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

Phase 3
Recruiting
Conditions
Chronic Spontaneous Urticaria
Interventions
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
915
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
barzolvolimab 150 mgbarzolvolimabbarzolvolimab given once as a 300 mg subcutaneous injection followed by 150 mg administered every 4 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.
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 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 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.
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
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 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.

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.

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.

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 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 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.

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.

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.

Trial Locations

Locations (148)

LEADER research

🇨🇦

Hamilton, Ontario, Canada

Allervie Clinical Research - Cullman

🇺🇸

Cullman, Alabama, United States

Research Solutions of Arizona PC

🇺🇸

Litchfield Park, Arizona, United States

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

Kern Research, Inc.

🇺🇸

Bakersfield, California, United States

California Allergy and Asthma Medical Group

🇺🇸

Los Angeles, California, United States

LA Universal Research Center, Inc.

🇺🇸

Los Angeles, California, 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

Clarity Dermatology, PLLC

🇺🇸

Castle Rock, Colorado, United States

Asthma and Allergy Associates

🇺🇸

Colorado Springs, Colorado, United States

ClearlyDerm Boca Raton - ClinEdge - PPDS

🇺🇸

Boca Raton, Florida, United States

Driven Research LLC

🇺🇸

Coral Gables, Florida, United States

Dolphin Medical Research

🇺🇸

Doral, Florida, United States

Deluxe Health Center

🇺🇸

Tampa, 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

Midwest Clinical Research, LLC

🇺🇸

Saint Louis, Missouri, 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

University of Texas Health McGovern Medical

🇺🇸

Bellaire, Texas, United States

Western Sky Medical Research

🇺🇸

El Paso, Texas, United States

Austin Institute for Clinical Research, Inc.

🇺🇸

Pflugerville, Texas, United States

Rainey & Finklea San Antonio Dermatology

🇺🇸

San Antonio, Texas, United States

Allergy Associates of Utah - Sandy

🇺🇸

Murray, Utah, United States

Jordan Valley Dermatology Center-South Jordan

🇺🇸

South Jordan, Utah, United States

Kalo Clinical Research

🇺🇸

West Valley City, Utah, United States

Virginia Dermatology and Skin Cancer Center - Norfolk

🇺🇸

Norfolk, Virginia, United States

Skin and Cancer Foundation - The Skin Hospital

🇦🇺

Darlinghurst, New South Wales, Australia

St George Dermatology and Skin Cancer Center

🇦🇺

Kogarah, New South Wales, Australia

Novatrials

🇦🇺

Kotara, New South Wales, Australia

Momentum Darlinghurst

🇦🇺

Sydney, New South Wales, Australia

Westmead Hospital

🇦🇺

Westmead, New South Wales, Australia

Cornerstone Dermatology

🇦🇺

Coorparoo, QSL, Australia

Box Hill Hospital

🇦🇺

Box Hill, Victoria, Australia

Dr Rodney Sinclair Pty Ltd

🇦🇺

East Melbourne, Victoria, Australia

The Alfred Hospital

🇦🇺

Melbourne, Victoria, Australia

Medical Centre Asklepii OOD

🇧🇬

Dupnitsa, Bulgaria

Medical Center - Pulmo 2018

🇧🇬

Haskovo, Bulgaria

Medical Center Medconsult Pleven

🇧🇬

Lovech, Bulgaria

Multiprofile Hospital for Active Treatment - Pazardzhik AD

🇧🇬

Pazardzhik, Bulgaria

Medical Center Prolet

🇧🇬

Ruse, Bulgaria

Medical Center Unimed EOOD

🇧🇬

Sevlievo, Bulgaria

Diagnostic-consultative center Ascendent EOOD

🇧🇬

Sofia, Bulgaria

Diagnostic and Consultative Center Aleksandrovska EOOD

🇧🇬

Sofia, Bulgaria

Diagnostic-Consultative Centre Convex EOOD

🇧🇬

Sofia, Bulgaria

Vida Clinical Research

🇨🇦

Edmonton, Alberta, Canada

North Bay Dermatology Centre

🇨🇦

North Bay, Ontario, Canada

Ottawa Allergy Research Corporation

🇨🇦

Ottawa, Ontario, Canada

York Dermatology Clinic & Research Centre

🇨🇦

Richmond Hill, Ontario, Canada

North York Research Inc.

🇨🇦

Toronto, Ontario, Canada

Joel Liem Medicine Professional Corporation

🇨🇦

Windsor, Ontario, Canada

Saskatoon Dermatology Centre

🇨🇦

Saskatoon, Saskatchewan, Canada

Clinica MEDS La Dehesa

🇨🇱

Lo Barnechea, Chile

Enroll SpA - Dr. Manuel Barros Borgono

🇨🇱

Providencia, Chile

Centro Internacional de Estudios Clinicos (CIEC)

🇨🇱

Recoleta, Chile

BIOCINETIC Ltda

🇨🇱

Santiago, Chile

Dermacross Clinica Dermatologica

🇨🇱

Vitacura, Chile

Centro de Inmunología y Genética - CIGE S.A.S

🇨🇴

Medellin, Colombia

LTD" Healthy Future"

🇬🇪

Tbilisi, Georgia

LTD "Center of Allergy and Immunology"

🇬🇪

Tbilisi, Georgia

David Abuladze Georgian Italian Clinic

🇬🇪

Tbilisi, Georgia

LTD "Multiprofile Clinic Consilium Medulla"

🇬🇪

Tbilisi, Georgia

Fachklinik Bad Bentheim

🇩🇪

Bad Bentheim, Germany

Emovis GmbH

🇩🇪

Berlin, Germany

Klinische Forschung Dresden GmbH

🇩🇪

Dresden, Germany

Universitätsklinikum Essen

🇩🇪

Essen, Germany

Eurofins bioskin Research Center Dermalology

🇩🇪

Hamburg, Germany

UKSH Lübeck, Institut für Entzündungsmedizin

🇩🇪

Lübeck, Germany

Hautarztpraxis Dariusch Mortazawi

🇩🇪

Remscheid, Germany

Universitäts-Hautklinik, Studienzentrum Immundermatologie

🇩🇪

Tübingen, Germany

Allergo-Derm Bakos Kft.

🇭🇺

Szolnok, Hungary

Nirmal Hospital PVT LTD

🇮🇳

Surat, Gujarat, India

Medical College Baroda & SSG Hospital

🇮🇳

Vadodara, Gujarat, India

Shree Hospital & Critical Care Centre

🇮🇳

Nagpur, Maharashtra, India

Assured Care Plus Hospital

🇮🇳

Nashik, Maharashtra, India

Oyster & Pearl Hospitals

🇮🇳

Pune, Maharashtra, India

Excelcare Hospital

🇮🇳

Jaipur, Rajasthan, India

G.S.V.M. Medical College - Kanpur

🇮🇳

Kanpur, Uttar Pradesh, India

B. J. Medical College and Civil Hospital

🇮🇳

Ahmedabad, India

K R Hospital

🇮🇳

Mysore, India

Asst Fbf Sacco

🇮🇹

Milano, Italy

AOU San Giovanni di Dio e Ruggi d'Aragona

🇮🇹

Salerno, Italy

CD8 Klinika

🇱🇹

Kaunas, Lithuania

UAB Ausros Medicinos Centras

🇱🇹

Kaunas, Lithuania

Santaros KTC (klinikiniu tyrimu centras)

🇱🇹

Vilnius, Lithuania

Bravis Hospital

🇳🇱

Roosendaal, Netherlands

University Medical Center Utrecht

🇳🇱

Utrecht, Netherlands

Klinika Dermatologii i Dermatologii Onkologicznej

🇵🇱

Częstochowa, Poland

Centrum Medyczne Pratia Częstochowa

🇵🇱

Częstochowa, Poland

Synexus Polska Sp. z o.o.

