Dupilumab for the Treatment of Chronic Inducible Cold Urticaria in Patients Who Remain Symptomatic Despite the Use of H1-antihistamine (LIBERTY-CINDU CUrIADS)
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| ClinicalTrials.gov Identifier: NCT04681729 |
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Recruitment Status :
Completed
First Posted : December 23, 2020
Last Update Posted : May 3, 2023
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Sponsor:
Sanofi
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
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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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Cold Urticaria | Drug: Dupilumab SAR231893 Drug: Placebo Drug: Non sedating H1-antihistamine | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 82 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | December 10, 2020 |
| Actual Primary Completion Date : | February 2, 2023 |
| Actual Study Completion Date : | April 20, 2023 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Dupilumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dupilumab
Dose regimens, on top of regular or as needed non-sedating H1-antihistamine
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Drug: Dupilumab SAR231893
Pharmaceutical form:Injection solution Route of administration: Subcutaneous Drug: Non sedating H1-antihistamine Pharmaceutical form:Tablet Route of administration: Oral |
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Placebo Comparator: Matched Placebo
Placebo,on top of regular/as needed non-sedating H1-antihistamine
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Drug: Placebo
Pharmaceutical form:Injection solution Route of administration: Subcutaneous Drug: Non sedating H1-antihistamine Pharmaceutical form:Tablet Route of administration: Oral |
Primary Outcome Measures :
- Proportion of participants with negative ice cube provocation test at Week 24 compared with placebo [ Time Frame: Week 24 ]Negative ice cube provocation test is defined as the absence of a confluent hives/wheal at the entire skin site of exposure after ice cube provocation test.
Secondary Outcome Measures :
- Change from baseline in urticaria control test at Week 24 compared with placebo [ Time Frame: Baseline to Week 24 ]The UCT is a PRO questionnaire for assessing urticaria control. It is comprised of 4 items (UCT-4). The UCT-4 total score is 0-16, with a score of 16 for complete disease control.
- Proportion of well-controlled participants at Week 24 compared with placebo [ Time Frame: Week 24 ]The UCT is a PRO questionnaire for assessing urticaria control. It is comprised of 4 items (UCT-4). The UCT-4 total score is 0-16, with a score of 16 for complete disease control. Well-controlled is UCT-4 total score ≥12.
- Proportion of participants with an improvement of ≥3 in UCT-4 item from baseline to Week 24 compared with placebo [ Time Frame: Baseline to Week 24 ]The UCT is a PRO questionnaire for assessing urticaria control. It is comprised of 4 items (UCT-4). The UCT-4 total score is 0-16, with a score of 16 for complete disease control.
- Change from baseline in local wheal intensity at the provocation site at Week 12 and 24 using the wheal intensity Likert scale compared with placebo [ Time Frame: Baseline to Week 12 and Week 24 ]The Wheal intensity Likert scale (ranging from 0 to 5) is a clinician-reported outcome measure comprised of a single item assessing the intensity of patients' cutaneous reaction rated as follows: 0=no wheals; 1=numerous small, noncoalescent wheals; 2= a large, regular, slightly edematous, coalescent wheal; 3=a large and moderately edematous wheal; 4=a large, regular, and significantly edematous wheal without pseudopodia; and 5=a large, very edematous wheal with pseudopodia.
- Change from baseline in local itch severity at the provocation site at Week 12 and 24 using the Peak Pruritus Numerical Rating Scale (NRS) compared with placebo [ Time Frame: Baseline to Week 12 and Week 24 ]The peak pruritus NRS is a patient-reported outcome (PRO) comprised of a single item rated on a scale from 0 ("No itch") to 10 ("Worst itch imaginable").
- Change from baseline in local skin burning sensation at the provocation site at Week 12 and Week 24 using the peak burning sensation NRS compared with placebo [ Time Frame: Baseline to Week 12 and Week 24 ]The peak burning sensation NRS is a PRO comprised of a single item rated on a scale from 0 ("No burning sensation") to 10 ("Worst imaginable burning sensation").
