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

Phase 2
Recruiting
Conditions
Psoriatic Arthritis
Interventions
Drug: HS-10374-matched placebo tablets
Registration Number
NCT06176508
Lead Sponsor
Hansoh BioMedical R&D Company
Brief Summary

This study has been designed to explore the clinical efficacy and safety of HS-10374 in the treatment of active psoriatic arthritis. Additionally, this study is to find the optimal dosing for the future clinical development of HS-10374.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
160
Inclusion Criteria
  1. Male or female subjects between the ages of 18-75 years.
  2. Has a history of psoriatic arthritis (PsA) for at least 6 months, and meets the Classification Criteria for Psoriatic Arthritis (CASPAR) at screening.
  3. Active arthritis as shown ≥ 3 swollen joints (66 joints) and ≥ 3 tender joints (68 joints) at both screening and baseline.
  4. Active plague psoriatic skin lesion or documented history of plague psoriatic at screening.
  5. hs-CRP ≥ 3mg/L at screening.
  6. Subjects either (i) do not have prior exposure to biologics (biologic-naïve) or (ii) have failed or been intolerant to 1 TNF-inhibitor (TNFi-experienced).
Exclusion Criteria
  1. Non-plaque psoriasis (ie, guttate, inverse, pustular, erythrodermic or drug-induced psoriasis), with the exception of nail psoriasis, which is allowed.
  2. Other autoimmune or autoinflammatory condition ( ie, rheumatoid arthritis, systemic lupus erythematous, gout), with the exception of inflammatory bowel disease and/or autoimmune uveitis being inactive at least 12 months before the screening, as assessed by the investigator.
  3. Active fibromyalgia syndrome
  4. Recent history of active infection, chronic infection history or risk of serious infection.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
HS-10374 Dose 1HS-10374-
PlaceboHS-10374-matched placebo tablets-
tofacitinibTofacitinib 5Mg Tab,Oral-
HS-10374 Dose 2HS-10374-
Primary Outcome Measures
NameTimeMethod
Proportion of participants meeting American College of Rheumatology improvement of 20% (ACR20) response at Week 16At week 16

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).

Secondary Outcome Measures
NameTimeMethod
Change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) score at week 16At week 16

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.

Proportion of participants meeting Psoriasis Area and Severity Index (PASI) 75/90 responses at week 16At week 16

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.

Proportion of participants meeting Static physician's global assessment (sPGA) 0/1 score at week 16At week 16

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.

Change from baseline in the dermatology life quality index (DLQI) scores at week 16At week 16

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).

Proportion of participants meeting American College of Rheumatology improvement of 20% (ACR20) response at Week 12At week 12

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).

Proportion of participants meeting American College of Rheumatology improvement of 50% (ACR50) response at Week 16At week 16

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).

Incidence of adverse events (AEs), serious adverse events (SAEs)Baseline to Week 20
Change from baseline in the Disease Activity Index for Psoriatic Arthritis Score (DAPSA) at week 16At week 16

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.

Proportion of participants meeting Minimal Disease Activity (MDA) response at week 16At week 16

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

Change from baseline in dactylitis by Leed's dactylitis index (LDI) at week 16At week 16

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.

Ctrough of HS-10374Baseline to Week 16

Trough observed plasma concentration of HS-10374

Proportion of participants meeting American College of Rheumatology improvement of 70% (ACR70) response at Week 16At week 16

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).

Change from baseline in Psoriasis body surface area (BSA) at week 16At week 16

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.

Change from baseline in Disease Activity Score 28 with C-reactive protein (DAS28-CRP) score at week 16At week 16

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.

Change from baseline in Psoriatic Arthritis Disease Activity Score (PASDAS) at week 16At week 16

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.

Change from baseline in enthesitis by Leed's enthesitis index (LEI) at week 16At week 16

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.

Proportion of participants achieving Psoriatic Arthritis Response Criteria (PsARC) at week 16At week 16

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.

Change from baseline in the Short Form-36 Survey (SF-36) score at week 16At week 16

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.

Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score among participants with spondylitis as one of their presentations of PsA at week 16At week 16

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.

Trial Locations

Locations (1)

Huashan Hospital affiliated to Fudan University

🇨🇳

Shanghai, Shanghai, China

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