Efficacy and Safety of HS-10374 Compared to Placebo in Adults With Active Psoriatic Arthritis

The ACR 20, ACR 50 or ACR 70 definition of improvement is a 20%, 50% or 70% improvement, respectively, over baseline in tender and swollen joint counts and a 20%, 50% or 70% improvement, respectively, in 3 of the 5 remaining core data set measures (Subject Global Assessment of disease activity, Physician Global Assessment of psoriatic arthritis, Subject global assessment of pain, HAQ-DI, hs-CRP).

The ACR 20, ACR 50 or ACR 70 definition of improvement is a 20%, 50% or 70% improvement, respectively, over baseline in tender and swollen joint counts and a 20%, 50% or 70% improvement, respectively, in 3 of the 5 remaining core data set measures (Subject Global Assessment of disease activity, Physician Global Assessment of psoriatic arthritis, Subject global assessment of pain, HAQ-DI, hs-CRP).

The ACR 20, ACR 50 or ACR 70 definition of improvement is a 20%, 50% or 70% improvement, respectively, over baseline in tender and swollen joint counts and a 20%, 50% or 70% improvement, respectively, in 3 of the 5 remaining core data set measures (Subject Global Assessment of disease activity, Physician Global Assessment of psoriatic arthritis, Subject global assessment of pain, HAQ-DI, hs-CRP).

The HAQ-DI is a patient-reported outcome measure that assesses the degree of difficulty a subject has experienced during the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2 to 3 items. For reach item in the questionnaire the level of activity is cored from 0 to 3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as much "difficulty", and 3 has "unable to do". Any activity that requires assistance from another individual or requires the use of an assistive device adjusts to a score of 2 or more.

Psoriasis Area and Severity Index (PASI) is a scoring system quantifying the severity of psoriasis based on both lesion severity and area of involvement. PASI assessment is performed by investigators, and the numeric score ranges from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 75, PASI 90 responses are defined as 75% or 90% improvement in PASI score from baseline.

Static physician's global assessment (sPGA) of psoriasis is an average assessment of all psoriatic lesions based on erythema, induration, and scale. It's a 5-point scale performed by investigators. A sPGA score of 0 or 1 means "clear" or "almost clear" respectively.

Psoriasis body surface area (BSA) involvement is measured using the handprint method with the size of a patient's handprint representing ~1% of body surface area involved.

The dermatology life quality index (DLQI) is a patient reported outcome measurement. It's a questionnaire consisting of 10 questions concerning patients' perception of the impact of skin diseases on different aspects of their health-related quality of life over the last week. Each question is scored on a scale of 0 to 3, and the sum of each scores range from 0 (no impairment of life quality) to 30 (maximum impairment).

DAS28-CRP is a composite outcome measure that assesses: Numbers of joints in the hands (including metacarpophalangeal and proximal interphalangeal joints, except for distal interphalangeal joints), wrists, elbows, shoulders, and knees are swollen and/or tender over a total of 28; Hypersensitive-CRP in the blood to measure the degree of inflammation; Subject Global Assessment of disease activity.

The results are combined to produce the DAS28-CRP score, which correlates with the extent of disease activity: ≤2.6: Disease remission; 2.6 - 3.2: Low disease activity; 3.2 - 5.1: Moderate disease activity; >5.1: High disease activity.

The Disease Activity Index for Psoriatic Arthritis Score (DAPSA) is a composite measure to assess peripheral joint involvement that is based upon numerical summation of 5 variables of disease activity: tender/painful joint count, swollen joint count, Subject Global Assessment of disease activity, Subject Global Assessment of pain, and hs-CRP.

Minimal Disease Activity (MDA) response is defined as a subject fulfilling 5 of 7 of the following outcomes: tender joint count ≤ 1; swollen joint count ≤ 1; PASI ≤ 1 or body surface area (BSA) ≤ 3%; Subject Global Assessment of pain ≤ 15; Subject Global Assessment of disease activity ≤ 20; HAQ-DI ≤ 0.5; Tender entheseal points ≤ 1

A composite measure calculated from the Physician Global Assessment of psoriatic arthritis, the Subject Global Assessment of disease activity, the Short Form Health Survey-36 Item (SF-36) Physical Component Summary (PCS), the swollen joint count, the tender joint count, the LEI, the tendor dactylitis count and the hs-CRP.

The Psoriatic Arthritis Response Criteria (PsARC) consists of 4 measurements: tender/painful joint count, swollen joint count, Physician Global Assessment of psoriatic arthritis, and Subject Global Assessment of psoriatic arthritis. In order to be classified as a PsARC responder, subjects must achieve improvement in 2 of 4 measures, one of which must be joint pain or swelling, without worsening in any measure.

The SF-36 is a patient-reported outcome measure in clinical practice and research. The instrument includes 36 items to measure the following 8 health dimensions over the past 4 week: 1) limitations in physical activities, such as bathing or dressing; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality; and 8) general health perceptions.

Symptoms of spondylitis over the past week will be evaluated using the BASDAI, which consists of a 0 to 100 scale measuring discomfort, pain, and fatigue in response to 6 questions pertaining to the 5 major symptoms of ankylosing spondylitis:

• Fatigue
• Spinal pain
• Joint pain and swelling
• Areas of localized tenderness
• Morning stiffness duration
• Morning stiffness severity A higher count indicates worse disease.

Leed's Dactylitis Index (LDI) is a quantitative measurement of dactylitis in the 20 digits using a dactylometer. The circumference of the affected and contralateral digits, and tenderness of the affected digits are measured to generate a total score. A higher score indicates worse dactylitis and is based on the current evaluation.

The Leed's enthesitis index (LEI) was developed specifically for PsA. An overall score of 0 to 6 is derived from the presence or absence of tenderness at 6 entheseal sites (right and left: lateral epicondyle, medial femoral condyle, and Achilles tendon insertion) at the time of evaluation. A higher count indicates a greater enthesitis burden.

Trough observed plasma concentration of HS-10374