BARZOLVOLIMAB for Cold-induced urticaria | Symptomatic dermographism

Inclusion criteria

• {"criterion_text":"- 1. 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."}
• {"criterion_text":"- 10. 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."}
• {"criterion_text":"- 2. Male or female, ≥ 18 years of age at the time of signing of the informed consent."}
• {"criterion_text":"- 3. 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])."}
• {"criterion_text":"- 4. 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."}
• {"criterion_text":"- 5. ColdU: Positive ice-cube test resulting in hives at the provocation site for participants at Screening."}
• {"criterion_text":"- 6. 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"}
• {"criterion_text":"- 7. 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 9. 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."}

Exclusion criteria

• {"criterion_text":"- 1. 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)."}
• {"criterion_text":"- 10.Intravenous immunoglobulin or plasmapheresis within 30 days prior to Screening."}
• {"criterion_text":"- 11.Planned or anticipated use of medications or major surgery prohibited by the protocol."}
• {"criterion_text":"- 12. 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."}
• {"criterion_text":"- 14. Women who are pregnant or nursing. All female participants with reproductive potential must have a negative pregnancy test prior to starting study treatment."}
• {"criterion_text":"- 15. 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."}
• {"criterion_text":"- 16. Participants with moderate-to-severe pulmonary or cardiovascular diseases."}
• {"criterion_text":"- 18. Known active hepatitis B, hepatitis C, or HIV infection."}
• {"criterion_text":"- 19. 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."}
• {"criterion_text":"- 20. 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."}
• {"criterion_text":"- 21. 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."}
• {"criterion_text":"- 2. Active CSU at Screening. Participants with resolved CSU at the time of screening can be included in the study."}
• {"criterion_text":"- 22. 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."}
• {"criterion_text":"- 23. Participants who live in detention on court order or on regulatory action will not be enrolled."}
• {"criterion_text":"- 24. 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."}
• {"criterion_text":"- 3. 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."}
• {"criterion_text":"- 4. Familial cold urticaria, also known as familial cold autoinflammatory syndrome."}
• {"criterion_text":"- 5. 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."}
• {"criterion_text":"- 6. 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."}
• {"criterion_text":"- 7. Non-biologic systemic (oral or injectable) agents, including investigational agents, within 4 weeks or 5 half-lives, whichever is longer, prior to Screening."}
• {"criterion_text":"- 8. Prior receipt of barzolvolimab or other anti-KIT therapy."}
• {"criterion_text":"- 9. Immuno-modulatory biologic therapy or other investigational mAb therapy within 3 months prior to Screening."}

Primary endpoints

• {"endpoint_text":"- • ColdU: Proportion of participants with complete response in Critical Temperature Threshold (CTT) following the TempTest® 4.0 at Week 12","definition_or_measurement_approach":"Measured using the TempTest® 4.0 provocation test to determine Critical Temperature Threshold (CTT) and proportion with complete response at Week 12."}
• {"endpoint_text":"- • SD: Proportion of participants with complete response in Critical Friction Threshold (CFT) following the FricTest® 4.0 at Week 12","definition_or_measurement_approach":"Measured using the FricTest® 4.0 provocation test to determine Critical Friction Threshold (CFT) and proportion with complete response at Week 12."}

Secondary endpoints

• {"endpoint_text":"- • ColdU: Change from baseline in CTT following the TempTest® at Week 12 • SD: Change from baseline in CFT following the FricTest® at Week 12","definition_or_measurement_approach":"Change from baseline in CTT (TempTest®) for ColdU and change from baseline in CFT (FricTest®) for SD at Week 12."}
• {"endpoint_text":"- • ColdU: Proportion of participants with complete response in CTT following the TempTest® at Week 24 • SD: Proportion of participants with complete response in CFT following FricTest® at Week 24","definition_or_measurement_approach":"Proportion with complete response assessed by TempTest® (CTT) and FricTest® (CFT) at Week 24."}
• {"endpoint_text":"- • ColdU: Change from baseline in CTT following the TempTest® at Week 24 • SD: Change from baseline in CFT following the FricTest® at Week 24\"","definition_or_measurement_approach":"Change from baseline in CTT (TempTest®) and CFT (FricTest®) at Week 24."}
• {"endpoint_text":"- • ColdU: Change from baseline in worst itch-numeric rating scale (WI-NRS) at Week 12 • SD: Change from baseline in worst itch-numeric rating scale (WI-NRS) at Week 12","definition_or_measurement_approach":"Change from baseline in WI-NRS at Week 12 for both ColdU and SD."}
• {"endpoint_text":"- • ColdU: Change from baseline in WI-NRS at Week 24 • SD: Change from baseline in WI-NRS at Week 24","definition_or_measurement_approach":"Change from baseline in WI-NRS at Week 24 for both ColdU and SD."}
• {"endpoint_text":"- • ColdU: Change from baseline in WI-NRSprovo following the TempTest® at Week 12 • SD: Change from baseline in WI-NRSprovo following the FricTest® at Week 12","definition_or_measurement_approach":"Change from baseline in WI-NRSprovo (post-provocation itch score) following TempTest® (ColdU) or FricTest® (SD) at Week 12."}
• {"endpoint_text":"- • ColdU: Proportion of participants with complete response in CTT following the TempTest® at Week 4 • SD: Proportion of participants with complete response in CFT following FricTest® at Week 4","definition_or_measurement_approach":"Proportion with complete response by TempTest® (CTT) and FricTest® (CFT) at Week 4."}
• {"endpoint_text":"- • ColdU: Change from baseline in CTT following the TempTest® at Week 4 • SD: Change from baseline in CFT following the FricTest® at Week 4","definition_or_measurement_approach":"Change from baseline in CTT (TempTest®) and CFT (FricTest®) at Week 4."}
• {"endpoint_text":"- • ColdU: Change from baseline in worst hives-numeric rating scale (WH-NRS) at Week 12 • SD: Change from baseline in WH-NRS at Week 12","definition_or_measurement_approach":"Change from baseline in WH-NRS at Week 12 for ColdU and SD."}
• {"endpoint_text":"- • ColdU: Change from baseline in WH-NRS at Week 24 • SD: Change from baseline in WH-NRS at Week 24","definition_or_measurement_approach":"Change from baseline in WH-NRS at Week 24 for ColdU and SD."}
• {"endpoint_text":"- • ColdU: Proportion of participants with DLQI = 0-1 at Week 12 • SD: Proportion of participants with DLQI = 0-1 at Week 12","definition_or_measurement_approach":"Proportion achieving Dermatology Life Quality Index (DLQI) score 0–1 at Week 12."}
• {"endpoint_text":"- • Safety endpoints will include but not be limited to: • Incidence of treatment-emergent adverse events • Incidence of treatment-emergent serious adverse events • Incidence of treatment-emergent adverse events of special interest","definition_or_measurement_approach":"Safety measured by incidence of treatment-emergent adverse events, serious adverse events, and adverse events of special interest as recorded during the study."}

Methods

• Site-based recruitment using prepared recruitment materials (recruitment brochures, posters, tear-off flyers, appointment reminder cards, fact sheets) as evidenced by country-specific recruitment arrangements documents (K1/K2) for Poland, Lithuania, Spain, Germany.
• Study-marketing-materials and recruitment brochures localized per country (documents labelled K2 and K1 for DEU, POL, LTU, ESP) for site-level outreach.

Germany

Earliest CTIS Part Ii Submission Date

14-01-2026

Latest Decision Or Authorization Date

25-03-2026

Processing Time Days

70

Number Of Sites

14

Number Of Participants

43

Lithuania

Earliest CTIS Part Ii Submission Date

24-02-2026

Latest Decision Or Authorization Date

25-03-2026

Processing Time Days

29

Number Of Sites

4

Number Of Participants

37

Spain

Earliest CTIS Part Ii Submission Date

26-02-2026

Latest Decision Or Authorization Date

27-03-2026

Processing Time Days

29

Number Of Sites

2

Number Of Participants

9

Poland

Earliest CTIS Part Ii Submission Date

20-02-2026

Latest Decision Or Authorization Date

27-03-2026

Processing Time Days

35

Number Of Sites

15

Number Of Participants

37

Primary sponsor

Full Name

Celldex Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Catalent Germany Schorndorf GmbH

Responsibilities

Study drug labeling and supply

Name

Suvoda LLC

Responsibilities

Development and hosting of electronic patient diaries, Interactive Response Technology

Name

Intuvigilance Limited

Responsibilities

SAE Case Processing, Regulatory Safety Reporting Submissions

Name

Optimapharm Nordic Oy

Responsibilities

Provider of regulatory service in Lithuania

Name

PPD Development LP

Responsibilities

Barzolvolimab pharmacokinetic and immunogenicity testing

Name

Medidata Solutions Inc.

Name

Scout Clinical

Responsibilities

Patient Travel and Reimbursement

Name

PPD Global Central Labs

Responsibilities

Centralized Clinical Testing

Third parties

• {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"Study drug labeling and supply","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"Development and hosting of electronic patient diaries, Interactive Response Technology","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Intuvigilance Limited","duties_or_roles":"SAE Case Processing, Regulatory Safety Reporting Submissions","organisation_type":"Industry"}
• {"country":"Finland","full_name":"Optimapharm Nordic Oy","duties_or_roles":"Provider of regulatory service in Lithuania","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Barzolvolimab pharmacokinetic and immunogenicity testing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Travel and Reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"Centralized Clinical Testing","organisation_type":"Pharmaceutical company"}