A Neurokinin-1 Receptor Antagonist for the Treatment of Pruritus in Patients With Epidermolysis Bullosa
Condition: Epidermolysis Bullosa
MeSH terms: Epidermolysis Bullosa; Pruritus
Intervention: Serlopitant Tablet; Placebo Oral Tablet
Intervention description: 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.; The placebo is a tablet that looks like a drug but has no drug or other active ingredient in it.
Intervention MeSH terms: Serlopitant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: This is a double-blind study.
Enrollment: 28.0
Sex: All
Minimum age: 13 Years
Healthy volunteers: No

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

Eligibility 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, 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.