Celldex Reports 80% Complete Response Rate in Interim Data Update from Phase 1b study of CDX-0159 in Chronic Inducible Urticaria
--CDX-0159 generally well tolerated to date--
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“CDX-0159 is having a profound, beneficial impact for patients in this study, all of whom entered with significant disease which was refractory to antihistamines,” said
Fifteen out of 20 planned patients with antihistamine refractory CIndU have received a single intravenous infusion of CDX-0159 at 3 mg/kg, including nine patients with cold contact urticaria (ColdU) and six patients with symptomatic dermographism (SD). Safety results are reported for all 15 patients; activity results are reported for all patients assessed for at least 15 days/2 weeks after treatment (n=10; 7 ColdU and 3 SD). Patients had high disease activity as assessed by provocation threshold testing. In ColdU and SD pts, baseline critical temperature thresholds were 18.7 +/- 2.7 °C (range: 5-27°C) and FricTest® thresholds were 3.7 +/- 0.3 (range: 3-4) of 4.
- Eight of 10 patients (7 ColdU; 1 SD) experienced a complete response (CR) as assessed by provocation threshold testing through their latest assessment. The remaining two patients (both with SD) were recently treated and have been followed for two weeks. One patient experienced a partial response (PR) thus far, and one patient has reported symptomatic improvement (decreased itching). All patients will continue to be assessed for response through week 12.
- Patient global assessment (Pat-GA) and physician global assessment (Phy-GA) results are consistent with provocation testing results.
- Measurements of serum tryptase levels are available for only the first six patients evaluated for activity, all with ColdU. The mean baseline was 3.3 +/- 0.2 ng/ml and levels on day 15 after treatment were at or below the limit of detection. These patients all experienced complete responses.
- CDX-0159 was generally well tolerated. Six of 15 patients had mild infusion reactions, generally areas of localized redness and itching, which resolved rapidly. A single severe infusion reaction was observed (brief loss of consciousness, followed by shaking and sweating). The patient was treated with antihistamines and steroids; no epinephrine was administered. The patient rapidly recovered and was hospitalized for observation with no further manifestations of this event. Importantly, there was no evidence of mast cell activation as measured by decreases in serum tryptase levels shortly after the infusion and further at a later time point.
- Through day 15, three patients had transient, mild decreases in hemoglobin, and no patients had meaningful declines in white blood cells.
“The interim results reported today further reinforce our enthusiasm for CDX-0159,” said
CIndUs are forms of urticaria that have an attributable cause or trigger associated with them, typically resulting in wheals (hives) or angioedema. Approximately 0.5% of the total population suffers from CIndUs. Celldex is exploring the three most common forms of CIndU, cold-induced, dermographism (scratch-induced) and cholinergic (exercise/sweat-induced). People afflicted with ColdU experience symptoms like itching, burning wheals and angioedema when their skin is exposed to temperatures below skin temperature. Symptomatic dermographism is characterized by the development of a wheal and flare reaction in response to stroking, scratching or rubbing of the skin and usually occurs within minutes of the inciting stimulus. Cholinergic urticaria is triggered by the body’s sweating response to active or passive body warming, and is characterized by small (1–4 mm) wheals surrounded by bright red flares. Common triggers include exercise, hot baths/showers, fever, occlusive dressings, eating spicy foods and emotional stress. For these diseases, mast cell activation leading to release of soluble mediators is thought to be the driving mechanism leading to the wheals and other symptoms. There are currently no approved therapies for CIndUs other than antihistamines and patients attempt to manage symptoms associated with their disease through avoidance of triggers. Celldex believes that CDX-0159 has significant potential to directly ablate and/or inhibit mast cells and this, in turn, could benefit patients with CIndU or other mast cell-driven diseases.
Phase 1b CIndU Study Design
The Phase 1b study (NCT04548869) is an open label clinical trial designed to evaluate the safety of a single dose of CDX-0159 in up to 20 patients with cold contact urticaria (n=10) or symptomatic dermographism (n=10) who are refractory to antihistamines. The study has been amended to also add a cohort of 10 patients with cholinergic urticaria. Patients' symptoms are induced via provocation testing that resembles real life triggering situations. Secondary and exploratory objectives include pharmacokinetic and pharmacodynamic assessments, including changes from baseline provocation thresholds, measurement of tryptase and stem cell factor levels, clinical activity outcomes (impact on urticaria symptoms, disease control, clinical response), quality of life assessments and measurement of tissue mast cells through skin biopsies. CDX-0159 is administered intravenously (3.0 mg/kg) as add on treatment to H1-antihistamines and patients are followed for 12 weeks after dosing.
Webcast and Conference Call
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CDX-0159 is a humanized monoclonal antibody developed by Celldex that binds the KIT receptor with high specificity and potently inhibits its activity. The KIT receptor tyrosine kinase is expressed in a variety of cells, including mast cells, which mediate inflammatory responses such as hypersensitivity and allergic reactions. KIT signaling controls the differentiation, tissue recruitment, survival and activity of mast cells. In a Phase 1a single dose, healthy volunteer study, CDX-0159 demonstrated a favorable safety profile as well as profound and durable reductions of plasma tryptase, indicative of systemic mast cell ablation or suppression. Based on these data, Celldex has initiated two Phase 1b studies in the mast cell-driven disease chronic spontaneous urticaria (CSU) and the three most common forms of chronic inducible urticaria (CIndU)—cold contact urticaria, symptomatic dermographism and cholinergic urticaria. The Company is also planning a third study in prurigo nodularis (PN), where mast cells through their interactions with sensory neurons and other immune cells are believed to play an important role in amplifying chronic itch and neurogenic inflammation.
Celldex is a clinical stage biotechnology company dedicated to developing monoclonal and bispecific antibodies that address devastating diseases for which available treatments are inadequate. Our pipeline includes antibody-based therapeutics which have the ability to engage the human immune system and/or directly affect critical pathways to improve the lives of patients with inflammatory diseases and many forms of cancer. Visit www.celldex.com.
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Source: Celldex Therapeutics, Inc.