Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as CDX-0159
Barzolvolimab · 12 trials · 11 indications
Proportion of Cold Induced Urticaria \[ColdU\] participants with complete response in Critical Temperature Threshold (CTT) or proportion of Symptomatic Dermographism \[SD\] participants with complete response in Critical Friction Threshold at Week 12. * For ColdU patients, a complete response is defined as absence of wheals at the provocation site within 10 min at ≤ 4°C after provocation using TempTest® * For SD patients, a complete response test is defined as absence of wheals at the provocation site within 10 min at 0 pins after provocation using the FricTest®
The UAS7 is a simple scoring system to evaluate urticaria signs and symptoms. It is based on scoring wheals (hive severity score) and itch (itch severity score) separately on a scale of 0 (no signs/symptoms) to 3 (intense signs/symptoms) over 7 days. The final score is calculated by adding together the daily scores, which can range from 0 to 6, for 7 days. This results in a maximum total score of 42, and a minimum possible score of 0.
Evaluate duration of efficacy of barzolvolimab on urticaria activity or to a treatment related adverse event.
Evaluate duration of efficacy of barzolvolimab on urticaria activity leading to initiation of either a confounding prohibited medication (Group 1 or 2) or barzolvolimab in Group 1.
Evaluate efficacy of barzolvolimab on urticaria activity as measured by urticaria activity score (UAS). The UAS7 is a simple scoring system to evaluate urticaria signs and symptoms. It is based on scoring wheals (hive severity score) and itch (itch severity score) separately on a scale of 0 (no signs/symptoms) to 3 (intense signs/symptoms) over 7 days. The final score is calculated by adding together the daily scores, which can range from 0 to 6, for 7 days. This results in a maximum total score of 42, and a minimum possible score of 0.
Evaluate the clinical efficacy of 2 dose levels (150 mg and 300 mg) of barzolvolimab, compared to placebo, in adult participants with moderate to severe atopic dermatitis (AD) using the PP-NRS. The PP-NRS ranges from 0 = "no itch" to 10 ="worst imaginable itch" for the worst intensity itch in the preceding 24-hr period.
WI-NRS is a validated measure of itch severity. Participants are asked daily to rate the intensity of their worst pruritis (itch) over the past 24 hours using an 11-point scale ranging from 0= no itch to 10= worst imaginable itch. Higher scores indicate more severity.
Peak esophageal intraepithelial mast cell counts will be determined by counting mast cells in the most inflamed high-power field (hpf) of each of the 3 esophageal (proximal, mid, distal) levels and reported as mast cells/hpf.
Percentage of patients with a negative provocation test for Cold Inducible Urticaria \[ColdU\] or Symptomatic Dermographism \[SD\]) at week 12 * For ColdU patients, a negative provocation test is defined as absence of wheals at the provocation site within 10 min at ≤ 4°C after provocation using TempTest® * For SD patients, a negative provocation test is defined as absence of wheals at the provocation site within 10 min at 0 pins after provocation using the FricTest®
Safety and tolerability of multiple dose levels of CDX-0159 as determined by drug related adverse events
Safety of a single dose of CDX-0159 as determined by adverse events
| Arm | Type | Description |
|---|---|---|
| barzolvolimab in patients with Cold Induced Urticaria | EXPERIMENTAL | barzolvolimab 450mg injection subcutaneously at randomization , then 150mg injection subcutaneously every 4 weeks for 24 weeks followed by 300mg barzolvolimab every 8 weeks for 28 weeks. |
| Placebo in patients with Cold Induced Urticaria | PLACEBO_COMPARATOR | Placebo injection subcutaneously every 4 weeks for 24 weeks followed by 300mg barzolvolimab every 8 weeks for 28 weeks. |
| barzolvolimab in patients with Symptomatic Dermographism | EXPERIMENTAL | barzolvolimab 450mg injection subcutaneously at randomization, then 150mg injection subcutaneously every 4 weeks for 24 weeks followed by 300mg barzolvolimab every 8 weeks for 28 weeks. |
| Placebo in patients with Symptomatic Dermographism | PLACEBO_COMPARATOR | Placebo injection subcutaneously every 4 weeks for 24 weeks followed by 300mg barzolvolimab every 8 weeks for 28 weeks. |
| Group 1 Observation Group | EXPERIMENTAL | Standard of care treatment (at least 2nd generation Type 1 antihistamines \[H1AH\] with or without other permitted background medications) for 52 weeks. For participants with worsening disease (UAS7 score of 16 or greater at any time between Weeks 0-24), barzolvolimab will be administered once as a 300 mg subcutaneous injection followed by 150 mg every 4 weeks for up to 52 weeks. |
| Group 2 Barzolvolimab Retreatment Group | EXPERIMENTAL | Barzolvolimab given once as a 300 mg subcutaneous injection followed by 150 mg administered every 4 weeks for 52 weeks |
| barzolvolimab 150 mg | EXPERIMENTAL | barzolvolimab given once as a 300 mg subcutaneous injection followed by 150 mg administered every 4 weeks for 52 weeks |
| barzolvolimab 300 mg | EXPERIMENTAL | barzolvolimab given once as a 450 mg subcutaneous injection followed by 300 mg administered every 8 weeks for 52 weeks |
| Placebo then barzolvolimab 150 mg | EXPERIMENTAL | 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. |
| Placebo then barzolvolimab 300 mg | EXPERIMENTAL | 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. |
| Barzolvolimab 450 mg, then 150 mg Q4W | EXPERIMENTAL | 450 mg subcutaneous administration loading dose on Day 1 followed by 150 mg subcutaneous administration every 4 weeks, starting on Week 4, to Week 24. |
| Barzolvolimab 450 mg, then 300 mg Q4W | EXPERIMENTAL | 450 mg subcutaneous administration loading dose on Day 1 followed by 300 mg subcutaneous administration every 4 weeks, starting on Week 4, to Week 24. |
| Placebo | PLACEBO_COMPARATOR | Matching placebo subcutaneous administration every 4 weeks, starting on Week 4, to Week 24. |
| Barzolvolimab (CDX-0159) | ACTIVE_COMPARATOR | 300 mg subcutaneous administration every 4 weeks through week 24 |
| Placebo then barzolvolimab (CDX-0159) 300mg | PLACEBO_COMPARATOR | Matching placebo subcutaneous administration every 4 weeks through week 16, then 300mg subcutaneous administration every 4 weeks through week 24 |
| barzolvolimab 150 mg in patients with Symptomatic Dermographism | EXPERIMENTAL | barzolvolimab 150 mg injection subcutaneous every 4 weeks for 20 weeks |
| barzolvolimab 300 mg in patients with Symptomatic Dermographism | EXPERIMENTAL | barzolvolimab 300 mg injection subcutaneous every 8 weeks for 20 weeks |
| Placebo Comparator in patients with Symptomatic Dermographism | PLACEBO_COMPARATOR | Placebo injection subcutaneous every 4 weeks for 20 weeks |
| barzolvolimab 150 mg in patients with Chronic Inducible Cold Urticaria | EXPERIMENTAL | barzolvolimab 150 mg injection subcutaneous every 4 weeks for 20 weeks |
| barzolvolimab 300 mg in patients with Chronic Inducible Cold Urticaria | EXPERIMENTAL | barzolvolimab 300 mg injection subcutaneous every 8 weeks for 20 weeks |
| Placebo Comparator in patients with Chronic Inducible Cold Urticaria | PLACEBO_COMPARATOR | Placebo injection subcutaneous every 4 weeks for 20 weeks |
| barzolvolimab 75 mg then 150 mg | EXPERIMENTAL | barzolvolimab 75 mg injection subcutaneous every 4 weeks for 16 weeks and then 150 mg injection subcutaneous every 4 weeks for 36 weeks |
| barzolvolimab 75 mg then 300 mg | EXPERIMENTAL | barzolvolimab 75 mg injection subcutaneous every 4 weeks for 16 weeks and then 300 mg injection subcutaneous every 8 weeks for 36 weeks |
| CDX-0159 1.5mg/kg | EXPERIMENTAL | CDX-0159 1.5mg/kg administered once |
| CDX-0159 3mg/kg | EXPERIMENTAL | CDX-0159 3.0 mg/kg administered once |
| CDX-0159 | EXPERIMENTAL | 20 patients with Cold Contact Urticaria, 10 patients with Symptomatic Dermographism, and 10 patients with Cholinergic Urticaria will be enrolled and treated with a single dose of CDX-0159 |
| Normal Saline | PLACEBO_COMPARATOR | Normal saline every 4-8 weeks |
| Name | Type | Description |
|---|---|---|
| Barzolvolimab | DRUG | Subcutaneous Administration |
| Matching Placebo | DRUG | Subcutaneous Administration |
| Standard of Care | OTHER | Observational/Standard of Care |
| CDX-0159 | BIOLOGICAL | administered intravenously |
| Normal saline | DRUG | administered intravenously |
Key Inclusion Criteria: 1. Males and females, \>/= 18 years of age. 2. Diagnosis of cold induced urticaria or symptomatic dermographism \>/= 3 months. 3. Diagnosis of cold induced urticaria or symptomatic dermographism despite the use of a stable regimen of second generation non-sedating H1-antihis...
Barzolvolimab is an investigational monoclonal antibody being studied for chronic spontaneous urticaria, chronic inducible urticaria including cold urticaria and symptomatic dermographism, atopic dermatitis, eosinophilic esophagitis, and prurigo nodularis. It is designed for patients whose symptoms are inadequately controlled by H1-antihistamines, and it remains in clinical development rather than approved for commercial use.
Barzolvolimab targets KIT, also known as CD117, the receptor tyrosine kinase that drives mast cell survival and activation. By binding KIT, the antibody is intended to reduce mast cell numbers and activity, which is the proposed mechanism behind its use in urticaria, atopic dermatitis, and other mast cell driven conditions.
Barzolvolimab is developed by Celldex Therapeutics, Inc., which trades on the Nasdaq under the ticker CLDX. Celldex is running the clinical program across dermatology and related indications, including the Phase 3 urticaria studies and a Phase 2 atopic dermatitis study.
Barzolvolimab is in Phase 3 development for chronic spontaneous urticaria and for chronic inducible urticaria, including cold urticaria and symptomatic dermographism, and in Phase 2 for atopic dermatitis. It is investigational and has not been approved by the FDA for any indication.
Barzolvolimab is being studied in four registered trials. These include NCT06455202, a Phase 3 chronic spontaneous urticaria study; NCT07256392, a Phase 3 long-term extension in chronic spontaneous urticaria; NCT07266402, a Phase 3 trial in cold induced urticaria and symptomatic dermographism; and NCT06727552, a Phase 2 atopic dermatitis study.
The barzolvolimab clinical program has a combined planned enrollment of about 3,517 participants across four trials. The largest is the Phase 3 long-term extension in chronic spontaneous urticaria with 1,370 participants, followed by the Phase 3 chronic spontaneous urticaria study with 976 and the Phase 3 cold urticaria and symptomatic dermographism study with 240.