Clinical trial • Phase III • Dermatology
Barzolvolimab for Chronic spontaneous urticaria
Phase III trial of Barzolvolimab for Chronic spontaneous urticaria.
Overview
- Trial Therapeutic Area
- Dermatology
- Trial Disease
- Chronic spontaneous urticaria
- Trial Stage
- Phase III
- Drug Modality
- Monoclonal antibody
Key dates
- Initial CTIS Submission Date
- 19-07-2024
- First CTIS Authorization Date
- 05-11-2024
Trial design
Randomised, placebo (prefilled syringes identical to barzolvolimab vehicle, 0 mg/ml) administered q4w during the 24-week placebo-controlled treatment phase; active arms: barzolvolimab sc 150 mg every 4 weeks (q4w) following an initial loading dose of 300 mg; barzolvolimab 300 mg every 8 weeks (q8w) following an initial loading dose of 450 mg, adaptive Phase III trial in Poland, Czechia, Bulgaria and others.
- Randomised
- Yes
- Comparator
- Placebo (prefilled syringes identical to barzolvolimab vehicle, 0 mg/mL) administered Q4W during the 24-week placebo-controlled treatment phase; active arms: barzolvolimab SC 150 mg every 4 weeks (Q4W) following an initial loading dose of 300 mg; barzolvolimab 300 mg every 8 weeks (Q8W) following an initial loading dose of 450 mg
- Adaptive
- True, Participants in Arm 3 (placebo) will be re-randomised 1:1 in the Active Treatment Phase to receive barzolvolimab either 150 mg Q4W (after loading 300 mg) or 300 mg Q8W (after loading 450 mg); protocol includes staged phases (screening, placebo-controlled, active treatment re-randomisation, follow-up).
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 682
- Trial Duration For Participant
- 504
Eligibility
Recruits 682 The protocol indicates participants must be able to provide informed consent themselves ("Participants must be able to provide informed consent themselves."). The trial materials include pregnancy/partner and newborn-data ICFs and multiple country-specific ICFs; vulnerable population selection flag is set in the record but the protocol text requires written informed consent from participants (no assent procedures for minors are specified)..
- Vulnerable Population
- The protocol indicates participants must be able to provide informed consent themselves ("Participants must be able to provide informed consent themselves."). The trial materials include pregnancy/partner and newborn-data ICFs and multiple country-specific ICFs; vulnerable population selection flag is set in the record but the protocol text requires written informed consent from participants (no assent procedures for minors are specified).
Inclusion criteria
- {"criterion_text":"- Read, understood, and provided 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.\n- Male or female, ≥ 18 years of age at the time of signing the informed consent.\n- CSU ≥ 6 months prior to Screening. Note: the investigator should establish the presence of CSU for the noted duration based on all available supporting documentation, including written medical records and communication with the participants’ previous healthcare providers, if applicable.\n- CSU refractory to a stable dose and regimen containing a second-generation H1AH as defined by all of the following: • Recurrent pruritic wheals with or without angioedema for ≥ 6 weeks at any time prior to Screening (Visit 1) despite treatment with a H1AH (hives consistent with CSU should be documented and confirmed by the investigator prior to randomization) • Participants must have been on a stable dose and regimen containing a secondgeneration H1 antihistamine (H1AH) at approved or increased (up to 4x approved) dose as background therapy for the treatment of CSU for ≥ 4 weeks prior to randomization and which is expected to remain stable throughout the study. • UAS7 (range: 0 to 42) ≥ 16 and ISS7 (range: 0 to 21) ≥ 8 during the 7-day period (Day -7 to Day -1) immediately prior to randomization.\n- Willing and able to comply with all study requirements and procedures, including the completion of a daily symptom diary during screening and throughout the study."}
Exclusion criteria
- {"criterion_text":"- 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).\n- Chronic urticaria whose predominant manifestation is due to CIndU including symptomatic dermographism [urticaria factitia], cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact urticaria Note: CIndU is not excluded per se\n- Any other active pruritic skin diseases that would confound CSU assessments (e.g., atopic dermatitis, psoriasis, bullous pemphigoid, dermatitis herpetiformis, prurigo nodularis, chronic pruritus of unknown origin) based on the investigator's clinical judgment.\n- Prior receipt of barzolvolimab or other anti-KIT therapy."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Mean change from baseline in UAS7 at Week 12","definition_or_measurement_approach":"Change from baseline measured using the weekly urticaria activity score (UAS7) at Week 12"}
Secondary endpoints
- {"endpoint_text":"- 1. Mean change from baseline in ISS7 and HSS7 at Week 12","definition_or_measurement_approach":"Change from baseline measured using weekly itch severity score (ISS7) and weekly hive severity score (HSS7) at Week 12"}
