A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of Barzolvolimab in Participants with Cold-Induced Urticaria and Symptomatic Dermographism
- Trial ID
- 2025-522583-32-00
- Protocol
- CDX0159-16
- Sponsor
- Celldex Therapeutics Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the efficacy of barzolvolimab compared to placebo in achieving a complete response to provocation tests for cold-induced urticaria and symptomatic dermographism at week 12. Secondary objectives include assessing changes from baseline in cold urticaria threshold (CTT) and dermographism wheal circumference threshold (CFT) at weeks 4, 12, and 24. Additional clinical outcomes being evaluated include complete response rates at weeks 4 and 24, improvements in itch and hives symptoms at weeks 12 and 24, and changes in the visual analog scale for itch following provocation (WI-NRSprovo) at week 12. The study also examines the impact on the Dermatology Life Quality Index (DLQI) at week 12 and monitors safety profiles. 5, 4.
Participants
This study involves 114 participants diagnosed with cold urticaria or symptomatic dermographism. The study population consists of male and female patients aged 18 years or older. Eligible individuals must have experienced symptoms for at least 3 months and have uncontrolled disease despite a stable regimen of a second-generation non-sedating histamine H1 antagonist. For those with cold urticaria, a positive ice-cube test and specific thermal thresholds are required, while those with symptomatic dermographism must meet defined friction thresholds. Participants are required to maintain a daily symptom diary and adhere to specific contraception requirements based on childbearing potential. Hematological and hepatic parameters, including white blood cell count, absolute neutrophil count, platelet count, hemoglobin, aspartate aminotransferase, alanine aminotransferase, and total bilirubin, must be within specified clinical limits.
Plans and Procedures
This Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multi-center study is designed to evaluate the efficacy and safety of barzolvolimab in participants diagnosed with cold urticaria or symptomatic dermographism. Following a screening visit, which includes diagnostic provocation tests and laboratory assessments, eligible participants will be randomized to receive either barzolvolimab or a placebo via subcutaneous injection. The study involves monitoring participants through scheduled follow-up visits to assess clinical responses, such as the critical temperature threshold and critical friction threshold, as well as various safety endpoints. The primary efficacy objectives are measured at Week 12. Participant involvement includes the maintenance of a daily symptom diary throughout the study period. While the specific end-of-study visit details are not provided, the clinical course is structured to monitor therapeutic response and adverse events over the treatment duration.
Treatment
Barzolvolimab is administered as a 450 mg subcutaneous injection using a concentrate for solution for infusion. This experimental medication is investigated for the treatment of cold urticaria and symptomatic dermographism.
A placebo consisting of prefilled syringes containing only the vehicle with 0 mg/mL of the active substance is utilized for comparison.
Epinephrine, provided as a 600 mg solution for injection in a pre-filled pen via subcutaneous administration, is utilized as an auxiliary treatment.
Efficacy
The efficacy of barzolvolimab in participants with cold urticaria and symptomatic dermographism is evaluated through several primary and secondary endpoints. The primary efficacy assessment at Week 12 consists of the proportion of participants achieving a complete response to provocation testing. For cold urticaria, this is measured by the critical temperature threshold (CTT) using the TempTest® 4.0. For symptomatic dermographism, this is measured by the critical friction threshold (CFT) using the FricTest® 4.0.
Secondary efficacy parameters include:
- Changes from baseline in CTT and CFT at Week 4, Week 12, and Week 24.
- Proportions of participants with a complete response in CTT and CFT at Week 4 and Week 24.
- Changes from baseline in the worst itch-numeric rating scale (WI-NRS) and worst hives-numeric rating scale (WH-NRS) at Week 12 and Week 24.
- Changes from baseline in WI-NRSprovo following provocation testing at Week 12.
- Proportion of participants achieving a Dermatology Life Quality Index (DLQI) score of 0-1 at Week 12.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Able to read, understand, and provide written informed consent, and Health Insurance Portability and Accountability Act (HIPAA) authorization if applicable, after the nature of the study has been fully explained. Participants must be able to provide informed consent themselves.
- Male or female, ≥ 18 years of age at the time of signing of the informed consent.
