Clinical trial NCT04180488: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Spontaneous Urticaria
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2019-11-27
Enrollment: 397
Sex: ALL
Minimum age (years): 6
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in weekly itch severity score (except EU and EU reference countries)
timeFrame: Baseline to Week 24
measure: For EU and EU reference countries only: change from baseline in weekly urticaria activity score
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Change from baseline in weekly urticaria activity score
timeFrame: Baseline to Week 12 and Week 24
measure: Change from baseline in ISS7
timeFrame: Baseline to Week 12 and Week 24
measure: Change from baseline in weekly hives severity score
timeFrame: Baseline to Week 12 and Week 24
measure: 4. Time to ISS7 minimally important (MID) (ISS7 ≥5) response
timeFrame: 4. Baseline over time until Week 24
measure: Proportion of ISS7 MID (≥5 points) responders
timeFrame: Week 12 and Week 24
measure: Change from baseline in ISS7 at all time points
timeFrame: Baseline to Week 24
measure: Proportion of patients with UAS7 ≤6
timeFrame: Week 12 and Week 24
measure: Proportion of patients with UAS7=0
timeFrame: Week 12 and Week 24
measure: Change from baseline in angioedema activity score over 7 days (AAS7)
timeFrame: Baseline to Week 12 and Week 24
measure: Change from baseline in urticaria control test (UCT)
timeFrame: Baseline to Week 12 and Week 24
measure: Proportion of well controlled patients (UCT ≥12)
timeFrame: Week 12 and Week 24
measure: Change from baseline in health-related quality-of-life - DLQI
timeFrame: Baseline to Week 12 and Week 24
measure: Change from baseline in health-related quality-of-life - CDLQI
timeFrame: Baseline to Week 12 and Week 24
measure: Patient Global Assessment of Change (PGIC) of CSU
timeFrame: Week 12 and Week 24
measure: Change from baseline in Patient Global Impression of Severity (PGIS) of CSU
timeFrame: Baseline to Week 12 and Week 24
measure: Proportion of patients receiving OCS for CSU during the planned treatment period
timeFrame: Baseline over time to Week 24
measure: Time to event of patients receiving OCS for CSU during the planned treatment period
timeFrame: Baseline over time to Week 24
measure: Percentage of participants experiencing treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs)
timeFrame: Baseline to Week 24
measure: Incidence of treatment-emergent ADA against dupilumab over time
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: California Allergy and Asthma Medical Group, Inc. Site Number : 8400019
state: California
city: Sarasota
country: United States
facility: Sarasota Clinical Research Site Number : 8400017
state: Florida
city: Sweetwater
country: United States
facility: Lenus Research & Medical Group Site Number : 8400001
state: Florida
city: Tampa
country: United States
facility: University of South Florida Site Number : 8400006
state: Florida
city: Savannah
country: United States
facility: Aeroallergy Research Laboratories of Savannah, INC Site Number : 8400018
state: Georgia
city: Owensboro
country: United States
facility: Allergy & Asthma Specialists, PSC Site Number : 8400020
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University (Asthma and Allergy Center) Site Number : 8400016
state: Maryland
city: Saint Louis
country: United States
facility: The Clinical Research Center, LLC Site Number : 8400009
state: Missouri
city: Rochester
country: United States
facility: UR Dermatology at College Town Site Number : 8400008
state: New York
city: Charlotte
country: United States
facility: Immunocarolina LLC Site Number : 8400010
state: North Carolina
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center Site Number : 8400014
state: Ohio
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute, P.C. Site Number : 8400015
state: Oklahoma
city: Pittsburgh
country: United States
facility: Allergy and Clinical Immunology Associates Site Number : 8400024
state: Pennsylvania
city: Charleston
country: United States
facility: National Allergy and ENT Site Number : 8400011
state: South Carolina
city: Dallas
country: United States
facility: Pharmaceutical Research & Consulting, Inc. Site Number : 8400003
state: Texas
city: San Antonio
country: United States
facility: STAAMP Research, LLC Site Number : 8400007
state: Texas
city: Caba
country: Argentina
facility: Investigational Site Number : 0320008
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigational Site Number : 0320004
state: Buenos Aires
city: Rosario
country: Argentina
facility: Investigational Site Number : 0320006
state: Santa Fe
city: Rosario
country: Argentina
facility: Investigational Site Number : 0320007
state: Santa Fe
city: Rosario
country: Argentina
facility: Investigational Site Number : 0320005
state: Santa Fe
city: San Miguel de Tucuman
country: Argentina
facility: Investigational Site Number : 0320003
state: Tucumán
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320001
city: Calgary
country: Canada
facility: Investigational Site Number : 1240009
state: Alberta
city: Edmonton
country: Canada
facility: Investigational Site Number : 1240010
state: Alberta
city: Hamilton
country: Canada
facility: Investigational Site Number : 1240014
state: Ontario
city: Markham
country: Canada
facility: Investigational Site Number : 1240013
state: Ontario
city: Niagara Falls
country: Canada
facility: Investigational Site Number : 1240003
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number : 1240005
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number : 1240002
state: Ontario
city: Windsor
country: Canada
facility: Investigational Site Number : 1240007
state: Ontario
city: Sherbrooke
country: Canada
facility: Investigational Site Number : 1240016
state: Quebec
city: Trois-Rivieres
country: Canada
facility: Investigational Site Number : 1240006
state: Quebec
city: Quebec
country: Canada
facility: Investigational Site Number : 1240004
city: Quebec
country: Canada
facility: Investigational Site Number : 1240011
city: Beijing
country: China
facility: Investigational Site Number : 1560010
city: Beijing
country: China
facility: Investigational Site Number : 1560004
city: Chengdu
country: China
facility: Investigational Site Number : 1560001
city: Guangzhou
country: China
facility: Investigational Site Number : 1560007
city: Hangzhou
country: China
facility: Investigational Site Number : 1560002
city: Hangzhou
country: China
facility: Investigational Site Number : 1560008
city: Jinan
country: China
facility: Investigational Site Number : 1560006
city: Shanghai
country: China
facility: Investigational Site Number : 1560003
city: Wuxi
country: China
facility: Investigational Site Number : 1560005
city: Ars-Laquenexy
country: France
facility: Investigational Site Number : 2500008
city: Calais
country: France
facility: Investigational Site Number : 2500009
city: Lille
country: France
facility: Investigational Site Number : 2500002
city: Mont de Marsan
country: France
facility: Investigational Site Number : 2500011
city: Nantes
country: France
facility: Investigational Site Number : 2500004
city: Nice
country: France
facility: Investigational Site Number : 2500012
city: Nice
country: France
facility: Investigational Site Number : 2500003
city: Paris
country: France
facility: Investigational Site Number : 2500006
city: Pierre Benite
country: France
facility: Investigational Site Number : 2500005
city: Valence
country: France
facility: Investigational Site Number : 2500007
city: Berlin
country: Germany
facility: Investigational Site Number : 2760001
city: Bramsche
country: Germany
facility: Investigational Site Number : 2760010
city: Dresden
country: Germany
facility: Investigational Site Number : 2760006
city: Kiel
country: Germany
facility: Investigational Site Number : 2760007
city: Langenau
country: Germany
facility: Investigational Site Number : 2760011
city: Tübingen
country: Germany
facility: Investigational Site Number : 2760008
city: Debrecen
country: Hungary
facility: Investigational Site Number : 3480005
city: Szeged
country: Hungary
facility: Investigational Site Number : 3480004
city: Szolnok
country: Hungary
facility: Investigational Site Number : 3480003
city: Szombathely
country: Hungary
facility: Investigational Site Number : 3480002
city: Hiroshima-shi
country: Japan
facility: Investigational Site Number : 3920005
state: Hiroshima
city: Sapporo-shi
country: Japan
facility: Investigational Site Number : 3920009
state: Hokkaido
city: Kobe-shi
country: Japan
facility: Investigational Site Number : 3920002
state: Hyogo
city: Kagoshima-Shi
country: Japan
facility: Investigational Site Number : 3920011
state: Kagoshima
city: Yokohama-Shi
country: Japan
facility: Investigational Site Number : 3920013
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Investigational Site Number : 3920008
state: Kanagawa
city: Suita-shi
country: Japan
facility: Investigational Site Number : 3920003
state: Osaka
city: Izumo-shi
country: Japan
facility: Investigational Site Number : 3920007
state: Shimane
city: Itabashi-ku
country: Japan
facility: Investigational Site Number : 3920006
state: Tokyo
city: Shinagawa-Ku
country: Japan
facility: Investigational Site Number : 3920001
state: Tokyo
city: Tachikawa-shi
country: Japan
facility: Investigational Site Number : 3920010
state: Tokyo
city: Nagoya-shi
country: Japan
facility: Investigational Site Number : 3920004
city: Chelyabinsk
country: Russian Federation
facility: Investigational Site Number : 6430008
city: Kazan
country: Russian Federation
facility: Investigational Site Number : 6430006
city: Krasnodar
country: Russian Federation
facility: Investigational Site Number : 6430007
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430005
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430010
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430002
city: Saratov
country: Russian Federation
facility: Investigational Site Number : 6430009
city: Smolensk
country: Russian Federation
facility: Investigational Site Number : 6430004
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number : 6430003
city: Stavropol
country: Russian Federation
facility: Investigational Site Number : 6430001
city: Santiago de Compostela
country: Spain
facility: Investigational Site Number : 7240012
state: A Coruña [La Coruña]
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240003
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240008
state: Barcelona [Barcelona]
city: Hospitalet de Llobregat
country: Spain
facility: Investigational Site Number : 7240014
state: Barcelona [Barcelona]
city: Esplugues de Llobregat
country: Spain
facility: Investigational Site Number : 7240010
state: Catalunya [Cataluña]
city: Las Palmas de Gran Canaria
country: Spain
facility: Investigational Site Number : 7240005
state: Las Palmas
city: Madrid
country: Spain
facility: Investigational Site Number : 7240007
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Investigational Site Number : 7240001
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Investigational Site Number : 7240006
state: Madrid, Comunidad De
city: Pamplona
country: Spain
facility: Investigational Site Number : 7240002
state: Navarra
city: Burjassot - Valencia
country: Spain
facility: Investigational Site Number : 7240013
state: Valenciana, Comunidad
city: Córdoba
country: Spain
facility: Investigational Site Number : 7240004
city: Villareal
country: Spain
facility: Investigational Site Number : 7240011
city: London
country: United Kingdom
facility: Investigational Site Number : 8260002
state: London, City Of
city: Manchester
country: United Kingdom
facility: Investigational Site Number : 8260001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: