An Open Label Study of Apremilast in Chronic Idiopathic Pruritus
Phase: PHASE2
Conditions: Itch
Sponsor: Washington University School of Medicine

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

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

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

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