Dupilumab for the Treatment of Chronic Inducible Cold Urticaria in Patients Who Remain Symptomatic Despite the Use of H1-antihistamine (LIBERTY-CINDU CUrIADS)

NCT04681729 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: EFC167202020-003756-33U1111-1246-6913
• Study Type: interventional
• Target: 82
• Locations: 5 countries
• Sites: 33

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

Conditions

Cold Urticaria

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Negative Ice Cube Provocation Test at Week 24

  The ice cube provocation test is the most frequently used provocation method for cold urticaria (ColdU). A negative ice cube provocation test was defined as the absence of confluent hives/wheal at the entire skin site of exposure after ice cube provocation test. Ice cube was applied on forearm skin for 5 minutes. Provocation test reading time was 10 minutes after removal of ice cube.

  Week 24

Secondary Outcomes (16)

• Change From Baseline in Urticaria Control Test (UCT) Scale Scores at Week 24

  Baseline to Week 24

• Percentage of Participants With Urticaria Control Test Score >=12 at Week 24

  Week 24

• Percentage of Participants With an Improvement of >=3 Points From Baseline in Urticaria Control Test Score at Week 24

  Baseline to Week 24

• Change From Baseline in Local Wheal Intensity Likert Scale Score at Weeks 12 and 24

  Baseline, Week 12 and Week 24

• Change From Baseline in Local Itch Severity Scale Score at Weeks 12 and 24

  Baseline, Week 12 and Week 24

Study Arms (2)

Dupilumab

EXPERIMENTAL

Dose regimens, on top of regular or as needed non-sedating H1-antihistamine

Drug: Dupilumab SAR231893; Drug: Non sedating H1-antihistamine

Matched Placebo

PLACEBO COMPARATOR

Placebo, on top of regular/as needed non-sedating H1-antihistamine

Drug: Placebo; Drug: Non sedating H1-antihistamine

Interventions

Dupilumab SAR231893 DRUG

Pharmaceutical form: Injection solution Route of administration: Subcutaneous

Dupilumab

Placebo DRUG

Pharmaceutical form: Injection solution Route of administration: Subcutaneous

Matched Placebo

Non sedating H1-antihistamine DRUG

Pharmaceutical form: Tablet Route of administration: Oral

Dupilumab; Matched Placebo

Eligibility Criteria

• Age: 12 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (33)

Allergy and Asthma Medical Group and Research Center-Site Number:8400001

San Diego, California, 92123, United States

Location

Treasure Valley Medical Research-Site Number:8400007

Boise, Idaho, 83706, United States

Location

Allergy & Asthma Specialists, PSC-Site Number:8400003

Owensboro, Kentucky, 42301, United States

Location

Johns Hopkins University (Asthma and Allergy Center)-Site Number:8400005

Baltimore, Maryland, 21224, United States

Location

Bernstein Allergy Group Inc-Site Number:8400004

Cincinnati, Ohio, 45231, United States

Location

Investigational Site Number :0320001

CABA, Buenos Aires, C1023AAB, Argentina

Location

Investigational Site Number :0320005

CABA, Buenos Aires, C1181ACH, Argentina

Location

Investigational Site Number :0320006

CABA, Buenos Aires, C1414AIF, Argentina

Location

Investigational Site Number :0320002

Rosario, Santa Fe Province, 2000, Argentina

Location

Investigational Site Number :0320004

San Miguel de Tucumán, Tucumán Province, T4000AXL, Argentina

Location

Investigational Site Number :0320003

Buenos Aires, C1121ABE, Argentina

Location

Investigational Site Number :1240008

Edmonton, Alberta, T5J 3S9, Canada

Location

Investigational Site Number :1240010

Edmonton, Alberta, T6G 1C3, Canada

Location

Investigational Site Number :1240007

Hamilton, Ontario, L8L 3C3, Canada

Location

Investigational Site Number :1240009

Hamilton, Ontario, L8S1G5, Canada

Location

Investigational Site Number :1240001

Toronto, Ontario, M3B 3S6, Canada

Location

Investigational Site Number :1240011

Montreal, Quebec, H4A 3T2, Canada

Location

Investigational Site Number :1240005

Saint-Charles-Borromée, Quebec, J6E 2B4, Canada

Location

Investigational Site Number :1240006

Sherbrooke, Quebec, J1L 0H8, Canada

Location

Investigational Site Number :1240002

Québec, G1V 4W2, Canada

Location

Investigational Site Number :2760002

Berlin, 10117, Germany

Location

Investigational Site Number :2760004

Dresden, 01307, Germany

Location

Investigational Site Number :2760007

Erlangen, 91054, Germany

Location

Investigational Site Number :2760006

Hanover, 30625, Germany

Location

Investigational Site Number :2760005

Leipzig, 04103, Germany

Location

Investigational Site Number :2760001

Mainz, 55131, Germany

Location

Investigational Site Number :3920002

Nagoya, Aichi-ken, 454-8509, Japan

Location

Investigational Site Number :3920003

Hiroshima, Hiroshima, 734-8551, Japan

Location

Investigational Site Number :3920008

Kamimashiki Gun, Kumamoto, 861-3106, Japan

Location

Investigational Site Number :3920007

Sakai-shi, Osaka, 593-8324, Japan

Location

Investigational Site Number :3920010

Koto-ku, Tokyo, 136-0074, Japan

Location

Investigational Site Number :3920011

Tachikawa-shi, Tokyo, 190-0023, Japan

Location

Investigational Site Number :3920009

Habikino-Shi, 583-0872, Japan

Location

Related Links

• EFC16720 Plain Language Results Summary

MeSH Terms

Conditions

Cold Urticaria

Interventions

dupilumab

Condition Hierarchy (Ancestors)

Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2020
• First Posted: December 23, 2020
• Study Start: December 10, 2020
• Primary Completion: February 2, 2023
• Study Completion: April 20, 2023
• Last Updated: September 10, 2025
• Results First Posted: February 21, 2024

Record last verified: 2025-09-02

Data Sharing

• IPD Sharing: Will share

Locations

AR (6); CA (9); US (5); JP (7); DE (6)