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

Phase 3
Recruiting
Conditions
Chronic Spontaneous Urticaria
Interventions
Biological: barzolvolimab
Biological: Matching placebo
Registration Number
NCT06445023
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.

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
GroupInterventionDescription
Placebo then barzolvolimab 150 mgbarzolvolimabPlacebo 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 mgbarzolvolimabPlacebo 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 150 mgbarzolvolimabbarzolvolimab given once as a 300 mg subcutaneous injection followed by 150 mg administered every 4 weeks for 52 weeks
barzolvolimab 300 mgbarzolvolimabbarzolvolimab given once as a 450 mg subcutaneous injection followed by 300 mg administered every 8 weeks for 52 weeks
Placebo then barzolvolimab 150 mgMatching placeboPlacebo 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 mgMatching placeboPlacebo injection subcutaneous every 4 weeks for 24 weeks and then barzolvolimab 450 mg followed by 300 mg administered every 8 weeks for 28 weeks.
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
Percentage of participants with UAS7 = 0 at Week 12From 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 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 participants with UAS7 ≤ 6 at Week 12From 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.

Mean change from baseline in UAS7 at Week 4From 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.

Proportion of participants with UAS7 = 0 in participants refractory to omalizumab treatment at Week 12From 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 in participants refractory to omalizumab treatment at Week 12From 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.

Mean change from baseline in UAS7 at Week 24From 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.

Incidence of Treatment-Emergent Adverse EventsFrom 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.

Percentage of participants with UAS7 = 0 at Week 24From 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.

Trial Locations

Locations (70)

Laser Clinic S.C

🇵🇱

Szczecin, Poland

Klinika Ambroziak Dermatologia

🇵🇱

Warsaw, Poland

Diagnostic Consultative Center Pulmed

🇵🇱

Wrocław, Poland

EuroMediCare Szpital Specjalistyczny z Przychodnia we Wroclawiu

🇵🇱

Wrocław, Poland

Santa Familia PTG Łódź

🇵🇱

Łódź, Poland

Hospital Universitari Vall d'Hebron

🇪🇸

Barcelona, Spain

Future Meds Madrid

🇪🇸

Madrid, Spain

Endeavor Health

🇺🇸

Skokie, Illinois, United States

DermAssociates, LLC

🇺🇸

Rockville, Maryland, United States

Bernstein Clinical Research Center, LLC

🇺🇸

Cincinnati, Ohio, United States

Dermatologie Maldegem

🇧🇪

Maldegem, Belgium

Aipsimpa D-R Talyat Sali Cholak Eood

🇧🇬

Razgrad, Bulgaria

Medical Center Hera EOOD

🇧🇬

Sofia, Bulgaria

Medical Center "Zara-Med" EOOD

🇧🇬

Stara Zagora, Bulgaria

Sanatorium profesora Arenbergera

🇨🇿

Praha 1, Czechia

Kožní ambulance Fialová, s.r.o.

🇨🇿

Praha 6, Czechia

Praxis Dr. Beate Schwarz

🇩🇪

Langenau, Baden-Württemberg, Germany

ProDerma

🇩🇪

Dülmen, Nordrhein-Westfalen, Germany

Medizinisches Versorgungszentrum DermaKiel GmbH

🇩🇪

Kiel, Schleswig-Holstein, Germany

Naval Hospital of Athens

🇬🇷

Athens, Greece

Andreas Syggros Hospital

🇬🇷

Athens, Greece

General Hospital of Thessaloniki 'Papageorgiou'

🇬🇷

Thessaloníki, Greece

"SYNEXUS POLSKA" sp. z o.o. Odział w Katowicach

🇵🇱

Katowice, Poland

Hospital Universitario de la Plana

🇪🇸

Villareal, Spain

Cahaba Dermatology Skin Health Center

🇺🇸

Birmingham, Alabama, United States

Clear Dermatology & Aesthetics Center Scottsdale

🇺🇸

Scottsdale, Arizona, United States

First OC Dermatology - Fountain Valley

🇺🇸

Fountain Valley, California, United States

Dermatology Research Associates

🇺🇸

Los Angeles, California, United States

Cura Clinical Research

🇺🇸

Oxnard, California, United States

Allergy and Asthma Consultants

🇺🇸

Redwood City, California, United States

West Dermatology Research Center

🇺🇸

San Diego, California, United States

Therapeutics Clinical Research

🇺🇸

San Diego, California, United States

Integrated Research of Inland, Inc.

🇺🇸

Upland, California, United States

Western States Clinical Research Inc

🇺🇸

Wheat Ridge, Colorado, United States

Encore Medical Research Boynton Beach

🇺🇸

Boynton Beach, Florida, United States

Florida Academic Centers Research

🇺🇸

Coral Gables, Florida, United States

Direct Helpers Research Center

🇺🇸

Hialeah, Florida, United States

GSI Clinical Research

🇺🇸

Margate, Florida, United States

International Dermatology Research Inc - Miami

🇺🇸

Miami, Florida, United States

Miami Dade Medical Research Institute, LLC

🇺🇸

Miami, Florida, United States

GCP Global Clinical Professionals, LLC

🇺🇸

Saint Petersburg, Florida, United States

Sarasota Clinical Research

🇺🇸

Sarasota, Florida, United States

Alliance Clinical Research of Tampa

🇺🇸

Tampa, Florida, United States

DS Research - 1005 E. Lewis & Clark Pkwy Indiana Location

🇺🇸

Clarksville, Indiana, United States

Dawes Fretzin Clinical Research Group-7910 N Shadeland Ave

🇺🇸

Indianapolis, Indiana, United States

DS Research of Kentucky, LLC

🇺🇸

Louisville, Kentucky, United States

Allergy and Asthma Specialists PSC

🇺🇸

Owensboro, Kentucky, United States

Clinical Trials Management LLC - Southshore Office

🇺🇸

Metairie, Louisiana, United States

Institute For Asthma and Allergy

🇺🇸

Wheaton, Maryland, United States

David Fivenson MD Dermatolgy PLLC

🇺🇸

Ann Arbor, Michigan, United States

Oakland Hills Dermatology

🇺🇸

Auburn Hills, Michigan, United States

Resp Medicine Research Institute of MI

🇺🇸

Ypsilanti, Michigan, United States

Dermatolgy and Skin Cancer Center

🇺🇸

Lee's Summit, Missouri, United States

MediSearch, LLC

🇺🇸

Saint Joseph, Missouri, United States

Montana Medical Research

🇺🇸

Missoula, Montana, United States

Smith Allergy & Asthma Specialists of Central New York

🇺🇸

Cortland, New York, United States

Sadick Research Group

🇺🇸

New York, New York, United States

Bexley Dermatology Research

🇺🇸

Bexley, Ohio, United States

Auni Allergy

🇺🇸

Findlay, Ohio, United States

Apex Clinical Research Center

🇺🇸

Mayfield Heights, Ohio, United States

Toledo Institute of Clinical Research

🇺🇸

Toledo, Ohio, United States

Southern Plains Medical Center - Chickasha

🇺🇸

Oklahoma City, Oklahoma, United States

Portland Allergy and Asthma

🇺🇸

Clackamas, Oregon, United States

Oregon Medical Research Center

🇺🇸

Portland, Oregon, United States

Clinical Research Philadelphia, LLC

🇺🇸

Philadelphia, Pennsylvania, United States

National Allergy and Asthma Research, LLC - CRN - PPDS

🇺🇸

North Charleston, South Carolina, United States

Alina Clinical Trials

🇺🇸

Dallas, Texas, United States

VAST Clinical Research - Plano

🇺🇸

Plano, Texas, United States

Allergy and Asthma Care of Waco

🇺🇸

Waco, Texas, United States

Premier Clinical Research

🇺🇸

Spokane, Washington, United States

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