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)
- Conditions
- Chronic Spontaneous Urticaria
- Interventions
- Registration Number
- NCT04180488
- Lead Sponsor
- Sanofi
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 397
- 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
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Study A Matched Placebo Placebo placebo, on top of non-sedating H1-antihistamine Study A Matched Placebo non sedating H1-antihistamine placebo, on top of non-sedating H1-antihistamine Study A Dupilumab Dupilumab SAR231893 dose regimens, on top of non-sedating H1-antihistamine Study A Dupilumab non sedating H1-antihistamine dose regimens, on top of non-sedating H1-antihistamine Study B Dupilumab Dupilumab SAR231893 dose regimens, on top of non-sedating H1-antihistamine Study B Dupilumab non sedating H1-antihistamine dose regimens, on top of non-sedating H1-antihistamine Study B Matched Placebo Placebo placebo, on top of non-sedating H1-antihistamine Study B Matched Placebo non sedating H1-antihistamine placebo, on top of non-sedating H1-antihistamine Study C Dupilumab Dupilumab SAR231893 dose regimens, on top of non-sedating H1-antihistamine Study C Dupilumab non sedating H1-antihistamine dose regimens, on top of non-sedating H1-antihistamine Study C Matched Placebo Placebo placebo, on top of non-sedating H1-antihistamine Study C Matched Placebo non sedating H1-antihistamine placebo, on top of non-sedating H1-antihistamine
- Primary Outcome Measures
Name Time Method Change from baseline in weekly itch severity score (except EU and EU reference countries) Baseline to Week 24 Change from baseline in weekly itch severity score (ISS7) at Week 24.
For EU and EU reference countries only: change from baseline in weekly urticaria activity score Baseline to Week 24 Change from baseline in weekly urticaria activity score (UAS7, composite patient reported itch and hive score) at Week 24.
- Secondary Outcome Measures
Name Time Method Change from baseline in weekly urticaria activity score Baseline to Week 12 and Week 24 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).
Change from baseline in ISS7 Baseline to Week 12 and Week 24 Change from baseline in ISS7 at Week 12 and Week 24 (in EU and EU reference countries).
Change from baseline in weekly hives severity score Baseline to Week 12 and Week 24 Change from baseline in weekly hives severity score (HSS7) at Week 12 and Week 24.
4. Time to ISS7 minimally important (MID) (ISS7 ≥5) response 4. Baseline over time until Week 24 4. Time to ISS7 minimally important (MID) (ISS7 ≥5) response.
Proportion of patients receiving OCS for CSU during the planned treatment period Baseline over time to Week 24 Proportion of patients receiving OCS for CSU during the planned treatment period.
Proportion of ISS7 MID (≥5 points) responders Week 12 and Week 24 Proportion of ISS7 MID (≥5 points) responders at Week 12 and Week 24.
Proportion of patients with UAS7 ≤6 Week 12 and Week 24 Proportion of patients with UAS7 ≤6 at Week 12 and Week 24.
Change from baseline in ISS7 at all time points Baseline to Week 24 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).
Proportion of patients with UAS7=0 Week 12 and Week 24 Proportion of patients with UAS7=0 at Week 12 and Week 24.
Change from baseline in angioedema activity score over 7 days (AAS7) Baseline to Week 12 and Week 24 Change from baseline in angioedema activity score over 7 days (AAS7) at Week 12 and Week 24.
Change from baseline in urticaria control test (UCT) Baseline to Week 12 and Week 24 Change from baseline in urticaria control test (UCT) at Week 12 and Week 24.
Proportion of well controlled patients (UCT ≥12) Week 12 and Week 24 Proportion of well controlled patients (UCT ≥12) at Week 12 and Week 24.
Change from baseline in health-related quality-of-life - DLQI Baseline to Week 12 and Week 24 Change from baseline in health-related quality-of-life (HRQoL) as measured by Dermatology Life Quality Index (DLQI) in patients ≥16 years old.
Change from baseline in health-related quality-of-life - CDLQI Baseline to Week 12 and Week 24 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.
Patient Global Assessment of Change (PGIC) of CSU Week 12 and Week 24 Patient Global Assessment of Change (PGIC) of CSU at Week 12 and Week 24.
Change from baseline in Patient Global Impression of Severity (PGIS) of CSU Baseline to Week 12 and Week 24 Change from baseline in Patient Global Impression of Severity (PGIS) of CSU at Week 12 and Week 24.