🇵🇱

Warszawa, Poland

Mazowieckie Centrum Badań Klinicznych SC IWONA CZAJKOWSKA ANNA PODRAZKA-SZCZEAPANIAK

🇵🇱

Grodzisk Mazowiecki, Poland

Centrum Medyczne "All-Med" Badania Kliniczne

🇵🇱

Kraków, Poland

Velocity Nova Sp. z o.o.

🇵🇱

Lublin, Poland

Pro Life Medica ETG Lublin

🇵🇱

Lublin, Poland

LUXDERM Specjalistyczny Gabinet Dermatologiczny Prof. dr hab. n. med. Dorota Krasowska

🇵🇱

Lublin, Poland

Medicome Sp. Z O.O.

🇵🇱

Oświęcim, Poland

Centrum Alergologii Teresa Hofman Sp. z.o.o.

🇵🇱

Poznań, Poland

Specjalistyczny Niepubliczny Zaklad Opieki Zdrowotnej Alergologia Plus Osrodek Diagnostyki I Terapii Uczulen

🇵🇱

Poznań, Poland

Uniwersytecki Szpital Kliniczny im. Fryderka Chopina w Rzeszowie Klinika Dermatologii i Dermatologii Onkologicznej

🇵🇱

Rzeszów, Poland

EMED Centrum Usług Medycznych Ewa Śmiałek

🇵🇱

Rzeszów, Poland

ALERGO-MED SPECJALISTYCZNA PRZYCHODNIA LEKARSKA Spolka. z o. o.

🇵🇱

Tarnów, Poland

Medicover Integrated Clinical Services Sp. z o.o. Centrum Medyczne Warszawa

🇵🇱

Warszawa, Poland

ETG Warszawa

🇵🇱

Warszawa, Poland

Cliniq s.r.o.

🇸🇰

Bratislava, Slovakia

Derma therapy spol. s.r.o.

🇸🇰

Bratislava, Slovakia

ALERSA, sro

🇸🇰

Košice, Slovakia

Hospital del Mar

🇪🇸

Barcelona, Spain

Hospital Universitari Puerta del Mar

🇪🇸

Cadiz, Spain

Hospital Universitario de La Princesa

🇪🇸

Madrid, Spain

Clinica Universidad Navarra- Madrid

🇪🇸

Madrid, Spain

Hospital 12 De Octubre

🇪🇸

Madrid, Spain

Hospital Universitario Fundación Alcorcón

🇪🇸

Madrid, Spain

Clinica Universidad Navarra- Pamplona

🇪🇸

Pamplona, Spain

Complejo Hospitalario Universitario de Pontevedra- Centro Especialidades de Mollabao

🇪🇸

Pontevedra, Spain

Hospital Quironsalud Madrid

🇪🇸

Pozuelo De Alarcón, Spain

Hospital universitario Virgen Macarena

🇪🇸

Sevilla, Spain

FutureMeds Sevilla

🇪🇸

Sevilla, Spain

Hospital Universitario de Torrejón

🇪🇸

Torrejón De Ardoz, Spain

Hospital Universitari i Politecnic La Fe de Valencia

🇪🇸

Valencia, Spain

Hospital de Manises

🇪🇸

Valencia, Spain

Siriraj Hospital

🇹🇭

Bangkok Noi, Thailand

Maharaj Nakorn Chiang Mai Hospital

🇹🇭

Chiang Mai, Thailand

Thammasat University Hospital

🇹🇭

Khlong Luang, Thailand

Khon Kaen University

🇹🇭

Khon Kaen, Thailand

Cambridge University Hospitals, Addenbrooke's Hospital

🇬🇧

Cambridge, United Kingdom

Queen Elizabeth University Hospital

🇬🇧

Glasgow, United Kingdom

The Royal London Hospital

🇬🇧

London, United Kingdom

Velocity Clinical Research, North London - PPDS

🇬🇧

North Finchley, United Kingdom

University Hospitals Plymouth NHS Trust

🇬🇧

Plymouth, United Kingdom

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