Celldex Begins Phase 2 Barzolvolimab Trial for Prurigo Nodularis

May 15, 2024 - Celldex Therapeutics, Inc. (NASDAQ:CLDX) has commenced the Phase 2 subcutaneous trial of barzolvolimab for treating prurigo nodularis (PN), marking the first patient being dosed. Barzolvolimab is a humanized monoclonal antibody targeting the receptor tyrosine kinase KIT with high specificity, significantly inhibiting its activity, essential for the function and survival of mast cells. These cells are implicated in chronic itch and neuroinflammation, particularly in PN where they are linked with pruritic sensory neurons in PN lesions.

Celldex had previously presented pioneering data from their Phase 1b study in November 2023, showcasing the potential of barzolvolimab and its unique mast cell-depleting mechanism in disrupting the persistent scratch/itch cycle characteristic of PN, leading to lesion healing.

Diane C. Young, M.D., Senior Vice President and Chief Medical Officer of Celldex Therapeutics, expressed optimism about the new study. "Prurigo nodularis is a distressing condition requiring treatments that provide rapid and lasting relief from relentless itching and promote lesion healing," she stated. "Our Phase 1b study demonstrated remarkable clinical results with just one dose of barzolvolimab. We are eager to explore the outcomes with multiple doses in this crucial Phase 2 study."

The Phase 2 study is a randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of two dose levels of barzolvolimab compared to a placebo in around 120 patients with moderate to severe PN who have not responded adequately to prescription topical medications or for whom these medications are medically inadvisable. Participants, some of whom have received prior biologics, will be randomized in a 1:1:1 ratio to receive barzolvolimab injections of either 150 mg every four weeks following an initial 450 mg dose, 300 mg every four weeks following an initial 450 mg dose, or a placebo over a 24-week treatment phase. This will be followed by a 16-week follow-up phase without study treatment.

The primary goal of the study is to evaluate the clinical effect of barzolvolimab on itch response, measured by the proportion of participants achieving a ≥ 4-point improvement in the worst intensity itch on a numeric rating scale. Secondary objectives include assessing additional measures of itch response at different timepoints compared to baseline, evaluating skin lesions with the Investigator Global Assessment (IGA), quality of life outcomes, and safety. The study will be conducted across approximately 50 clinical trial centers globally, including in the United States.

Prurigo nodularis (PN) is a chronic skin condition characterized by hard, intensely itchy nodules on the skin. The severe itching leads to scratching that can cause bleeding or pain, forming lesions that perpetuate the disease cycle. With limited treatment options, PN significantly impacts quality of life, causing sleep disturbances, psychological distress, social isolation, anxiety, and depression. Mast cells play a crucial role in chronic itch and neuroinflammation in PN, being associated with pruritic sensory neurons in PN lesions.

Barzolvolimab, a humanized monoclonal antibody, targets the receptor tyrosine kinase KIT with high specificity, potently inhibiting its activity. KIT is expressed in various cells, including mast cells, which mediate inflammatory responses like hypersensitivity and allergic reactions. KIT signaling governs the differentiation, tissue recruitment, survival, and activity of mast cells. Mast cell activation is central to the onset and progression of certain inflammatory diseases, such as chronic urticaria. Barzolvolimab is currently under investigation for chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU), prurigo nodularis (PN), and eosinophilic esophagitis (EOE), with plans to explore additional indications, including atopic dermatitis (AD).

Celldex Therapeutics, Inc. is a clinical-stage biotechnology company pioneering advances at the intersection of mast cell biology and the development of transformative therapeutics for patients. Their pipeline includes antibody-based treatments designed to engage the human immune system and address critical pathways to improve the lives of individuals suffering from severe inflammatory, allergic, autoimmune, and other debilitating conditions.

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