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)

• ClinicalTrials.gov Identifier: NCT04180488
• Recruitment Status: Active, not recruiting
• First Posted: November 27, 2019
• Last Update Posted: April 11, 2024
• Sponsor: Sanofi
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Sanofi

Tracking Information

• First Submitted Date: November 25, 2019
• First Posted Date: November 27, 2019
• Last Update Posted Date: April 11, 2024
• Actual Study Start Date: December 11, 2019
• Estimated Primary Completion Date: August 22, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 9, 2020)

• Change from baseline in weekly itch severity score (except EU and EU reference countries) [ Time Frame: 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 [ Time Frame: Baseline to Week 24 ]
  Change from baseline in weekly urticaria activity score (UAS7, composite patient reported itch and hive score) at Week 24.

Original Primary Outcome Measures (submitted: November 26, 2019)

Change from baseline in weekly itch severity score [ Time Frame: Baseline to Week 24 ]

Change from baseline in weekly itch severity score (ISS7) at Week 24.

Current Secondary Outcome Measures (submitted: June 9, 2020)

• Change from baseline in weekly urticaria activity score [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 4. Baseline over time until Week 24 ]
  4. Time to ISS7 minimally important (MID) (ISS7 ≥5) response.
• Proportion of ISS7 MID (≥5 points) responders [ Time Frame: Week 12 and Week 24 ]
  Proportion of ISS7 MID (≥5 points) responders at Week 12 and Week 24.
• Change from baseline in ISS7 at all time points [ Time Frame: 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 ≤6 [ Time Frame: Week 12 and Week 24 ]
  Proportion of patients with UAS7 ≤6 at Week 12 and Week 24.
• Proportion of patients with UAS7=0 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
• Proportion of patients receiving OCS for CSU during the planned treatment period [ Time Frame: Baseline over time to Week 24 ]
  Proportion of patients receiving OCS for CSU during the planned treatment period.
• Time to event of patients receiving OCS for CSU during the planned treatment period [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Baseline to Week 24 ]
  Incidence of treatment-emergent ADA against dupilumab over time.

Original Secondary Outcome Measures (submitted: November 26, 2019)

• Change from baseline in weekly urticaria activity score [ Time Frame: 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.
• Change from baseline in ISS7 [ Time Frame: Baseline to Week 12 ]
  Change from baseline in ISS7 at Week 12.
• Change from baseline in weekly hives severity score [ Time Frame: 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 [ Time Frame: 4. Baseline over time until Week 24 ]
  4. Time to ISS7 minimally important (MID) (ISS7 ≥5) response.
• Proportion of ISS7 MID (≥5 points) responders [ Time Frame: Week 12 and Week 24 ]
  Proportion of ISS7 MID (≥5 points) responders at Week 12 and Week 24.
• Change from baseline in ISS7 at all time points [ Time Frame: 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 ≤6 [ Time Frame: Week 12 and Week 24 ]
  Proportion of patients with UAS7 ≤6 at Week 12 and Week 24.
• Proportion of patients with UAS7=0 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 ≥12 - <16 years old at Week 12 and Week 24.
• Patient Global Assessment of Change (PGIC) of CSU [ Time Frame: 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 [ Time Frame: 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.
• Proportion of patients receiving OCS for CSU during the planned treatment period [ Time Frame: Baseline over time to Week 24 ]
  Proportion of patients receiving OCS for CSU during the planned treatment period.
• Time to event of patients receiving OCS for CSU during the planned treatment period [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Baseline to Week 24 ]
  Incidence of treatment-emergent ADA against dupilumab over time.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Chronic Spontaneous Urticaria

Intervention

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

Study Arms

• Experimental: Study A Dupilumab
  dose regimens, on top of non-sedating H1-antihistamine
  Interventions:

  • Drug: Dupilumab SAR231893
  • Drug: non sedating H1-antihistamine
• Placebo Comparator: Study A Matched Placebo
  placebo, on top of non-sedating H1-antihistamine
  Interventions:

  • Drug: Placebo
  • Drug: non sedating H1-antihistamine
• Experimental: Study B Dupilumab
  dose regimens, on top of non-sedating H1-antihistamine
  Interventions:

  • Drug: Dupilumab SAR231893
  • Drug: non sedating H1-antihistamine
• Placebo Comparator: Study B Matched Placebo
  placebo, on top of non-sedating H1-antihistamine
  Interventions:

  • Drug: Placebo
  • Drug: non sedating H1-antihistamine
• Experimental: Study C Dupilumab
  dose regimens, on top of non-sedating H1-antihistamine
  Interventions:

  • Drug: Dupilumab SAR231893
  • Drug: non sedating H1-antihistamine
• Placebo Comparator: Study C Matched Placebo
  placebo, on top of non-sedating H1-antihistamine
  Interventions:

  • Drug: Placebo
  • Drug: non sedating H1-antihistamine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 9, 2024): 397
• Original Estimated Enrollment (submitted: November 26, 2019): 184
• Estimated Study Completion Date: October 24, 2024
• Estimated Primary Completion Date: August 22, 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years to 80 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Canada, China, France, Germany, Hungary, Japan, Russian Federation, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04180488
• Other Study ID Numbers: EFC16461; U1111-1241-8208 ( Registry Identifier: ICTRP ); 2019-003775-19 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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

• Current Responsible Party: Sanofi
• Original Responsible Party: Same as current
• Current Study Sponsor: Sanofi
• Original Study Sponsor: Same as current
• Collaborators: Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: April 2024