Clinical trial NCT03239106
Conditions: Itch
Keywords: itch pruritus CIP
Sponsor: Washington University School of Medicine
Start date: 2017-12-01; Completion date: 2019-09-19
Enrollment: 10 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Chronic Itch is a debilitating condition affecting many people. Currently, there are no FDA-approved treatments. Apremilast is an FDA-approved oral medication used to successfully treat the inflammatory skin disorder psoriasis and the inflammatory disorder psoriatic arthritis. This study examines if apremiliast taken twice daily relieves chronic itch.

Detailed description:
There is no FDA-approved medication for chronic idiopathic pruritus (CIP). Apremilast has demonstrated notable activity and is approved for treatment in other pruritic inflammatory skin conditions such as psoriasis. The drug is currently being investigated as therapy for atopic dermatitis. Additionally, the investigators have preliminary data to suggest that apremilast's anti-inflammatory properties may work via neuromodulation targeting neuronal cytokine pathways. The proposed study plans to assess the efficacy of apremilast 30 mg BID in the setting of CIP. Durable response to a medication is typically seen within one to two months of starting an efficacious medication in subjects who respond. Therefore, the investigators have designed this study to end at Week 16 to definitively determine efficacy and conclude the study with confidence with regard to both efficacy and failure.

Arms: arm 1: All participants will receive Apremilast 30 mg BID.
Interventions: intervention 1: Apremilast
Intervention descriptions: intervention 1: Apremilast 30 mg BID daily

Protocol documents:
ICF_002.pdf: 
 
                                                                                                         
Brian S Kim, MD, MTR, FAAD 
Associate Professor of Medicine 
Co-Director, Center for the Study of Itch and Sensory Disorders 
Department of Medicine                 
 
Division of Dermatology 
St. Louis, MO 63110                    
                       
                                                                                                          
                                       
Washington University School of Medicine, Campus Box 8123, 660 S. Euclid Avenue, 
 St. Louis, Missouri 63110, (314) 747-6556, Fax (314) 362-8159     
16 March 2020 
 
 
 
 
 
To Whom it May Concern: 
 
 
Please find enclosed the protocol and informed consent form for the proof-of-concept open-label 
clinical trial entitled listed as “A Study Examining the Medication Apremilast as Treatment 
for Chronic Itch” on ClinicalTrials.gov (NCT03239106).  
 
Please see attached/uploaded documents.  
 
Please do not hesitate to contact me directly should anyone have questions at (314) 273-1376. 
 
 
 
Sincerely,  
 
 
 
 
 
 
Brian S. Kim, MD, MTR, FAAD 
Associate Professor of Medicine (Dermatology), Anesthesiology, and Pathology and Immunology 
Co-Director, Center for the Study of Itch and Sensory Disorders 
Department of Medicine/Division of Dermatology 
Washington University School of Medicine 


 
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INFORMED CONSENT DOCUMENT 
 
Project Title:       An Open-Label Pilot Study of Apremilast in Chronic Idiopathic Pruritus 
 
Principal Investigator: 
Brian S. Kim, MD 
 
Research Team Contact: 
Nancy Bodet, RN  
(314) 273-1376 
 
 
 
This consent form describes the research study and helps you decide if you want to participate.  It 
provides important information about what you will be asked to do during the study, about the risks and 
benefits of the study, and about your rights and responsibilities as a research participant.  By signing this 
form you are agreeing to participate in this study. 
• You should read and understand the information in this document including the procedures, risks 
and potential benefits.  
• If you have questions about anything in this form, you should ask the research team for more 
information before you agree to participate.   
• You may also wish to talk to your family or friends about your participation in this study. 
• Do not agree to participate in this study unless the research team has answered your questions and 
you decide that you want to be part of this study.  
 
WHAT IS THE PURPOSE OF THIS STUDY? 
This is a research study.  We invite you to participate in this research study because you have chronic 
idiopathic pruritus (CIP).  CIP is an unpleasant sensation of the skin that provokes the urge to scratch, 
and is of unknown cause.  
 
The purpose of this research study is to determine the effectiveness of Apremilast (the study drug) in 
relieving the itching associated with CIP. Apremilast is approved for treatment in other inflammatory 
skin conditions such as psoriasis.  There is no approved treatment for CIP. 
 
Apremilast is considered investigational, which means that it has not been approved by the U.S. Food 
and Drug Administration for CIP. 
 
WHAT WILL HAPPEN DURING THIS STUDY? 
You will complete a screening visit in order to assess your eligibility to take part in the study.  The 
screening period may last up to 28 days.  After your screening visit, if you are eligible to continue to 
take part in the study, you will start treatment with the study drug at your baseline/Day 1 visit.  Study 
visits will take place at Weeks 2, 4, 8, 12, and 16.  You will return to the clinic at Week 18 for a follow-
up visit. 
 
