Vunakizumab for the Treatment of Mild to Moderate Systemic Lupus Erythematosus

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

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

Study Overview

• Status: Recruiting
• Conditions: Lupus Erythematosus, Systemic
• Intervention / Treatment: Drug: Vunakizumab (IL-17A inhibitor)

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Mengtao Li, Doctor; Phone Number: China 6915-9958; Email: mengtao.li@cstar.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients aged 18-65 years meeting the 2019 EULAR/ACR classification criteria for SLE.
2. SLEDAI score was within 2-12 scores (with clinical SLEDAI [cSLEDAI] ≠ 0).
3. Occurence of new or recurrent mucocutaneous or joint involvement.
4. 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.
5. Body mass index (BMI) 18-35 kg/m² at screening.
6. Clinically eligible for Vunakizumab combination therapy with corticosteroids after investigator assessment.
7. Willing to provide written informed consent with demonstrated compliance.

Exclusion Criteria:

1. SLE with major organ dysfunction including Encephalopathy/cognitive impairment, Renal insufficiency, Cardiac insufficiency (NYHA class III-IV), Pulmonary hypertension/interstitial lung disease
2. 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
3. Concurrent autoimmune diseases affecting efficacy assessment (e.g., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis).
4. Liver dysfunction: ALT/AST >1.5×ULN or total bilirubin >1×ULN.
5. Active malignancy within 5 years or history of malignancy.
6. Comorbidities requiring corticosteroids (e.g., asthma, Crohn's disease).
7. Active infections requiring treatment:Tuberculosis, HBV/HCV/HIV/CMV infections
8. Major surgery within 3 months prior to screening.
9. Hypersensitivity or intolerance to funakizumab.
10. Pregnancy, lactation, or planned pregnancy.
11. Biologic therapy within 3 months (anti-CD20 agents, belimumab, TNF-α inhibitors).
12. Recent intensive therapies: Systemic corticosteroids within 3 months/ Plasmapheresis/IVIG/cyclophosphamide within 3 months
13. Any condition deemed by investigators to compromise study completion or patient safety.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vunakizumab	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the percentage of patients achieving an BICLA response at the end of 24 weeks	The BICLA response was defined as a reduction of all severe (BILAG-2004 A) or moderately severe (BILAG-2004 B) disease activity at baseline to lower levels (BILAG-2004 B, C, or D and C or D, respectively) and no worsening in other organ systems (with worsening defined as ≥1 new BILAG-2004 A item or ≥2 new BILAG-2004 B items); no worsening in disease activity, as determined by the SLEDAI-2K score (no increase from baseline) and by the PGA score (no increase of ≥0.3 points from baseline)	From enrollment to the end of treatment at 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the percentage of patients achieving an BICLA response at the end of 12 weeks	The BICLA response was defined as a reduction of all severe (BILAG-2004 A) or moderately severe (BILAG-2004 B) disease activity at baseline to lower levels (BILAG-2004 B, C, or D and C or D, respectively) and no worsening in other organ systems (with worsening defined as ≥1 new BILAG-2004 A item or ≥2 new BILAG-2004 B items); no worsening in disease activity, as determined by the SLEDAI-2K score (no increase from baseline) and by the PGA score (no increase of ≥0.3 points from baseline)	From enrollment to the end of treatment at 12 weeks
the percentage of patients achieving SRI-4 response at the end of 24 weeks.	The SRI-4 (SLE Responder Index-4) response was defined as a reduction of at least 4 points in SLEDAI score compared with the baseline level, no new British Isles Lupus Assessment Group (BILAG) A organ domain score or no more than one new BILAG B organ domain score, and no worsening in the Physician's Global Assessment (PGA) (<0.3 points worsening from the baseline level).	From enrollment to the end of treatment at 24 weeks
the percentage of patients achieving SRI-4 response at the end of 12 weeks.	The SRI-4（SLE Responder Index-4） response was defined as a reduction of at least 4 points in SLEDAI score compared with the baseline level, no new British Isles Lupus Assessment Group (BILAG) A organ domain score or no more than one new BILAG B organ domain score, and no worsening in the Physician's Global Assessment (PGA) (<0.3 points worsening from the baseline level).	From enrollment to the end of treatment at 12 weeks
Changes from baseline in SLEDAI at 24 weeks	SLEDAI stands for Systemic Lupus Erythematosus Disease Activity Index, with a score of 0-6 representing mild disease activity, 7-12 representing moderate disease activity, and 12-16 representing severe disease activity	From enrollment to the end of treatment at 24 weeks
Changes from baseline in CLASI at 24 weeks.	CLASI stands for Cutaneous Lupus Erythematosus Disease Area and Severity Index. It is a measure of the severity of skin disease, with scores ranging from 0 to 70, with higher scores indicating more severe disease activity	From enrollment to the end of treatment at 24 weeks
Changes from baseline in PGA at 24 weeks	PGA stands for Physician's Global Assessment (PGA ) . It is used to assess the activity of systemic lupus erythematosus on a scale ranging from 0 to 3, where 0 indicates no disease activity and 3 indicates the most severe disease activity.	From enrollment to the end of treatment at 24 weeks
Changes from baseline of the SJC and TJC at 24 weeks	Swollen Joint Count(SJC) and Tender Joint Count(TJC) indicate the number of swollen and tender joints in 28 joints, respectively. 28 joints refer to both shoulders, both elbows, both wrists, both knees, 10 metacarpophalangeal joints, and 10 proximal interphalangeal joints, which ranging from 0 to 28, the higher value means more serious disease activity.	From enrollment to the end of treatment at 24 weeks

Collaborators and Investigators

• Sponsor: Chinese SLE Treatment And Research Group

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2025
• Primary Completion (Estimated): November 20, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: March 10, 2025
• First Submitted That Met QC Criteria: March 11, 2025
• First Posted (Actual): March 18, 2025

Study Record Updates

• Last Update Posted (Actual): July 10, 2025
• Last Update Submitted That Met QC Criteria: July 7, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Systemic lupus erythematosus; Vunakizumab
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: CSTAR011

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No