Zasocitinib

ACR responses are the numerical measurement of improvement in multiple disease assessment criteria. It is a composite clinical outcome assessment (COA) measure that includes both clinician-reported outcome (ClinROs) and participant-reported outcome (PROs). An ACR20 response is defined as: greater than or equal to (\>=) 20 percent (%) improvement from baseline in both swollen joint count in 66 joints (SJC66) and tender joint count in 68 joints (TJC68), and \>=20% improvement from baseline in 3 of the following 5 assessments: participant's global assessment (PtGA) of PsA pain; PtGA of PsA; physician's global assessment (PGA) of PsA; participant's assessment of physical function as measured by health assessment questionnaire-disability index (HAQ-DI); high-sensitivity C-reactive protein (hsCRP). Percentage of participants achieving ACR20 response at Week 24 for zasocitinib compared to placebo will be reported.

The ppIGA is a 5-point score ranging from 0 to 4, based on the investigator's assessment of the average erythema (redness), induration (thickness), scaling and fissures of all palmoplantar (non-pustular) psoriatic lesions. A lower score indicates lower severity, with 0 being "clear" and 1 being "almost clear."

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of the trial intervention, whether or not the occurrence is considered related to the trial intervention. TEAE is defined as any AE emerging or manifesting at or after the initiation of treatment in the LTE study with a trial intervention or medicinal product or any existing AE that worsens in either intensity or frequency following exposure to the trial intervention or medicinal product. SAE is any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, or is an important medical event.

An AESI is an adverse event of scientific and medical concern specific to the compound or program, for which ongoing monitoring and rapid communication by the investigator may be appropriate.

Vital signs will include measurement of body temperature, respiratory rate, sitting blood pressure and pulse rate. Any clinically significant change in vital signs will be determined at the investigator's discretion.

Laboratory parameters will include hematology, chemistry and urinalysis. Any clinically significant change in laboratory values will be determined at the investigator's discretion.

The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA composite score ranges from 0 to 4 and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean greater than (\>) 0, less than (\<) 1.5; Mild (2) = mean \>= 1.5, \<2.5; Moderate (3) = mean \>=2.5, \<3.5; and Severe (4) = mean \>=3.5. The percentage of participants achieving an sPGA of Clear (0) or Almost Clear (1) with a \>= 2-point decrease from baseline at Week 16 will be reported.

The PASI is a measure of the average redness, thickness and scaliness of psoriatic skin lesions (each graded on a 0 to 4 scale; 0 = none to 4 = very severe), weighted by the area of involvement (head, upper extremities, trunk, and lower extremities). The PASI score ranges from 0 to 72, with higher PASI scores denoting more severe disease activity (less than or equal to \[\<=\] 3 representing mild disease, \>= 3 to 15 representing moderate disease, and \>= 15 indicating severe disease). The PASI-75 is defined as 75% improvement from baseline in PASI score. The percentage of participants achieving \>= 75% improvement from baseline in PASI score at Week 16 will be reported.

Cmax of zasocitinib in plasma will be assessed.

Tmax of zasocitinib in plasma will be assessed.

AUC0-Last of zasocitinib in plasma will be assessed.

PASI is a measure of the average erythema, induration/infiltration, and desquamation/scaling of psoriatic skin lesions (each graded on a 0 to 4 scale; 0 = none to 4 = very severe), weighted by the area of involvement (head, upper extremities, trunk, and lower extremities). The PASI produces a numeric score that can range from 0 to 72 (less than or equal to \[\<=\] 3 representing mild disease, greater than or equal to \[\>=3\] to 15 representing moderate disease, and \>=15 indicating severe disease) with higher PASI scores denoting more severe disease activity. Percentage of participants showing 100 percentage (%) improvement in PASI score relative to baseline PASI score will be reported.

ACR responses are the numerical measurement of improvement in multiple disease assessment criteria. It is a composite clinical outcome assessment (COA) measure that includes both clinician-reported outcome assessments (ClinROs) and patient-reported outcomes (PROs). An ACR20 response is defined as: greater than or equal to (\>=) 20 percent (%) improvement from baseline in both swollen joint count 66 joints (SJC66) and tender joint count 68 joints (TJC68), and \>=20% improvement from baseline in 3 of the following 5 assessments: Patient's global assessment (PtGA) of psoriatic arthritis (PsA) pain; PtGA of PsA; physician's global assessment of disease activity (PGA) of PsA; participant's assessment of physical function as measured by health assessment questionnaire-disability index (HAQ-DI); high-sensitivity C-reactive protein (hsCRP). Percentage of participants achieving ACR20 response at Week 16 for zasocitinib Dose A and B compared to placebo will be reported.

A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. An SAE is any untoward medical occurrence that at any dose: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event in the opinion of the healthcare provider, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above. TEAEs consist of both serious and non-serious adverse events.

The sPGA is a 5-point scale of an average assessment of all psoriatic lesions based on erythema, scaling, and induration. The average of the 3 scales, rounded to the nearest whole number, is the final sPGA score. The sPGA score ranges from 0 to 4 (0 = Clear; 1 = Almost clear; 2 = Mild; 3 = Moderate; 4 = Severe). Higher scores indicate more severe disease activity. 'Clear' and 'Almost clear' will include all participants who score a 0 or 1.

