Clinical trial NCT04681729: Dupilumab for the Treatment of Chronic Inducible Cold Urticaria in Patients Who Remain Symptomatic Despite the Use of H1-antihistamine (LIBERTY-CINDU CUrIADS)
Official title: A Randomized, Double-blind, Placebo-controlled, Multi-center, Parallel-group Study of Dupilumab in Patients With Chronic Inducible Cold Urticaria Who Remain Symptomatic Despite the Use of H1-antihistamine Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cold Urticaria
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2020-12-23
Enrollment: 82
Sex: ALL
Minimum age (years): 12
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To demonstrate the efficacy of dupilumab in adult and adolescent participants with primary acquired chronic inducible cold urticaria (ColdU) who remain symptomatic despite the use of an H1-antihistamine

Secondary Objectives:

To demonstrate the efficacy of dupilumab on primary acquired chronic inducible ColdU disease control To demonstrate the efficacy of dupilumab on primary acquired chronic inducible ColdU local signs and symptoms (hives/wheals, itch, burning sensation and pain) after provocation test To demonstrate the efficacy of dupilumab on primary acquired chronic inducible ColdU disease activity To demonstrate improvement in health-related quality-of-life and overall disease status and severity To evaluate the ability of dupilumab in reducing the proportion of participants who require rescue therapy To evaluate the proportion of participants with cold exposure triggered urticaria To evaluate safety outcome measures To evaluate immunogenicity of dupilumab

Detailed description: The duration of study for each participant included 2-4 weeks of screening period, 24 weeks of treatment period and 12 weeks of post treatment period.

Eligibility criteria: Inclusion Criteria:

* Participant had to be ≥12 years to 80 years of age inclusive at the time of signing the informed consent
* Participants who had a diagnosis of primary acquired chronic inducible ColdU defined as recurrence of itchy wheals and/or angioedema due to cold for longer than 6 weeks prior to screening visit (Visit 1)
* Participants with positive ice cube provocation test, ie, presenting at least a confluent hive/wheal on the exposed skin area, at the screening visit (Visit 1) and randomization visit (Visit 2)
* Participants meeting at least 1 of the following criteria despite regular/daily or as needed use of H1-antihistamine (AH):

  * Urticaria Control Test (UCT) (4 item) \<12 at the screening visit (Visit 1) and randomization visit (Visit 2)
  * Within 6 months prior to the screening visit, documented medical history of cold exposure triggered anaphylaxis or oropharyngeal edema
  * Within 6 months prior to the screening visit, documented medical history of cold exposure triggered urticaria requiring emergency medical care visit or treatment with epinephrine
* Participants using a study defined H1-antihistamine regularly/daily or as needed for primary acquired chronic inducible cold urticaria
* Body weight ≥30 kg

Exclusion Criteria:

Participants were excluded from the study if any of the following criteria applied:

* Clearly defined underlying etiology for urticaria other than primary acquired chronic inducible ColdU
* Presence of skin morbidities other than cold urticaria that may interfere with the assessment of the study outcomes
* Active atopic dermatitis
* Severe concomitant illness(es) that, in the investigator's judgment, would have adversely affected the patient's participation in the study
* Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated.
* Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection
* Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the screening visit and during the screening period
* Known or suspected immunodeficiency
* Active malignancy or history of malignancy within 5 years before the baseline visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin
* History of systemic hypersensitivity or anaphylaxis to any other biologic therapy or any of its excipients.
* Participation in prior dupilumab clinical study, or have been treated with commercially available dupilumab.

