A Study of CDX-0159 in Patients With Chronic Inducible Urticaria

: A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Dose-ranging Study to Assess the Efficacy and Safety of CDX-0159 in Patients With Chronic Inducible Urticaria

The purpose of this study is to assess the clinical effect, the pharmacodynamics, the safety, and the pharmacokinetics of barzolvolimab (CDX-0159) in patients with Chronic Inducible Urticaria who remain symptomatic despite the use of H1-antihistamines.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Inducible Urticaria
• Intervention / Treatment: Biological: barzolvolimab; Drug: Matching Placebo

Detailed Description

The purpose of this study is to assess the clinical effect, the pharmacodynamics, the safety, and the pharmacokinetics of barzolvolimab in patients with Chronic Inducible Urticaria (Cold 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 20-week treatment period where patients will receive either barzolvolimab 150mg, 300mg or placebo, and then a 24-week follow up period where all patients are observed.

• Study Type: Interventional
• Enrollment (Actual): 196
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Celldex Therapeutics; Phone Number: 844-723-9363; Email: info@celldex.com

Study Locations

• Bulgaria
  • Razgrad, Bulgaria, 7200
    • Outpatient Clinic for Individual Practice for Specialized Outpatient
  • Sofia, Bulgaria, 1504
    • Medical Center Iskar- EOOD Office of Clinical Allergology
  • Sofia, Bulgaria
    • "Medical Center Ekselsior" OOD
  • Sofia, Bulgaria
    • "University Multiprofile Hospital for Active Treatment 'Aleksandrovska" EAD, Clinic of Clinical Allergology
  • Sofia, Bulgaria
    • Medical Center "SYNEXUS SOFIA", EOOD
  • Stara Zagora, Bulgaria
    • University Multiprofile Hospital for Active Treatment "Prof. Dr. Stoyan Kirkovich" AD
• Estonia
  • Tallinn, Estonia, 10134
    • Vahlberg & Pild Clinic
  • Tallinn, Estonia, 11312
    • East Tallin Central Hospital
• Georgia
  • Batumi, Georgia, 6000
    • High Technology Hospital Medcenter
  • Tbilisi, Georgia, 0186
    • Multiprofile Clinic Consilium Medulla
  • Tbilisi, Georgia, 0159
    • Center of Allergy and Immunology
  • Tbilisi, Georgia, 0119
    • Healthy Future
• Germany
  • Berlin, Germany, 12203
    • Institute of Allergology IFA
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg - Dermatologie
  • Bayern
    • Augsburg, Bayern, Germany, 86179
      • Universitätsklinikum Augsburg
    • München, Bayern, Germany, 80337
      • LMU Klinikum - Klinik und Poliklinik für Dermatologie und Allergologie DASZ-Dermato-Allergologisches Studien Zentrum
  • Hessen
    • Marburg, Hessen, Germany, 35043
      • Universitaetsklinikum Giessen u. Marburg GmbH
  • Niedersachsen
    • Buxtehude, Niedersachsen, Germany, 21614
      • Elbe Klinikum Buxtehude
    • Hannover, Niedersachsen, Germany, 30625
      • Hannover Medical University
    • Oldenburg, Niedersachsen, Germany, 26133
      • Klinikum Oldenburg gGmbH - Klinik f. Dermatologie u. Allergologie
  • Nordrhein-Westfalen
    • Düsseldorf, Nordrhein-Westfalen, Germany, 40225
      • Universitätsklinikum Düsseldorf - Dermatologie
    • Essen, Nordrhein-Westfalen, Germany, 45122
      • Universitätsklinikum Essen Klinikum f. Dermatologie, Venerologie u. Allergologie Hufelandstr
    • Münster, Nordrhein-Westfalen, Germany, 48149
      • Universitätsklinikum Münster Klinik u. Poliklinik f. Dermatologie
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Universitätsklinikum Dresden
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Universitätsklinikum Schleswig-Holstein - Zentrum für entzündliche Hauterkrankungen
• Hungary
  • Budapest, Hungary, 1085
    • Semmelweis Egyetem, ÁOK, Bőr-, Nemikórtani és Bőronkológiai Klinika
  • Budapest, Hungary
    • Semmelweis Egyetem, ÁOK, Bőr-, Nemikórtani és Bőronkológiai Klinika
  • Debrecen, Hungary, H-4032
    • Debreceni Egyetem Klinikai Központ (DEKK), Bőrgyógyászati Klinika
  • Szolnok, Hungary, 5000
    • Allergo-Derm Bakos Kft
  • Zalaegerszeg, Hungary, 8900
    • Óbudai Egészségügyi Centrum
• Latvia
  • Balvi, Latvia, LV-4501
    • Balvi and Gulbene Hospital Union
  • Riga, Latvia, LV-1002
    • Pauls Stradins Clinical University Hospital