The assessments performed at each visit are described below: 
 
Screening Visit  
• Informed consent 
• Review eligibility criteria 


 
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• Collect demographics (for example, age, race, and gender) and medical & medication history 
• Measure height and body weight 
• Physical examination 
• Measure vital signs (pulse, respiratory rate, blood pressure) 
• You will have blood drawn for laboratory assessments, including Hepatitis screening tests 
• You will provide a urine sample for urinalysis 
• A pregnancy test will be performed for women of childbearing potential. You will not be able to 
continue in the study if you are pregnant. 
• Chest X-ray 
• NRS itch score. You will report the intensity of your itch using a numbered scale. 
• Questionnaire to measure how much your skin problem has affected your life. You are free to skip 
any questions you prefer not to answer. 
• Review adverse (harmful) events 
 
The screening period may last up to 28 days to allow time to review your laboratory and chest X-ray 
results, and to provide flexibility for scheduling your baseline visit. 
 
Day 1/Baseline 
• Review eligibility criteria 
• Review medications 
• Physical examination 
• Measure vital signs 
• A pregnancy test will be performed for women of childbearing potential.  
• NRS itch score. You will report the intensity of your itch using a numbered scale. 
• Questionnaire to measure how much your skin problem has affected your life. You are free to skip 
any questions you prefer not to answer. 
• You will have a skin biopsy for bio-banking tissue. A skin biopsy is a procedure in which a sample 
of skin tissue is removed and examined under a microscope. 
• Review adverse events 
• Study drug dispensed. The study drug is taken by mouth and you will receive your first dose in the 
clinic. You will take the study drug at home beginning the next morning. Your dose will be 
increased to the maintenance dose of 30 mg twice daily as follows: 
o Day 2: 10 mg twice daily 
o Day 3: 10 mg in the morning and 20 mg in the evening 
o Day 4: 20 mg twice daily 
o Day 5: 20 mg in the morning and 30 mg in the evening 
o Day 6 – Week 16: 30 mg twice daily 
 
Week 2 
• Review medications 
• Physical examination 
• Measure vital signs 
• A pregnancy test will be performed for women of childbearing potential 
• NRS itch score. You will report the intensity of your itch using a numbered scale. 


 
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• Questionnaire to measure how much your skin problem has affected your life. You are free to skip 
any questions you prefer not to answer. 
• Review adverse events 
• Study drug collected/dispensed 
 
Week4 
• Review medications 
• Physical examination 
• Measure vital signs 
• A pregnancy test will be performed for women of childbearing potential 
• NRS itch score. You will report the intensity of your itch using a numbered scale. 
• Questionnaire to measure how much your skin problem has affected your life. You are free to skip 
any questions you prefer not to answer. 
• Review adverse events 
• Study drug collected/dispensed 
 
Week 8 
• Review medications 
• Physical examination 
• Measure vital signs 
• A pregnancy test will be performed for women of childbearing potential 
• NRS itch score. You will report the intensity of your itch using a numbered scale. 
• Questionnaire to measure how much your skin problem has affected your life. You are free to skip 
any questions you prefer not to answer. 
• You will have a skin biopsy for bio-banking tissue 
• Review adverse events 
• Study drug collected/dispensed 
 
Week 12 
• Review medications 
• Physical examination 
• Measure vital signs 
• A pregnancy test will be performed for women of childbearing potential 
• NRS itch score. You will report the intensity of your itch using a numbered scale. 
• Questionnaire to measure how much your skin problem has affected your life. You are free to skip 
any questions you prefer not to answer. 
• You will have a skin biopsy for bio-banking tissue 
• Review adverse events 
• Study drug collected/dispensed 
 
Week 16 
• Review medications 
• Physical examination 


 
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• Measure vital signs 
• A pregnancy test will be performed for women of childbearing potential 
• NRS itch score. You will report the intensity of your itch using a numbered scale. 
• Questionnaire to measure how much your skin problem has affected your life. You are free to skip 
any questions you prefer not to answer. 
• You will have a skin biopsy for bio-banking tissue. A skin biopsy is a procedure in which a sample 
of skin tissue is removed and examined under a microscope. 
• Review adverse events 
• You will have blood drawn for laboratory assessments 
• Study drug collected 
 
Week 18,  Follow-Up 
• Review medications 
• Physical examination 
• Measure vital signs 
• A pregnancy test will be performed for women of childbearing potential 
• NRS itch score. You will report the intensity of your itch using a numbered scale. 
• Questionnaire to measure how much your skin problem has affected your life. You are free to skip 
any questions you prefer not to answer. 
• Review adverse events 
 
Will you save my samples or research data to use in future research studies?  
As part of this study, we are obtaining blood, data and skin tissue from you.  We would like to use this 
blood, data and skin tissue for studies going on right now as well as studies that are conducted in the 
future.  These studies may provide additional information that will be helpful in understanding CIP, or 
other diseases or conditions, including research to develop investigational tests, treatments, drugs or 
devices that are not yet approved by the U.S. Food and Drug Administration.  It is unlikely that what we 
learn from these studies will have a direct benefit to you.  There are no plans to provide financial 
compensation to you should this occur.  By allowing us to use your blood and skin tissue you give up 
any property rights you may have in the blood and skin tissue. 
 