- {"endpoint_text":"- 2. Proportion of participants with UAS7 = 0 at Week 12","definition_or_measurement_approach":"Proportion of participants achieving a UAS7 score of 0 at Week 12"}
- {"endpoint_text":"- 3. Proportion of participants with UAS7 ≤ 6 at Week 12","definition_or_measurement_approach":"Proportion of participants with UAS7 score ≤ 6 at Week 12"}
- {"endpoint_text":"- 4. Proportion of participants with AAS7 = 0 at Week 12 in participants who have AAS7 > 0 at baseline","definition_or_measurement_approach":"Proportion achieving AAS7 = 0 at Week 12 among participants with baseline AAS7 > 0 (weekly angioedema activity score)"}
- {"endpoint_text":"- 5. Mean change from baseline in UAS7 in participants refractory to omalizumab treatment at Week 12","definition_or_measurement_approach":"Change from baseline in UAS7 at Week 12 in the subgroup refractory to omalizumab"}
- {"endpoint_text":"- 6. Proportion of participants with UAS7 = 0 in participants refractory to omalizumab treatment at Week 12","definition_or_measurement_approach":"Proportion with UAS7 = 0 at Week 12 in participants refractory to omalizumab"}
Recruitment
- Digital Remote Recruitment
- True, digital methods include country-specific landing pages (desktop and mobile), keyword-search advertising, social media creative (1080x1080 and 1200x628), online banners and carousels, and URLs/landing-page assets described in recruitment materials.
- Planned Sample Size
- 682
- Recruitment Window Months
- 29
- Consent Approach
- Written informed consent is required: "Read, understood, and provided 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." ICFs are provided in multiple country/language versions (country-specific Main ICFs, Other ICFs, Pregnant/Partner ICFs and Newborn Data ICFs are listed for several countries), and HIPAA authorization is included if applicable.
Methods
- Digital advertising: keyword-search ads, online banners, social media posts (assets 1080x1080 and 1200x628), and paid placement carousels (country-specific assets listed for PL, CZ, DE, FR, ES, IT, PT, BE, BG, GR)
- Study landing pages and mobile landing pages (country-specific landing-page wording and assets)
- Doctor-to-patient letters and GP/physician referral letters to reach target patients via clinicians
- Recruitment brochures, fact sheets and recruitment brochures for patient-facing distribution
- Appointment reminder cards and patient cards
- Site-specific recruitment webpages and site referral materials (site-specific recruitment materials listed for several sites)
- Patient-facing screening questionnaires (HIVES_PS / referral questionnaires) and eCOA materials
Geography
- Total Number Of Sites
- 106
- Total Number Of Participants
- 521
Poland
- Earliest CTIS Part Ii Submission Date
- 14-10-2024
- Latest Decision Or Authorization Date
- 05-05-2026
- Processing Time Days
- 568
- Number Of Sites
- 27
- Number Of Participants
- 130
Czechia
- Earliest CTIS Part Ii Submission Date
- 14-08-2024
- Latest Decision Or Authorization Date
- 04-05-2026
- Processing Time Days
- 628
- Number Of Sites
- 4
- Number Of Participants
- 20
Bulgaria
- Earliest CTIS Part Ii Submission Date
- 15-10-2024
- Latest Decision Or Authorization Date
- 05-05-2026
- Processing Time Days
- 568
- Number Of Sites
- 12
- Number Of Participants
- 70
Denmark
- Earliest CTIS Part Ii Submission Date
- 22-10-2024
- Latest Decision Or Authorization Date
- 01-05-2026
- Processing Time Days
- 557
- Number Of Sites
- 4
- Number Of Participants
- 20
France
- Earliest CTIS Part Ii Submission Date
- 23-10-2024
- Latest Decision Or Authorization Date
- 30-04-2026
- Processing Time Days
- 554
- Number Of Sites
- 7
- Number Of Participants
- 30
Portugal
- Earliest CTIS Part Ii Submission Date
- 21-10-2024
- Latest Decision Or Authorization Date
- 30-04-2026
- Processing Time Days
- 556
- Number Of Sites
- 10
- Number Of Participants
- 40
Italy
- Earliest CTIS Part Ii Submission Date
- 11-10-2024
- Latest Decision Or Authorization Date
- 05-05-2026
- Processing Time Days
- 571
- Number Of Sites
- 6
- Number Of Participants
- 30
Germany
- Earliest CTIS Part Ii Submission Date
- 18-09-2024
- Latest Decision Or Authorization Date
- 04-05-2026
- Processing Time Days
- 593
- Number Of Sites
- 12
- Number Of Participants
- 70
Spain
- Earliest CTIS Part Ii Submission Date
- 14-10-2024
- Latest Decision Or Authorization Date
- 05-05-2026
- Processing Time Days
- 568
- Number Of Sites
- 11
- Number Of Participants
- 50
Greece
- Earliest CTIS Part Ii Submission Date
- 02-10-2024
- Latest Decision Or Authorization Date
- 04-05-2026
- Processing Time Days
- 579
- Number Of Sites
- 4
- Number Of Participants
- 24
Belgium
- Earliest CTIS Part Ii Submission Date
- 10-10-2024
- Latest Decision Or Authorization Date
- 04-05-2026
- Processing Time Days
- 571
- Number Of Sites
- 9
- Number Of Participants
- 37
Sponsor
Primary sponsor
- Full Name
- Celldex Therapeutics Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- PPD Development LP
- Responsibilities
- ADA/PK; (multiple PPD entries provide ADA/PK, central lab and project management/monitoring/regulatory)
- Name
- PPD Global Ltd.