- Diagnosis of ColdU or SD for ≥ 3 months prior to Screening Visit 1 (defined as onset of ColdU or SD with supporting documentation [e.g., medical record, clinical history, photographs]).
- Participants with chronic ColdU or SD whose urticaria remains uncontrolled despite a stable dose and regimen of a second-generation non-sedating H1AH as defined by all of the following: a. Recurrent pruritic wheals with or without angioedema due to ColdU or SD for ≥ 6 weeks prior to Screening Visit 1 despite treatment with a H1AH b. Participants must have been on a stable regimen containing at least a secondgeneration non-sedating H1AH at an approved or increased (up to 4× the approved) dose for the treatment of ColdU or SD for ≥ 4 weeks prior to randomization and which is expected to remain stable throughout the study c. ColdU: A Critical Threshold Temperature (CTT) of ≥ 10 °C and < 37 °C using the TempTest® and a numerical rating scale score of ≥ 3 for itch after the provocation test. d. SD: A Critical Friction Threshold (CFT) of ≥ 3 using the FricTest® and a numerical rating scale score of ≥ 3 for itch after the provocation test.
- ColdU: Positive ice-cube test resulting in hives at the provocation site for participants at Screening.
- WBC, ANC, and platelet count ≥ LLN and hemoglobin no less than 1 g/dL below the LLN at Screening. If test results do not meet the above criteria, a repeat test may be performed once to determine eligibility
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2 × upper limit of normal (ULN), and total bilirubin ≤ 2 × ULN (unless elevated bilirubin is related to Gilbert's Syndrome [≤ 3 × ULN]), at Screening. If test results do not meet the above criteria, a repeat test may be performed once to determine eligibility.
- 8.Females must meet one of the following criteria: • If of childbearing potential, agrees to use highly effective contraception from the time of Screening and for ≥ 150 days after receipt of study treatment. Highly effective methods of contraception include the following: − combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation, administered as oral, intravaginal, or transdermal progestogen-only hormonal contraception associated with inhibition of ovulation administered as oral, injectable, or by implantable means − intrauterine device − intrauterine hormone-releasing system − tubal ligation − a vasectomized male partner (male sterilization ≥ 6 months prior to screening with a medical assessment of the surgical success) as the sole partner for the participant. Total abstinence is acceptable when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal postovulation methods) and withdrawal are not acceptable methods of contraception • Females of non-childbearing potential, who are surgically sterile (i.e., had undergone complete hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or in a menopausal state (≥ 1 year without menses), as confirmed by follicle stimulating hormone (FSH) levels, are eligible. Where documentation of FSH status is present in the medical history, retesting is not required unless the Investigator considers otherwise. If local regulations are more stringent than the contraceptive methods listed above to prevent pregnancy, local regulations apply and will be described in the Informed Consent Form.
- Male participants with female partners of childbearing potential must agree to use either a condom (with or without spermicide) or have undergone a vasectomy and agree to not donate sperm during the study and for ≥ 150 days after receipt of study treatment. Where a male participant has undergone a vasectomy, the participant medical history should show that the vasectomized participant has documented medical assessment confirming the surgical success of the vasectomy.
- Willing and able to comply with all study requirements and procedures, including the protocol defined provocation tests, visit schedule and completion of a daily symptom diary during screening and throughout of the study. Note: For study eligibility, participants need to complete the diary for ≥ 5 of the 7 days (from Day -7 to Day -1) immediately prior to randomization.
Exclusion Criteria
- Diseases with possible symptoms of urticaria or angioedema, such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), autoimmune syndromes with urticarial lesions (e.g., Schnitzler Syndrome) and hereditary or acquired angioedema (e.g., due to C1 inhibitor deficiency).
- Active CSU at Screening. Participants with resolved CSU at the time of screening can be included in the study.
- An alternative form of CIndU other than ColdU or SD, including cholinergic-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, or contact-urticaria that would confound assessments of ColdU or SD based on the Investigator’s clinical judgment.
- Familial cold urticaria, also known as familial cold autoinflammatory syndrome.
- Any other active pruritic skin diseases that would confound CIndU assessments (e.g., atopic dermatitis, psoriasis, bullous pemphigoid, dermatitis herpetiformis, prurigo nodularis, chronic pruritus of unknown origin, or senile pruritus) based on the Investigator's clinical judgment.
- Regular (3 or more days a week) use of topical corticosteroid, topical calcineurin inhibitors, topical antihistamines, first-generation sedating antihistamines, and other sedatives/hypnotics, within 1 week prior to Screening.
- Non-biologic systemic (oral or injectable) agents, including investigational agents, within 4 weeks or 5 half-lives, whichever is longer, prior to Screening.
- Prior receipt of barzolvolimab or other anti-KIT therapy.
- Immuno-modulatory biologic therapy or other investigational mAb therapy within 3 months prior to Screening.
- 10.Intravenous immunoglobulin or plasmapheresis within 30 days prior to Screening.
- 11.Planned or anticipated use of medications or major surgery prohibited by the protocol.
- Receipt of a live vaccine within 30 days prior to Screening. Seasonal influenza vaccines for injection are generally inactivated virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. Currently authorized COVID-19 vaccines are allowed.
- Women who are pregnant or nursing. All female participants with reproductive potential must have a negative pregnancy test prior to starting study treatment.
- Severe or uncontrolled chronic diseases (e.g., chronic hepatic or renal disease, diabetes mellitus) that might interfere with the evaluation of the clinical effect or safety of study treatment.
- Participants with moderate-to-severe pulmonary or cardiovascular diseases.
- Known active hepatitis B, hepatitis C, or HIV infection.
- Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antifungals, antiparasitics or antiprotozoals during the Screening Period. The Screening Period may be extended by 2 weeks (i.e., past 28 days) to allow for recovery of acute infections independent of requirement for anti-infective treatment. Note: Participants with active tuberculosis (TB), nontuberculous mycobacterial infection, or a history of incompletely treated or latent TB will be excluded from the study unless, in the medical judgment of a TB or infectious disease specialist, it is well documented that the participant has either been adequately treated and can now start treatment with a biological agent or, in the case of latent TB, receive concurrent treatment according to local guidelines. To obtain this judgment, and in consultation with the Medical Monitor, the Screening Period may be extended by a maximum of 2 weeks (i.e., past 28 days). TB testing will be performed on a country-by-country basis, according to local guidelines if required by regulatory authorities or ethics boards. In the event of indeterminate results of tuberculosis testing, testing may be repeated and if indeterminate results are confirmed, for the purpose of this study protocol, the participant will be considered as having latent TB.
- History of malignancy within 5 years before Screening, except fully treated carcinoma in-situ of the cervix, fully treated and resolved non-metastatic squamous or basal cell carcinoma of the skin.
- Any other acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with study participation or could interfere with the interpretation of study results and, in the judgment of the Investigator, would make the participant inappropriate for entry into the study.
- Procedures requiring general or epidural anaesthesia within 8 weeks prior to study treatment, minor procedures (e.g., dental) within 14 days prior to study treatment, or anticipation of procedures requiring general anaesthesia during study participation.
- Participants who live in detention on court order or on regulatory action will not be enrolled.
- Sponsor or contract research organization (CRO) staff directly involved in the conduct of the study, and site staff supervised by the Investigator, and their respective family members.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Recruiting | 30 Mar 2026 | 43 |
 Lithuania | Recruiting | 30 Mar 2026 | 37 |
 Poland | Recruiting | 30 Mar 2026 | 37 |
 Spain | Recruiting | 30 Mar 2026 | 9 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
FASTJEKT
300 Mikrogramm, Injektionslösung im Fertigpen | Other | INJEKTIONSLÖSUNG IM FERTIGPEN | SUBCUTANEOUS | 600 | 1 | PRD11537578 |
BARZOLVOLIMAB | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | SUBCUTANEOUS INJECTION | 450 | 24 | PRD8576244 |
Placebo prefilled syringes containing only the vehicle (containing 0 mg/mL barzolvolimab). | Placebo | N/A | — | — | — | N/A |