- Change from baseline in local pain severity at the provocation site at Week 12 and Week 24 using the peak pain sensation NRS compared with placebo [ Time Frame: Baseline to Week 12 and Week 24 ]The peak pain NRS is a PRO comprised of a single item rated on a scale from 0 ("No pain") to 10 ("Worst imaginable pain").
- Proportion of participants with negative ice cube provocation test at Week 12 compared with placebo [ Time Frame: Week 12 ]Negative ice cube provocation test is defined as the absence of a confluent hives/wheal at the entire skin site of exposure after ice cube provocation test.
- Change from baseline in cold urticaria signs and symptoms severity at Week 24 on cold exposure days as measured by ColdUAS compared with placebo [ Time Frame: Baseline to Week 24 ]Cold Urticaria Activity Score (ColdUAS) is a disease specific PRO questionnaire designed to determine cold urticaria disease activity.
- Change from baseline in the proportion of cold urticaria sign and symptom free days at Week 24 on cold exposure days as measured by ColdUAS, compared with placebo [ Time Frame: Baseline to Week 24 ]ColdUAS is a disease specific PRO questionnaire designed to determine cold urticaria disease activity.
- Change from baseline in health-related quality-of-life (HRQoL) as measured by Dermatology Life Quality Index (DLQI) at Week 24 compared with placebo [ Time Frame: Baseline to Week 24 ]The DLQI is a PRO developed to measure dermatology-specific HRQoL in patients ≥16 years old. Overall scoring ranges from 0 to 30, with a high score indicative of a poor HRQoL.
- Change from baseline in HRQoL as measured by Children's Dermatology Life Quality Index (CDLQI) at Week 24 compared with placebo [ Time Frame: Baseline to Week 24 ]The CDLQI is a validated questionnaire designed to measure the impact of skin disease on children's (≥12 to <16 years old) HRQoL. The CDLQI total score is 0-30. The higher the score, the greater the impact is on the child's HRQoL.
- Change from baseline in Cold Urticaria Quality of Life (ColdU QoL) at Week 24 compared with placebo [ Time Frame: Baseline to Week 24 ]ColdU-QoL questionnaire is a disease-specific PRO questionnaire designed to assess the impact of cold urticaria on patients' health-related QoL.
- Proportion of participants receiving rescue therapy for primary acquired chronic inducible ColdU during the planned treatment period compared with placebo [ Time Frame: Baseline to Week 24 ]
- Proportion of participants with cold exposure urticaria requiring emergency medical care visit or treatment with epinephrine [ Time Frame: Baseline to Week 24 ]At provocation test and/or at home.
- Percentages of participants experiencing treatment--emergent adverse events (TEAEs) or serious adverse events (SAEs) [ Time Frame: Throughout the study up to Week 36 ]
- Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab over time [ Time Frame: Throughout the study up to Week 36 ]
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| Ages Eligible for Study: | 12 Years to 80 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Participant must be ≥12 years to 80 years of age inclusive at the time of signing the informed consent
- Participants who have 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)
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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 are excluded from the study if any of the following criteria apply:
- 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 adversely affect 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 is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04681729
Locations
Show 33 study locations
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
| Study Director: | Clinical Sciences & Operations | Sanofi |
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT04681729 |
| Other Study ID Numbers: |
EFC16720 2020-003756-33 ( EudraCT Number ) U1111-1246-6913 ( Registry Identifier: ICTRP ) |
| First Posted: | December 23, 2020 Key Record Dates |
| Last Update Posted: | May 3, 2023 |
| Last Verified: | May 2, 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
Additional relevant MeSH terms:
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Urticaria Skin Diseases, Vascular Skin Diseases Hypersensitivity, Immediate Hypersensitivity Immune System Diseases Histamine Antagonists |
Histamine H1 Antagonists Histamine H1 Antagonists, Non-Sedating Histamine Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs |