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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of barzolvolimab, an anti-KIT monoclonal antibody, in treating chronic spontaneous urticaria (CSU), where patients frequently experience hives despite allergy medications. Researchers aim to evaluate barzolvolimab's effectiveness, safety, and comfort compared to a placebo. Participants will receive varying doses of the drug or a placebo to identify the best treatment approach. Individuals who have had hives for at least six months and find their current non-drowsy antihistamines insufficient may be suitable for this trial. As a Phase 3 trial, this study is the final step before potential FDA approval, offering participants a chance to contribute to a promising treatment's journey to market.

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.

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

Research has shown that barzolvolimab is generally safe for people. This treatment targets a specific protein in the body and has been tested in patients with conditions like chronic hives. In these studies, barzolvolimab significantly improved symptoms and was safe for most participants.

Evidence suggests that barzolvolimab reduces the activity of certain cells involved in allergic reactions. Reports from previous studies indicate that side effects were mostly mild and manageable, meaning the treatment does not cause serious problems for most people.

Since this trial is in a later phase, the treatment has already passed earlier safety tests. This indicates that barzolvolimab is likely safe for humans, although individual experiences may vary. ^{1 2 3 4 5}

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

Barzolvolimab is unique because it offers a new approach to treating hives by targeting the immune system in a novel way. While most treatments for hives, like antihistamines and corticosteroids, work by alleviating symptoms, barzolvolimab specifically targets key immune pathways involved in the condition. This drug acts by blocking the activity of certain proteins that trigger inflammation, potentially providing more effective and longer-lasting relief. Researchers are excited about barzolvolimab because it could offer an alternative for patients who do not respond well to current therapies, with the potential for fewer side effects and improved quality of life.

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

Research has shown that barzolvolimab may be a promising treatment for Chronic Spontaneous Urticaria (CSU), a condition that causes hives. In earlier studies, barzolvolimab significantly reduced symptoms in people with CSU and was well tolerated. Another study found that it led to quick and lasting improvements, regardless of the patient's IgE levels, a type of antibody. The drug targets mast cells, which are involved in causing hives, leading to improved symptoms. These findings suggest that barzolvolimab could be an effective option for those not helped by current antihistamines. Participants in this trial will receive different dosages of barzolvolimab or a placebo followed by barzolvolimab to further evaluate its effectiveness and safety. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

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

My blood counts and liver tests are normal.

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

- The presence of hives for >/= 6 weeks at any time prior to Visit 1 despite the use of non-sedating H1-antihistamines

Exclusion Criteria

History of anaphylaxis

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

I have conditions linked to chronic hives.

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 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

What Are the Treatments Tested in This Trial?

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.

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

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]

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]

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]

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 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]

Citations

1. ir.celldex.com ir.celldex.com/news-releases/news-release-details/celldex-presents-results-barzolvolimab-phase-2-study-cold

Up to 66% of Patients with ColdU and 49% with SD Obtain ... First large, randomized, placebo-controlled study to demonstrate clinical benefit in patients with Cold Urticaria (ColdU) and Symptomatic ...

2. 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.

3. 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 ...

4. 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 ...

5. 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.

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=AfmBOop1WaclB5Bx-1c6gjIpg3DR3rrde-B45JZdwp4VMPGi-xiaoINR

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.

9. 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.