Your skin tissue will be used to conduct analyses of your RNA (genetic material) and possible genomic 
analysis to study your response to treatment.  Genes are a unique combination of molecules (called 
DNA) that we inherit from our parents.  There are millions of tiny differences in our genes that 
determine things like our height or the color of our eyes.  Some of these differences may make some 
people more or less likely to develop certain diseases or conditions or to have certain characteristics 
 
We will share your blood, data and skin tissue with other researchers.  They may be doing research in 
areas similar to this research or in other unrelated areas.  These researchers may be at Washington 
University, at other research centers and institutions, or industry sponsors of research.  We may also 
share your research data with large data repositories (a repository is a database of information) for broad 
sharing with the research community.   If your individual research data is placed in one of these 
repositories only qualified researchers, who have received prior approval from individuals that monitor 
the use of the data, will be able to look at your information.   


 
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If you change your mind and do not want us to store and use your blood, data and skin tissue for future 
research you should contact the research team member identified at the top of this document.  The 
blood, data and skin tissue will no longer be used for research purposes.  However, if some research 
with your blood, data and skin tissue has already been completed, the information from that research 
may still be used.  Also, if the blood and skin tissue has been shared with other researchers it might not 
be possible to withdraw the blood and skin tissue to the extent it has been shared. 
 
Please place your initials in the blank next to Yes or No for each of the questions below: 
 
My blood, data and skin tissue may be stored and used for genetic/genomic research as described 
above. 
 
_____ Yes  
_____ No 
Initials  
Initials 
 
My blood, data and skin tissue may be stored and used for future research as described above. 
 
_____ Yes 
_____ No 
Initials  
Initials 
 
My blood, data and skin tissue may be shared with other researchers and used by these 
researchers for the future research as described above. 
 
_____ Yes  
_____ No 
Initials  
Initials 
 
HOW MANY PEOPLE WILL PARTICIPATE? 
Approximately 10 people will take part in this study conducted by investigators at Washington 
University.   
 
HOW LONG WILL I BE IN THIS STUDY? 
If you agree to take part in this study, your involvement will last for approximately 22 weeks.  This 
includes the screening period which may last up to 28 days, a 16-week treatment period, and a 2 week 
follow-up visit.  Visits can range in time from 30 minutes-2 hours. 
 
WHAT ARE THE RISKS OF THIS STUDY? 
You may experience one or more of the risks indicated below from being in this study.  In addition to 
these, there may be other unknown risks, or risks that we did not anticipate, associated with being in this 
study.  
 
Some risks described in this consent document, if severe, may cause death. 
 
As of 30 Nov 2017, apremilast has been given to more than 6800 subjects (people) in studies conducted 
by Celgene.  The following are the most commonly seen risks, discomforts and side effects in subjects 
who have taken apremilast: headache including tension headache, stuffiness or infections of the nose 


 
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and throat (upper respiratory tract infections including nasopharyngitis), stomach upset (nausea), 
vomiting and diarrhea.  Most of these side effects were mild to moderate in intensity and resolved with 
continued treatment.  Similar side effects have been observed in studies that are running now.  About 8 
out of every 100 subjects treated have discontinued the study drug because of side effects.   
 
Very common:  
• Diarrhea 
• Nausea (stomach upset)  
• Vomiting  
 
Common:  
• Upper abdominal (stomach) pain 
• Indigestion 
• Frequent bowel movement  
• Heartburn  
• Fatigue 
• Bronchitis (infection of the tubes to the lungs)  
• Redness/swelling/pain in the sinuses  
• Inflammation or infections of the nose and throat  
• Weight loss  
• Decreased appetite 
• Back pain  
• Headache including tension and migraine  
• Difficulty sleeping  
• Depression  
• Cough  
• Rash  
• Dizziness  
• Weakness  
• Flu  
• Muscle pain  
• Numbness  
• Itchiness 
 
Uncommon:  
• Allergic reaction 
 
Reports of various types of cancers, heart problems, and serious infections have been found from 
apremilast studies.  However, these events in patients being treated with apremilast happened as often as 
those being treated with placebo (sugar pill).  
 
