Clinical trial NCT03836001
Conditions: Epidermolysis Bullosa
Sponsor: Stanford University
Start date: 2019-04-18; Completion date: 2022-06-24
Enrollment: 28 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To determine if Serlopitant (when taken by mouth) is safe and works on itch in patients aged 13 and above with EB.

Detailed description:
The investigator will determine whether more patients taking serlopitant 5 mg daily as compared to placebo can achieve at least a 3-point reduction in the 24-hour Average Itch Numeric Rating Scale (NRS) following two months of treatment.

Secondary objectives include;

1. comparative weekly change in daily worst itch NRS,
2. comparative weekly change in daily average itch NRS,
3. the proportion of patients who achieve at least 30% or 50% reduction in Average Itch NRS at month 2,
4. proportion of patients achieving 2-point and 4-point reductions in Average Itch NRS at month 2,
5. Patient Global Impression of Change (PGIC) at month 2, the change in participant static assessment of itch at month 2, and
6. assessment of the safety of serlopitant in adolescents (≥13 y.o.) and adults with epidermolysis bullosa-related itch.

Arms: arm 1: Participants will undergo two months of dosing with a placebo (inactive drug or sugar pill), followed by one month of washout. After the washout period, all participants were invited to participate in an open-label extension study with serlopitant 5 mg daily. The duration of the open-label extension study was either 12 months (for those who enrolled before May 2020) or 3 months (for those who registered after May 2020) due to drug availability. arm 2: Participants will undergo two months of Serlopitant 5mg daily per oral, followed by one month of washout. After the washout period, all participants were invited to participate in an open-label extension study with serlopitant 5 mg daily. The duration of the open-label extension study was either 12 months (for those who enrolled before May 2020) or 3 months (for those who registered after May 2020) due to drug availability.
Interventions: intervention 1: Serlopitant Tablet intervention 2: Placebo Oral Tablet
Intervention descriptions: intervention 1: Serlopitant is a small molecule, highly selective NK1-R (neurokinin-1 receptor) antagonist. Two critical mediators of the urge to scratch are Substance P, or SP, and its receptor, NK1-R. SP is a naturally occurring peptide in the tachykinin neuropeptide family. Tachykinins have a broad range of functions in the nervous and immune systems. SP binding of NK1-R has been shown to be a key mediator of sensory nerve signaling, including the itch-scratch reflex and the vomiting reflex. intervention 2: The placebo is a tablet that looks like a drug but has no drug or other active ingredient in it.

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
A Neurokinin-1 Receptor Antagonist for the Treatment of Pruritus in 
Patients With Epidermolysis Bullosa 
Study Protocol and Statistical Analysis Plan 
NCT03836001 
March 25, 2021 


EB Serlopitant Itch Clinical Protocol 
(IRB #: 49084, IND: 
) 
 
 
 
 
 
Stanford Dermatology, PI: Albert Chiou, MD 
 
    
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1. Title: A Phase 2 trial of Neurokinin-1 Receptor Antagonist for the Treatment of Itch in Epidermolysis 
Bullosa Patients 
 
2. PI: Albert Chiou, MD 
 
Co-PI: Jean Tang, MD, PhD 
 
3. Funding sources for this project:  
Epidermolysis Bullosa Research Partnership (EBRP) – providing funding (SPO # 
) 
Menlo Therapeutics, Inc. – providing study medication 
 
4. Abstract: 
This is a follow-up study to a prior pilot phase 2 trial conducted here at Stanford and will assess the effect of 
serlopitant (5 mg daily) on EB-related itch in adolescents (≥13 y.o.) and adults with EB. We will evaluate the 
degree of itch relief in participants taking serlopitant as compared to placebo. This will be determined by 
comparing the proportion of participants with 3 point or greater reduction in average daily itch severity as 
measured by numeric rating scale (NRS) score following two months of treatment. Secondary aims include 
continuous change in average daily NRS and worst itch NRS over time, proportion of participants achieving 2-
point and 4-point reductions in average itch severity following two months of treatment and change in median 
NRS as compared to baseline. Finally, we will assess the safety profile of serlopitant in study participants. It is 
our hope that serlopitant will reduce itch in adolescents and adults with EB.  
 
5. General background: 
Management of chronic pruritus is notoriously challenging for patients with epidermolysis bullosa (EB). In a 
comprehensive survey of 146 EB patients, itch was reported as the most bothersome EB symptom, ranking 
higher than acute or chronic pain or problems eating.1 Furthermore, pruritus can induce an itch-scratch-blister 
cycle, which can exacerbate existing wounds or induce new wounds.2 There have been no new drugs for 
chronic pruritus, and the current management of pruritus in EB with antihistamines and topical steroids only 
minimally relieve itch.3  
 
Recent insights into the underlying pathogenesis of pruritus have revealed that substance P and its receptor, 
neurokinin-1 (NK1), are key transmitters of the itch signal. By inhibiting the NK1 receptor, serlopitant blocks 
the transmission of itch from the skin to the central nervous system. NK1 receptor antagonists (aprepitant and 
serlopitant) were originally tested in clinical trials as antiemetics and medications to treat overactive bladder.1  
Since 2005, NK1 receptor antagonists have been evaluated in more than a dozen completed Phase 1 studies and 
two Phase 2b studies (N=300 participants).  
 
Serlopitant was evaluated in a multi-center, double blind, 6-week randomized trial of 257 adults with chronic 
pruritus for the treatment of severe, chronic pruritus.2 There was a statistically significant and dose-dependent 
reduction in pruritus at the end of six weeks at the 1 mg and 5 mg doses. Participants in this study had chronic 
pruritus due to a variety of dermatologic, neuropathic, and psychogenic causes that was unresponsive to topical 
steroids and antihistamines. Serlopitant was well tolerated and safe in doses up to 5 mg daily, and there were no 
treatment related serious adverse events. When assessed with a visual analog scale (VAS), pruritus was 
significantly reduced in both the 1 mg (p = 0.001) and the 5 mg (p = 0.002) groups compared to placebo. After 
6 weeks of treatment, nearly 70% of participants taking 5 mg of serlopitant reported a 2-point reduction in VAS 
while nearly 50% of participants reported a 4-point decrease in VAS. 
 
We recently reported the results of a prior phase 2 randomized, double blind, placebo-controlled trial evaluating 
the effects of serlopitant over 8 weeks for treatment of EB-related itch.3 Participants were age > 13 years old, 


EB Serlopitant Itch Clinical Protocol 
(IRB #: 49084, IND: 
) 
 
 
 
 
 
Stanford Dermatology, PI: Albert Chiou, MD 
 
    
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with any EB subtype. Although the 14 participant trial was only powered to detect large differences in numeric 
rating scale (NRS) itch scores, we observed a small magnitude reduction in NRS itch score over time in favor of 
serlopitant relative to placebo (0.08 point/week comparative reduction) although this difference did not meet 
statistical significance (p=0.11). This was equivalent to a 0.64-point reduction in the NRS itch score (rated 0-
10) by the end of the active treatment period. In post-hoc analysis, we found a significant majority of 
participants in the serlopitant arm (86%) experienced at least a 1-point reduction in NRS score by end of 
treatment. More participants in the active group (43% vs. 14%) achieved at least a 3-point reduction in NRS itch 
score by the end of treatment as compared to placebo, although this was not statistically significant (p=0.35). 
Serlopitant was well tolerated, with no new safety signals observed.  
 
6. Study design: 
This is an investigator-initiated, single-center, randomized, double-blind, placebo controlled, parallel arm trial 
evaluating the effects of serlopitant at 5 mg by mouth daily on EB-related itch. Eligible participants must have a 
clinical diagnosis of EB and average daily pruritus rated at least 5 based on a 0-10 Numeric Rating Scale (NRS) 
persistent for at least 6 weeks.  
 
We aim to recruit at least 40 participants, age 13 and older, of all EB subtypes. Participants will be assigned to 
placebo or serlopitant in a 1:1 ratio. Participants randomized to serlopitant will receive a loading dose of 
serlopitant 15 mg PO once, followed by serlopitant 5 mg PO daily for 2 months. This dosing regimen is 
identical to that investigated during our pilot phase 2 trial. 
 
After completing the double-blind phase of the trial, all participants will undergo one month of wash-out before 
being offered the option of participating in an open label extension phase with serlopitant 5 mg PO daily for 
continued monitoring of toxicity and efficacy. This extension phase will be 12 months for participants enrolled 
prior to May 2020, and 3 months for participants enrolled after May 2020, due to drug availability. 
 
Due to the potential pain and skin injury that can be incurred with travel for participants with more severe EB 
subtypes, this trial is intentionally designed to minimize the number of in-person clinic visits through use of 
home itch diaries and phone follow-up, as recommended by the FDA in their EB-specific guidance document.4  
 
7. Efficacy Endpoints: 
Based on the data from our pilot study, the primary statistical endpoint will be the proportion of participants 
who achieve at least a 3-point reduction in average daily NRS itch severity from baseline at the end of the two-
month double-blind phase.   
 
Secondary endpoints will include: 
1. Comparative weekly change in daily worst-itch NRS during the double-blind phase 
2. Safety, as measured by adverse events during the course of the double-blind and open label phases of the 
trial. These will also include changes in ECG parameters and safety labs following drug exposure. 
3. Comparative weekly change in average daily NRS itch severity during the double-blind phase 
4. Proportion of participants who achieve at least 2 and 4-point reductions in average daily NRS itch 
severity from baseline at the end of the double-blind phase 
5. Proportion of participants who achieve at least a 30% or 50% reduction in average daily NRS itch 
severity from baseline at the end of the double-blind phase 
6. Change in participant-reported outcomes of global assessment of change in itch and overall 
improvement as measured by static participant assessment of itch, participant global assessment of 
change in itch severity, and caregiver global assessment of change in itch severity. 
 
The Stanford EB Itch Survey also captures additional measures related to symptoms during dressing changes, 
sleep quality, and other quality of life measures which may be explored.  


EB Serlopitant Itch Clinical Protocol 
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Additional exploratory endpoints will revolve around mean comparative change in wound surface areas, 
comparative change in NRS itch severity at target wounds, and the change in median NRS score by group from 
baseline at month 1, month 2, and month 3. 
 
We will also assess participant and caregiver perceived change in wound size and number, and pain as 
measured with the Wong-Baker FACES5 scale, and changes in quality of life assessed with ItchyQoL,6 and the 
Dermatology Quality of Life Index (DLQI).7  
 
Further exploratory analysis comparing multiple pruritus-related instruments will be explored to determine the 
most appropriate measures of pruritus for this participant population. 
 
8. Inclusion / Exclusion Criteria: 
Inclusion criteria: 
1. Males or females who are at least 13 years of age. 
2. Willing and able to understand and sign informed assent/consent. Adolescents will need a parent or 
guardian willing and able to give consent. 
3. Clinical diagnosis of epidermolysis bullosa (Dystrophic EB, EB Simplex, Junctional EB, or Kindler 
syndrome). 
4. History of chronic pruritus of at least 6 weeks in duration 
5. NRS pruritus score of at least 5 on average itch score in the past 24 hours at Screening Visit or Pre-
Screening Phone Call 
6. Female participants of childbearing potential, must have a confirmed negative urine pregnancy test prior 
to study treatment and be willing to use effective contraception for the duration of the trial  
7. Judged to be in good health based upon the results of a physical examination, medical history, and safety 
laboratory tests. 
 
Exclusion criteria: 
1. Have any medical condition or disability that would interfere with the assessment of safety or efficacy in 
this trial or would compromise the ability of the participant to travel to Stanford, to undergo study 
procedures, or to give informed consent. 
2. History of sensitivity to any components of the study material. 
3. Females of childbearing potential who are unwilling to use adequate contraception or who are breast 
feeding. 
4. Have any chronic or acute medical condition that, in the opinion of the investigator, might interfere with 
the study results or place the participant at undue risk. 
5. Have chronic renal disease, i.e., serum creatinine greater than 2 times the upper limit of normal. 
6. Have chronic liver disease, i.e., AST or ALT greater than 2 times the upper limit of normal. Participants 
with hepatitis B and C who have normal liver function may be enrolled. 
7. Have a current malignancy (e.g. Hodgkin’s lymphoma, myeloma, B or T cell lymphoma) or blood cell 
dyscrasia (e.g., polycythemia or myelofibrosis) that could lead to systemic chronic pruritus. 
8. History of thyroid cancer, thyroid nodules, inadequately treated thyroid disease, or abnormal TSH or 
free T4 at screening: TSH >10, TSH > 5 with low free T4, TSH <0.1, TSH < 0.4 with high free T4. 
9. Known history of abnormalities in adrenal or pituitary function (pituitary adenoma, adrenal 
insufficiency, or adrenal nodule).  
10. Screening cortisol < 3 mcg/dL  
11. Unevaluated abnormalities in cortisol, ACTH, or prolactin. 
12. Have pruritus of psychogenic etiology (delusions of parasitosis, obsessive compulsive disorder and 
major depression) or neuropathic etiology (due to shingles, spinal cord injury or with neurologic deficit). 


EB Serlopitant Itch Clinical Protocol 
(IRB #: 49084, IND: 
) 
 
 
 
 
 
Stanford Dermatology, PI: Albert Chiou, MD 
 
    
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13. Have pruritus due to urticaria, drug allergy, or infection (such as pityriasis rosacea or tinea or active 
human immunodeficiency virus [HIV]). Note: Participants with HIV who have undetectable viral load, 
CD 4 counts >200 cells/cc, and stable retroviral therapy may enroll. 
14. Have taken investigational medications within 30 days prior to Screening. 
15. Are unwilling to discontinue specific medications that, in the view of the investigator may have 
significant interactions with the trial drug, for at least 30 days prior to initiation of study and throughout 
the study period (all severe CYP34A inhibitors - this includes miconazole, delavirdine, conivaptan, 
clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, indinavir, lopinavir, 
nelfinavir, ritonavir, saquinavir). 
16. Are unable or unwilling to maintain their current anti-itch and opioid-based pain medications at a stable 
dosage through the course of the two months of active treatment (including but not limited to opioid 
pain medications, antihistamines, tri-cyclic antidepressants, and gabapentin) 
17. Started or changed medications, creams, or emollients including over the counter preparations or bath 
oils specifically for treatment of pruritus within 30 days prior to Screening. 
18. Have expressed suicidal ideation with some intent to act in the past 12 months 
19. Have any social or medical condition (e.g. alcoholism, drug dependency, psychotic state) that, in the 
investigator’s opinion, might interfere with the participant’s ability to comply with the requirements of 
the protocol. 
 
