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)

Chronic Spontaneous Urticaria Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04180488
• Other study ID #: EFC16461
• Secondary ID: U1111-1241-82082
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 11, 2019
• Est. completion date: October 24, 2024

Study information

• Verified date: April 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 397
• Est. completion date: October 24, 2024
• Est. primary completion date: August 22, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Spontaneous Urticaria
• Chronic Urticaria
• Urticaria

Intervention

Drug:
• Dupilumab SAR231893
Pharmaceutical form:Injection solution Route of administration: Subcutaneous
• Placebo
Pharmaceutical form:Injection solution Route of administration: Subcutaneous
• non sedating H1-antihistamine
Pharmaceutical form:Tablet Route of administration: oral administration

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320001	Buenos Aires
Argentina	Investigational Site Number : 0320004	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320008	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320005	Rosario	Santa Fe
Argentina	Investigational Site Number : 0320006	Rosario	Santa Fe
Argentina	Investigational Site Number : 0320007	Rosario	Santa Fe
Argentina	Investigational Site Number : 0320003	San Miguel de Tucuman	Tucumán
Canada	Investigational Site Number : 1240009	Calgary	Alberta
Canada	Investigational Site Number : 1240010	Edmonton	Alberta
Canada	Investigational Site Number : 1240014	Hamilton	Ontario
Canada	Investigational Site Number : 1240013	Markham	Ontario
Canada	Investigational Site Number : 1240003	Niagara Falls	Ontario
Canada	Investigational Site Number : 1240004	Quebec
Canada	Investigational Site Number : 1240011	Quebec
Canada	Investigational Site Number : 1240016	Sherbrooke	Quebec
Canada	Investigational Site Number : 1240002	Toronto	Ontario
Canada	Investigational Site Number : 1240005	Toronto	Ontario
Canada	Investigational Site Number : 1240006	Trois-Rivieres	Quebec
Canada	Investigational Site Number : 1240007	Windsor	Ontario
China	Investigational Site Number : 1560004	Beijing
China	Investigational Site Number : 1560010	Beijing
China	Investigational Site Number : 1560001	Chengdu
China	Investigational Site Number : 1560007	Guangzhou
China	Investigational Site Number : 1560002	Hangzhou
China	Investigational Site Number : 1560008	Hangzhou
China	Investigational Site Number : 1560006	Jinan
China	Investigational Site Number : 1560003	Shanghai
China	Investigational Site Number : 1560005	Wuxi
France	Investigational Site Number : 2500008	Ars-Laquenexy
France	Investigational Site Number : 2500009	Calais
France	Investigational Site Number : 2500002	Lille
France	Investigational Site Number : 2500011	Mont de Marsan
France	Investigational Site Number : 2500004	Nantes
France	Investigational Site Number : 2500003	Nice
France	Investigational Site Number : 2500012	Nice
France	Investigational Site Number : 2500006	Paris
France	Investigational Site Number : 2500005	Pierre Benite
France	Investigational Site Number : 2500007	Valence
Germany	Investigational Site Number : 2760001	Berlin
Germany	Investigational Site Number : 2760010	Bramsche
Germany	Investigational Site Number : 2760006	Dresden
Germany	Investigational Site Number : 2760007	Kiel
Germany	Investigational Site Number : 2760011	Langenau
Germany	Investigational Site Number : 2760008	Tübingen
Hungary	Investigational Site Number : 3480005	Debrecen
Hungary	Investigational Site Number : 3480004	Szeged
Hungary	Investigational Site Number : 3480003	Szolnok
Hungary	Investigational Site Number : 3480002	Szombathely
Japan	Investigational Site Number : 3920005	Hiroshima-shi	Hiroshima
Japan	Investigational Site Number : 3920006	Itabashi-ku	Tokyo
Japan	Investigational Site Number : 3920007	Izumo-shi	Shimane
Japan	Investigational Site Number : 3920011	Kagoshima-Shi	Kagoshima
Japan	Investigational Site Number : 3920002	Kobe-shi	Hyogo
Japan	Investigational Site Number : 3920004	Nagoya-shi
Japan	Investigational Site Number : 3920009	Sapporo-shi	Hokkaido
Japan	Investigational Site Number : 3920001	Shinagawa-Ku	Tokyo
Japan	Investigational Site Number : 3920003	Suita-shi	Osaka
Japan	Investigational Site Number : 3920010	Tachikawa-shi	Tokyo
Japan	Investigational Site Number : 3920008	Yokohama-shi	Kanagawa
Japan	Investigational Site Number : 3920013	Yokohama-Shi	Kanagawa
Russian Federation	Investigational Site Number : 6430008	Chelyabinsk
Russian Federation	Investigational Site Number : 6430006	Kazan
Russian Federation	Investigational Site Number : 6430007	Krasnodar
Russian Federation	Investigational Site Number : 6430002	Moscow
Russian Federation	Investigational Site Number : 6430005	Moscow
Russian Federation	Investigational Site Number : 6430010	Moscow
Russian Federation	Investigational Site Number : 6430009	Saratov
Russian Federation	Investigational Site Number : 6430004	Smolensk
Russian Federation	Investigational Site Number : 6430003	St-Petersburg
Russian Federation	Investigational Site Number : 6430001	Stavropol
Spain	Investigational Site Number : 7240003	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240008	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240013	Burjassot - Valencia	Valenciana, Comunidad
Spain	Investigational Site Number : 7240004	Córdoba
Spain	Investigational Site Number : 7240010	Esplugues de Llobregat	Catalunya [Cataluña]
Spain	Investigational Site Number : 7240014	Hospitalet de Llobregat	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240005	Las Palmas de Gran Canaria	Las Palmas
Spain	Investigational Site Number : 7240001	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240006	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240007	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240002	Pamplona	Navarra
Spain	Investigational Site Number : 7240012	Santiago de Compostela	A Coruña [La Coruña]
Spain	Investigational Site Number : 7240011	Villareal
United Kingdom	Investigational Site Number : 8260002	London	London, City Of
United Kingdom	Investigational Site Number : 8260001	Manchester
United States	Johns Hopkins University (Asthma and Allergy Center) Site Number : 8400016	Baltimore	Maryland
United States	National Allergy and ENT Site Number : 8400011	Charleston	South Carolina
United States	Immunocarolina LLC Site Number : 8400010	Charlotte	North Carolina
United States	Bernstein Clinical Research Center Site Number : 8400014	Cincinnati	Ohio
United States	Pharmaceutical Research & Consulting, Inc. Site Number : 8400003	Dallas	Texas
United States	California Allergy and Asthma Medical Group, Inc. Site Number : 8400019	Los Angeles	California
United States	Allergy & Asthma Specialists, PSC Site Number : 8400020	Owensboro	Kentucky
United States	Allergy and Clinical Immunology Associates Site Number : 8400024	Pittsburgh	Pennsylvania
United States	UR Dermatology at College Town Site Number : 8400008	Rochester	New York
United States	The Clinical Research Center, LLC Site Number : 8400009	Saint Louis	Missouri
United States	STAAMP Research, LLC Site Number : 8400007	San Antonio	Texas
United States	Sarasota Clinical Research Site Number : 8400017	Sarasota	Florida
United States	Aeroallergy Research Laboratories of Savannah, INC Site Number : 8400018	Savannah	Georgia
United States	Lenus Research & Medical Group Site Number : 8400001	Sweetwater	Florida
United States	University of South Florida Site Number : 8400006	Tampa	Florida
United States	Vital Prospects Clinical Research Institute, P.C. Site Number : 8400015	Tulsa	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  China,  France,  Germany,  Hungary,  Japan,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Proportion of patients with UAS7 =6	Proportion of patients with UAS7 =6 at Week 12 and Week 24.	Week 12 and Week 24
Secondary	Proportion of patients with UAS7=0	Proportion of patients with UAS7=0 at Week 12 and Week 24.	Week 12 and Week 24
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Incidence of treatment-emergent ADA against dupilumab over time	Incidence of treatment-emergent ADA against dupilumab over time.	Baseline to Week 24