Time to event of patients receiving OCS for CSU during the planned treatment period Baseline over time to Week 24 Tme to event of patients receiving OCS for CSU during the planned treatment period.
Percentage of participants experiencing treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) Baseline to Week 24 Percentage of participants experiencing treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs).
Incidence of treatment-emergent ADA against dupilumab over time Baseline to Week 24 Incidence of treatment-emergent ADA against dupilumab over time.
Trial Locations
- Locations (101)
Allergy & Asthma Specialists, PSC Site Number : 8400020
🇺🇸Owensboro, Kentucky, United States
Johns Hopkins University (Asthma and Allergy Center) Site Number : 8400016
🇺🇸Baltimore, Maryland, United States
Allergy and Clinical Immunology Associates Site Number : 8400024
🇺🇸Pittsburgh, Pennsylvania, United States
Pharmaceutical Research & Consulting, Inc. Site Number : 8400003
🇺🇸Dallas, Texas, United States
Bernstein Clinical Research Center Site Number : 8400014
🇺🇸Cincinnati, Ohio, United States
Investigational Site Number : 8260002
🇬🇧London, London, City Of, United Kingdom
Investigational Site Number : 2760001
🇩🇪Berlin, Germany
Investigational Site Number : 3920005
🇯🇵Hiroshima-shi, Hiroshima, Japan
Investigational Site Number : 3920009
🇯🇵Sapporo-shi, Hokkaido, Japan
Investigational Site Number : 3920008
🇯🇵Yokohama-shi, Kanagawa, Japan
Investigational Site Number : 3920001
🇯🇵Shinagawa-Ku, Tokyo, Japan
Investigational Site Number : 0320003
🇦🇷San Miguel de Tucuman, Tucumán, Argentina
Investigational Site Number : 0320007
🇦🇷Rosario, Santa Fe, Argentina
Investigational Site Number : 7240005
🇪🇸Las Palmas de Gran Canaria, Las Palmas, Spain
Investigational Site Number : 3920010
🇯🇵Tachikawa-shi, Tokyo, Japan
Investigational Site Number : 1240002
🇨🇦Toronto, Ontario, Canada
Investigational Site Number : 3920004
🇯🇵Nagoya-shi, Japan
Investigational Site Number : 8260001
🇬🇧Manchester, United Kingdom
Investigational Site Number : 2760011
🇩🇪Langenau, Germany
Investigational Site Number : 7240007
🇪🇸Madrid, Madrid, Comunidad De, Spain
Investigational Site Number : 6430010
🇷🇺Moscow, Russian Federation
Investigational Site Number : 1560003
🇨🇳Shanghai, China
California Allergy and Asthma Medical Group, Inc. Site Number : 8400019
🇺🇸Los Angeles, California, United States
The Clinical Research Center, LLC Site Number : 8400009
🇺🇸Saint Louis, Missouri, United States
Lenus Research & Medical Group Site Number : 8400001
🇺🇸Sweetwater, Florida, United States
UR Dermatology at College Town Site Number : 8400008
🇺🇸Rochester, New York, United States
Aeroallergy Research Laboratories of Savannah, INC Site Number : 8400018
🇺🇸Savannah, Georgia, United States
Vital Prospects Clinical Research Institute, P.C. Site Number : 8400015
🇺🇸Tulsa, Oklahoma, United States
STAAMP Research, LLC Site Number : 8400007
🇺🇸San Antonio, Texas, United States
Investigational Site Number : 0320004
🇦🇷Caba, Buenos Aires, Argentina
Investigational Site Number : 0320008
🇦🇷Caba, Buenos Aires, Argentina
Investigational Site Number : 0320006
🇦🇷Rosario, Santa Fe, Argentina
Investigational Site Number : 1240010
🇨🇦Edmonton, Alberta, Canada
Investigational Site Number : 1240013
🇨🇦Markham, Ontario, Canada
Investigational Site Number : 0320005
🇦🇷Rosario, Santa Fe, Argentina
Investigational Site Number : 1240005
🇨🇦Toronto, Ontario, Canada
Investigational Site Number : 1240007
🇨🇦Windsor, Ontario, Canada
Investigational Site Number : 1240004
🇨🇦Quebec, Canada
Investigational Site Number : 1240006
🇨🇦Trois-Rivieres, Quebec, Canada
Investigational Site Number : 1240016
🇨🇦Sherbrooke, Quebec, Canada
Investigational Site Number : 1560006