9. Study visits: (see Appendix, Schedule of Events) 
9.A. Screening Visit: 
Participants will be pre-screened over the phone prior to the screening visit to assess inclusion criteria. During 
the screening visit, following informed consent (and assent as applicable for adolescents), medical history, 
medication history, and relevant medical records will be collected. Vital signs (including weight) will be 
recorded and a physical examination will be performed.  
 
When obtaining medical history in female participants we will specifically inquire about: 
- 
Menstruation: Amenorrhea (in participants that had previously reached menarche), abnormal menses, 
significant abnormal vaginal bleeding 
- 
Significant abnormal vaginal discharge.  
- 
Known breast lumps, nipple discharge 
- 
Participants > 40 years old: if they have had previous mammograms, when their last mammogram 
occurred, if any mammograms have been abnormal. 
If any of the above abnormalities are present, they will evaluated prior to trial entry. 
 
9.A.i. Wound Assessments: 
Investigators will quantify and assess affected skin surface area with body map diagrams and photography. 
Photography may be obtained using the Tissue Analytics smartphone app. This is a HIPAA-compliant app that 
is able to photograph a wound, measure the wound, and track it over time. Wounds will be classified as chronic 
open (unhealed for > 12 weeks) or recurrent (heals in < 12 weeks and re-opens).  
 
If applicable, we will identify up to 4 target wounds that meet the following criteria: 
1) Measure at least 10 cm2  
2) Wound-specific NRS itch score of at least 5 during the past 24 hours  
We will aim to capture the participant’s most pruritic wounds as target wounds.8 Target wounds will be 
photographed.  
 
Participants will evaluate the following characteristics of each target wound: average itch in past 24 hours 
(NRS), worst itch in past 24 hours (NRS), average pain in past 24 hours (Wong Baker FACES Pain Scale). If 


EB Serlopitant Itch Clinical Protocol 
(IRB #: 49084, IND: 
) 
 
 
 
 
 
Stanford Dermatology, PI: Albert Chiou, MD 
 
    
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the participant’s most pruritic wounds do not meet criteria for inclusion as target wounds, we will not 
photograph any wounds, but will ask participants to evaluate wound characteristics. 
 
9.A.ii. Global Pruritus Assessments: 
In addition to the NRS, pruritus will be evaluated with the following questionnaires:  
1) Stanford EB Itch Survey 
2) Itch Man9 
3) Dermatology Quality of Life Index (DLQI)7 
4) ItchyQoL6 
5) Leuven Itch Scale10 
6) Static Participant Global Assessment of Itch Severity 
7) PROMIS Scales – Pediatric versions for participants <18y 
8) Itch Controlled Days Questionnaire 
 
9.A.iii. Electrocardiogram: 
Baseline electrocardiogram (ECG) will be performed, using our established technique using non-stick pads to 
prevent injury due to electrodes. The overall ECG assessment (abnormal or normal) will be summarized. We 
will review whether the participant has had previous echocardiogram and the results will be included in the 
chart. 
 
9.A.iv. Safety Laboratory Assessments: 
We will assess the following labs:  
1) Complete blood count (CBC) 
2) Complete metabolic panel (CMP) 
3) Urinalysis 
4) Urine pregnancy test (if applicable) 
5) Thyroid stimulating hormone (TSH) 
6) Free T4 
7) Cortisol  
8) ACTH 
9) Prolactin 
 
Labs will ideally be drawn in the morning.  Participants with low cortisol will be referred to their primary care 
physician or endocrinologist for further evaluation which may include AM cortisol level or dynamic testing 
with a standard cosyntropin stimulation test. If prolactin is abnormal, participants will be required to have this 
evaluated prior to study participation. 
 
At the discretion of the investigator, labs drawn by non-study providers within 60 days of screening and 
baseline may be substituted for the trial screening labs so long as they include the same studies of interest. This 
is in order to reduce unnecessary skin trauma and a potentially psychologically traumatic blood draw. 
 
9.A.v. Home Diaries and Preparation for Month 1: 
Participants will be asked to complete a daily itch diary with their average itch score (NRS) over the past 24 
hours and their itch score during dressing changes or bathing (NRS). This may either be an online diary 
(administered securely through REDCap11) or a paper diary, based on participant preference. 
 
Female participants of childbearing potential (including participants that have not yet undergone menarche) 
who are not using hormonal contraception will be provided with a menstrual diary to complete.  
 


EB Serlopitant Itch Clinical Protocol 
(IRB #: 49084, IND: 
) 
 
 
 
 
 
Stanford Dermatology, PI: Albert Chiou, MD 
 
    
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Participants will be provided with a lab requisition form to have their Month 1 labs drawn at a Quest lab near 
their home. 
 
Participants will also be specifically educated about the signs and symptoms of adrenal insufficiency (e.g. 
fatigue, abdominal pain, dizziness, etc.) and will be instructed to report these symptoms to study investigators.  
 
9.B. Baseline Visit (Within 30 Days of Screening):   
Participants will return to Stanford for a baseline visit within 30 days of screening.  Per the discretion of the 
investigator(s), screening and baseline may be combined into the same visit. Outside of this window, 
participants will be considered a “screen fail” and would have to undergo another screening visit. 
 
9.B.i Eligibility Confirmation and Randomization: 
Vital signs, medical history, concomitant medications, ECG results, and safety lab results obtained at screening 
will be reviewed for eligibility. Once participant eligibility is confirmed, randomization will occur.  
 
9.B.ii. Assessments: 
Target wounds will again be characterized and photographed. The study diary will be reviewed to assess 
participants’ mean daily pruritus rating and variation of itch scores at baseline.  
 
If the baseline and screening visit are combined, participants will be instructed to complete a minimum of 7 
days of their nightly itch diary prior to starting medication in order to establish baseline itch severity.   
 
Study medication will be dispensed one week after eligibility is confirmed to reduce confusion about when to 
begin study medication.  
 
The scheduling of the Month 1 phone call will account for this 1-week lag prior to starting medication.  
 
9.C. Month 1 Phone Call: 
Month 1 phone call will occur 30 days after starting the study medication, +/- 14 days. 
 
9.C.i. Safety Laboratory Assessments: 
Safety labs will be drawn as early as 10 days prior to scheduled phone follow-up at month 1 following initiation 
of active treatment.  Labs will be drawn at a local laboratory convenient for the participant. They will have the 
option to have labs drawn at Stanford if they prefer. 
 
At the discretion of the investigator, labs drawn by non-study providers within this time window (1 month after 
medication initiation, +/- 10 days) may be substituted for the study lab draw, as long as they include the same 
studies of interest. This is in order to reduce unnecessary skin trauma and a potentially psychologically 
traumatic blood draw. 
 