  • Riga, Latvia, LV-1004
    • "LOR" Clinic
  • Riga, Latvia, LV-1004
    • Children Clinical University Hospital
  • Riga, Latvia, LV-1010
    • Consilium Medicum
• Lithuania
  • Kaunas, Lithuania, 49387
    • JSC Ausros Medicinos Centras
  • Vilnius, Lithuania, 08406
    • JSC Inlita
  • Vilnius, Lithuania, LT-09109
    • Center of Allergy Diagnosis and Treatment
• Poland
  • Krakow, Poland, 30-363
    • Centrum Medyczne Plejady
  • Krakow, Poland, 31-624
    • Malopolskie Centrum Alergologii
  • Lodz, Poland, 90-153
    • Uniwersytecki Szpital Kliniczny nr 1 w Lodzi
  • Lublin, Poland, 20-573
    • Luxderm Specjalistyczny Gabinet Dermatologiczny Prof. Doroty Krasowskiej
  • Opole, Poland, 45-401
    • Uniwersytecki Szpital Kliniczny w Opolu, Pododdział Chorób Wewnętrznych i Alergologii
  • Oświęcim, Poland, 32600
    • Medicome Sp. z o.o.
  • Torun, Poland, 87-100
    • Medicover Integrated Clinical Services Sp. zo.o.
  • Warsaw, Poland, 02-953
    • Klinika Ambroziak Sp. Z O.O.
• South Africa
  • Free State
    • Bloemfontein, Free State, South Africa, 9324
      • Iatros International
  • Gauteng
    • Benoni, Gauteng, South Africa, 1500
      • Worthwhile Clinical Trials
    • Johannesburg, Gauteng, South Africa, 2113
      • Newtown Clinical Research
    • Lenasia, Gauteng, South Africa, 1827
      • Ubuntu Clinical Research
    • Vereeniging, Gauteng, South Africa, 1935
      • FCRN Clinical Trial Centre Vaal Triangle
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4001
      • Synapta Clinical Research
    • Durban, KwaZulu-Natal, South Africa, 4092
      • Dr Pj Sebastian
  • Mowbray
    • Cape Town, Mowbray, South Africa, 7700
      • The University of Cape Town - Lung Institute
• Spain
  • Alicante, Spain, 03010
    • HGU de Alicante
  • Barcelona, Spain, 8907
    • Hospital Bellvitge
  • Barcelona, Spain, 9035
    • Hospital Vall d´ Hebron
  • Madrid, Spain, 28027
    • Universidad de Navarra
  • Málaga, Spain, 29009
    • Hospital Regional Universitario de Málaga
  • Valencia, Spain, 46015
    • Hospital Arnau de Vilanova
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Clinical Research Center of Alabama
    • Montgomery, Alabama, United States, 36106
      • Allervie Clinical Research
  • Arizona
    • Paradise Valley, Arizona, United States, 85253
      • One of a Kind Clinical Research Center, LLC
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Little Rock Allergy & Asthma CRC
  • California
    • Bakersfield, California, United States, 93301
      • Kern Research, Inc
    • Redwood City, California, United States, 94063
      • Allergy & Asthma Consultants
  • Colorado
    • Centennial, Colorado, United States, 80112
      • IMMUNOe Research Centers
  • Florida
    • Sarasota, Florida, United States, 34239
      • Sarasota Clinical Research
  • Idaho
    • Boise, Idaho, United States, 83706
      • Treasure Valley Medical Research
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Dawes Fretzin Dermatology Group, LLC
  • Kentucky
    • Owensboro, Kentucky, United States, 42301
      • Allergy & Asthma Specialists, PSC
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Institute for Asthma and Allergy, PC/Department of Clinical Research
  • Michigan
    • Ypsilanti, Michigan, United States, 48197
      • Respiratory Medicine Research Institute of Michigan, PLC
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
  • Texas
    • Kerrville, Texas, United States, 78028
      • Allergy Partners of Kerrville
  • Utah
    • Murray, Utah, United States, 84107
      • Allergy Associates of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key inclusion criteria:

1. Males and females, >/= 18 years of age.
2. Diagnosis of chronic ColdU or SD >/= 3 months.

3. Diagnosis of ColdU or SD despite the use of a stable regimen of second generation non-sedating H1-antihistamine as defined by:

   1. Recurrent pruritic wheals with or without angioedema due to ColdU or SD for >/= 6 weeks at any time prior to Visit 1 despite the use of H1-antihistamines.
   2. Must be on a stable regimen of second generation non-sedating H1-antihistamine for >/= 4 weeks prior to study treatment and agree to stay on through trial.
   3. UCT < 12 during the 14 days prior to treatment.

4. Positive provocation test

   1. for ColdU patients: developing a wheal at the test site within 10 min after using TempTest® at any temperature at both screening (Visit 1) and randomization (Visit 3)
   2. for SD patients: developing a wheal at the test site within 10 min after using FricTest® with ≥ 3 pins at both screening (Visit 1) and randomization (Visit 3)
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.

Key exclusion criteria:

1. Women who are pregnant or nursing.
2. Active Chronic spontaneous urticaria or other forms of CIndU besides ColdU or SD that may interfere with study assessments.
3. Active, pruritic skin condition in addition to CIndU.
4. Medical condition that would cause additional risk or interfere with study procedures.
5. Known active HIV, hepatitis B or hepatitis C infection.
6. Vaccination of a live vaccine within 2 months prior to study treatment (subjects must agree to avoid vaccination during the study). Inactivated vaccines are allowed such as seasonal influenza injection or COVID-19 vaccine.
7. History of anaphylaxis

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: barzolvolimab 150 mg in patients with Symptomatic Dermographism; barzolvolimab 150 mg injection subcutaneous every 4 weeks for 20 weeks	Biological: barzolvolimab; Subcutaneous Administration; Other Names: CDX-0159
Experimental: barzolvolimab 300 mg in patients with Symptomatic Dermographism; barzolvolimab 300 mg injection subcutaneous every 8 weeks for 20 weeks	Biological: barzolvolimab; Subcutaneous Administration; Other Names: CDX-0159
Placebo Comparator: Placebo Comparator in patients with Symptomatic Dermographism; Placebo injection subcutaneous every 4 weeks for 20 weeks	Drug: Matching Placebo; Subcutaneous Administration
Experimental: barzolvolimab 150 mg in patients with Chronic Inducible Cold Urticaria; barzolvolimab 150 mg injection subcutaneous every 4 weeks for 20 weeks	Biological: barzolvolimab; Subcutaneous Administration; Other Names: CDX-0159
Experimental: barzolvolimab 300 mg in patients with Chronic Inducible Cold Urticaria; barzolvolimab 300 mg injection subcutaneous every 8 weeks for 20 weeks	Biological: barzolvolimab; Subcutaneous Administration; Other Names: CDX-0159
Placebo Comparator: Placebo Comparator in patients with Chronic Inducible Cold Urticaria; Placebo injection subcutaneous every 4 weeks for 20 weeks	Drug: Matching Placebo; Subcutaneous Administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with a negative provocation test at week 12	Percentage of patients with a negative provocation test for Cold Inducible Urticaria [ColdU] or Symptomatic Dermographism [SD]) at week 12; For ColdU patients, a negative provocation test is defined as absence of wheals at the provocation site within 10 min at ≤ 4°C after provocation using TempTest®; For SD patients, a negative provocation test is defined as absence of wheals at the provocation site within 10 min at 0 pins after provocation using the FricTest®	From baseline to week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in provocation threshold and itch for ColdU	Mean change from baseline to week 12 in critical temperature threshold (CTT) in patients with ColdU CTT is defined as threshold temperature at which wheals are triggered (highest temperature for cold), assessed at the 10-minute mark	From baseline to week 12
Change in provocation threshold for SD	Mean change from baseline to Week 12 in Critical Friction Threshold (CFT) in patients with SD CFT is the threshold pin number at which wheals are triggered, assessed at the 10-minute mark	From baseline to week 12
Change in worst itch reported after provocation for ColdU	Mean change in worst itch reported by numerical rating scale after provocation testing from baseline to week 12 in patients with ColdU	From baseline to week 12
Combined patients with a negative provocation test at week 12	Percentage of combined patients with a negative TempTest (ColdU) or FricTest (SD) at week 12	From baseline to week 12
Change in worst itch reported after provocation for SD	Mean change in worst itch reported by numerical rating scale after provocation testing from baseline to week 12 in patients with SD	From baseline to week 12
Change in worst itch reported after provocation in both SD and ColdU	Mean change in worst itch reported by numerical rating scale after provocation testing from baseline to week 12 in patients with SD and ColdU combined	From baseline to week 12
Percentage of patients experiencing adverse events	Percentage of patients experiencing treatment-emergent adverse events (TEAE) examined by ColdU patients, SD patients and in combination. A TEAE is any untoward medical occurrence in a patient administered a study treatment.	From baseline to week 20

Collaborators and Investigators

• Sponsor: Celldex Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2022
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: June 1, 2022
• First Submitted That Met QC Criteria: June 1, 2022
• First Posted (Actual): June 6, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: CDX-0159; barzolvolimab
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Disease Attributes; Skin Diseases, Vascular; Hypersensitivity; Chronic Disease; Chronic Urticaria; Urticaria; Chronic Inducible Urticaria
• Other Study ID Numbers: CDX0159-07; 2021-006447-95 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No