Barzolvolimab for Hives

(EMBARQ-CSU1 Trial)

Recruiting in Palo Alto (17 mi)

+69 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Celldex Therapeutics

Must be taking: H1-antihistamines

Disqualifiers: Pregnancy, Chronic inducible urticaria, HIV, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study is to establish the efficacy, safety and tolerability of barzolvolimab in adult participants with Chronic Spontaneous Urticaria (CSU) inadequately controlled by non-sedating second generation H1-antihistamines in comparison to placebo.

Will I have to stop taking my current medications?

The trial requires that you continue taking a stable regimen of second generation non-sedating H1-antihistamines for at least 4 weeks before starting the study treatment.

What data supports the effectiveness of the drug Barzolvolimab for treating hives?

Research shows that Barzolvolimab, an anti-KIT antibody, reduces skin mast cells and disease activity in chronic inducible urticaria, a type of hives. This suggests it may help control hives by targeting mast cells, which are involved in allergic reactions.

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How is the drug Barzolvolimab different from other treatments for hives?

Barzolvolimab is unique because it targets and inhibits the KIT receptor, which is essential for mast cell function, leading to a reduction in mast cells that cause hives. This mechanism is different from other treatments like Omalizumab, which targets IgE antibodies involved in allergic reactions.

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Eligibility Criteria

Adults over 18 with chronic hives for at least 6 months, not relieved by standard antihistamines. They must have had symptoms for more than 6 weeks and be on a stable antihistamine regimen for at least 4 weeks. Participants need normal blood counts, liver function, agree to use contraception, and can manage a daily symptom diary.

Inclusion Criteria

- UAS7 of >/= 16 and ISS7 of >/= 8 during the 7 days prior to treatment

My blood counts and liver tests are normal.

I am 18 years old or older.

Exclusion Criteria

History of anaphylaxis

I have conditions linked to chronic hives.

Medical condition that would cause additional risk or interfere with study procedures

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Placebo-Controlled Treatment

Participants receive placebo injections every 4 weeks for 24 weeks

24 weeks

Active Treatment

All participants receive barzolvolimab for 28 weeks

28 weeks

Treatment-Free Period

Participants undergo a treatment-free period to monitor for safety and effectiveness

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Participant Groups

The trial is testing the effectiveness of barzolvolimab against placebo in adults with Chronic Spontaneous Urticaria (CSU) that's not controlled by second-generation non-sedating H1-antihistamines. It aims to determine if barzolvolimab can better manage their symptoms.

Group I: barzolvolimab 300 mg Experimental Treatment 1 Intervention

barzolvolimab given once as a 450 mg subcutaneous injection followed by 300 mg administered every 8 weeks for 52 weeks

Group II: barzolvolimab 150 mg Experimental Treatment 1 Intervention

barzolvolimab given once as a 300 mg subcutaneous injection followed by 150 mg administered every 4 weeks for 52 weeks

Group III: Placebo then barzolvolimab 300 mg Experimental Treatment 2 Interventions

Placebo injection subcutaneous every 4 weeks for 24 weeks and then barzolvolimab 450 mg followed by 300 mg administered every 8 weeks for 28 weeks.

Group IV: Placebo then barzolvolimab 150 mg Experimental Treatment 2 Interventions

Placebo injection subcutaneous every 4 weeks for 24 weeks and then barzolvolimab 300 mg followed by 150 mg administered every 4 weeks for 28 weeks.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Clear Dermatology & Aesthetics Center Scottsdale Scottsdale, AZ

First OC Dermatology - Fountain Valley Fountain Valley, CA

GSI Clinical Research Margate, FL

Alliance Clinical Research of Tampa Tampa, FL

More Trial Locations

Who Is Running the Clinical Trial?

Celldex Therapeutics Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Omalizumab Drug Survival in Chronic Urticaria: A Retrospective Multicentric French Study. [2023] Omalizumab (OMA) dramatically improves disease control and quality of life in patients with chronic urticaria (CU).

2. England pubmed.ncbi.nlm.nih.gov

Ligelizumab in adolescents with chronic spontaneous urticaria: Results of a dedicated phase 2b randomized clinical trial supported with pharmacometric analysis. [2023] Chronic spontaneous urticaria (CSU), a long-lasting disease in children, impacts their quality of life. We report the results of a phase 2b dose-finding trial of ligelizumab (NCT03437278) and a high-affinity humanized monoclonal anti-IgE antibody, in adolescents with CSU, supported by modeling and simulation analyses, mitigating challenges in pediatric drug development.

3. Denmark pubmed.ncbi.nlm.nih.gov

Anti-KIT monoclonal antibody CDX-0159 induces profound and durable mast cell suppression in a healthy volunteer study. [2022] Mast cells (MC) are powerful inflammatory immune sentinel cells that drive numerous allergic, inflammatory, and pruritic disorders when activated. MC-targeted therapies are approved in several disorders, yet many patients have limited benefit suggesting the need for approaches that more broadly inhibit MC activity. MCs require the KIT receptor and its ligand stem cell factor (SCF) for differentiation, maturation, and survival. Here we describe CDX-0159, an anti-KIT monoclonal antibody that potently suppresses MCs in human healthy volunteers.

4. United States pubmed.ncbi.nlm.nih.gov

IL-24 is a common and specific autoantigen of IgE in patients with chronic spontaneous urticaria. [2019] The efficacy of omalizumab (anti-IgE) and increased IgE levels in patients with chronic spontaneous urticaria (CSU) suggest autoallergic mechanisms.

5. Denmark pubmed.ncbi.nlm.nih.gov

Anti-KIT antibody, barzolvolimab, reduces skin mast cells and disease activity in chronic inducible urticaria. [2023] Chronic inducible urticaria (CIndU) is characterized by mast cell (MC)-mediated wheals in response to triggers: cold in cold urticaria (ColdU) and friction in symptomatic dermographism (SD). KIT receptor activation by stem cell factor (SCF) is essential for MC function. Barzolvolimab (CDX-0159) is a humanized antibody that inhibits KIT activation by SCF and was well tolerated in healthy volunteers with dose-dependent plasma tryptase suppression indicative of systemic mast cell ablation.

6. New Zealand pubmed.ncbi.nlm.nih.gov

Omalizumab: anti-IgE monoclonal antibody E25, E25, humanised anti-IgE MAb, IGE 025, monoclonal antibody E25, Olizumab, Xolair, rhuMAb-E25. [2018] Omalizumab [anti-IgE monoclonal antibody E25, E25, humanised anti-IgE MAb, IGE 025, monoclonal antibody E25, olizumab, rhuMAb-E25, Xolair] is a chimeric monoclonal antibody. It binds specifically to the Cepsilon3 domain of immunoglobulin E (IgE). Cepsilon3 is the site of high-affinity IgE receptor binding. IgE plays a major role in allergic disease by causing the release of histamine and other inflammatory mediators from mast cells. Omalizumab binds to and neutralises circulating IgE by preventing IgE from binding to its high-affinity mast-cell receptor. In addition, omalizumab does not bind to or induce histamine release from basophils, nor does it bind to or recognise IgG. The immune complexes formed between IgE and omalizumab in vivo are relatively small (molecular weight

7. United States pubmed.ncbi.nlm.nih.gov

Effects of omalizumab on basophil and mast cell responses using an intranasal cat allergen challenge. [2021] Omalizumab treatment suppresses FcepsilonRI expression faster on blood basophils than skin mast cells.