The above information was not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Percentage of Participants With Negative Ice Cube Provocation Test at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Change From Baseline in Urticaria Control Test (UCT) Scale Scores at Week 24
timeFrame: Baseline to Week 24
measure: Percentage of Participants With Urticaria Control Test Score >=12 at Week 24
timeFrame: Week 24
measure: Percentage of Participants With an Improvement of >=3 Points From Baseline in Urticaria Control Test Score at Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in Local Wheal Intensity Likert Scale Score at Weeks 12 and 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change From Baseline in Local Itch Severity Scale Score at Weeks 12 and 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change From Baseline in Local Skin Burning Sensation Scale Score at Weeks 12 and 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change From Baseline in Local Pain Severity Scale Score at Weeks 12 and 24
timeFrame: Baseline, Week 12 and Week 24
measure: Percentage of Participants With Negative Ice Cube Provocation Test at Week 12
timeFrame: Week 12
measure: Change From Baseline in Cold Urticaria Signs and Symptoms Severity Scale Score at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Percentage of Cold Urticaria Sign and Symptom-Free Days at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) Scale Scores at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Cold Urticaria Quality of Life (ColdU-QoL) Scale Score at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants Receiving Rescue Therapy for Primary Acquired Chronic Inducible Cold Urticaria
timeFrame: From first investigational medicinal product (IMP) administration (Day 1) up to Week 24
measure: Percentage of Participants With Cold Exposure Triggered Urticaria That Required Hospitalization/Emergency Medical Care Visit or Treatment With Epinephrine
timeFrame: From first IMP administration (Day 1) up to 14 weeks after last IMP administration (i.e., up to Week 36)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From first IMP administration (Day 1) up to 14 weeks after last IMP administration (i.e., up to Week 36)
measure: Number of Participants With Treatment-emergent Antidrug Antibodies (ADA) Response
timeFrame: From first IMP administration (Day 1) up to 14 weeks after last IMP administration (i.e., up to Week 36)
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Allergy and Asthma Medical Group and Research Center-Site Number:8400001
state: California
city: Boise
country: United States
facility: Treasure Valley Medical Research-Site Number:8400007
state: Idaho
city: Owensboro
country: United States
facility: Allergy & Asthma Specialists, PSC-Site Number:8400003
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University (Asthma and Allergy Center)-Site Number:8400005
state: Maryland
city: Cincinnati
country: United States
facility: Bernstein Allergy Group Inc-Site Number:8400004
state: Ohio
city: Caba
country: Argentina
facility: Investigational Site Number :0320001
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigational Site Number :0320005
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigational Site Number :0320006
state: Buenos Aires
city: Rosario
country: Argentina
facility: Investigational Site Number :0320002
state: Santa Fe
city: San Miguel de Tucuman
country: Argentina
facility: Investigational Site Number :0320004
state: Tucumán
city: Buenos Aires
country: Argentina
facility: Investigational Site Number :0320003
city: Edmonton
country: Canada
facility: Investigational Site Number :1240008
state: Alberta
city: Edmonton
country: Canada
facility: Investigational Site Number :1240010
state: Alberta
city: Hamilton
country: Canada
facility: Investigational Site Number :1240007
state: Ontario
city: Hamilton
country: Canada
facility: Investigational Site Number :1240009
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number :1240001
state: Ontario
city: Montreal
country: Canada
facility: Investigational Site Number :1240011
state: Quebec
city: Saint-Charles-Borromée
country: Canada
facility: Investigational Site Number :1240005
state: Quebec
city: Sherbrooke
country: Canada
facility: Investigational Site Number :1240006
state: Quebec
city: Quebec
country: Canada
facility: Investigational Site Number :1240002
city: Berlin
country: Germany
facility: Investigational Site Number :2760002
city: Dresden
country: Germany
facility: Investigational Site Number :2760004
city: Erlangen
country: Germany
facility: Investigational Site Number :2760007
city: Hannover
country: Germany
facility: Investigational Site Number :2760006
city: Leipzig
country: Germany
facility: Investigational Site Number :2760005
city: Mainz
country: Germany
facility: Investigational Site Number :2760001
city: Nagoya-shi
country: Japan
facility: Investigational Site Number :3920002
state: Aichi
city: Hiroshima-shi
country: Japan
facility: Investigational Site Number :3920003
state: Hiroshima
city: Kamimashiki Gun
country: Japan
facility: Investigational Site Number :3920008
state: Kumamoto
city: Sakai-shi
country: Japan
facility: Investigational Site Number :3920007
state: Osaka
city: Koto-ku
country: Japan
facility: Investigational Site Number :3920010
state: Tokyo
city: Tachikawa-shi
country: Japan
facility: Investigational Site Number :3920011
state: Tokyo
city: Habikino-Shi
country: Japan
facility: Investigational Site Number :3920009
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: