Celldex Therapeutics, Inc. announced positive topline results from the Company?s Phase 2 clinical trial of barzolvolimab in patients with moderate to severe chronic spontaneous urticaria (CSU) refractory to antihistamines, including patients who received prior biologics. Barzolvolimab is a humanized monoclonal antibody that specifically binds the receptor tyrosine kinase KIT with high specificity and potently inhibits its activity, which is required for mast cell function and survival. CSU is characterized by the occurrence of hives or wheals for 6 weeks or longer without identifiable specific triggers or causes.

Treatment options for patients with CSU are limited and there are no approved therapies for patients who do not respond to omalizumab. Data from the 208 patients randomized in the study showed that barzolvolimab achieved the primary efficacy endpoint, with a statistically significant mean change from baseline to week 12 of UAS7 (urticaria activity score) compared to placebo. Barzolvolimab demonstrated rapid, durable and clinically meaningful responses in patients with moderate to severe CSU refractory to antihistamines, including patients with prior omalizumab treatment.

Demographics and baseline disease characteristics were well balanced across treatment groups. Approximately 20% of enrolled patients received prior treatment with omalizumab. These patients experienced a similar clinical benefit as the overall treated population within their individual dosing groups.

Barzolvolimab was generally well tolerated with a favorable safety profile. Most adverse events were mild to moderate in severity; through 12 weeks, the most common treatment emergent adverse events in barzolvolimab treated patients were hair color changes (9%), urticaria (9%) and neutropenia (8%). The rate of infections was similar between barzolvolimab-treated patients and placebo with no apparent association between neutropenia and infections.

Phase 2 Study Design The randomized, double-blind, placebo-controlled, parallel group Phase 2 study is evaluating the efficacy and safety profile of multiple dose regimens of barzolvolimab in patients with CSU who remain symptomatic despite antihistamine therapy, to determine the optimal dosing strategy. 208 patients were randomly assigned on a 1:1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 75 mg every 4 weeks, 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a 16-week placebo-controlled treatment period. After 16 weeks, patients then enter a 36-week active treatment period, in which patients not already randomized to barzolvolimab at 150 mg every 4 weeks or 300 mg every 8 weeks are randomized 1:1 to receive one of these two dose regimens; patients already randomized to these treatment arms remain on the same regimen as during the placebo-controlled treatment period.

After 52 weeks, patients then enter a follow-up period for an additional 24 weeks. The primary endpoint of the study is mean change in baseline to Week 12 in UAS7. Secondary endpoints include other assessments of safety and clinical activity including ISS7, HSS7 and AAS7.