A Study to Evaluate the Efficacy and Safety of CS32582 in Participants With Moderate to Severe Plaque Psoriasis

Official title

A Multi-center, Randomized, Double-blind, Placebo-controlled Phase Ib/II Study to Evaluate the Efficacy and Safety of CS32582 Capsule in Adult Patients With Moderate to Severe Plaque Psoriasis

Overview

" This study consists of two parts: Part 1 (Dose Escalation): A randomized, double-blind, placebo-controlled phase in which approximately 20 to 30 adult patients with plaque psoriasis will receive the investigational treatment for 4 weeks. Part 2 (Efficacy and Safety Assessment): A randomized, double-blind, placebo-controlled evaluation where approximately 200 adult patients with plaque psoriasis will undergo 12 weeks of treatment. The resulting data will provide preliminary evidence on the safety and efficacy profile of CS32582, informing its subsequent development strategy.

Interventions

• Drug CS32582 capsule（low dose） or matched placebo
  CS32582 capsule（low dose） or matched placebo，4 weeks
• Drug CS32582 capsule（high dose） or matched placebo
  CS32582 capsule（high dose） or matched placebo，4 weeks
• Drug CS32582 capsule（low dose）
  CS32582 capsule（low dose），12 weeks
• Drug CS32582 capsule（medium dose）
  CS32582 capsule（medium dose），12 weeks
• Drug CS32582 capsule（high dose）
  CS32582 capsule（high dose），12 weeks

Primary outcome measures

• Part 1：Incidence and Severity of Adverse Events (AEs) [Time frame: 5 weeks]
• Part 2：Proportion of patients achieved Psoriasis Area Severity Index (PASI) 75 at Week 12 [Time frame: Week 12]

Secondary outcome measures (12)

• Part 1： Changes from baseline in PASI [Time frame: Week 4]
• Part 1： Changes from baseline in sPGA [Time frame: Week 4]
• Part 1： Changes from baseline in BSA [Time frame: Week 4]
• Part 1： Changes from baseline in DLQI [Time frame: Week 4]
• Part 1：Proportion of patients achieving PASI 50/75/90/100 [Time frame: Week 4]
• Part 2：Incidence and Severity of Adverse Events (AEs) [Time frame: 16 weeks]
• Part 2：Proportion of patients achieving PASI 75 [Time frame: Week 4 and 8]
• Part 2：Proportion of patients achieving PASI 50/90/100 [Time frame: Week 4，8 and 12]
• Part 2：Proportion of patients achieving: (a) sPGA score of 0 or 1 with ≥2-point reduction from baseline (b) sPGA clearance (score 0) (c) Disease remission [Time frame: Week 4，8 and 12]
• Part 2： Changes from baseline in PASI [Time frame: Week 4，8 and 12]
• Part 2： Changes from baseline in BSA [Time frame: Week 4，8 and 12]
• Part 2： Changes from baseline in sPGA [Time frame: Week 4，8 and 12]

Eligibility criteria

Inclusion criteria

• Voluntarily sign the informed consent form (ICF) after fully understanding the trial.
• Age 18-70 years (inclusive) at consent, any gender
• Clinically diagnosed with chronic plaque psoriasis, defined as disease duration ≥ 6 months at screening.
• Stable plaque psoriasis at screening, defined as no significant flare-ups or morphological changes during the 6 months prior to screening (investigator-assessed).
• Moderate-to-severe disease at screening/randomization: PASI≥12, sPGA≥3, and BSA≥10%;
• Candidate for phototherapy or systemic therapy per investigator's judgment.
• Women of childbearing potential and males: Agreement to use highly effective contraception from consent until 30 days post-last dose.

