Vunakizumab for the Treatment of Mild to Moderate Systemic Lupus Erythematosus

Официальное название

Pilot Study on the Treatment of Vunakizumab in Mild to Moderate Systemic Lupus Erythematosus

Обзор

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by heterogeneous clinical manifestations ranging from mild cutaneous involvement to severe multi-organ damage. While its pathogenesis involves complex cytokine dysregulation, emerging evidence implicates IL-17 as a potential contributor. Elevated serum IL-17 levels have been observed in SLE patients compared to healthy controls, with heightened expression detected in renal and cutaneous lesions. Ustekinumab, a monoclonal antibody targeting IL-23/IL-12 that indirectly modulates IL-17 signaling, demonstrated superior efficacy and safety to placebo in an SLE clinical trial, particularly in glucocorticoid dose reduction. Notably, no clinical trials have directly evaluated IL-17-targeted therapies for SLE, though case reports suggest secukinumab (an anti-IL-17A agent) may improve cutaneous manifestations in psoriasis-SLE overlap patients. Vunakizumab, a humanized anti-IL-17A monoclonal antibody (IgG1/κ) with a unique epitope-binding profile, selectively inhibits IL-17A-mediated inflammatory signaling. Its established safety profile and infrequent dosing regimen in IL-17-mediated diseases (e.g., psoriasis, psoriatic arthritis) warrant investigation in SLE. The investigators aim to provide new treatment options for SLE patients

Вмешательства

• Препарат Vunakizumab (IL-17A inhibitor)
  Vunakizumab combined with glucocorticoid therapy: Vunakizumab is administered subcutaneously at 240 mg at weeks 0, 2, and 4, followed by maintenance dosing every 4 weeks at 240 mg per dose.

Первичные конечные точки

• the percentage of patients achieving an BICLA response at the end of 24 weeks [Срок оценки: From enrollment to the end of treatment at 24 weeks]

Вторичные конечные точки (7)

• the percentage of patients achieving an BICLA response at the end of 12 weeks [Срок оценки: From enrollment to the end of treatment at 12 weeks]
• the percentage of patients achieving SRI-4 response at the end of 24 weeks. [Срок оценки: From enrollment to the end of treatment at 24 weeks]
• the percentage of patients achieving SRI-4 response at the end of 12 weeks. [Срок оценки: From enrollment to the end of treatment at 12 weeks]
• Changes from baseline in SLEDAI at 24 weeks [Срок оценки: From enrollment to the end of treatment at 24 weeks]
• Changes from baseline in CLASI at 24 weeks. [Срок оценки: From enrollment to the end of treatment at 24 weeks]
• Changes from baseline in PGA at 24 weeks [Срок оценки: From enrollment to the end of treatment at 24 weeks]
• Changes from baseline of the SJC and TJC at 24 weeks [Срок оценки: From enrollment to the end of treatment at 24 weeks]

Критерии участия

Критерии включения

• Patients aged 18-65 years meeting the 2019 EULAR/ACR classification criteria for SLE.
• SLEDAI score was within 2-12 scores (with clinical SLEDAI \[cSLEDAI\] ≠ 0).
• Occurence of new or recurrent mucocutaneous or joint involvement.
• Stable standard treatment regimen prior to study entry but not effect: Prednisone or equivalent corticosteroid dose ≤ 20 mg per day for more than 4 weeks; Immunosuppressant less than 1 type for more than 12 weeks, including methotrexate ≤15 mg per week, azathioprine ≤100mg per day, mycophenolate mofetil ≤1.5 g per day, tacrolimus ≤2 mg per day, cyclosporine ≤150 mg per day). Antimalarials was permitted.
• Body mass index (BMI) 18-35 kg/m² at screening.
• Clinically eligible for Vunakizumab combination therapy with corticosteroids after investigator assessment.
• Willing to provide written informed consent with demonstrated compliance.

Критерии исключения

• SLE with major organ dysfunction including Encephalopathy/cognitive impairment, Renal insufficiency, Cardiac insufficiency (NYHA class III-IV), Pulmonary hypertension/interstitial lung disease
• Active SLE-related organ involvement: Lupus cerebritis, Active lupus nephritis (proteinuria ≥1g/24h), Myocardial involvement, Gastrointestinal vasculitis, Diffuse alveolar hemorrhage, Thrombocytopenic purpura, Hemophagocytic syndrome, Retinopathy
• Concurrent autoimmune diseases affecting efficacy assessment (e.g., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis).
• Liver dysfunction: ALT/AST >1.5×ULN or total bilirubin >1×ULN.
• Active malignancy within 5 years or history of malignancy.
• Comorbidities requiring corticosteroids (e.g., asthma, Crohn's disease).
• Active infections requiring treatment:Tuberculosis, HBV/HCV/HIV/CMV infections
• Major surgery within 3 months prior to screening.
• Hypersensitivity or intolerance to funakizumab.
• Pregnancy, lactation, or planned pregnancy.
• Biologic therapy within 3 months (anti-CD20 agents, belimumab, TNF-α inhibitors).
• Recent intensive therapies: Systemic corticosteroids within 3 months/ Plasmapheresis/IVIG/cyclophosphamide within 3 months
• Any condition deemed by investigators to compromise study completion or patient safety.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Peking Union Medical College Hospital — Пекин

Идентификаторы

NCT: NCT06881290 · CSTAR011

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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