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

Sponsor

Sanofi (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04681729

Collaborator

Regeneron Pharmaceuticals (Industry)

Enrollment

Locations

Arms

28.9

Anticipated Duration (Months)

2.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Detailed Description

The duration of study for each participant will include 2-4 weeks of screening period, 24 weeks of treatment period and 12 weeks of post treatment period.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

78 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 :

Dec 10, 2020

Anticipated Primary Completion Date :

Oct 14, 2022

Anticipated Study Completion Date :

May 9, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dupilumab Dose regimens, on top of regular or as needed non-sedating H1-antihistamine	Drug: Dupilumab SAR231893 Pharmaceutical form:Injection solution Route of administration: Subcutaneous Drug: Non sedating H1-antihistamine Pharmaceutical form:Tablet Route of administration: Oral
Placebo Comparator: Matched Placebo Placebo,on top of regular/as needed non-sedating H1-antihistamine	Drug: Placebo Pharmaceutical form:Injection solution Route of administration: Subcutaneous Drug: Non sedating H1-antihistamine Pharmaceutical form:Tablet Route of administration: Oral

Arm

Intervention/Treatment

Experimental: Dupilumab

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

Drug: Dupilumab SAR231893

Pharmaceutical form:Injection solution Route of administration: Subcutaneous

Drug: Non sedating H1-antihistamine

Pharmaceutical form:Tablet Route of administration: Oral

Placebo Comparator: Matched Placebo

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

Drug: Placebo

Pharmaceutical form:Injection solution Route of administration: Subcutaneous

Drug: Non sedating H1-antihistamine

Pharmaceutical form:Tablet Route of administration: Oral

Outcome Measures

Primary Outcome Measures

Proportion of participants with negative ice cube provocation test at Week 24 compared with placebo [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 [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 [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 [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 [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 [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 [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 [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 [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.
Proportion of participants with cold exposure triggered urticaria signs and symptoms at Week 12 and Week 24 as measured by ColdUAS compared with placebo [Week 12 and Week 24]
Cold Urticaria Activity Score (ColdUAS) is a disease specific PRO questionnaire designed to determine cold urticaria disease activity.
Proportion of days with cold exposure triggered urticaria signs and symptoms at Week 12 and Week 24 as measured by ColdUAS compared with placebo [Week 12 and Week 24]
Cold Urticaria Activity Score (ColdUAS) is a disease specific PRO questionnaire designed to determine cold urticaria disease activity.
Proportion of participants with severe cold exposure triggered urticaria signs and symptoms at Week 12 and Week 24 as measured by ColdUAS compared with placebo [Week 12 and Week 24]
Cold Urticaria Activity Score (ColdUAS) is a disease specific PRO questionnaire designed to determine cold urticaria disease activity.
Proportion of days with severe cold exposure triggered urticaria signs and symptoms at Week 12 and Week 24 as measured by ColdUAS compared with placebo [Week 12 and Week 24]
Cold Urticaria Activity Score (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 [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 [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.
Patient Global Impression of Change (PGIC) of primary acquired chronic inducible ColdU at Week 12 and Week 24 compared with placebo [Week 12 and Week 24]
The PGIC is a 1-item questionnaire that asks the participant to provide the overall self-assessment of change in their chronic inducible ColdU on a 7-point scale, compared with just before participant started taking the study treatment. Response choices are: 0="Very much better", 1= "Moderately better", 2="A little better", 3="No change", 4="A little worse", 5="Moderately worse", 6="Very much worse".
Change from baseline in Patient Global Impression of Severity (PGIS) of primary acquired chronic inducible ColdU at Week 12 and Week 24 compared with placebo [Baseline to Week 12 and Week 24]
The PGIS is a 1-item questionnaire that asks participants to provide the overall self-assessment of their chronic inducible ColdU current severity on a 4 point scale. Response choices are: 1= "None", 2="Mild", 3="Moderate", 4="Severe".
Change from baseline in Cold Urticaria Quality of Life (ColdU QoL) at Week 24 compared with placebo [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.
Time to first rescue therapy for primary acquired chronic induced ColdU during the planned treatment period compared with placebo [Baseline to Week 24]
Proportion of participants receiving rescue therapy for primary acquired chronic inducible ColdU during the planned treatment period compared with placebo [Baseline to Week 24]
Proportion of participants with cold exposure urticaria requiring emergency medical care visit or treatment with epinephrine [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) [Throughout the study up to Week 36]
Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab over time [Throughout the study up to Week 36]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)
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:

