Barzolvolimab for Hives

(EMBARQ-CSU1 Trial)

Recruiting at 69 trial locations

Overseen By Celldex Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Celldex Therapeutics

Must be taking: H1-antihistamines

Disqualifiers: Pregnancy, Chronic inducible urticaria, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

915 Participants Needed

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. ^{1 2 3 4 5}

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. ^{1 3 5 6 7}

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

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

Treatment Details

Interventions

• Barzolvolimab

Trial Overview 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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Celldex Therapeutics

Lead Sponsor

Trials

66

Recruited

5,900+

Anthony S. Marucci

Celldex Therapeutics

Chief Executive Officer since 2008

MBA from Columbia University, MHL from Brown University

Diane C. Young

Celldex Therapeutics

Chief Medical Officer since 2019

MD from Harvard Medical School, AB in Biochemical Sciences from Harvard University

Findings from Research

In a study of 878 French patients with chronic urticaria, omalizumab (OMA) showed a longer drug survival rate compared to previous studies, with 50% of patients still on treatment 2.4 years after starting.

The main reason for discontinuing OMA was achieving well-controlled disease in 50% of patients, but many were able to restart treatment, indicating its effectiveness in managing chronic urticaria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab Drug Survival in Chronic Urticaria: A Retrospective Multicentric French Study. Litovsky, J., Hacard, F., Tétart, F., et al.[2023]

In a phase 2b trial involving adolescents aged 12-18 with chronic spontaneous urticaria (CSU), ligelizumab demonstrated significant efficacy in reducing urticaria symptoms, with a notable decrease in the Urticaria Activity Score (UAS7) compared to placebo.

Ligelizumab was well-tolerated in this population, and the pharmacokinetics of the drug were not significantly affected by age, suggesting that the same dosing can be safely used for both adolescents and adults with CSU.

NCBI (Pubmed)

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. Staubach, P., Alvaro-Lozano, M., Sekerel, BE., et al.[2023]

CDX-0159, an anti-KIT monoclonal antibody, effectively inhibits mast cell activation and has shown promising results in both in vitro studies and a phase 1a clinical trial with 32 healthy volunteers, indicating its potential as a treatment for mast cell-driven disorders.

The treatment was well tolerated in humans and demonstrated a significant reduction in plasma tryptase levels, a marker of mast cell activity, suggesting that CDX-0159 can safely suppress mast cell function systemically.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-KIT monoclonal antibody CDX-0159 induces profound and durable mast cell suppression in a healthy volunteer study. Alvarado, D., Maurer, M., Gedrich, R., et al.[2022]

In patients with chronic spontaneous urticaria (CSU), over 200 IgE autoantigens were identified, with IL-24 being a specific autoantigen found in all patients, suggesting a potential autoallergic mechanism in CSU.

IgE autoantibodies to IL-24 were shown to trigger histamine release from mast cells, indicating that targeting IL-24 could be a key therapeutic strategy for managing CSU symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-24 is a common and specific autoantigen of IgE in patients with chronic spontaneous urticaria. Schmetzer, O., Lakin, E., Topal, FA., et al.[2019]

Barzolvolimab (CDX-0159) was well tolerated in patients with antihistamine-refractory chronic inducible urticaria, showing significant depletion of skin mast cells and reduction in serum tryptase levels, indicating effective systemic mast cell ablation.

The treatment led to complete responses in 95% of patients and significant improvements in urticaria control and quality of life, suggesting its potential as a therapeutic option for mast cell-mediated disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-KIT antibody, barzolvolimab, reduces skin mast cells and disease activity in chronic inducible urticaria. Terhorst-Molawi, D., Hawro, T., Grekowitz, E., et al.[2023]

Omalizumab is an effective treatment for allergic asthma as it binds to IgE, preventing it from triggering allergic reactions, and has been shown to be safe in clinical trials with no significant thrombocytopenia reported in humans despite concerns in preclinical studies.

The drug received its first marketing approval in Australia in June 2002 for adults and adolescents with moderate allergic asthma, following extensive phase III trials that demonstrated its efficacy and safety.

NCBI (Pubmed)

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]

In a study involving 18 cat-allergic subjects, omalizumab treatment led to a significant 74% reduction in basophil histamine release in response to cat allergens after 3.5 months, indicating its efficacy in modulating basophil activity during allergic reactions.

The treatment also resulted in a 50% decrease in nasal symptoms and a 59% reduction in total sneeze counts, suggesting that basophils play a crucial role in the acute allergic response, while mast cell responses were only significantly affected later in the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of omalizumab on basophil and mast cell responses using an intranasal cat allergen challenge. Eckman, JA., Sterba, PM., Kelly, D., et al.[2021]

References

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

Omalizumab Drug Survival in Chronic Urticaria: A Retrospective Multicentric French Study. [2023]

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]

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]

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]

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

Anti-KIT antibody, barzolvolimab, reduces skin mast cells and disease activity in chronic inducible urticaria. [2023]

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]

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

Effects of omalizumab on basophil and mast cell responses using an intranasal cat allergen challenge. [2021]