PRISM Study-Pruritus Relief Through Itch Scratch Modulation

Inclusion Criteria

• Individuals diagnosed with generalized nodular PN, covering 2 separate body parts, and 10 or more pruriginous nodules
• Severe itch due to PN
• Age 18 years and older at the time of consent, and a life expectancy of at least 18 months.
• Individuals using antidepressants must be on a stable dose for a minimum of 4 weeks prior to screening.
• Participants with a history of acute secondary dermatoses within the preceding 6 months may enroll only if the dermatosis has resolved completely as follows per medical history or participant self-report and current clinical assessment: (a) Localized contact dermatitis, environmental exposures, superficial burns, or viral exanthems must have been resolved for at least 4 weeks prior to screening. (b) Skin or environmental infestations, such as scabies, lice, or bed bugs, must have been resolved for at least 8 weeks prior to screening.
• Any identified systemic, non-dermatologic disease that could be a potential cause of concomitant pruritus (e.g., thyroid disease, celiac disease, hepatitis C virus [HCV]) must either have resolved, been successfully treated [i.e., HCV ribonucleic acid (RNA) negative], or must be successfully managed with stable, optimized treatment (e.g., thyroid replacement, dietary management with resolution of symptoms, respectively) for at least 3 months prior to screening.
• Participants who are human immunodeficiency virus (HIV) positive may enroll if they meet the following criteria: (a) currently on a stable (> 6 months stable use) and well tolerated highly active antiretroviral therapy regimen; (b) cluster of differentiation 4 (CD4) count > 500 cells/mL; and (c) HIV ribonucleic acid (RNA) < 50 copies/mL documented for at least 6 months prior to enrollment.

Exclusion Criteria

• Pruritus due to localized PN (only one body part affected), or less than 10 nodules
• Active, uncontrolled, pruritic dermatoses in need of treatment (such as atopic dermatitis or bullous pemphigoid for example).
• History of a major psychiatric disorder such as bipolar disorder or schizophrenia. History of active substance abuse in the last 3 years.
• Known intolerance [gastrointestinal (GI), central nervous system (CNS) symptoms] or hypersensitivity/drug allergy to opioids.
• Use of certain concomitant medications and treatments within a period prior to the study, or requirement for these medications during the study:
• Potential participants taking opiates, gabapentin, pregabalin, calcineurin inhibitors, cannabinoid agonists, capsaicin, cryosurgery, topical doxepin, thalidomide or methotrexate, topical antihistamines or topical corticosteroids require a 14-day washout.
• Within 4 weeks prior to screening: ultraviolet (UV)-therapy, exposure to any investigational medication, including placebo
• Within 3 months prior to screening: Non-insulin biologics (including monoclonal antibodies) that modify the immune system,
• Individuals taking monoamine oxidase inhibitors are excluded, as concomitant opiate use may increase the risk for serotonin syndrome.
• Myocardial infarction or acute coronary syndrome within the previous 3 months, as reported by the participant.
• Individuals with prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF).

Note: Other Inclusion/Exclusion criteria may apply.