A Phase 3 Study of Barzolvolimab in Participants With Chronic Spontaneous Urticaria (CSU)

Phase 3

Recruiting

• Conditions: Chronic Spontaneous Urticaria
• Interventions: Biological: barzolvolimab; Biological: Matching placebo

• Registration Number: NCT06455202
• Lead Sponsor: Celldex Therapeutics

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.

Study Timeline

• Study First Submitted: 2024-06-07
• Study First Submitted QC: 2024-06-07
• Study First Posted: 2024-06-12
• Study Start: 2024-07-19
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-23
• Last Update Posted: 2024-12-27
• Primary Completion: 2026-10
• Study Completion: 2027-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 915

Inclusion Criteria

1. Males and females, >/= 18 years of age.

2. Diagnosis of chronic spontaneous urticaria (CSU) >/= 6 months.

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 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

Read More

Exclusion Criteria

1. Women who are pregnant or nursing.
2. Chronic inducible urticaria that would confound the study endpoints.
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 2 months prior to study treatment (subjects must agree to avoid live vaccinations during the study). Inactivated vaccines are allowed such as seasonal influenza injection or 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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
barzolvolimab 150 mg	barzolvolimab	barzolvolimab given once as a 300 mg subcutaneous injection followed by 150 mg administered every 4 weeks for 52 weeks
Placebo then barzolvolimab 150 mg	Matching placebo	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	Matching placebo	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.
Placebo then barzolvolimab 300 mg	barzolvolimab	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 300 mg	barzolvolimab	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	barzolvolimab	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
Mean change from baseline in UAS7 at Week 24	From Day 1 (first dose) to Day 169 (Week 24)	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.
Mean change from baseline in UAS7 at Week 4	From Day 1 (first dose) to Day 29 (Week 4)	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.
Percentage of participants with UAS7 = 0 at Week 24	From Day 1 (first dose) to Day 169 (Week 24)	Proportion of participants who achieve complete absence of hives and itch (UAS7 = 0) at Week 24.
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.
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.
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.
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.
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.
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.

Trial Locations

Locations (46)

Allervie Clinical Research - Cullman; 🇺🇸 Cullman, Alabama, United States

Research Solutions of Arizona PC; 🇺🇸 Litchfield Park, Arizona, United States

Allergy and Asthma Associates of Southern Cal; 🇺🇸 Mission Viejo, California, United States

WR-MCCR; 🇺🇸 San Diego, California, United States

University Clinical Trials; 🇺🇸 San Diego, California, United States

Clinical Science Institute; 🇺🇸 Santa Monica, California, United States

Raffi Tachdjian MD, Inc; 🇺🇸 Santa Monica, California, United States

Asthma and Allergy Associates; 🇺🇸 Colorado Springs, Colorado, United States

ClearlyDerm Boca Raton - ClinEdge - PPDS; 🇺🇸 Boca Raton, Florida, United States

Dolphin Medical Research; 🇺🇸 Doral, Florida, United States

Midwest Clinical Research, LLC; 🇺🇸 Saint Louis, Missouri, United States

University of Texas Health McGovern Medical; 🇺🇸 Bellaire, Texas, United States

Western Sky Medical Research; 🇺🇸 El Paso, Texas, United States

Rainey & Finklea San Antonio Dermatology; 🇺🇸 San Antonio, Texas, United States

Kalo Clinical Research; 🇺🇸 West Valley City, Utah, United States

Novatrials; 🇦🇺 Kotara, New South Wales, Australia

Cornerstone Dermatology; 🇦🇺 Coorparoo, QSL, Australia

Ottawa Allergy Research Corporation; 🇨🇦 Ottawa, Ontario, Canada

Medical Research of Arizona a division of Allergy, Asthma, & Immunology, Assoc. Ltd.; 🇺🇸 Scottsdale, Arizona, United States

Center for Dermatology & Plastic Surgery; 🇺🇸 Scottsdale, Arizona, United States

Burke Pharmaceutical Research; 🇺🇸 Hot Springs, Arkansas, United States

California Allergy and Asthma Medical Group; 🇺🇸 Los Angeles, California, United States

LA Universal Research Center, Inc.; 🇺🇸 Los Angeles, California, United States

Clarity Dermatology, PLLC; 🇺🇸 Castle Rock, Colorado, United States

Driven Research LLC; 🇺🇸 Coral Gables, Florida, United States

Deluxe Health Center; 🇺🇸 Miami Lakes, Florida, United States

Revival Clinical Research; 🇺🇸 Orlando, Florida, United States

Allergy and Asthma Diagnostic treatment Center - CRN - PPDS; 🇺🇸 Tallahassee, Florida, United States

Advanced Clinical Research Institute (ACRI) - Florida; 🇺🇸 Tampa, Florida, United States

Lane Dermatology Research - Centricity - PPDS; 🇺🇸 Columbus, Georgia, United States

Treasure Valley Medical Research; 🇺🇸 Boise, Idaho, United States

The Indiana Clinical Trials Center, PC; 🇺🇸 Plainfield, Indiana, United States

South Bend Clinic; 🇺🇸 South Bend, Indiana, United States

Henry J. Kanarek - Allergy,Asthma&Immunology; 🇺🇸 Overland Park, Kansas, United States

Velocity Clinical Research - The Dermatology Clinic - Baton Rouge - PPDS; 🇺🇸 Baton Rouge, Louisiana, United States

Continental Clinical Research Solutions, LLC - ClinEdge - PPDS; 🇺🇸 Towson, Maryland, United States

Derm Institute of Western Michigan; 🇺🇸 Caledonia, Michigan, United States

Clarkston Skin Research - Clarkston; 🇺🇸 Clarkston, Michigan, United States

Grekin Skin Institute; 🇺🇸 Warren, Michigan, United States

Skin Specialists PC; 🇺🇸 Omaha, Nebraska, United States

OptiSkin Medical; 🇺🇸 New York, New York, United States

Optimed Research Ltd - ClinEdge - PPDS; 🇺🇸 Columbus, Ohio, United States

Clinical Partners LLC; 🇺🇸 Johnston, Rhode Island, United States

Austin Institute for Clinical Research, Inc.; 🇺🇸 Pflugerville, Texas, United States

Jordan Valley Dermatology Center-South Jordan; 🇺🇸 South Jordan, Utah, United States

Virginia Dermatology and Skin Cancer Center - Norfolk; 🇺🇸 Norfolk, Virginia, United States