- Responsibilities
- Project management duties and monitoring/regulatory
- Name
- PPD Global Central Labs
- Responsibilities
- Biopsy storage and shipment
- Name
- Scout Clinical
- Responsibilities
- Patient concierge
Third parties
- {"country":"United States","full_name":"National Jewish Health","duties_or_roles":"IgE receptor Antibody","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient concierge","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"France","full_name":"Inato","duties_or_roles":"Site selection","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"ADA/PK","organisation_type":"Pharmaceutical company"}
- {"country":"Greece","full_name":"PPD Global Ltd.","duties_or_roles":"Project management duties and monitoring/regulatory","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"PPD Development LP (Wilmington address)","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Intuvigilance Limited","duties_or_roles":"Safety","organisation_type":"Industry"}
- {"country":"Croatia","full_name":"Optimapharm d.o.o.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"biopsy storage and shipment","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Canfield Scientific Inc.","duties_or_roles":"Photo collection services","organisation_type":"Pharmaceutical company"}
- {"country":"Ireland","full_name":"Signant Health Global Solutions Limited","duties_or_roles":"eCOA","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":"Arup Laboratories Inc.","duties_or_roles":"thyroid peroxidase","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Quest Diagnostics Inc.","duties_or_roles":"Anti-IgE IgG","organisation_type":"Laboratory/Research/Testing facility"}
Investigational products
- Investigational Product Name
- BARZOLVOLIMAB
- Active Substance
- Barzolvolimab
- Modality
- Monoclonal antibody
- Routes Of Administration
- Subcutaneous
- Route
- Subcutaneous
- Authorisation Status
- Investigational (MIA number DE_BW_01_MIA_2022_0034)
- Starting Dose
- Loading dose: 300 mg (for 150 mg Q4W arm) or 450 mg (for 300 mg Q8W arm)
- Dose Levels
- 150 mg Q4W (maintenance) following 300 mg loading; 300 mg Q8W (maintenance) following 450 mg loading
- Frequency
- 150 mg every 4 weeks (after 300 mg loading) OR 300 mg every 8 weeks (after 450 mg loading)
- Maximum Dose
- 450 mg (max daily per product data); max total treatment amount reported 2400 mg
- Dose Escalation Increase
- Initial loading doses: 300 mg (then 150 mg Q4W) and 450 mg (then 300 mg Q8W)
- Investigational Product Name
- Placebo (prefilled syringes identical to barzolvolimab vehicle)
- Active Substance
- N/A (vehicle only)
- Modality
- Other
- Routes Of Administration
- Subcutaneous (matching barzolvolimab prefilled syringes)
- Route
- Subcutaneous
- Authorisation Status
- Not applicable (placebo comparator)
- Frequency
- Q4W during 24-week placebo-controlled phase (matching active schedule)
- Investigational Product Name
- FASTJEKT 300 Mikrogramm, Injektionslösung im Fertigpen
- Active Substance
- Epinephrine (adrenaline)
- Modality
- Small molecule
- Routes Of Administration
- Subcutaneous
- Route
- Subcutaneous
- Authorisation Status
- Authorized product (marketing authorisation number listed for DE)
- Starting Dose
- 300 µg (product presentation)
- Frequency
- As required (rescue medication); product max daily dose 600 µg
- Maximum Dose
- 600 µg (max daily amount indicated)
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