Clinical trial NCT03791060
Conditions: Necrobiosis Lipoidica Diabeticorum
Keywords: Necrobiosis lipoidica NLD
Sponsor: Beth Israel Deaconess Medical Center
Start date: 2019-04-03; Completion date: 2021-04-10
Enrollment: 4 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study investigates the efficacy of secukinumab in necrobiosis lipoidica diabeticorum (NLD).

Detailed description:
Necrobiosis lipoidica diabeticorum (NLD) is a rare granulomatous condition of the skin often presenting with papules and eventually atrophic plaques, most commonly on the distal extensor lower extremities, which can be painful and disfiguring. Currently no FDA-approved treatment exists, and no well-established treatment algorithm has been described. Reports on successful therapeutic interventions have generally been small and inconsistent.

Recent literature expanding on the previously poorly understood pathogenesis of NLD has suggested a potential role for IL-17 in the development of this condition. Thus blockade of IL-17 may be a potential therapeutic strategy in patients with NLD. Secukinumab (Cosentyx) is a human monoclonal antibody that targets IL-17a and is FDA approved for the treatment of psoriasis.

This open-label, proof of concept study regarding the use of Secukinumab in patients with NLD may be a first step in elucidating and defining a treatment for this chronic and potentially debilitating condition for which no FDA approved treatment currently exists.

Arms: arm 1: 300 mg q weekly for 5 weeks followed by 300 mg q 4 weeks.

Each subject will receive 300mg of Secukinumab by using 2 syringes of 150mg each as a subcutaneous injection at weeks 0,1,2,3,4 then every 4 weeks for a total of 9 doses over 24 weeks.
Interventions: intervention 1: Secukinumab
Intervention descriptions: intervention 1: Secukinumab is selective for human IL-17A and potently neutralizes the bioactivity of this cytokine. IL-17A is the central cytokine in multiple autoimmune and inflammatory processes. It is being recognized as one of the principal pro-inflammatory cytokines in autoimmune diseases such as psoriasis, PsA and AS, uveitis and is thought to play a role in other inflammatory conditions.

Protocol documents:
ICF_005.pdf: 
/NCT Number: 
NCT03791060 
Official Title: 
Secukinumab for NLD (Cosentyx) in Patients With Necrobiosis Lipoidica 
Diabeticorum (NLD)  
Document Type: 
Informed Consent  
Document Date: 
09/18/2020 


[CCI] Committee on Clinical Investigations 
 
Page 1 of 19 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date:09/11/2020     
 
**FOR CCI USE ONLY** 
Approved by the Beth Israel Deaconess Medical Center  
Committee on Clinical Investigations:  
 
Consent Approval Date:   
 
9/18/2020 
 
 
Protocol Number:  
 
 
2018P000634 
   
 
 
 
INFORMED CONSENT FORM TO TAKE PART IN A RESEARCH STUDY 
 
SUBJECT’S NAME:        
TITLE OF RESEARCH PROTOCOL:  An open-label proof of concept study regarding the use of 
Secukinumab (Cosentyx) in patients with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR:     Martina Porter, MD 
PROTOCOL NUMBER:       2018P000634 
 
INTRODUCTION: 
 This is a research study; 
 Your participation is voluntary; 
 A research study includes only people who choose to take part; 
 You may or may not benefit from participating in the study.  However, your participation 
may help others in the future as a result of knowledge gained from the research; 
 You may leave the study at any time; 
 If you choose not to take part, or if you leave the study, your decision will in no way harm 
your relationship with any member of the research team or any other individuals at Beth 
Israel Deaconess Medical Center. 
 
Please read this consent form carefully and ask the investigators or study staff to explain any words or 
information that you do not clearly understand.  Once you read this consent form and understand what 
your participation in this study will involve, you will be asked to sign this form if you wish to take part.  
You will be given a signed copy of the form to keep for your records. 
 
DISCLOSURE OF SPECIAL INTERESTS OF BIDMC AND INVESTIGATORS 
 
This study is being conducted by Dr. Martina Porter and is funded by Novartis.  The funding agency in 
this study, Novartis, is paying Beth Israel Deaconess Medical Center and Dr. Martina Porter to perform 
this research.  Drs. Alexa Kimball and Martina Porter are paid consultants for Novartis. 
 
WHOM TO CONTACT IF YOU HAVE QUESTIONS OR PROBLEMS 
 
If you have any questions, concerns or complaints about this research or experience any problems, 
you should contact Dr. Martina Porter at (617) 667-5834. 
 
PURPOSE 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
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[CCI] Committee on Clinical Investigations 
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SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
The study is being done to see and how well secukinumab will work to help people with Necrobiosis 
Lipoidica Diabeticorum (NLD).  We are also conducting this study to see if there are any changes to 
your skin under the microscope after you receive secukinumab. 
 
The drug involved in this study is investigational.  This means that the study drug is still being tested in 
research studies and is not approved by the Food and Drug Administration [FDA] for the way that it is 
being used in this study.  This particular investigational agent, Secukinumab, has been approved by 
the FDA for use in other diseases or conditions, but we do not yet know if it is useful or safe as a 
treatment for NLD . 
 
Secukinumab is a medicine called a biologic that works by suppressing the immune system. 
Specifically, secukinumab targets a protein in the body called IL-17. There is some evidence to 
suggest that IL-17 may play a role in the development of NLD. Therefore, inhibiting IL-17 with 
secukinumab may be a potential treatment for NLD.   
 
STUDY PARTICIPANTS 
You have been asked to be in the study because you have Necrobiosis Lipoidica Diabeticorum (NLD). 
 
Approximately 18 people will take part in this study at Beth Israel Deaconess Medical Center.  A total 
of 18 people will take part in this study at all study sites. 
 
DESCRIPTION OF STUDY DETAILS 
 
If you agree to be in this study, you will be asked to read and sign this consent form.  After you sign the 
consent form, the following things will happen: 
 
The study has 3 periods: 
 Screening period (up to 4 weeks before you receive your first dose of study drug) 
 Treatment period (26 weeks) 
 Follow-up period (12 weeks) 
 
1. Screening Period (Visit 1, approx. 3 hours):  Screening procedures are tests and procedures 
that will be done to determine if you are eligible to take part in the research study.  For this 
research study, the screening procedures include:   
 
 
Test your urine for pregnancy, if you are a female able to become pregnant. 
Pregnant women can't take part in this research study. 
 
Take your medical history, including any medications you are currently taking or 
have taken in the past. You will need to tell the study doctor about all medications 
or therapies you have used for your NLD in the past, even if you are not using them 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
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[CCI] Committee on Clinical Investigations 
Page 3 of 19 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
now. 
 
Physical exam, may include a measurement of your weight, height, blood 
pressure, heart rate, body temperature   
 
Examine and grade your NLD. 
 
The study doctor will ask you to rate your pain from your NLD  
 
Have blood drawn (to test your blood counts, electrolytes, kidney and liver 
function tests, HIV screening, Hepatitis B screening, Hepatitis C screening, and 
tuberculosis screening test) 
 
Take photos of your NLD. 
 
2. Treatment Period (10-11 visits, approx. 1-3 hours per visit):  Visits will occur every week 
through week 4, then every four weeks through week 24, then at week 26. If you qualify to 
take part in this research study, you will undergo these research procedures:   
 
 
Test your urine for pregnancy, if you are a female able to become pregnant. 
Pregnant women can't take part in this research study. 
 
Ask you about any changes in your health and medications since your last visit.  
 
Physical exam, may include a measurement of your weight, height, blood 
pressure, heart rate, body temperature   
 
Examine and grade your NLD. 
 
Questionnaires: you will be asked to rate your pain from your NLD and how it 
impacts your quality of life 
 
Blood for routine laboratory tests:  have blood drawn to test your blood counts, 
electrolytes, kidney and liver function tests 
o 
The amount of blood collected at each visit is as follows 
 
Screening: approximately 33 milliliters  
 
Baseline: approximately 9 milliliters 
 
Visits 4, 8, 12, 16, 20, 24 – approximately 9 milliliters at each visit   
 
In total approximately 96 milliliters will be collected 
 
Take photos of your NLD. 
 
A skin biopsy will be taken from one area where you have NLD 
 
Administration of study drug 
o 
Secukinumab will be given for 24 weeks 
 
It will be given weekly a week 0, 1, 2, 3 and 4 then every four weeks 
after that for a total of 9 doses 
 
It is dosed at 300 mg of secukinumab at each visit (given as 2 
injections of 150 mg each) and is given subcutaneously (meaning 
under the skin) 
 
Suture removal: Removal of any stitches placed 2 weeks after the skin biopsy 
 
 
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APPROVAL EXPIRATION DATE 
 
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[CCI] Committee on Clinical Investigations 
Page 4 of 19 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
See Table 1 below for a summary of study procedures. 
 
3. 
Monitoring/Follow-Up Period (One telephone call, approx. 30 min).  Procedures 
performed to evaluate the effectiveness and safety of the research procedures are called 
“monitoring” or “follow-up” procedures.   
 
You will be asked to complete one study visit after you have stopped taking the study drug 
that will occur over the phone. You will receive a phone call from our study staff at Week 36.  
During this phone call, we will ask about any changes in your health and medications since 
your last visit. 
 
4. Early Termination Visit 
If you stop or you are withdrawn from the study, you will be asked to return for an early termination 
visit. This visit will occur within 2 weeks after study withdrawal. The procedures at this visit will be the 
same as at the week 26 visit.  
 
Review adverse events 
 
Suture removal, if applicable 
 
See Table 1 below for a summary of study procedures. 
 
Table 1.  Summary of Study Procedures 
 
Study Procedures 
Screening  
BASELINE/WK0 
Wk1 
Wk2 
Wk3 
Wk4 
Wk8 
Wk12 Wk16 Wk20 Wk24 Wk26* 
Follow 
Up Call 
(Wk 
36) 
Medical history, including any 
medications you are currently 
taking or have taken in the past  


NLD history 

Eligibility criteria 


Vital signs 











Complete Physical 
 
Exam, including height and weight 



 


 
Any changes in your health 
and medications since your 
last visit 












 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
08/23/2021


[CCI] Committee on Clinical Investigations 
Page 5 of 19 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
Examination and grading of 
your NLD 
 
 
 
 
 
 
 
 
 
 
 
Questionnaires 
 
 
 
 
 
 
 
 
 
 
 
If you are a woman who can 
have children, a pregnancy 
test will be done 
 
 
 
 
 
 
 
 
 
 
 
Blood for routine laboratory 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood for HIV,  Hepatitis B 
screening, Hepatitis C 
screening, and tuberculosis 
screening test 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Photographs of your NLD 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review Adverse Events 
 
 
 
 
 
 
 
 
 
 
 
 
 
Skin biopsy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Suture removal* 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administration of the Study 
Drug 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HOW ARE THE SKIN BIOPSY SPECIMENS COLLECTED AND STORED? 
 
Skin Samples to be Collected 
The skin samples will be collected by a procedure called a skin biopsy.  The procedure will be 
performed by your study doctor. 
 
At the baseline visit (Week 0), a skin biopsy will be taken from an area of your skin that is affected 
by NLD.  The study doctor will determine the exact location after examining your skin. 
 
At Week 24), a skin biopsy will only be taken from an area of your skin that is affected by NLD.   
 
Before each of the skin biopsies, the area of your skin will be cleansed with an antiseptic solution 
(alcohol), and then numbed with a local anesthetic such as lidocaine, similar to what is used by a 
dentist.  Injection of the lidocaine may cause a brief burning sensation.  The doctor will use a small 
tube-like instrument, which will remove a very small piece of skin (4 mm) from your affected skin.  
The area may need to be closed with one or two stiches or gel foam, and then covered with a 
Vaseline and bandage.  The doctor will give you instructions on how to care for the area after the 
procedure.  After 2 weeks, you will need to come to the study site so the study staff can remove your 
stitches. 
 
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APPROVAL EXPIRATION DATE 
 
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Page 6 of 19 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
 
Skin Biopsy Evaluation 
A dermatopathologist, who is a specially trained doctor that looks at skin biopsies under the 
microscope, will review your skin biopsies for signs of inflammation.  He will also evaluate for 
biomarkers, or compounds in your body that can be used to tell if people suffer from certain diseases and 
how they may respond to medication, to see if your skin has changed under the microscope in response to 
the study drug.  Your skin biopsies will be stored in the pathology laboratory at BIDMC during the course of 
the entire study and will be destroyed upon study completion. 
 
RISKS AND DISCOMFORTS 
A risk to taking part in this study is the likelihood of receiving a drug or dose of a drug that may not 
be effective in helping to treat your disease.  This means that you may spend time and experience 
side effects taking a drug that may not provide you with any health-related benefits. 
 
As a result of your participation in this study, you are at risk for side effects listed in this section.  
You should discuss these with the investigator and with your regular doctor if you choose. 
 
Common 
• 
Sore throat and stuffy nose (upper respiratory tract infection, nasopharyngitis),  
• 
Runny nose (rhinitis), diarrhea 
• 
Cold sores (oral herpes) 
 
Rare 
• 
Oral thrush (oral candidiasis),  
• 
signs of low levels of white blood cells, such as fever, sore throat or mouth ulcers due 
to infections (neutropenia),  
• 
athlete’s foot (tinea pedis),  
• 
infection of the external ear (otitis externa),  
• 
discharge from the eye with itching,  
• 
redness and swelling (conjunctivitis),  
• 
itchy rash (urticaria) 
 
 
Pre-treatment Evaluation for Tuberculosis: Before receiving treatment with Secukinumab you will be 
evaluated for tuberculosis (TB) infection. You will not be eligible for this study, if you have an active 
TB infection or latent TB infection.  
 
Those subjects found to have latent TB will be referred to Infectious Disease for treatment.   
 
Hypersensitivity reactions: Allergic reactions have been seen in patients treated with Secukinumab 
 
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SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
during studies, including nettle rash or hives in up to 10% of patients, but most reactions were not 
serious and were mild to moderate in nature. If you have a history of severe hypersensitivity to any 
of the ingredients of the medicine, you should not be treated with Secukinumab and cannot 
participate in this trial.  The removable cap of the Secukinumab prefilled syringe contains natural 
rubber latex which may cause an allergic reaction in latex-sensitive individuals.  Severe allergic 
reaction with shock (anaphylactic reaction) and cases of urticaria occurred rarely in Secukinumab 
treated patients in clinical trials (<0.1% of treated patients). If a serious allergic reaction occurs, 
Secukinumab treatment should be stopped immediately and appropriate therapy started.  Signs of 
serious allergic reaction may include difficulty breathing or swallowing, low blood pressure, which 
can cause dizziness or light-headedness, swelling of the face, lips, tongue or throat, severe itching 
of the skin, with a red rash or raised bumps.   
 
Cancers and tumors that may be malignant:  Some medicines that influence the immune system 
may increase the risk of developing cancers. This is therefore a theoretical risk with Secukinumab, 
although currently there is no evidence that Secukinumab increases the risk of cancer. There is no 
adequate data available on the use of Secukinumab in patients who have, or have previously had, 
cancer. 
 
If you are pregnant or become pregnant, this treatment may involve risks to the embryo or fetus 
which are currently unforeseeable. 
 
PREGNANCY 
 
Because of the effects of this (these) study medication(s) on the developing fetus is (are) not known, you may 
not participate in this study if you are pregnant. You will be required to take a pregnancy test to verify that you 
are not pregnant before receiving your first dose of the study medication(s). 
 
For the duration of the study, if you are engaged in sexual activity that could cause you or your partner(s) to 
become pregnant, you and your partner(s) must agree to use a highly effective method of birth control or 
abstain from sexual activity that could cause you or your partner(s) to become pregnant. 
 
The methods of highly effective birth control for this study are below: 
1. Contraceptive implant, such as Nexplanon or Implanon 
2. Levonorgestrel or copper intrauterine device (IUD), such as Mirena, Skyla, ParaGard or Liletta 
3. Permanent female sterilization, such as tubal ligation or Essure with confirmed tubal occlusion 
4. Male partner(s) has had a vasectomy more than three months before study enrollment 
5. Oral contraceptives pill, patch or ring 
6. Injectable contraception, such as Depo Provera 
7. Consistent use of a barrier method, such as diaphragm with spermicide or condoms 
 
If you believe you have become pregnant while participating in this study, you must inform your study doctor 
 
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SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
immediately. Participants who become pregnant during the course of the study will immediately be withdrawn 
from the study, and the study doctors may ask to monitor your pregnancy, your health, and your baby’s 
health after you are withdrawn from the study. 
 
If you are a man capable of fathering children, you must use adequate contraception while participating in this 
study.  For the purposes of this study, adequate birth control means; 
 
1. use of a condom 
2. your partner must use an approved method of birth control as listed above. 
 
Other Risks Related to Study Procedures 
 Blood Tests: The risks and discomforts of blood drawing from a vein include the possibility of 
pain or bruising at the site of the blood draw, occasional feeling of lightheadedness, and 
rarely, infection at the site of the blood draw. 
 
 Subcutaneous (SC) Injection: A needle will be used to inject the medicine in the tissues 
under your skin, causing a small hole or puncture.  For most people, needle punctures for SC 
shots do not cause any serious problems.  Sometimes they may cause bleeding or bruising 
where the shot is given.  Sometimes people complain of discomfort, infections, and/or pain at 
the site of the shot.  Infection may happen with SC shots because the needle breaks the skin. 
 Then germs can get into the skin underneath. Shots may cause abscesses or skin and soft 
tissue infections.  Additionally, if a blood vessel is hit by the needle, the risk of infection will be 
even greater if germs are taken into the blood system. 
 
 Skin Biopsy: Minor bleeding at the site of the skin removal is the most common side effect.  
The biopsy may cause pain that typically resolves within several hours.  There is a small risk 
of infection at the biopsy sites.  After the procedure, if you have any bleeding, feel warmth, 
swelling, tenderness, or redness at the biopsy site, contact the study doctor.  You may have 
to come to the clinic so the doctor can check your biopsy site.  Additionally, although rare, the 
biopsy site may develop a small scar. 
 
 Surveys/Questionnaires: Some of the questions we will ask as part of this study may make 
you feel uncomfortable.  You may refuse to answer any of the questions and you may take a 
break at any time during the study.  You may stop your participation in the study at any time. 
 