PASI is a measure of the average redness, thickness, and scaliness of psoriatic skin lesions (each graded on a 0 to 4 scale; 0 = none to 4 = very severe), weighted by the area of involvement (head, upper extremities, trunk, and lower extremities). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. Percentage of participants showing at least 75% improvement in PASI score relative to baseline PASI score will be reported.

The sPGA is a 5-point scale of an average assessment of all psoriatic lesions based on erythema, scaling, and induration. The average of the 3 scales, rounded to the nearest whole number, is the final sPGA score. The sPGA score ranges from 0 to 4 (0 = Clear; 1 = Almost clear; 2 = Mild; 3 = Moderate; 4 = Severe). Higher scores indicate more severe disease activity. 'Clear' and 'Almost clear' will include all participants who score a 0 or 1.

PASI is a measure of the average redness, thickness, and scaliness of psoriatic skin lesions (each graded on a 0 to 4 scale; 0 = none to 4 = very severe), weighted by the area of involvement (head, upper extremities, trunk, and lower extremities). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. Percentage of participants showing at least 75% improvement in PASI score relative to baseline PASI score will be reported.

The sPGA is a 5-point scale of an average assessment of all psoriatic lesions based on erythema, scaling, and induration. The average of the 3 scales, rounded to the nearest whole number, is the final sPGA score. The sPGA score ranges from 0 to 4 (0 = Clear; 1 = Almost clear; 2 = Mild; 3 = Moderate; 4 = Severe). Higher scores indicate more severe disease activity. 'Clear' and 'Almost clear' will include all participants who score a 0 or 1.

PASI is a measure of the average redness, thickness, and scaliness of psoriatic skin lesions (each graded on a 0 to 4 scale; 0 = none to 4 = very severe), weighted by the area of involvement (head, upper extremities, trunk, and lower extremities). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. Percentage of participants showing at least 75% improvement in PASI score relative to baseline PASI score will be reported.

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of the trial intervention, whether or not the occurrence is considered related to the trial intervention. A TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with a trial intervention or medicinal product or any existing event that worsens in either intensity or frequency after exposure to the trial intervention. An AESI is an adverse event of scientific and medical concern specific to the compound or program, for which ongoing monitoring and rapid communication by the investigator may be appropriate.

HiSCR75 is defined as at least a 75% reduction in the total abscess and inflammatory nodule (AN) count with no increase in abscess or draining tunnel count relative to baseline.

The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. The F-VASI includes contributions from the face, with a possible range from 0 to 3.5, with higher scores indicating more severe disease. Negative changes from baseline indicate improvement. This is recorded as either Yes (achieved \>= 75% improvement) or No (did not achieve).

TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with a study intervention or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the study intervention or medicinal product. An AESI is an adverse event of scientific and medical concern specific to the compound or program, for which ongoing monitoring and rapid communication by the investigator may be appropriate.

Vital sign values include body temperature, respiratory rate, sitting blood pressure (systolic and diastolic, resting more than 5 minutes), pulse (beats per minute). Clinical significance of vital signs will be determined at the investigator's discretion.

Laboratory parameters include hematology, clinical chemistry and urinalysis. Clinical significance of laboratory values will be determined at the investigator's discretion.

ECGs will be performed with the participant in the supine or semi-supine position and after resting comfortably for at least 5 minutes. Clinical significance of 12-lead ECG values will be determined at the investigator's discretion.

The mMS is a composite score of 3 assessments consisting of stool frequency (SF), rectal bleeding (RB), and endoscopic score (ES). Each component subscore ranges from 0 to 3 and total score range of the mMS is from 0 to 9, with higher scores indicating more severe disease. Clinical remission is defined an mMS of ≤2 with SF subscore ≤ 1, RB subscore = 0, and ES ≤ 1 (score of 1 modified to exclude friability).

Endoscopic response is defined by decrease in SES-CD \>50% from baseline (or for participants with isolated ileal disease, SES-CD \<=4 or at least a 2-point reduction from baseline). SES-CD evaluates 4 endoscopic variables (the intestinal surface affected by ulcers, the intestinal surface affected by other inflammatory lesions, the presence of ulcers, and the presence of narrowing).

ACR20 is composite measure defined as improvement of 20 percent(%) from baseline in both number of tender (68) \& number of swollen (66) joints \& a 20% improvement in at least 3 of following 5 criteria: patient global assessment of psoriatic arthritis (PGA-PsA) \[visual analog scale (VAS) where, 0=very good, no symptoms \& 100=very poor, severe symptoms\], physician global assessment of psoriatic arthritis (PhGA-PsA) \[(VAS) where 0=no disease activity \& 100=maximum disease activity\], patient global assessment of psoriatic arthritis pain (PGAAP) \[(VAS) where 0=no pain \& 100=most severe pain\], disability history questionnaire i.e., Health Assessment Questionnaire-Disability Index \[HAQ-DI\] (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip \& activities, 0=without difficulty to 3=unable to do) \& acute phase reactant like high sensitivity C-reactive protein \[hsCRP\]). Percentages are rounded off to the nearest decimal.