Dupilumab for the Treatment of Chronic Spontaneous Urticaria in Patients Who Remain Symptomatic Despite the Use of H1 Antihistamine and Who Are naïve to, Intolerant of, or Incomplete Responders to Omalizumab (LIBERTY-CSU CUPID)

Master Protocol of Three Randomized, Double-blind, Placebo Controlled, Multi-center, Parallel-group Studies of Dupilumab in Patients With Chronic Spontaneous Urticaria (CSU) Who Remain Symptomatic Despite the Use of H1 Antihistamine Treatment in Patients naïve to Omalizumab and in Patients Who Are Intolerant or Incomplete Responders to Omalizumab

Primary Objective:

This study aimed to demonstrate the efficacy of dupilumab in study participants with CSU who remained symptomatic despite the use of H1 antihistamine (Study A and C: omalizumab naïve; Study B: omalizumab intolerant or incomplete responders)

Secondary Objectives:

This study aimed to demonstrate the efficacy of dupilumab on urticaria activity composite endpoint and itch or hives, separately, at various timepoints This study aimed to demonstrate the efficacy of dupilumab on angioedema This study aimed to demonstrate the efficacy of dupilumab on urticaria control This study aimed to demonstrate improvement in health-related quality of life and overall disease status and severity This study aimed to evaluate the ability of dupilumab in reducing the proportion of participants who require treatment with oral corticosteroids (OCS) This study aimed to evaluate safety outcome measures This study aimed to evaluate immunogenicity of dupilumab

Study Overview

• Status: Completed
• Conditions: Chronic Spontaneous Urticaria
• Intervention / Treatment: Drug: Dupilumab SAR231893; Drug: Placebo; Drug: non sedating H1-antihistamine

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.