Drugs in the same family as apremilast have been shown to produce inflammation around the vessels of 
the skin (vasculitis) in rats and mice.  Skin vasculitis has been rarely reported equally in patient taking 
apremilast or placebo.  If you have any unexplained swelling, pain, tenderness or redness, please tell 


 
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your study doctor.   
 
Depression has been reported with the use of apremilast.  If you have a history of depression and/or 
suicidal thoughts or behavior, please tell your study doctor.  If you have any symptoms of depression or 
if your depression becomes worse, or if you have suicidal thoughts or other mood changes, contact your 
study doctor immediately.   
 
In clinical studies, weight loss has been observed.  If you experience unintentional or unexplained 
weight loss (for example, if you have weight loss without actively trying to lose weight), please notify 
your study doctor immediately.  
 
Severe diarrhea, nausea, and vomiting has been reported with the use of apremilast.  Some patients were 
hospitalized.  If you are 65 years of age or older, and/or become dehydrated or experience low blood 
pressure, you may be at a higher risk of complications.  If you experience severe diarrhea, nausea, or 
vomiting please notify your study doctor immediately.  
 
Tell your study doctor if you are taking any other medication, including over-the-counter medications, 
since some medications could interfere with the effects of apremilast. 
 
It is possible that the condition for which you are being treated may worsen during the study.   
  
Blood Drawing- Blood samples will be taken by single needle-sticks.  Risks associated with 
drawing blood from your arm include pain, bruising or bleeding from the site of the needle puncture, 
lightheadedness or fainting, and infection. 
 
Skin Biopsy- A skin biopsy is a generally safe procedure, but complications can occur, including 
bleeding, bruising, scarring, infection, and allergic reaction to the topical antibiotic. 
 
Local Anesthesia- The side effects of local anesthetic agents include prolonged anesthesia (numbness) 
and paresthesia (tingling, feeling of "pins and needles", or strange sensations).  These are symptoms of 
localized nerve impairment or nerve damage.  
 
Chest X-Ray- This study will expose you to radiation from chest x-ray.  The amount of radiation from this, 
when averaged over your entire body, is 2% of the amount of radiation exposure all people in St. Louis 
receive each year from naturally occurring radiation sources.  The risk from the radiation exposure in this 
study is too small to be measured.  It is not a big risk when compared with other risks you take every day.  If 
you want to know more about radiation exposure, please see the “Radiation Fact Sheet” located at 
http://hrpo.wustl.edu or ask the study staff for a copy 
 
Women Capable of Becoming Pregnant- Apremilast should not be administered to pregnant or 
nursing women. If you are a woman capable of becoming pregnant, we will ask you to have a pregnancy 
test before beginning this study.  You must use effective birth control methods as described below and 
try not to become pregnant while participating in this study and for at least 28 days after your last dose 
of study drug.  If you become pregnant, there may be unknown risks to your unborn child, or risks to 
your unborn child that we did not anticipate.  There may be long-term effects of the treatment being 


 
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studied that could increase the risk of harm to an unborn child.  You must tell the doctor if your birth 
control method fails while you are on the study.  If you believe or know you have become pregnant 
while participating in this research study, please contact the research team member identified at the top 
of this document as soon as possible. We would like to follow your pregnancy until its conclusion. If 
this happens, we will ask you to sign a separate informed consent form to permit this data collection.    
 
Sexually Active Male- If you are a sexually active male it is important that your partner not become 
pregnant during your participation in this study.  There may be unknown risks to the unborn child or 
risks we did not anticipate.  You and your partner must agree to use birth control if you want to take part 
in this study.  If you believe or know that your partner has become pregnant during your participation in 
this study, please contact the research team member identified at the top of this document as soon as 
possible 
 
Approved options for birth control are: 
• Any one of the following highly effective methods: Hormonal contraception (for example, birth 
control pills, intravaginal ring, transdermal patch, injection, implant); intrauterine device (IUD); 
tubal ligation (tying your tubes); or a partner with a vasectomy. Certain drugs may reduce the 
effectiveness of hormonal contraceptives during and up to one month after discontinuation of these 
concomitant therapies. Please talk to your doctor for further information about contraceptives. 
OR 
• Double barrier method: Male or female condom (latex condom or any nonlatex condom NOT made 
out of natural [animal] membrane [for example, polyurethane]) PLUS one of the following 
additional barrier methods: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) 
contraceptive sponge with spermicide. 
 
If at any time during the study your birth control method changes, or you experience a problem with 
your current birth control method, or your ability to become pregnant changes (for example, you have an 
IUD removed, accidently miss taking any of your birth control pills, or enter menopause), you must 
inform the study doctor and have a discussion with the study doctor or study nurse about an alternative 
birth control method. 
 
Genetics- There is a federal law called the Genetic Information Nondiscrimination Act (GINA).  In 
general, this law makes it illegal for health insurance companies, group health plans and employers with 
greater than 15 employees to discriminate against you based on your genetic information.  However, it 
does not protect you against discrimination by companies that sell life insurance, disability insurance or 
long term-care insurance.  
 
Breach of Confidentiality- One risk of participating in this study is that confidential information about 
you may be accidentally disclosed.  We will use our best efforts to keep the information about you 
secure.  Please see the section in this consent form titled “How will you keep my information 
confidential?” for more information. 
 
WHAT ARE THE BENEFITS OF THIS STUDY? 
You may or may not benefit from being in this study. 
 


 
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However, we hope that, in the future, other people might benefit from this study because of the 
information that is learned. 
 
WHAT OTHER TREATMENT OPTIONS ARE THERE? 
Before you decide whether or not to be in this study, your doctor will discuss the other options that are 
available to you.  Instead of being in this study, you could try neuromodulators such as gabapentin or 
pregabalin, topical steroids, oral steroids, or other immunosuppressive agents such as cyclosporine, 
azathioprine, and mycophenalate mofetil.  However, currently, there are no agents available for your 
condition that are similar to the study drug. 
 
WILL IT COST ME ANYTHING TO BE IN THIS STUDY? 
You will not have any additional costs for being in this research study. 
 
You and/or your medical/hospital insurance provider will remain responsible for your regular medical 
care expenses. 
 
WILL I BE PAID FOR PARTICIPATING? 
You will be paid for being in this research study.  You will need to provide your social security number 
(SSN) in order for us to pay you.  You may choose to participate without being paid if you do not wish 
to provide your social security number (SSN) for this purpose.  If your social security number is 
obtained for payment purposes only, it will not be retained for research purposes.    
 
You will be paid $50 per study visit, up to $400 if you complete the study.  You will only be paid for the 
visits you complete.  A check will be mailed to you approximately 2-4 weeks after your last study visit. 
 
WHO IS FUNDING THIS STUDY? 
Celgene is funding this research study.  This means that Washington University is receiving payments 
from Celgene to support the activities that are required to conduct the study.  No one on the research 
team will receive a direct payment or increase in salary from Celgene for conducting this study. 
 
WHAT IF I AM INJURED AS A RESULT OF THIS STUDY? 
Washington University investigators and staff will try to reduce, control, and treat any complications 
from this research.  If you feel you are injured because of the study, please contact the investigator at 
(314) 747-6556 and/or the Human Research Protection Office at 1-(800)-438-0445.  
 
Decisions about whether payment for medical treatment for injuries relating to your participation in 
research will be made by Washington University.  If you need to seek medical care for a research-related 
injury, please notify the investigator as soon as possible.  
 
HOW WILL YOU KEEP MY INFORMATION CONFIDENTIAL? 
Other people such as those indicated below may become aware of your participation in this study and 
may inspect and copy records pertaining to this research.  Some of these records could contain 
information that personally identifies you. We will keep your participation in this research study 
confidential to the extent permitted by law.   
• Government representatives, (including the Office for Human Research Protections) to complete 


 
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federal or state responsibilities 
• The U.S. Food and Drug Administration 
• Celgene 
• Your primary care physician if a medical condition that needs urgent attention is discovered 
• Public health agencies to complete public health reporting requirements 
• Hospital or University representatives, to complete Hospital or University responsibilities 
• Information about your participation in this study may be documented in your health care records 
and will be available to anyone with access to your health care record, including your health 
insurance company.  This information may also be released as part of a release of information 
request. 
• The last four digits of your social security number may be used in hospital or University systems to 
track billing information for research procedures 
• Washington University’s Institutional Review Board (a committee that oversees the conduct of 
research involving human participants) and the Human Research Protection Office. The Institutional 
Review Board has reviewed and approved this study.  
  
The research team will send study results to Celgene.  Information sent to Celgene will contain 
identifiers such as your study ID number, and date of birth.  Celgene will use your data to study the 
effectiveness of Apremilast in relieving the itch associated with CIP. In the future, Celgene may 
continue to use your health information that is collected as part of this study.  For example, Celgene may 
combine information from this study with the results of other studies to re-analyze the safety and 
effectiveness of the study medication, to evaluate other products or therapies, to develop a better 
understanding of a disease, or to improve the design of future research studies.  Celgene may also share 
information from the study with regulatory agencies in foreign countries. 
 
If you receive Medicare benefits, are injured as part of your participation in this research study and 
medical treatment relating to this injury is paid by anyone other than you or your insurance company, 
that payer will need to collect personal information about you.  This information includes your name, 
date of birth, gender, social security number, Medicare identification number and information related to 
this research study.  The payer will report this information to the Centers for Medicare & Medicaid 
Services (CMS), the federal agency that oversees the Medicare program, during your participation in the 
study and for as long as the payer is required by CMS to report this information.  If you do not want to 
release your personal or treatment related information you have the right to refuse reimbursement by the 
payer for any research injury.  The payer will not use this information for any other purpose. 
 
