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:

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

Secondary Objectives:

To demonstrate the efficacy of dupilumab on urticaria activity composite endpoint and itch or hives, separately, at various timepoints To demonstrate the efficacy of dupilumab on angioedema To demonstrate the efficacy of dupilumab on urticaria control 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 patients who require treatment with oral corticosteroids (OCS) To evaluate safety outcome measures To evaluate immunogenicity of dupilumab

Study Overview

• Status: Active, not recruiting
• 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 will include 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 Contact: Name: Trial Transparency email recommended (Toll free number for US & Canada); Phone Number: option 6 800-633-1610; Email: contact-us@sanofi.com

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
  • Ars-Laquenexy, France, 57085
    • Investigational Site Number : 2500008
  • 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
  • Valence, France, 26953
    • Investigational Site Number : 2500007
• 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
  • Langenau, Germany, 89129
    • Investigational Site Number : 2760011
  • 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 must be ≥6 years to 80 years of age at the time of signing the informed consent.
• Study B: Participant must be ≥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 have 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 this time period
• Using 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 must be willing and able to complete a daily symptom e-Diary for the duration of the study

Exclusion Criteria:

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

• Weight is 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
• Presence 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 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.

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; dose regimens, on top of 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 administration
Placebo Comparator: Study A Matched Placebo; placebo, on top of 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 administration
Experimental: Study B Dupilumab; dose regimens, on top of 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 administration
Placebo Comparator: Study B Matched Placebo; placebo, on top of 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 administration
Experimental: Study C Dupilumab; dose regimens, on top of 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 administration
Placebo Comparator: Study C Matched Placebo; placebo, on top of 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 administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in weekly itch severity score (except EU and EU reference countries)	Change from baseline in weekly itch severity score (ISS7) at Week 24.	Baseline to Week 24
For EU and EU reference countries only: change from baseline in weekly urticaria activity score	Change from baseline in weekly urticaria activity score (UAS7, composite patient reported itch and hive score) at Week 24.	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in weekly urticaria activity score	Change from baseline in weekly urticaria activity score (UAS7, composite patient reported itch and hive score) at Week 12 and Week 24 (except EU and EU reference countries).	Baseline to Week 12 and Week 24
Change from baseline in ISS7	Change from baseline in ISS7 at Week 12 and Week 24 (in EU and EU reference countries).	Baseline to Week 12 and Week 24
Change from baseline in weekly hives severity score	Change from baseline in weekly hives severity score (HSS7) at Week 12 and Week 24.	Baseline to Week 12 and Week 24
4. Time to ISS7 minimally important (MID) (ISS7 ≥5) response	4. Time to ISS7 minimally important (MID) (ISS7 ≥5) response.	4. Baseline over time until Week 24
Proportion of ISS7 MID (≥5 points) responders	Proportion of ISS7 MID (≥5 points) responders at Week 12 and Week 24.	Week 12 and Week 24
Change from baseline in ISS7 at all time points	Change from baseline in ISS7 at all time points (onset of action is assessed by the first p<0.05 that remains significant at subsequent measures until Week 24).	Baseline to Week 24
Proportion of patients with UAS7 ≤6	Proportion of patients with UAS7 ≤6 at Week 12 and Week 24.	Week 12 and Week 24
Proportion of patients with UAS7=0	Proportion of patients with UAS7=0 at Week 12 and Week 24.	Week 12 and Week 24
Change from baseline in angioedema activity score over 7 days (AAS7)	Change from baseline in angioedema activity score over 7 days (AAS7) at Week 12 and Week 24.	Baseline to Week 12 and Week 24
Change from baseline in urticaria control test (UCT)	Change from baseline in urticaria control test (UCT) at Week 12 and Week 24.	Baseline to Week 12 and Week 24
Proportion of well controlled patients (UCT ≥12)	Proportion of well controlled patients (UCT ≥12) at Week 12 and Week 24.	Week 12 and Week 24
Change from baseline in health-related quality-of-life - DLQI	Change from baseline in health-related quality-of-life (HRQoL) as measured by Dermatology Life Quality Index (DLQI) in patients ≥16 years old.	Baseline to Week 12 and Week 24
Change from baseline in health-related quality-of-life - CDLQI	Change from baseline in health-related quality-of-life (HRQoL) as measured by Children's Dermatology Life Quality Index (CDLQI) in patients ≥6 - <16 years old at Week 12 and Week 24.	Baseline to Week 12 and Week 24
Patient Global Assessment of Change (PGIC) of CSU	Patient Global Assessment of Change (PGIC) of CSU at Week 12 and Week 24.	Week 12 and Week 24
Change from baseline in Patient Global Impression of Severity (PGIS) of CSU	Change from baseline in Patient Global Impression of Severity (PGIS) of CSU at Week 12 and Week 24.	Baseline to Week 12 and Week 24
Proportion of patients receiving OCS for CSU during the planned treatment period	Proportion of patients receiving OCS for CSU during the planned treatment period.	Baseline over time to Week 24
Time to event of patients receiving OCS for CSU during the planned treatment period	Tme to event of patients receiving OCS for CSU during the planned treatment period.	Baseline over time to Week 24
Percentage of participants experiencing treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs)	Percentage of participants experiencing treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs).	Baseline to Week 24
Incidence of treatment-emergent ADA against dupilumab over time	Incidence of treatment-emergent ADA against dupilumab over time.	Baseline 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 Chronic Urticarial Pruritus Itch Dupilumab Trial website

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2019
• Primary Completion (Estimated): August 22, 2024
• Study Completion (Estimated): October 24, 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): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Disease Attributes; Skin Diseases, Vascular; Hypersensitivity; Chronic Disease; Urticaria; Chronic Urticaria; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Histamine 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