Clinical trial NCT03403036
Conditions: Psoriasis
Keywords: Psoriasis brodalumab
Sponsor: Icahn School of Medicine at Mount Sinai
Start date: 2017-10-31; Completion date: 2018-08-18
Enrollment: 39 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study will evaluate the safety and efficacy of brodalumab in the treatment of moderate-to-severe psoriasis in patients who have previously failed treatment with interleukin (IL)-17A therapies. Forty patients will be enrolled in this 16-week open-label study. Patients will receive 210 mg of brodalumab subcutaneous injection at weeks 0, 1, and 2, followed by 210 mg every 2 weeks. The primary efficacy endpoint will be the proportion of patients achieving a score of "0-clear" or "1-almost clear" in the sPGA score after 16 weeks of treatment. After completion of the 16-week trial, patients may desire to continue treatment with brodalumab.

Detailed description:
This study will evaluate the safety and efficacy of brodalumab in the treatment of moderate-to-severe psoriasis in patients who have previously failed treatment with interleukin (IL)-17A therapies. Failure of IL-17A therapy will be defined as previous treatment with either secukinumab or ixekizumab for at least 3 months without achieving PASI-75 response or a 50% loss of original improvement. Forty patients will be enrolled in this 16-week open-label study. Patients will be enrolled at three to four different sites in the US. After enrollment, study visits will occur at monthly intervals, with patients receiving 210 mg of brodalumab subcutaneous injection at weeks 0, 1, and 2, followed by 210 mg every 2 weeks. At each visit, patients will be evaluated for change in sPGA (Physician's Global Assessment), PASI score, and any signs or symptoms of adverse events. Laboratory screening will include tests for tuberculosis and neutropenia. After completion of the 16-week trial, patients may desire to continue treatment with brodalumab. Efforts will be made to provide drug to these study patients, including those who do not have insurance.

Arms: arm 1: Brodalumab (210 mg) via subcutaneous injection using prefilled syringes
Interventions: intervention 1: Brodalumab
Intervention descriptions: intervention 1: Weeks 0, 1, 2, and every 2 weeks thereafter through and including Week 16.

Protocol documents:
Prot_SAP_000.pdf: 
A Study to Evaluate the Safety and Efficacy of Brodalumab in Subjects With Moderate to 
Severe Plaque Psoriasis Who Have Failed IL-17A Therapies.
PI: Dr. Mark Lebwohl
NCT03403036
Document Date: Oct 12, 2017


1 
 
A Study to Evaluate the Safety and Efficacy of Brodalumab in 
Subjects With Moderate to Severe Plaque Psoriasis Who Have Failed 
IL-17A Therapies. 
 
Protocol Version Date:  July 18, 2017 
 
Amendment #1: 
 
October 2, 2017 
 
Amendment #2: 
 
October 12, 2017 
 
 
Lead Investigator:  
Mark Lebwohl, MD 
 
Lead Site: 
 
 
Icahn School of Medicine at Mount Sinai 
Department of Dermatology  
5 East 98th Street - 
, Box 1048 
New York, NY 10029 
Tel:  212-241-3288 
 
 
Additional Sites: 
 
Soo Jung Kim, MD, PhD 
 
 
 
 
 
Baylor College of Medicine 
 
 
 
 
1977 Butler Boulevard, 
 
 
Houston, TX 77030 
Tel: 713-798-6131 
 
 
 
 
 
Jerry Bagel, MD 
Windsor Dermatology 
D.B.A.Psoriasis Treatment Center of Central New Jersey 
59 One Mile Road 
East Windsor, NJ 08520 
Tel: 609-443-4500 ext 1402  
 
 
 
 
 
 
 


2 
 
INTRODUCTION/BACKGROUND 
Psoriasis is a common, chronic inflammatory skin disease that is characterized by the 
formation of sharply demarcated, scaly, erythematous plaques. It is a prevalent disease, 
affecting about 2.2% of the population in the United States.[1] Psoriasis has a high 
impact on patients’ quality of life, with many reporting discomfort, itching, and significant 
social and emotional burden secondary to the disease. [2, 3] Without treatment, 
remission from psoriasis is unlikely. [4] Traditional treatment options include topical 
steroids and vitamin D analogues, and systemic immunosuppressive agents such as 
cyclosporine and methotrexate. However, these treatments are often not as efficacious 
as would be desirable, and are associated with significant side effects and risks. In the 
past several years, the development of biologic agents, in particular monoclonal 
antibodies, has revolutionized the treatment of psoriasis. 
Brodalumab is a human interleukin-17 receptor A (IL-17RA) antagonist recently 
approved for the treatment of moderate-to-severe plaque psoriasis. Clinical trials of 
brodalumab included 3 multicenter, randomized, double-blind, controlled trials which 
enrolled a total of 4373 adult subjects with moderate-to-severe plaque psoriasis.[5] At 
week 12, PASI-75 and PASI-100 responses were seen in about 85% and 40% of 
patients, respectively. Nearly 80% of patients achieved static Physician’s Global 
Assessment (sPGA) scores of clear (0) or almost clear (1) at week 12. Maintenance of 
treatment effect was also established, with high response rates seen through week 52. 
Of note, approximately 30% of patients reported previous treatment with a biologic, and 
12% reported treatment failure with a previous biologic. [5] At present, other biologic 
drugs that target the IL-17 signaling pathway include secukinumab and ixekizumab, 
although these agents inhibit the IL-17A ligand, rather than its receptor. It is unknown 
how patients who have failed treatment specifically with other IL-17 targeting agents 
respond to brodalumab treatment.  
This study will evaluate the safety and efficacy of brodalumab in the treatment of 
moderate-to-severe psoriasis in patients who have previously failed treatment with 
interleukin (IL)-17A therapies. Failure of IL-17A therapy will be defined as previous 
treatment with either secukinumab or ixekizumab for at least 3 months without achieving 
PASI-75 response or a 50% loss of original improvement. Forty patients will be enrolled 
in this 16-week open-label study. Patients will be enrolled at three to four different sites 
in the US. After enrollment, study visits will occur at monthly intervals, with patients 
receiving 210 mg of brodalumab subcutaneous injection at weeks 0, 1, and 2, followed 
by 210 mg every 2 weeks. At each visit, patients will be evaluated for change in sPGA 
(Physician’s Global Assessment), PASI score, and any signs or symptoms of adverse 
events. Laboratory screening will include tests for tuberculosis and neutropenia. The 
primary efficacy endpoint will be the proportion of patients achieving a score of “0-clear” 
or “1-almost clear” in the sPGA score after 16 weeks of treatment. After completion of 
the 16-week trial, patients may desire to continue treatment with brodalumab. Efforts will 
be made to provide drug to these study patients, including those who do not have 
insurance.  
 


3 
 
HYPOTHESIS: 
 
Primary Hypothesis: 
1. It is hypothesized that treatment with brodalumab, an IL-17RA antagonist, will be 
effective in the treatment of moderate-to-severe psoriasis patients who have 
previously failed treatment with IL-17A therapies.  
 
OBJECTIVES:  
 
Primary objective: To evaluate the efficacy of brodalumab in the treatment of 
moderate-to-severe psoriasis patients who have previously failed treatment with IL-17A 
therapies by measuring different scoring systems for psoriasis (PASI, BSA, sPGA; see 
appendix) at week 16.  
 
Secondary objective: To determine the safety of brodalumab in the treatments of 
moderate-to-severe psoriasis patients who have previously failed treatment with IL-17A 
therapies. 
 
ENDPOINTS:  
 
Primary endpoint: Proportion of patients achieving a score of “0-clear” or “1-almost 
clear” in the sPGA score after 16 weeks of treatment. 
  
Secondary endpoints:  
1. Proportion of patients achieving PASI-100 response after 16 weeks of treatment. 
2. The proportion of patients who achieve an improvement of 50% or greater in 
BSA involvement after 16 weeks of treatment. 
3. Proportion of patients achieving PASI-75 response after 16 weeks of treatment. 
4. Proportion of patients achieving PASI-90 response after 16 weeks of treatment. 
  
 
RESEARCH DESIGN: 
 
This is an open-label study of a total of 40 subjects enrolled at 3 to 4 sites, with 
moderate-to-severe psoriasis who have previously failed treatment with an IL-17A 
agent. Subjects will receive brodalumab 210 mg of via subcutaneous injection at weeks 
0, 1, and 2, followed by 210 mg every 2 weeks; total study length is 16 weeks.  
 
METHODS: 
 
Informed consent will be obtained at the study site at the time of the first consultation for 
participation in this study.  
 
After providing informed consent, subjects will be assessed for study eligibility at the 
Screening visit (day -28 to day -1). At the Screening visit the following procedures will 
be performed:  


4 
 
1. Medical history and concomitant as well as prior medications/treatments will be 
reviewed 
2. Skin examination will be performed (including assessment of PASI, sPGA, and 
BSA)  
3. Approximately 14 cc (approximately 3 teaspoons) of blood will be drawn for a 
complete blood count (including differential) (not required if subject can provide 
results from a previous test performed within 4 months of screening visit). 
4. Approximately 5 cc (approximately 1 teaspoon) of blood will be drawn for a 
QuantiFERON TB-Gold test (QFT) assay; or subjects will undergo tuberculin 
purified protein derivative (PPD) testing (not required if subject can provide 
results of a negative test performed within 8 months of screening visit).  
5. Females of child bearing potential will have 5 cc (approximately 1 teaspoon) of 
urine collected for a pregnancy test. This test must be negative in order to qualify 
for the study.   
 
Subjects will be deemed eligible as per inclusion/exclusion criteria. Qualified subjects 
meeting all the inclusion and exclusion criteria will be start treatment at Day 0/Baseline 
(within 28 days of signing the consent form). Female subjects of child-bearing potential 
will have 2 teaspoons of urine collected for a pregnancy test prior to treatment. This test 
must be negative in order to continue to qualify for the study.  Assessments at this Day 
0/Baseline visit include skin examination with assessment of PASI, sPGA, and BSA 
scores.  
 
Subjects will receive brodalumab (210 mg) via subcutaneous injection using prefilled 
syringes at Weeks 0, 1, 2, and every 2 weeks thereafter through and including Week 
16. Patients will be taught how to administer the drug subcutaneously by a study 
investigator or designated research staff member at the Baseline visit. They will be 
dispensed a one-month supply of medication at baseline and each subsequent visit for 
self-administration at home.  
 
At Weeks 4, 8, 12 and 16 subjects will return for assessment of concomitant 
medications and adverse events, and skin assessments including PASI, sPGA,  BSA 
scores, and photography of target lesion(s). In addition, females of child-bearing 
potential will have 2 teaspoons of urine collected for a pregnancy test at each visit.   
 
PATIENT POPULATION:  
 
Prior to enrollment, all subjects must meet the following inclusion and exclusion criteria: 
 
Inclusion criteria:  
 
1. Male or female subject at least 18 years of age 
2. Subject is able to provide written informed consent and comply with the 
requirements of this study protocol.  
3. Have both a sPGA score of ≥3  and BSA ≥ 5% prior to randomization.  


5 
 
4. Subjects who are women of childbearing potential must have a negative urine 
pregnancy test at screening and must be practicing an adequate, medically 
acceptable method of birth control for at least 30 days before Day 0 and at least 
6 months after the last study drug administration. Acceptable methods of birth 
control include intrauterine device (IUD); oral, transdermal, implanted or injected 
hormonal contraceptives (must have been initiated at least 1 month before 
entering the study); tubal ligation; abstinence and barrier methods with 
spermicide. Otherwise, if not of childbearing potential, subjects must: have a 
sterile or vasectomized partner; have had a hysterectomy, a bilateral 
oophorectomy or be clinically diagnosed infertile; or be in a menopausal state for 
at least a year. 
5. Tuberculin purified protein derivative (PPD) or QuantiFERON TB-Gold test (QFT) 
negative at the time of screening, or if patient has a history of positive PPD or 
QuantiFERON, he/she has initiated or completed the appropriate prophylaxis.   
6. Subject is judged to be in good general health as determined by the principal 
investigator based upon the results of medical history and laboratory profile. 
7. Subject has previously failed treatment with an IL-17A agent,  secukinumab or 
ixekizumab, (where available, defined as previous treatment with either drug for 
at least 3 months without achieving PASI-75 response or a 50% loss of original 
improvement). 
8. Last administration of secukinumab or ixekizumab ≥ 28 days prior to Baseline. 
 
 
Exclusion criteria:  
 
1. Have predominantly pustular, erythrodermic, and/or guttate forms of psoriasis.  
2. History of an ongoing, chronic or recurrent infectious disease, or evidence of 
tuberculosis infection as defined by a positive tuberculin purified protein 
derivative (PPD) or QuantiFERON TB-Gold test (QFT) at Screening. Subjects 
with a positive or indeterminate PPD or QFT test may participate in the study if a 
full tuberculosis work up (according to local practice/guidelines) is completed 
within 12 weeks prior to randomization and establishes conclusively that the 
subject has no evidence of active tuberculosis. If presence of latent tuberculosis 
is established, then treatment must have been initiated at least for 4 weeks prior 
to randomization and the course of prophylaxis is planned to be completed. 
3. Subjects with a history of HIV, or history of positive HCV or HBV 
4. Use of any of the following therapies within 4 weeks prior to Baseline (Visit 2): 
systemic non-biologic psoriasis therapies (including, but not limited to): psoralens 
and ultraviolet A (PUVA) therapy, cyclosporine, methotrexate, azathioprine, 
corticosteroids, apremilast, tofacitinib, oral retinoids, mycophenolate mofetil, 
sirolimus; 1, 25 dihydroxyvitamin D analogs; or phototherapy (including UVB or 
self-treatment with tanning beds or therapeutic sunbathing) or topical psoriasis 
therapy with psoralens. 
5. Use of topical corticosteroid preparations, topical calcineurin inhibitors, or other 
topical preparations with immunomodulatory properties within 2 weeks prior to 
Baseline (Visit 2).  


6 
 
6. Use of any investigational drug or any systemic drug for psoriasis within four 
weeks prior to Baseline (Visit 2).  
7. Serious concomitant illness that could require the use of systemic corticosteroids 
or otherwise interfere with the patient’s participation in the trial. 
8. Clinically important deviation as judged by the investigator (such WBC< 3) from 
normal limits in physical examination, vital sign measurements, clinical laboratory 
tests results, not associated with a chronic, well-controlled medical condition. 
 
9. Any active live-vaccines 3 months prior to baseline and throughout the study. 
10. Have a current or history of lymphoproliferative disease within 5 years prior to 
Baseline (Visit 2); or have current or history of any malignant disease within 5 
years prior to Baseline (Visit 2). 
11. History of suicide attempt, or are clinically judged by investigator to be at risk of 
suicide.  
12. History of Crohn’s disease.  
13. Had a serious infection, been hospitalized, or received IV antibiotics for an 
infection, within 12 weeks prior to Baseline (Visit 2). 
14. Known immunodeficiency, or history of infection typical of an 
immunocompromised host.  
15. At screening, have a neutrophil count <1500 cells/uL.  
16. At screening, have a lymphocyte count <800 cells/uL. 
17. At screening, have a platelet count <100,000 cells/uL.  
18. At screening, have a total white blood count (WBC) < 3000 cells/uL. 
19. At screening, have a hemoglobin <8.5 g/dL.  
20. Have donated >450 mL of blood within 4 weeks prior to screening (Visit 1), or 
intend to donate blood during the course of the study.  
21. Women who are lactating or breastfeeding.  
22. Any other condition that precludes the patient from following and completing the 
protocol, in the opinion of the investigator.  
 
 
STATISTICAL METHODS: 
 
Individual efficacy variables, the sum of those variables, and safety parameters will be 
analyzed separately. Subjects who discontinue prematurely because of inadequate 
response or because of adverse events will have their last results carried forward for 
purposes of analysis. 
 
ADVERSE EVENTS: 
 
As of July 19, 2016, the brodalumab safety package across multiple indications included 
6243 brodalumab-treated patients. The majority of patients were followed for 1 to 2 
years, with 102 having follow up for over 5 years. The safety profile of brodalumab in 
psoriasis patients include 4464 patients, using integrated safety data from the phase 2 
and phase 3 trials, and their open-label extensions. Overall, the safety profile of 
brodalumab was found to be consistent with other biologic agents targeting the IL-17 
pathway.   


7 
 
 
The most common adverse events (>2% of patients) in patients exposed to brodalumab 
210 mg q2w were nasopharyngitis, upper respiratory tract infection, arthralgia, and 
headache. Adverse drug reactions include headache, arthralgia, fatigue, oropharyngeal 
pain, diarrhea, nausea, myalgia, influenza, injection site reactions, neutropenia, and 
tinea infections, conjunctivitis, and candida infections.  
 
Through the end of the psoriasis studies, a total of 23 deaths were reported among the 
patients who received brodalumab. This includes a total of 4 completed suicides, 
including one reported as an intentional overdose. There was no increase in overall risk 
of death above what would be expected in the patient population. 
 
There were no differences in the rates of serious adverse events at week 12 of 
treatment between brodalumab, ustekinumab, or placebo. Overall, the rates of adverse 
events leading to discontinuation of treatment were low and comparable to placebo at 
week 12 and ustekinumab at week 52, with no increase through the long term period. 
Serious adverse events with incidence rates >0.1% in the brodalumab patients at week 
12 were cellulitis, appendicitis, gastroenteritis, and acute pancreatitis. Major Adverse 
Cardiovascular Events (MACE) were reported at 0.2% at 12 weeks in brodalumab 
exposed patients, and 0.61 per 100 patient years in the all-brodalumab group at week 
52 as compared to 0.40 in the ustekinumab group. The sponsor concluded that there 
was no evidence for a causal association between MACE and brodalumab.  
Other identified and potential risks of brodalumab treatment include: worsening of 
Chron’s disease; higher rate of infections with the majority reported as nonserious, mild, 
and self-limited; neutropenia at a rate of 0.7% in the 12-week trial, with most cases 
reported as transient and reversible; hypersensitivity at a rate of 1.7% for brodalumab 
210 mg q2w; and malignancy, with exposure-adjusted event rates at 52 weeks of 0.3 in 
the all-brodalumab group as compared to 0.4 in the ustekinumab group, with no 
increase over long term follow up. [5, 6] 
 
Brodalumab was FDA-approved in February, 2017 with a Risk Evaluation and Mitigation 
Strategy to ensure that prescribers and patients are aware of the risk of suicidal 
ideation. Investigators will be REMS certified and Study Subjects will sign the Patient-
Prescriber Agreement Form prior to initiating study drug.    
 
SAFETY MONITORING 
The study will be conducted in accordance with our department’s Standard Operating 
Procedures, which are based on US FDA Title 21 Code of Federal Regulations and ICH 
Good Clinical Practice guidelines.   
 
An investigator will review all laboratory results and assess for adverse events.  The 
principal investigator will be informed of all adverse events.  In the event that a subject’s 
safety is compromised, the investigator will discontinue the subject immediately.   
   


8 
 
A DSMB will be formed and will be comprised of two board certified dermatologists 
experienced in prescribing biologic treatments. All SAEs will be reported to the DSMB 
board within 24 hours of our being informed of the event. In addition, the DSMB will 
receive a compiled list of all related adverse events, from all sites, every three months, 
so that they can determine if the risks have changed and whether or not the study 
should continue as planned. 
 
Definition of an AE: Any untoward medical occurrence in a subject administered a 
pharmaceutical product that does not necessarily have a causal relationship with the 
treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of 
a medicinal (investigational) product, whether or not considered related to the 
investigational medicinal product. 
 
Investigational Medicinal Product (IMP) includes the drug under evaluation and the 
comparator drug(s) if specified as part of the research objective, given at any time 
during the study. Medical conditions/diseases present before starting the drug of 
interest are only considered adverse events if they worsen after starting the drug of 
interest. 
 
The occurrence of adverse events will be sought by non-directive questioning of the 
patient at each visit during the study. Adverse events also may be detected when they 
are volunteered by the patient during or between visits or through physical examination, 
laboratory test, or other assessments. All adverse events will be recorded in the study 
database including the following information: 
1. the severity grade (mild, moderate, severe)  
2. its relationship to the drug(s) of interest (suspected/not suspected) 
3. its duration (start and end dates or if continuing at final exam) 
4. whether it constitutes a serious adverse event (SAE) 
 
A SAE is any untoward medical occurrence that at any dose: 
- 
results in death, 
- 
is life-threatening, 
- 
requires inpatient hospitalization or prolongation of existing hospitalization, 
- 
results in persistent or significant disability/incapacity, 
- 
is a congenital anomaly/birth defect,  
- 
is otherwise a significant medical event. 
 
This includes any SAEs likely to arise from the trial indication or progression of 
underlying/concomitant illness (es) (e.g. progression of cancer in oncology trials), 
unless specified in the protocol as study specific exemptions. 
 
Any SAE, irrespective of causality, occurring after the subject has provided informed 
consent and until four weeks after the subject has stopped study participation must be 
reported unless otherwise stated in the protocol. SAEs occurring after four weeks from 
ending study participation should only be reported if considered by the Investigator 


9 
 
attributable to the exposure to the investigational drug(s) during the trial period. This 
includes the period in which the study protocol interferes with the standard medical 
treatment given to a subject, even if study treatment has not yet started (e.g. withdrawal 
of previous treatment during washout period, change in treatment to a fixed dose of 
concomitant medication). 
 
Timelines: All serious adverse events (SAEs) from interventional clinical trials must be 
reported by the sites to the Lead PI within 24 hours of occurrence of the SAE and to the 
site’s own IRB as required. The Lead PI will then report to the manufacturer and any 
other authorities.  
 
Follow-up reports: All related SAEs will be followed until resolution or until it is judged 
to be permanent, and an assessment will be made at each visit (or more frequently, if 
necessary) of any changes in severity, the suspected relationship to the drug of interest, 
the interventions required to treat it, and the outcome.  
 
Pregnancies: Any occurrences of a pregnancy in a patient (or a patients partner) 
during study participation will be collected. All pregnancies will be followed up to 
determine outcome, including spontaneous or voluntary termination, details of the birth, 
and the presence or absence of any birth defects, congenital abnormalities, or maternal 
and/or newborn complications. 
 
Should a temporary or permanent suspension occur, we would report the occurrence to 
all appropriate authorities. 
 
EARLY TERMINATION 
 
Any individual whose health or well-being may be threatened by continuation in this 
study will be discontinued by the investigator.  
 
If a female subject becomes pregnant at any time during the study, she will be 
discontinued immediately.  She will be asked to provide the investigator with medical 
updates throughout her pregnancy and on the final outcome of the pregnancy.   
 
Any subject who chooses to discontinue the study, or is discontinued from the study by 
the investigator will be asked to return for a final visit to have some or all of the following 
procedures: assessment of adverse events and concomitant medications, 
questionnaires, pregnancy test, blood draw for complete blood count, and skin 
evaluation including PASI, sPGA, and BSA.  
 
INVESTIGATIONAL DRUG SUPPLY 
 
In this open-label study, Brodalumab will be provided by Valeant Pharmaceuticals as  
210 mg brodalumab pre-filled syringes. Each site will be provided with a supply of  
brodalumab 210 mg for up to 15 subjects.  
 


10 
 
All study medication will be shipped to and stored by a REMS certified pharmacy in a 
secure cool area between 2-80C (under refrigeration).  Study drug will be dispensed to 
subjects at each visit, and any unused study drug will be kept at the study site. Subjects 
will be given a cooler to transport medication home, and instructed to keep the 
medication refrigerated. The number of missed doses will be documented for each 
subject.  Each investigative site will account for all study drug dispensed and stored 
during the study.   
 
 
LABORATORY SPECIMEN 
 
All blood and urine samples will be processed through the investigative’s site local lab. 
 
 
INSTITUTIONAL REVIEW BOARD 
 
Prior to beginning this study, approval for all study related documents (protocol, consent 
form, advertising) will be obtained from the investigative site’s IRB.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


11 
 
REFERENCES 
 
1. 
Lebwohl MG, Bachelez H, Barker J, Girolomoni G, Kavanaugh A, Langley RG, 
Paul CF, Puig L, Reich K, van de Kerkhof PC: Patient perspectives in the 
management of psoriasis: results from the population-based Multinational 
Assessment of Psoriasis and Psoriatic Arthritis Survey. Journal of the 
American Academy of Dermatology 2014, 70(5):871-881.e871-830. 
2. 
Krueger G, Koo J, Lebwohl M, Menter A, Stern RS, Rolstad T: The impact of 
psoriasis on quality of life: results of a 1998 National Psoriasis Foundation 
patient-membership survey. Archives of dermatology 2001, 137(3):280-284. 
3. 
Pariser D, Schenkel B, Carter C, Farahi K, Brown TM, Ellis CN: A multicenter, 
non-interventional study to evaluate patient-reported experiences of living 
with psoriasis. The Journal of dermatological treatment 2016, 27(1):19-26. 
4. 
Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, 
Lebwohl M, Koo JYM, Elmets CA, Korman NJ et al: Guidelines of care for the 
management of psoriasis and psoriatic arthritis: Section 1. Overview of 
psoriasis and guidelines of care for the treatment of psoriasis with 
biologics. Journal of the American Academy of Dermatology 2008, 58(5):826-
850. 
5. 
Valeant Pharmaceuticals International ,Inc: SILIQ (Package Insert).  2017. 
6. 
Valeant Pharmaceuticals International, Inc: BRODALUMAB Injection. Sponsor 
Briefing Document, Food and Drug Administration Dermatologic and 
Ophthalmic Drugs Advisory Committee (DODAC). July 19, 2016. 
 


12 
 
Appendix A 
Schedule of Events 
  
Screening 
Baseline/Randomization 
Treatment Phase 
Visit number 
V1 
V2 
V3 
V4 
V5 
V6/ET 
Weeks since randomization 
-4 
0 
w4 
w8 
w12 
w16 
Informed Consent 
x 
  
  
  
  
  
Patient-Prescriber Agreement Form 
x 
Medical History 
x 
  
  
  
  
  
Demographics 
x 
  
  
  
  
  
Inclusion/Exclusion 
x 
x 
  
  
  
  
Concomitant Medications 
x  
x 
x 
x 
x 
x 
Adverse Events 
  
x 
x 
x 
x 
x 
Administer IP 
  
x 
x 
x 
x 
  
Dispense IP 
  
x 
x 
x 
x 
  
Clinical Efficacy 
sPGA 
x 
x 
x 
x 
x 
x 
PASI 
x 
x 
x 
x 
x 
x 
BSA 
x 
x 
x 
x 
x 
x 
Photographs of target lesion(s) 1 
x 
x 
x 
x 
x 
Laboratory Tests 
Quantiferon Gold/PPD (if not done in 
past 8 months) 
x 
  
  
  
  
  
Urine Pregnancy (Females of child 
bearing potential) 
x 
x 
x 
x 
x 
x 
Complete Blood Count w/ differential (if 
not performed in past 4 months) 
x 
  
  
  
  
  
1 – Photographs of at least one target lesion should be taken at baseline and then again at every visit thereafter.  
      The same target lesion is to be photographed at each visit according to the site’s SOPs.  
 
 


13 
 
Appendix B 
Psoriasis Area and Severity Index (PASI): 
PASI 
Head 
Trunk 
Upper 
Limbs 
Lower 
Limbs 
 Symptom Score 
Erythema (E)  
 
 
 
 
0 = None 
1 = Slight           
2 = Moderate 
3 = Severe         
4 = Very Severe 
Infiltration (I) 
 
 
 
 
Desquamation (D) 
 
 
 
 
Sum = E + I + D 
 
 
 
 
  
Area Score 
 
 
 
 
0 = none   1 = <10%   2 = 10-29%   3 = 30-49% 
4 = 50-69%      5= 70-89%      6 = 90-100% 
Sum x Area 
 
 
 
 
 
x 
x 0.1 
x 0.3 
x 0.2 
x 0.4 
  
Total 
+ 
+ 
+ 
=  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


14 
 
Appendix C 
Static Physician Global Assessment (sPGA) 
 
Add I + E + S = _________ / 3 = __________ (Total Average) 
 
 
 
 
 
 
 
 
 
 
sPGA 
0 
1 
2 
3 
4 
Induration  
(I) 
Averaged over all 
lesions 
no evidence 
of plaque 
elevation 
minimal plaque 
elevation 
(0.25 mm) 
mild 
plaque 
elevation  
(0.5 mm) 
moderate 
plaque 
elevation  
(0.75 mm) 
severe plaque 
elevation  
(> 1 mm) 
Erythema  
(E)  
Averaged over all 
lesions 
no erythema, 
hyperpigment
ation may be 
present 
 
faint erythema 
light red 
coloration 
moderate red 
coloration 
bright red 
coloration 
Scaling  
(S) 
Averaged over all 
lesions 
no evidence 
of scaling 
minimal; 
occasional fine 
scale over <5% 
of lesion 
mild; fine 
scale 
dominates 
moderate; 
coarse scale 
predominates 
severe; thick 
scale 
predominates