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)

NCT04180488 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: EFC16461U1111-1241-82082019-003775-19
• Study Type: interventional
• Target: 397
• Locations: 11 countries
• Sites: 98

Brief Summary

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

Conditions

Chronic Spontaneous Urticaria

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (24)

• Change From Baseline in Weekly Urticaria Activity Score at Week 24

  Baseline (Day 1) and Week 24

• Change From Baseline in Weekly Hives Severity Score at Week 24

  Baseline (Day 1) and Week 24

• Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference (MID) at Week 24

  Week 24

• Percentage of Participants With Weekly Urticaria Activity Score <=6 at Week 24

  Week 24

• Percentage of Participants With Weekly Urticaria Activity Score =0 at Week 24

  Week 24

Study Arms (6)

Study A Dupilumab

EXPERIMENTAL

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; Drug: non sedating H1-antihistamine

Study A Placebo

PLACEBO COMPARATOR

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; Drug: non sedating H1-antihistamine

Study B Dupilumab

EXPERIMENTAL

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; Drug: non sedating H1-antihistamine

Study B Placebo

PLACEBO COMPARATOR

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; Drug: non sedating H1-antihistamine

Study C Dupilumab

EXPERIMENTAL

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; Drug: non sedating H1-antihistamine

Study C Placebo

PLACEBO COMPARATOR

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; Drug: non sedating H1-antihistamine

Interventions

Dupilumab SAR231893 DRUG

Pharmaceutical form:Injection solution Route of administration: Subcutaneous

Study A Dupilumab; Study B Dupilumab; Study C Dupilumab

Placebo DRUG

Pharmaceutical form:Injection solution Route of administration: Subcutaneous

Study A Placebo; Study B Placebo; Study C Placebo

non sedating H1-antihistamine DRUG

Pharmaceutical form:Tablet Route of administration: oral administration

Study A Dupilumab; Study A Placebo; Study B Dupilumab; Study B Placebo; Study C Dupilumab; Study C Placebo

Eligibility Criteria

• Age: 6 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (98)

California Allergy and Asthma Medical Group, Inc. Site Number : 8400019

Los Angeles, California, 90025, United States

Location

Sarasota Clinical Research Site Number : 8400017

Sarasota, Florida, 34239, United States

Location

Lenus Research & Medical Group Site Number : 8400001

Sweetwater, Florida, 33172, United States

Location

University of South Florida Site Number : 8400006

Tampa, Florida, 33613, United States

Location

Aeroallergy Research Laboratories of Savannah, INC Site Number : 8400018

Savannah, Georgia, 31406, United States

Location

Allergy & Asthma Specialists, PSC Site Number : 8400020

Owensboro, Kentucky, 42301, United States

Location

Johns Hopkins University (Asthma and Allergy Center) Site Number : 8400016

Baltimore, Maryland, 21224, United States

Location

The Clinical Research Center, LLC Site Number : 8400009

St Louis, Missouri, 63141, United States

Location

UR Dermatology at College Town Site Number : 8400008

Rochester, New York, 14642, United States

Location

Immunocarolina LLC Site Number : 8400010

Charlotte, North Carolina, 28277, United States

Location

Bernstein Clinical Research Center Site Number : 8400014

Cincinnati, Ohio, 45236, United States

Location

Vital Prospects Clinical Research Institute, P.C. Site Number : 8400015

Tulsa, Oklahoma, 74136, United States

Location

Allergy and Clinical Immunology Associates Site Number : 8400024

Pittsburgh, Pennsylvania, 15241, United States

Location

National Allergy and ENT Site Number : 8400011

Charleston, South Carolina, 29420, United States

Location

Pharmaceutical Research & Consulting, Inc. Site Number : 8400003

Dallas, Texas, 75231, United States

Location

STAAMP Research, LLC Site Number : 8400007

San Antonio, Texas, 78229, United States

Location

Investigational Site Number : 0320008

CABA, Buenos Aires, C1023AAB, Argentina

Location

Investigational Site Number : 0320004

CABA, Buenos Aires, C1414AIF, Argentina

Location

Investigational Site Number : 0320006

Rosario, Santa Fe Province, 2000, Argentina

Location

Investigational Site Number : 0320007

Rosario, Santa Fe Province, S2000BRH, Argentina

Location

Investigational Site Number : 0320005

Rosario, Santa Fe Province, S2000JKR, Argentina

Location

Investigational Site Number : 0320003

San Miguel de Tucumán, Tucumán Province, T4000AXL, Argentina

Location

Investigational Site Number : 0320001

Buenos Aires, C1121ABE, Argentina

Location

Investigational Site Number : 1240009

Calgary, Alberta, T2J 7E1, Canada

Location

Investigational Site Number : 1240010

Edmonton, Alberta, T6G 1C3, Canada

Location

Investigational Site Number : 1240014

Hamilton, Ontario, L8L 3C3, Canada

Location

Investigational Site Number : 1240013

Markham, Ontario, L3P 1X3, Canada

Location

Investigational Site Number : 1240003

Niagara Falls, Ontario, L2H 1H5, Canada

Location

Investigational Site Number : 1240005

Toronto, Ontario, M3B 3S6, Canada

Location

Investigational Site Number : 1240002

Toronto, Ontario, M5G 1E2, Canada

Location

Investigational Site Number : 1240007

Windsor, Ontario, N8X 2G1, Canada

Location

Investigational Site Number : 1240016

Sherbrooke, Quebec, J1G 1X9, Canada

Location

Investigational Site Number : 1240006

Trois-Rivières, Quebec, G8T 7A1, Canada

Location

Investigational Site Number : 1240004

Québec, G1V 4W2, Canada

Location

Investigational Site Number : 1240011

Québec, G1W 4R4, Canada

Location

Investigational Site Number : 1560010

Beijing, 100045, China

Location

Investigational Site Number : 1560004

Beijing, 100050, China

Location

Investigational Site Number : 1560001

Chengdu, 610041, China

Location

Investigational Site Number : 1560007

Guangzhou, 510630, China

Location

Investigational Site Number : 1560002

Hangzhou, 310006, China

Location

Investigational Site Number : 1560008

Hangzhou, 310016, China

Location

Investigational Site Number : 1560006

Jinan, 250013, China

Location

Investigational Site Number : 1560003

Shanghai, 200040, China

Location

Investigational Site Number : 1560005

Wuxi, 214002, China

Location

Investigational Site Number : 2500009

Calais, 62107, France

Location

Investigational Site Number : 2500002

Lille, 59037, France

Location

Investigational Site Number : 2500011

Mont-de-Marsan, 40000, France

Location

Investigational Site Number : 2500004

Nantes, 44093, France

Location

Investigational Site Number : 2500012

Nice, 06000, France

Location

Investigational Site Number : 2500003

Nice, 06200, France

Location

Investigational Site Number : 2500006

Paris, 75970, France

Location

Investigational Site Number : 2500005

Pierre-Bénite, 69495, France

Location

Investigational Site Number : 2760001

Berlin, 10117, Germany

Location

Investigational Site Number : 2760010

Bramsche, 49565, Germany

Location

Investigational Site Number : 2760006

Dresden, 01307, Germany

Location

Investigational Site Number : 2760007

Kiel, 24148, Germany

Location

Investigational Site Number : 2760008

Tübingen, 72076, Germany

Location

Investigational Site Number : 3480005

Debrecen, 4031, Hungary

Location

Investigational Site Number : 3480004

