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

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.

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, junctional or simplex).
4. History of chronic pruritus of at least 6 weeks in duration
5. On the Screening Visit or Screening phone call, patients must have an NRS pruritus score of at least 5 on average itch score in the past 24 hours
6. Female subjects must be of non-childbearing potential (ie, post-menopausal for at least 1 year, had a hysterectomy, or had a tubal ligation) or, if 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. Effective contraception is defined as follows: oral/implant/injectable/ transdermal contraceptives, intrauterine device, condom with spermicide, or diaphragm with spermicide. Abstinence or partner's vasectomy is acceptable if the female agrees to use effective contraception if she decides to discontinue abstinence or to have sexual intercourse with a non-vasectomized partner.
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 subject to travel to Stanford or to undergo study procedures or to give informed consent.
2. Have a history of sensitivity to any components of the study material.
3. Are 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 subject 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. Subjects with hepatitis B and C who have normal liver function may be enrolled.
7. Have a current malignancy (such as Hodgkin's lymphoma, B or T cell lymphoma, or myeloma) or blood cell dyscrasia (e.g., polycythemia or myelofibrosis) that would lead to systemic chronic pruritus.
8. Have a history of thyroid cancer, thyroid nodules, inadequately treated thyroid disease, or abnormal TSH or free T4 at screening.
9. Have a history of abnormalities in adrenal or pituitary function (pituitary adenoma, adrenal insufficiency, or adrenal nodule).
10. Screening cortisol level < 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).
13. Have pruritus due to urticaria, drug allergy, or infection (such as pityriasis rosacea or tinea or active human immunodeficiency virus [HIV]). Note: Subjects with HIV who have undetectable viral load, and stable retro-viral 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 two weeks prior to initiation of study and throughout the study period (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, and gabapentin)
17. Started or changed medications, creams, or emollients including over-the-counter (OTC) preparations or bath oil treatment specifically for relief of pruritus within 30 days prior to Screening.
18. Within in the past 12 months, have expressed suicidal ideation with some intent to act.
19. Have any social or medical condition (e.g. alcoholism, drug dependency, psychotic state) that, in the investigator's opinion, might interfere with the subject's ability to comply with the requirements of the protocol.

Up to 15 months

The primary limitation of the study is the small sample size due to the rarity of EB, the COVID-19 pandemic-related disruptions, and limited drug availability.

This is a double-blind study.