A Study to Investigate Efficacy, Safety and Tolerability of Barzolvolimab Versus Placebo in Adults With Cold Induced Urticaria and Symptomatic Dermographism Inadequately Controlled by H1-antihistamines (EMBARQ - ColdU and SD)

Official title

A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group Study of Barzolvolimab in Participants With Cold Induced Urticaria and Symptomatic Dermographism (EMBARQ-COLDU and SD)

Overview

The purpose of this Phase 3, randomized, double-blind, placebo-controlled study is to assess the activity and safety of barzolvolimab compared to placebo in participants with cold induced urticaria or symptomatic dermographism who remain symptomatic despite the use of H1-antihistamines.

Detailed description

The purpose of this Phase 3, randomized, double-blind, placebo-controlled study is to assess the activity and safety of barzolvolimab compared to placebo in participants with cold induced urticaria (ColdU) or symptomatic dermographism (SD) who remain symptomatic despite the use of H1-antihistamines.

There is a Screening Period of up to 4 weeks, followed by a 24-week treatment period where patients will receive barzolvolimab or placebo. Patients receiving barzolvolimab will receive 450mg at the start of the treatment period and then 150mg every 4 weeks. Then there is a 28-week treatment period where all patients will receive 300mg barzolvolimab every 8 weeks, followed by a 16-week follow-up period where all patients are observed.

Interventions

• Drug Barzolvolimab
  Subcutaneous Administration
• Drug Matching Placebo
  Subcutaneous Administration

Primary outcome measures

• Complete response to provocation testing at Week 12 [Time frame: From Day 1 (first dose) to Week 12]

Secondary outcome measures (12)

• Complete response to provocation testing at Week 24 for Cold Induced Urticaria participants [Time frame: From Day 1 (first dose) to Week 24]
• Complete response to provocation testing at Week 24 for Symptomatic Dermographism [Time frame: From Day 1 (first dose) to Week 24]
• Improvement in clinical symptoms of itch at Week 12 [Time frame: From Day 1 (first dose) to Week 12]
• Improvement in clinical symptoms of itch at Week 24 [Time frame: From Day 1 (first dose) to Week 24]
• Improvement in clinical symptoms of itch following provocation testing (WI-NRSprovo) at Week 12 [Time frame: From Day 1 (first dose) to Week 12]
• Complete response to provocation testing at Week 4 [Time frame: From Day 1 (first dose) to Week 4]
• Improvement in clinical symptoms of hives at Week 12 [Time frame: From Day 1 (first dose) to Week 12]
• Improvement in clinical symptoms of hives at Week 24 [Time frame: From Day 1 (first dose) to Week 24]
• Change from baseline in Critical Temperature Threshold (CTT) at Week 12 [Time frame: From Day 1 (first dose) to Week 12]
• Change from baseline in Critical Friction Threshold (CFT) at Week 12 [Time frame: From Day 1 (first dose) to Week 12]
• Change from baseline in Critical Temperature Threshold (CTT) at Week 24 [Time frame: From Day 1 (first dose) to Week 24]
• Change from baseline in Critical Friction Threshold (CFT) at Week 24 [Time frame: From Day 1 (first dose) to Week 24]

Eligibility criteria

Inclusion criteria

• Males and females, >/= 18 years of age.
• Diagnosis of cold induced urticaria or symptomatic dermographism >/= 3 months.
• Diagnosis of cold induced urticaria or symptomatic dermographism despite the use of a stable regimen of second generation non-sedating H1-antihistamine as defined by:

• The presence of hives for >/= 6 weeks at any time prior to Visit 1 despite the use of H1-antihistamines.
• Must be on a stable regimen of second generation non-sedating H1-antihistamine for >/= 4 weeks prior to study treatment.
• Cold induced urticaria: A Critical Threshold Temperature (CTT) of ≥ 15 °C and < 37 °C using the TempTest® and a numerical rating scale score of ≥ 5 for itch after the provocation test.
• Symptomatic dermographism: A Critical Friction Threshold (CFT) of ≥ 3 using the FricTest® and a numerical rating scale score of ≥ 5 for itch after the provocation test.
• Cold induced urticaria: Positive ice-cube test resulting in hives at the provocation site during Screening
• Normal blood counts and liver function tests.
• Both males and females of child-bearing potential must agree to use highly effective contraceptives during the study and for ≥ 150 days after treatment.
• Willing and able to complete a daily symptom electronic diary and comply with study visits.
• Participants with and without prior biologic experience are eligible.

Exclusion criteria

• Women who are pregnant or nursing.
• Clearly defined cause for chronic urticaria.
• Active, pruritic skin condition in addition to cold induced urticaria or symptomatic dermographism.
• Medical condition that would cause additional risk or interfere with study procedures.
• Known HIV, hepatitis B or hepatitis C infection.
• Vaccination with a live vaccine within 30 days prior to screening (subjects must agree to avoid vaccination with a live vaccine during the study). Inactivated vaccines are allowed such as seasonal influenza injection or COVID-19 vaccine.
• History of anaphylaxis, unless due to cold exposure over a large part of the body (such as swimming in cold water).
• Prior treatment with barzolvolimab

There are additional criteria that your study doctor will review with you to confirm you are eligible for the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 26 centers

• Cahaba Dermatology & Skin Health Center, LLC — Birmingham
• One of a Kind Clinical Research Center, LLC — Scottsdale
• Kern Research, Inc. — Bakersfield
• One of a Kind Clinical Research Center — Napa
• Allergy & Asthma Consultants — Redwood City
• Amicis Research Center — Sherman Oaks
• FOMAT - Allergy, Asthma & Immunology Medical Group — Ventura
• Direct Helpers Research Center — Hialeah
• … and 18 more centers

Germany · 14 centers

• Universitätsklinikum Augsburg, Klinik für Dermatologie und Allergologie — Augsburg
• Fraunhofer-Institut für Translationale Medizin und Pharmakologie ITMP Immunologie und Alle — Berlin
• Elbe Kliniken Buxtehude Dermatologie — Buxtehude
• Rosenpark Research GmbH — Darmstadt
• Universitätsklinikum Carl Gustav Carus Dresden, Klinik und Poliklinik für Dermatologie — Dresden
• Department of Dermatology, University Hospital Dusseldorf — Düsseldorf
• Hautklinik, Uniklinkum Erlangen — Erlangen
• Universitätsklinikum Göttingen -- George-August-Universitat Göttinggen, Klinik für Dermato — Göttingen
• … and 6 more centers

Poland · 14 centers

• Synexus Polska Sp. z o.o. Oddział w Gdańsku — Gdansk
• Centrum Badań Klinicznych PI-House Sp. z o.o. — Gdansk
• Centrum Medyczne ALL-MED Badania Kliniczne — Krakow
• Centrum Nowoczesnych Terapii Dobry Lekarz Sp. z o.o. — Krakow
• Oddzial Kliniczny Chorob Wewnetrznych, Astmy i Alergii z Odcinkiem dla Dzieci, Uniwersytec — Lodz
• Santa Familia PTG Lodz — Lodz
• Luxderm Specjalistyczny Gabinet Dermatologiczny Prof. dr hab. N. med. Dorota Krasowska — Lublin
• Uniwersytecki Szpital Kliniczny w Opolu — Opole
• … and 6 more centers

South Africa · 9 centers

• Worthwhile Clinical Trials — Benoni
• Allergy & Immunology Unit, University of Cape Town Lung Institute — Cape Town
• Dr. PJ Sebastian — Durban
• Infinity Dermatology Inc — Durban
• Synapta Clinical Research Centre — Durban
• Newtown Clinical Research Centre — Johannesburg
• Sandton Medical Research Centre — Johannesburg
• Global Clinical Trials (Pty) Ltd — Pretoria
• … and 1 more center

Lithuania · 4 centers

• CD8 Klinika — Kaunas
• UAB Ausros Medicinos Centras — Kaunas
• Santaros KTC (klinikiniu tyrimu centras) — Vilnius
• UAB Alerginių susirgimų diagnostikos ir gydymo centras — Vilnius

United Kingdom · 3 centers

• Addenbrooke's Hospital — Cambridge
• Queen Elizabeth University Hospital — Glasgow
• Salford Care Organisation NCA NHS Trust — Manchester

Spain · 2 centers

• Hospital del Mar — Barcelona
• Clinica Universidad de Navarra — Pamplona

Identifiers

NCT: NCT07266402 · CDX0159-16

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