Safety labs will include: 
1) Complete blood count (CBC) 
2) Complete metabolic panel (CMP) 
3) Urinalysis 
4) Urine pregnancy test (if applicable) 
 
Medication will not be sent until safety labs have been reviewed by the investigator. Any abnormal labs will be 
reviewed by investigator and appropriate follow-up will be initiated as needed.  
 
9.C.ii. Assessments by Phone: 


EB Serlopitant Itch Clinical Protocol 
(IRB #: 49084, IND: 
) 
 
 
 
 
 
Stanford Dermatology, PI: Albert Chiou, MD 
 
    
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Participants will be queried for any adverse events and changes to concomitant medications or wound dressing 
regimen. These will be assessed by investigators.  
 
Participants will specifically be asked about any symptoms of adrenal insufficiency (e.g. fatigue, abdominal 
pain, dizziness, etc.). Participants who report symptoms concerning for adrenal insufficiency will be evaluated 
with instructions to follow-up urgently with their primary care provider for further evaluation, which should 
include an AM cortisol.  If this is abnormal, we will coordinate with their primary care provider for urgent 
referral to endocrinology for further evaluation including cosyntropin stimulation testing. 
 
Female participants will specifically be queried regarding abnormal vaginal bleeding (new and different from 
any related to any known EB wounds in the genital area), new breast findings (not related to EB wounds), 
expulsion of an intrauterine device or implant, or vaginal discharge. If any of these concerns are identified, the 
participant will be urgently referred to their primary care provider for further evaluation.   
 
9.C.iii. Assessments via REDCap: 
A link will be sent to the participant to complete the following assessments via REDCap: 
1. Stanford EB Itch Survey 
2. Itch Man 
3. DLQI 
4. ItchyQoL 
5. Leuven Itch Scale 
6. Static Participant Global Assessment of Itch Severity (sPGAIS) 
7. Participant Global Impression of Change in Itch Severity (pGICIS) 
8. Caregiver Global Impression of Change in Itch Severity (cGICIS) 
9. PROMIS scales – Pediatric versions for participants <18y 
10. Itch Controlled Days Questionnaire 
 
If a participant is unable to access REDCap, these questionnaires will be administered over the phone.  
Instruments requiring visual analog scale (VAS), such as the Leuven Itch Scale, will be mailed, faxed, or 
emailed to enable the participant to physically complete the VAS. 
 
9.C.iv. Reminders and Instructions: 
Participants will be reminded to comply with completing their itch journals and medication.  
 
Participants will be instructed to mail back their month 1 itch diaries once they receive their new itch diaries 
(not applicable if participant has chosen to utilize a REDCap based online diary). Additional medication will be 
dispensed pending acceptable safety labs and mailed to participants along with new Month 2 itch diaries (if 
participant has chosen physical diary). Participants will be asked to set aside any medication from their month 1 
medication bottle and seal the bottle to be returned at their next visit and begin month 2 treatment from the new 
bottle. 
 
9.D. Month 2 Study Visit: 
At 60 days following initiation of study medication (+/- 14 days), participants will return to Stanford for a 
follow up clinic visit.  
 
Participants will be queried for any adverse events and changes to concomitant medications or wound dressing 
regimen. These will be assessed by investigators. Menstrual diaries will be collected and reviewed. Participants 
will be asked to submit their nightly itch diary (NRS), along with any unused medications from the prior two 
months of treatment for assessment of medication adherence.   
 


EB Serlopitant Itch Clinical Protocol 
(IRB #: 49084, IND: 
) 
 
 
 
 
 
Stanford Dermatology, PI: Albert Chiou, MD 
 
    
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Participants will specifically be asked about any symptoms of adrenal insufficiency (e.g. fatigue, abdominal 
pain, dizziness, etc.).  Participants who report symptoms concerning for adrenal insufficiency will be evaluated 
with instructions to follow-up urgently with their primary care provider for further evaluation, which should 
include an AM cortisol. If this is abnormal, the participant will be referred urgently to endocrinology for further 
evaluation including cosyntropin stimulation testing. 
 
Female participants will again be queried regarding abnormal vaginal bleeding (new and different from any 
related to any known EB wounds in the genital area), new breast findings (not related to EB wounds) and 
vaginal discharge.  If any of these concerns are identified, the woman will be referred to their primary care 
provider for evaluation.   
 
Vital signs (including weight) will be recorded. Physical examination will be performed. 
 
9.D.i. Wound Assessments: 
Participants will be reminded of the location of their target wound(s). Target wounds will be photographed. 
Participants will evaluate the following characteristics of each target wound: average itch in past 24 hours 
(NRS), worst itch in past 24 hours (NRS), average pain in past 24 hours (Wong Baker FACES Pain Scale). 
 
If the participant’s most pruritic wounds did not meet initial criteria for inclusion as target wounds, we will ask 
participants to evaluate wound characteristics of these same wounds evaluated at Screening. 
 
Participants and caregivers will be asked about their perceived change in wound size for each target wound and 
for perceived change in total wound number. 
 
9.D.ii. Global Pruritus Assessments: 
The following questionnaires will be completed: 
1) Stanford EB Itch Survey 
2) Itch Man 
3) Dermatology Quality of Life Index (DLQI) 
4) ItchyQoL 
5) Leuven Itch Scale 
6) Static Participant Global Assessment of Itch Severity 
7) Participant Global Impression of Change in Itch Severity 
8) Caregiver Global Impression of Change in Itch Severity 
9) PROMIS scales – Pediatric versions for participants <18y 
10) Itch Controlled Days Questionnaire 
 
9.D.iii. Electrocardiogram: 
Electrocardiogram (ECG) will be performed, using our established technique using non-stick pads to prevent 
injury due to electrodes. The overall ECG assessment (abnormal or normal) will be summarized and changes 
from baseline will be descriptively characterized. 
 
9.D.iv. Safety Laboratory Assessments: 
Safety labs will again be assessed: 
1) Complete blood count (CBC) 
2) Complete metabolic panel (CMP) 
3) Urinalysis 
4) Urine pregnancy test (if applicable) 
5) Thyroid stimulating hormone (TSH) 
6) Free T4 


EB Serlopitant Itch Clinical Protocol 
(IRB #: 49084, IND: 
) 
 
 
 
 
 
Stanford Dermatology, PI: Albert Chiou, MD 
 
    
Version Date: Mar 25, 2021 
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7) Cortisol  
8) ACTH 
9) Prolactin 
 
Labs will ideally be drawn in the morning.  At the discretion of the investigator, labs drawn by non-study 
providers within this time window (2 months after medication initiation, +/- 10 days) may be substituted for the 
study lab draw, as long as they include the same studies of interest. This is in order to reduce unnecessary skin 
trauma and a potentially psychologically traumatic blood draw. 
 
Any abnormal labs will be reviewed by investigator and appropriate follow-up will be initiated as needed.  
 
Any clinically significant abnormalities identified in prolactin or thyroid function will be followed until the 
level returns to baseline or appropriate follow-up can be established with a local provider.   
 
