Inclusion criteria:
Participant Willingness:
1. The participant is willing and able to understand and fully comply with trial procedures and requirements (including digital tools and applications), in the opinion of the investigator.
2. The participant has provided informed consent and any required privacy authorization before the initiation of any trial procedures.
Disease Characteristics:
3. The participant has a diagnosis of chronic non-pustular palmoplantar psoriasis for greater than or equal to (\>=) 6 months prior to the screening visit.
4. Participant has moderate-to-severe palmoplantar psoriasis, as defined by a ppIGA score \>=3 at screening and Day 1 (Baseline).
5. At screening and Day 1 (Baseline), the participant meets all of the following criteria:
* Moderate-to-severe plaque psoriasis as defined by an sPGA \>=3
* Moderate-to-severe palmoplantar psoriasis, as defined by a PPASI \>=8
* Plaque psoriasis BSA involvement of \>=0.25 percent (%) and up to 10%, excluding the palms and soles
6. Participant must be a candidate for phototherapy or systemic therapy.
7. Previously had inadequately controlled disease by topicals, phototherapy and/or systemic treatments.
Age and Reproductive Status:
8. Participant is aged 18 years or older at the time of consent.
9. Participant meets the following birth control requirement: An individual with potential for pregnancy who is now surgically sterile; or a participant of nonchildbearing potential with laboratory confirmation of postmenopausal status; or, if sexually active with a nonsterilized individual who produces sperm, an individual with potential for pregnancy who agrees to use a highly effective method of contraception from the time of signing of the informed consent throughout the duration of the trial and for at least 10 days after the last study dose of trial intervention. The use of effective contraception will be required for assigned male sex at birth participants.
Exclusion criteria:
Target Disease-Related Exclusions:
1. Participant has evidence of nonplaque PsO (pustular PsO, palmoplantar pustulosis, acrodermatitis continua of Hallopeau, erythrodermic, or guttate PsO) or presence of pustules.
2. Participant has a concomitant comorbid skin condition that, in the opinion of the investigator, would interfere with the trial assessments.
Prohibited Psoriasis Treatments Exclusions:
For the below prohibited psoriasis treatments, the washout period prior to Day 1 must be within the time frame indicated or 5 half-lives, whichever is longer, regardless of whether they are prescribed for psoriasis or another condition:
Participant has received any of the following biologics or biosimilar versions within the time frame indicated:
3. Antibodies to interleukin (IL)-12/23.
4. Antibodies to IL-23. There will be an allowance for up to 10 percent (%) of participants with previous IL-23 exposure to enroll. A washout period of 6 months prior to day 1 is required.
5. Previous exposure to Janus Kinase (JAK) inhibitors.
6. Previous exposure to Tyrosine Kinase 2 (TYK2) inhibitors.
Recent/Concurrent Infections Disease Exclusions:
7. History of active tuberculosis (TB), signs or symptoms of active TB. Evidence of latent TB infection, active Herpes infection at screening, history of serious herpetic infection or recurrent herpes zoster, evidence of Hepatitis C virus (HCV), evidence of Hepatitis B Virus (HBV) or HIV-positive status.
Noninfectious Disorders Exclusions:
8. Participant has any clinically significant medical condition, evidence of an unstable clinical condition (for example, cardiovascular, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, or immunologic), or vital signs/physical/laboratory/ECG abnormality that would, in the opinion of the investigator, put the participant at undue risk or interfere with interpretation of trial results. These include but are not limited to:
1. Participant has significant/uncontrolled psychiatric illness, in the opinion of the investigator.
2. Participant has any lifetime history of suicidal ideation, suicidal behavior, or suicidal attempts.
3. Participant has a history of clinically significant drug or alcohol abuse within 12 months prior to Day 1
Allergies and Adverse Drug Reactions Exclusions:
9. Participant has history of significant drug allergy (such as anaphylaxis).
10. Participant has a known or suspected allergy to zasocitinib or any of their components.