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 omalizumab or any biologic therapy, including any 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Allergy and Asthma Medical Group and Research Center-Site Number:8400001	San Diego	California	United States	92123
2	Treasure Valley Medical Research-Site Number:8400007	Boise	Idaho	United States	83706
3	Allergy & Asthma Specialists, PSC-Site Number:8400003	Owensboro	Kentucky	United States	42301
4	Johns Hopkins University (Asthma and Allergy Center)-Site Number:8400005	Baltimore	Maryland	United States	21224
5	Bernstein Allergy Group Inc-Site Number:8400004	Cincinnati	Ohio	United States	45231
6	Investigational Site Number :0320001	Caba	Buenos Aires	Argentina	C1023AAB
7	Investigational Site Number :0320005	Caba	Buenos Aires	Argentina	C1181ACH
8	Investigational Site Number :0320006	Caba	Buenos Aires	Argentina	C1414AIF
9	Investigational Site Number :0320002	Rosario	Santa Fe	Argentina	2000
10	Investigational Site Number :0320003	Buenos Aires		Argentina	C1121ABE
11	Investigational Site Number :0320004	San Miguel de Tucuman		Argentina	T4000AXL
12	Investigational Site Number :1240008	Edmonton	Alberta	Canada	T5J 3S9
13	Investigational Site Number :1240010	Edmonton	Alberta	Canada	T6G 1C3
14	Investigational Site Number :1240007	Hamilton	Ontario	Canada	L8L 3C3
15	Investigational Site Number :1240009	Hamilton	Ontario	Canada	L8S1G5
16	Investigational Site Number :1240001	Toronto	Ontario	Canada	M3B 3S6
17	Investigational Site Number :1240011	Montreal	Quebec	Canada	H4A 3T2
18	Investigational Site Number :1240005	Saint-Charles-Borromée	Quebec	Canada	J6E 2B4
19	Investigational Site Number :1240006	Sherbrooke	Quebec	Canada	J1L 0H8
20	Investigational Site Number :1240002	Quebec		Canada	G1V 4W2
21	Investigational Site Number :2760002	Berlin		Germany	10117
22	Investigational Site Number :2760004	Dresden		Germany	01307
23	Investigational Site Number :2760007	Erlangen		Germany	91054
24	Investigational Site Number :2760006	Hannover		Germany	30625
25	Investigational Site Number :2760005	Leipzig		Germany	04103
26	Investigational Site Number :2760001	Mainz		Germany	55131
27	Investigational Site Number :3920003	Hiroshima-shi	Hiroshima	Japan	734-8551
28	Investigational Site Number :3920005	Sapporo-shi	Hokkaido	Japan	063-0005
29	Investigational Site Number :3920008	Kamimashiki Gun	Kumamoto	Japan	861-3101
30	Investigational Site Number :3920007	Sakai-shi	Osaka	Japan	593-8324
31	Investigational Site Number :3920004	Izumo-shi	Shimane	Japan	693-8501
32	Investigational Site Number :3920001	Itabashi-ku	Tokyo	Japan	173-8610
33	Investigational Site Number :3920010	Koto-ku	Tokyo	Japan	136-0074
34	Investigational Site Number :3920011	Tachikawa-shi	Tokyo	Japan	190-0023
35	Investigational Site Number :3920009	Habikino-shi		Japan	583-8588
36	Investigational Site Number :3920002	Nagoya-shi		Japan	454-8509

Sponsors and Collaborators

Sanofi
Regeneron Pharmaceuticals

Investigators

Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sanofi

ClinicalTrials.gov Identifier:

NCT04681729

Other Study ID Numbers:

EFC16720
2020-003756-33
U1111-1246-6913

First Posted:

Dec 23, 2020

Last Update Posted:

Aug 23, 2022

Last Verified:

Aug 22, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Urticaria

Histamine Antagonists

Histamine H1 Antagonists

Histamine H1 Antagonists, Non-Sedating

Study Results

No Results Posted as of Aug 23, 2022