9.D.v. Reminders and Home Diaries: 
Participants will be given new daily itch diaries to complete during the wash-out period. They will be reminded 
to continue to complete their daily diary entries.  
 
Female participants of childbearing potential (including participants that have not yet undergone menarche) 
who are not using hormonal contraception will be provided with a menstrual diary to complete.  
 
Female participants of childbearing potential will be reminded to continue their acceptable form of 
contraception until 2 weeks after study drug discontinuation.  
 
9.E. Month 3 Phone Call / End of Wash Out Phase:  
One month (30 days, +/- 14 days) after completing the double-blind phase participants will be contacted by 
phone. 
 
9.E.i. Assessments by Phone: 
Participants will be queried for any adverse events and changes to concomitant medications or wound dressing 
regimen. These will be assessed by investigators. Participants will specifically be asked about any symptoms of 
adrenal insufficiency (e.g. fatigue, abdominal pain, dizziness, etc.). 
 
Female participants will specifically be queried regarding abnormal vaginal bleeding (new and different from 
any related to any known EB wounds in the genital area), new breast findings (not related to EB wounds), 
expulsion of an intrauterine device or implant, or vaginal discharge. If any of these concerns are identified, the 
participant will be referred to their primary care provider for further evaluation.   
 
9.E.ii. Global Pruritus Assessments by REDCap: 
A link will be sent to the participant to complete the following assessments via REDCap: 
1. Stanford EB Itch Survey 
2. Itch Man 
3. DLQI 
4. ItchyQoL 
5. Leuven Itch Scale 
6. Static Patient Global Assessment of Itch Severity (sPGAIS) 
7. Patient Global Impression of Change in Itch Severity (pGICIS) 
8. Caregiver Global Impression of Change in Itch Severity (cGICIS) 
9. PROMIS scales – Pediatric versions for participants <18y 
10. Itch Controlled Days Questionnaire 


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If a participant is unable to access REDCap, these questionnaires will be administered over the phone.  
Instruments requiring visual analog scale (VAS), such as the Leuven Itch Scale, will be mailed, faxed, or 
emailed to enable the participant to physically complete the VAS. 
 
9.E.iii. Safety Laboratory Assessments: 
Safety labs will again be assessed: 
1) Complete blood count (CBC) 
2) Complete metabolic panel (CMP) 
3) Urinalysis 
4) Urine pregnancy test (if applicable) 
5) Thyroid stimulating hormone (TSH) 
6) Free T4 
7) Cortisol  
8) ACTH 
9) Prolactin 
 
Labs will ideally be drawn in the morning.  At the discretion of the investigator, labs drawn by non-study 
providers within this time window (30 days, +/- 10 days) after completing the double-blind phase may be 
substituted for the study lab draw, as long as they include the same studies of interest. This is in order to reduce 
unnecessary skin trauma and a potentially psychologically traumatic blood draw. 
 
Any abnormal labs will be reviewed by investigator and appropriate follow-up will be initiated as needed.  
 
Any clinically significant abnormalities identified in prolactin or thyroid function will be followed until the 
level returns to baseline or appropriate follow-up can be established with a local provider.   
 
 
9.F. Continuation of Optional Open Label Phase: 
Participants who are eligible for the Open Label Phase in the opinion of the investigators (taking into 
consideration participant’s prior documented adverse events, current medical status, and adherence to trial 
protocol) and who elect to participate in the Open Label Phase will then be mailed serlopitant 5mg tablets as 
well as a new study diary to be completed weekly. 
 
This extension phase will be 12 months for participants enrolled prior to May 2020, and 3 months for 
participants enrolled after May 2020, due to drug availability. 
 
Participants who elect to participate in the open label study (who enrolled prior to May 2020) will undergo open 
label study phone visits at Baseline, Open Label Month 1, Open Label Month 3, Open Label Month 6, and 
Open Label Month 12. 
 
Participants who elect to participate in the open label study (who enrolled after May 2020) will undergo open 
label study phone visits at Baseline, Open Label Month 1, and Open Label Month 3. 
 
9.F.i. Safety Laboratory Assessments: 
The safety labs obtained for the Month 3 visit may be used as baseline labs for the Open Label Phase, as long as 
the labs are drawn within 4 months of the open label baseline visit. Safety labs will be drawn as early as 10 days 
prior to scheduled phone follow-ups. Labs will be drawn at a local laboratory convenient for the participant. 
They will have the option to have labs drawn at Stanford if they prefer. 
 


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Safety labs will include: 
1) Complete blood count (CBC) 
2) Complete metabolic panel (CMP) 
3) Urinalysis 
4) Urine pregnancy test (if applicable) 
5) Thyroid stimulating hormone (TSH) 
6) Free T4  
7) Cortisol  
8) ACTH  
9) Prolactin  
 
Serlopitant will not be sent until safety labs have been reviewed by the investigator. Any abnormal labs will be 
reviewed by investigator and appropriate follow-up will be initiated as needed.  
 
9.F.ii. Assessments by phone: 
Participants will be queried for any adverse events and changes to concomitant medications or wound dressing 
regimen. These will be assessed by investigators. Participants will specifically be asked about any symptoms of 
adrenal insufficiency (e.g. fatigue, abdominal pain, dizziness, etc.). Participants who report symptoms 
concerning for adrenal insufficiency will be instructed to follow-up urgently with their primary care provider 
including an AM cortisol assessment. If this is abnormal, we will coordinate with their primary care provider 
for urgent referral to endocrinology for further evaluation including cosyntropin stimulation testing. 
 
Female participants will specifically be queried regarding abnormal vaginal bleeding (new and different from 
any related to any known EB wounds in the genital area), new breast findings (not related to EB wounds), 
expulsion of an intrauterine device or implant, or vaginal discharge. If any of these concerns are identified, the 
participant will be referred to their primary care provider for further evaluation.   
 
9.F.iii. Assessments via REDCap: 
A link will be sent to the participant to complete the following assessments via REDCap: 
1. Stanford EB Itch Survey 
2. Itch Man 
3. DLQI 
4. ItchyQoL 
5. Leuven Itch Scale 
6. Static Patient Global Assessment of Itch Severity (sPGAIS) 
7. Patient Global Impression of Change in Itch Severity (pGICIS) 
8. Caregiver Global Impression of Change in Itch Severity (cGICIS) 
9. PROMIS scales – Pediatric version for participants <18y 
10. Itch Controlled Days Questionnaire 
 
If a participant is unable to access REDCap, these questionnaires will be administered over the phone.  
Instruments requiring visual analog scale (VAS), such as the Leuven Itch Scale, will be mailed, faxed, or 
emailed to enable the participant to physically complete the VAS. 
 
Participant Instruments requiring visual analog scale (VAS), such as the Leuven Itch Scale, will be mailed, 
faxed, or emailed to enable the participant to physically complete the VAS. 
 
9.C.iv. Reminders and Instructions: 
Participants will be instructed to mail back their diaries, remaining serlopitant, and empty bottles.  
 


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9.C.v. Dispensing Serlopitant: 
Additional serlopitant will be dispensed pending investigator review of safety labs. 
 
9.G. Early Termination Protocol: 
 
9.G.i. Early Termination in Double Blind Phase: 
If a participant terminates study participation early, while in the double-blind phase, they will be asked to return 
to Stanford for an Early Termination visit. 
 