HIV testing: Because the results of the HIV test done as part of this study may become a permanent 
part of your medical record, and because disclosure of a positive HIV test may have a negative impact 
on your insurability, employment, and social relationships, you may wish to seek a private confidential 
HIV test before enrolling in this study.  Again, if you choose to enroll in this study even after having the 
HIV test done privately, the HIV test will be done again as part of your participation in the study and 
therefore the results may become a permanent part of your medical record.  HIV is the cause of AIDS 
 
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SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
(the Acquired Immunodeficiency Syndrome).  A positive test result means that you are infected by 
HIV, but does not tell you that you have AIDS.  For antibody tests, a negative test usually means that 
a person is not infected.  However, it can take 3 to 6 months for the HIV antibody test to become 
positive after infection.  Having an HIV test is voluntary; however, if you choose to participate in this 
study HIV testing must be done to assure your safety (for example, in circumstances where a study 
drug would potentially have a negative effect on your ability to fight off infection and disease if you are 
HIV positive), to establish whether you are eligible to participate, and/or for other reasons required by 
the research protocol.  If you choose not to have HIV testing, you will not be able to participate in this 
study.  Massachusetts state law requires that you provide verbal informed consent before diagnostic 
testing for HIV is performed, and additional information relevant to the decision whether to get tested 
may be provided to you in connection with receiving the test; you are free to ask questions specifically 
about the implications of HIV testing.   
If you decide to participate and agree to be tested for HIV, the results of the HIV testing will be 
entered into your study chart in Dr. Martina Porter’s office, and may also be added to your medical 
record.  Information derived from this study and from your medical record may be reviewed and 
photocopied by state and federal regulatory agencies, including the Food and Drug Administration (FDA) 
and the Office of Human Research Protections (OHRP) where applicable, and the Committee on Clinical 
Investigations of the Beth Israel Deaconess Medical Center, with protection of confidentiality so far as 
permitted by applicable law.  Your physician is required by law to report positive HIV test results to 
health officials, including the Massachusetts Department of Public Health (MDPH) HIV/AIDS 
Surveillance Program.  Reports to the MDPH will include your full name, address, medical record 
number, social security number, date or birth and gender.  These reports may also include information 
about your medical history, health condition, and treatment.  Your written approval is not required for 
this mandatory reporting, assuming you agree to participate in this study and receive an HIV test as a 
result of that participation.  In general, releases of your HIV test results outside BIDMC (with the 
exception of required reporting to public health officials) require your written informed consent.  By 
signing this form, you agree that those individuals who need to see your medical information, including 
the results of your HIV test, in order to conduct the study (including the BIDMC researchers, any 
collaborators, the sponsor of the study, the BIDMC Committee on Clinical Investigations and other 
groups that oversee the research at BIDMC, and the government agencies that have jurisdiction over 
the research) may receive the results of your test.    
By signing here you acknowledge that all of your questions have been answered and you consent to 
the release of your HIV test results by BIDMC as necessary to complete the research study. 
 
 
Patient name (print):                                                             
Date 
 
 
LOSS OF CONFIDENTIALITY 
There is the potential for loss of confidentiality by participating in this study.  Every effort will be 
made to protect the confidentiality of your identifiable information.   
 
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SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
 
CONFIDENTIALITY 
 
Information learned from your participation in this study and from your medical record may be 
reviewed and photocopied by the Food and Drug Administration (FDA) and/or other federal and 
state regulatory agencies, and by the drug manufacturer, Novartis, accreditation agencies, the 
Committee on Clinical Investigations, the Human Subjects Protection Office and others involved in 
research administration of the Beth Israel Deaconess Medical Center.  Information resulting from 
this study and from your medical record may be used for research purposes and may be published; 
however, you will not be identified by name in such publications. 
 
MEDICAL RECORD 
A copy of this consent form and information collected during this research may become part of your 
medical record, if the information is relevant to the care you receive at Beth Israel Deaconess 
Medical Center.  Medical records are considered permanent records; therefore, information cannot 
be deleted from the record.  Medical records are available to health care professionals at Beth Israel 
Deaconess Medical Center and may be reviewed by staff when carrying out their responsibilities, as 
well as by external parties such as health care insurers and others in certain circumstances.  If you 
are not currently a patient at Beth Israel Deaconess Medical Center and do not have a medical 
record at Beth Israel Deaconess Medical Center, one may be created for you for your participation in 
this research.  You may also be required to register as a patient of Beth Israel Deaconess Medical 
Center in order to participate in this research. 
 
POSSIBLE BENEFITS 
 
It is not possible to predict whether you will benefit directly from participation in this study.  However, 
your participation may help others in the future as a result of knowledge gained from the research. 
 
OTHER AVAILABLE OPTIONS 
 
Taking part in this study is voluntary.  Instead of being in this study, you have the following options: 
 
 Topical steroids – topical means that the medicine is applied to the surface of the skin  
 Intralesional steroids – intralesional means that the medicine is injected under the surface of 
the skin  
 
 Surgery, laser, or phototherapy (phototherapy is when light treatments are used to help treat 
skin conditions) 
 Other immunosuppressive medications – these are medications that decrease the immune 
system 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
08/23/2021


[CCI] Committee on Clinical Investigations 
Page 11 of 19 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
 
It is important to note that it is possible to get Secukinumab at this institution and other locations 
even if you do not take part in the study.  Secukinumab has not been approved by the FDA for 
treatment of your condition, however, many doctors in the community commonly prescribe the drug 
to treat psoriasis, psoriatic arthritis, and ankylosing spondylitis.  Please be aware that not all doctors 
may agree to prescribe this drug for you, and that not all health insurance companies will pay for the 
drug when it is prescribed for NLD. 
 
This research study is not meant to diagnose or treat medical problems.  Participation in this 
research study does not take the place of routine physical examinations or visits to your regular 
doctor. 
 
We recommend that you discuss these and other options with the investigator and your regular 
doctor so that you can make a well-informed decision about participating in this study. 
 
IF YOU DECIDE NOT TO TAKE PART IN THE STUDY 
 
Participation in this study is voluntary.  You have the right to decide not to take part in this study.  If 
you choose to participate, you have the right to leave the study at any time. Your decision to not 
participate will not result in any penalties or loss of benefits to you. The investigators will tell you 
about new information that may affect your willingness to stay in this study.  
 
If you decide not to participate in the study or decide to leave the study early, your decision will not 
affect your relationship with the research team or any other individual at Beth Israel Deaconess 
Medical Center.   
 
INVESTIGATORS RIGHT TO STOP THE STUDY 
 
The investigators have the right to end your participation in this study if they determine that you no 
longer qualify to take part, or if it would be dangerous for you to continue, or if you do not follow 
study procedures as directed by the investigators.  Beth Israel Deaconess Medical Center or the 
funding source may stop the study at any time. 
 
COSTS AND/OR PAYMENTS TO YOU 
 
COSTS COVERED BY STUDY 
You will not be charged for tests, procedures, or medications that are part of this research study.  
However, you and your insurance company will be charged for other tests, procedures or 
medications of this study that are considered standard treatment for your medical condition.  
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
08/23/2021


[CCI] Committee on Clinical Investigations 
Page 12 of 19 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
PAYMENTS TO YOU: 
 
You will be paid for the following: $50 per scheduled study visit from Screening to Week 26 and an 
additional $100 for visits where a biopsy is performed (Week 0/baseline and Week 26 or Early 
Termination Visit).  
 
 If you complete the entire study, the total payment will be in the amount of $600. If you complete both 
biopsies, you will receive an extra $200.  Payment will be made by check after every 2 visits.  If you do not 
complete all visits, you can get paid at any time. Your payment will be prorated based on the number of visits 
that you completed. 
 
It may take up to 8 weeks for you to receive payment by check. 
 
Any payments made to you may be taxable income to you. This does not include any payments you 
may receive to reimburse (pay you back) you for certain expenses like parking fees or travel.  We 
are required to obtain your name and social security number for preparation and submission of 
Internal Revenue Service (IRS) Form 1099-Misc.  You may receive an Internal Revenue Service 
Form 1099 from BIDMC if you receive more than $600 or more in one calendar year for taking part 
in one or more research studies at BIDMC.  Questions about your own tax status should be referred 
to your personal tax advisor. 
 
You will be reimbursed for the following: parking 
The amount of reimbursement will be based on receipts for these expenses up to $20 per visit. 
 
COST OF RESEARCH RELATED INJURY: 
 
If you are injured as a direct result of your participation in this study, you should contact the 
Investigator at the number provided under the section “Who to Call if You Have Questions” in this 
form.  You will be offered the necessary care to treat your injury. We reserve the right to bill your 
insurance company or the sponsor, if appropriate, for the care you get for the injury.   We will try to 
get these costs paid for, but you may be responsible for some of them.  You may be responsible for 
all co-payments and deductibles required under your insurance.   At this time there is no plan to 
reimburse you for items such as lost wages or lost time from work.  By signing this consent form you 
have not given up any legal rights. 
 
OTHER IMPORTANT INFORMATION  
 
A description of this clinical trial will be available on www.ClinicalTrials.gov as required by U.S. 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. 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
08/23/2021


[CCI] Committee on Clinical Investigations 
Page 13 of 19 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
 
AUTHORIZATION FOR USE AND DISCLOSURE OF YOUR PROTECTED HEALTH 
INFORMATION 
As part of this study, we will be collecting, using and sharing with others information about you.  
Please review this section carefully as it contains information about the federal privacy rules and the 
use and disclosure of your information.   
 
PROTECTED HEALTH INFORMATION [PHI] 
By signing this informed consent document, you are allowing the investigators and other authorized 
personnel to use [internally at BIDMC] and disclose [to people and organizations outside the BIDMC 
workforce identified in this consent] health information about you.  This may include information 
about you that already exists (for example: your medical records and other sources of health 
information, demographic information, the results of any laboratory tests, and mental health records 
if applicable as well as any new information generated as part of this study.  This is your Protected 
Health Information. 
 
PEOPLE/GROUPS AT BIDMC WHO WILL SHARE AND USE YOUR PROTECTED HEALTH INFORMATION 
Your Protected Health Information may be shared with and used by investigators working on this 
study, including the supporting research team (such as research assistants and coordinators, 
statisticians, data managers, laboratory personnel, pharmacy personnel, and administrative 
assistants), and may also be shared and used by other health care providers at BIDMC who have 
treated you in the past and have information relevant to the research, or who provide services to you 
in connection with the research.  Your Protected Health Information may also be shared with the 
members and staff of the Committee on Clinical Investigations of Beth Israel Deaconess Medical 
Center, which is responsible for reviewing studies for the protection of the research subjects.  
 
PEOPLE/GROUPS OUTSIDE OF BIDMC WITH WHOM YOUR PROTECTED HEALTH INFORMATION WILL BE 
SHARED 
We will take care to maintain confidentiality and privacy about you and your Protected Health 
Information.  We may share your Protected Health Information with the following groups so that they 
may carry out their duties related to this study: 
 
 The other hospitals and medical centers taking part in this study and research collaborators 
at those institutions 
 Any external health care providers who provide services to you in connection with this 
research 
 Laboratories not affiliated with BIDMC that are involved in conducting tests related to the 
research 
 Statisticians and other data monitors not affiliated with BIDMC 
 The members and staff of any other IRBs (beyond the BIDMC Committee on Clinical 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
08/23/2021


[CCI] Committee on Clinical Investigations 
Page 14 of 19 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
Investigations) that oversee the research  
 Centralized data collectors  
 Your health insurance company 
 The Food and Drug Administration [FDA], the Department of Health and Human Services 
[DHHS], the National Institute of Health [NIH], the Office for Human Research Protections 
[OHRP], and other federal and state agencies that may have jurisdiction over the research 
 Hospital and Clinical Research Accrediting Agencies 
 Data and Safety Monitoring boards that oversee this study (if applicable) 
 
Those who receive your Protected Health Information during the course of the research may not be 
required by the federal privacy regulations to protect it, and they may make further disclosures to 
others and use your information without being subject to penalties under those laws.   
 
WHY WE ARE USING AND SHARING YOUR PROTECTED HEALTH INFORMATION 
The main reason for using and sharing your Protected Health Information is to conduct and oversee 
the research as described in this Informed Consent Document.  There are many other reasons 
beyond the research for which BIDMC may use or disclose your Protected Health Information.  Not 
all of these reasons require your express written authorization.  For example, we will use and share 
your Protected Health Information to ensure that the research meets legal, institutional and 
accreditation requirements and to conduct public health activities.  The various ways in which 
BIDMC may use and disclose your protected health information without your authorization are 
explained in a document called the Notice of Privacy Practices.  If you have not received a copy of 
BIDMC’s Notice of Privacy Practices, please ask us for one and review it before signing this form.  In 
addition to signing this document, you may also be asked to sign a BIDMC General Agreement form 
acknowledging that you have received the BIDMC Notice of Privacy Practices.   
 
NO EXPIRATION DATE – RIGHT TO WITHDRAW AUTHORIZATION 
Your authorization for the use and disclosure of your Protected Health Information in this Study shall 
never expire.  However, you may withdraw your authorization for the use and disclosure of your 
Protected Health Information at any time provided you notify the Principal Investigator in writing.  If 
you would like to take back your authorization so that your Protected Health Information can no 
longer be used in this study, please send a letter notifying the Principal Investigator of your 
withdrawal of your authorization to Martina Porter, 330 Brookline Ave., Boston, MA  02215. Please 
be aware that the investigators in this study will not be required to destroy or retrieve any of your 
Protected Health Information that has already been used or disclosed before the Principal 
Investigator receives your letter, and they are permitted to continue to use and disclose your 
previously collected information as necessary to complete the research. 
 
REFUSAL TO SIGN 
Your clinical treatment may not be conditioned upon whether you sign the Authorization for 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
08/23/2021


[CCI] Committee on Clinical Investigations 
Page 15 of 19 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
Research. However, if you choose not to sign this informed consent document and authorization for 
the use and disclosure of your Protected Health Information, you will not be allowed to take part in 
the research study. 
 
RIGHT TO ACCESS AND COPY YOUR PHI 
If you wish to review or copy your Protected Health Information as it is made part of your medical 
record, you may do so after the completion or termination of the study by sending a letter to the 
Principal Investigator requesting a copy of your Protected Health Information.  You may not be 
allowed to inspect or copy your Protected Health Information until this study is completed or 
terminated. 
 
ADDITIONAL CONTACT FOR QUESTIONS OR CONCERNS 
You may contact the Human Subjects Protection Office at [617] 975-8500 in the event that you 
would like to obtain information or to offer input about the research study.   This office is 
independent of the investigator or investigator’s research staff and can also assist with questions 
relating to your rights as a participant in research, which may include questions, concerns or 
complaints about your participation in the study. 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
08/23/2021


[CCI] Committee on Clinical Investigations 
Page 16 of 19 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
THE FOLLOWING PARAGRAPHS CONTAIN SOME STANDARD INFORMATION WHICH 
GENERALLY APPLIES TO INDIVIDUALS PARTICIPATING IN A RESEARCH STUDY. 
 
CONSENT FORM FOR CLINICAL RESEARCH 
I have read the previous page[s] of the consent form and the investigator has explained the details 
of the study.  I understand that I am free to ask additional questions. 
 
If I wish additional information regarding this research and my rights as a research subject, or if I 
believe I have been harmed by this study, I may contact the Human Subjects Protection Office 
(HSPO). 
 
I am aware that this is a research project and that unforeseen side effects may occur. 
 
I understand that the Beth Israel Deaconess Medical Center has no formal program for 
compensating patients for medical injuries arising from this research.  Medical treatment will be 
provided for injuries at the usual charge to me or to my insurer unless payment is otherwise provided 
for in this consent form. 
 
I understand that participation in this study is voluntary and I may refuse to participate or may 
discontinue participation at any time without penalty, loss of benefits, or prejudice to the quality of 
care which I will receive. 
 
I acknowledge that no guarantees have been made to me regarding the results of the treatment 
involved in this study, and I consent to participate in the study and have been given a copy of this 
form. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Subject 
or 
 
 
 
 
Date 
Legally Authorized Representative   
(Parent if the subject is a minor) 
 
 
 
 
 
 
 
 
 
 
 
 
Relationship of Legally Authorized Representative to Subject   
 
 
The subject has been given the opportunity to read this consent form and to ask questions 
before signing, and has been given a copy. 
 
___________________________________________________________ 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
08/23/2021


[CCI] Committee on Clinical Investigations 
Page 17 of 19 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
SIGNATURE OF INVESTIGATOR/Co-Investigator   
DATE 
 
__________________________________________________________ 
PRINT INVESTIGATOR’S/Co-Investigator’s  
NAME 
A signing co-investigator must be listed on the study’s approved Research Staffing Form at 
the time of consent. 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
08/23/2021


[CCI] Committee on Clinical Investigations 
Page 18 of 19 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
THE FOLLOWING SECTIONS ARE NOT NEEDED FOR ALL STUDIES AND SHOULD BE 
UTILIZED AS INDICATED: 
 
If the subject is able to speak and understand English but is not able to read or write  
 
I was present during the entire oral presentation of the informed consent and witnessed the 
subject’s agreement to participate in the study. 
 
Signature of Witness:  
 
Printed Name of Witness:  
 
Date:   
 
 
If the subject is able to understand English but is not physically able to read or write or see 
 
I was present during the entire oral presentation of the informed consent and witnessed the 
subject’s agreement to participate in the study. 
 
Signature of Witness:  
 
Printed Name of Witness:  
 
Date:   
 
 
 
If the subject is not English speaking and signed the translated Short Form in lieu of the 
English consent document. 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
08/23/2021


[CCI] Committee on Clinical Investigations 
Page 19 of 19 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: An open-label proof of concept 
study regarding the use of Secukinumab (Cosentyx) in patients 
with necrobiosis lipoidica diabeticorum 
PRINCIPAL INVESTIGATOR'S NAME: Martina Porter, MD 
PROTOCOL #: 2018P000634 
 
Informed Consent – Part D 
CCI Form: 4-2018 
PI Revision Date: 09/11/2020    
 
As someone who understands both English and the language spoken by the subject, I interpreted, in 
the subject’s language, the researcher’s presentation of the English consent form.  The subject was 
given the opportunity to ask questions.  
Signature of Interpreter:  
 
Printed name of Interpreter:  
 
Date:  
 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
08/23/2021

Prot_SAP_002.pdf: 
 
PROTOCOL DOCUMENT WITH STATISTICAL ANALYSIS INCLUDED 
 
 
Title: Secukinumab for NLD (Cosentyx) in Patients With Necrobiosis 
Lipoidica Diabeticorum (NLD) 
 
 
NCT: NCT03791060 
 
 
Document Date: 11-10-2020 


(CCI) Committee on Clinical Investigations 
Page 1 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
PART B 
STUDY DESCRIPTION 
 
TITLE OF PROTOCOL 
An open-label proof of concept study regarding the use of Secukinumab 
(Cosentyx) in patients with necrobiosis lipoidica diabeticorum (NLD) 
 
Principal Investigator 
Martina Porter, MD 
 
 
 
B1. 
PURPOSE OF PROTOCOL 
The objective of this study is to evaluate whether the IL-17 inhibitor, secukinumab shows evidence of efficacy 
in the treatment of Necrobiosis Lipoidica Diabeticorum (NLD).  
 
 
B2. 
SIGNIFICANCE AND BACKGROUND FOR THE STUDY 
Background: 
Necrobiosis lipoidica diabeticorum (NLD) is a rare granulomatous condition of the skin that is over-
represented in patients with diabetes.  Classically, this condition presents with papules and plaques, most 
commonly on the distal extensor lower extremities. These plaques can become atrophic over time displaying a 
characteristic yellow hue, and may subsequently ulcerate. Although in many patients the lesions are not 
painful, in approximately 25% of patients the lesions can be very painful, particularly among patients who 
develop ulcerations.  
 
The nature of the relationship between NLD and diabetes mellitus is poorly understood. The incidence of NLD 
in people with diabetes mellitus is estimated to be 0.3% to 1.2%.  Initial studies from the 1960’s suggested 
that approximately 60% of patients with NLD also had diabetes, however subsequent studies reported lower 
estimates of diabetes in patients with NLD (11%), and further epidemiologic studies have not been performed.  
 
The condition may be challenging to manage, as currently no FDA-approved treatment exists, and no well-
established treatment algorithm has been described. Reports on successful therapeutic interventions have 
generally been small and inconsistent.  
 
The pathogenesis of NLD is poorly understood, however associations with vascular changes and immune 
dysregulation have been explored. Recent literature has suggested a potential role for IL-17 in the 
development of this condition.  In 2012, Wakusawa et al reported a case of a 37 year old woman with NLD and 
insulin dependent diabetes mellitus. Immunohistochemical staining was performed on a biopsy specimen and 
revealed a significant number of IL-17 positive cells present throughout the granuloma. [1] 
 
Kato et al subsequently reported a 66 year old woman with typical clinical and histopathological features of 
NLD without diabetes mellitus. [2] In their report, immunohistochemical staining found IL-17 expression 
present in lymphocytes, macrophages, multinucleated giant cells, and a high density of IL-17 expressing T-cells 
in granulomatous regions and around blood vessels.  Together these cases suggest that NLD may be an 
inflammatory disorder involving TH17 cells and that vessels may be the target of inflammation. This may, in 
part explain, previous reports of patients with NLD who have been successfully treated with TNF-alpha 
antagonists. Finally, Wakatsuki has reported a patient with concurrent NLD and palmoplantar pustulosis (PPP). 
Immunohistochemistry performed on biopsy specimens found IL-17 producing cells densely associated with 
NLD lesions, as well as PPP lesions. 
 
 


(CCI) Committee on Clinical Investigations 
Page 2 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
 
Rationale: 
The reports described above suggest a possible role for IL-17 in the pathogenesis of NLD, and raise the 
possibility that blockade of IL-17 may be a potential therapeutic strategy in patients with NLD. Secukinumab is 
a human monoclonal antibody that targets IL-17a, approved by the FDA for the treatment of psoriasis. Several 
phase III studies have found this medication to be largely safe with nasopharyngitis and headache reported as 
the most frequently observed adverse events.  
 
An open-label proof of concept study regarding the use of secukinumab in patients with NLD may be a first 
step in elucidating and defining a definitive treatment for this chronic and potentially debilitating condition for 
which no FDA approved treatment currently exists.  
 
 
B3. 
DESCRIPTION OF RESEARCH PROTOCOL 
A. 
Study Design – Overview, Methods, Procedures 
 
Study Design 
This study is a non-randomized, open-label, proof of concept study.  Eighteen patients aged 18 and over with 
histopathologically-proven NLD will be included in a prospective non-controlled study. Dosage of Secukinumab 
will be given according to the standard therapy regimen for psoriasis (300 mg q weekly for 5 weeks followed 
by 300 mg q 4 weeks).  The study compromises a 2-week screening period, a 24-week open-label study period, 
and a 12-week follow-up period. The follow-up period consists of a phone call 16 weeks after the last study 
drug dose. 
 
Population 
Patients potentially eligible for this study are at least 18 years of age and have histologically 
confirmed necrobiosis lipoidica diabeticorum. A total of 18 subjects will be enrolled in the study. 
Potential patients will be assessed for eligibility to participate in this clinical study using the criteria 
for inclusion and exclusion listed under “Subject Selection” section.  
 
Methods 
Study Endpoints: 
1. Primary Endpoint 
- 
Proportion of patients achieving remission or clinical improvement based on Investigator 
Global Assessment Score as measured at week 24.  
 
2. Secondary Endpoints 
- 
Proportion of subjects achieving improvement based upon histological score 
- 
Proportion of subjects improving based upon patient-reported outcomes (pain score and 
Dermatology Quality of Life Index Score) 
 


(CCI) Committee on Clinical Investigations 
Page 3 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
Investigator Global Assessment (IGA) of Efficacy Score (See Investigator Global Assessment of 
Efficacy Score) 
(adapted from scoring system for published pyoderma gangrenosum trials) 
Score 
Description 
0 
Completely clear: except for possible residual hyperpigmentation 
1 
Almost clear: very significant clearance (about 90%); however, patchy remnants of 
dusky erythema and/or very small ulcerations 
2 
Marked improvement: significant improvement (about 75%); however, a small 
amount of disease remaining (i.e. remaining ulcers, although have decreased in size, 
minimal erythema and/or active boarder) 
3 
Moderate improvement: intermediate between slight and marked; representing 
about 50% improvement 
4 
Slight improvement: some improvement (about 25%); however, significant disease 
remaining (i.e. remaining ulcers with only minor decrease in size, erythema or 
boarder activity) 
5 
No change from baseline 
6 
Worse 
Scoring system based on the following trial [4]:  
An open-label pilot study of alefacept for the treatment of pyoderma gangrenosum. European 
Academy of Dermatology and Venereology 2008 22, pp943–949 
 
Histological Score 
 
a. 
Inflammatory infiltrate (0, none; 1, slight; 2, moderate; 3, severe) 
b. 
collagen degeneration (0, none; 1, slight; 2, moderate; 3, severe) 
c. 
epithelioid histiocytes, (0, none; 1, slight; 2, moderate; 3, severe) 
d.  
qualitative expression of IL-17 (0, none;  1, slight; 2 moderate; 3, severe) 
 
Scoring system based on the following trial [5]:  
Fumaric acid esters in necrobiosis lipoidica: results of a prospective noncontrolled study. British 


(CCI) Committee on Clinical Investigations 
Page 4 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
Journal of Dermatology 2005 153, pp802–807 
 
Patient-Reported Outcomes 
Pain Score 
 (i) 
Resolved 
(ii) 
Improved 
(iii) 
Stable 
(iv) 
Worsened  
 
Dermatology Life Quality Index (DLQI) 
A Quality of Life Score will be calculated based upon the Dermatology Life Quality Index (DLQI).    
The DLQI is a validated general dermatology questionnaire that consists of 10 items that assess 
subject health-related quality of life (daily activities, personal relationships, symptoms and feelings, 
leisure, work and school, and treatment) (See Dermatology Life Quality Index). [7] It has been 
extensively used in dermatology clinical trials for AD. The DLQI is a psychometrically valid and reliable 
instrument that has been translated into several languages, and the DLQI total scores have been 
shown to be responsive to change. The minimally important difference for the DLQI 
has been estimated as a 2 to 5 point change from baseline.  
 
Other study parameters 
Safety Parameters 
Safety evaluations include adverse event (AE) monitoring, physical examinations, vital sign measurements, and 
clinical laboratory testing (hematology and chemistry) as a measure of safety and tolerability for the entire 
study duration. 
At every visit adverse events will be registered.  
 
Randomization, blinding and treatment allocation 
This is an open-label proof of concept study. There will be no randomization or blinding.  All subjects 
will receive study treatment.   
 
Study Procedures 


(CCI) Committee on Clinical Investigations 
Page 5 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
Prior to performing any study related procedures, the investigator will discuss with each subject the 
nature of the study, its requirements and its restrictions. A written informed consent form will be 
obtained from each participant prior to any procedure.   
 
Each subject with a signed informed consent form will be screened at the first visit, to ensure all the 
inclusion criteria are met and none of the exclusion criteria.  
 
Study procedures are described in detail below and an overview of the study procedures during each 
visit. 
Medical history 
• A complete medical history, including history of diabetes, will be taken at screening. The 
subject's medical history will be updated at the Baseline visit. This updated medical history 
will serve as the baseline for clinical assessment. 
 
• Demographic information, including subject self-reported gender, race, age, ethnicity, and 
child-bearing potential will be recorded. 
 
• Nicotine and alcohol history will be obtained 
 
• NLD history: Date of onset of NLD, all previous and current medical and procedural 
treatments for NLD, and reasons for discontinuation or outcomes of previous treatments will 
be obtained. 
 
Vital signs 
Vital sign determinations of systolic and diastolic blood pressure, pulse rate, and body temperature 
will be obtained at visits as specified in the Overview of Study Procedures.   Blood pressure and pulse 
rate should be measured after the subject has been sitting for at least 3 minutes. 
 