Szeged, 6720, Hungary

Location

Investigational Site Number : 3480003

Szolnok, 5000, Hungary

Location

Investigational Site Number : 3480002

Szombathely, 9700, Hungary

Location

Investigational Site Number : 3920005

Hiroshima, Hiroshima, 734-8551, Japan

Location

Investigational Site Number : 3920009

Sapporo, Hokkaido, 060-0807, Japan

Location

Investigational Site Number : 3920002

Kobe, Hyōgo, 650-0017, Japan

Location

Investigational Site Number : 3920011

Kagoshima, Kagoshima-ken, 890-0063, Japan

Location

Investigational Site Number : 3920013

Yokohama, Kanagawa, 221-0825, Japan

Location

Investigational Site Number : 3920008

Yokohama, Kanagawa, 236-0004, Japan

Location

Investigational Site Number : 3920003

Suita-shi, Osaka, 565-0871, Japan

Location

Investigational Site Number : 3920007

Izumo-shi, Shimane, 693-8501, Japan

Location

Investigational Site Number : 3920006

Itabashi-ku, Tokyo, 173-8610, Japan

Location

Investigational Site Number : 3920001

Shinagawa-Ku, Tokyo, 141-8625, Japan

Location

Investigational Site Number : 3920010

Tachikawa-shi, Tokyo, 190-0023, Japan

Location

Investigational Site Number : 3920004

Nagoya, 454-8509, Japan

Location

Investigational Site Number : 6430008

Chelyabinsk, 454048, Russia

Location

Investigational Site Number : 6430006

Kazan', 420064, Russia

Location

Investigational Site Number : 6430007

Krasnodar, 350020, Russia

Location

Investigational Site Number : 6430005

Moscow, 115522, Russia

Location

Investigational Site Number : 6430010

Moscow, 115522, Russia

Location

Investigational Site Number : 6430002

Moscow, 123182, Russia

Location

Investigational Site Number : 6430003

Saint Petersburg, 193231, Russia

Location

Investigational Site Number : 6430009

Saratov, 410028, Russia

Location

Investigational Site Number : 6430004

Smolensk, 214006, Russia

Location

Investigational Site Number : 6430001

Stavropol, 355030, Russia

Location

Investigational Site Number : 7240012

Santiago de Compostela, A Coruña [La Coruña], 15702, Spain

Location

Investigational Site Number : 7240003

Barcelona, Barcelona [Barcelona], 08003, Spain

Location

Investigational Site Number : 7240008

Barcelona, Barcelona [Barcelona], 08036, Spain

Location

Investigational Site Number : 7240014

L'Hospitalet de Llobregat, Barcelona [Barcelona], 08907, Spain

Location

Investigational Site Number : 7240010

Esplugues de Llobregat, Catalunya [Cataluña], 08950, Spain

Location

Investigational Site Number : 7240005

Las Palmas de Gran Canaria, Las Palmas, 35010, Spain

Location

Investigational Site Number : 7240007

Madrid, Madrid, Comunidad de, 28027, Spain

Location

Investigational Site Number : 7240001

Madrid, Madrid, Comunidad de, 28040, Spain

Location

Investigational Site Number : 7240006

Madrid, Madrid, Comunidad de, 28041, Spain

Location

Investigational Site Number : 7240002

Pamplona, Navarre, 31008, Spain

Location

Investigational Site Number : 7240013

Burjassot - Valencia, Valenciana, Comunidad, 46100, Spain

Location

Investigational Site Number : 7240004

Córdoba, 14004, Spain

Location

Investigational Site Number : 7240011

Villarreal de Huerva, 12540, Spain

Location

Investigational Site Number : 8260002

London, London, City of, E1 1BB, United Kingdom

Location

Investigational Site Number : 8260001

Manchester, M23 9QZ,, United Kingdom

Location

Related Publications (3)

• Gimenez-Arnau AM, Casale TB, Yosipovitch G, Ensina LF, Inomata N, Msihid J, Makhija M, Radin A, Cyr SL, Sugerman P, Thomas RB, Chuang CC. Dupilumab Improves Health-Related Quality of Life in Omalizumab-Naive Patients with Chronic Spontaneous Urticaria. Dermatol Ther (Heidelb). 2025 Dec 2. doi: 10.1007/s13555-025-01605-w. Online ahead of print.

  PMID: 41326897 DERIVED

• Yosipovitch G, Kim BS, Koo JY, Chen Z, Wiggins S, Zahn J, Sugerman P, Haddad EB, Cyr SL. Dupilumab Reduces Pruritus in Clinically Distinct Dermatologic Diseases: Data from Clinical Trials on Atopic Dermatitis, Prurigo Nodularis, and Chronic Spontaneous Urticaria. Dermatol Ther (Heidelb). 2025 Nov 22. doi: 10.1007/s13555-025-01596-8. Online ahead of print.

  PMID: 41272364 DERIVED

• Maurer M, Casale TB, Saini SS, Ben-Shoshan M, Laws E, Maloney J, Bauer D, Radin A, Makhija M. Dupilumab Reduces Urticaria Activity, Itch, and Hives in Patients with Chronic Spontaneous Urticaria Regardless of Baseline Serum Immunoglobulin E Levels. Dermatol Ther (Heidelb). 2024 Sep;14(9):2427-2441. doi: 10.1007/s13555-024-01231-y. Epub 2024 Jul 27.

  PMID: 39066978 DERIVED

Related Links

• EFC16461 Plain language Results Summary

MeSH Terms

Conditions

Chronic Urticaria

Interventions

dupilumab

Condition Hierarchy (Ancestors)

Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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: November 25, 2019
• First Posted: November 27, 2019
• Study Start: December 11, 2019
• Primary Completion: August 1, 2024
• Study Completion: October 25, 2024
• Last Updated: August 20, 2025
• Results First Posted: August 20, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

CN (9); CA (12); FR (8); RU (10); US (16); GB (2); HU (4); DE (5); ES (13); JP (12); AR (7)