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)

Sanofi

Status and phase: Completed; Phase 3

Conditions: Chronic Spontaneous Urticaria

Treatments: Drug: Placebo; Drug: Dupilumab SAR231893; Drug: non sedating H1-antihistamine

Study type: Interventional

Funder types: Industry

Identifiers

NCT04180488

U1111-1241-8208 (Other Identifier)

EFC16461

2019-003775-19 (EudraCT Number)

Details and patient eligibility

About

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

Full description

The duration of study for each participant included 2-4 weeks of screening period, 24 weeks of treatment period and 12 weeks of post treatment period.

Enrollment: 397 patients

Sex: All

Ages: 6 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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397 participants in 6 patient groups, including a placebo group

Study A Dupilumab

Experimental group

Description:

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.

Treatment:

Drug: non sedating H1-antihistamine

Drug: Dupilumab SAR231893

Study A Placebo

Placebo Comparator group

Description:

Participants who were omalizumab naïve received placebo matched to dupilumab as subcutaneous (SC) injection including loading dose from Day 1 up to 24 weeks.

Treatment:

Drug: non sedating H1-antihistamine

Drug: Placebo

Study B Dupilumab

Experimental group

Description:

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.

Treatment:

Drug: non sedating H1-antihistamine

Drug: Dupilumab SAR231893

Study B Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: non sedating H1-antihistamine

Drug: Placebo

Study C Dupilumab

Experimental group

Description:

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.

Treatment:

Drug: non sedating H1-antihistamine

Drug: Dupilumab SAR231893

Study C Placebo

Placebo Comparator group

Description:

Participants who were omalizumab naïve received placebo matched to dupilumab as SC injection including loading dose from Day 1 up to 24 weeks.

Treatment:

Drug: non sedating H1-antihistamine

Drug: Placebo