To help protect your confidentiality, we will store your paper study records in a locked cabinet in a 
locked office.  Your electronic study records will be accessible only by a unique username/password 
given to the study team member.  Biological samples will be labeled with a code. Any report or article 
that we write will not include information that can directly identify you.  The journals that publish these 
reports or articles require that we share your information that was collected for this study with others. 
Sharing this information will allow others to make sure the results of this study are correct and help 
develop new ideas for research. Your information will be shared in a way that cannot directly identify 
you.  
 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 


 
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Law.  This Web site will not include information that can identify you.  At most, the Web site will 
include a summary of the results.  You can search this Web site at any time. 
 
Are there additional protections for my health information? 
Protected Health Information (PHI) is health information that identifies you.  PHI is protected by federal 
law under HIPAA (the Health Insurance Portability and Accountability Act).  To take part in this 
research, you must give the research team permission to use and disclose (share) your PHI for the study 
as explained in this consent form.  The research team will follow state and federal laws and may share 
your health information with the agencies and people listed under the previous section titled, “How will 
you keep my information confidential?” 
 
Once your health information is shared with someone outside of the research team, it may no longer be 
protected by HIPAA.   
 
The research team will only use and share your information as talked about in this form or as permitted 
or required by law.  When possible, the research team will make sure information cannot be linked to 
you (de-identified).  Once information is de-identified, it may be used and shared for other purposes not 
discussed in this consent form.  If you have questions or concerns about your privacy and the use of your 
PHI, please contact the University’s Privacy Officer at 866-747-4975.  
 
Although you will not be allowed to see the study information, you may be given access to your health 
care records by contacting your health care provider.  
 
If you decide not to sign this form, it will not affect 
• your treatment or the care given by your health provider. 
• your insurance payment or enrollment in any health plans.   
• any benefits to which you are entitled. 
However, it will not be possible for you to take part in the study. 
 
If you sign this form: 
• You authorize the use of your PHI for this research. 
• This authorization does not expire. 
• You may later change your mind and not let the research team use or share your information 
(you may revoke your authorization).  
• To revoke your authorization, complete the withdrawal letter, found in the Participant section 
of the Human Research Protection Office website at 
http://hrpo.wustl.edu/participants/withdrawing-from-a-study/ or you may request that the 
investigator send you a copy of the letter.    
 
 
 
o If you revoke your authorization: 
 The research team may only use and share information already collected for 
the study. 
 Your information may still be used and shared as necessary to maintain the 
integrity of the research, for example, to account for a participant’s 
withdrawal from the research study or for safety reasons. 
 You will not be allowed to continue to participate in the study. 


 
FOR IRB USE ONLY 
IRB ID #: 201709093 
APPROVAL DATE: 08/20/19 
RELEASED DATE: 08/26/19 
EXPIRATION DATE: 08/18/20 
 
APREMILAST (CC-10004) 
 
Version #3 (22 March 2018) 
 
Page 12 of 13 
IS BEING IN THIS STUDY VOLUNTARY? 
Taking part in this research study is completely voluntary.  You may choose not to take part at all.  If 
you decide to be in this study, you may stop participating at any time.  Any data that was collected as 
part of your participation in the study will remain as part of the study records and cannot be removed.   
 
If you decide not to be in this study, or if you stop participating at any time, you won’t be penalized or 
lose any benefits for which you otherwise qualify.   
 
What if I decide to withdraw from the study? 
You may withdraw by telling the study team you are no longer interested in participating in the study or 
you may send in a withdrawal letter.  A sample withdrawal letter can be found at 
https://hrpo.wustl.edu/participants/withdrawing-from-a-study/under Withdrawing from a Research 
Study. 
 
If you decide to leave the study early, we will ask you to return and complete the follow-up visit. 
 
Will I receive new information about the study while participating? 
If we obtain any new information during this study that might affect your willingness to continue 
participating in the study, we’ll promptly provide you with that information. 
 
Can someone else end my participation in this study? 
Under certain circumstances, the investigator might decide to end your participation in this research 
study earlier than planned.  This might happen for no reason or because: 
• You become pregnant 
• You do not follow the study doctor’s instructions 
• The doctor does not feel it is safe for you to continue 
• The study is ended by the sponsor or the institutional review board 
 
WHAT IF I HAVE QUESTIONS? 
We encourage you to ask questions.  If you have any questions about the research study itself, please 
contact: Nancy Bodet, RN at (314) 273-1376 or Brian S. Kim, MD at (314) 362-8171.  If you experience 
a research-related injury, please contact: Brian S. Kim, MD at (314) 362-8171. 
 
