Phase 2b Trial Shows Vixarelimab Improves Itch and Lesions in Prurigo Nodularis

A phase 2b clinical trial of vixarelimab to treat patients with prurigo nodularis (PN) demonstrated rapid and sustained clinical benefits and a favorable safety profile, according to a new study published in JAMA Dermatology.¹

PN is a chronic, immune-mediated, inflammatory skin disorder that causes cycles of itching and scratching, leading to inflammation and dermal fibrosis. The prevalence of PN in the last decade has ranged from 36.7 to 148.3 per 100,000 people; however, experts say that many adults with PN are often misdiagnosed and labeled psychogenic, waiting years for a proper diagnosis, which presents as fear of their symptoms being related to cancer.² PN significantly impacts patients' quality of life, including sleep, work, and social functioning, further exacerbating mental health comorbidities such as anxiety and depression.¹ Prior research and FDA approvals have supported monoclonal antibody medications to treat adults with PN; however, there is still an unmet need for therapies providing adequate symptom relief and disease regression in patients with PN.

This phase 2c clinical trial (NCT03816891) assessed the percentage change from baseline in the Worst Itch Numeric Rating Scale (WI-NRS), the percentage of patients achieving at least a 4-point reduction in WI-NRS, and those achieving a score of 0 or 1 in the PN investigator global assessment (PN-IGA), all at 16 weeks. The study was conducted from December 2020 to August 2023 and broken up into a 4-week screening period, a 16-week double-blind period, followed by a 36-week open-label extension (OLE) period.

Participants were required to be between 18 and 80 years of age, with a physician-documented diagnosis of PN of at least 6 months' duration and experiencing moderate to severe pruritus at screening. Severe pruritus was classified as a 7 out of 10 or higher on the WI-NRS scale.

There were 190 participants accepted into the study of the 443 screened. Patients were randomized 1:1:1:1 to receive vixarelimab 540 mg, 360 mg, 120 mg, or a placebo. Of them, 141 were randomized to one of the vixarelimab arms and 49 to the placebo. Only 96.5% of patients in the vixarelimab arms and 95.9% in the placebo arm completed the treatments. Once the treatment was completed, 181 patients consented to complete the OLE treatment, of whom 86.7% finished.

Out of the 190 participants, 114 were female, and the mean age was 55.4 years. Additionally, 2.1% of patients were American Indian or Alaska Native, 18% were Asian, 11.6% were Black or African American, 64% were White, and 4.2% were multiracial or had another race. Participants had been living with PN nodules for a mean of 11 years and had been diagnosed with PN for a mean of 6.2 years.

Vixarelimab demonstrated a significant reduction in disease progression and relief of symptoms from baseline to 16 weeks when compared with the placebo at all doses (placebo, −14.5% [4.76]; high-dose vixarelimab, −56.2% [4.84]; P < .001; mid-dose vixarelimab, −51.0% [4.83]; P < .001; low-dose vixarelimab, −33.0% [4.86]; P = .006).

There were significantly more patients who received vixarelimab and achieved a 6-point or greater reduction from baseline in WI-NRS at 16 weeks when compared with the placebo and achieved a clear or almost clear score in the PN-IGA score.

Regarding safety, treatment-emergent adverse events (TEAEs) were more prevalent in patients randomized to the vixarelimab arms when compared with the placebo (placebo, 26 [54.2%]; high-dose vixarelimab, 35 [74.5%]; mid-dose vixarelimab, 29 [61.7%]; low-dose vixarelimab, 21 [44.7%]). The most common TEAEs in the vixarelimab arms were headache, eczema, and fatigue; in the placebo group, the most common TEAEs were COVID-19, insomnia, and hypertension.

This study was limited by the 16-week double-blind period when compared with the 36-week OLE period that was not placebo-controlled. Patients experience further improvement in the WI-NRS period when compared with the 16-week double-blind period; however, potential bias could not be ruled out.

“These results demonstrate a clear improvement in pruritus symptoms and lesion burden in participants who received vixarelimab versus placebo,” the study authors concluded.

References

1. Ständer S, Yosipovitch G, Sofen H, et al. Vixarelimab in patients with prurigo nodularis: a randomized clinical trial. JAMA Dermatol. Published online December 17, 2025. doi:10.1001/jamadermatol.2025.495

2. Silverberg J. The impact of atopic dermatitis and prurigo nodularis. AJMC®. August 3, 2024. Accessed December 18, 2025. https://www.ajmc.com/view/the-impact-of-atopic-dermatitis-and-prurigo-nodularis