• Study Type: Interventional
• Enrollment (Actual): 397
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1121ABE
    • Investigational Site Number : 0320001
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1414AIF
      • Investigational Site Number : 0320004
    • Caba, Buenos Aires, Argentina, C1023AAB
      • Investigational Site Number : 0320008
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Investigational Site Number : 0320006
    • Rosario, Santa Fe, Argentina, S2000JKR
      • Investigational Site Number : 0320005
    • Rosario, Santa Fe, Argentina, S2000BRH
      • Investigational Site Number : 0320007
  • Tucumán
    • San Miguel de Tucuman, Tucumán, Argentina, T4000AXL
      • Investigational Site Number : 0320003
• Canada
  • Quebec, Canada, G1V 4W2
    • Investigational Site Number : 1240004
  • Quebec, Canada, G1W 4R4
    • Investigational Site Number : 1240011
  • Alberta
    • Calgary, Alberta, Canada, T2J 7E1
      • Investigational Site Number : 1240009
    • Edmonton, Alberta, Canada, T6G 1C3
      • Investigational Site Number : 1240010
  • Ontario
    • Hamilton, Ontario, Canada, L8L 3C3
      • Investigational Site Number : 1240014
    • Markham, Ontario, Canada, L3P 1X3
      • Investigational Site Number : 1240013
    • Niagara Falls, Ontario, Canada, L2H 1H5
      • Investigational Site Number : 1240003
    • Toronto, Ontario, Canada, M3B 3S6
      • Investigational Site Number : 1240005
    • Toronto, Ontario, Canada, M5G 1E2
      • Investigational Site Number : 1240002
    • Windsor, Ontario, Canada, N8X 2G1
      • Investigational Site Number : 1240007
  • Quebec
    • Sherbrooke, Quebec, Canada, J1G 1X9
      • Investigational Site Number : 1240016
    • Trois-Rivieres, Quebec, Canada, G8T 7A1
      • Investigational Site Number : 1240006
• China
  • Beijing, China, 100045
    • Investigational Site Number : 1560010
  • Beijing, China, 100050
    • Investigational Site Number : 1560004
  • Chengdu, China, 610041
    • Investigational Site Number : 1560001
  • Guangzhou, China, 510630
    • Investigational Site Number : 1560007
  • Hangzhou, China, 310006
    • Investigational Site Number : 1560002
  • Hangzhou, China, 310016
    • Investigational Site Number : 1560008
  • Jinan, China, 250013
    • Investigational Site Number : 1560006
  • Shanghai, China, 200040
    • Investigational Site Number : 1560003
  • Wuxi, China, 214002
    • Investigational Site Number : 1560005
• France
  • Calais, France, 62107
    • Investigational Site Number : 2500009
  • Lille, France, 59037
    • Investigational Site Number : 2500002
  • Mont de Marsan, France, 40000
    • Investigational Site Number : 2500011
  • Nantes, France, 44093
    • Investigational Site Number : 2500004
  • Nice, France, 06000
    • Investigational Site Number : 2500012
  • Nice, France, 06200
    • Investigational Site Number : 2500003
  • Paris, France, 75970
    • Investigational Site Number : 2500006
  • Pierre Benite, France, 69495
    • Investigational Site Number : 2500005
• Germany
  • Berlin, Germany, 10117
    • Investigational Site Number : 2760001
  • Bramsche, Germany, 49565
    • Investigational Site Number : 2760010
  • Dresden, Germany, 01307
    • Investigational Site Number : 2760006
  • Kiel, Germany, 24148
    • Investigational Site Number : 2760007
  • Tübingen, Germany, 72076
    • Investigational Site Number : 2760008
• Hungary
  • Debrecen, Hungary, 4031
    • Investigational Site Number : 3480005
  • Szeged, Hungary, 6720
    • Investigational Site Number : 3480004
  • Szolnok, Hungary, 5000
    • Investigational Site Number : 3480003
  • Szombathely, Hungary, 9700
    • Investigational Site Number : 3480002
• Japan
  • Nagoya-shi, Japan, 454-8509
    • Investigational Site Number : 3920004
  • Hiroshima
    • Hiroshima-shi, Hiroshima, Japan, 734-8551
      • Investigational Site Number : 3920005
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 060-0807
      • Investigational Site Number : 3920009
  • Hyogo
    • Kobe-shi, Hyogo, Japan, 650-0017
      • Investigational Site Number : 3920002
  • Kagoshima
    • Kagoshima-Shi, Kagoshima, Japan, 890-0063
      • Investigational Site Number : 3920011
  • Kanagawa
    • Yokohama-Shi, Kanagawa, Japan, 221-0825
      • Investigational Site Number : 3920013
    • Yokohama-shi, Kanagawa, Japan, 236-0004
      • Investigational Site Number : 3920008
  • Osaka
    • Suita-shi, Osaka, Japan, 565-0871
      • Investigational Site Number : 3920003
  • Shimane
    • Izumo-shi, Shimane, Japan, 693-8501
      • Investigational Site Number : 3920007
  • Tokyo
    • Itabashi-ku, Tokyo, Japan, 173-8610
