Key Inclusion Criteria:
* Participant must be ≥ 18 years of age, at the time of signing the informed consent.
* Participants with chronic pruritus for at least 4 months prior to screening.
* Chronic pruritus considered of unknown origin as assessed by the investigator at baseline (e.g., excluding chronic pruritus related to primary dermatological or systemic conditions, neuropathic or psychogenic origin or secondary to drugs or other allergen exposures).
* Chronic pruritus must affect at least 2 of the following body areas: trunk, arms, or legs (cannot be unilateral and/or dermatomal in distribution).
* Participants with ongoing, severe chronic pruritus despite the use of emollients and who are candidates for systemic therapy.
* Participants must have severe itch defined by a WI-NRS ≥7 at screening; score scale ranges from 0 to 10; higher score indicates worse itch.
* Participants must have an average WI-NRS ≥7 over the 7 days prior to randomization/baseline visit.
* The average WI-NRS score over the preceding 7 days prior to the randomization/baseline visit will be calculated based on the daily WI-NRS scores (0-10).
* Participants must have PGIS of pruritus scored as 3 "severe" at screening and baseline visits.
Key Exclusion Criteria:
* Any active skin conditions (e.g., atopic dermatitis, psoriasis, etc.) that may interfere with the assessment of CPUO.
* Known systemic condition(s) or medication(s) that are considered by the investigator to be the primary cause of current pruritus.
* Known or suspected infectious disease that is active, chronic or recurrent which precludes the participant from participating in the clinical trial as per Investigator´s assessment. These infectious diseases include but are not limited to opportunistic infections (e.g., tuberculosis, atypical mycobacterioses, listeriosis or aspergillosis) and/or known or suspected HIV infection.
* History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
* Significant bleeding risk or coagulation disorders. History of gastrointestinal bleeding, e.g., in association with use of nonsteroidal anti-inflammatory drugs (NSAIDs), that was clinically relevant (e.g., where intervention was indicated or requiring hospitalization or blood transfusion). Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited.
* History or current hepatic disease, including but not limited to, acute or chronic hepatitis, cirrhosis or hepatic failure or aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) levels of more than 1.5 x upper limit of normal (ULN) or International Normalized Ratio (INR) of more than 1.5 at screening.
