaluate reduction in ISS, and ISS subset measures for erythema and scaling (ISS-E, ISS-S) at 
months 7, 13, 19 and 25 after study drug initiation. 
• 
To evaluate improvement in quality of life assessments at months 7, 13, 19, and 25 after study 
drug initiation (Dermatology Life Quality Index/DLQI for 16 years and older; Children’s 
Dermatology Life Quality Index/CDLQI for children 6-15 years; specific questions about impact 
of scaling on daily life) 
• 
To evaluate non-infectious AEs and all SAEs related to ustekinumab use, particularly injection 
reactions 


Page 8 of 60 
 
 
These clinical indices will be assessed as per the Schedule of Assessments flowchart (Appendix 1) and 
require minimal input or time commitment from the study participants but are critical to analyze trends 
over time. 
 
Study Design: Patients will be screened for inclusion and exclusion criteria. If using a systemic retinoid 
or immunomodulatory agent, the patient will wait four weeks to initiate therapy. Washout for topical 
steroids will be one week. If the patient has not had testing for TB (QuantiFERON gold, given that the 
generalized skin scaling and erythema precludes PPDi) in the previous three months, testing will be 
performed at screening and must be negative before starting ustekinumab. All patients who have not had 
genetic testing (research or a CLIA-approved lab) will be required to have testing sent to Dr. Keith 
Choate at Yale University and will enroll in Dr. Paller’s “Screening for the Genetic Basis of 
Dermatologic Disease” study IRB# 2009-13803. As long as the clinical diagnosis is ichthyosis / an 
ichthyotic disorder, having a known gene with mutation is not required before entry into this study, but is 
required before study end. Each subject will receive ustekinumab at Baseline (Day 0), month 1, and then 
every 8 weeks thereafter (months 3, 5, 7, 9, and 11). Subjects who do not achieve a 25% reduction in the 
Ichthyosis Severity Score (ISS) at month 7 (Visit 6) will be withdrawn from the study due to lack of 
efficacy. The final assessment of the open label period will be month 13. Those subjects who have 
evidence of improvement (per the subject) will have the option to continue in the Long Term Extension 
(LTE) portion of the study for an additional 12 months. 
 
Month 13 may duplicate as a subject’s baseline visit of the LTE, or a subject can return for an LTE 
baseline visit any time after completion of the open-label phase. During the LTE, subjects will have visits 
every 8 weeks (months 13, 15, 17, 19, 21, 23 and 25). Safety labs including hematology, chemistry and 
QuantiFERON gold will be repeated at months 13 and 25. 
 
Visit 
Number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
 
 
 
 
 
 
 
 
 
OL end 
LTE 
start 
 
 
 
 
 
End of 
LTE 
 
Screen 
(28 d-21 
d of Day 
0) 
Week -4 
Baseline/ 
Day 0/ 
Week 0 
Month 
1/ 
Week 
4 
Month 
3/ 
Week 
12 
Month 
5/ 
Week 
20 
Month 
7/ 
Week 
28 
Month 
9/ 
Week 
36 
Month 
11/ 
Week 
44 
Month 
13/ 
Week 
52 
Month 
15/ 
Week 
60 
Month 
17/ 
Week 
68 
Month 
19/ 
Week 76 
Month 
21/ 
Week 
84  
Month 
23/ 
Week 
92 
Month 
25/ 
Week 
96 
Drug 
supplied 
0 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
0 
 
Number of Centers: 
 
1 
 
Blinding: Not applicable—Open-label treatment 
 
 
Study Duration: The clinical portion of the study will include 6 months for patient recruitment and up to 
100 weeks (25 months plus at least 4 weeks for screening) of subject treatment, bringing the total 
maximum clinical study duration to 2.6 years.  
 
Test Medication: 
 
Ustekinumab (STELARA®)  


Page 9 of 60 
 
 
Study Population:  
 
15 evaluable subjects 
  
Subjects must be at least 6 years of age with a diagnosis of 
ichthyosis/ichthyotic disorder and must show at least moderate erythema. 
These subjects will primarily come from the Chicago/Midwest region, 
but the study is open to anyone meeting criteria, wishing to travel to 
Chicago to be in the study and able to comply with study requirements. 
Inclusion Criteria 
● Subject has provided informed consent; parental consent for patients under 18 years of age (plus 
assent for subjects age ≥ 12 and < 18). 
● Subjects are at least 6 years of age or older at the time of screening. 
● Before screening visit, females must be: 
• 
Postmenopausal, defined as 
≥ 45 years of age with amenorrhea for at least 18 months, 
OR  
• 
≥ 45 years of age with amenorrhea for at least 6 months and a serum FSH level > 40 IU/mL 
OR 
• 
Of childbearing potential, in which case she must satisfy at least one of the below: 
 
Surgically sterile (has had a hysterectomy or bilateral oophorectomy, tubal ligation, 
or otherwise be incapable of pregnancy), or 
 
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 (e.g., condoms, 
diaphragm, or cervical cap, with spermicidal foam, cream, film, gel or suppository), 
or male partner sterilization, consistent with local regulations regarding 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  
 
Not heterosexually active. Abstinence is allowed as an acceptable form of 
contraception. 
 
Note: If a woman participant’s childbearing potential changes after start of the study 
(e.g., a premenarchal 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. 
 
Female participants of childbearing potential (menstrual and not surgically sterile), 
must have a negative serum beta-human chorionic gonadotropin (ᵦ-hCG) pregnancy 
test at screening and a negative urine pregnancy test at Week 0 (prior to screening 
visit) 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. 
• 
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., 


Page 10 of 60 
 
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. 
● Subjects must have a confirmed clinical diagnosis of ichthyosis/ichthyotic disorder, and either 
have completed genotype or be willing to be genotyped (genotype results will not be required for 
entry into the study). 
● Subjects must have at least moderate erythema (ISS-erythema score ≥ 2) related to his/her 
ichthyosis/ichthyotic disorder. 
● Subjects must be clinically judged to be immunocompetent based on baseline laboratory testing 
(chemistry and hematology), medical history and physical examination. 
● Subjects will have baseline negative QuantiFERON®-TB gold, Hepatitis B, Hepatitis C, and HIV 
laboratory testing. 
 
Exclusion criteria 
● Subjects who are unable to provide informed consent or assent (or who do not have consent from 
a Legally Authorized Representative if < 18 years).  
● Subjects with ichthyosis vulgaris or X-linked recessive ichthyosis. 
● Subjects who have a known allergy to ustekinumab or its products. 
● Female subjects who are pregnant or breastfeeding, or who are considering becoming pregnant.  
● Subjects who have prior biologic use targeting IL-12/IL-23 monoclonal antibody. 
● Subjects who have used a systemic retinoid or systemic anti-inflammatory agent within 4 weeks 
prior to baseline. 
● Subjects who have used topical steroid in the previous week, retinoid or keratolytic agent in the 
previous 24 hours. 
● Subjects with active infections or recent history of serious infections, malignancies or history of 
malignancies, recent immunizations with live vaccines, or any severe, progressive, or 
uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic, psychiatric, 
or cerebral disease, or signs or symptoms thereof 
● Subjects who are under 6 years of age at the time of screening. 
 
Ustekinumab is approved for Crohn's disease and has been tested/ found to be safe for psoriasis as young 
as 6 years of age with pK and safety validation to this age level. Although we would love to use in 
younger children with ichthyosis, we chose 6 years of age because of the extensive experience and safety 
testing to this age level. 
 
We are focusing on inflammatory forms of ichthyosis with Th17 skewing in the skin and blood.  Neither 
ichthyosis vulgaris nor recessive X-linked ichthyosis are inflammatory forms of ichthyosis and neither 
has been tested for Th17 skewing; both are easily amenable to available topical and OTC interventions 
and thus have little need for new interventions, especially using a systemic agent. 
 
Duration of Treatment: 15 ichthyosis-affected subjects will be studied up to 25 months. The study will 
include an initial 13-month open-label phase, and a 12-month long-term extension to assure long-term 
safety. 


Page 11 of 60 
 
 
Each subject will receive ustekinumab at Baseline (Day 0) and Months 1, 3, 5, 7, 9, and 11. During the 
LTE, subjects will receive injections every 8 weeks for one year: Month 13, Month 15, Month 17, Month 
19, Month 21, and Month 23. Subjects will come back in for a follow-up visit at Month 25 for an end of 
study visit (no drug administration).    
 
Efficacy Assessments  
● ISS: Ichthyosis Severity Score and subscores (ISS-E, ISS-S) 
● Ichthyosis Severity Self-Assessment 
● DLQI: Dermatology Life Quality Index (for those 16 years and older) 
● CDLQI: Children’s Dermatology Life Quality Index (for those 6 - 16 years of age) 
● IFTB: Ichthyosis Financial and Time Burden 
● 8-item short form PROMIS itch and Stigma score for children 8 and above (parent proxy for 
under age 8) 
● Itch and Pain NRS: Numerical Rating Systems (0-10) for pruritus and pain  
● TEWL (transepidermal water loss): Functional assessment of barrier 
 
Note the severity assessments will be performed by a trained study team member with PI supervision.  
 
Safety Assessments 
● Adverse events and serious adverse events monitoring 
• Adverse events of special interest include all malignancies and all cases of active 
tuberculosis (TB). 
● Laboratory assessments: QuantiFERON Gold, chemistry, hematology 
● Vital signs, physical examination 
 
Other Assessments 
● Photography 
● Serum samples for cytokine analysis or proteomics 
● Microbiome samples 
● Tape strips to evaluate mRNA expression and lipidomics  
● Saliva for DNA analysis (stored; 2nd sample sent to Dr. Keith Choate at Yale University if gene 
unknown/untested and subject consents to IRB# 2009-13803). IRB 2009-13803 is separately 
supported only by the Department of Dermatology at Northwestern University.  
 
Data Analysis 
Statistical analysis will be performed by statisticians at Northwestern University. 
 
The primary analysis population will be based on a modified intention-to-treat (mITT) population, which 
is defined as all patients who received at least one dose of the treatment. Because the loading dose is 
given at baseline, this should effectively include all the treated patients. 
 
Efficacy and other data will be summarized. Descriptive statistics of demographics and other baseline 
characteristics will be presented for all subjects. The primary efficacy variable is the ISS (composite) at 7 


Page 12 of 60 
 
months after study drug initiation. The primary safety variable is t occurrence of bacterial and fungal 
mucocutaneous infections by 13 months after study drug initiation. Safety will be evaluated by 
tabulations of adverse events and will be presented with descriptive statistics at each visit. The number 
and percentage of subjects experiencing an AE/SAE will be stratified by organ system class, or a 
preferred term, and severity of the adverse event, and recorded and tabulated overall by each sub-strata.  
 
Key Words: Ichthyosis, ustekinumab, IL-12, IL-23, biologic, monoclonal antibody 
 
 


 
Page 13 of 60 
 
1. BACKGROUND AND RATIONALE  
1.1 Disease 
 
The ichthyoses are a group of lifelong genetic disorders that share characteristics of skin thickening, 
scaling and underlying cutaneous inflammation. Other than ichthyosis vulgaris (commonly associated 
with atopic dermatitis) and recessive X-linked ichthyosis (1:1500 boys), the >30 subtypes of ichthyosis 
are rare (<1:100,000 individuals). Among these rare subtypes are (i) epidermolytic ichthyosis (mutation in 
one of the genes encoding suprabasal keratins), (ii) Netherton syndrome (mutations in SPINK5, leading to 
excessive epidermal protease activity), (iii) autosomal recessive congenital ichthyosis or ARCI 
(associated with biallelic mutations in a dozen genes and ranges in appearance from darker, plate-like 
scaling as in lamellar ichthyosis or LI to intense erythema with fine scaling as in congenital ichthyosiform 
erythroderma or CIE, which includes harlequin ichthyosis, the most severe form), (iv) various forms of 
erythrokeratodermas (often defects in genes that encode connexins or desmosomal components), and (v) 
other ichthyosiform disorders, such as IFAP. All ichthyosis types share a defective protein and lipid 
barrier, which manifests functionally as increased transepidermal water loss and percutaneous absorption. 
 
These forms of ichthyosis lead to life-long disfigurement due to the highly visible erythema and scaling. 
The quality of life of affected children and adults is poor, not only because of their appearance and social 
ostracism, but also because of the frequent associated itchiness (pruritus) and functional limitations 
related to the inflamed, often fissured, skin and limited joint mobility related to skin tightness and pain. 
Affected individuals also have a markedly reduced ability to sweat, restricting sports and outdoor 
activities in warmer weather.  
 
Therapy for the ichthyoses is supportive and time-consuming for patients. Most use long baths, emollients 
and agents that peel the thick scale, specifically keratolytics and topical retinoids. Oral retinoids are most 
effective at removing scale and skin thickening but tend to increase skin and mucosal inflammation and 
have potential side effects (most commonly hypertriglyceridemia, teratogenicity and, with chronic use, 
hyperostosis). The high risk of systemic absorption of topical steroids (and side effects of systemic 
steroids) restricts their use for the cutaneous inflammation associated with these lifelong diseases. There 
remains a huge unmet need for more effective and safer treatments, ideally therapy that improves both the 
scaling and the cutaneous inflammation with its associated pruritus and discomfort.  
1.2 Clinical Hypotheses 
We hypothesize that: a) intervention with ustekinumab will improve the severity of ichthyosis features; 
and b) the administration of ustekinumab will be well-tolerated. 
1.3 Rationale for Ustekinumab Use 
Ustekinumab is a fully human immunoglobulin G1 kappa monoclonal antibody (mAb) that binds 
both human interleukin (IL)-12 and IL-23 via a common IL-12/23p40 subunit. Ustekinumab 
neutralizes the activities of IL-12 and IL-23 by preventing these cytokines from binding to the 
IL-12 receptor beta-1 receptor protein, which is expressed on the surface of immune cells. 
Ustekinumab has been shown to be an effective treatment and has a favorable benefit risk profile 
for adult and pediatric psoriasis patients age 12 and older. Its use in psoriasis patients ages ≥ 6 


 
Page 14 of 60 
 
and < 12 is currently being investigated 
(https://clinicaltrials.gov/ct2/show/NCT02698475?term=ustekinumab&cond=psoriasis&rank=1). 
We have recently found marked elevations in Th17/IL-23 pathway cytokines and chemokines in 
the skin of individuals with ichthyosis, most similar to the inflammatory pattern of psoriasis. 
While the significance of the high expression of Th17/IL-23 pathway genes across all forms of 
ichthyosis studied to date is unknown, the high expression of genes of the Th17/IL-23 pathway 
in psoriasis is thought to be causative for the disease manifestations.  We had experience with 
initiation of ustekinumab in a 10 year old patient with erythrokeratoderma with cardiomyopathy; 
despite courses of numerous immunosuppressants and retinoids (and being on oral 
tacrolimus/rapamycin after cardiac transplant), her erythroderma was intense and her scaling was 
uncomfortable. We found high levels of Th17/IL-23 cytokines in her skin and blood.  Within 4 
months of ustekinumab use (and with continued improvement thereafter), her skin color had 
normalized, and her scaling was dramatically improved (Paller et al. The spectrum of 
manifestations in desmoplakin gene (DSP) spectrin repeat 6 domain mutations: 
immunophenotyping and response to ustekinumab. J Am Acad Dermatol. 2018;78:498-505). We 
propose that IL-12/IL-23 -targeting therapeutics will safely suppress the inflammation and 
possibly the other features of ichthyosis, improving quality of life. 
1.4 Risks of Ustekinumab 
Per the STELARA® (ustekinumab) Prescribing Information (version June 2018): 
 
The most common (≥ 3%) adverse reactions associated with ustekinumab in patients being treated for 
psoriasis were nasopharyngitis, upper respiratory tract infection, headache, and fatigue. Sometimes 
serious infections have occurred in patients on ustekinumab. There is a theoretical risk for infections from 
mycobacteria, salmonella, and Bacillus Calmette-Guerin (BCG) vaccination in patients deficient in IL-
12/IL-23. Patients will be evaluated for mycobacterium tuberculosis and treated for latent TB prior to 
administration of ustekinumab. Ustekinumab may increase the risk of malignancy; the safety of 
ustekinumab in patients with history of or a known malignancy has not been evaluated. Anaphylaxis or 
other clinically significant hypersensitivity reactions may occur. Cases of noninfectious pneumonia, 
including interstitial pneumonia, eosinophilic pneumonia and cryptogenic organizing pneumonia have 
been reported during post-approval monitoring of ustekinumab. Allergic alveolitis has also been reported 
during the post-approval monitoring period. One case of Reversible Posterior Leukoencephalopathy 
Syndrome (RPLS) was also reported. The potential discomforts, side effects and risks associated with 
ustekinumab will be discussed with all subjects during the informed consent process.  
2. STUDY ENDPOINTS 
2.1 Primary Endpoints 
Co-primary objectives:  
• 
To evaluate the efficacy of ustekinumab for ichthyosis, as measured by an at least 50% reduction 
in severity (using the Ichthyosis Severity Score (ISS) measure) at 7 months after initiation of 
study drug (Visit 6) 
• 
To evaluate the safety of ustekinumab for ichthyosis, based on occurrence of bacterial and fungal 
infections  


 
Page 15 of 60 
 
2.2 Secondary Objectives:  
• 
To evaluate reduction in ISS, and ISS subset measures for erythema and scaling (ISS-E, ISS-S) at 
months 7, 13, 19 and 25 after study drug initiation. 
• 
To evaluate improvement in quality of life assessments at months 7, 13, 19, and 25 after study 
drug initiation (Dermatology Life Quality Index/DLQI for 16 years and older; Children’s 
Dermatology Life Quality Index/CDLQI for children 6-15 years; specific questions about impact 
of scaling on daily life) 
• 
To evaluate non-infectious AEs and all SAEs related to ustekinumab use, particularly injection 
reactions 
 
Exploratory objectives: 
• 
Skin and blood biomarkers will be stored. In the future, should ustekinumab prove effective, 
investigators will seek funding (ideally, through the NIH) to evaluate the reduction in stratum 
corneum and blood IL-12/IL-23 and Th17 marker expression, along with other involved 
biomarkers 
 
These clinical indices will be assessed as per the Schedule of Assessments flowchart (Appendix 1) and 
require minimal input or time commitment from the study participants but are critical to analyze trends 
over time. 
3. INVESTIGATIONAL PLAN  
3.1 Study Centers 
This study will be performed at one site: the Department of Dermatology at Northwestern University 
Feinberg School of Medicine/Lurie Children’s Hospital in Chicago. The entire clinical component will be 
performed and database housed at Northwestern University.  
3.2 Study Organization 
The Principal Investigator (PI) or the delegated sub-investigators of this project will be responsible for 
protocol development, consenting of subjects, performing skin biopsies, treatment and evaluation of 
subjects, review of adverse events, and reporting adverse events to the IRB. Our site will have a project 
manager whose duties will include protocol development, grant administration for the individual study site, 
purchasing, case report form and source document design and development, and oversight of the project at 
the study site. The project manager at Northwestern will also be responsible for any reporting needed to 
Company.   
 
The site project manager will also review consents, serious adverse events, and source verification on a 
quarterly basis throughout the study. The site project manager will work with the statisticians to complete 
any statistical analysis. Data will be entered by study coordinators in a central REDCap database based at 
Northwestern University. The Dermatology Clinical Trials Unit currently manages both international and 
national multisite REDCap databases.  


 
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3.3 Study Duration  
The total clinical study duration will be 25 months. Patient recruitment and enrollment is expected to take 
approximately 6 months. The treatment period will include an initial 13-month open-label phase and a 12-
month long-term extension phase. Complete data analysis and manuscript preparation will require 
approximately another 6 months. 
3.4 Biomarker Analyses 
Tape strips of the outer epidermis of the skin will be collected at Baseline, Month 7, Month 13, Month 19 
and Month 25. A 15.0 mL blood sample will also be collected at Screening, Month 13, and Month 25. 
These samples will be labeled with the subject’s study ID, study visit number, and visit date and stored at 
-80oC at Northwestern University for possible future analysis of inflammatory biomarkers, including IL-
12/23p40, IL-23p19 and Th17, as a function of clinical response. Such analysis will be conducted with 
future funding and will occur at Northwestern University only. Samples will not be shipped to outside 
individuals or institutions.   
4. SUBJECT ELIGIBILITY 
Subjects must be at least 6 years of age with a diagnosis of ichthyosis/ichthyotic disorder and must show 
at least moderate erythema (see specific inclusion criteria below). These subjects will primarily come 
from the Chicago/Midwest region, but the study is open to anyone meeting criteria, wishing to travel to 
Chicago to be in the study and able to comply with study requirements. 
4.1 Inclusion Criteria 
● Subject has provided informed consent; parental consent for patients under 18 years of age (plus 
assent for subjects age ≥ 12 and < 18). 
● Subjects are at least 6 years of age or older at the time of screening. 
● Before screening visit, females must be: 
• 
Postmenopausal, defined as 
≥ 45 years of age with amenorrhea for at least 18 months, 
OR  
• 
≥ 45 years of age with amenorrhea for at least 6 months and a serum FSH level > 40 IU/mL 
OR 
• 
Of childbearing potential, in which case she must satisfy at least one of the below: 
 
Surgically sterile (has had a hysterectomy or bilateral oophorectomy, tubal ligation, 
or otherwise be incapable of pregnancy), or 
 
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 (e.g., condoms, 
diaphragm, or cervical cap, with spermicidal foam, cream, film, gel or suppository), 
or male partner sterilization, consistent with local regulations regarding 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  


 
Page 17 of 60 
 
 
Not heterosexually active. Abstinence is allowed as an acceptable form of 
contraception. 
 
Note: If a woman participant’s childbearing potential changes after start of the study 
(e.g., a premenarchal 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. 
 
Female participants of childbearing potential (menstrual and not surgically sterile), 
must have a negative serum beta-human chorionic gonadotropin (ᵦ-hCG) pregnancy 
test at screening and a negative urine pregnancy test at Week 0 (prior to screening 
visit) 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. 
• 
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. 
● Subjects must have a confirmed clinical diagnosis of ichthyosis/ichthyotic disorder, and either 
have completed genotype or be willing to be genotyped (genotype results will not be required for 
entry into the study). 
● Subjects must have at least moderate erythema (ISS-erythema score ≥ 2) related to his/her 
ichthyosis/ichthyotic disorder. 
● Subjects must be clinically judged to be immunocompetent based on baseline laboratory testing 
(chemistry and hematology), medical history and physical examination. 
● Subjects will have baseline negative QuantiFERON®-TB gold, Hepatitis B, Hepatitis C, and HIV 
laboratory testing. 
4.2 Exclusion criteria 
● Subjects who are unable to provide informed consent or assent (or who do not have consent from 
a Legally Authorized Representative if < 18 years).  
● Subjects with ichthyosis vulgaris or X-linked recessive ichthyosis. 
● Subjects who have a known allergy to ustekinumab or its products. 
● Female subjects who are pregnant or breastfeeding, or who are considering becoming pregnant.  
● Subjects who have prior biologic use targeting IL-12/IL-23 monoclonal antibody. 
● Subjects who have used a systemic retinoid or systemic anti-inflammatory agent within 4 weeks 
prior to baseline. 
● Subjects who have used topical steroid in the previous week, retinoid or keratolytic agent in the 
previous 24 hours. 
● Subjects with active infections or recent history of serious infections, malignancies or history of 
malignancies, recent immunizations with live vaccines, or any severe, progressive, or 
uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic, psychiatric, 
or cerebral disease, or signs or symptoms thereof 


 
Page 18 of 60 
 
● Subjects who are under 6 years of age at the time of screening. 
 
Ustekinumab is approved for Crohn's disease and has been tested/ found to be safe for psoriasis as young 
as 6 years of age with pK and safety validation to this age level. Although we would love to use in 
younger children with ichthyosis, we chose 6 years of age because of the extensive experience and safety 
testing to this age level. 
 
We are focusing on inflammatory forms of ichthyosis with Th17 skewing in the skin and blood.  Neither 
ichthyosis vulgaris nor recessive X-linked ichthyosis are inflammatory forms of ichthyosis and neither 
has been tested for Th17 skewing; both are easily amenable to available topical and OTC interventions 
and thus have little need for new interventions, especially using a systemic agent. 
 
All screened subjects initially considered for this study will be documented. Study staff will create and 
maintain pre-screening logs and will contact potential subjects through IRB-approved recruitment 
methods. If the subject is excluded from the study, reasons for exclusion will be documented in the pre-
screening log.  
5. TREATMENT PROCEDURES  
5.1 Investigational Treatment  
The following study treatment will be used: 
● Ustekinumab (STELARA®) 
5.2 Dispense and Use of Investigational Treatment  
5.2.1 Dispensing the Investigational Treatment 
The research pharmacy at Lurie Children’s Hospital will be supplied with ustekinumab (STELARA®) 
from the Company. Ustekinumab will be shipped to a designated, licensed pharmacist at the 
investigational pharmacy at Lurie Children’s Hospital. 
 
When delivery of a test medication is received at the investigational site, the Pharmacist, or a member of 
their staff specifically authorized and delegated by the Investigator, will check for accurate delivery and 
acknowledge receipt by signing (or initialing) and dating the required documentation and returning it as 
instructed. The date, time and condition of the package should also be documented at the time of receipt. 
A copy of this documentation will be retained for the Investigator file. This individual must store the 
treatment according to instructions specified on the packaging. An accurate record of the shipment and 
dispensing of these study agents will be kept by the respective pharmacist at each site. All unused study 
material will be returned by study subjects to the dispensary site.  
 
The ustekinumab for this study will be supplied as final vialed product (FVP), single-use 2 mL Schott 
Type I glass vial closed with a Daikyo D777-1 FluroTec®-coated stopper and a West 13 mm aluminum 
seal and plastic light green flip-off button. The FVP formulation is composed of 90 mg/mL ustekinumab 


 
Page 19 of 60 
 
with excipient concentrations of 6.7 mM L-histidine, 7.6% (w/v) sucrose, and 0.004% (w/v) polysorbate 
80, pH 6.0. There is 1 dose strength (i.e. 45 mg in 0.5 mL volume). No preservatives are present.    
5.2.2 Instructions for prescribing and taking study treatment  
Throughout the study, treatment will be via subcutaneous injection of ustekinumab, administered by a 
physician or nurse licensed in the state of Illinois. All subjects enrolled in the study will receive 
ustekinumab at Baseline (Day 0), Month 1, and then every 8 weeks thereafter (Months 3, 5, 7, 9, and 11). 
Dosing every 8 weeks is based on a case report of a pediatric patient with autosomal recessive congenital 
ichthyosis (ARCI) who had initial dramatic improvement with ustekinumab injection but subsequent 
worsening of skin symptoms prior to dosing every 12 weeks (Poulton, 2019). Improvements were 
sustained by dosing every 8 weeks. This patient did not experience any adverse events related to 
increased dosing frequency. While psoriasis patients treated with ustekinumab generally receive dosing 
every 12 weeks, patients with inflammatory bowel disease receive ustekinumab every 8 weeks The safety 
profile in clinical trials with dosing every 8 weeks (i.e. those for inflammatory bowel disease) has been 
consistent with the safety profile in clinical trials with dosing every 12 weeks (i.e. those for psoriasis and 
psoriatic arthritis) (Ghosh, 2019).   
 
 Subjects who have evidence of improvement (per the subject) will have the option to continue in the 
Long-Term Extension portion of the study for an additional 12 months and will receive ustekinumab 
every 8 weeks (Months 13, 15, 17, 19, 21, and 23). At each dosing visit, subject weight will be measured 
and the dose of ustekinumab will be adjusted accordingly.  The weight-based dosing used will be the 
standard dosing used in clinical trials for pediatric patients receiving ustekinumab for psoriasis (Landells, 
2015; Phillipp 2020). Subjects will receive one of the following dose levels depending on their weight: 
 
• 
Weight < 60 kg: 0.75 mg/kg 
• 
Weight ≥ 60 kg to ≤ 100 kg: 45 mg 
• 
Weight > 100 kg: 90 mg  
5.2.3 Prohibited treatment 
If subjects are using a systemic retinoid or immunomodulatory agent, the patient will wait four weeks to 
initiate therapy with ustekinumab. Washout for topical steroids will be one week.  
 
While enrolled in the study, subjects may not use any topical agent for the treatment of ichthyosis during 
the first 6 months other than bland emollients. After the 6-month time point, keratolytics, including but 
not limited to agents containing tazarotene, salicylic acid, alpha-hydroxyacids, and urea, can be added to 
the regimen as per investigator discretion. Subjects may not be on any systemic agents for the treatment 
of ichthyosis. Subjects who experience skin infection requiring antibiotics during the study may continue 
on study drug and stay in the study, unless per investigator discretion. These therapies will be noted by 
the investigator on the concomitant therapy form.  
 
All concomitant therapies (including prescription medications, over-the-counter medications, vitamins, 
herbal supplements) will be recorded throughout the study.  


 
Page 20 of 60 
 
5.3 Subject Withdrawal/Discontinuation 
Subjects will be evaluable if they complete all required assessments and visits through and including 
Month 13. If subjects fail to return for study visits, or become lost to follow up, subjects will be 
considered withdrawn. The PI and/or designated study staff will attempt to follow up with these 
individuals to discern the reason for their withdrawal. Similarly, if subjects choose to discontinue their 
participation in the study, which can be done at any time per subject discretion, study staff will attempt to 
contact the subject to determine their reason for discontinuation.  
 
Subjects who do not achieve a 25% reduction in the Ichthyosis Severity Score (ISS) at month 7 (Visit 6) 
will be withdrawn from the study due to lack of efficacy. 
 
Treatment must be discontinued under the following circumstances due to concern for subject safety: 
 
• 
The investigator believes that for safety reasons (e.g., AE or SAE) it is in the best interest of the 
subject to discontinue study treatment; 
• 
An AE temporally associated with study drug injection, resulting in bronchospasm with wheezing 
and/or dyspnea requiring ventilatory support, or symptomatic hypotension with a greater than 40 
mm Hg decrease in systolic blood pressure; 
• 
A severe study drug injection-site reaction; 
• 
The subject or their legally acceptable representative withdraws consent/assent for administration 
of study drug; 
• 
Pregnancy, or pregnancy planned within the study period or within 6 months after the last study 
drug injection; 
• 
Malignancy; 
• 
An opportunistic infection; 
• 
A recurrent or chronic serious infection; 
• 
The subject is deemed ineligible according to the following TB screening criteria: 
− 
A diagnosis of active TB is made. 
− 
A subject has symptoms suggestive of active TB based on history or physical 
examination, or has had recent close contact with a person with active TB. 
− 
A subject undergoing evaluation has a positive QuantiFERON®-TB Gold test result 
and/or an indeterminate QuantiFERON®-TB Gold test result on repeat. 
 
Subjects who discontinue study treatment will return at next scheduled visit to undergo an end of study 
visit and then be discontinued from the trial.  
5.4 Study Completion and Post-study Treatment  
Study participation is completed for the subject at the conclusion of either their Month 13 study visit or, if 
participating in the long-term extension, their Month 25 study visit. Adverse events that occur within 30 
days of the End of Study visit must be documented and reported by the PI.  
 
The study in its entirety will be completed when 15 subjects have completed their treatment course as per 
the protocol and the complete data analysis has been performed.  
 
Upon completion of their study participation, subjects will return to individual treatment, as determined 
by their regular treating physician.  


 
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6. VISIT SCHEDULE AND ASSESSMENTS  
Appendix 1 lists the assessments and indicates with an “X” the visits at which each assessment will be 
performed. Subjects should be seen for all visits on the designated day or as close as possible to the 
original planned visit schedule (recommended visit windows are provided in Appendix 1).  
 
In the event subjects do not present for their study visit, study staff will document their attempts to 
contact these individuals.  
6.1 Screening/Baseline Visit 
The Screening and Baseline visit procedures may be combined on the same day if the subject meets all 
screening eligibility criteria. All patients who have not had genetic testing (research or a CLIA-approved 
lab) will enroll in Dr. Paller’s “Screening for the Genetic Basis of Dermatologic Disease” IRB# 2009-
13803 and have testing sent to Dr. Keith Choate at Yale University. If the clinical diagnosis is ichthyosis / 
ichthyotic disorder, having a known gene mutation is not required before entry into the study. The saliva 
sample for genetic testing will be obtained at the screening visit and before drug dosing/Baseline Visit. 
Urine pregnancy test (female subjects of childbearing potential only) will be completed prior to any 
baseline study procedures and ustekinumab injection. The saliva sample is part of study #2009-13803. 
6.1.1 Consent  
Consent will be obtained by the study investigator or by approved study team member at the screening 
visit (Visit 1) as indicated in Appendix 1 and before any study procedures take place. All participants will 
be given time to read the IRB-approved consent form and ask any questions they may have. The 
consenter will emphasize that the study is voluntary. Consent forms will be kept in subject source binders 
in a locked office in the Department of Dermatology.  
6.1.2 Medical and Medication History 
A PI or designated study team member will collect information regarding relevant medical history/current 
medical conditions at every study visit as indicated in Appendix 1. All collected information will be 
documented. When possible, diagnoses (rather than symptoms) will be recorded. The history regarding 
the patient’s ichthyosis will also be obtained including date of diagnosis and prior treatments. 
Medications including current medications and those taken within six months preceding enrollment will 
be recorded. Attention should also be paid to current treatments for ichthyosis (including bleach baths, 
any recent topical or systemic antibiotic use, skin care regimen and use of any topical or systemic 
medication).  
6.1.3 Vital Signs and Height/Weight 
Vital signs, including blood pressure, pulse, respiratory rate, temperature, and weight will be collected at 
Screening, Baseline, and every visit at which there is study drug administration, as indicated in Appendix 
1. Height will be recorded at the first visit, the end of the open label phase, and the end of the long-term 
extension, as indicated in Appendix 1.  


 
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6.1.4 Complete Physical Examination & Skin Examination 
A complete physical examination will be performed by a physician at the screening and baseline visits, as 
well as the end of the open label phase and the end of the long-term extension. A full skin exam will 
occur at Baseline and then at every visit at which there is study drug administration, as indicated in 
Appendix 1. If the history and/or skin examination at interim visits suggests an additional issue, an 
unscheduled physical examination may be needed. Results will be documented in the Medical History if 
present before signing the informed consent. If examination shows abnormal findings that meet criteria 
for an AE after the informed consent form has been signed and the subject has been enrolled with study 
drug initiation, these findings will be documented as such in the subject’s file.  
6.1.5 Safety Labs and Pregnancy Testing 
Clinical lab evaluations at screening visit include QuantiFERON gold, Hepatitis B, Hepatitis C, HIV, 
chemistry and hematology testing to be resulted at local site hospitals. Blood will be drawn by a licensed 
phlebotomist or trained study team member per hospital requirements. QuantiFERON gold, chemistry 
and hematology testing will also be done at visits for Months 13 and 25.  
 
All female study subjects of child-bearing potential (i.e. female subjects who have experienced menarche) 
will be tested for pregnancy at the screening and baseline as indicated in Appendix 1. Urine HCG testing 
will be obtained. Any woman with a confirmed positive pregnancy test during screening is not eligible for 
participation in this study. In addition, female subjects of child-bearing potential will have urine HCG 
testing prior to every administration of the study drug. 
6.1.6 Severity Evaluations - ISS and Ichthyosis Severity Self-Assessment 
Physician severity evaluations will be performed at every in-person study visit. Severity assessments will 
be performed by Ichthyosis Severity Score (ISS). ISS is a composite score that captures differences in 
severity in different body regions as a function of their body surface area. As in the EASI score for atopic 
dermatitis and the PASI score for psoriasis, ISS evaluates erythema and scaling as a 0-4+ scale and 
provides pictorial representations for comparisons. Severity is determined at each of four locations: head 
and neck (including scalp); arms (including palms); legs (including soles); and trunk, prorated based on 
body surface area. Separate scores are given for face, scalp, neck, groin, palms, soles, elbows and knees 
within their regions to allow for serial assessments of specific body regions that may cause special 
functional or psychosocial effects.  
6.1.7 TEWL and Tape Strips 
TEWL (transepidermal water loss) will be performed on the nondominant upper outer arm to assess the 
skin barrier at all in-person study visits. Tape strips will be also be obtained from subjects at Baseline, 
Month 7, Month 13, Month 19, and Month 25. TEWL will be performed at four different times during 
visits in combination with tape stripping: prior to applying tape strips, after application of the 6th tape 
strip, after application of the 11th tape strip, and after application of the 16th tape strip. TEWL 
measurements at each time will be collected in triplicate. Tape strips are purchased from CuDerm. Tape 
stripping will be performed on the nondominant upper outer arm using circular 2x2 or 3x3 cm transparent 
tape strips at lesional skin sites. Equal pressure will be applied to affected areas for 10 seconds. Up to 16 


 
Page 23 of 60 
 
tape strips will be serially extracted on skin sites. Tape stripping is painless and, in our experience and 
that of the literature, has no adverse sequelae. Subjects will be asked not to apply emollient or moisturizer 
for at least 24 hours prior to tape stripping. The tape strips will be stored on site at the Paller Laboratory at 
Northwestern University. Depending on efficacy of ustekinumab for ichthyosis, in the future the study 
team may apply for additional funding to analyze the tape strips possible for detection of alterations of 
epidermal lipids and proteins in the outer stratum corneum of epidermis. Proteomics and lipidomics 
analysis will occur at Northwestern University only. Samples will not be shipped to outside individuals or 
institutions.  
6.1.8 Microbiome Sampling 
Microbiome sampling will be done at baseline, Month 7, Month 13, Month 19, and Month 25. This 
sampling will involve swabbing the lesional skin with three separate swabs in three different areas on the 
nondominant upper outer arm. Early skin microbiome studies have shown healthy skin has more 
microbial diversity. The contribution of alterations in the microbiome to skin disease pathology and 
severity is of growing interest. Subjects will be asked not to shower or apply emollient or moisturizer for 
at least 24 hours prior to sampling.  
6.1.9 Photography  
Photography will be done at Baseline, Month 7, Month 13, Month 19, and Month 25 as indicated in 
Appendix 1 and will be of assessment areas only. Photos will be labeled using subject’s study ID as well 
as subject visit number and date of the photo. Photos will be uploaded to a secure, research server 
maintained by Northwestern University within the Department of Dermatology and deleted from the 
camera memory card as soon as possible. Photos will be used to track visible skin changes that may occur 
throughout the duration of the study. Photographs may be taken of lesional skin at ad hoc times 
throughout the study if the subject experiences changes in their ichthyosis.  
6.1.10  Blood Samples for Biomarkers  
A 15.0ml blood sample will be collected at Screening, Month 13 and Month 25, as indicated in Appendix 
1. Blood will be drawn by a licensed phlebotomist or trained study team member per hospital 
requirements. Samples will be centrifuged and serum separated within one hour of collection, labeled 
with the subject’s study ID, study visit number, and visit date and stored at -80oC at Northwestern 
University. Samples will stay at Northwestern University only. Samples will not be shipped to outside 
individuals or institutions.  
6.1.11  DLQI / CDLQI  and IFTB 
Quality of life measures will be obtained at the baseline, Month 7, Month 13, Month 19, and Month 25 
visit as indicated in Appendix 1. The Dermatology Life Quality Index (DLQI; Appendix 3) is the most 
commonly used and first dermatology-specific quality of life assessment tool (Basra et al 2008) used for 
ages 16 and older. It can be used to assess various dermatologic conditions and has been a reliable 
measure of quality of life (Finlay 1994). CDLQI (Appendix 4) is designated for use in children as young 
as four and has been validated (Lewis-Jones and Finlay, 1993). CDLQI will be used for ages 6-15 years. 
The Ichthyosis Financial and Time Burden (IFTB) is an ichthyosis-specific questionnaire with a scale that 


 
Page 24 of 60 
 
aims to capture novel QoL data and better capture data specific to the time and financial burden of the 
disease. The IFTB is currently in development with plans for future validation. IFTB will be collected 
from all subject ages, with proxy assisting if the subject is 17 years or younger.  
6.1.12  STIGMA Questionnaire 
STIGMA Questionnaire (Appendix 7) is used to assess subjects’ perceived social stigma in regard to their 
condition and will be administered at the Baseline, Month 7, Month 13, Month 19, and Month 25 visits 
(Appendix 1). All subjects will complete, and a proxy survey will also be collected if the subject is 
between the ages of 6yo-17yo.  
6.1.13  Itch and Pain NRS/PROMIS Itch 
A Numerical Rating Score (NRS) from 0-10 for both itch and pain will be administered to all subjects at 
every in-person study visit (Appendix 1). Parent proxy will be used for children 6 to 17 years of age. 
Patient-Reported Outcomes Measurement Information System (PROMIS) is a patient-centered measure 
that evaluates physical, mental and social health in adults and children with regards to impact of their itch. 
PROMIS Itch evaluation (Appendix 6) will be conducted at Month 0, Month 7, Month 13, Month 19, and 
Month 25 if the subject scores ≥ 2 on the Itch NRS (Appendix 6). All subjects will complete and a parent 
proxy will also be collected for children 6 to 17 years of age. 
 
6.2 Open Label and Long Term Extension Rollover 
Subjects will be examined at in-person study visits at Screening, Baseline, and Months 1, 3, 5, 7, 9, 11, 
and 13 for the open label phase. Specific study procedures conducted during each of these visits are 
outlined in Appendix 1. Should the subject find ustekinumab to be beneficial, they may have the option to 
continue to the Long-Term Extension with in-person study visits every 8 weeks (Months 15, 17, 19, 21, 
23, and 25). The final in-person study visit will be at Month 25, with the final administration of study 
drug at Month 23 (Appendix 1). 
6.2.1 Adverse Event Assessment  
Adverse event assessments will occur at all study visits after Baseline. Adverse event definitions are 
detailed in section 7.  
6.3 Unscheduled Visits 
In the event of a suspected AE that needs evaluation by the PI or needs laboratory testing or intervention, 
a subject may schedule a visit at any time. During their baseline visit, instructions will be provided 
detailing how to schedule a visit. These instructions will include a phone number and office address that 
subjects may use to contact the study group. During unscheduled visits, study treatment will not be 
administered, and assessments will not be performed. 


 
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6.4 Sample Collection, Preparation, Labeling and Shipment  
 
6.4.1 Sample collection  
All samples will be collected as specified in the Schedule of Assessments flowchart. 
6.4.2 Labeling and de-identifying specimens  
Specimens will not have patient identifiers attached to them (i.e., name, initials, DOB, or Social  
Security number). They will be labeled with a unique patient ID number or code and date of visit. The 
key to the code will be kept at each institution in study files on a secure research server within the 
Department of Dermatology maintained by Northwestern University.   
6.4.3 Transporting specimens 
Specimens needing transport to outside collaborating laboratories will be done so using a competent 
courier (e.g. FedEx or World Courier). Samples will be retained in the Paller Lab at Northwestern 
University until shipment. The shipment will be traceable, and the chain of custody will be documented. 
The specimens will be delivered to a competent member of the study team at the collaborating laboratory, 
who will assure that the specimens have been properly de-identified and stored/transported in the proper 
environment.  
6.4.4 Specimen management 
Samples will be stored at Northwestern University following the date the analysis is complete and used 
solely for objectives outlined in this study. Patient confidentiality will be maintained. Results of all 
experiments will be reviewed by the PI and the source of the data will be verified. Regular meetings of 
the specimen/data analysis team will occur. Regular study monitoring will also occur by qualified 
members of the research team. The samples will be retained until data analysis is complete for this the 
study. In addition, samples can be destroyed at any time at the request of the subject. 
7. 
SAFETY DATA COLLECTION, RECORDING AND REPORTING  
7.1 
Adverse Events 
An adverse event (AE) is any untoward medical occurrence experienced by a subject after completing 
written informed consent to participate in a clinical study. AEs may not be causally or temporally 
associated with the investigational product or procedure. AEs include 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. Lack of drug effect is not considered an AE because 
the purpose of the study is to establish drug effect.  
 
All AEs, SAEs, pregnancies, adverse events of special interest, special reporting situations, and product 
quality complaints (PQCs) will be recorded and reported from the time the subject signs the informed 
consent form to 30 days after administration of the last dose of test article. Subjects will be instructed to 
report AEs and Serious AEs (SAEs) during this time period. The investigators will follow up on all AEs 


 
Page 26 of 60 
 
and SAEs until the events have subsided, returned to baseline, or in case of permanent impairment, until 
the condition stabilizes.  
 
Aggregated AEs will be evaluated monthly by the PI/research team. Safety data will be reviewed by the 
investigators, study team, biostatisticians and project manager unrelated to the study approximately every 
3 months, depending on the number of subjects enrolled.   
 
In psoriasis trials, the most common adverse reactions per ustekinumab studies include nasopharyngitis, 
upper respiratory tract infection, headache and fatigue.  
7.2     Follow-up of Subjects with Adverse Events 
If subjects are experiencing unresolved adverse events at the time of study completion or early 
termination, then the investigator will schedule a follow-up visit to determine the outcome of the adverse 
event. At study close, study staff will document any outstanding adverse events and communicate with 
each study subject's primary care physician for continuity of care and ongoing subject safety. 
7.3 
Serious Adverse Events  
7.3.1. Definition of SAE 
A serious adverse event (SAE) is any adverse event which: 
● is fatal or life-threatening  
● results in persistent or significant disability/incapacity 
● constitutes a congenital anomaly/birth defect 
● requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 
○ routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition 
○ elective or pre-planned treatment for a pre-existing condition that is unrelated to 
indication under study and has not worsened since signing the informed consent 
○ treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission 
○ social reasons and respite care in the absence of any deterioration in the subject’s general 
condition 
● is medically significant, i.e., defined as an event that jeopardizes the subject or may require 
medical or surgical intervention 
● is suspected transmission of any infectious agent via a medicinal product 
 
All malignant neoplasms will be assessed as serious under “medically significant” if other seriousness 
criteria are not met.  
 
Life-threatening in the context of a SAE refers to a reaction in which the subject was at risk of death at 
the time of the reaction; it does not refer to a reaction that hypothetically might have caused death if more 
severe or ongoing.  


 
Page 27 of 60 
 
 
Medical and scientific judgment should be exercised in deciding whether other situations should be 
considered serious reactions, such as important medical events that might not be immediately life 
threatening or result in death or hospitalization but might jeopardize the subject or might require 
intervention to prevent one of the other outcomes listed above. Examples of such events are intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions 
that do not result in hospitalization or development of dependency or abuse. 
 
Death for any reason will be reported as a serious adverse event.  
 
All AEs (serious and non-serious) are captured on the case report form; SAEs also require individual 
reporting to Company as per Section 7.3.2. 
7.3.2. SAE, Adverse Events of Special Interest, and Special Reporting Situations 
To ensure subject safety, every SAE, regardless of causality, adverse events of special interest and special 
reporting situations occurring after the subject has provided informed consent and until 30 days after the 
last study visit, will be reported to the IRB and Company within 24 hours of the study team becoming 
aware of the event. Any SAEs experienced after the 30-day period should be reported to Janssen 
Pharmaceutical Companies if the investigator suspects a causal relationship to study treatment.  
 
Recurrent episodes, complications, or progression of the initial SAE must be reported as follow-up to the 
original episode, regardless of when the event occurs. An SAE that is considered completely unrelated to 
a previously reported one should be reported separately as a new event. 
 
Information about all SAEs (either initial or follow up information) is collected and recorded on the paper 
Serious Adverse Event Report Form. The investigator must assess the relationship of each SAE to study 
treatment, complete the SAE Report Form in English, and send the completed, signed form by fax within 
24 hours after awareness of the SAE to the Company and IRB. The original copy of the SAE Report 
Form and the fax confirmation sheet must be kept with the subject’s source documentation at the study 
site. Follow-up information should be provided using a new paper SAE Report Form stating that this is a 
follow-up to a previously reported SAE. 
 
Follow-up information provided should describe whether the event has resolved or continues, if and how 
it was treated, and whether the subject continued or withdrew from study participation. Each re-
occurrence, complication, or progression of the original event should be reported as a follow-up to that 
event regardless of when it occurs. 
 
Deaths will be reported to the IRB and Company within 24 hours of becoming aware of the event. This 
information will be communicated by the PI via email. All serious adverse events will be reported to the 
IRB according to their policies, and these events will also be reported to the Company. Non-serious 
adverse events will be reported per their IRB policies and to the Company annually and at the end of the 
study. SAEs will be reported to PI immediately, and if the number of subjects experiencing AEs exceeds 
the pre-determined threshold, the PI will evaluate and determine if an early termination is needed.  


 
Page 28 of 60 
 
7.4. 
Adverse Events of Special Interest  
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 the Company 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) 
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 (e.g., hospitalization). 
7.5. 
Pregnancy Reporting 
To ensure subject safety, each pregnancy occurring while the subject is on study treatment must be 
reported to the IRB and Company within 24 hours of learning of its occurrence using the Serious Adverse 
Event Form. The pregnancy should be followed up to determine outcome, including spontaneous or 
voluntary termination, details of the birth, and the presence or absence of any birth defects, congenital 
abnormalities, or maternal and/or newborn complications.  
 
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 to the 
Company within 24 hours of learning of its occurrence using the Serious Adverse Event Form. 
Depending on local legislation this may require prior consent of the partner. 
7.6. 
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 
 


 
Page 29 of 60 
 
These safety events will be treated in the same manner as adverse events. Special situations will be 
recorded on the Adverse Event page of the CRF. 
 
Any special situation that meets the criteria of a serious adverse event will be recorded on a Serious 
Adverse Event Report Form and be reported to the Company within 24 hours of becoming aware of the 
event. 
 
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 
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. 
8. 
DATA REVIEW AND DATABASE MANAGEMENT 
The project manager at Northwestern will be responsible for grant applications and yearly reports. Data 
will be entered by study coordinators in a central REDCap database based at Northwestern. The 
Dermatology Clinical Trials Unit currently manages both international and national multisite REDCap 
databases. The statistician will meet with the project manager to discuss the progress of the study.  
8.1. 
Site Monitoring 
The Project Manager at Northwestern will monitor the site. The site will also be monitored internally by 
the IRB. 


 
Page 30 of 60 
 
8.2. 
Data Collection 
Demographics, medical information, and data points will be recorded. Once collected by the study staff, 
data for each subject will be transferred to a secure REDCap database.  
 
8.3  
Data Disclosure and Subject Confidentiality 
Each subject will be given a unique identifier code. The subject’s name and code will be maintained on a 
Coded Identifier List (CIL), on a secure research server maintained by Northwestern University.  
  
Subject medical information obtained as a result of this study is considered confidential and disclosure to 
third parties other than the principal investigators and the study team is prohibited. Data generated as a 
result of this study will be available for inspection on request by the Institutional Review Board. Subjects’ 
personal information collected from medical records and paper source documents will be maintained 
within study files that will be kept in a locked room in the Department of Dermatology. Any electronic 
documents will be saved on a secure research server within the Department of Dermatology and 
maintained by Northwestern University.  
9. 
DATA ANALYSIS 
Statistical analysis will be performed by statisticians at Northwestern University. Since this is a pilot 
study, data will be gathered to analyze efficacy to potentially develop a larger trial in the future.  
9.1. 
Analysis Sets 
Definition of Trial Analysis Sets: All subjects who provide informed consent and are registered in the trial 
will be accounted for in the clinical trial report.  
 
‘Modified Intention-to-Treat’ Analysis Set: The primary analysis population will be based on a modified 
intention-to-treat (mITT) population, which is defined as all patients who received at least one dose of the 
treatment. Because the loading dose is given at baseline, this should effectively include all enrolled 
patients.  
9.2. 
Subject Demographics and Other Baseline Characteristics 
Descriptive statistics of demographics and other baseline characteristics will be presented for all subjects. 
Demographics include age, sex, race, ethnicity, and skin type. Other baseline characteristics include 
height, weight, and vital signs, concurrent diagnoses (from medical history and indications for 
concomitant medication), concomitant medications, and previous treatments. Due to the small subject 
population size, we will not adjust for demographics or baseline characteristics during analysis and 
assume that patients will be homogenous in these variables.  


 
Page 31 of 60 
 
9.3. 
Efficacy Analyses 
Primary and secondary endpoints will be analyzed at the time points specified in Section 2.0 
(adjusting for baseline scores) using a paired T-test. The percent change from baseline will also 
be calculated. Data will be plotted across time to visually analyze for trends.  
9.4 
Safety Variables 
Safety will be evaluated by tabulations of adverse events and will be presented with descriptive statistics 
at each visit. The number and percentage of subjects experiencing an AE/SAE will be stratified by system 
organ class, or a preferred term, and severity of the adverse event, and recorded and tabulated overall by 
each sub-strata. Each subject will be counted only once within a system organ class or a preferred term 
using the adverse events with the highest severity within each category. All information pertaining to 
adverse events noted during the study will be listed by subject, detailing verbatim given by the 
investigator, preferred term, system organ class, date of onset, date of resolution, severity, and 
relationship to treatment. A tabulation of Serious Adverse Events (SAEs) will be provided by subject. The 
specific system organ classes and preferred terms analyzed will be those that are reported by at least five 
percent of the subjects. 
9.5   Sample Size Justification 
This is a pilot study and a power analysis is not needed.  
10. 
ETHICAL CONSIDERATIONS. 
10.1. Informed Consent 
This clinical study was designed and shall be implemented and reported in accordance with the ICH 
Harmonized Tripartite Guidelines for Good Clinical Practice, and with the ethical principles presented in 
the Declaration of Helsinki. 
10.2. Consent Forms 
Prior to study entry, a written informed consent must be obtained from the subject (≥ 18 years old) or 
parent/proxy and written assent from subjects 12-17 years of age (Lurie Children’s Hospital IRB requires 
written assent for children over 12 years of age only). A copy of the subject’s signed consent/assent form 
must be retained in the study file. Documentation of consent/assent process will be placed in source 
document for each study subject.  
10.3. Responsibilities of the Investigator and IRB 
A periodic review will be submitted to the IRB at least once per year. The IRB will be notified of 
completion of the study. After study completion or termination, a final report will be provided to 
the IRB to close the study. The investigator will maintain an accurate and complete record of all 
submissions made to the IRB, including a list of all reports and documents submitted. 
  


 
Page 32 of 60 
 
At least once per year, the IRB will review and give written approval in order to continue the 
study. This trial will be conducted in accordance with Good Clinical Practices and the 
Declaration of Helsinki. 
10.4. Publication of Study Protocol and Results 
The Principal Investigator and co-investigators may publish the results of this study in conjunction with 
appropriate scientific and medical personnel of Northwestern University. Information obtained from this 
study may be used for teaching, research, publications, or presentations at scientific meetings. If 
individual results are discussed, subject identities will be protected by using a subject number rather than 
name or other identifying information. 
11. 
PROTOCOL ADHERENCE 
This protocol defines the study objectives, the study procedures and the data to be collected on study 
participants. Additional assessments required to ensure safety of subjects should be administered as 
deemed necessary on a case by case basis. Under no circumstances should an investigator collect 
additional data or conduct any additional procedures for any research related purpose involving any 
investigational drugs. 
 
 
 
 
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an investigator feels a 
protocol deviation would improve the conduct of the study this must be considered a protocol 
amendment, and unless such an amendment is agreed upon by the Company and approved by the IRB and 
health authorities, where required, it cannot be implemented. All significant protocol deviations will be 
recorded and reported.   
11.1. Protocol Amendments 
All changes must be submitted to the IRB. Protocol modifications that impact subject safety or the 
validity of the study must be approved by the IRB and Company. 
12. 
REFERENCES 
Ghosh S, Gensler LS, Yang Z, et al. Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn's 
Disease: An Integrated Analysis of Phase II/III Clinical Development Programs [published correction 
appears in Drug Saf. 2019 Apr 22;:]. Drug Saf. 2019;42(6):751‐768. doi:10.1007/s40264-019-00797-3 
 
Landells I, Marano C, Hsu MC, et al. Ustekinumab in adolescent patients age 12 to 17 years with 
moderate-to-severe plaque psoriasis: results of the randomized phase 3 CADMUS study. J Am Acad 
Dermatol. 2015;73(4):594‐603. doi:10.1016/j.jaad.2015.07.002 
 
Philipp S, Menter A, Nikkels AF, et al. Ustekinumab for the treatment of moderate-to-severe plaque 
psoriasis in paediatric patients (≥ 6 to < 12 years of age): efficacy, safety, pharmacokinetic and biomarker 
results from the open-label CADMUS Jr study [published online ahead of print, 2020 Mar 16]. Br J 
Dermatol. 2020;10.1111/bjd.19018. doi:10.1111/bjd.19018 
 


 
Page 33 of 60 
 
Poulton, C., Gration, D., Murray, K., Baynam, G. and Halbert, A. (2019), Autosomal recessive congenital 
ichthyosis due to homozygous variants in NIPAL4 with a dramatic response to ustekinumab. Pediatr 
Dermatol, 36: 1002-1003. doi:10.1111/pde.13995 
 
Additional references are available upon request


 
 
 
Appendix 1: Schedule of Assessments Flowchart  
 
  
Screening 
Baseline 
Month 1 
Month 3 
Month 5 
Month 7 
Month 9 
Month 11 
Month 13 
 
Week -4 
Week 0  
Week 4  
Week 12 
Week 20 
Week 28 
Week 36 
Week 44 
Week 52/ 
OL end  
Procedures 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Consent  
X 
  
  
  
  
  
  
  
  
Demographics 
X 
  
  
  
  
  
  
  
  
Inclusion/Exclusion 
X 
X 
  
  
  
  
  
  
  
Medical History (baseline or interim) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Meds 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Event Assessment 
  
X 
X 
X 
X 
X 
X 
X 
X 
Full physical exam, including skin 
X 
X 
 
 
 
 
 
 
X 
Full Skin Examination 
 X 
 X 
X 
X 
X 
X 
Vital Signs (incl. weight) 
X 
X 
X 
 X 
X 
X 
X 
X 
X 
Height 
X 
  
  
  
  
  
  
  
X 
Severity evaluations  
X 
X 
X 
X  
X 
X 
X 
X 
X 
Venipuncture 
X 
  
  
  
  
  
  
  
X 
Saliva collection and DNA extraction  
X 
  
  
  
  
  
  
  
  
Collection of PAX RNA and protein   
X 
  
  
  
  
  
  
  
X 
Tape Strip collection 
  
X 
  
  
  
X 
  
  
X 
Microbiome collection  
  
X 
  
  
  
X 
  
  
X 
TEWL 
  
X 
X 
X 
X 
X 
X 
X 
X 
NRS Pain and Itch 
  
X 
X 
X  
X 
X 
X 
X 
X 
PROMIS Itch (if >2 on NRS, 
otherwise subject does not need to 
complete) 
  
X 
  
  
X 
  
  
X 
DLQI/CDLQI and IFTB 
  
X 
  
  
  
 X 
  
  
X 
STIGMA questionnaire 
  
X 
  
  
X 
  
  
X 
Subject severity self-assessment 
  
X 
X 
X 
X 
X 
X 
X 
X 
Photography 
  
X 
  
  
  
X 
  
  
X 
QuantiFERON®-TB gold 
X 
  
  
  
  
  
  
  
X 
Hep B/C, HIV testing  
X 
  
  
  
  
  
  
  
Chemistry, hematology testing 
X 
 
 
 
 
 
 
 
X 
Urine HCG (if applicable) 
X 
 X 
X 
X 
X 
X 
X 
X 
X 
Injection 
  
X 
X 
 X 
X 
X 
X 
X 


 
 
 
**If subject continues to LTE, procedures above will be followed which include injection of study drug. If not continuing to LTE, 
then subject will follow procedures for OL End in the table preceding. 
  
Month 13 
 
Month 15 
Month 17 
 
Month 19 
Month 21 
Month 23 
Month 25 
 
 Week 52/LTE Start** 
Week 60 
Week 68 
Week 76 
Week 84 
Week 92 
Week 96/End of LTE 
Procedures 
Visit 9 
Visit 10 
Visit 11 
Visit 12 
Visit 13 
Visit 14 
Visit 15 
Consent  
  
 
  
  
  
  
  
Demographics 
  
 
  
  
  
  
  
Inclusion/Exclusion 
  
 
  
  
  
  
Medical History (baseline or 
interim) 
X 
X 
X 
X 
X 
X 
X 
Concomitant Meds 
X 
X 
X 
X 
X 
X 
X 
Adverse Event Assessment 
X 
X 
X 
X 
X 
X 
X 
Full physical examination, 
including skin 
X 
 
 
 
 
 
X 
Full Skin Examination 
X 
X 
X 
 X 
 X 
 
Vital Signs (incl. weight) 
X 
X 
X 
X 
 X 
 X 
X 
Height 
X 
  
  
  
  
X 
Severity evaluations  
X 
X 
X 
X 
 X 
 X 
X 
Venipuncture 
X 
  
  
X 
  
  
X 
Saliva collection and DNA 
extraction  
  
  
  
  
  
  
 
Collection of PAX RNA and 
protein   
X 
  
  
  
  
X 
Tape Strip collection 
X 
 
X 
  
  
X 
Microbiome collection  
X 
 
X 
  
  
X 
TEWL 
X 
X 
X 
X 
X  
X  
X 
NRS Pain and Itch 
X 
X 
X 
X 
X  
X  
X 
PROMIS Itch (if >2 on NRS, 
otherwise subject does not 
need to complete) 
X 
 
X 
 
X 
DLQI/CDLQI and IFTB 
X 
 
X 
  
X 
STIGMA questionnaire 
X 
 
X 
 
  
X 
Subject severity self-
assessment 
X 
X 
X 
X 
 X 
X 
X 
Photography 
X 
  
X 
  
  
X 
QuantiFERON®-TB gold 
X 
  
  
  
  
X 
Hep B/C, HIV testing  
  
  
  
  
 
Chemistry, hematology testing 
X 
 
 
 
 
 
X 
Urine HCG (if applicable) 
X 
X 
X 
X 
X 
X 
X 
Injection 
 X 
X 
X 
X 
X 
X  
 


 
 
 
Appendix 2: Ichthyosis Severity Score (ISS) 
What is the ichthyosis scoring system (ISS)?  
  
The ISS is a comprehensive and user-friendly instrument for assessing the extent 
and clinical severity of ichthyosis. It aims to be a validated tool that will be 
adopted by the FDA. We addressed several of the FDA’s concerns and 
specifications through developing new descriptors for severity and developing two 
separate scoring systems for patients under 8 years of age and patients older than 8 
years in order to take into account differences in relative body proportions.   
  
Scores will grade: 1) scale severity and 2) erythema.   
 
Scoring overview  
Scoring for scale (0-4) should be done for the entire region. It should be an 
average of affected areas, not the worst score for that region.   
  
Half-points are allowed. 2 limbs=one body region.  
  
Erythema score (0-4) for a particular region should be the worst score for that 
region because erythema can be obscured by scale.   
  
Body regions scored for each patient:  
 
Each region will be scored separately  
 
 
 
 
 
 
Anatomical definitions of body parts:  
  
1. 
Head and neck: Scalp, face, neck  
2. 
Trunk: Groin and chest/abdomen/back  
3. 
Upper extremities: Elbow and palms  
4. 
Lower Extremities: Knees and soles   


 
 
 
Head and neck   
• 
Head  
o Face: extends from the forehead to the chin and includes the mouth, nose, cheeks, 
eyes, and ears. It excludes the neck. (1/3)  
o Scalp: extends from the junction of forehead skin to the occiput (back of head). It 
excludes the face. (1/3)  
• 
Neck: extends from the mandible to the attachment of the sternocleidomastoid at the 
clavicle. It also includes the back of the neck, which extends from the C1 vertebrae to the 
trapezius muscle. (1/3)  
  
Torso – Includes back, chest, abdomen, and groin  
• 
Chest, abdomen, groin: extends from one anterior axillary fold to the other and from the 
clavicles to the anterior iliac spine   
• 
Back: extends laterally from one posterior axillary fold to the other and from T1-S1.  It 
excludes posterior arms and neck.  
  
Upper extremities: extends from the acromial process to the fingers and includes the anterior 
axillary fold and antecubital fossa.  (It excludes the elbow and any portion of the trunk that may 
be visible.)  
  
Lower extremities: extends from the superior iliac spine to the toes and includes the buttocks.  
  
Elbows and knees  
• 
Elbows: Includes attachment of the humerus to the proximal radius and ulna. It excludes 
antecubital fossa.   
• 
Knees: Includes attachment of the femur to the tibia and patella. It excludes the popliteal 
fossa.   
  
Palms: extends from the tip of the phalanges to the carpal bones (wrist joint) and includes the 
area between the five phalanges. It includes glabrous skin.  
  
Soles: extends from the tip of the toes to the calcaneus (heel). It includes glabrous skin.  By 
contrast, because erythema can be obscured by scale, the erythema score for a particular 
region should be the worst score for that region.   
  
  
  
  


 
 
 
  
 
 
 
 
 
Scale descriptors for all sites but the palms and soles  
0  
Normal skin; no perceptible scale, and no loss of normal skin markings  
1  
Normal skin intermixed with small scales or areas of minimally 
shiny/waxy/thickened skin and/or partial loss of normal skin markings  
2  
Several areas of scaling upon a background of mildly thickened skin often with 
some loss of normal skin markings  
3  
Confluent scales with or without focal areas of thick, piled scales and moderately 
thickened skin  
4  
Extensive areas of confluent, primarily thick, piled scale and severely thickened skin 
  
 
 
Scale descriptors for the palms and soles  
0  
Normal skin; no perceptible scale or accentuated skin markings  
1  
Minimal, confluent or focal thickening with continued visibility of normal skin 
lines. May have minimal desquamative scale.   
2  
Mild, confluent or focal thickening that at least partially obscures skin lines. May 
have mild desquamative scale, some accentuation of coarse skin lines and/or mild 
fissuring.   
3  
Moderate, confluent or focal piled or desquamative scale or yellow thickening. 
Often with accentuated coarse skin lines with or without fissures.   
4  
Thick, confluent or focal yellow piled scale and/or severe desquamative scale with 
or without fissures.   


 
 
 
 UNDER 8 YEARS OLD 
 
 
8 YEARS AND OLDER 
 
 
 


 
 
 
Appendix 3: DERMATOLOGY LIFE QUALITY INDEX (DLQI) 
Site  No: 
 
 
 
 
 
 
 
 
 
 
Date 
: 
 
 
 
 
 
 
 
 
 
Score: 
Visit Number: 
 
 
 
 
 
 
 
 
 
 
The aim of this questionnaire is to measure how much your skin problem has affected your life OVER 
THE LAST WEEK.  Please tick  one box for each question. 
 
1. 
Over the last week, how itchy, sore,  
 
 
 
Very much 
 
 
painful or stinging has your skin   
 
 
A lot 
 
 
 
been?   
 
 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
 
Not at all 
 
 
2. 
Over the last week, how embarrassed 
 
 
Very much 
 
 
or self conscious have you been because   
 
A lot 
 
 
 
of your skin? 
 
  
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
 
Not at all 
 
 
3. 
Over the last week, how much has your  
 
 
Very much 
 
 
skin interfered with you going 
 
  
 
 
A lot 
 
 
 
shopping or looking after your home or   
 
A little  
 
 
garden?        
 
 
 
 
 
 
Not at all 
 
 
Not relevant      
 
4. 
Over the last week, how much has your  
 
 
Very much 
 
 
skin influenced the clothes  
 
 
 
 
A lot 
 
 
 
you wear? 
 
 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
 
Not at all 
 
 
Not relevant      
 
5. 
Over the last week, how much has your  
 
 
Very much 
 
 
skin affected any social or  
 
 
 
 
A lot 
 
 
 
leisure activities? 
 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
 
Not at all 
 
 
Not relevant      
 
 
 
6. 
Over the last week, how much has your  
 
 
Very much 
 
 
skin made it difficult for   
 
 
 
A lot 
 
 
 
you to do any sport? 
 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
 
Not at all 
 
 
Not relevant      
 
7. 
Over the last week, has your skin prevented 
 
 
Yes 
 
 
 
you from working or studying?  
 
 
No 
 
 
 
Not relevant      
 
 
 
If "No", over the last week how much has   
 
A lot 
 
 
 
your skin been a problem at  
 
 
 
 
A little  
 
 
work or studying? 
 
 
 
 
 
Not at all 
 


 
 
 
 
8. 
Over the last week, how much has your  
 
 
Very much 
 
 
skin created problems with your   
 
 
A lot 
 
 
 
partner or any of your close friends 
 
 
 
A little  
 
 
or relatives?  
 
 
 
 
 
 
Not at all 
 
 
Not relevant      
 
9. 
Over the last week, how much has your  
 
 
Very much 
 
 
skin caused any sexual   
 
 
 
A lot 
 
 
 
difficulties? 
 
 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
 
Not at all 
 
 
Not relevant      
 
10. 
Over the last week, how much of a  
 
 
 
Very much 
 
 
problem has the treatment for your 
 
 
 
A lot 
 
 
 
skin been, for example by making  
 
 
A little  
 
 
your home messy, or by taking up time?   
 
Not at all 
 
 
Not relevant      
 
Please check you have answered EVERY question. Thank you.  
AY Finlay, GK Khan, April 1992 www.dermatology.org.uk, this must not be copied without the permission of the authors. 
 
 
 


 
 
 
Appendix 4: CHILDREN'S DERMATOLOGY LIFE QUALITY INDEX (CDLQI) 
Name: 
 
 
 
 
Diagnosis: 
 
 
 
 
CDLQI  
Age: 
 
 
 
 
 
 
 
 
 
 
SCORE: 
Address:  
 
 
Date: 
 
The aim of this questionnaire is to measure how much your skin problem has affected you OVER THE LAST WEEK. 
Please tick  one box for each question. 
 


 
 
 
Appendix 5: CHILDREN'S DERMATOLOGY LIFE QUALITY INDEX (CDLQI) 
Cartoon  
 
Separate worksheet for subjects of a young age who would prefer to complete the cartoon 
version of the questionnaire. 
 
 
 
 


 
 
 
Appendix 6: NRS Itch/Pain and PROMIS Itch Scores 
 
Numerical Rating Scale (NRS) for Pruritus (over past 3 days and nights) 
 
 
 
 
Numerical Rating Scale (NRS) for Pain (over past 3 days and nights) 
 
 
No pain 
 
 
 
 
 
Worst imaginable pain 
 
 
 
 


 
 
 
 
PROMIS Itch Scores 
 
 
 
 


 
 
 
 
 


 
 
 
Appendix 7: Stigma Questionnaire 
 
STIGMA-Child Questionnaire 
NQSTGped03c 
Lately (in 
the last 1-2 
months) 
Because of my condition, others 
my age avoided me. 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
NQSTGped04c 
Lately (in 
the last 1-2 
months) 
 Because of my condition, I felt left 
out of things. 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
NQSTGped06c 
Lately (in 
the last 1-2 
months) 
Because of my condition, others 
my age made fun of me. 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
NQSTGped07c 
Lately (in 
the last 1-2 
months) 
Because of my condition, I felt 
embarrassed when I was in front of 
others my age 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
NQSTGped10c 
Lately (in 
the last 1-2 
months) 
 Because of my condition, I was 
treated unfairly by others my age. 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
DermSTGped0
7 
Lately (in 
the last 1-2 
months) 
Because of my condition, others 
my age didn't see the good things 
about me.  
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
NQSTGped17c 
Lately (in 
the last 1-2 
months) 
Because of my condition, I felt 
different from others my age. 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
NQSTGped19c 
Lately (in 
the last 1-2 
months) 
I avoided making new friends to 
avoid talking about my condition. 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
NQSTGped01c 
Lately (in 
the last 1-2 
months) 
Because of my condition, others 
my age bullied me.  
1 = Never 
2 = Rarely 
3 = Sometimes 


 
 
 
4 = Often 
5 = Always 
NQSTGped02c 
Lately (in 
the last 1-2 
months) 
Because of my condition, others 
my age seemed uncomfortable with 
me 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
NQSTGped05c 
Lately (in 
the last 1-2 
months) 
Because of my condition, others 
my age were mean to me. 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
NQSTGped08c 
Lately (in 
the last 1-2 
months) 
Because of my condition, others 
my age tended to stare at me. 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
NQSTGped09c 
Lately (in 
the last 1-2 
months) 
Because of my condition, I worried 
about what others my age thought 
about me. 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
NQSTGped11c 
Lately (in 
the last 1-2 
months) 
I was unhappy about how my 
condition affected my appearance. 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
NQSTGped14c 
Lately (in 
the last 1-2 
months) 
Because of my condition, I worried 
that I made life harder for my 
parents or guardians. 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
NQSTGped15c 
Lately (in 
the last 1-2 
months) 
 I felt embarrassed about my 
condition 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
NQSTGped20c 
Lately (in 
the last 1-2 
months) 
I lost friends by telling them that I 
have this condition. 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
DermSTGped0
1 
Lately (in 
the last 1-2 
months) 
Because of my condition, people 
thought I wasn't clean. 
1 = Never 
2 = Rarely 
3 = Sometimes 


 
 
 
4 = Often 
5 = Always 
DermSTGped0
2 
Lately (in 
the last 1-2 
months) 
Because of my condition, others 
avoided touching me (ex: holding 
my hand). 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
DermSTGped0
3 
Lately (in 
the last 1-2 
months) 
I wished my condition wasn't 
visible to other people. 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
DermSTGped0
4 
Lately (in 
the last 1-2 
months) 
 I felt embarrassed when others my 
age asked about my condition. 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
DermSTGped0
8 
Lately (in 
the last 1-2 
months) 
Because of my condition, I couldn’t 
wear the clothing/shoes I wanted to 
wear. 
1 = Never 
2 = Rarely 
3 = Sometimes 
4 = Often 
5 = Always 
 
STIGMA-Proxy 
QuestionnaireNQSTGprox03 
Lately (in the 
last 1-2 
months) 
Other children avoided my child 
because of his/her condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
NQSTGprox04 
Lately (in the 
last 1-2 
months) 
My child felt left out of things 
because of his/her condition 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
NQSTGprox06 
Lately (in the 
last 1-2 
months) 
Other children made fun of my 
child because of his/her 
condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 


 
 
 
NQSTGprox07 
Lately (in the 
last 1-2 
months) 
My child felt embarrassed in 
front of other children because 
of his/her condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
NQSTGprox10 
Lately (in the 
last 1-2 
months) 
My child was treated unfairly by 
other children because of his/her 
condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
DermSTGprox07 
Lately (in the 
last 1-2 
months) 
Other children didn't see the 
good things about my child 
because of his/her condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
NQSTGprox17 
Lately (in the 
last 1-2 
months) 
My child felt different from other 
children because of his/her 
condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
NQSTGprox19 
Lately (in the 
last 1-2 
months) 
My child avoided making new 
friends to avoid talking about 
his/her condition 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
NQSTGprox01 
Lately (in the 
last 1-2 
months) 
Other children bullied my child 
because of his/her condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
NQSTGprox02 
Lately (in the 
last 1-2 
months) 
Other children seemed 
uncomfortable with my child 
because of his/her condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 


 
 
 
NQSTGprox05 
Lately (in the 
last 1-2 
months) 
Other children were mean to my 
child because of his/her 
condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
NQSTGprox08 
Lately (in the 
last 1-2 
months) 
Other children tend to stare at 
my child because of his/her 
condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
NQSTGprox09 
Lately (in the 
last 1-2 
months) 
My child worried what other 
children thought of him/her 
because of his/her condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
NQSTGprox11 
Lately (in the 
last 1-2 
months) 
My child was unhappy about 
how this condition affected 
his/her appearance. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
NQSTGprox14 
Lately (in the 
last 1-2 
months) 
My child worried that he/she 
made life harder for us (parents 
or guardians) because of his/her 
condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
NQSTGprox15 
Lately (in the 
last 1-2 
months) 
My child felt embarrassed about 
his/her condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
NQSTGprox20 
Lately (in the 
last 1-2 
months) 
My child lost friends by telling 
them that he/she has this 
condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 


 
 
 
DermSTGprox01 
Lately (in the 
last 1-2 
months) 
Others thought my child wasn’t 
clean because of his/her 
condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
DermSTGprox02 
Lately (in the 
last 1-2 
months) 
Others avoided touching my 
child (ex: holding his/her hand) 
because of his/her condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
DermSTGprox03 
Lately (in the 
last 1-2 
months) 
My child wished his/her 
condition wasn’t visible to other 
people my age. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
DermSTGprox04 
Lately (in the 
last 1-2 
months) 
My child felt embarrassed when 
other children asked about 
his/her condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
DermSTGprox08 
Lately (in the 
last 1-2 
months) 
My child couldn’t wear the 
clothing/shoes he/she wanted to 
wear because of his/her 
condition. 
1 = Never 
2 = Rarely 
3 = 
Sometimes 
4 = Often 
5 = Always 
 
 
 


 
 
 
Appendix 8: Photography Protocol 
Prior to photography: Have patient remove all wristbands and jewelry. Bras and underwear do 
not need to be removed. Photography should be performed on blue background. 
 
This protocol is a general outline to follow to capture each body area. Per this protocol, 
only assessment area/target lesions should be photographed.  
 
PHOTOGRAPHS 
1. First, take a photograph of a card with subject ID, visit number, date of visit. 
 
2. Take photo of face and shoulders with eyes open. 
 
3. Take photo with body perpendicular to backdrop, left ear, eyes open. 
 
4. Take photo with body perpendicular to backdrop, right ear, eyes open. 
 
5. Take photo of shoulders and back of head. 
 
6. Take photo of scalp directly perpendicular to camera, capturing crown and tip of nose. 
 
7. Take photo of abdomen to neck, capturing drape. 


 
 
 
 
8. With patient's arms raised and hands behind head, take photo from elbows to drape. 
 
9. Take photo of back to neck, capturing drape. 
 
10. Have patient put arm parallel to floor, and bring arm back to expose flank.  Rest closed fist on 
abdomen.  Left side. 
 
11. Have patient put arm parallel to floor, and bring arm back to expose flank.  Rest closed fist on 
abdomen.  Right side. 
 
12. Raise drape as high as possible, take photo toes to drape. 
 
13. Zoom in to capture upper legs from knee to drape in more detail. 
 
14. Zoom in to capture lower legs from knee to foot in more detail. 


 
 
 
 
15. Raise drape as high as possible, take photo heels to drape. 
 
 
16. Zoom in to capture upper legs from posterior knee to drape in more detail. 
 
17. Zoom in to capture lower legs from posterior knee to foot in more detail.  
 
18. Have patient kneel on block or chair draped with blue cloth, take photo of soles. 
 
19. Have patient stand on blue cloth, take photo of dorsal feet. 


 
 
 
 
20. Take photo of palms with fingers flat, forearms together and fingers evenly spaced. 
 
21.  Flip hands over, take photo of dorsal hands with thumbs touching and fingers evenly spaced. 
 
22. Bring finders together take photo capturing nails and fingertips.  Pose is relaxed, not tightly 
clenched. 
 
 
 
 


 
 
 
Appendix 9: Ichthyosis Severity Self-Assessment 
 
Surface Area Affected by Ichthyosis:   
Using the drawing below, please list the numbers that correspond to which areas of your skin are 
affected. 
 
 
 
Intensity of Symptoms:  
Please rate your skin symptoms according to the following scale 
0 = none 
1 = mild 
2 = moderate 
3 = severe 
 
Symptom 
Intensity (0-3) 
Scaling / Flaking  
 
Redness 
 
Tightness 
 
Pain 
 
Itch 
 
 
 
 
 
 


 
 
 
Appendix 10: Ichthyosis Financial and Time Burden 
The following questions ask about different periods of time. Please think about the past 4 
weeks when answering. There are no right or wrong answers. Please answer each question 
as spontaneously as possible by checking the box with the answer that is closest to your 
opinion. 
 
1. Does your ichthyosis cause you to lose sleep (because of itching, pain, lack of time due to 
caring for ichthyosis, etc.)?  
 
Not at all 
      A little bit                     Somewhat                   Quite a bit                Very much 
    
   
 
  
 
 
  
 
 
  
 
          
  
 
 
2. Over a typical week, on how many nights have you lost sleep because of your ichthyosis?  
 
Not applicable          1-2 days                    3-4 days                       5-6 days                 Every day 
    
   
 
 
  
 
 
  
 
 
  
 
          
  
 
 
3. Because of your ichthyosis, do you feel fatigue during the day? 
 
Not at all 
      A little bit                     Somewhat                   Quite a bit                Very much 
    
   
 
  
 
 
  
 
 
  
 
          
  
 
 
4. Over a typical week, on how many days do you feel fatigue because of your ichthyosis? 
 
Not applicable          1-2 days                    3-4 days                       5-6 days                 Every day 
    
   
 
 
  
 
 
  
 
 
  
 
          
  
 
 
5. Over a typical week, on how many days was housework performed specifically for your 
ichthyosis (vacuuming around the house, etc.)? 
 
Not applicable          1-2 days                    3-4 days                       5-6 days                  Every day 
    
   
 
 
  
 
 
  
 
 
  
 
          
  
 
 
6. Because of your ichthyosis, do you feel that you have to do extra steps or feel that there is 
extra work involved when you do housework? 
 
Not at all 
      A little bit                     Somewhat                   Quite a bit                Very much 
    
   
 
  
 
 
  
 
 
  
 
          
  
 
7. Over a typical week, on how many days did you or others do your laundry because of 
your ichthyosis? 


 
 
 
 
Not applicable          1-2 days                    3-4 days                       5-6 days                   Every day 
    
   
 
 
  
 
 
  
 
 
  
 
          
  
 
 
8. Because of your ichthyosis, do you feel that you have to do extra steps or feel that there is 
extra work involved when you do laundry? 
 
Not at all 
      A little bit                     Somewhat                   Quite a bit                Very much 
    
   
 
  
 
 
  
 
 
  
 
          
  
 
 
9. Does your ichthyosis affect your choice of clothing to wear (cannot wear black clothing, 
certain colors or fabrics, etc.)? 
 
Not at all 
      A little bit                     Somewhat                   Quite a bit                Very much 
    
   
 
  
 
 
  
 
 
  
 
          
  
 
 
10. Because of your ichthyosis, do you have to throw away or replace clothing (socks, 
underwear, etc.) due to factors (moisturizers, excess washing, etc.) related to your 
ichthyosis? 
 
Not at all 
      A little bit                     Somewhat                   Quite a bit                Very much 
    
   
 
  
 
 
  
 
 
  
 
          
  
 
 
11. How often do you have to throw away or replace clothing (socks, underwear, etc.) due 
to factors (moisturizers, excess washing, etc.) related to your ichthyosis? 
 
Not applicable      Every year             Every 2-3 months 
   Every month              Every week 
    
   
 
  
 
 
  
 
 
  
 
          
 
 
 
12. Are your daily activities or work impacted by hot weather due to factors relating to 
your ichthyosis?  
 
Not at all 
      A little bit                     Somewhat                   Quite a bit                Very much 
    
   
 
  
 
 
  
 
 
  
 
          
  
 
 
13a. On a typical day, how much time did you spend bathing/showering and scrubbing skin 
because of your ichthyosis? 
 
<30 minutes        1 hour  
 
      1.5 hours  
        2 hours         
   >2 hours 
    
   
 
  
 
 
  
 
 
  
 
          
  


 
 
 
 
 
13b. On a typical day, how much time did you spend caring for your skin (moisturizing, 
trimming skin, etc.) because of your ichthyosis? 
 
<15 minutes        30 minutes.               45 minutes  
         1 hour 
       
   75 minutes 
    
   
 
  
 
 
  
 
 
  
 
          
  
 
 
13c. Overall, on a typical day, how much time do you spend caring for your skin (include 
bathing/showering, scrubbing skin, moisturizers, etc.) because of your ichthyosis? 
 
<30 minutes        1 hour  
 
      1.5 hours  
        2 hours         
   >2 hours 
    
   
 
  
 
 
  
 
 
  
 
          
  
 
 
14. Based on how severe your ichthyosis is now, if you had enough time, how many times a 
day would you apply moisturizer over your whole body? 
 
     0 
                        1                                  2                                 3                             > 4 
    
   
 
  
 
 
  
 
 
  
 
          
  
 
 
15. In a typical week, how often do you or others have to clean your bed (brushing/shaking 
off skin, etc.) or change your sheets due to your ichthyosis? 
 
     0 
                        1                                  2                                 3                             > 4 
    
   
 
  
 
 
  
 
 
  
 
          
  
 
 
16. Does your ichthyosis interfere with your performance in work/school? 
  
Not at all 
      A little bit                     Somewhat                   Quite a bit                Very much 
    
   
 
  
 
 
  
 
 
  
 
          
  
 
 
17. Do you feel that because of your ichthyosis, you spend too much money or are burdened 
financially? 
 
Not at all 
      A little bit                     Somewhat                   Quite a bit                Very much 
    
   
 
  
 
 
  
 
 
  
 
          
  
 
 
 

ICF_001.pdf: 
 
 
 
 
 
 
 
 
 
Adult Consent 
Version Date: 8NOV2022 
Page 1 of 19 
 
Affix Patient Label Here 
Note:  Label required for cover page, but is optional for 
other pages if the following information is provided: 
Patient Name: 
MRN: 
Approved by IRB on: 03/20/2023 
IRB Approval Expires on: 02/29/2024 
Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
 
Adult Consent to Take Part in a Research Study 
 
Name of Study: An Open-Label and Long-Term Extension Study to Evaluate the Efficacy and 
Safety of Ustekinumab in the Treatment of Patients with Ichthyoses. 
Drug and Funding Support Provided by: Janssen Scientific Affairs, LLC (Company) 
Name of Researcher (referred to as the study doctor): Amy S. Paller, M.D. 
 
This consent form describes a research study for which you might qualify at Ann & Robert H. 
Lurie Children's Hospital of Chicago (“Lurie Children’s”) and NU/NMH. Research studies help 
us learn more about conditions and develop new treatments. Taking part in a research study is 
voluntary. It is your choice to take part in this research study. Please read this consent form and 
ask questions about anything you do not understand. You may talk to others such as your family 
or healthcare providers before you decide to take part in this study. The study staff will also 
explain the study to you and answer any questions that you may have. Your decision will not 
affect your regular care.  
 
Key Study Information: 
 
What are the purpose and goals of this study? 
You are being asked for your consent to take part in this study because you have been diagnosed 
with ichthyosis (severe and lasting problems with dry skin). This research is being done to look 
at safety and how well ustekinumab works in the treatment of individuals with ichthyosis. 
Ustekinumab is an investigational drug. "Investigational" means this drug has not been approved 
by the United States Food and Drug Administration (FDA) for treatment of ichthyosis. 
 
Ichthyosis is a lifelong genetic disorder that may cause thickening, scaling and inflammation 
(redness, heat, swelling and pain) of the skin. Ichthyosis is commonly associated with impaired 
quality of life, social exclusion due to an altered appearance, itchiness, discomfort, and 
functional limitations. Therapy for ichthyosis is supportive, focused on clearing skin scales, and 
is often time-consuming for patients. Currently, there are no standard therapies based on what 
causes ichthyosis.  
 
The investigational drug used in this study is called ustekinumab. Ustekinumab is a monoclonal 
antibody. An antibody is a type of protein that helps protect the body against foreign materials 
such as germs. A monoclonal antibody is a laboratory-made substance that recognizes a specific 
region of a protein. Ustekinumab regulates proteins in the body called IL-12 and IL-23. 
Abnormal regulation of IL-12 and IL-23 has been associated with a variety of autoimmune 
diseases (when your body attacks normal cells) including psoriasis. Recent studies have shown 
that a specific protein called interleukin-23 (IL-23) is increased in the skin of ichthyosis. IL-23 is 
known to be increased in another skin disorder with redness and scaling called psoriasis. 
Reducing IL-23 levels in skin with ustekinumab has been found to markedly improve psoriasis. 
 
This study seeks to understand if ustekinumab works better than standard treatment for 
ichthyosis. It also seeks to learn about the safety of ustekinumab in those with ichthyosis. 


 
 
 
 
 
 
 
 
 
Adult Consent 
Version Date: 8NOV2022 
Page 2 of 19 
 
Affix Patient Label Here 
Note:  Label required for cover page, but is optional for 
other pages if the following information is provided: 
Patient Name: 
MRN: 
Approved by IRB on: 03/20/2023 
IRB Approval Expires on: 02/29/2024 
Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
 
We expect about 15-20 people here at Lurie Children’s Hospital/Northwestern University will be 
in this research study. 
 
What are the main procedures of this study?   
We expect that you will be in this research study for about 2 years (25 months). There will be a 
screening period, an initial 13 month open-label (OL) phase in which you will receive 
ustekinumab, followed by a 12 month long-term extension (LTE) to assure long-term safety 
during which you will continue to receive ustekinumab. You will have approximately 15 visits to 
the study site. 
 
Each subject will receive ustekinumab at Baseline (Week 0) and Month 1 (Week 4), Month 3 
(Week 12), Month 5 (Week 20), Month 7 (Week 28), Month 9 (Week 36), and Month 11 (Week 
44). During the LTE, subjects will receive injections every 8 weeks for one year: Month 13 
(Week 52), Month 15 (Week 60), Month 17 (Week 68), Month 19 (Week 76), Month 21 (Week 
84), and Month 23 (Week 92). Subjects will come back in for a follow-up visit at Month 25 
(Week 96) for an end of study visit (no drug administration).    
 
What are the important risks and side effects from this study? 
The most common (≥ 3%) harmful reactions associated with ustekinumab in patients being 
treated for psoriasis were nasopharyngitis swelling of the nasal passages and the back of the 
throat), upper respiratory tract infection, headache, and fatigue. 
 
What are the benefits from this study? 
Your ichthyosis may improve from taking part in this study. The information learned from this 
study may also help others in the future with ichthyosis.  
 
Details of Taking Part in this Study: 
 If I agree to take part in this study, what would I need to do? 
You will be asked to come to these study sites for the study visits. Any visits that do not require 
an injection of the study drug may occur in the Northbrook location per your request. All study 
visits requiring an injection will need to occur at the downtown location. 
• Ann & Robert H. Lurie Children’s Hospital of Chicago, 225 E. Chicago Ave, Chicago, 
IL 60611 
o Outpatient Clinic, 3rd Floor; or 
o Clinical Research Unit (CRU), 19th Floor 
• Ann & Robert H. Lurie Children’s Hospital of Chicago Outpatient Center in Northbrook, 
1131 Techny Rd., Northbrook, IL 60062 
 
The below tables outline the study procedures that will be conducted at each visit.  
 
 
 
 


 
 
 
 
 
 
 
 
 
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Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
 
  
Screening 
Baseline 
Month 
1 
Month 
3 
Month 5 
Month 7 
Month 9 
Month 
11 
Month 13 
 
Week -4 
Week 0  
Week 
4  
Week 
12 
Week 
20 
Week 
28 
Week 36 
Week 44 
Week 52/ 
OL end  
Procedures 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Consent  
X 
  
  
  
  
  
  
  
  
Demographics 
X 
  
  
  
  
  
  
  
  
Inclusion/Exclusion 
X 
X 
  
  
  
  
  
  
  
Medical History  
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Meds 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Event Assessment 
  
X 
X 
X 
X 
X 
X 
X 
X 
Full complete physical exam, 
including skin exam 
X 
X 
 
 
 
 
 
 
X 
Full skin exam 
 X 
 X 
X 
X 
X 
X 
Vital Signs (incl. weight) 
X 
X 
X 
 X 
X 
X 
X 
X 
X 
Height 
X 
  
  
  
  
  
  
  
X 
Severity evaluations  
X 
X 
X 
X  
X 
X 
X 
X 
X 
Venipuncture 
X 
  
  
  
  
  
  
  
X 
Saliva collection  
X 
  
  
  
  
  
  
  
  
Blood collection 
X 
  
  
  
  
  
  
  
X 
Tape Strip collection 
  
X 
  
  
  
X 
  
  
X 
Microbiome collection  
  
X 
  
  
  
X 
  
  
X 
Skin water loss 
measurements 
  
X 
X 
X 
X 
X 
X 
X 
X 
Pain and Itch scores 
  
X 
X 
X  
X 
X 
X 
X 
X 
PROMIS Itch (if >2 on NRS, 
otherwise subject does not 
need to complete) 
  
X 
  
  
X 
  
  
X 
Patient reported outcomes 
  
X 
  
  
  
 X 
  
  
X 
Subject severity self-
assessment 
  
X 
X 
X 
X 
X 
X 
X 
X 
Photography 
  
X 
  
  
  
X 
  
  
X 
QuantiFERON®-TB gold 
X 
  
  
  
  
  
  
  
X 
Hematology and Chemistry 
testing 
X 
 
 
 
 
 
 
 
X 
Hep B/C, HIV testing  
X 
  
  
  
  
  
  
  
Urine HCG (if applicable) 
X 
 X 
X 
X 
X 
X 
X 
X 
X 
Injection 
  
X 
X 
 X 
X 
X 
X 
X 


 
 
 
 
 
 
 
 
 
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Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
 
 
 
 
  
Month 13 
 
Month 15 
Month 17 
 
Month 19 
Month 21 
Month 23 
Month 25 
 
 Week 52/LTE 
Start** 
Week 60 
Week 68 
Week 76 
Week 84 
Week 92 
Week 96/ 
End of LTE 
Procedures 
Visit 9 
Visit 10 
Visit 11 
Visit 12 
Visit 13 
Visit 14 
Visit 15 
Consent  
  
 
  
  
  
  
  
Demographics 
  
 
  
  
  
  
  
Inclusion/Exclusion 
  
 
  
  
  
  
Medical History  
X 
X 
X 
X 
X 
X 
X 
Concomitant Meds 
X 
X 
X 
X 
X 
X 
X 
Adverse Event 
Assessment 
X 
X 
X 
X 
X 
X 
X 
Full complete 
physical exam, 
including skin 
X 
 
 
 
 
 
X 
Full skin exam 
X 
X 
X 
 X 
 X 
 
Vital Signs (incl. 
weight) 
X 
X 
X 
X 
 X 
 X 
X 
Height 
X 
  
  
  
  
X 
Severity evaluations  
X 
X 
X 
X 
 X 
 X 
X 
Venipuncture 
X 
  
  
X 
  
  
X 
Saliva collection   
  
  
  
  
  
  
 
Blood collection   
X 
  
  
  
  
X 
Tape Strip collection 
X 
 
X 
  
  
X 
Microbiome collection  
X 
 
X 
  
  
X 
Skin water loss 
measurements 
X 
X 
X 
X 
X  
X  
X 
Pain and Itch Scores 
X 
X 
X 
X 
X  
X  
X 
PROMIS Itch (if >2 
on NRS, otherwise 
subject does not 
need to complete) 
X 
 
X 
 
X 
Patient reported 
outcomes 
X 
 
X 
  
X 
Subject severity self-
assessment 
X 
  
X 
  
  
X 
Photography 
X 
  
  
  
  
X 
QuantiFERON®-TB 
gold 
X 
  
  
  
  
X 
Hematology and 
Chemistry testing 
X 
 
 
 
 
 
X 
Hep B/C, HIV testing  
 
 
 
Urine HCG(if 
applicable) 
 X 
X 
X 
X 
X 
X  
 
Injection 
X 
X 
X 
X 
X 
X 
 


 
 
 
 
 
 
 
 
 
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IRB Approval Expires on: 02/29/2024 
Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
 
Screening/Baseline Visit 
The Screening and Baseline visit procedures may be combined on the same day if you meet all 
screening eligibility criteria. If you have not had genetic testing (research or a CLIA-approved 
lab), you will also be asked to enroll in Dr. Paller’s “Screening for the Genetic Basis of 
Dermatologic Disease” IRB# 2009-13803 and have testing sent to Dr. Keith Choate at Yale 
University. If the clinical diagnosis is ichthyosis / ichthyotic disorder, having a known gene 
mutation is not required before randomization and entry into the study, however it is required 
that genetic testing is performed before end of study.  
 
Urine pregnancy test (subjects of childbearing potential only) will be completed prior to any 
baseline study procedures and ustekinumab injection. 
 
Medical and Medication History 
The study doctor or designated study team member will collect information regarding your 
relevant medical history/current medical conditions at every study visit as indicated in the above 
tables. All collected information will be documented. When possible, diagnoses (rather than 
symptoms) will be recorded. Your history regarding your ichthyosis will also be obtained 
including date of diagnosis and prior treatments. Medications including current medications and 
those taken within six months preceding enrollment will be recorded.  
 
While enrolled in the study, you may not use any topical agent for the treatment of ichthyosis 
during the first 6 months other than bland emollients. After the 6-month time point, the following 
keratolytics, including but not limited to agents containing tazarotene, salicylic acid, alpha-
hydroxyacids, and urea, can be added to the regimen as per your study doctor’s discretion. 
 
Vital Signs and Height/Weight 
Vital signs, including blood pressure, pulse, respiratory rate, temperature, and weight will be 
collected at every visit. Height will be recorded at the first visit, the end of the open label phase 
(OL) and the end of the long-term extension (LTE).  
 
Complete Physical Examination & Skin Examination 
A complete physical examination will be performed by a physician at the screening and baseline 
visits, as well as the end of the open label phase and the end of the long-term extension. This will 
involve an evaluation of the major body systems. A full skin exam (which will involve 
evaluation only of the skin) will occur at baseline and then at every visit at which there is study 
drug administration, as indicated in the above tables.  
 
Safety Labs and Pregnancy Testing 
Clinical lab evaluations (blood tests) at screening visit include hematology and chemistry panels, 
QuantiFERON gold, Hepatitis B, Hepatitis C and HIV testing to be resulted at Lurie Children’s 
Hospital. Approximately 15 ml, about 3 teaspoons, of blood will be drawn by a licensed 
phlebotomist per hospital requirements. Hematology/chemistry panels and QuantiFERON gold 
will also be drawn at visits for Months 13 and 25.  
 


 
 
 
 
 
 
 
 
 
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Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
If you are female and of child-bearing potential (i.e. female subjects who have experienced their 
first menstrual period) you will be tested for pregnancy at the screening and baseline visit. Urine 
HCG testing will be obtained. Anyone with a confirmed positive pregnancy test during screening 
is not eligible for participation in this study. In addition, if you are a female  of child-bearing 
potential, you will have urine HCG testing prior to every administration of the study drug.   
 
Severity Evaluations - IIS and Ichthyosis Severity Self-Assessment 
Physician severity evaluations will be performed at every study visit. A severity assessment will 
be collected which will include the Ichthyosis Severity Index (ISS). In addition, you will be 
asked to complete a severity self-assessment at every visit. These are surveys. 
 
TEWL and Tape Strips 
Transepidermal Water Loss (TEWL) skin measurements will be performed on the nondominant 
arm to assess the skin barrier at all study visits. TEWL measurements address the level of 
moisture that is lost from the skin (how dry the skin is). This procedure involves placing a small 
measurement device on your skin for a few seconds to get a reading. The measurements will be 
repeated up to four times, with each time having the device read measurements in triplicate.  
 
Tape strips will be also be obtained from your skin at Baseline, Month 7, Month 13, Month 19, 
and Month 25. Tape stripping is painless and involves the application and removal of small 
circular tape discs to your skin. Tape stripping will be performed on your upper arm using 
circular 2x2 or 3x3 cm transparent tape strips. Up to 16 tape strips will be serially extracted on 
each skin site. You will be asked not to apply emollient or moisturizer for at least 24 hours prior 
to tape stripping. The tape strips will be stored on site at the Paller Laboratory at Northwestern 
University. Tape strips will be used for biomarker analysis. 
 
Microbiome Sampling 
Microbiome sampling will be done at baseline, Month 7, Month 13, Month 19, and Month 25. 
The microbiome is the collection of organisms living in and on our bodies. This sampling will 
involve swabbing your skin with three separate swabs in three different areas on your 
nondominant upper outer arm. You will be asked not to shower or apply emollient or moisturizer 
for at least 24 hours prior to sampling.  
 
Photography  
Full body photography (including face) will be done at Baseline, Month 7, Month 13, Month 19, 
and Month 25. Photos may also be taken at additional visits if your ichthyosis severity changes 
outside of these mentioned time points. Photos will be labeled using your study ID as well as 
your visit number and date of the photo. Photos will be uploaded to a secure, research server 
maintained by Northwestern University within the Department of Dermatology and deleted from 
the camera memory card as soon as possible.  
 
Blood Samples for Biomarkers  
A 15.0mL, about 3 teaspoons, blood sample will be collected at Screening, Month 13 and Month 
25. Blood will be drawn by a licensed phlebotomist per hospital requirements and numbing 
solution may be applied to your skin prior to the blood draw to reduce pain. Your samples will 


 
 
 
 
 
 
 
 
 
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Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
be labeled with your study ID, study visit number, and visit date and stored at Northwestern 
University. Samples will be banked at Northwestern University for future analysis.  
 
Patient Reported Outcomes  
You will be asked to complete several patient reported quality of life measures that will take 
approximately 15-20 minutes to complete. These will include the following surveys: 
-Dermatology Life Quality Index (DLQI) OR Children’s Dermatology Life Quality Index 
(CDLQI)  
-Ichthyosis Financial and Time Burden (IFTB)  
-Stigma questionnaire 
 
Collected at Month 0, Month 7, Month 13, Month 19, and Month 25 
-Itch and Pain Numerical Rating Scale 
 
Collected at all visits  
-PROMIS Itch 
PROMIS Itch survey will be conducted at Month 0, Month 7, Month 13, Month 
19, and Month 25 if the subject scores ≥ 2 on the Itch NRS.  
 
Open Label and Long Term Extension Rollover 
You will have visits at Screening, Baseline, and Months 1, 3, 5, 7, 9, 11 and 13 for the open label 
phase (OL). Should you and the investigator find ustekinumab to be beneficial, you may have the 
option to continue to the Long-Term Extension (LTE) with in-person study visits every 8 weeks 
(Months 15, 17, 19, 21, 23 and 25). The final in-person study visit will be at Month 25, with the 
final administration of study drug at Month 23. 
 
What are the risks, side effects, or discomforts related to the study? 
You may have some side effects and discomfort while in this research. If you have any side 
effects, you should tell the study doctor or staff as soon as possible. They will monitor you 
closely. This research may also have risks or side effects that are not well known or understood 
at this time.  
 
Risks related to ustekinumab: 
The possible discomforts, side effects and risks related to ustekinumab treatment are not all 
known. Most side effects are not serious. Some may be serious and may require treatment or 
additional testing. This section describes how frequently side effects occurred in subjects who 
were treated with ustekinumab. In this section, the following terms are used:   
 
• Very common:  affects more than 1 user in 10 
• Common:  affects 1 to10 users in 100 
• Uncommon:  affects 1 to 10 users in 1,000 
• Rare:  affects 1 to 10 users in 10,000 
• Very rare: affects less than 1 in 10,000 
 
 
 


 
 
 
 
 
 
 
 
 
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Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
Very Common: 
 
• None  
 
 
Common: 
• Infection of the throat or airways 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: 
• 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 
 
Rare: 
• 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 your skin or your 
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)  
 
 
 
 


 
 
 
 
 
 
 
 
 
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Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
Infections 
Ustekinumab is a drug that may change how your 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. 
 
Tell your study doctor if you have a new infection, if an infection keeps coming back, or if you 
have any signs of infection such as:  
• 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 
orswelling 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 you 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. You should find out from your study 
doctor which fungal infections are common where you live or travel and what symptoms they 
cause. Tell your study doctor and family physician right away if you develop symptoms of such 
illnesses. 
 
Subjects who receive ustekinumab may also be at a greater risk for certain serious infections 
such as tuberculosis. Tell your study doctor if you have ever had tuberculosis or anybody in your 
family has ever had tuberculosis or if you come in contact with someone who has tuberculosis. 
Tell your study doctor if you develop: 
• a cough that does not go away 
• coughing up blood 
• shortness of breath 
• fever 
• night sweats 
• weight loss  
 
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 your immune system, it is possible that it may increase your risk of developing 
cancer, including skin cancers. Subjects who have been diagnosed with psoriasis have a higher 


 
 
 
 
 
 
 
 
 
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Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
chance of developing skin cancers. Tell your doctor if you 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 use immunosuppressive 
therapies (such as, azathioprine, methotrexate etc.) for a long time have a higher risk of 
developing cancer. These people get cancer of the lymph nodes more often than other people.  
 
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 following can be symptoms of 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. If this happens during the infusion, the infusion will be stopped. Signs of a serious 
allergic reaction include skin rash, swollen face, mouth, lips, and/or throat, and trouble breathing. 
Tell your doctor or get emergency medical help right away if you have an allergic reaction. If 
you experience a serious reaction to an injection or an infusion, you will not receive any more 
study treatments. 
 
If you have an infusion reaction or an allergic reaction at the doctor’s office, additional necessary 
treatment will be provided immediately. Your study doctor may give you an antihistamine 
(medication used to treat allergic symptoms such as hay fever) or other medications used for 
treating an allergy. Antihistamines can make you sleepy, so please use caution when driving a 
car or operating machinery.  
 
Another type of allergic reaction has occurred in some subjects 1-14 days after receiving some 
similar medications. The symptoms of this type of allergic reaction may include fever, rash, 
muscle aches and joint pain.    
 
Antibodies to ustekinumab 
Sometimes the body can make special antibodies that may increase the risk of an allergic 
reaction to either ustekinumab or other antibody medicines. If you have an allergic reaction, you 
may not be able to have these types of medications in the future. You should always tell your 
doctors that you have been treated with human antibodies in this study. 
 
 


 
 
 
 
 
 
 
 
 
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Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
Latex allergy 
The needle cover for the prefilled syringe that contains study drug contains dry natural rubber (a 
form of latex). This may cause allergic reactions in people who are sensitive to latex. Please tell 
your study doctor if you have ever had an allergic reaction to latex. 
 
Cardiac and Vascular 
Heart attacks and strokes have been reported in subjects who have received ustekinumab. These 
events have rarely resulted in death. It is unknown whether taking ustekinumab increases your 
risk for developing these events.   
 
People who have psoriasis, and certain other inflammatory diseases, have a higher risk of having 
heart attacks. These people have heart attacks more often than other people. Seek medical care 
immediately if you develop;  
• chest pain or discomfort  
• trouble breathing 
• irregular heartbeats  
• dizziness  
• loss of balance  
• new numbness or weakness  
• visual or speech changes 
 
Vaccination 
Vaccines are made to help protect people from certain illnesses. Some vaccines are made from 
live bacteria or live viruses. You cannot receive most kinds of live vaccines (for example, 
FluMist™, varicella/chicken pox) during the study or for 3 months after the last study injection. 
Another kind of live vaccine is BCG, which is a vaccine against tuberculosis. You cannot receive 
a BCG vaccine during this study or for 16 weeks after the last study injection. You could get sick 
from these kinds of vaccines while on ustekinumab. If you do get a live vaccination during this 
study, you must tell your study doctor immediately. 
 
Tell your study doctor if anyone living in your home needs a live vaccine. Some viruses used in 
live vaccines can spread from a close contact (someone living in your home) to people with a 
weakened immune system. 
 
Other kinds of vaccines, like tetanus,flu shots, and COVID vaccines that are not live are allowed. 
It is not known if ustekinumab may interfere with them from working. Tell your study doctor 
before getting any vaccine while you are in this study.   
 
Other Therapies 
Tell your doctor if you are receiving treatments that weaken the immune system while using 
ustekinumab (for example, oral steroid medicines). These treatment combinations have not each 
been studied with ustekinumab, so it is unknown if they could possibly increase the risk of 
diseases related to a weakened immune system. 
 
Allergy Immunotherapy (Allergy Injections)   
 Tell your study doctor if you have ever had or are now getting allergy injections. Ustekinumab 
may affect your response to allergy injections. 


 
 
 
 
 
 
 
 
 
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Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
 
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 your risk of developing 
PRES/RPLS. 
Symptoms of this condition are: 
• headache 
 
• seizures 
• confusion 
• loss of eyesight


 
 
 
 
 
 
 
 
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Stamped by: EJK 
Tell your study doctor if you experience any of these symptoms. There may be other discomforts 
or risks to you from this study that are not yet known. Your study doctor and staff will ask you 
about any side affects you may have at every visit. If you have any problems, you should let your 
study doctor know right away. 
 
Tell your doctors or dentist that you are or have been in a study where anti IL-12 and anti-IL-23 
is the study drug. This is important if you have any surgery, dental procedures, or receive 
treatment for any other medical condition.  
  
Risks related to study procedures and tests: 
 
Blood Draws Risks 
You may have discomfort or pain when blood is collected. You may feel faint or pass out. There 
is a risk of infection, bleeding, or bruising at the puncture site. You may develop a small scar at 
the puncture site where several blood samples are taken.  
 
Confidentiality: 
There is a risk of loss of confidentiality. However, steps will be taken to maintain confidentiality.  
Only authorized study staff will have access to your information.  
 
Risks related to pregnancy: 
The effects of the study drug on the reproductive system (sperm, eggs) or to an unborn baby are 
unknown. It is important that when in this study, participants do not become or make their 
partner pregnant. Those who are pregnant or nursing will not be allowed to take part in this 
study. Everyone in this study must agree to use a reliable method of birth control or not have 
sexual intercourse during the study. The study doctor/staff will talk about this with you and 
provide information on the best methods of birth control.   
 
Pregnancy testing may be required at some visits while you are in this study. During the course 
of the study, if there is any chance you may be pregnant (late or missed menstrual period), please 
contact the study doctor right away. If you become pregnant when taking part in this study, you 
may be asked to stop the study. However, follow-up visits to review the effects on you and/or the 
baby may be needed. 
 
It’s also important that you tell your baby’s doctor and other health care professionals that you 
received treatment with Ustekinumab while pregnant, because a 6-month waiting period 
following birth may be recommended before the administration of a live vaccine (like BCG and 
rotavirus) to the baby. 
 
Risks related to genetic testing: 
Genetic information is like a fingerprint and it is unique for each person. Many of the risks 
linked with genetic testing include the loss of confidentiality and privacy. There is a risk that 


 
 
 
 
 
 
 
 
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Patient Name: 
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IRB Approval Expires on: 02/29/2024 
Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
someone could trace the genetic data back to you. This could happen even if the genetic data is 
stored without your name or other information that can identify you. This risk may increase in 
the future as people come up with new ways of tracing information. 
 
Many people are worried that the results of genetic testing might be held against them. There are 
federal and state laws to protect people. The federal law is the Genetic Information 
Nondiscrimination Act (GINA). The state law is the Genetic Information Privacy Act (GIPA). 
GINA and GIPA generally make it unlawful for health insurance companies, group health plans, 
and employers to discriminate based on genetic information. This law does not protect against 
discrimination by companies that sell life, disability, or long-term care insurance. Ask the study 
doctor for more information on these laws. 
 
What other options do I have? 
You do not have to participate in this study if you do not want to. The alternative is to not take 
part in this research study. If you choose not to participate in this study, it will not impact your 
medical treatment for ichthyosis in any way. 
 
What if my study doctor or I do not think I should stay in the study? 
You can stop taking part in this study at any time. Your decision will not affect your regular care. 
 
Returning Study Results: 
The study team will not return study results to you. You still have a right to request a copy of 
your medical record. 
 
The overall results of the study will be published; however, personal information that could 
identify you will not be used or made available. 
 
Important New Information: 
We will tell you if we learn new information that may make you change your mind about being 
in this study. 
 
Planned Sharing of Your Information:    
If you agree to take part in this study, you also give permission for the use and sharing of your 
information. This permission lasts until the study is completed.  
 
The information that may be collected and shared will include your: 
• Personal and health information  
• Past and present medical records 
• Records from study visits and phone calls  
 


 
 
 
 
 
 
 
 
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Note:  Label required for cover page, but is optional for 
other pages if the following information is provided: 
Patient Name: 
MRN: 
Approved by IRB on: 03/20/2023 
IRB Approval Expires on: 02/29/2024 
Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
The study staff, including Lurie Children’s employees and Medical Staff, Northwestern 
Memorial Hospital (NMH) and Northwestern University (NU) may use your information and 
samples for this study and share it with: 
• The study company, Janssen, and those working with the company.  
• Northwestern University  
• The Institutional Review Board (the committee that is in charge of protecting the rights of 
all adults and children who take part in research studies). 
• Your other providers and their staff directly involved in your care, if your provider is a 
part of the Lurie Children’s electronic health information exchange. 
• The Office of Human Research Protections (OHRP), the Food and Drug Administration 
(FDA), or other government offices. 
 
These are the only people to which we will give your information. We cannot guarantee that 
those listed above will not share it with others without your permission.    
 
Your name will not be included in any written or verbal reports of study results.  
 
What if I decide not to give permission to use and give out my information? 
If you decide not to allow the release your information, you will not be able to take part in this 
study. If you give permission to the use of your information, you can withdraw it at any time. 
Your request should be in writing and sent to the study doctor. The study team can still use any 
information collected before you tell them to stop.  
 
Can I review or get a copy my study information?   
You cannot see your study records while the study is ongoing. However, any testing that relates 
to your medical care will be put in your medical record. You still have a right to request a copy 
of your medical record and tests related to regular medical care that is given during the same 
time as the study. 
 
Will my information or samples be used in future research studies? 
The data and samples collected from your participation in the study will be analyzed with those 
of all other study participants. The Study Doctor will use your data for future decision making, 
such as to plan other studies, to better understand the disease including diagnosis and associated 
health problems, as well as to understand how ichthyosis drugs work in the body. 
 
In this research we will be looking at the DNA/RNA in your cells. Your sample will be identified 
by their subject number. Only the study doctor and site staff can link the number to you. During 
this time, your sample will be stored securely at Northwestern University.    
 
Costs Related to this Study:  
The study sponsor will pay for the tests, procedures, and/or medications for the study.  
 


 
 
 
 
 
 
 
 
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Patient Name: 
MRN: 
Approved by IRB on: 03/20/2023 
IRB Approval Expires on: 02/29/2024 
Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
Payment for Taking Part in this Study:  
You will be paid $800 for taking part in this study. This will be given in $50 increments as a 
check mailed to your home after the completion of each study visit. You will only be paid for 
completed study visits. 
 
You will be asked to fill out a W-9 tax form. This form will collect your name, address, social 
security or individual taxpayer identification number. It will be used for processing your check 
or reporting to the IRS if you are paid more than $600 in a calendar year. This reporting is 
required under federal tax law.  
 
In the Event of Injury:  
Contact the study doctor as soon as possible, if you are injured while taking part in this study. 
Lurie Children’s will assist you in finding medical care if needed. You or your insurer may be 
billed for such treatment.      
 
Your Rights When Taking Part in this Study: 
If you agree to take part in this study, you are not giving up any of your legal rights. You can 
stop participating in this study at any time. Your decision will not affect your regular care.  
 
Additional Information: 
Who can answer my questions about this study? 
If you have any questions, contact the study doctor, Dr. Amy Paller, at 312-695-3721 or a 
member of the research team at 312-227-6486 during a workday or 312-695-7787 at night or on 
weekends. 
 
If you have questions about your rights or if you have a complaint, you can call the IRB Office at 
(312) 503-7110; or via email at IRB@luriechildrens.org. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. law. This website will not include information that can identify you. At most, the 
website will include a summary of the results. You can search this website at any time. 
 
Please be advised that Dr. Amy Paller is receiving funding support from the company (Janssen) 
to conduct the study. You may request additional information about this relationship from the 
study doctor at any time. 
 
You will be given a copy of this consent form. A copy will also be placed in your medical 
record.  
 


 
 
 
 
 
 
 
 
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Note:  Label required for cover page, but is optional for 
other pages if the following information is provided: 
Patient Name: 
MRN: 
Approved by IRB on: 03/20/2023 
IRB Approval Expires on: 02/29/2024 
Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
 
Optional Research: 
You can still take part in the study if you do not agree to the optional research below.  
 
What are the purpose and procedures of this optional research? 
In addition to study information, portions of samples of your specimens will be banked and 
stored indefinitely for future use by the research team at Lurie Children’s and Northwestern. If 
the samples are no longer useful for research purposes at some time in the future or if you 
instruct us to do so, they will be destroyed. 
 
What information or samples will be kept for this optional research? 
Samples and data will be labeled only with a code number. This code number will be able to link 
your study data to the banked sample, but no identifying information will be recorded on the 
sample itself.  
 
Who will have access to my information or samples for this optional research and how will 
it be kept private? 
The study team at Lurie Children’s and Northwestern University will have access to the data and 
samples in this optional research. 
 
Can I take back (withdraw) my permission for this optional research? 
If you would like to withdraw your permission to have your samples banked for future research 
studies, you can do so by emailing Dr. Paller or her study team.   
 
Please initial next to your choice below regarding the optional testing: 
 
YES – I agree to the storing and future use of my data and samples.  
Initials 
 
 
 
NO – I do not agree to the storing and future use of my data and samples. 
Initials 
 
 


 
 
 
 
 
 
 
 
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Note:  Label required for cover page, but is optional for 
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Patient Name: 
MRN: 
Approved by IRB on: 03/20/2023 
IRB Approval Expires on: 02/29/2024 
Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
Signatures: 
Participant Signature: 
By signing this form, I affirm:   
1) I have read this form.  
2) The research has been explained to me. 
3) All of my questions have been answered.   
4) I give my consent to take part in this research study. 
Signature of Participant or Legally Authorized Representative (LAR):   
 
 
Date: 
Printed Full Name: 
 
 
 
Signature of Authorized Person Obtaining Consent: 
I certify that I have explained the above to the participant/LAR and the signature was obtained 
voluntarily.  
Signature: 
 
Date: 
Printed Full Name: 
 
 
 
Signature of Interpreter/Witness*: 
      
        Not applicable, no interpreter used. 
 
I attest that the study information has been presented to the participant/ LAR in their native 
language.  
Signature of Interpreter/Witness: 
 
 
Printed Full Name or Unique Phone ID/Company Name: 
 
 
 


 
 
 
 
 
 
 
 
Adult Consent 
Version Date: 8NOV2022 
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Affix Patient Label Here 
Note:  Label required for cover page, but is optional for 
other pages if the following information is provided: 
Patient Name: 
MRN: 
Approved by IRB on: 03/20/2023 
IRB Approval Expires on: 02/29/2024 
Lurie Children’s IRB#: 2020-3233 
Stamped by: EJK 
 
Note to Investigators: When obtaining consent from a non-English speaking 
participant/LAR 
When a study-specific translated consent document is not available, a translated “short form” 
(available in several languages on the IRB website) may be used, in combination with a verbal 
presentation of study information (as outlined in this English consent) with the aid of an 
interpreter.    
a. The consent process must be witnessed by an individual who is fluent in both English and the 
language understandable the subject. The interpreter may serve as the witness and should 
sign both the English consent document and short form. 
b. The participant/LAR should sign the short form (in the language they understand). 
c. The investigator and/or study staff authorized by the IRB to obtain consent must sign the 
approved English version of the consent form. 
d. A copy of both the IRB-approved English consent form (i.e., the summary) and the translated 
version of the short form must be given to the participant/LAR.