Chronic Spontaneous Urticaria
Conditions
Keywords
CDX-0159, barzolvolimab, chronic spontaneous urticaria, CSU, urticaria activity score, itch severity score, hives severity score
Brief summary
The purpose of this study is to establish the efficacy, safety and tolerability of barzolvolimab in adult participants with Chronic Spontaneous Urticaria (CSU) inadequately controlled by non-sedating second generation H1-antihistamines in comparison to placebo.
Detailed description
This is a global, multicenter, randomized, double-blind, parallel group, placebo-controlled phase 3 study investigating the efficacy, safety and tolerability of barzolvolimab in adult participants with Chronic Spontaneous Urticaria (CSU) who are symptomatic despite treatment with non-sedating second generation H1-antihistamines at 1-4 times the locally approved dose. There is a screening period of up to 4 weeks, followed by a 24-week placebo-controlled treatment period, a 28-week active treatment period where all participants receive barzolvolimab followed by a 16-week treatment free period. Approximately 915 adult participants (610 in the active arms and 305 in the placebo arm) will be randomly assigned to the treatment arms.
Interventions
BIOLOGICALbarzolvolimab
Subcutaneous Administration
BIOLOGICALMatching placebo
Matching placebo Subcutaneous Administration
Sponsors
Celldex Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Males and females, \>/= 18 years of age. 2. Chronic spontaneous urticaria (CSU) \>/= 6 months prior to Screening (Visit 1). 3. CSU despite the use of a stable regimen of second generation non-sedating H1-antihistamine as defined by: 1. The presence of hives for \>/= 6 weeks at any time prior to Visit 1 despite the use of non-sedating H1-antihistamines. 2. Must be on a stable regimen of second generation non-sedating H1-antihistamine for \>/= 4 weeks prior to study treatment. 3. UAS7 of \>/= 16 and ISS7 of \>/= 8 during the 7 days prior to study treatment. 4. Normal blood counts and liver function tests. 5. Both males and females of child-bearing potential must agree to use highly effective contraceptives during the study and for 150 days after treatment. 6. Willing and able to complete a daily symptom electronic diary and comply with study visits. 7. Participants with and without prior biologic experience are eligible. Key
Exclusion criteria
1. Women who are pregnant or nursing. 2. Chronic urticaria whose predominant manifestation is due to CIndU. 3. Other diseases associated with urticaria. 4. Active pruritic skin condition in addition to CSU. 5. Medical condition that would cause additional risk or interfere with study procedures. 6. Known HIV, hepatitis B or hepatitis C infection. 7. Vaccination of a live vaccine within 30 days prior to Screening (Visit 1) (subjects must agree to avoid live vaccinations during the study). Inactivated vaccines are allowed such as seasonal influenza injection or authorized COVID-19 vaccine. 8. History of anaphylaxis 9. Prior treatment with barzolvolimab There are additional criteria that your study doctor will review with you to confirm you are eligible for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean change from baseline to Week 12 of UAS7 (Urticaria Activity Score) | From Day 1 (first dose) to Day 85 (Week 12) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean change from baseline to Week 12 of ISS7 (Itch Severity Score) | From Day 1 (first dose) to Day 85 (Week 12) | The ISS7 and HSS7 combined together make up the UAS7 scoring system to evaluate urticaria signs and symptoms. The ISS7 is the itch severity score for 7 days, the scores range from 0 to 21. |
| Mean change from baseline to Week 12 of HSS7 (Hives Severity Score) | From Day 1 (first dose) to Day 85 (Week 12) | The ISS7 and HSS7 combined together make up the UAS7 scoring system to evaluate urticaria signs and symptoms. The HSS7 score is the wheal/hives severity score for 7 days, the scores range from 0 to 21. |
| Percentage of patients with UAS7=0 at Week 12 | From Day 1 (first dose) to Day 85 (Week 12) | Proportion of participants who achieve complete absence of hives and itch (UAS7 = 0) at Week 12. |
| Percentage of participants with UAS7 ≤ 6 at Week 12 | From Day 1 (first dose) to Day 85 (Week 12) | Proportion of participants who achieve control of their urticaria signs and symptoms (UAS7≤6) at Week 12. |
| Percentage of participants with AAS7 > 0 at baseline with AAS7 = 0 at Week 12 | From Day 1 (first dose) to Day 85 (Week 12) | Proportion of participants with AAS7 \> 0 at Day 1 who achieved complete control (AAS7 = 0) at Week 12 Angioedema Activity Score over 7 days \[AAS7\] describes the effect of angioedema on five categories with 0 being none and 3 being most severe. The final score is calculated by adding together daily scores which can range from 0-15 for 7 days. The resulting maximum score is then 105. |
| Mean change from baseline in UAS7 in participants refractory to omalizumab treatment at Week 12 | From Day 1 (first dose) to Day 85 (Week 12) | Evaluate efficacy of barzolvolimab on urticaria activity as measured by urticaria activity score (UAS) in participants who did not respond to or did not tolerate omalizumab. 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. |
| Proportion of participants with UAS7 = 0 in participants refractory to omalizumab treatment at Week 12 | From Day 1 (first dose) to Day 85 (Week 12) | Proportion of participants who achieve complete absence of hives and itch (UAS7 = 0) at Week 12 in participants who did not respond to or did not tolerate omalizumab. |
| Incidence of Treatment-Emergent Adverse Events | From Day 1 (first dose) to Day 477 (Week 68) | Occurrence of treatment emergent adverse events and serious adverse events during the study. |
Countries
Australia, Bulgaria, Canada, Chile, Colombia, Croatia, Georgia, Germany, Hungary, India, Italy, Lithuania, Mexico, Netherlands, New Zealand, Poland, Slovakia, Spain, Thailand, Tunisia, United Kingdom, United States
Outcome results
None listed