🇨🇳Jinan, China
Investigational Site Number : 1560001
🇨🇳Chengdu, China
Investigational Site Number : 1240011
🇨🇦Quebec, Canada
Investigational Site Number : 1560010
🇨🇳Beijing, China
Investigational Site Number : 1560007
🇨🇳Guangzhou, China
Investigational Site Number : 1560002
🇨🇳Hangzhou, China
Investigational Site Number : 1560004
🇨🇳Beijing, China
Investigational Site Number : 1560008
🇨🇳Hangzhou, China
Investigational Site Number : 1560005
🇨🇳Wuxi, China
Investigational Site Number : 2500008
🇫🇷Ars-Laquenexy, France
Investigational Site Number : 2500009
🇫🇷Calais, France
Investigational Site Number : 2500002
🇫🇷Lille, France
Investigational Site Number : 2500012
🇫🇷Nice, France
Investigational Site Number : 2500011
🇫🇷Mont de Marsan, France
Investigational Site Number : 2500004
🇫🇷Nantes, France
Investigational Site Number : 2500003
🇫🇷Nice, France
Investigational Site Number : 2500006
🇫🇷Paris, France
Investigational Site Number : 2500005
🇫🇷Pierre Benite, France
Investigational Site Number : 2500007
🇫🇷Valence, France
Investigational Site Number : 2760010
🇩🇪Bramsche, Germany
Investigational Site Number : 2760006
🇩🇪Dresden, Germany
Investigational Site Number : 2760007
🇩🇪Kiel, Germany
Investigational Site Number : 2760008
🇩🇪Tübingen, Germany
Investigational Site Number : 3480005
🇭🇺Debrecen, Hungary
Investigational Site Number : 3480003
🇭🇺Szolnok, Hungary
Investigational Site Number : 3480004
🇭🇺Szeged, Hungary
Investigational Site Number : 3480002
🇭🇺Szombathely, Hungary
Investigational Site Number : 3920002
🇯🇵Kobe-shi, Hyogo, Japan
Investigational Site Number : 3920011
🇯🇵Kagoshima-Shi, Kagoshima, Japan
Investigational Site Number : 3920013
🇯🇵Yokohama-Shi, Kanagawa, Japan
Investigational Site Number : 3920007
🇯🇵Izumo-shi, Shimane, Japan
Investigational Site Number : 3920006
🇯🇵Itabashi-ku, Tokyo, Japan
Investigational Site Number : 3920003
🇯🇵Suita-shi, Osaka, Japan
Investigational Site Number : 6430008
🇷🇺Chelyabinsk, Russian Federation
Investigational Site Number : 6430005
🇷🇺Moscow, Russian Federation
Investigational Site Number : 6430007
🇷🇺Krasnodar, Russian Federation
Investigational Site Number : 6430006
🇷🇺Kazan, Russian Federation
Investigational Site Number : 6430002
🇷🇺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, Russian Federation
Investigational Site Number : 7240012
🇪🇸Santiago de Compostela, A Coruña [La Coruña], Spain
Investigational Site Number : 7240003
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number : 7240008
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number : 7240014
🇪🇸Hospitalet de Llobregat, Barcelona [Barcelona], Spain
Investigational Site Number : 7240010
🇪🇸Esplugues de Llobregat, Catalunya [Cataluña], Spain
Investigational Site Number : 7240013
🇪🇸Burjassot - Valencia, Valenciana, Comunidad, Spain
Investigational Site Number : 7240002
🇪🇸Pamplona, Navarra, Spain
Investigational Site Number : 7240006
🇪🇸Madrid, Madrid, Comunidad De, Spain
Investigational Site Number : 7240004
🇪🇸Córdoba, Spain
Investigational Site Number : 7240011
🇪🇸Villareal, Spain
Investigational Site Number : 0320001
🇦🇷Buenos Aires, Argentina
Immunocarolina LLC Site Number : 8400010
🇺🇸Charlotte, North Carolina, United States
Sarasota Clinical Research Site Number : 8400017
🇺🇸Sarasota, Florida, United States
Investigational Site Number : 1240014
🇨🇦Hamilton, Ontario, Canada
Investigational Site Number : 1240009
🇨🇦Calgary, Alberta, Canada
Investigational Site Number : 1240003
🇨🇦Niagara Falls, Ontario, Canada
Investigational Site Number : 7240001
🇪🇸Madrid, Madrid, Comunidad De, Spain
University of South Florida Site Number : 8400006
🇺🇸Tampa, Florida, United States
National Allergy and ENT Site Number : 8400011
🇺🇸Charleston, South Carolina, United States