Complete Physical exam, including height and weight.  
Height will be measured at screening only.  Body weight will be measured at all scheduled visits as 
specified in Overview of Study Procedures. The subject will wear lightweight clothing and no shoes 


(CCI) Committee on Clinical Investigations 
Page 6 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
during weighing. A complete physical examination, including cutaneous examination to evaluate for 
skin malignancies, will be performed at the designated study visits as specified in Overview of Study 
Procedures. The physical examination performed on Study Day 0 will serve as the baseline physical 
examination for the entire study. If appropriate, a targeted physical exam should be performed at 
any other visit (e.g., to evaluate a reported adverse event). Any significant physical examination 
findings after the first dose will be recorded as adverse events, while any findings prior to the first 
dose will be recorded as medical history. All findings, whether related to an AE or part of each 
subject's medical history, will be captured on the appropriate AE report form. At any time, a 
symptom‐directed physical examination can be performed as deemed necessary by the Investigator. 
 
Efficacy assessment:  
IGA of Disease Severity will be performed by the investigator.  Patient-reported outcomes, including 
DLQI and Pain score, will be administered to subjects as subject questionnaires prior to any 
assessment of disease severity or laboratory testing.  See Overview of Study Procedures for schedule 
and Study Parameters for further details on efficacy assessments. 
 
Laboratory Testing 
Blood samples will be collected at scheduled visits as listed in Overview of Study Procedures.  A 
certified laboratory at Beth Israel Deaconess Medical Center (BIDMC) through the Clinical Research 
Center will be utilized to process and provide results for the clinical laboratory tests. 
Laboratory reference ranges will be obtained prior to the initiation of the study. The Baseline 
laboratory test results for clinical assessment for a particular test will be defined as the last 
measurement prior to the initial dose of study drug. 
 
Whether action needs to be taken to address notable laboratory values will be decided by the investigator, 
taking into account the overall status of the subject.  
 
The following laboratory tests will be performed according to the study procedures schedule listed in 
Overview of Study Procedures: 
 
• Complete Blood Count (CBC):  automated WBC, RBC, hemoglobin, hematocrit, platelet count 


(CCI) Committee on Clinical Investigations 
Page 7 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
and RBC indices 
• Complete Metabolic Panel (CMP):  Sodium, Potassium, Chloride, Bicarbonate, BUN, 
Creatinine, Glucose, Alk Phos, ALT, AST, Total Bilirubin, GGT, Albumin, Albumin/Globulin Ratio 
(calculated), BUN/Creatinine Ratio (calculated), Calcium, Globulin (calculated), Total Protein 
• HIV: HIV1&2 Antibody/Antigen Combo Assay 
• Hepatitis B: Hep B Core Ab (Hep B Cab), Hep B Surface Antigen (Hep B Sag), and Hep B surface 
antibody (Hep B Sab) 
• Hepatitis C: Hepatitis C antibody 
• Tuberculosis: Quantiferon-TB Gold 
Subjects who test positive for TB (quantiferon gold), Hepatitis C antibody, or Hepatitis B Sag or 
Hepatitis B Core antibody will be excluded from the study. Patients with a positive quantiferon gold 
will be referred to ID. If a patient has an indeterminate quantiferon gold that test will be repeated. If 
there are two indeterminate quantiferon gold results, then the patient will be referred to ID. If ID 
thinks the patient (with an indeterminate quant gold) needs to be treated for latent TB, then the patient 
will be treated for latent TB (see below). If ID does not think the patient (with an indeterminate quant 
gold) needs treatment for latent TB then the patient will be eligible to enroll in the clinical trial 
 
After one month of treatment for latent TB, a subject would be considered eligible for participation in 
the trial.  
 
Skin Biopsy 
A 4 mm punch biopsy will be obtained from lesional skin at the baseline and week 26 visit.  Skin 
biopsy location will be determined by the investigator and standard procedures for skin biopsy will 
be employed.  Subjects may have lesions closed with suture or gelfoam, depending on nature of 
lesion and biopsy.   
 
Skin biopsies will be sent to Dermatopathology lab at BIDMC for further Immunohistochemistry 
analysis as below.  Samples will be preserved in formalin jars and sent to the histology lab to be 
processed within 48 hours.   The paraffin blocks will be sectioned and stained at the histology lab, 
and then blocks and slides will be returned to the Dermatopathologist and stored securely at BIDMC, 
Dept of Pathology. Samples are retained for the duration of the project, through publication.  If all 


(CCI) Committee on Clinical Investigations 
Page 8 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
members of the study team deem they are no longer needed, they will then be destroyed.  
 
Immunohistochemistry 
Each biopsy will be fixed in formalin, bisected vertically, dehydrated by routine histologic methods, 
and embedded in a paraffin block.  5-µm-thick surface sections will be cut, mounted on glass slides, 
and baked for 60 minutes at 60C.  The first slide will be stained with Hematoxylin and Eosin. The next 
slide will be loaded into the Bond III staining platform and antigen retrieved by immersion in Bond 
Epitope Retrieval 2 for 30 minutes. It will then incubated at room temperature for 30 minutes with 
Anti-Human IL17A antibody [Abcam 4K5F6] at a concentration of 0.5–10 μg/ml.  After appropriate 
washes, antibody detection will be performed using Bond Polymer Refine Detection kit.  Slides will be 
developed in DAB, then dehydrated and coverslipped.  A biopsy of an active psoriatic skin lesion and 
a slide of the case with no antibody applied will be run in parallel as positive and negative controls, 
respectively. 
 
Evaluation of immunohistochemistry 
IL-17A expression levels will be scored as follows:  A three tier stratification threshold for percentage 
of positive lymphocytes will be established after review of the pre-treatment biopsies, and classified 
as absent, low, or high.  Cellular staining intensity will be scored as 0 (no staining), 1 (weak staining), 
2 (moderate staining), or 3 (strong staining). 
Pre- and post-treatment expression levels will be compared using Fisher’s exact test. Pre-treatment 
IL17A expression level will be compared with clinical response parameters and evaluated as a 
possible predictor of response to therapy. 
 
In case of an adverse event or disease progression, patients are instructed to call and/or visit the 
clinic trials unit at Beth Israel Deaconess Medical Center. Any visits will be recorded on source 
documentation as Unscheduled Visits.  Any o fthe procedures may be performed at an unscheduled 
visit at the discretion of the investigator.  
 
Follow up phone call at Week 36 
Study personnel will call subjects to collect information regarding the status of any ongoing AEs/SAEs 
or the occurrence of any new AEs/SAEs since last study visit. 


(CCI) Committee on Clinical Investigations 
Page 9 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
 
EARLY TERMINATION VISIT 
If a subject is withdrawn from the study for any reason, including withdrawing informed consent, 
he/she will be asked to return for an early termination visit within 2 weeks of being withdrawn from 
the study.  Procedures performed at Early Termination Visit will be identical to Week 26 visit. 
 
Treatment of Subjects 
Investigational Treatment: Secukinumab (Cosentyx)  
Secukinumab (Cosentyx) is a human monoclonal antibody that targets IL-17a and is FDA-approved for 
the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis. Recent literature expanding 
on the previously poorly understood pathogenesis of NLD has suggested a potential role for IL-17 in 
the development of this condition. Thus blockade of IL-17 may be a potential therapeutic strategy in 
patients with NLD 
Dosage 
Dosage of Secukinumab will be given according to the standard therapy regimen for psoriasis and 
administered for 24 weeks. Each subject will receive 300mg of Secukinumab by using 2 syringes of 
150mg each as a subcutaneous injection at weeks 0,1,2,3,4 then every 4 weeks for a total of 9 doses 
over 24 weeks.  Medication will be administered during scheduled study visits by study personnel. 
Use of Co-intervention 
Co-medication 
A full list of current medication, including over-the counter medicines, will be noted for each subject 
at time of screening visit and will updated at each visit in their medical chart/report form. 
Analgesic Therapy 
If a subject develops more than transient pain or the subject’s pain increases after starting 
treatment, they are allowed to start analgesic therapy. In case of NLD-related pain, the subject will 
be asked to report this at the next visit.  
Exacerbation/Intervention 
In case exacerbations of NLD lesions occur in the treatment areas and an intervention is required, the 
investigator may decide to treat with standard therapies not anticipated to decrease size of active 
areas such as antibiotics.  Use of any of the prohibited treatments listed below could that could 


(CCI) Committee on Clinical Investigations 
Page 10 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
confound the efficacy assessment are NOT allowed during the study.  If the subject requires 
treatment with any of the prohibited treatments listed below, the subject should be discontinued 
from the study treatment will proceed to an early termination visit. 
Any medication or surgical treatment that will be used to treat AEs will be recorded on the electronic 
case report forms (eCRF). 
Prohibited Therapy 
The treatments listed below are prohibited for all subjects during the study: 
 
Any investigational agent 
 
Any immunosuppressive systemic therapy started within 28 days prior to baseline, including 
but not limited to oral corticosteroids, adalimumab or other biologic agent, etc. 
 
Surgical intervention on the treatment areas 
Investigational Product/Study Drug 
Secukinumab (Cosentyx) 
Secukinumab (Cosentyx) is a human monoclonal antibody that targets IL-17a and is FDA approved for 
the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis.     
 
COSENTYX injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly 
yellow solution. COSENTYX is supplied in a single-use Sensoready pen with a 27-gauge fixed ½-inch 
needle, or a single-use prefilled syringe with a 27-gauge fixed ½-inch needle. The removable cap of 
the COSENTYX Sensoready pen or prefilled syringe contains natural rubber latex. 
 
Each COSENTYX Sensoready pen or prefilled syringe contains 150 mg of secukinumab formulated in: 
Lhistidine/histidine hydrochloride monohydrate (3.103 mg), L-methionine (0.746 mg), polysorbate 80 
(0.2 mg), trehalose dihydrate (75.67 mg), and Sterile Water for Injection, USP, at pH of 5.8. 
 
Secukinumab will be supplied by the sponsor, Novartis, and will be packaged in quantities sufficient 
to accommodate study design.  Each kit will be labeled per local requirements and this label must 
remain affixed to the kit.  Upon receipt, study drug should be stored as specified on the label in their 
original packaging and kept in a secure location. A temperature log will be maintained for 
documentation in the research pharmacy.  Administration of the study drug will be recorded by study 


(CCI) Committee on Clinical Investigations 
Page 11 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
personnel at scheduled study visits.  
Summary of findings from clinical and non-clinical studies 
Secukinumab is a recombinant human monoclonal IgG1/κ antibody that binds specifically to IL-17A. It 
is expressed in a recombinant Chinese Hamster Ovary (CHO) cell line. Secukinumab has a molecular 
mass of approximately 151 kDa; both heavy chains of secukinumab contain oligosaccharide chains.  
Please refer to the local label available to you for information regarding the efficacy and safety of this 
product. 
 
Overview of Study Procedures: 
Evaluation Schedule: 
Activity 
Screening  
BASELINE/WK0 
Wk1 
Wk2 
Wk3 
Wk4 
Wk8 
Wk12 
Wk16 
Wk20 
Wk24 Wk26* 
Follow 
Up Call 
(Wk 
36) 
 
 Informed consent 
 
Demographics 
 
 Medical history 
 
 
Nicotine use and alcohol 
history
 
NLD history 
 
Eligibility criteria 
 
 
Prior/concomitant therapy 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs 
 
 
 
 
 
 
 
 
 
 
 
Complete Physical 
 
Exam, including height and 
weight
 
 
 
 
 
 
 
Adverse event assessment 
 
 
 
 
 
 
 
 
 
 
 
IGA of disease severity 
 
 
 
 
 
 
 
 
 
 
 
Pain Score 
 
 
 
 
 
 
 
 
 
 
 
DLQI 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test for 
women of childbearing 
potential 
 
 
 
 
 
 
 
 
 
 
 
CMP & CBC 
 
 
 
 
 
 
 
 
 
 
 
 
 
TB Screening  
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV, Hepatitis B (Hep B Sag, 
Hep B Sab, Hep B Cab) and 
Hepatitis C Screening (Hep 
C ab) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Digital photography of 
l
i
 
 
 
 
 
 
 
 
 
 
 
 
 


(CCI) Committee on Clinical Investigations 
Page 12 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
Skin biopsy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Suture removal* 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer Secukinumab 
 
 
 
 
 
 
 
 
 
 
 
 
 
* = if suture is placed following skin biopsy 
 
Multi-Site: Joslin Diabetes Center 
The Co-Investigator at Joslin Dr. Giulio Romeo will be responsible for generating a list of patient MRNs with 
NLD diagnosis in their records. The list will generate a list of patients seen at Joslin as well as BIDMC. The list 
will be shared with BIDMC study team, who will then contact the patients via letters. Patients will be pre-
screened by BIDMC study team only. Patient study visits will take place at BIDMC and Dr. Romeo will not be 
involved in the study visits at BIDMC. Patients study related records will only be stored at BIDMC and not 
shared with Joslin or Dr. Romeo.  
After study completion follow up call: 
We want to call patients who have completed the study (n=3) and had an early termination (n=1) for a follow 
up call. We will ask them general question about well-being, any side effects, and option to send photos of 
their NLD lesions. Patients can send photo to secure telederm or clinical trials email account.  
B. 
Statistical Considerations 
Sample Size Calculation 
A sample size calculation is not applicable, for this is an early feasibility and tolerability pilot study. 
Data/statistical analysis 
Study Parameters 
The clinical efficacy will be measured by physician assessments and standardized scoring tools as 
noted in Main Study Parameters and Secondary Parameters.  Because of the small number of 
patients in the study, and absence of a control group, primarily descriptive statistics will be used to 
report data from measured endpoints. 
Main Study parameters 
Primary Endpoint 
• 
Proportion of patients achieving remission or clinical improvement based on Investigator Global 
Assessment Score as measured at week 24.  
We will assess the proportion of patients achieving remission or clinical improvement based upon 
the previously published Investigator Global Assessment Score. Remission correlates with a score of 0 
or 1 and clinical improvement correlates with at least a -1 change from baseline.  
 
Secondary study parameters 


(CCI) Committee on Clinical Investigations 
Page 13 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
Secondary Endpoints 
Because of the small sample size, primarily descriptive statistics will be used. 
• Proportion of subjects achieving improvement based upon histological score 
• Proportion of subjects achieving improvement based upon patient-reported outcomes (pain 
score and Dermatology Quality of Life Index Score) 
Other study parameter(s) 
Patient characteristics and demographic data will be presented using descriptive statistics. 
Histological Score 
In addition, a histological score will be calculated as a secondary endpoint. The score is calculated by 
adding sub scores as listed below, which will be evaluated by the dermatopathologist.  Average of 
pre and post scores and overall change in score will be calculated and compared using a paired T-
test.  See Secondary Study Parameters for details regarding histologic analysis. 
Pain Score 
A Pain Score will be calculated based upon the Wong-Baker 10-point pain score, which has been 
widely used to rate pain in both children and adults and has also been used in dermatology clinical 
trials.[6] 
Response based on an improvement from baseline in the Wong-Baker pain score at all scheduled 
time points will be calculated. We will compare pre and post treatment pain values and categorize 
patients as  
Dermatology Life Quality Index (DLQI) 
A Quality of Life Score will be calculated based upon the Dermatology Life Quality Index (DLQI).    
 
 
 
 
 
 


(CCI) Committee on Clinical Investigations 
Page 14 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
C. 
Subject Selection 
Inclusion Criteria 
A subject must meet all of the following criteria in order to be eligible to participate in this study: 
1. Adults, age 18 and over 
2. Previous diagnosis of biopsy-proven NLD  
3. Active NLD lesions, defined as 
(i) clinical signs of inflammation, for example erythematous margins, sensations of itch, pain, 
dysaesthesia  
(ii) lesions increasing in size or appearance of new lesions within the last 3 months  
(iii) ulcerations 
4. Subjects must be able to understand and communicate with the investigator and comply with 
the requirements of the study and must give a written, signed and dated informed consent 
before any study related activity is performed. 
Exclusion Criteria 
Eligible subjects will be excluded from participation if they meet any of the following criteria: 
1. History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis 
infection as defined by a positive QuantiFERON TB-Gold test at screening.  
2. Are currently pregnant, breastfeeding, or planning to get pregnant during the study. 
3. Previous hypersensitivity reaction to secukinumab or to any of the components.  
4. History of Inflammatory Bowel Disease (Crohn’s Disease or Ulcerative Colitis) 
5. Allergy to Latex  
6. Currently on any other immunosuppressant systemic medication or within 28 days of 
baseline visit 
7. Women of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant, unwilling to use effective contraception during the study and for 16 
weeks after stopping treatment.  Methods of acceptable birth control are listed below 
under “Women of Childbearing Potential” 
8. Subjects with a serum creatinine level exceeding 176.8 μmol/L (2.0 mg/dL) 
9. Screening total WBC count <2,500/μL, or platelets <100,000/μL or neutrophils <1,500/μL or 
hemoglobin <8.5 g/dL 
10. Known infection with HIV, hepatitis B or hepatitis C at screening or randomization.  Patients 
who are Hepatitis B Core antibody and/or Hep B Surface Antigen positive will be excluded 
from this study.  Patients who are Hepatitis C ab positive will also be excluded from this 
study. 
11. History of lymphoproliferative disease or any known malignancy or history of malignancy of 
any organ system within the past 5 years (except for non-melanoma skin cancer and 
carcinoma in situ of the cervix) 
12. Are participating in another study using an investigational agent or procedure during 
participation in this study or within 28 days prior to baseline visit.  
13. Plans for administration of live vaccines during the study period or 6 weeks prior to randomization 
14. Any other procedural treatment for NLD with 28 days prior to baseline visit, including 
phototherapy, surgical intervention, laser therapy, or cryotherapy. 
15. Any other active skin disease or condition (e.g., bacterial, fungal or viral infection) that may 
interfere with assessment of NLD; 
16. Underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, 
pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the 


(CCI) Committee on Clinical Investigations 
Page 15 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
opinion of the investigator significantly immunocompromises the subject and/or places the 
subject at unacceptable risk for receiving an immunomodulatory therapy 
Women of Childbearing Potential 
Women of child-bearing potential, defined as all women physiologically capable of becoming 
pregnant, unwilling to use effective contraception during the study and for 16 weeks after stopping 
treatment. Effective contraception is defined as one of the following: 
• 
Combined (estrogen and progestogen containing) hormonal birth control (oral, 
intravaginal, transdermal) associated with inhibition of ovulation 
• 
Progestogen-only hormonal birth control (oral, injectable, transdermal) associated 
with inhibition of ovulation 
• 
Bilateral tubal occlusion/ligation 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS ). 
• 
Vasectomized sexual partner(s) (the vasectomized partner should have received 
medical assessment of the surgical success and is the sole sexual partner of the trial 
participant). 
• 
True abstinence: Refraining from heterosexual intercourse when this is in line with the 
preferred and usual lifestyle of the subject (periodic abstinence [e.g., calendar, ovulation, 
symptothermal, post-ovulation methods] and withdrawal are not acceptable). 
 
 
 
  
 
 
B4. 
POSSIBLE BENEFITS 
It is not possible to predict whether you will benefit directly from participation in this study.  
However, your participation may help others in the future as a result of knowledge gained from the 
research. 
 
 
 
 
 
 
B5. 
POSSIBLE RISKS AND ANALYSIS OF RISK/BENEFIT RATIO 
RISKS AND DISCOMFORTS 
Summary of known and potential risks and benefits. 
Benefits: there are no FDA-approved treatments for NLD.  Subjects enrolled in this study may 
improve with study treatment.  It is not possible to predict whether subjects will benefit directly from 
participation in this study.  However, subject participation may help others in the future as a result of 
knowledge gained from the research. 
 
Infections  
Cosentyx may increase the risk of infections. In clinical trials, a higher rate of infections was observed 
in Cosentyx treated subjects compared to placebo-treated subjects. In placebo-controlled clinical trials 
in patients with moderate to severe plaque psoriasis, higher rates of common infections such as 


(CCI) Committee on Clinical Investigations 
Page 16 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
nasopharyngitis (11.4% versus 8.6%), upper respiratory tract infection (2.5% versus 0.7%) and 
mucocutaneous infections with candida (1.2% versus 0.3%) were observed with COSENTYX 
compared with placebo. A similar increase in risk of infection was seen in placebo-controlled trials in 
patients with psoriatic arthritis and ankylosing spondylitis. The incidence of some types of infections 
appeared to be dose-dependent in clinical studies. 
 
We will evaluate patients for tuberculosis (TB) infection prior to initiating treatment with 
COSENTYX. A positive TB test would lead to exclusion from the trial. 
  
Inflammatory Bowel Disease 
Exacerbations of inflammatory bowel disease (IBD), in some cases serious, occurred in COSENTYX 
treated patients during clinical trials in plaque psoriasis, psoriatic arthritis and ankylosing spondylitis. 
In addition, new onset inflammatory bowel disease cases occurred in clinical trials with COSENTYX. 
In an exploratory study in 59 patients with active Crohn’s disease, there were trends toward greater 
disease activity and increased adverse events in the secukinumab group as compared to the placebo 
group.   
 
Patients will be screened prior to inclusion in trial for a history of IBD. Patients who are treated with 
Cosentyx should be monitored for signs and symptoms of inflammatory bowel disease.  
 
Hypersensitivity Reaction 
Anaphylaxis and cases of urticaria occurred in Cosentyx treated patients in clinical trials. If an 
anaphylactic or other serious allergic reaction occurs, administration of Cosentyx should be 
discontinued immediately and appropriate therapy initiated. 
 
Risk of Hypersensitivity in Latex-sensitive Individuals  
The removable cap of the Cosentyx Sensoready pen and the Cosentyx prefilled syringe contains 
natural rubber latex which may cause an allergic reaction in latex-sensitive individuals. The safe use of 
Cosentyx Sensoready pen or prefilled syringe in latex-sensitive individuals has not been studied.  
 
 
Vaccinations  
Patients treated with Cosentyx should not receive live vaccines. Prior to initiating therapy with 
Cosentyx, we will consider completion of all age appropriate immunizations according to current 
immunization guidelines. 
 
Non-live vaccinations received during a course of Cosentyx may not elicit an immune response 
sufficient to prevent disease. 
 
Risks listed in the consent form are the following: 
Common 
• 
Sore throat and stuffy nose (upper respiratory tract infection, nasopharyngitis),  
• 
Runny nose (rhinitis), diarrhea 
• 
Cold sores (oral herpes) 
 
Rare 
• 
Oral thrush (oral candidiasis),  
• 
signs of low levels of white blood cells, such as fever, sore throat or mouth ulcers due 
to infections (neutropenia),  


(CCI) Committee on Clinical Investigations 
Page 17 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
• 
athlete’s foot (tinea pedis),  
• 
infection of the external ear (otitis externa),  
• 
discharge from the eye with itching,  
• 
redness and swelling (conjunctivitis),  
• 
itchy rash (urticaria) 
Other Risks Related to Study Procedures: 
• Blood Tests: The risks and discomforts of blood draws 
• Subcutaneous (SC) Injection: discomfort, infections, and/or pain at the site of the injection.  
Skin Biopsy: bleeding, pain, infection, scar 
 
 
 
B6. 
RECRUITMENT AND CONSENT PROCEDURES 
Recruitment 
Dermatologists and Dermatopathologists from Beth Israel Deaconess Medical Center will be 
informed using IRB approved recruitment letters of this study and asked to refer eligible patients to 
our research unit. These letters will explain the purpose of the research, including a brief description 
of the nature and extent of involvement, and the investigator's email and phone number will be 
included.  A research advertisement will also be posted in the dermatology clinic. 
 
A list of potential subjects will be compiled from  all BIDMC Dermatology physicians’ patient 
population using ICD codes for necrobiosis lipoidica diabeticorum. These identified patients will be sent 
recruitment letters informing them of the study and to contact Dr. Porter if they are interested. 
 
The study will also be placed on TrialX as well as skinstudies.com, craigslist, twitter and BU quickie 
jobs. TrialX will use clinicaltrials.gov information; skinstudies.com, craigslist, twitter and BU quickie 
jobs will use the recruitment flyer and language from the targeted provider email.  
 
We will advertise the study on Twitter as well with the following posting: “Do you have necrobiosis 
lipoidica diabeticorum? You may be eligible to participate in a clinical trial. If you are interested visit 
our website skintudies.com, email us at clears@bidmc.harvard.edu or call at 617-667-5834.”  
 
The flyer will also be posted at the Dimock Center.  
 
Joslin will generate a list of patient with NLD diagnosis in their records.  
 
Consent 
Prior to entering the study, a licensed physician investigator will explain to the potential subject the 
nature of the study, its purpose, procedures, expected duration, and the benefits and risks involved 
in study participation.  The licensed physician will explain the main study. 
 
Subjects will be given the opportunity to ask questions and be informed of their right of study 
withdrawal.  After this explanation and before any study-specific procedures have been performed, 
the potential subject may voluntarily sign and date the informed consent form, thereby giving 
permission for the subject to enter the study.  


(CCI) Committee on Clinical Investigations 
Page 18 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
 
Prior to participation in the study, the subject will receive a copy of the signed and dated written 
informed consent form and any other written information provided to the subject. If, for any reason, the 
subject desires more time to consider the decision, the subject will be given a copy of the unsigned 
consent form for reference and instructed to call the office if they decide to participate in the study. 
 
Subject Protection 
In order to address the issue of patients feeling pressured to participate, a standard approach was 
developed and implemented years ago. This gives the patient the opportunity to actively 
demonstrate their interest before enrolling in the study. If a discussion about the study presents 
itself during a clinical encounter, the patient is offered to take the consent home and read and then 
asked to follow up with the clinic if they are interested. It is also attempted to have a physician who 
is not involved in their clinical care go over their consent form in order to provide further separation.  
 
B7. 
STUDY LOCATION 
 Privacy  
Subject visits will be conducted in the CRC at BIDMC or, rarely, in private patient exam rooms in the 
dermatology clinic if the CRC is not available at the time of subject visits.  Both locations should 
ensure adequate privacy for patients.  Patients will complete all study related procedures in these 
private settings, including questionnaires.  Questionnaires will be in written form and returned 
directly to the investigators or study staff. 
 
Pre-screening telephone calls and subject visits will be limited only to the minimum amount of data 
necessary to accomplish the research purposes.  No sensitive questions will be discussed by 
telephone. 
 
Physical Setting 
 
Subject visits will be conducted in the CRC at BIDMC or, rarely, in private patient exam rooms in the 
dermatology clinic if the CRC is not available at the time of subject visits.  Both locations should 
ensure adequate privacy for patients.  Patients will complete all study related procedures in these 
private settings, including questionnaires. 
 
 
 


(CCI) Committee on Clinical Investigations 
Page 19 of 19 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 11-10-2020 
 
B8. 
DATA SECURITY 
All subjects will be assigned a subject number at their screening visit.  Only investigators and study 
staff at BIDMC will have access to the subject’s identifiable health information. To ensure 
appropriate privacy and confidentiality, any paper source documentation and questionnaires will be 
stored in a locked cabinet.  Only the PI, sub-investigator, and study staff will have access to this 
locked cabinet. This documentation will all be coded.  Subject’s identifiable health information will 
be kept separate from coded documentation.  Any electronic data containing PHI will be stored on a 
password protected computer in a locked office and on a secure server behind the BIDMC firewall.  
 
The Investigator will maintain adequate records for the study, including source documentation, 
Informed Consent documents, drug dispensing and disposition records, information regarding 
participants who discontinued, adverse events, and other pertinent data. All essential documents 
will retained by the Investigators for at least 10 years in a long-term storage facility as arranged 
through the CTO. 
 
 
 
 
B9 
Multi-Site Studies 
 
Is the BIDMC the coordinating site?       
 Yes    
 No  
 
Is the BIDMC PI the lead investigator of the multi-site study?     
 Yes    
 No  
 
 
 
 
B10 
Dissemination of Research Results 
 
Subjects will be thanked for their participation in the study immediately following their last visit.  
Because we are not able to anticipate the final completion date of the study, which may take years, 
and because we are not primarily responsible for analyzing and publishing the data, it will not be 
feasible for investigators to provide results to individual subjects.  Subjects may contact the PI 
following their completion of the study to inquire about the final findings of the study, if available to 
the investigators, at that time. 
 
Planned dissemination of research results may include abstract presentations at dermatology 
conferences and submission of data for publication in academic journals as an original research 
article.