If you have questions, concerns, or complaints about your rights as a research participant, please contact 
the Human Research Protection Office at 660 South Euclid Avenue, Campus Box 8089, St. Louis, MO  
63110, 1-(800)-438-0445, or email hrpo@wustl.edu.  General information about being a research 
participant can be found on the Human Research Protection Office web site, http://hrpo.wustl.edu.  To 
offer input about your experiences as a research participant or to speak to someone other than the 
research staff, call the Human Research Protection Office at the number above. 
 
 
 
This consent form is not a contract.  It is a written explanation of what will happen during the study if 
you decide to participate.  You are not waiving any legal rights by agreeing to participate in this study. 
As a participant you have rights and responsibilities as described in this document and including: 


 
FOR IRB USE ONLY 
IRB ID #: 201709093 
APPROVAL DATE: 08/20/19 
RELEASED DATE: 08/26/19 
EXPIRATION DATE: 08/18/20 
 
APREMILAST (CC-10004) 
 
Version #3 (22 March 2018) 
 
Page 13 of 13 
• To be given enough time before signing below to weigh the risks and potential benefits and decide if 
you want to participate without any pressure from the research team or others. 
• To understand all of the information included in the document, have your questions answered, and 
receive an explanation of anything you do not understand. 
• To follow the procedures described in this document and the instructions of the research team to the 
best of your ability unless you choose to stop your participation in the research study. 
• To give the research team accurate and complete information. 
• To tell the research team promptly about any problems you have related to your participation, or if 
you are unable to continue and wish to stop participating in the research study. 
 
Your signature indicates that this research study has been explained to you, that your questions have 
been answered, and that you agree to take part in this study.  You will receive a signed and dated copy 
of this form. 
 
 
Do not sign this form if today’s date is after EXPIRATION DATE: 08/18/20. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Participant) 
 
 
 
 
(Date) 
 
 
____________________________________________ 
(Participant's name – printed) 
 
 
Statement of Person Who Obtained Consent 
 
The information in this document has been discussed with the participant or, where appropriate, with the 
participant’s legally authorized representative.  The participant has indicated that they understand the 
risks, benefits, and procedures involved with participation in this research study. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Person who Obtained Consent) 
 
(Date) 
 
 
___________________________________________ 
(Name of Person who Obtained Consent - printed) 
 
 

Prot_SAP_000.pdf: 
 
                                                                                                         
Brian S Kim, MD, MTR, FAAD 
Associate Professor of Medicine 
Co-Director, Center for the Study of Itch and Sensory Disorders 
Department of Medicine                 
 
Division of Dermatology 
St. Louis, MO 63110                    
                       
                                                                                                          
                                       
Washington University School of Medicine, Campus Box 8123, 660 S. Euclid Avenue, 
 St. Louis, Missouri 63110, (314) 747-6556, Fax (314) 362-8159     
16 March 2020 
 
 
 
 
 
To Whom it May Concern: 
 
 
Please find enclosed the protocol and informed consent form for the proof-of-concept open-label 
clinical trial entitled listed as “A Study Examining the Medication Apremilast as Treatment 
for Chronic Itch” on ClinicalTrials.gov (NCT03239106).  
 
Please see attached/uploaded documents.  
 
Please do not hesitate to contact me directly should anyone have questions at (314) 273-1376. 
 
 
 
Sincerely,  
 
 
 
 
 
 
Brian S. Kim, MD, MTR, FAAD 
Associate Professor of Medicine (Dermatology), Anesthesiology, and Pathology and Immunology 
Co-Director, Center for the Study of Itch and Sensory Disorders 
Department of Medicine/Division of Dermatology 
Washington University School of Medicine 






























Page 15 of 50 
fold body water volume, suggesting blood tissue distribution of this compound. The 
·.'--
terminal half-lives of apremilast in animals were short and ranged from 1 to 3 hours. The 
oral absorption of apremilast was high in mice and monkeys (Ĥ 70%). The oral 
bioavailability of apremilast was moderate (mouse and rat) to negligible (rabbit), 
suggesting that it is subject to first-pass extraction to varying degrees in animals. 
Notable gender differences were observed in rats, but not in mice and monkeys. When 
administered PO over a wide dose range, the exposure of apremilast increased in a 
less than dose-proportional manner, suggesting that apremilast absorption is solubility 
limited. On multiple dosing, a consistent trend of either decreasing or increasing 
exposures was not observed in mice and monkeys. The asymmetric center of 
apremilast was resistant to inversion in all the 4 animal models used for toxicity 
assessments. Apremilast was evaluated for photoxicity and showed no phototoxic or 
cytotoxic effect. 
\, __ 
Additional details as to the pharmacology of apremilast may be found in the 
Investigator's Brochure (see attached). 
1.6. 
Clinical Experience 
As of 30 Nov 2015, apremilast had been administered at daily doses ranging from 10 
to100 mg/day to over 5500 subjects in Celgene-sponsored studies, including over 4800 
subjects who received apremilast in Phase 2 or Phase 3 studies in psoriasis, PsA, AS, 
ulcerative colitis (UC), AD, Behcet's disease (BD), or RA 
To date, 28 clinical studies have been completed, including 20 Phase 1 studies and 8 
Phase 2 studies. A total of 15 clinical studies are currently ongoing: 4 Phase 2 studies 
(2 in subjects with psoriasis [including 1 pediatric study], 1 in subjects with AD, and 1 in 
subjects with UC), 10 Phase 3 studies (5 insubjects with PsA, 3 in subjects with 
psoriasis, 1 in subjects with BD, and 1 in subjects with AS), and 1 Phase 4 study (in 
subjects with psoriasis). A summary of all completed and ongoing Celgene-sponsored 
clinical studies with apremilast as of 30 Nov 2015 is presented. In addition, there have 
been 10 investigator-initiated trials (IITs) completed in subjects with AD, contact 
dermatitis, AS, cutaneous lupus, cutaneous sarcoidosis, lichen planus, osteoarthritis, 
prostatitis, vulvodynia, and rosacea. Additionally, 2 IIT studies (1 in plaque psoriasis and 
1 in palmo-plantar psoriasis) are onging as of November 2015. 
1.6.1. 
Phase 1 Apremilast Studies 
The clinical pharmacology program includes 20 completed studies. In these studies, 
716 healthy subjects were exposed to apremilast and 16 subjects with moderate or 
severe hepatic impairment, 8 subjects with severe renal impairment, 16 subjects with 
mild to moderate renal impairment, and 15 subjects with PsA or RA were exposed to 
apremilast. Single doses of apremilast over the dose range of 10 to 80 mg and multiple 
doses of up to 100 mg/day have been evaluated in Phase 1 studies. 
The PK of apremilast in healthy subjects under fasting conditions is characterized by 
rapid absorption, with Cmax occurring at a median time to maximum concentration 
(tmax ) of approximately 2.5 hours post-dose and an average absolute bioavailability of 
approximately 73%. 
CONFIDENTIAL 






















































Page42 of 50 
captured with a small sample size. Based on this amount of variance and starting NRS 
·'-..,
score, n = 10 is sufficient. 
"-
·-
9.4.2. 
Safety Analyses 
9.4.2.1. 
Adverse Events 
A treatment-emergent adverse event (TEAE) is any AE either reported for the first time 
or worsening of a pre-existing event after first dose of study drug. Analysis of AEs will 
be limited to TEAEs, but data listings will include all AEs regardless of their timing to 
study drug administration. 
The subset of AEs considered by the investigator to have a relationship to study drug 
will be considered to be treatment-related AEs. If the investigator does not specify the 
relationship of the AE to study drug, the AE will be considered treatment-related. The 
incidence of AEs and treatment-related AEs will be tabulated. 
9.4.2.2. 
Clinical Laboratory Tests 
Laboratory test values outside the normal range will be assessed for severity based on 
the normal ranges for the clinical reference laboratory. The incidence of abnormal 
laboratory values and shift tables relative to baseline will be tabulated. 
9.4.2.3. 
Vital Signs 
Descriptive statistics and mean change from baseline will be determined for vital signs 
(blood pressure, pulse, respiratory rate, and body temperature) at each assessment 
time. Electrocardiograms 
9.4.3. 
RNA seq Analysis 
Skin gene expression signatures will be performed at baseline and Week 12 to identify 
RNA signatures associated with treatment response. 
10.
ETHICAL CONSIDERATIONS AND ADMINISTRATIVE
PROCEDURES
10.1. 
Investigator Responsibilities
This study will be performed in accordance with ethical principles that originate in the 
Declaration of Helsinki and conducted in adherence to the study Protocol; GCPs as 
defined in Title 21 of the US CFR Parts 11, 50, 54, 56, and 312; ICH E6 GCP 
consolidated guidelines; and local regulatory requirements as applicable to the study 
locations. 
The investigator will be responsible for: 
CONFIDENTIAL 














Page 49 of 50 
3 Vasectomised partner is a highly effective method provided of avoiding pregnancy that partner is the 
© 
sole sexual partner of the WOCBP trial participant and that the vasectomised partner has received 
medical assessment of the surgical success. 
¾._,-
\..__.., 
4 In the context of this guidance, sexual abstinence is considered a highly effective method only if defined 
as refraining from heterosexual intercourse during the entire period of risk associated with the study 
treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the subject. 
CONFIDENTIAL