Intervention: ABROCITINIB
Trial phase: Phase 2
ATC code: D11AH08
SMILES: CCCS(=O)(=O)N[C@H]1C[C@@H](N(C)c2ncnc3[nH]ccc23)C1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 10
Group description: Chronic Pruritus of Unknown Origin (CPUO) patients only: Study Design: Subjects meeting study criteria will undergo a 4-week washout period of other therapies that could impact pruritus through the end of the study (including antihistamines, topical steroids, systemic antipruritic therapies or immunosuppressants).

Abrocitinib: During the study period, subjects will take one Abrocitinib 200 mg tablet once daily orally. Subjects will be directed to take doses of Abrocitinib at approximately the same time of day.
Eligibility criteria:
Inclusion Criteria:

Males or female participants between ages 18-80 years at time of signing informed consent
A clinical diagnosis of prurigo nodularis, defined by the presence of at least 10 pruritic nodules on at least 2 different anatomic locations (with each arm, leg, and anterior and posterior trunk considered distinct anatomic locations)

OR

Subject has ongoing chronic pruritus of unknown origin, which must be present on multiple segments on the body. CPUO patients must not have known dermatologic or systemic conditions, that in the opinion of the investigator, are the cause of patient's pruritus
Subject has moderate to severe pruritus, defined as average peak pruritus numeric rating scale - (PP-NRS) > 7 (range 0-10, higher score indicating greater degree of pruritus severity) in the 7 days prior to the Screening Visit.
Female participants are eligible for the study if they are not pregnant, planning to become pregnant or breastfeeding during the study or not a woman of child bearing potential (WOCBP)

Exclusion Criteria:

Infected with hepatitis B or hepatitis C viruses.
Infected with Herpes Simplex or Herpes zoster.
Positive HIV serology at screening,
Evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)
History of lymphoproliferative disease, or active primary or recurrent malignancy
History of recurrent (≥ 2) venous thromboembolism (VTE) or (DVT/PE) - deep vein thrombosis and pulmonary embolism
Untreated thyroid, adrenal, or pituitary disease or nodules, or history of thyroid malignancy

Have received any of the following treatment regiments specified in the timeframes outlined below:

Within 6 months of first dose of study drug: Rituximab, any other B cell depleting therapies, or intravenous immunoglobulin (IVIg)
Within 12 weeks of first dose of study drug: Any studies with Janus kinase (JAK) inhibitors; Cyclophosphamide (or any other cytotoxic agent), belimumab, or anifrolumab (or another anti-interferon (IFN) therapy)
Within 8 weeks of first dose of study drug: Other biologics
Within 6 weeks: Have been vaccinated with live or attenuated live vaccine.
Within 4 weeks: Participation in other studies involving investigational drug(s)
Within 4 weeks: Use of oral immune suppressants; systemic immunosuppressive therapies, neuromodulatory therapies, Phototherapy (NB UVB) or broad band phototherapy; Regular use (more than 2 visits per week) of a tanning booth/parlor.
Within 1 week of first dose of study drug: Topical treatments that could affect PN; Herbal medications with unknown properties or known beneficial effects for PN.