Study staff will review the reason for early termination and investigators will facilitate medical follow-up as 
needed. Study staff will review adverse events, changes to concomitant medications, diaries, medication 
adherence, and will administer questionnaires.  
 
We will request that the participant have safety labs drawn. 
 
They will be instructed to return study diaries, remaining medication, and empty medication bottles. 
 
If the participant is willing to come to Stanford, we will perform vital signs, physical examination, target wound 
assessment and photographs, and ECG. 
 
9.G.ii. Early Termination in Open Label Phase: 
If a participant terminates study participation early, while in the open label phase, study staff will call the 
participant for an Early Termination call. 
 
Study staff will review the reason for early termination and investigators will facilitate medical follow-up as 
needed. Study staff will review adverse events, changes to concomitant medications, diaries, medication 
adherence, and will administer questionnaires.  
 
We will request that the participant have safety labs drawn. 
 
They will be instructed to return study diaries, remaining medication, and empty medication bottles. 
 
9.H Modification to Study Procedures Due to COVID-19  
Due to the pandemic caused by the COVID-19 virus, at the discretion of the Principal Investigator, it may be 
necessary for participants and staff welfare that study visits under this protocol are conducted remotely. This 
may apply to both initial enrollment visits, alongside follow up visits. All remote study visits will be conducted 
securely using HIPAA compliant telemedicine tools, including but not limited to the integrated EPIC 
telemedicine system, ensuring patient confidentiality and data security. As a consequence of conducting 
remote study visits, it may not be feasible to conduct all study related procedures as documented in the 
schedule of events.  
As such, the following modifications to these procedures may be required:  
9.H. i. Consent: Potential participants will be provided with advanced copies of the informed consent form 
either by mail or email. During the remote combined screening/baseline visit, participants will be consented 
remotely and will then return the signed consent form by mail or secure email. Participants may sign consent 
electronically via secure database.  
9.H. ii. Physical Exam: Examination elements that are feasible will be conducted remotely using video 
streaming. All practical attempts will be made to obtain physical examination records from the last 12 months.  
9.H. iii. Vital Signs, Height & Weight: These events will be omitted during remote study visits, as it is not 
feasible to conduct these measurements remotely. As these do not contribute to the eligibility assessment nor 


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adversely affect Serlopitant’s safety profile, they are not necessary for study participation. If there are concerns 
about participant’s medical stability, investigators may refer patients to their primary care physicians or other 
providers for their assessment prior to making determination of eligibility for the study.  
 
9.H. iv. Electrocardiogram (ECG): This test will be omitted during remote study visits to avoid potential harm to 
the participant, as ECG leads will tear their fragile skin and result in painful wounds. At Stanford, we have 
developed a protocol to perform ECGs on EB patients safely by knowledgeable, specifically trained personnel. 
Therefore, we will only perform ECGs at in-person visits at Stanford. 31 patients previously completed 
Serlopitant in studies where ECGs were not performed.  
9.H. v. We will schedule lab draws and urine tests at local labs convenient for the participant. Labs and urine 
test will ideally be drawn within 72 hours of remote visit.  
9.H. vi. Photographs: A subset of participants with target wounds as defined in the protocol will be asked to 
securely send digital photos during or after combined screening/baseline visit (or follow up visits as applicable) 
using Tissue Analytics smart phone application or secure email. Participants will be instructed on how to take 
these photos, which will include a ruler for measurement. Measurements will be taken from these photos and 
used for analysis.  
9.H. vii. Serlopitant Drug Dosing & Dispensing: Serlopitant dosing instructions will be provided during the 
combined screening/baseline visit as usual. Study drug will be dispensed only after consent has been 
obtained, eligibility verified, and participant randomized to receive placebo or active drug. Medication will be 
shipped to patients overnight at ambient temperature. Adult signature will be required for delivery.  
 
 
10. Statistical Analysis Plan: 
10.A. Randomization Plan 
Participants who are determined to be eligible and proceed to randomization will be assigned a unique 
randomization code. The randomization key will be held by the trial statistician or a blinded member of the 
study team. Unblinding for each participant will occur for each participant once they complete the randomized 
phase AND their data is locked, or if a trial participant experiences an adverse event or any other significant 
safety concern where the investigator deems unblinding of that individual necessary for participant safety. This 
unblinding strategy was chosen to facilitate participants’ decisions on whether to participate in the open label 
phase. Given that the critical endpoints in this trial are participant-reported, the investigators deemed that 
equipoise would be maintained under these circumstances.   
 
In order to prevent operational bias (which could theoretically arise should interim aggregate analysis be 
performed), individual participants’ itch scores will be data locked upon completion of the randomized phase 
and accessible thereafter only to their assigned coordinators and/or coordinators tasked with auditing a 
participant’s data for data integrity. Investigators will not be provided REDCap access for aggregate analysis 
until the final participant has completed the randomized phase of the trial. 
 
In order to balance allocation of more severe EB subtypes, participants with either dystrophic EB (including 
both dominant and recessive types) or junctional EB will receive a separate set of randomization codes for 
binary stratification of these more severe EB subtypes among the two treatment arms. 
 
10.B. Sample Size Calculation:  
This Phase 2 clinical trial involving at least 40 participants is powered to determine statistically significant 
differences in the placebo (N=20 participants) vs. 5 mg (N=20 participants) groups. The sample size is powered 
to detect moderate differences in the proportion of responders (3-point NRS decrease in itch) between the active 
and placebo groups.  
 


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Results from our Phase 2 trial showed that 43% of active participants were responders vs. only 14% in placebo 
were responders (1 out of 7). Using a one-sided Fisher’s exact test, our power calculations show that we need to 
enroll a total of 40 participants (1:1) to have 80% power to detect a difference of 50% vs 10% responder rates in 
active and placebo groups, respectively. 
 
Responder 
None 
Total 
Active 
10 
10 
20 
Placebo 
2 
18 
20 
Total 
12 
28 
40 
Fisher's exact test 
The two-tailed P value equals 0.01 
 
Because itch is subjective and varies daily, participants will be asked to keep an itch diary nightly before 
bedtime when itch has been reported to be the worst.  According to recent psychometric studies, the important 
difference for clinical improvement of chronic pruritus ranks between a drop of 2 to 3 points on the NRS78.8,12 
This trial is powered to be able to detect this level of clinically meaningful reduction in itch. 
 
10.C. Statistical plan for efficacy endpoints:  
The proportion of participants achieving 2, 3, and 4-point reductions in average daily NRS with serlopitant at 
the end of 8 weeks of active treatment will be compared to placebo using Fisher’s Exact test. A similar 
approach will be utilized to compare the proportion of participants achieving at least a 30% or 50% reduction in 
itch as measured by NRS from baseline at 8 weeks.   
 
We will also measure continuous change in average daily NRS and worst-itch NRS score by group over time. 
For each participant, we will plot their average itch scores over time before and after drug intervention. For each 
dosage group, we will use linear regression methods with mixed effects (GLM, SAS) to track the change in itch 
in each of the groups from baseline.   
 
