Barzolvolimab for Hives

(EMBARQ-CSU2 Trial)

Recruiting at 277 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, 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: 8

915 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called barzolvolimab, an anti-KIT monoclonal antibody, to help people with chronic spontaneous urticaria (a type of hives) who haven't found relief with common antihistamines. Researchers aim to determine if barzolvolimab is safe and effective compared to a placebo, a substance with no active drug. Participants will receive either a regular dose of barzolvolimab or a placebo, with some switching to barzolvolimab later in the study. The trial seeks individuals over 18 who have had persistent hives for at least six months, even while on non-sedating antihistamines. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires participants to continue taking a stable regimen of second generation non-sedating H1-antihistamines for at least 4 weeks before starting the study treatment. It does not specify if other medications need to be stopped.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that barzolvolimab, a monoclonal antibody, is generally safe for people. Studies have found that it effectively targets and reduces mast cells, which are linked to hives, without causing serious side effects. In earlier trials, participants mostly experienced only mild to moderate side effects. This suggests that barzolvolimab is relatively safe for treating chronic spontaneous urticaria, especially compared to other treatments. While some mild reactions might occur, the overall safety appears promising based on current data. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hives?

Barzolvolimab is unique because it targets the root cause of hives by acting on the immune system's pathway, specifically inhibiting a protein called KIT, which plays a key role in mast cell activation and histamine release. This is different from most current treatments, which typically focus on managing symptoms rather than addressing the underlying causes. Researchers are excited about barzolvolimab because it offers a targeted approach that might provide longer-lasting relief with fewer doses, and it holds the potential to be more effective for patients who do not respond well to standard antihistamines or biologics.

What evidence suggests that barzolvolimab might be an effective treatment for Chronic Spontaneous Urticaria?

Research has shown that barzolvolimab may help treat Chronic Spontaneous Urticaria (CSU), a condition that causes hives. Studies have found that it can greatly reduce symptoms and improve the condition for people with CSU. The drug targets and reduces mast cells, which play a role in the allergic reactions that cause hives. Early results suggest that barzolvolimab offers quick and lasting relief, even for patients with varying levels of IgE, an antibody often linked to allergies. These findings are based on previous studies that demonstrated both its effectiveness and a good safety record. Participants in this trial will receive different dosages of barzolvolimab or a placebo followed by barzolvolimab, to further evaluate its efficacy and safety. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

Adults over 18 with Chronic Spontaneous Urticaria (CSU) not well-controlled by antihistamines can join. They must have had hives for at least 6 weeks, a certain severity of symptoms, and be willing to keep a symptom diary. People with or without prior biologic treatment are eligible if they've been on stable antihistamine use for 4 weeks and have normal blood and liver tests.

Inclusion Criteria

I have had chronic hives for 6 months or more.

I have been taking a specific allergy medication regularly for at least 4 weeks.

My blood and liver tests are normal.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Placebo-Controlled Treatment

Participants receive placebo or barzolvolimab to assess efficacy and safety

24 weeks

Subcutaneous injections every 4 weeks

Active Treatment

All participants receive barzolvolimab to further assess efficacy and safety

28 weeks

Subcutaneous injections every 4 or 8 weeks

Treatment-Free Period

Participants are monitored without treatment to assess long-term effects

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Barzolvolimab

Trial Overview The trial is testing the effectiveness of Barzolvolimab against a placebo in adults with CSU whose symptoms persist despite taking non-sedating H1-antihistamines. It aims to see if this new treatment can better manage their condition.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12368744/

Anti‐KIT Barzolvolimab for Chronic Spontaneous Urticaria Sustained clinical response with barzolvolimab mirrored the changes in tryptase and SCF, suggesting that depleting MCs is effective in improving CSU symptoms.

2. ir.celldex.com ir.celldex.com/news-releases/news-release-details/celldex-presents-data-demonstrating-barzolvolimab-improves

Release Details Barzolvolimab demonstrated rapid and sustained efficacy in patients with CSU with both low (<40) and normal/high (>40) IgE levels. Similar ...

3. globenewswire.com globenewswire.com/news-release/2025/11/06/3182511/24180/en/Celldex-Presents-Results-from-Barzolvolimab-Phase-2-Study-in-Cold-Urticaria-ColdU-and-Symptomatic-Dermographism-SD-Demonstrating-Sustained-Efficacy-and-Favorable-Safety-Profile-ove.html

Celldex Presents Results from Barzolvolimab Phase 2 Study “Barzolvolimab is the first drug to achieve success in a large, randomized, placebo-controlled study in chronic inducible urticaria—providing ...

4. jacionline.org jacionline.org/article/S0091-6749(23)02364-3/fulltext

Top Line Results from a Phase 2 Trial Barzolvolimab Significantly Decreases Chronic Spontaneous Urticaria Disease Activity and is Well Tolerated: Top Line Results from a Phase 2 Trial · Rationale.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1081120624015655

Positive efficacy and favorable safety of barzolvolimab in ... This phase II barzolvolimab study is the first large, randomized placebo-controlled study to achieve a successful outcome for CIndU.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9544977/

Anti‐KIT monoclonal antibody CDX‐0159 induces profound ... In summary, the preclinical and clinical safety and pharmacodynamic data presented in this manuscript show that CDX‐0159 is well tolerated and impacts ...

7. jacionline.org jacionline.org/article/S0091-6749(22)02072-3/fulltext

Safety and Clinical Activity of Multiple Doses ... Barzolvolimab (BAR/CDX-0159), a monoclonal anti-KIT antibody, has been demonstrated to deplete skin MCs in chronic inducible urticaria and reduce disease ...

8. medchemexpress.com medchemexpress.com/barzolvolimab.html?srsltid=AfmBOoo1mDIF3ExoqngIAwHh1j9LE3OB96Aaj7FBEuN8O0i2ykNglVEe

Barzolvolimab (CDX-0159) | Anti-KIT Antibody Barzolvolimab (CDX 0159) is a humanized anti-KIT IgG1 monoclonal antibody. Barzolvolimab specificity and potently inhibits KIT activation by SCF.