      • Investigational Site Number : 3920006
    • Shinagawa-Ku, Tokyo, Japan, 141-8625
      • Investigational Site Number : 3920001
    • Tachikawa-shi, Tokyo, Japan, 190-0023
      • Investigational Site Number : 3920010
• Russian Federation
  • Chelyabinsk, Russian Federation, 454048
    • Investigational Site Number : 6430008
  • Kazan, Russian Federation, 420064
    • Investigational Site Number : 6430006
  • Krasnodar, Russian Federation, 350020
    • Investigational Site Number : 6430007
  • Moscow, Russian Federation, 115522
    • Investigational Site Number : 6430005
  • Moscow, Russian Federation, 115522
    • Investigational Site Number : 6430010
  • Moscow, Russian Federation, 123182
    • Investigational Site Number : 6430002
  • Saratov, Russian Federation, 410028
    • Investigational Site Number : 6430009
  • Smolensk, Russian Federation, 214006
    • Investigational Site Number : 6430004
  • St-Petersburg, Russian Federation, 193231
    • Investigational Site Number : 6430003
  • Stavropol, Russian Federation, 355030
    • Investigational Site Number : 6430001
• Spain
  • Córdoba, Spain, 14004
    • Investigational Site Number : 7240004
  • Villareal, Spain, 12540
    • Investigational Site Number : 7240011
  • A Coruña [La Coruña]
    • Santiago de Compostela, A Coruña [La Coruña], Spain, 15702
      • Investigational Site Number : 7240012
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08003
      • Investigational Site Number : 7240003
    • Barcelona, Barcelona [Barcelona], Spain, 08036
      • Investigational Site Number : 7240008
    • Hospitalet de Llobregat, Barcelona [Barcelona], Spain, 08907
      • Investigational Site Number : 7240014
  • Catalunya [Cataluña]
    • Esplugues de Llobregat, Catalunya [Cataluña], Spain, 08950
      • Investigational Site Number : 7240010
  • Las Palmas
    • Las Palmas de Gran Canaria, Las Palmas, Spain, 35010
      • Investigational Site Number : 7240005
  • Madrid, Comunidad De
    • Madrid, Madrid, Comunidad De, Spain, 28040
      • Investigational Site Number : 7240001
    • Madrid, Madrid, Comunidad De, Spain, 28027
      • Investigational Site Number : 7240007
    • Madrid, Madrid, Comunidad De, Spain, 28041
      • Investigational Site Number : 7240006
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Investigational Site Number : 7240002
  • Valenciana, Comunidad
    • Burjassot - Valencia, Valenciana, Comunidad, Spain, 46100
      • Investigational Site Number : 7240013
• United Kingdom
  • Manchester, United Kingdom, M23 9QZ,
    • Investigational Site Number : 8260001
  • London, City Of
    • London, London, City Of, United Kingdom, E1 1BB
      • Investigational Site Number : 8260002
• United States
  • California
    • Los Angeles, California, United States, 90025
      • California Allergy and Asthma Medical Group, Inc. Site Number : 8400019
  • Florida
    • Sarasota, Florida, United States, 34239
      • Sarasota Clinical Research Site Number : 8400017
    • Sweetwater, Florida, United States, 33172
      • Lenus Research & Medical Group Site Number : 8400001
    • Tampa, Florida, United States, 33613
      • University of South Florida Site Number : 8400006
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Aeroallergy Research Laboratories of Savannah, INC Site Number : 8400018
  • Kentucky
    • Owensboro, Kentucky, United States, 42301
      • Allergy & Asthma Specialists, PSC Site Number : 8400020
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University (Asthma and Allergy Center) Site Number : 8400016
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • The Clinical Research Center, LLC Site Number : 8400009
  • New York
    • Rochester, New York, United States, 14642
      • UR Dermatology at College Town Site Number : 8400008
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • Immunocarolina LLC Site Number : 8400010
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Bernstein Clinical Research Center Site Number : 8400014
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Vital Prospects Clinical Research Institute, P.C. Site Number : 8400015
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15241
      • Allergy and Clinical Immunology Associates Site Number : 8400024
  • South Carolina
    • Charleston, South Carolina, United States, 29420
      • National Allergy and ENT Site Number : 8400011
  • Texas
    • Dallas, Texas, United States, 75231
      • Pharmaceutical Research & Consulting, Inc. Site Number : 8400003
    • San Antonio, Texas, United States, 78229
      • STAAMP Research, LLC Site Number : 8400007