Exclusion criteria

• Forms of psoriasis other than plaque-type (e.g., erythrodermic, pustular, guttate, or drug-induced psoriasis) .
• Presence of other skin conditions that in the judgement of the Investigator could interfere with study assessment.
• Immune-mediated diseases requiring systemic therapy (e.g., inflammatory bowel disease), except NSAIDs.
• History of severe drug allergies.
• Major surgery within 2 months before randomization or planned during the study.
• Drug/alcohol abuse within 6 months before screening.
• Uncontrolled hypertension at screening (SBP >160 mmHg or DBP >100 mmHg).
• Myocardial infarction, unstable angina, TIA, stroke, PCI, or CABG within 6 months before screening.
• NYHA Class III/IV heart failure at screening.
• History of malignancy or lymphoproliferative disorders within 5 years (exceptions: basal cell carcinoma, localized squamous cell carcinoma, or cervical carcinoma in situ cured ≥1 year).
• Prosthetic joint infection (unless prosthesis removed/replaced ≥2 months before randomization).
• History of opportunistic infections (e.g., PJP, histoplasmosis, coccidioidomycosis).
• Active/latent TB infection (positive IGRA without clinical manifestations).
• Herpes infection:a) Active herpes zoster/simplex (HSV-1/2) at screening;b) History of severe herpes (disseminated disease, multidermatomal HSV, encephalitis, ophthalmic herpes, or recurrent zoster \[≥2 episodes in 2 years\]).
• History of severe bacterial, fungal, or viral infection requiring hospitalization for IV antibiotic or antiviral administration within 2 months before randomization.
• History of live vaccine administration within 2 months before randomization or plans to receive a live vaccine during the study period.
• Evidence of active infection and/or febrile illness requiring systemic anti-infective therapy within 2 weeks before randomization.
• Abnormal virology at screening:

• HBsAg(+) or HBcAb(+) with detectable HBV-DNA
• HCV Ab(+) with detectable HCV-RNA
• History of HIV infection or HIV Ab(+)
• Treponema pallidum Ab(+) with positive RPR/TRUST
• Prior use of TYK2 inhibitors (e.g., deucravacitinib).
• Use of any of the following therapeutic agents within 6 months before randomization:

• IL-12/23, IL-17, or IL-23 inhibitors (ustekinumab, secukinumab, tildrakizumab, ixekizumab, guselkumab)
• Rituximab or other B-cell depleting agents
• Leflunomide
• Use of any of the following therapeutic agents within 3 months before randomization: Integrin pathway modulators (natalizumab) or B/T-cell modulators (alemtuzumab, abatacept, vedolizumab).
• Use of TNF inhibitors (etanercept, adalimumab, infliximab, certolizumab) within 2 months before randomization.
• Any biologic psoriasis therapy within 3 months or 5 half-lives (whichever longer) before randomization.
• Use of systemic non-biologic psoriasis agents and/or any systemic immunosuppressants within 4 weeks before randomization, including but not limited to: apremilast, methotrexate, azathioprine, cyclosporine, JAK inhibitors, 6-thioguanine, mercaptopurine, mycophenolate, hydroxyurea, tacrolimus, oral/injectable corticosteroids, retinoids, calcitriol/analogs, psoralen, sulfasalazine, fumarates).
• Use of Lithium, antimalarials, or intramuscular gold preparations within 4 weeks before randomization.
• Use of any botanical agents for the treatment of psoriasis or other immune disorders within 4 weeks before randomization, including herbal supplements or traditional Chinese medicines derived from plants, minerals, or animals.
• Received phototherapy within 4 weeks before randomization.
• Use of medicated shampoos and/or body washes within 2 weeks before randomization, including but not limited to products containing: corticosteroids, coal tar, >3% salicylic acid, vitamin D3 analogs.
• Use of any topical agents that may affect psoriasis symptoms within 2 weeks before randomization.
• Received any investigational therapy within 30 days or 5 half-lives (whichever is longer) before randomization, OR current participation in other trial.
• Laboratory values meeting any of the following criteria during screening or before randomization:

• Liver: ALT/AST ≥3×ULN; total bilirubin >2×ULN
• Hematology: WBC <3.0×10⁹/L (3000/mm³); ANC <1.0×10⁹/L (1000/mm³); lymphocyte count <0.5×10⁹/L (500/mm³); platelets <100×10⁹/L (100,000/mm³); hemoglobin <9.0 g/dL (90 g/L)
• Renal: eGFR <60 mL/min/1.73m² (CKD-EPI equation)
• Pregnant or lactating women.
• Any condition deemed unsuitable by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 11 centers

• Beijing Friendship Hospital, Capital Medical University — Beijing
• Peking University People's Hospital — Beijing
• Affiliated Hospital of Chengde Medical University — Chengde
• The First Hospital of Hebei Medical University — Shijiazhuang
• Shiyan People's Hospital — Shiyan
• Shandong Provincial Hospital for Skin Diseases — Jinan
• First Hospital of Shanxi Medical University — Taiyuan
• The Second Affiliated Hospital of Xi'an Jiaotong University(Xibei Hospital ) — Xi’an
• … and 3 more centers

Identifiers

NCT: NCT07129382 · CS32582-201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