Furthermore, we will evaluate monthly change in median NRS itch scores by group as compared to baseline, 
which will enable evaluation of durability through assessment of NRS itch scores at month 3 of washout.   
 
Primary and secondary endpoints will be performed on an intention to treat basis.  This study will provide the 
effect size, standard deviation and range of itch scores in EB participants in order to properly power a phase 3 
trial.  
 
11. Safety Assessment and Monitoring 
 
11.A. Pregnancies and Contraception Requirements for Females 
For the purposes of this study, a female of childbearing potential is defined as any female who has experienced 
menarche and is pre-menopausal, unless permanently surgically sterile (e.g., hysterectomy, bilateral 
salpingectomy, bilateral oophorectomy). A postmenopausal state is defined as no menses for 12 months without 
an alternative medical cause in a previously menstruating female. We note that many adolescents with severe 
subtypes of epidermolysis bullosa have may significantly delayed age of menarche. 
 
For the purposes of this study, all female participants of childbearing potential must use highly effective 
contraception (i.e. pregnancy prevention method with a failure rate of <1% per year) from the time of the 
Screening visit until 2 weeks after the last dose of study drug. This includes the use of one or more of the 
following acceptable methods:  
 


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1. Surgical sterilization (e.g., bilateral tubal occlusion or ligation, hysterectomy, bilateral salpingectomy, 
bilateral oophorectomy). 
2. Total (as opposed to periodic or cyclic) abstinence from heterosexual intercourse, only if planned for the 
entire duration of the study period and consistent with the preferred and usual lifestyle for the participant 
3. Hormonal contraception associated with consistent inhibition of ovulation; these may include (but are 
not necessarily limited to) oral, intravaginal, implantable, injectable, or transdermal delivery methods 
4. Intrauterine device/system 
5. Exclusive (sole) monogamous intercourse with a sterilized (i.e., vasectomized) or otherwise non-fertile 
(e.g., castrated) male partner; the male partner must have received medical assessment of the surgical 
success 
 
Any pregnancy occurring in a female participant or the female partner of a male participant, from the first study 
drug administration through the required follow-up visit will be reported within 24 hours of the investigator’s 
awareness of the pregnancy. Any pregnancies that occur will be dated for time of conception through 
coordination with participants’ family medicine or obstetrics provider based on ultrasound findings, quantitative 
serum BHCG results, last menstrual period, physical examination, and timing of coitus.   
 
The investigators will follow the pregnancy to delivery or other pregnancy outcome. Pregnancy in a female 
clinical trial participant or female partner of a male clinical trial participant is not an SAE per se.  
 
Any abnormal pregnancies that occur during the trial will be flagged as a serious adverse event and all available 
information will be captured as part of the CRF. Abnormal pregnancies include (but are not limited to): 
spontaneous abortion, missed abortion, benign hydatidiform mole, blighted ovum, fetal death, intrauterine 
death, miscarriage, and stillbirth). 
 
Complications during pregnancies will be reported as such even if they occur after the Follow-up visit. All 
exposed infants will be followed and assessed at birth. Any congenital anomalies/birth defects will be recorded 
in the CRF and reported as SAEs.  
 
11.B. Study Drug Discontinuation 
 
Participants should be discontinued from study drug treatment in any of the following situations: 
1. A female participant desires to become pregnant at the current time, stops contraception, expels her 
intrauterine device/implant, or becomes pregnant 
2. A female participant has new breast findings (e.g. a palpable mass or abnormal mammography, 
discharge), or has abnormal vaginal discharge or bleeding 
3. The participant decides to discontinue study drug treatment, or withdraws consent from the study 
4. The participant receives a strong CYP3A4 inhibitor  
5. Any medical condition that may jeopardize the participant’s safety if study drug is continued, in the 
investigator’s opinion; this may include the development of persistently (2 successive occasions) 
abnormal thyroid function tests (TSH >10, or TSH > 5 with low free T4; TSH <0.1, or TSH < 0.4 with 
high free T4); abnormal morning prolactin >100 ng/mL, cortisol, or corticotropin levels; or signs and 
symptoms of adrenal insufficiency.  Participants with abnormal endocrine assessments will be referred 
to an endocrinologist for evaluation, which may include repeat laboratory assessment for participants 
with abnormal thyroid levels every 4-6 weeks until the abnormalities resolve. 
6. Discontinuation is deemed to be in the best interest of the participant, in the investigator’s opinion, 
including evidence that the participant does not meet inclusion/exclusion criteria intended primarily for 
safety reasons, or a persistent lack of adherence to study procedures 
 
11.C. Definition of Adverse Events: 


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An adverse event (AEs) or suspected adverse reaction is considered “serious” (SAE) if, in the view of the 
investigator, it results in any of the following outcomes: Death, a life-threatening adverse event, inpatient 
hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial 
disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Important 
medical events that may not result in death, be life-threatening, or require hospitalization may be considered 
serious when, based upon appropriate medical judgment, they may jeopardize the participant or participant and 
may require medical or surgical intervention to prevent one of the outcomes listed in this definition.  
 
The Principal Investigator will provide oversight on monitoring safety/AEs/SAEs at this site. For data safety 
monitoring, the principal investigator, co-principal investigator, and any sub-investigators will formally meet 
monthly to review all new AEs, SAEs, and any safety concerns that arose in the past month.  
 
11.C.i. Criteria for Unanticipated Problems: 
The investigators as a group will assess whether the AE represents an unanticipated problem (UP) based on the 
following criteria: 
 
Events (internal or external, deaths, life-threatening experiences, injuries, or other) occurring during the 
research study, which in the opinion of the PI meet all of the following criteria:  
 
a) Unexpected in terms of nature, severity, or frequency, given (a) the research procedures described in the 
protocol-related documents, and (b) the characteristics of the participant population being studied; AND  
b) Related to participation in the research or there is a reasonable possibility or likelihood that the incident, 
experience, or outcome may have been caused by the procedures involved in the research; AND  
c) Harmful that the research places participants or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized. 
 
11.D. Reporting Adverse Events: 
 
11.D.i. Reporting UPs: 
If the investigator determines that the AE represents a UP, the investigator will report the AE to the IRB within 
10 working days from when the PI learns of the event.  
 
If the adverse event does not qualify as a UP, the adverse event should be reported at continuing review.  
 
11.D.ii. Reporting SAEs: 
Unexpected deaths or life-threatening experiences related to the research will be reported to the IRB within 5 
working days from PI learning of event.  
 
Reporting any unexpected fatal or life-threatening suspected adverse reactions to the FDA will occur no later 
than 7 calendar days after initial receipt of the information.  
 
Reporting any (1) serious, unexpected suspected adverse reactions, (2) findings from other clinical, animal or 
in-vitro studies that suggest significant human risk, and (3) a clinically important increase in the rate of a 
serious suspected adverse reaction to the FDA and all investigators will occur no later than 15 calendar days 
after determining that the information qualifies for reporting. 
 
11.D.iii. Reporting AEs: 
In this study, the occurrence of any AE from the time of informed consent until 4 weeks after the last dose of 
study drug will be reported to the Stanford IRB and the FDA. 