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Study A and C: Participant were ≥6 years to 80 years of age at the time of signing the informed consent.
• Study B: Participant were ≥12 years (or the minimum legal age for adolescents in the country of the investigational site) to 80 years of age at the time of signing the informed consent
• Participants who had a diagnosis of CSU refractory to H1 antihistamines (H1-AH) at the time of randomization defined by
• Diagnosis of CSU>6 months prior to screening visit
• Presence of itch and hives for >6 consecutive weeks at any time prior to screening visit despite the use of H1-AH during that time period
• Used a study defined H1-antihistamine for CSU treatment
• During the 7 days before randomization:

UAS7≥16 ISS7≥ 8

• Study A and C: omalizumab naïve, Study B; intolerant or incomplete responder to omalizumab
• Participants were willing and able to complete a daily symptom e-Diary for the duration of the study

Exclusion Criteria:

Participants were excluded from any of the studies if any of the following criteria apply:

• Weight was less than 30 kg in adults and adolescents and 15 kg in children aged 6 to<12years
• Clearly defined underlying etiology for chronic urticarias other than CSU
• Presented of skin morbidities other than CSU 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 participant'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 participant's potential participation in a clinical trial.

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: Study A Dupilumab; Participants who were omalizumab naïve received dupilumab for 24 weeks as follows: 300 milligrams (mg) SC injection every 2 weeks (q2w) for adults and those adolescents who weighed >=60 kilograms (kg) at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1,; 200 mg SC injection q2w for adolescents who weighed <60 kg and children (>=6 to <12 years of age) who weighed >=30 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1 and; 300 mg SC injection every 4 weeks (q4w) for children (>=6 to <12 years of age) who weighed <30 kg and >=15 kg at screening starting from Week 4 following a loading dose of 600 mg (2×300 mg injections) on Day 1.	Drug: Dupilumab SAR231893; Pharmaceutical form:Injection solution Route of administration: Subcutaneous; Drug: non sedating H1-antihistamine; Pharmaceutical form:Tablet Route of administration: oral administration
Placebo Comparator: Study A Placebo; Participants who were omalizumab naïve received placebo matched to dupilumab as subcutaneous (SC) injection including loading dose from Day 1 up to 24 weeks.	Drug: Placebo; Pharmaceutical form:Injection solution Route of administration: Subcutaneous; Drug: non sedating H1-antihistamine; Pharmaceutical form:Tablet Route of administration: oral administration
Experimental: Study B Dupilumab; Participants who were intolerant or incomplete responders to omalizumab received dupilumab for 24 weeks as follows: 300 mg SC injection q2w for adults and those adolescents weighing >=60 kg at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1 or; 200 mg SC injection q2w for adolescents weighing <60 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1.	Drug: Dupilumab SAR231893; Pharmaceutical form:Injection solution Route of administration: Subcutaneous; Drug: non sedating H1-antihistamine; Pharmaceutical form:Tablet Route of administration: oral administration
Placebo Comparator: Study B Placebo; Participants who were intolerant or incomplete responders to omalizumab received placebo matched to dupilumab as SC injection including loading dose from Day 1 up to 24 weeks.	Drug: Placebo; Pharmaceutical form:Injection solution Route of administration: Subcutaneous; Drug: non sedating H1-antihistamine; Pharmaceutical form:Tablet Route of administration: oral administration
Experimental: Study C Dupilumab; Participants who were omalizumab naïve received dupilumab for 24 weeks as follows: 300 mg SC injection q2w for adults and those adolescents who weighed >=60 kg at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1,; 200 mg SC injection q2w for adolescents who weighed <60 kg and children (>=6 to <12 years of age) who weighed >=30 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1 and; 300 mg SC injection q4w for children (>=6 to <12 years of age) who weighed <30 kg and >=15 kg at screening starting from Week 4 following a loading dose of 600 mg (2×300 mg injections) on Day 1.	Drug: Dupilumab SAR231893; Pharmaceutical form:Injection solution Route of administration: Subcutaneous; Drug: non sedating H1-antihistamine; Pharmaceutical form:Tablet Route of administration: oral administration
Placebo Comparator: Study C Placebo; Participants who were omalizumab naïve received placebo matched to dupilumab as SC injection including loading dose from Day 1 up to 24 weeks.	Drug: Placebo; Pharmaceutical form:Injection solution Route of administration: Subcutaneous; Drug: non sedating H1-antihistamine; Pharmaceutical form:Tablet Route of administration: oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weekly Itch Severity Score at Week 24	ISS was recorded in e-diary. The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. Least squares (LS) mean is presented. Baseline was defined as the sum of daily scores obtained for 7 days prior to randomization.	Baseline (Day 1) and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weekly Urticaria Activity Score at Week 24	UAS is a validated composite patient-reported outcome (PRO) measure for assessing chronic spontaneous urticaria (CSU) activity. The once daily UAS is the sum of the daily hives severity score (HSS) and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. LS mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.	Baseline (Day 1) and Week 24
Change From Baseline in Weekly Hives Severity Score at Week 24	Daily HSS was recorded in e-diary. The HSS7 score is the sum of daily HSS ranging from 0 (none) to 3 (more than 50 hives) recorded by a participant at the same time of each day over 7 days with an overall scale of 0 (no hives) to 21 (severe hives). Higher scores indicate greater intensity of hives. LS mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.	Baseline (Day 1) and Week 24
Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference (MID) at Week 24	The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. An ISS7 MID response was defined as >=5 points decrease from baseline after study intervention.	Week 24
Percentage of Participants With Weekly Urticaria Activity Score <=6 at Week 24	UAS is a validated composite PRO measure for assessing CSU activity. The once daily UAS is the sum of the daily HSS and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. In evaluating urticaria control using UAS7, an UAS7 score of <=6 indicated a well-controlled urticaria.	Week 24
Percentage of Participants With Weekly Urticaria Activity Score =0 at Week 24	UAS is a validated composite PRO measure for assessing CSU activity. The once daily UAS is the sum of the daily HSS and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. In evaluating urticaria control using UAS7, an UAS7 score of 0 indicated an absence of both itch and hives and a complete resolution of CSU symptoms.	Week 24
Change From Baseline in Urticaria Control Test (UCT) at Week 24	The UCT assessed urticaria control based on 4 items (severity of pruritus and wheals urticaria symptoms; frequency of treatment being not sufficient; quality-of-life [QoL] impairment; overall urticarial control). Each item was rated on a 5-point Likert-type scale from 0 (no control) to 4 (maximum control). The overall UCT score was the sum of all 4 individual item scores with a range of 0 (no disease control) to 16 (complete disease control). Higher scores indicated greater disease control. LS mean is presented. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention.	Baseline (Day 1) and Week 24
Change From Baseline in Weekly Itch Severity Score at Week 12	ISS was recorded in e-diary. The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. LS mean is presented. Baseline was defined as the sum of daily scores obtained for 7 days prior to randomization.	Baseline (Day 1) and Week 12
Change From Baseline in Weekly Urticaria Activity Score at Week 12	UAS is a validated composite PRO measure for assessing CSU activity. The once daily UAS is the sum of the daily HSS and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. LS mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.	Baseline (Day 1) and Week 12
Percentage of Participants With Weekly Urticaria Activity Score <=6 and =0 at Week 12	UAS is a validated composite PRO measure for assessing CSU activity. The once daily UAS is the sum of the daily HSS and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. In evaluating urticaria control using UAS7, an UAS7 score of <=6 indicated a well-controlled urticaria and an UAS7 score of 0 indicated an absence of both itch and hives and a complete resolution of CSU symptoms.	Week 12
Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference at Week 12	The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. An ISS7 MID response was defined as >=5 points decrease from baseline after study intervention.	Week 12
Change From Baseline in Weekly Hives Severity Score at Week 12	Daily HSS was recorded in e-diary. The HSS7 score is the sum of daily HSS ranging from 0 (none) to 3 (more than 50 hives) recorded by a participant at the same time of each day over 7 days with an overall scale of 0 (no hives) to 21 (severe hives). Higher scores indicate greater intensity of hives. LS mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.	Baseline (Day 1) and Week 12
Change From Baseline in Urticaria Control Test at Week 12	The UCT assessed urticaria control based on 4 items (severity of pruritus and wheals urticaria symptoms; frequency of treatment being not sufficient; quality-of-life [QoL] impairment; overall urticarial control). Each item was rated on a 5-point Likert-type scale from 0 (no control) to 4 (maximum control). The overall UCT score was the sum of all 4 individual item scores with a range of 0 (no disease control) to 16 (complete disease control). Higher scores indicated greater disease control. LS mean is presented. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention.	Baseline (Day 1) and Week 12
Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20	ISS was recorded in e-diary. The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. Mean is presented. Baseline was defined as the sum of daily scores obtained for 7 days prior to randomization.	Baseline (Day 1) and Weeks 4, 8, 16 and 20
Time to First Weekly Itch Severity Score Minimally Important Difference Response During the 24-Week Treatment Period	The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. The MID for ISS7 was a change of 5.0 points. Time to first ISS7 MID response (ISS7 >=5) was defined as time to reduction from baseline of 5 points or more. Kaplan-Meier estimate is presented. Baseline was defined as the sum of daily scores obtained for 7 days prior to randomization.	Baseline (Day 1) up to Week 24
Change From Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Weeks 12 and 24	The AAS is a diary in which participants document on a daily basis the presence or absence of angioedema during the past 24 hours. If angioedema is present, participants answer 5 additional questions about the time of the day the swelling episode occurred and the severity and impact on daily functioning and appearance this swelling episode has had. Each AAS item is scored between 0 (minimum) and 3 (maximum). The daily AASs range from 0 (no episode) to 15 (severe) points. The AAS7 score is the sum of daily AAS scores reported by a participant at the same time of each day over 7 days, with a range of 0 (no angioedema episodes) to 105 (highest angioedema severity). Higher scores indicate greater angioedema activity. Mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.	Baseline (Day 1) and Weeks 12 and 24
Percentage of Well-controlled Participants (Urticaria Control Test >=12) at Weeks 12 and 24	The UCT assessed urticaria control based on 4 items (severity of pruritus and wheals urticaria symptoms; frequency of treatment being not sufficient; QoL impairment; overall urticarial control). Each item was rated on a 5-point Likert-type scale from 0 (no control) to 4 (maximum control). The overall UCT score was the sum of all 4 individual item scores with a range of 0 (no disease control) to 16 (complete disease control). Higher scores indicated greater disease control. An UCT score of >=12 (out of maximum 16) indicated a well-controlled urticaria disease status.	Weeks 12 and 24
Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) in Participants >=16 Years Old at Weeks 12 and 24	The DLQI is an assessment assessing the impact of skin disease on participants' HRQoL over the previous week and contains 10 questions related to symptoms, leisure activities, work/school or holiday time, personal relationships including intimate, the side effects of treatment, and emotional reactions to having a skin disease. The questions (except question 7) were scored on a 4-point Likert scale: 0 (not at all), 1 (a little), 2 (a lot), 3 (very much). Question 7 about work/studying asked whether work/study had been prevented and then (if "No") to what degree the skin condition has been a problem at work/study; the item was again rated on a 3-point Likert scale: 0 (not at all) to 3 (a lot). Total DLQI was calculated by summing the score of each question and ranged from 0 (no impact) to 30 (severe impact). Higher scores indicated poor HRQoL. Mean is presented. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention.	Baseline (Day 1) and Weeks 12 and 24
Change From Baseline in Health-related Quality-of-life as Measured by Children's Dermatology Life Quality Index (CDLQI) in Participants >=6 to <16 Years Old at Weeks 12 and 24	The CDLQI is a validated questionnaire designed to measure the impact of skin disease on children's HRQoL. Participants provide responses to 10 questions (symptoms feelings associated with disease, the impact of the disease on leisure, school or holidays, personal relationships, sleep, and side effects of treatment for the skin disease). The instrument has a recall period of 7 days. 9 of the 10 questions are scored on a 4-point Likert scale ranging from 0 (not at all/question unanswered) to 3 (very much). Question 7 has an additional possible response (prevented school) which is assigned a score of 3 (0 [not at all] to 3 [definitely]). The total CDLQI score is the sum of the score of each question ranging 0 (no impact) to 30 (severe impact). The higher the score, the greater the impact is on the child's HRQoL. Mean is presented. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention.	Baseline (Day 1) and Weeks 12 and 24
Patient Global Impression of Change (PGIC) of Chronic Spontaneous Urticaria at Weeks 12 and 24	The PGIC is a 1-item questionnaire that asks the participant to provide the overall self-assessment of change in their CSU on a 7-point scale compared to just before participant started taking the study intervention. 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). Higher score indicate worsening.	Weeks 12 and 24
Change From Baseline in Patient Global Impression of Severity (PGIS) of Chronic Spontaneous Urticaria at Weeks 12 and 24	The PGIS is a 1-item questionnaire that asks participants to provide the overall self-assessment of their disease severity on a 4-point scale for the past week. Response choices are: 1 (none), 2 (mild), 3 (moderate), 4 (severe). Higher score indicate more severity. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention.	Baseline (Day 1) and Weeks 12 and 24
Time to First Oral Corticosteroid (OCS) Use for Chronic Spontaneous Urticaria During the 24-week Treatment Period	Participants receiving OCS as rescue medications for CSU were recorded by the Investigator in e-case report form (eCRF) during the 24-week treatment period. Kaplan-Meier estimate for time to first OCS use is presented.	Baseline (Day 1) up to Week 24
Percentage of Participants Receiving Oral Corticosteroid for Chronic Spontaneous Urticaria During the 24-week Treatment Period	Percentage of participants receiving OCS as rescue medications for CSU were recorded by the Investigator in eCRF during the 24-week treatment period.	Baseline (Day 1) up to Week 24
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened or became serious during the TE period.	From first dose of study intervention (Day 1) up to end of follow-up, approximately 36 weeks each for Study A, B and C
Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) Against Dupilumab	Blood samples were collected at specified timepoints and ADA samples were assayed using validated methods. Treatment-emergent ADA response was defined as a positive response in the ADA assay post first dose when baseline results were negative or missing. Number of participants with treatment-emergent ADA response is presented.	Up to Week 24

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

Helpful Links

• EFC16461 Plain language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2019
• Primary Completion (Actual): August 1, 2024
• Study Completion (Actual): October 25, 2024

Study Registration Dates

• First Submitted: November 25, 2019
• First Submitted That Met QC Criteria: November 26, 2019
• First Posted (Actual): November 27, 2019

Study Record Updates

• Last Update Posted (Actual): August 20, 2025
• Last Update Submitted That Met QC Criteria: August 18, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Skin Diseases, Vascular; Chronic Urticaria; Urticaria; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Histamine Agents; Neurotransmitter Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine H1 Antagonists, Non-Sedating
• Other Study ID Numbers: EFC16461; 2019-003775-19 (EudraCT Number); U1111-1241-8208 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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