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Submission of annual progress reports will occur within 60 days of the anniversary of the date that the IND 
went into effect (date that clinical studies were permitted to begin). 
 
11.E. Data Monitoring Plan: 
Monthly to bimonthly, study staff will perform an internal quality control check of data to confirm that Good 
Clinical Practices are upheld and compliance with all regulations. This will include a review of source 
documents including the study paper chart, the informed consent, lab reports, physician notes, adverse event 
documentation, concomitant medication documentation, and online case report forms. CRFs may be used as 
source documents per PI discretion. 
 
12. References: 
1. 
Frenkl TL, Zhu H, Reiss T, Seltzer O, Rosenberg E, Green S. A Multicenter, Double-Blind, 
Randomized, Placebo Controlled Trial of a Neurokinin-1 Receptor Antagonist for Overactive Bladder. 
The Journal of Urology. 2010;184(2):616-622. 
2. 
Yosipovitch G, Ständer S, Kerby MB, et al. Serlopitant for the treatment of chronic pruritus: Results of a 
randomized, multicenter, placebo-controlled phase 2 clinical trial. Journal of the American Academy of 
Dermatology. 2018;78(5):882-891.e810. 
3. 
Chiou AS, Choi S, Barriga M, et al. Phase 2 Trial of a Neurokinin-1 Receptor Antagonist for the 
Treatment of Chronic Itch in Epidermolysis Bullosa Patients: A Randomized Clinical Trial. Journal of 
the American Academy of Dermatology. 2019. 
4. 
CDER, CBER. Epidermolysis Bullosa: Developing Drugs for Treatment of Cutaneous Manifestations. 
Guidance for Industry. . In: FDA, ed2019. 
5. 
Wong DL, Baker CM. Smiling face as anchor for pain intensity scales. Pain. 2001;89(2):295-297. 
6. 
Desai NS, Poindexter GB, Monthrope YM, Bendeck SE, Swerlick RA, Chen SC. A pilot quality-of-life 
instrument for pruritus. Journal of the American Academy of Dermatology. 2008;59(2):234-244. 
7. 
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)--a simple practical measure for routine 
clinical use. Clin Exp Dermatol. 1994;19(3):210-216. 
8. 
Reich A, Riepe C, Anastasiadou Z, et al. Itch Assessment with Visual Analogue Scale and Numerical 
Rating Scale: Determination of Minimal Clinically Important Difference in Chronic Itch. Acta Derm 
Venereol. 2016;96(7):978-980. 
9. 
Morris V ML, Rosenberg M, Rosenberg L, Holzer CE, Meyer WJ. Itch assessment scale for the 
pediatric burn survivor. J Burn Care Res. 2012;33(3):419-424. 
10. 
Haest C, Casaer MP, Daems A, et al. Measurement of itching: validation of the Leuven Itch Scale. 
Burns. 2011;37(6):939-950. 
11. 
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture 
(REDCap)--a metadata-driven methodology and workflow process for providing translational research 
informatics support. J Biomed Inform. 2009;42(2):377-381. 
12. 
Kimball AB, Naegeli AN, Edson-Heredia E, et al. Psychometric properties of the Itch Numeric Rating 
Scale in patients with moderate-to-severe plaque psoriasis. British Journal of Dermatology. 
2016;175(1):157-162. 


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Appendix: Schedule of Events Table 
 
Screening 
Double-Blind Phase 
Optional Open-Label Phase 
 
Pre-
Screening 
Screening 
Baseline 
Month 
1 
Month 
2 
Month 
3 
Baseline 
Month 
1 
Month 
3 
Month 
615 
Month 
1215 
 
Phone 
Call 
Clinic 
Visit 
Clinic 
Visit 
Phone 
Call 
Clinic 
Visit 
Phone 
Call 
Phone 
Call 
Phone 
Call 
Phone 
Call 
Phone 
Call 
Phone 
Call 
Informed Consent 
 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
X 
 
 
 
 
 
 
 
 
 
Medical History 
X 
X 
 
 
 
 
 
 
 
 
 
Medication Review 
X1 
X1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Review Inclusion / Exclusion Criteria 
X 
X 
X 
 
 
 
 
 
 
 
 
Vital Signs2 
 
X 
X 
 
X 
 
 
 
 
 
 
Physical Examination 
 
X 
X 
 
X 
 
 
 
 
 
 
Electrocardiogram (ECG) 
 
X 
 
 
X 
 
 
 
 
 
 
Target Wound Selection 
 
X 
 
 
 
 
 
 
 
 
 
Target Wound Photographs3 
 
X 
X 
 
X 
 
 
 
 
 
 
Target Wound Assessments4 
 
X 
X 
 
X 
 
 
 
 
 
 
Questionnaire Completion5 
 
X 
X 
X6 
X6 
X6 
X6 
X6 
X6 
X6 
X6 
Dispense Study Diary(ies)7 
 
X 
X 
X 
X 
X14 
X 
X 
X 
X 
 
Safety Laboratory Assessments8, 9 
 
X10 
 
X11 
X10 
X10,11 
X10,11 
X11 
X10,11 
X11 
X10,11 
Determination of Eligibility12 
 
 
X 
 
 
 
 
 
 
 
 
Randomization 
 
 
X 
 
 
 
 
 
 
 
 
Dispense Study Medication or Placebo 
 
 
X 
X 
 
 
 
 
 
 
 
Dispense Serlopitant 
 
 
 
 
 
X14 
X 
X 
X 
X 
 
Review Adverse Events 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Review Study Diary(ies) 
 
 
X 
X 
X 
X 
X13 
X13 
X13 
X13 
X13 
1: Includes a review of all medications taken within the previous 30 days 
2: Includes height, weight, blood pressure, heart rate, temperature 
3: Photographs only if participant has target wounds and has given consent for photography 
4: Target wound assessment includes: average itch in past 24h, worst itch in past 24h, average pain in past 24h 
5: Questionnaires include: Stanford EB Itch Survey, ItchMan, DLQI, ItchyQoL, Leuven Itch Scale, sPGAIS, PROMIS scales (pediatric versions for participants <18y), Itch Controlled Day Questionnaire. 
 
6: Will also assess participant (pGICIS) and caregiver (cGICIS) impression of change in itch severity 
7: Either electronic REDCap diary or paper diary. Completed paper diaries will be mailed back to Stanford; new paper diaries will be mailed to participant. Females of childbearing potential not on hormonal 
contraception will be given a menstruation diary in addition to the study diary. 
8: Labs include: CBC, CMP, UA, UPT (if female of child-bearing potential) 
9: Labs obtained from outside providers up to 60 days prior to Screening can be used as Screening labs for study purposes. as long as they contain the equivalent labs of interest  
10: Additional labs obtained at Screening, Month 2, Month 3, Open Label: TSH, FT4, ACTH, cortisol, prolactin 
11: Labs will be obtained at a local laboratory convenient for the participant, at +/- 10 days from target date of study visit.  
12: Will determine if 30-day washout is needed from prohibited study medication 
13: Open label phase diaries will be completed weekly 
14: Will be performed only if participant elects to pursue optional open label phase 
15: For participants enrolled prior to May 2020 who elect to continue in open label phase